The Medical & Surgical Practice of NaProTechnology (2004, Hilgers)

THE
MEDICAL & SURGICAL

PRACTICE
OF
NaProTECHNOLOGY
Tho1nas W. Hilgers, M.D.

Pope Paul VI Institute Press • Omaha, Nebraska • 2004
Copyright 2004, Pope Paul VI lnstitute Press
All Rights Reserved*
With the exception of short exerpts fo r critica! reviews, no pan of this

book may be reproduced in any manner wharsoever wirhout permis-
si n in writing from the publisher.
lntemational Standard Book Number: 0-9744147-0-0

Library of Congress Cata logue Card umber: 2004102823
Textbook (and cove r) des ign and layo ut: Victoria L. Sage, B.Sc.
Medi ca! photography: Th om as W . Hilgers, M.D .

C reighton Model C harts: M ary P at Wilson
First Edirion July 2004
Published by:
Pope Paul VI lnstitute Press
6901 Merey Road
Omaha , Nebraska 68106
USA
* The term "NaProTECHNOLOGY" has been regisrered in rhe U. . Parenr and Trad emark Office by the Pope Pau l Vl
lnstitute fo r rhe Stucly of Hum an Reproducrion . Ir can be free ly used by any pe rso n or enrity as long as its use refl ects
the medica! co nce pts and va lu es presented in this textbook.
Thi s book is ve ry sin ce rely d ed ica ted to those wh o have give n so much to make this wo rk poss ib le.
~ Susa n Hi lge rs, my beau tiful wife, mo th er of o ur wo nd erfu l ch ildren , and co-founder
of th e Po pe Paul Vl lnstitute fo r the Study of Human Reprodu ctio n
~ Ou r child ren : Paul , Step hen, Mi chae l, Teresa and Matthew H ilge rs
~ Th ose coupl es and th e Practiti oners, ln stru cto rs, Educato rs, Superviso rs, Medica!
Consu ltants, clergy and religio us whom we have educa ted
~ Our patients, who have served th is work so ge nero usly
~ Po pe Paul VI and his encyclical letter Hu manae Vitae
~ Pope Jo hn Paul 11 and his magnifi ce nt co ntributi o ns: Familiaris Consortio, Donum
Vitae, Evangelium Vitae and Fides et Ratio.
About the Author
Thomas W. Hilgers, MD, Dip. ABOG , ABLS , SRS

Director of th e Pope Paul VI Jnstitute for the Study of H um an Reproduction in Omaha, Ne-
braska. He began hi s first research in th e natural regu lation of human fertility in 1968 as a senior
medi ca ! student. Dr. Hil gers is currently a senior medica! consu ltant in obstetrics, gynecology, re-
producti ve medicine and surge ry at the Pope Pau l VI lnstitute and is a cl ini ca l professor in the
Department of Obstetrics and Gynecology at Creighton Univers ity School of Medicine. ln 1994,
Dr. Hilgers, along with his wife Susan , was named by Pope John Paul 11 to a five-year term to the
Pontifical Council for the Fami ly, and he was also appo inted an active member of the Pontifical
Academy for Life.
Special Contributors
Philip c. Boyle, MICGP, MRCGP, Renée Mirkes, OSF, PhD

CNFPMC Director, Center for NaProEthics
Founder, Pope Paul VI lnstitute for the Study
Natural Procreat ive Technology of Human Reproduction
Medica! Services O maha, Ne braska
Ga lway, lreland
Tracey Parnell, MD, NFPMC

Linda Cady, RN , BSN , CFCP Hannah Centre for Women 's Hea lth Research
Head N urse, Patient Serv ices Di vision Cranbrook, British Co lumbi a, Canada
Pope Paul VI In sti tute, Omaha Nebraska
Dana Reed-Kane, Pharm. D, FCP,

Peter Danis, MD, CNFPM C CNFP PhC
Chainnan , Departm ent of Fam ily Practice Reed 's Compounding Pharmacy
St. John 's Merey Medica! Center Tucson , Arizona
St. Loui s, Missouri
Joseph B. Stanford, MD, MSPH ,

G. Randle McCaslin, CFCP CNFPMC
FertilityCare™ Center ofCentral Texas Assoc iate Professor, Department of Fami ly and
Austin , Texas Preventative Medic ine, Health Research Center
Un ivers ity of Utah School of Medicine
Salt Lake C ity, Utah
For further information consult the following websites:
www.naprotechnology.com
www.popepaulvi.com
www.creightonmodel .com
www.fertilitycare .org
www.aafcp .org
xi
Table of Contents
About the Author vii
Special Contributors ix
Preface XXV
Acknowledgements xxxiv
List of Abbreviations xli
Special Note xliii
e1""'~pée:, 1
_ _ _ _ Disturbing Trends in the Health Care ofWomen, Children and Families_ _ __ 1
The Divorce Rate • Abortion in the United States • Unmarr ied Parenthood • Ch ild Abuse and Neglect•
Drug Use and Crime Rates • Sui cide and Depression • Teenage Sex uality • Prematurity and Low Birth
Weight • Multipl e Pregnancies • Jn fe rtil ity Rates • Sexuall y-transmi tted Diseases • Federal Funding •
Summary and Conclusions
19
The Un ion of Procreati ve Edu cati on and Medica! Technology • Approaching Women as Whole Per-
sons • Achi ev ing and Avo iding Pregnancy • Se lecti ve lntercourse vs . Spontaneous lntercourse •
Cerebrocentri c vs. Genitocentric Sex uality • Sexua l Freedom vs. Sex ual License • Prospecti ve vs.
Retrospective Data Co ll ection • Band-Aid Approaches vs. Getting to the Underlying Causes • Coop-
erati ve Approaches vs . Suppressive and Destructi ve Approaches • What NaProTECHNOLOGY is Not
• The Paradi gm Shi ft of NaProTECHNOLOGY • Thi s Textbook
xii
e1i-~ptet3
29 ---------~
'NaProTECHNOLOGY and the New Humanism ~--------~
Renée Mirkes, OSF, PhD

l - NPT: The Vi sion of lts Pioneer • Personal Virtues • Resea rch Ski li s • 11 - PT: The Visio n of lts
Science • lII - N PT: The Vi sio n ofi ts Ethi cs • IV - N PT: The Vision of its Faith • V - NPT: The Vision
of its Ecclesial Supporters • Codi cil
41 PART 1: lntroduction to the CREIGHTON MODEL System

eti-oc~pte t4
43 _ _ _ _ _ _ _ _ lntroduction to the CREIGHTON MODEL System_ _ _ _ _ _ __
The Need to A id and Support Couples • T he CREIGHTON MODEL FertilityCare™ System • Fe rtility
A pprec iati on • Background of the System • T he CrMS and the Use of Criteria • The Teachin g System
• C urri culum Co ncepts • An ln tegrated A lli ed Hea lth System • Co mprehensive Research Progra ms •
NaProEDUCATION Technology • Adva ntages ofthe CrMS • Edu cation ofTeac hers • Certifi cati on and
Accreditation Standards • Awareness, Acq uisition and lnte rn ali zation • lnfo nnati on vs . Edu cati on •
Q uali ties ofGood Teachers • Quality Assura nce in the CREIGHTON MODEL FertilityCare™ System •
Q ua liti es of Bein g a P rofess ional • Words Convey Att itudes • Fi na l ote
(!.,¡,~•p fot- S
57 _____________Standardization of Teaching _ _ _ _ _ _ _ _ _ _ _ __
The Tools o f Stand ardi zati on • The Teachin g Schedul e • The Picture Dicti onary of the CREIGHTON
MODEL System • The Presentation of the Pictu re Dicti onary • M aking Good Mucus Observa ti o ns •
Wo rd s that are Used in Describing the Mu cus • Observations of the Mucus Du rin g Menstruati on •
A Note Abo ut Sensati on • Genera l Hygiene • CREIGHTON MODEL Foll ow-up Fonn • Basic Prin-
cipies of Fol low-up • Sum mary
e1"~ptet 6
83 _ _ _ __ _ _ _ _ _ lntroductory Presentation of the CrMS_ _ _ _ _ _ _ _ __
Pri ority ltems in Presenting the lntrodu cto ry Session • Comm entary fo r lntroducto ry Slides
eiu~;o tn 7
107 _ __ _ _ _ _ _ _ _ _ Basic Charting and Chart Reading _ _ _ _ _ _ _ _ _ __
Basic C harting • Bas ic C hart Read ing
e1i-oc~pée-t 8
119 _ __ _ _ _ _ _ _ _ _ Charting Continuous Discharges_ _ _ _ _ _ _ _ _ __
The Use of Yell ow Stam ps •Post-Peak, Non -Peak-type Mucus • Post-Peak, Peak-type Mucus • Use of
Pre- Peak Yell ows Stamps: General Guidelines •Use ofYell ow Stam ps: Specific G uidelines ·Final Note
Bas ic Princ ipies • Definiti o ns • A Note o n the Peak Day • Bas ic lnstructi o ns of th e CrMS • Exampl es
of Bas ic lnstructio ns • Ach iev in g Pregnancy
xiii
(?jUl)'1Ü'l.- 10
_ _ _ _ _ _ _ _ _ _ _ Special lnstructions and Applications_ _ _ _ _ _ _ _ _ __ 141
Coming off Birth Control Pi lis • A Note about "Normal Cycles" • A Note on the Pre-Peak lnstructi ons
• Breast Feeding • Postpartum - Not Breast Feeding • Post-Abortion • Single - Not Genitall y Acti ve •
Premenopause • Post-sterili zation - Medical Reasons • ln fe rtility • Seminal Fluid lnstruction • Arousa l
Fluid Instruction • Earl y Ovulation • " Double" Pea k • "Split" Peak • Long Cycles • Anovulation •
Post-Peak, Non-Peak Mucus • Premenstrual Mucus • Premenstrual Spotting • Post-Peak, Pasty Di s-
charge • Dry Cycles
e1..~";"tet- 11
________________CaseManagement________________ 161
ldentification of Potential Situati ons/Problems • lnterpretation of ltems ldentified • lntegration of

Identified and ln terpreted ltems • Recommendati ons • The Case Management Sheet
~.._ptet- 12 e1..
_ _ _ _ _ _ _ _ _ _ __ _ Decision Making in the CrMS _ _ _ _ _ _ _ _ _ _ _ __ 169
The atu ra ! Means and Contracepti ve Practi ces are Di ffe rent • Decision Making • The Sacramental
Moment of Human Proc reation
~ptet.-13 ei..
_ _ _ _ _ _ _ _Achieving- and Avoiding-Related Behavior (Use)_ _ _ _ _ _ __ 173
e1....._ptet- 14
_ _ _ __ _____Objective Classification of the Mucus Cycle _ _ _ _ _ _ _ _ __ 177
e1..""J"tet- 1s
Scientific Foundations ofthe CrMS 183
------------- -------------
Background of the System • The Cervica l Mucus as a Biological Valve • The Work of Professor Erik
Odebl ad • Sperm Penetrati on • Hormone Assess ment and Correlation • Correlati on with Ultrasound •
The Karyopyknotic lndex Correlation • Breast Feeding • Mucus Observation Study • tati stica l Pa-
rameters of the Mucus Cyc le • Eva luation of the Education System • Spousal Communi cati on with the
CrMS • Effecti veness of the System • NaProEDUCATION Technology • Endnote
e1....._ptet- 16
_______ Measu ring Effectiveness and Pregnancy Rates of the CrMS _ _ _ _ __ _ 215
Joseph B. Stanford , MD
Terms Used to Describe Effecti veness • Features of a Good Effecti veness Study • Assessing Use to
Avo id and Ach ieve Pregnancy • Distingui shing Between Use to Avo id and Use to Ac hi eve Pregnancy
• Pregnancy Classifi cation • Effecti veness and Pregnancy Rates, Established Approach • Compari son
of Method and Use Effecti veness to Other Studi es • Achi eving-Related Pregnancy Rate • Effecti ve-
ness and Pregnancy Rates, New Approac h • Unreso lved Pregnancy and Time Peri ods of Use • Statis-
tica l Approaches • Current Data · Di scontinuati on Rates • Achieving Pregnancy in lnfertility • Areas
for Fu tu re Research
xiv
e1..,~;ote.i. 17
231 _ _ _ _ _ _Achieving-Related Pregnancy Rate and lts Natural Adaptability_ _ _ _ __
Thomas W. Hilgers , MD , and Joseph B. Stanford, MD
How Study was Done • Evaluation of Data • lrnportant Points to Consider • Addit iona l lnsights
ei..~;ote.i. 1s
241 - -------
Professional and Academic lnfrastructure ofthe CrMS- - - - - - - -
America n Academy ofNatural Family Planning • The Accrediting P rocess • Certification • America n
Academy of FertilityCare Professionals • Pope Paul VI Institute for the Study of Hum an Reproduc-
tion • FertilityCare™ Centers of America, FertilityCare™ Centers lnternational • Basic Philosophi-
cal Principies • A Final Note
249 PART 11: Laboratory Support for NaProTECHNOLOGY

e1..,~;ote.i. 19
251 ________Targeted Hormone Assessment of the Menstrual Cycle _ _ _ _ _ __
Targeting the Cycle
e1..,~;ote.i. 20
Disorders of Human Ovulation :
259 _ _ _ _ _ _ _ _ _ _ _ Sonographic Classification System ___________
ei..~;ote.i. 21
Disorders of Human Ovulation:
269 ______ Endocrine Validation ofthe Sonographic Classification System _ _ _ _ __
lmmunoassay Method
e1"'~;ote.i. 22
275 _ _ _ _ _ _Clinical Validation of the Sonographic Classification System _ _ _ _ __
Special Note
e..-1..,~}':Jte.t. 23
281 ____________Differences Between Laboratories _ _ _ _ _ _ _ _ _ _ __
ei..~;ote.i. 24
285 _ _ _ _ _ _ _ _ _ _ Establishing Normal Hormone Levels_ _ _ _ _ _ _ _ __
XV
PART 111: Medica! NaProTECHNOLOGY 291

e1..,~~pfet 25
____________ Ch ronic Discharges and the CrMS _ _ _ _ _ _ _ _ _ __ 293
ldentifi cation of Cervica l lnflammation (Cervica l Ectrop ion) • Criteri a for ldentifying Cerv ica l ln-
fl ammati on (Cervical Eversion) • Management Concepts • Frequent "2 W" Observations • Green Dis-
charge • lmpl antation Mucus • Continuous Peak-type Mucus
e1..,~~;ofet 26
lsomolecular Hormones versus Heteromolecular Artimones
______________for Use in Therapeutics ______________ 307
Overview of Stero id Biochemistry • Progesterone and Estrogen Receptors • Effects of Progesterone

and Estrogen • lsomolecu lar Hormones (IMH ) vs. Heteromolecular Artimones (HM A) • lsomolecular
Hormones • Clinica l Effects oflsomolecu lar Hormones · IMH Hormone Fom1L1 lation • Delivery Forms,
Dosi ng Amo unts and Dosing Schedu les • Absorption Patterns of Progesterone
e1..,.~pfet 21
______ Cooperative Progesterone and Estrogen Replacement Therapy_ _ _ _ __ 335
Types of Progesterone Support • Human Chorionic Gonadotropi n (HCG) • Cooperative Estrogen

Replacement Therapy (CERT) • CPRT and Regulation ofthe Menstrual Cycle
e1..,.~;o fet 28
Effects of Stress 341
----------------- - - - - -- - - - - - - - - - - -
e1..,~~;ofet 29
________ Premenstrual Syndrome: Evaluation and Treatment.________ 345
Exercise and Nutrition: Non-Pharmacologic Approaches to Treatment • Phannacologic Therapy •

Ro le ofOvarian Stero ids • Progesterone Treatment • Other Associated Findings • Pope Paul VI lnsti-
tute Evaluation and Treatment Protocol • Fi nal Note
e1..,,~;ofct 30
________ Postpartum Depression: Evaluation and Treatment________ 369
Etiology • Traditional Therapy • Phase 1 Progesterone Support Study • Phase 11 Progesterone Support
Study • Progesterone fo r Depression
e1..,,~pfct 31
_ _ _ _ _ _ _ _ _ _ Ovarian Cysts: Evaluation and Treatment_ _ _ _ _ _ _ _ __ 381
Persistent Fo lli cul ar Cysts • Persisten! Lutea l Cysts • Ovarian Cyst Assessment • Recurrent Ovarian
Cysts
xvi
e1..,~1--pte1- 32
387_ _ _ _ _ _ _ _ _Unusual Bleeding: Evaluation and Treatment_ _ _ _ _ _ _ _ __
No rm al Menstruati on • Characteri stics of Unu sual Bleedin g • Medi ca! De finiti ons • CREIGHTON
MODEL Definition s • Organi c Cau ses • Chronic Cerviciti s • Endometriti • Premenstru al Bleedin g •
End ometri a l Polyps • Excessivel y Heavy Menses • Endo metri al Hyperpla ia • Dysfuncti onal Uterine
Bl eeding Seconda ry to Polycysti c Ova ri es • Th yro id • Adeno myos is • Trunca ted Menstrua l Cycles •
Possible lmmunologica l Causes • Fina l Note
e1..,~1--pú1-33
407_ _ _ _ _ _ _ _ _ _ 0steoporosis and the Role of the CrMS _ _ _ _ _ _ _ _ __
Diagnosis of O steoporosis • Treatm ent • Horm onal Corre lati ons • Pope Paul VI lnstitute Research •
lmpl ications for Treatm ent
(!.,/..,4pú1-34
413__Cancer: NaProTECHNOLOGYand the Potential for Early Detection and Treatment __
Endo metri al Ca ncer • Breas! Ca ncer • Ova ri an Ca ncer • Final ote
(!.,/..,4pú1-35
Follicular and Luteal Phase Deficiency:
425_ _ _ _ _ _ _ _ _Advancing Concepts and New Terminology_ _ _ _ _ _ _ __
L im itati ons of Current A pproaches • Length of th e Luteal Phase • Eva luati on of Luteal Fun cti on •
Sho rtcuts • Type IV Lutea l Phase Defic iency • Type V Lutea l Phase Defi c iency • Follicul ar Phase
Function • Pregnancy Progesterone Leve ls in Luteal Phase Dys functi o n • CREIGHTON MODEL and
NaProTECHNOLOGY Correlates • Eti ology • Treatment and Luteal Support • Conclusio n
(!.,/..,4¡0ú1-36
453_ _ _ _ _ _ _ _ _ _ _ _Thyroid System Dysfunction _ _ _ _ _ _ _ _ _ _ __
Theory • Di agnosis • Treatment • Resu lts of Treatment • Final ote
e1..,~1--pú1-37
467_ _ _ _ _ _ _ _ _The Role of the Compounding Pharmacist_ _ _ _ _ _ _ __
Com po undin g : The Hi sto ry • Compoundin g: The Defin it ion • Compo unding : The Phamiac ist • Co m-
pounding : The eed • Com pounding: Regul ati on • Compounding : Locatin g a Pharmac ist in Your
A rea • Compounding: Quality Control • Co mpoundin g : Natu ra l Hormones • Compounding : Wh at
Consumers Reall y Want • Meeting th e eeds fo r th e Co nsum er • Compo undin g : The Hi story o f Natu-
ra l Ho rm ones • Compo und ing: Wh ere We are Today w ith Natu ra l Hormo nes • Compoundin g : Picki ng
p the Pieces after the WHI • Compo undin g: lnsurance Reim bursement
xvii
PART IV: lnfertility 475

(!.,¡.,~pée t.- 38
_ _ _ _ _ _Trends and Deficiencies in lnfertility Evaluation and Treatment_ _ _ _ __ 477
Eva luati on of lnfertility • Causes of ln fe rtility • Approaches to Treatment • Has There Reall y Been
Progress? • The Outcome of Pregnancies • The Empty Defic iencies of"Modern " Reproducti ve Tech-
nologies • Mi ssing Links • Fi nal Note
(!,l.,,oi,p éet.- 39
_ _ _ _ _ _ _ _ _ _ _ _ _ Medical Risks of lnfertility_ _ _ _ _ _ _ _ _ _ __ 495
Endometri os is • Hormonal Dysfuncti ons Associated with lnfe rtil ity • Pel vic Adhesive Disease • Poly-
cystic Ova rian Disease • Pelvic Pain, Dysmenorrhea, and Dyspareunia • Gastrointestinal Prob lems,
Irritable Bowel Synd rome • Metabolic Effects of PCOD • PCOD, Dysfunctional Bleed ing and Hirsut-
ism • Jnfertil ity and Cancer • Osteoporosis • lmmune Defi ci ency and lnfe rti lity • Salpingitis lsthmica
Nodosa and Ectopic Pregnancy • lnfertili ty and Subsequent Pregnancy Complicati ons • Genera l Medi-
ca! Problems • Socioeconomic and Health Costs of lnfe rtility Care • Summary and Conclusion
e1.,.i,péet.- 40
_ _ _ _ _ _NaProTECHNOLOGY in lnfertility: Evaluation and Treatment_ _ _ _ __ 509
The Missing Link • Philosophy of NaProTECHNOLOGY • Definin g ln fert ili ty • lnfe rtility Eva luation
Protocols • Timing of Fertility Tests • Classi fi cation of Mucus Cycles • Diagnosti c Summary • Treat-
ment • Case Presentati ons • What Does NaProTECHNOLOGY Accompli sh?
e1.,.i,péet.- 41
Hypothalamic-Pituitary-Ovarian Dysfunction
_ __ _ _ _ _and lts Target Organ Effects: lmplications for Treatment_ _ _ _ _ __ 541
Review of Basic Physiology • Hypothalamus and the GnRH Pu lse Generator • GnRH Receptor •
Gonadotropi n Biosynthesis and Secretion • Activin- lnhibin- Fo llistatin System • Pope Paul VI lnstitute
Effo rts • Role of Beta-Endorphin • Other Considerati ons • Receptor Physiology • Receptor Defi ciency
Syndrome?
e1.,.i,ptei- 42
_ _ _ _ _ _ _ _ _ _ Endometriosis and lts Effects on Fertility_ __ _ _ _ _ _ __ 561
Diagnosis • Locati on of Endometri os is • Pathogenesis • Associati on with lnfe rt ili ty • Effects on Fertil-
ity • Treatment • Final Cornment
e1.,. i,ptei- 43
_ _ _ _ _ Polycystic Ovarian Disease: Medical Effects and Effects on Fertility_ _ _ __ 573
Diagnosis • Etiology • Horm onal Correlates • Endometri osis and PCOD • Long-term Medica! Jmpact
• Hirsuti sm • lnsulin Resistance • 2 1-H ydroxy lase Defi ciency • Beta-Endorphin s • The CREIGHTON
MODEL System and PCOD • Progesterone Pro phylax is • lnfe rtili ty and PCOD
xvi ii
(!..,¡.._,,¡,y.rfoi- 44
591 _ _ _ _ _ _ _ _ Pelvic Adhes ive Disease and lts Effects on Fertility_ _ _ _ _ _ __
Sex uall y- tra nsmi tted Diseases • Proxim al Tuba! Occlusion • Adn exa l Adh es ions • Findings at
Sa lpingoscopy • The lncidence ofOvulation Defects and Hormonal Dysfun ction • CREIGHTON MODEL
Chart ing • ln fe rti lity Eva luation and Pelvi c Adhesive Di sease • Treatment of lnferti lity
e1..,&1-ptei- 4s
603 ~~~~~~~~~~~~~-
Amenorrhea and Anovulation -~~~~~~~~~~~~-
e 1..,. 1-;otei- 46
607 _______ Medical Treatment of Ovarian and Target Organ Dysfunction _ _ _ _ _ __
Keeping Perspective • Clom iphene Citrate • Human Menopausa l Gonadotropins • Gonadotropin-re-

leasing Hormone (G nRH ) • Low-dose Clomiphene Progress ion • Low-dose Menotropin Progression •
Use of HCG • High-dose Clomiphene Program • Treatment of Amenorrhea • Implementation of the
Protocols • Examples • Side Effects • Ovarian and Breast Cancer
e1..,,1-ptei- 47
635 _ _ _ _ _ _ _ _ _ _ Male lnfertility: Evaluation and Treatment_ _ _ _ _ _ _ _ __
Seminal Fluid Analysis • Treatment: lntrauterine lnseminati on and lCS I • Medica! Treatment • Vaginal
Lubricants • CREIGHTON MODEL FertilityCa re™ System and NaProTECHNOLOGY
(!..,/..,,1-pt ei- 48
643 _ _ _ _ _ Fecundity and the Mucus Cycle Score in Couples Using the CrMS _ _ _ __
Joseph B. Stanford , MD
Methods ofthe Creighton Model Mu lticenter Fecundity Study • Normall y Fertil e Couples • Subferti le
Coup les • Study Proced ures • Statistical Model • Mucus Cycle Score • Resul ts • Di scussion
e 1..,&1-ptei- 49
653 _ _ _ _NaProTECHNOLOGY and lnfertility: A Family Physician's Approach _ _ __
Dr. Phil C. Boyle
Initial Medica! Consultation • Consent Form • The Consultation Process • lniti al Medica! Consultation
• Mal e Ferti lity • Fema le Fertility • Overview of Treatment Course • Subsequent Medica! Consulta-
ti ons • Conclusion
(!..,/..,,1-ptei- so
667 _ _ _ _ _ _NaProTECHNOLOGY and Pregnancy Following Failed ART _ _ _ __ _
Dr. Phil C. Boyle
Background • Study Group • Results with NPT Treatment • Anal ysis of Pregnancies • Discussion •
Conclusion
(!..,/..,,1-püt. Sl
677 _ _ _ _ _ Effectiveness of NaProTECHNOLOGY in the Treatment of lnfertility_ _ _ __
Measuring Effectiveness • Results of NaProTECHNOLOGY • Conclusions

xix
PART V: Perinatal NaProTECHNOLOGY 695

e1..,"\.}"tet- 52
____Three-dimensional Ultrasound: Putting a Face on the Unborn Human Person_ __ 697
eiu\.p fot-53
_ _ _ _ _ _ _ _ _ _ _ Dating the Beginning of Pregnancy_ _ _ _ _ _ _ _ _ __ 707
e1..,~;o üt- 54
__________Assessing Progesterone During Pregnancy __________ 713
e1..,"\.ptet- 55
_ _ __ _ ____ Using Progesterone Support During Pregnancy _________ 725
lndications for the Use of Progesterone in Pregnancy • Pope Paul Vl lnstitu te Progesterone Suppo11
Protocol • Observed Effects of Progesterone Support • Safety of Progesterone Use in Pregnancy
e1..,"\.pÜt- 56
Prevention of Preterm Birth:
__________A Comprehensive and lntegrated Approach __________ 747
The Prematurity Preventi on Program of the Pope Paul VI lnstitute • Results of the Program • Bio-
chemical lndicators of Pretenn Birth • Specia l Case Examples
e1..,"\.;otet- 57
_______ Recurrent Spontaneous Abortion: Evaluation and Treatment_______ 775
The CREIGHTON MODEL System • Endocrine Parameters • Premenstrual Symptoms • Ovul ation
Disorders • Role of Endometriosis • Ultrasound Findings • Role of Progesterone • The Role of HCG •
Genetic and Autoimmune Studies • Eva luation and Treatment Protocol • Results ofTreatment
e1i-,\.ptet- 58
_ _ _ _ _ _ _ Early Pregnancy Loss : Challenging Current Paradigms _ _ _ _ _ __ 797
Pope Paul VI lnstitute Eva luati ons • Final Note
e1""\.pÜt- 59
Fertility, Conception, and Childbirth in Women of Mature Reproductive Age:
_ _ _ _ _ _ _ _ _ New Hope through NaProTECHNOLOGY_ _ _ _ _ _ _ __ 803
Tracey Parnell , MD
Review of the Problem • NaProTECHNOLOGY and Perinata l Outcomes • PT and ART Perinatal
Outcomes: Wh y the Difference? • Reproductive Potential • Reproductive Aging Theories • Summary
XX
e1.,~lo-JOfr-t- 60
Lethal Congenital Anomalies:
813 _ _ _ _ _ _ _ Prenatal Diagnosis and the Management of Pregnancy _ _ _ _ _ __ _
The Use of Ultraso und • Amniocentesi s • The Triple Test • Chorionic Villus Sampling • Percutaneous Cord
Blood Sampling • Fetal Skin Biopsy • Pre-lmplantati on Diagnosis • Supporting the Famil y and the Fetus • The
Future • Concluding Case Studies • Final ote
e1.,~1o-ptet- 61
825 _ _ _ _ _ _ _ Preconceptional Care and the CREIGHTON MODEL System_ _ _ _ _ __
Medi ca! Conditions • Li festyle Behaviors • Supplementati on Programs • Geneti c Diseases • Responsibl e
Parenthood ln struction • The CREIGHTON MODEL System in Primary Prevention • Final Comments
837 PART VI : Surgical NaProTECHNOLOGY

e1\,~lo-JOfr-t- 62
839 _ _ _ _ _ _ _ _ _ _ _What is Surgical NaProTECHNOLOGY?_ _ _ _ _ _ _ _ __
Qualifícations of the Phys ician • Selection of Patients • Pl anning the Surgical Approach
e1.,~1o-,otet- 63
845 _________ Diagnostic Laparoscopy : "Near-Contact" Approach _________
Techni cal Consideration • Nea r-Contact Laparoscopy (NCL)
e1.,~1o-,oéet- 64
855 _____________Visual Appearance of Endometriosis _ _ _ _ _ _ _ _ _ _ __
e1"~1o-1"'tet- 6s
863 ___________Atlas of Findings in Diagnostic Laparoscopy_ _ _ _ _ _ _ _ _ __
Peritonea l Endometri os is • Endometriosis: Peritonea l Pockets • Endometriosis: Posteri or Bl adder • Ova rian
Endometriosis • Tuba! Endometriosis • Salpingitis lsthmica Nodosa (SIN) • Endometriosis : Rectosigmoid
Colon • Endometriosis: Anteri or Rectum • Endometriosis: Appendi x • Endometriosis: Terminal ll eum • Pelvi c
Adhesions • Hydrosalpinges • Polycysti c Ovaries • Leiomyomata • Fall opi an Tube Anomalies • Fimbria Under
Water • Mi scellaneous Observati ons
e1.,~péet- 66
Selective Hysterosalpingography and
899 _ _ _ _ _ _ _ _Transcervical Catheterization of the Fallopian Tu bes _ _ _ _ _ _ __
Technique
xxi
e.A~pte :- 67
_________ Fundamental Anti-Adhesion Surgical Techniques _ _ _ _ _ _ __ 907
Developm ent of Adhes ions • Surgica l Anti- Ad hesion Mea ures • Adhes ion Prevention Review •
Examples of Postoperative Resul ts • Final No te
e1,,~púi- 68
_ _ _ _ _ _ _ Laparoscopic Laser Vaporization of Endometrial lmplants _ _ _ _ _ __ 933
Laser Physics • Laser Dosage: Pri ncipies · The Surgica l Effects of Laser • Laser Safety • Laparoscopi c
Laser Vaporizati on: The Techniq ue
e1,,.,i.-púi- 69
_ _ _ _ _ _ _ _ _ _ Laparoscopic Laser Lysis of Adhesions _ _ _ _ _ _ _ _ __ 945
e 1,,.,i.-}ot e:- 70
Pelvic Excision and Repair Surgery (PEARS):
Peritoneal and Ovarian Endometriosis
- - -- - -- - - - - - - - - - - - - - - - 951
Basic Techn ique • Other Applications • Final Commen t
etui.-púi- 71
PEARS for Bowel Endometriosis:
_ _ __ _ _ ____ Surgical Techniques for the Gynecologist_ _ _ _ _ _ _ _ __ 965
Appendectomy • Small Bowel • Rectos igmoid Colon • Anteri or Rectum
et,,.,i.-pte:- 72
PEARS for Bowel Endometriosis:
_ _ _ _ _ _ _ _ _Surgical Techniques for the General Surgeon _ _ _ _ _ _ _ __ 975
Anatomy ofth e Ileoceca l Region • Exc ision ofNon-Constricting Nodules • Hand-Sewn Small Bowel
Anastomos is · Stapl ed mall Bowel Anastomosis • Anato my of the Colon • Resection of Penetrating
odul es of th e Anteri or Rectum • Resecti on and Reanastomos is of the Rectos igmoid Co lon •
Melanos is Coli • Postoperati ve Care
e1,,.,i.-pú:- 73
PEARS for Extensive Pelvic Adhesions
- - --------- - - - - - - - - - - - 1001
Technique
et,,.,i.-pte:- 74
_ _ _ _ _ _ _ _ _ PEARS for Uterine Leiomyomata : Myomectomy_ _ _ _ _ _ _ __ 1013
Myo mectomy • lndicati ons fo r Myo mectomy • Techni que fo r Myo mectomy • Adhesion Prevention •
Conclusion
xxii
e1",~J"fr.,, 7s
PEARS for Polycystic Ovaries:
1023 _ _ _ _ _ _ _ _ _ _ _ _ _0varian Wedge Resection _ _ _ _ _ _ _ _ _ _ __ _
Surgical Techn ique
e1",~J"fr.,, 76
PEARS for Fallopian Tubes :
1031 _ _ _ _ _ _ _ _ _ Distal Tubal Occlusions and Other Applications _ _ _ _ _ _ _ __
Distal Tuba! Anomalies • Surgical Management • Di stal Tuba! Endometriosis • Fimbriop lasty •
Conclusion
e1"~~pfrt- 77
PEARS for Fallopian Tubes:
1045 ________ Proximal Tubal Occlusions and Tubal Reimplantation _ _ _ _ _ _ __
Technique
e1",~t:Jfrt- 78
1057 ___________ Management of Ectopic Pregnancies _ _ _ _ _ _ _ _ _ __
Risk Factors • The Types of Ectopic Pregnancies • Diagnosis • CrMS and Ecto pi c Pregnancy • Current
Treatment Approaches • Catholic Medica! Ethics and Ectopic Pregnancy • Estab li shin g the Presence or
Absence ofEmbryonic Life • Choo ing the Best Procedure • Transplantation ofa Tuba! Pregnancy
e1\,~~;ofr'l- 79
1069 Recurrence of Endometriosis after PEARS
---------- ----------
(!.,¡"'~Pte"' 80
1075 ___________ Chronic Pelvic Pain and Dysmenorrhea _ _ _ _ _ _ _ _ _ __
The LUNA Procedure: Technical Details • Results • Final Comment
(!.,/i,4pfrt- 81
Preventing Pelvic Adhesions:
1083 _ _ _ _ _ _ _ _The Cornerstone of Surgical NaProTECHNOLOGY_ _ _ _ _ _ __
eiu~pfrt- 82
Postoperative Care and the Management of Complications
1087 _ _ _ _ _ _ _ _ _ _ _ inSurgicalNaProTECHNOLOGY_ _ _ _ _ _ _ _ _ __
Laparoscopy: Postoperative Ca re • Laparotomy: Postoperative Care • Laparo copy: Comp lication s •

La parotom y: Compl ications • Comparison Data • Final Note
xxiii
PART VII : NaProTECHNOLOGY in Practice 1099

eiu~ptet- 83
_ _ _ _ _ _ A Family Physician 's Experience with NaProTECHNOLOGY_ _ _ _ _ _ 1101
Peter Danis, MD
Famil y Practice • Key Definiti ons • Contracepti on and Associated Hea lth Outcomes • Famil y Planning
• Medi ca! Consultati on in atu ra ! Famil y Planning: Keys to a Successful Prac ti ce • Pri ma ry Care
Approach to Common Reproducti ve and Gynecologic Problems • Stati stics fro m Five Years • Physician 's
Help Card • The Future and Other Responsibilities
e1.... ~pte t- 84
------
The Role ofthe FertilityCare™ Practidoner in NaProTECHNOLOGY- - - - - - 1115
G. Randall McCaslin , CFCP
Practitioner as a Resource to the Client • Providing NaProTECHNOLOGY without a Loca l Medi ca!
Consul tan! • Prov id ing NaProTECHNOLOGY with a Loca l Medi ca! Consultan! • ldentifying Other
Medica! Conditi ons • Success Stories from a FertilityCare™ Center
eiu~pte t- 85
_ _ _ _ _ _ _ _ _ _ _NaProTECHNOLOGY Nursing _ _ _ _ _ _ _ _ _ _ _ 1121
Linda Cady, RN
Ski lis and Duties • Profess ional Sati sfacti on
e1.... ~ptet- 86
_ _ _ _ _ _ _ _Summary of NaProTECHNOLOGY Biomarkers _ _ _ _ _ _ _ _ 1137
Famil y Planning • Targeting Hormone Eva luation • Ovulation Disorders • Chronic Di scharges • Dating
Pregnancy • Effects ofStress • Premenstrual Synd ro me • Ovarían Cysts • lnfe rtili ty •Endometriosis •
Pelvic Adhesions • Spontaneous Abort ion • Ectopi c Pregnancy • Prematu ri ty • Preconceptional Care •
Unusual Bleedi ng • Cancer • Osteo porosis
e1....~ptet- 87
Summary of Medica! Protocols
_ _ __ _ _ _ _ for the NaProTECHNOLOGY-trained Physician _ _ _ _ _ _ _ _ 1163
Chronic Di scharges • Targeted Hormone Profi le • CPRT/CE RT • Premenstrual Synd ro me • Ovarian

Cysts • Postpartum Depression •Foll icular Ultrasou nd Series • ln fertili ty • Recurrent Spontaneo us
Abortion •Progesterone Support • Prematuri ty Prevention • Chronic Pelvic Pain, Dysmenorrhea • Ec-
topic Pregnancy • Prematurity • Preconceptional Care • Unusual Bleeding • Cancer • Osteoporosis
e 1.... ~ptet- 88
Cost-Effectiveness of NaProTECHNOLOGY
- - - -------- - - - - - - - - - - - 1177
Fami ly Planning • Premenstrual Synd ro me • Prematurity • lnfertility • Summary • Cost of lnsura nce
Reimbursement • Other lssues
xxiv
e1\,,~pte:- a9
1185 ~---------------
Research End-notes- - - - - - - - - - - - - - - -
lnformed Consent • Researc h Strengths • Limitations of this Study • Evidence-Based Re producti ve

Medicine: Note ofCa ution
e1\,,~1~te:- 9o
1191 ~----------~
The Future ofNaProTECHNOLOGY ~----------~
CREIGHTON MODEL System • Laboratory Suppon • Medica! NaProTECHNOLOGY • Reproductive

Di sorders • Perin ata l NaProTECHNOLOGY • Surgical NaProTECHNOLOGY • Sociological Eva lua-
ti ons • Ex pans ion of Professio nal Suppon • lnsurance Refom1 • Protecti on ofCo nscie nce · Final Note
1201 Appendix
Progesterone Assessment in Pregnancy:

________ Presentation of Specific Conditions and Situations _________
ormal Controls • Previous History of Reproductive Prob lems • Current Pregnancy Misca rriage •
Abnomial Placen ta! Groups • Threatened Prematurity Group • Fetal Distress •M iscellaneou Group
1231 INDEX
XXV
Preface
On J uly 25, 1968, the direction of my profess ional li fe changed forever. On that date, the Catholic
Ch urch released the papal encyclica l (letter) Humanae Vitae. This was the instruction , written by
Pope Paul VI , which condemned contraception and abortion. As most everyone knows, it was met
with an enormous amount of dissent and criticism .
Nonethe less, because of many experiences in my life where 1 had grown to deepl y appreciate the
teaching wisdom ofthe Catholic Church , 1 worked hard to find a copy ofthe encyclical letter and to
read it. Over the years leading up to Humanae Vitae, 1 had also followed c losely the reports on the
meetings ofthe Papal Bi1ih Control Commission which voted 52-to-4 recommending that the Church
change Her position on contraception . 1 had thought, along w ith many others, that the Church would
change its position. And then , Humanae Vitae was released. Reading this letter not only challenged
me, but a lso convicted me to a new point of view.
ln Humana.e Vitae, Pope Paul VI wrote:
The problem of birth, like every other problem regarding human life, is to be considered,
beyond partial perspectives - whether of the biological or psychological , demographic or
sociological orders - in the light ofan integral vision ofman and of hi s vocatio n, not onl y hi s
natural and earth ly, but al so his superna tura! and eternal vocation. And since, in the attempt to
j usti fy artificia l methods of birth control , man y ha ve appealed ro the demands, both of conju-
ga! love and of ' responsible parenthood ' it is good to state very precisely the true concept of
these two great realities ofmarri ed life, referring principall y to what was recently et forth in
thi s regard,... and in a highly authoritative form , by the Second Vatican Cou nci l in its pastoral
constituti on Gaudium et Spes (The Constituti on on the Church in the Modern World). 1
Conjuga! love reveals its true nature and nobility when it is considered in it supreme origin ,
God, who is love, ' the Father, from whom every family in Heaven and on earth is named.'
Marriage is not, then, the effect of chance or the product of evolution of unconsc ious natural
forces ; it is the wise institution of the Creator to realize in mankind His design of !ove. By
means ofthe reciproca! personal gift ofself, proper and exclusive to them, husband and wife
tend towards the communion of thei r beings in view of mutual personal perfection , to col-
laborate with God in the generation and education of new li ves.
xxvi
For baptized persons, moreover, marriage invests the dignity of a sacramental sign of grace, ina muchas it
represents the union ofChrist and ofthe Chu rc h. '
lts Characteristics
Under this light, there clearly appear the characteristic marks and demands of conjuga! lave and it is of
supreme impo11ance to have an exact idea of these .
This !ove is first ofa ll ,/ 11/ly human , that is to say of the senses and ofthe spirit at the same time. lt is not,
then, a simple transport of instinct and sentiment. but also and principally, an act ofthe free will , intended to
endure and to grow by means of the joys and sorrows of daily life, in such a way that husband and wife
become one on ly heart and one onl y soul, and together attain their human perfection.
Then, this lave is total, that is to say. it is a very special form of personal friendship in which husband and
wife generously share everything, without undue reservation s or selfish calcu lations. Whoever truly !oves
hi s marriage partner, !oves not only for what he receives. but for the partner 's self, rejoicing that he can
enrich hi s partner with the gift of himself.
Again, this !ove isfaith/ 11/ ami exclusive until death . Thus, in fact, do bride and groom conceive it to be on
the day when they freely and in full awareness, assume the duty ofthe marriage bond. Fidel ity... can some-
times be difficult, but is always possi bl e, always noble and meritorious ... The example ofso many matTied
persons down through the centuries shows, not only that fidelity is according to the nature ofmarriage, but
also that it is a source of profound and lasting happiness, and finally, this /o ve is f ecund for it is not
exhausted by the communion between husband and wife, but is destined to continue, raising up new lives.
'Marriage and conjuga! lave are by their nature ordained toward the begetting and educating of children .
Children are rea/ly the supreme gift of marriage and contribute very substantially to the welfare of the
parents. 3 (Emphasis applied)
Resp onsib/e Parenthood

Hence conjuga! lave requires of a husband and wife an awa reness of their mission of '"responsible parent-
hood, " wh ich today is rightly much insisted upan, and which also must be exactly understood. Conse-
quently it is to be considered under diffe rent aspects whi ch are legi timate and connected with one another.
In relation to the biological processes. responsible pare111hood means the knowledge and respect of their
functions; human intellect discovers in the power of givi ng life biological laws which are part of the human
person.
ln relati on to the tendencies of instinct or passion, responsible pare111hood means that necessary dominion
whi ch reason and will must exercise over them.
In relation to phys ical, economic. psychol ogical and soc ial conditions, responsible parenlhood is exercised,
either by the deliberate and generous decision to raise a numerous family, or by the decision made for grave
motives and with due respect fo r the moral law, to avoi d for the time being, or even for an indeterminate
time, a new birth.
Responsible parenthood also and above ali implies a more profound relationsh ip to the objective moral
arder established by God, of which a ri ght conscience is the fai thful interpreter. The responsible exercise of
parenthood implies, therefore, that husband and wife recogni ze fully their own duties towards God, towards
!hemse/ves, towards the jami~I' and towards socierv. in a correct hierarchy oj values .
In the task of transmitting life, therefore, they are not free to proceed completely at will , as if they could
detennine in a wholly autonomous way the honest path to follow ; but they must conform their activity to the
creati ve intention of God, ex pressed in the very nature of marriage and of its acts, and manifested by the
constant teaching ofthe Church.' (Emphasis applied)
Respect for the Nature and Purpose of the M arriage Act

These acts, by which husband and wife are united in chaste intimacy, and by means ofwhich human life is
transmi tted, are, as the Council recalled, ··noble and worthy," and they do not cease to be lawful , if, for
causes independent of the will of husband and wife, they are fo reseen to be infec und, since they always
remain ordained towards ex pressing and consolidating their uni on. In fact, as experience bears witness, not
every conjuga! act is fo ll owed by a new life. God has wise ly disposed natural laws and rhythms offecundity
which, ofthemselves, cause a separa tion ofthe succession of births. Nonetheless, the Church, calling men
xxvii
back to the observance ofthe norms ofthe natural Jaw, as interpreted by its constan! doctrine, teaches that
each and every marriage act must remain open to the transmission of life. 5
The teaching, often set forth by the Magisterium, is founded upon the inseparable connection, willed by God
and unable to be broken by man on his own initiative, between the two meanings of the conjugal act: The
uniti ve meaning and the procreative meaning. lndeed, by its intimate structure, the conjuga! act, whi le most
closely uniting husband and wife, capacitates them for the generation of new lives. according to laws in-
scribed in the very being of man and ofwoman. By safeguarding both these essential aspects, the unitive and
th e procreative, the conjugal act preserves in its fullness, the sense of true mutual lovc and its ordination
towards man 's most high cal ling to parenthood. We believe that the men of our day are particularly capable
of seizing the deeply rcasonable and human character of this fundamental principie.''
After reading these paragraphs from Humanae Vitae, it became clear to me that the Church wished to preserve the
connections between !ove and li fe and that Her ultimate decision had to be a rejection ofcontraception, sterili za-
tion and abortion. To see that this was accomplished, Pope Paul VI iss ued what 1 have often referred to as the
"challenges of Humanae Vitae. " These were presented in Part 111 of the encyc li cal, The Pastoral Directives.
Unfortunately, these cha ll enges have not been met by a large number ofpeople, but there is always hope that that
will eventually occur. Two of the cha ll enges seemed to be addressed to me as a senior in medica! school at the
University ofMinnesota. These were:
To Men OfScience
We wish now to express our encouragement tomen ofscience who "can considerably advance the welfare
of marriage and the fami ly, along with peace of conscience, if by pooling their efforts, they labor to explain
more thoroughly the various conditions favoring a proper regulation of births. lt is particularly desirable,
that, according to the wish already expressed by Pope Pius XI 1, medical science succeed in providing a
sufficiently secure basis for a regulation ofbirth, founded on the observance ofnatura l rh ythm s. In this way,
sc ient ists and especially Catholic scientists, will clearly demonstrate in actual fact, that, as the Church
teaches, "a true contradiction cannot exist between the divine Jaws pertaining to the transmission of life and
those pertaining to the fostering ofauthentic conjugal love." 7
To Doctors and Medica/ Personnel

We hold those physicians and medica! personnel in the highest esteem who, in the exercise oftheir profes-
sion, va lue above every human interest the supe ri or demands of their Christian vocation. Let them perse-
vere, therefore, in promoting on every occasion, the discovery of so lutions inspired by fa ith and right rea-
son. Let them strive to arouse this conviction and this respect in their associates. Let them also consideras
their proper professional duty the task ofacquiring ali ofthe knowledge needed in this delicate sector, so as
to be ab le to give to those married persons who consult them wise counsel and healthy direction , such as
they have a right to expect. 8
When 1 read these "challenges of Humanae Vitae" 1 felt that the Church was speaking directly to me although 1
fully realized the Church was speak ing to a li of us. By December 1968, 1 had begun my very first research project
trying to understand better the natural methods of family planning. Working with six fema le medica! students, 1
evaluated the salivary a lbumin concentration as it cyc led with the menstrual and fertility cycles. lt was an interest-
ing research project, but one that did not lead very far.
At the time, 1 was the presiden! ofmy medica! fraternity. Sorne ofmy fraternity brothers ridiculed the Church's
position as they understood it from the national media. Many felt that what th e C hurch was asking was scientifica ll y
imposs ible. Yet, 1 remember very specificall y telling them , perhaps more as a wish and desire than anything e lse,
that 1thought an a nswer would be forthcoming wit hin the next five years.
In June 1972, four years later, 1 attended a marriage and family life workshop at St. John's University in Collegeville,
Minnesota along with my fiancée. Speaking at that conference was Dr. John Billings ofMelbourne, Austra lia. This
neurologist, motivated by the challenge of a Catho lic priest in 1954, had begun investigating and study ing the
menstrual cycle from a di fferent perspective and point of view. At the time, 1 was a resident in obstetrics and
gynecology a l the Mayo Graduate School of Medicine and 1 felt that, because Dr. Billings was a neurologist and,
most likely over the years, had developed good li stening skills, he was able to see things in his dialogue with
xxviii
patients that sorne of us w ho had less refi ned listening skills had missed ove r the man y yea rs of profess ional
involvement. We lea rned about the Billings Ovulation Method and my bride-to-be began to chart her cycles.
In 1975 , after our marriage and our first c hild , we trave led to A ustra li a and vis ited w ith Dr. John a nd his wife, Dr.
Lyn Billings, w ho hadjoined him in hi s work and hi s efforts. We learned everything that we cou ld about this system
a nd broug ht th at in formati o n back to the U nited tates.
In 1976, asa n ass istant pro fessor in the Depa rtment of Obstetrics and Gynecoiogy at St. Lo u is Uni ve rs ity School
ofMed icine, 1 rec ruited a team to begin a n independent in vesti gatio n ofthe Billin gs Method . Thi s work, supported
by a grant from the M issouri Division of Hea lth a nd the Nationa l lnstitutes fo r C hild Hea lth a nd Hu man Develo p-
ment, began to thoroughly in vestigare this system. Out of those in vesti gati ons carne th e standardi zation of the
vulvar mucus observati o n a nd the subsequent deve lopm ent of w ha t is now known as the CREIGHTON MODEL
FertilityCare™ System .
Our wo rk moved to the De pa rtment ofübstetri cs a nd Gynecology at Creighton Uni versity School of Medicin e in
Jul y 1977 and a specia l research center was deve lo ped wi thin that department which continued to work o n and
further deve lop this system. We continued o ur professional relationship w ith o ur tea m in St. Louis . In 1978, we
began the first c lass ofNatural Famil y Pl a nning Prac titi o ners in a 13-month all ied hea lth education prog ram . Th is
was developed thro ugh the educatio n and research efforts of ou r program at Creig hton University. Thi s progra m
has been ongo ing since that time. Our teachers are now ca ll ed FertilityCare™Practitioners, Educators and Super-
visors. The physicians trained in thi s system and in NaProTECHNOLOGY are e lig ibl e to be certified as FertilityCare™
Medica! Consulta nts. Thi s was the first and continues to be th e o nl y training program , whic h is full y desi gned to
rneet the academic de ma nds ofan a lli ed hea lth professional education program. We also train nurse practitioners,
physician ass i tants, nurse midwi ves and pharmacists.
On August 6, 1978, the Feast of the Transfiguration , Pope Pau l V I died. My w ife a nd l , go ing to a late Mass on that
Sunday aftemoon, heard of hi s death through a n extraordinary tear-filled eul ogy g iven by o ur pari sh pri est. On o ur
way home that evening, we turned to eac h other and said: " We must build a lasting me mo ri a l to Po pe Paul VJ and
his encyc li ca l Humanae Vitae a nd hi sca l! tomen ofsc ience a nd to doctors and medica! pe rsonnel. We wi lI ca l! thi s
the Pope Pau l V I ln stitute fo r the Study of Human Rep roductio n."
Severa! yea rs wen t by before we we re abl e to o pen th e doors ofthi new in stitute. Thi s institute, whi ch opened in
1985 , was dedicated to sc ientifi c and ed ucatio nal researc h in the field of huma n re producti o n, but would as k
questions from a uniquely Cath olic per pective . By this time, contraceptio n, terili zation, abo1tio n and the a1tificial
reproductive tech nologies had compl etely taken ho ld in the profess io n of o bsretri cs and gy neco logy. In fact, th is
mono lithi c view has continued up to the present day among pro fess iona ls in obstetri c , gyneco logy a nd reproduc-
ti ve medicine, and su pports this a pproach to the hea lth ca re ofwomen. The o nl y excepti o n is in the area ofabortion
where there still are a grou p ofobstetrician-gyneco logists w ho are ab le to ex press their oppos ition .
However, when it comes to contraception, sterili zati on or the artifi cia l reproductive tec hnol og ies, the re has de vel-
oped with in this profession , o ne view a nd one view o nl y. In fact, many o bstetri cian-gyneco logists have said over
the years th at yo u can not even practice this profession w ith o ut prescribing ora l contracepti ves, doing sterili zations
or referring peop le fo r the a rtifi c ial reproduct ive techno log ies suc h a in vi/ro ferti li zation or artificial insem ina-
tion . Duri ng these years, o ur research with the CREIGHTON MODEL System has shown, however, that this was not
correct. ln fact, serv ices can be provided to wo men which were completely con istent with Catholic teaching and ,
in fact, these services can be provi ded at a ve ry high leve ! of expertise and w ith excelle nt success.
In 199 1, I wrote a sma ll textbook ca ll ed The Medica/ Applications o/Natural Family Planning. 9 The subtitl e of
this book was "A Phys ic ian 's Guide to NaProTECHNOLOGY." Thi s was, in effect, the o ffici a l birth of a new
women 's hea lth sc ience. l ha ve been amazed by how thi s littl e textbook was a bl e to reach o ut to so ma n y phys icians
throughout this country and severa! fore ign co untri es. We have been able to observe, through training progra ms
that we ha ve condu cted over th ese years, the development ofthese phys ician s toward a practice ofm edicine wh ic h
is completely cons istent wi th their fa ith . Th ey ha ve often do ne th is, 1 mi ght point o ut, in the face of s ignifi cant
ridicule by th eir co ll eagues a nd peers. But, they ha ve o bserved the di sturbing trends in th e hea lthcare of women ,
ch ildren and fa mili es (see Chapte r 1 ofthi s textboo k), a nd th ey are deep ly concerned abo ut them. They do not w ish
xxix
to continue being a contributor to the role that either they have played or the medica! profess ion as a whole has
played in the cultivation of those trends. They ha ve, in effect, decided not to be a part of th at portion of medicine
whi ch cul ti vates these negative outcomes.
Sorne ofthe ridi cule has al so come as a result ofthe religious beliefs held by ph ys icians invol ved and the presu med
notion that one cannot " fo rce your morality on so meone el se." ln fact, that has been the clarion cal ! of the pro-
contraception and abortion movement for those of us who oppose it. But, they ha ve asked us to forego our ow n
deeply held moral and eth ica l bel iefs and adopt their new code. Ju st because so meone comes to a physician and
asks for the oral contraceptive or for an aborti on, or for a tuba! li gation , or fo r the abortifacient approach to the
treatment of in ferti lity, <loes not mean that the physician has either an ob ligati on ora re ponsibility to lead them to
that. ln fact, the physician has the responsibili ty to be faithfu l to the very truth ofhis or her belief and the sc ience
that leads him or her to that belief. o physici an should ever be asked to vio late hi s or her own deeply he ld moral
bel iefs.
Over the yea rs a num ber ofphysicians have fe lt it was " intell ectuall y and sc ientifically impossible" to accomp li sh
a Catholi c approach to reprod ucti ve hea lth care, and from this there has ex isted a prejudice against these views
among phys ici ans and sc ienti sts. These prejudices have often come from a deep-seated ignora nce with regard to
what is poss ibl e in this field. 1 ha ve often sa id to man y peopl e that there is nota physician whom 1 ha ve ever met
who <loes not have an opinion about natural fami ly planning even though 1 have met many phys icians who know
virtual/y nothing about it.
There has, over the yea rs, developed in Western soc iety, the thought that rel igion and sc ience are in conflict. But on
September 14, 1998, Pope John Paul I l issued an important response in hi s encyclical letter Fides et Ratio (Faith
and Reason). 10 For those who may hold sorne ofthese prej udi ces, it is important to understand that Pope John Paul
11 is clearly one of the greatest intell ects of the 20th and the new ly formed 21 st century. Whi le man y peopl e ha ve
been critica! of him over th e years, very few ha ve studi ed him . He is a trained phil osopher in the tradition of St.
Thomas Aq uinas. He has written extensive ly, co ntinuing the long-standi ng, 2000-year tradition in the Catholi c
Church ofintell ectual di scipline. lt is worth reciting so me ofwhat he has written in Fides et Ratio for he addresses
a number ofthe important que tion s that ha ve existed in the fa ith versus reason conflict. lt is not poss ible forme in
thi s preface to be abl e to conso lidate ali ofw hat the Holy Father has addressed in thi 57-page encyc lical, but l
wou ld very much like to share sorne excerpts from it so that perhaps we can ali learn from it:
lt should, nonetheless, be kept in mind that revelation remains charged with mystery. IL is true that Jes us,
with hi s entire li fe, revea led the countenance ofthe Father fa r he came to teac h the secrel thin gs of God . But
our vision of the face ofGod is always fragmentary and impaired by the limi ts of our understanding. Faith
alone makes it possible to penetrate the mystery in a way that all ows us to understand it coherently (empha-
sis app lied) ... the Church has always considered the ac t of entrustin g oneself to God to be a moment of
fundamental decisi on which engages the whole person. In that act, the intell ect and the will display their
spirinia l nature, enab ling the subj ect to act in a way whi ch realizes personal freedom to the full. 11
... the thoug ht o/ St. Thomas A quinas

A quite special place in thi s long development belongs to St. Thomas, not onl y beca use of what he taught,
but also beca use of the dialogue wh ich he undertook with the Arab and Jewish thought of hi s time. In an age
when Chri stian thinkers we re redi scoverin g the Lreasures of ancient philosophy, and more parti cul arly of
Aristotle, Thomas had the great merit of giving pride of pl ace to the harmony which ex ists between fa ith and
reason . Both the light of reason and the li ght of fa ith come from God, he arg ued; hence there can be no
contrad icti on between them.
More rad ica ll y, Thomas recognized that nature, phil osophy's proper concem, could contribute to the under-
standing ofd ivine revelati on. Faith , therefore, has no fear of reason, but seeks it out and has trust in it. Just
as grace builds on nature and builds it to fulfillment, so fait h builds upan and perfects reason ... Human
reason is neither annulled nor debased in assenting to contents of faith, which are, in any case, attai ned by
way of free and in forme d choice ... 11
lt is not too much to clai m that the development of a good part of modem philosophy has seen it move
further and furth er away from Chri stian revelati on, to th e point ofsetting itself quite ex plicitly in opposition
... In the fi eld of scientific research , a positivistic mentality took hold, whi ch not onl y abandoned the Chris-
XXX
tian visi on of the wo rld, but more especiall y rejected every appeal to a metaph ys ical or moral vision. lt
follows that certain scientists, lacking any ethi ca l point ofreference, are in danger ofputting at the centre of
their concern, somethi ng other than the human per on and the entirety of the person' li fe . Further sti ll , sorne
of these. ensing the opportunities oftechnological progress, seem to succumb, not onl y to a mark et-based
logic, but also to the temptation of a quas i-div ine power over nature and even over the human being.
As a res ult of the crisis of rationali sm, what has appeared finall y is nihili sm. As a philosophy ofnothingness
(em phasis applied) it has a certain attraction for people of our time. lts adherents claim that the search is an
end in itself, witho ut any hope or possibili ty ofever attaining the goal of truth. In the nihilist interpretation,
life is no more than an occasion ofsensations and experience, in which the ephemeral has pride ofplace.
Nihili sm is at the roo t of the widespread mentality, which claim s that a defínitive commitment should no
longer be made because everything is fi eetin g and provisional ... 13
lt is an illusion to think that fai th, tied to weak reasoning, might be more penetrat ing; on the contrary, fai th
then runs the grave risk ofwithering into myth or supersti ti on. By the same token, reason which is unrelated
toan adu lt fa ith is not prompted to turn its gaze to the newness and radicality of being. 14
lt is this question of faith being v iewed as " myth or s upe r tition " o r as 1 have hea rd some people say, right up there
next to "w itchcraft" which troubles muc h of modern society. There is the thought, for example, that huma n reason
can find the answers to ali things a nd that fa ith is not necessary. This te xtbook, however, is th e result of question s
that ha ve been asked because offa ith .
The nature of research is to ask questions. lt is the question that forms the fo undation of the investi gation . The
questions that are asked a re th e result of th e val ues that the in ves ti gator hold s. No matter what type ofresearch is
being conducted, it always emanates from th e va lues that the investi gator(s) holds. In fact, research becomes very
boring and empty if is it not stimulated by va lues.
People wi ll hold to different sets of va lues ...that is understood . 1f so meone approaches a particular topic from a
different set ofva lues, it sho uld not automatica ll y be e ithe r ridiculed or put aside. lt has always been interesting to
me to see the soc ial promotion of " di vers ity" as a great strength to society a nd yet how quickly the promoters of
diversity ridicul e a point ofv iew which is differe nt from theirs.
Thi textbook is the result of asking different questions. Secular reproductive sc ienti sts are, for the most pa11, not
terribly interested in questions re lated to the cycli c appearance offertility and infertility. They ha ve, over the last 40
years, adopted a position wh ic h suppresses or destroys fertility. That is the monolithic view in c urrent obstetrics
and gy neco logy. A nd yet, it is poss ibl e that question s ca n be asked that are quite different from this . And , as a res ult
of those questions, di fferent answers may arise. Thi s textbook is about a set of diffe rent questions and different
answers .
lt is importa nt fo r people who may no t agree with the contents of this textbook to ta ke a look at re productive
medicine and surgery from a different point of view. That point of view is found in those women patients that we
see on a daily bas is. 1 see pati e nts day in and day o ut, who are absolutely, l 00-percent opposed to man y of the
current eva luati o n and treatment approac hes in obstetri cs and gynecology. They will not, evento the ir own death ,
cap itul are to th ese cu rren! ap proac hes to their hea lthcare. These wo men , and there a re man y more out there than
one mi ght anticipate, have become my heroes . They have suffered ridicule and condescens ion , they have often
bee n humiliated and they have had peo pl e la ugh a t them. They ha ve litera lly been abandoned by our profession
and they feel disenfranchised. lt is beca use ofthese women, their desires and the ir va lues, and what th ey hold dear
to them, that thi s work has been made possible.
T here are other heroes that 1 ha ve come to deeply admire in my o ve r 28 yea rs of medica! practice and investigation
that has led to th e accumulation of the material in this textbook. Those heroes include the individua ls who have
comm itted the mse lves to be ing trained to prov ide these services to married couples. These indiv iduals are the
FertilityCare™Practitioners w ho are trained in the CREIGHTON MODEL System. This is no easy task for the
academic demands of this program are truly s ig nifi cant. Sorne of these Practitioners have gone on to beco me
FertilityCare™Educators a nd Supervisors. These indi vidual s ha ve taken the Core Curriculum ofthe CREIGHTON
xxxi
MODEL A lli ed Hea lth Education Progra m and deli vered it throug ho ut the U nited States, Canada, Mex ico and
Ireland . The progra m is now also in E ng land a nd in many countries of Europe, South A me rica and is beginning to
deve lo p in Afr ica . And now, new heroes are coming fo rwa rd to be tra ined- the phys ic ia ns w ho have e ndured
ridi cul e wh en they have inco rporated thi s in to their medi ca ! practi ce. A number of those phys icia ns have contrib-
uted in a pos iti ve way to thi s tex tbook.
For a moment, let me add ress furth er the question ofsuperstitio n a nd myth . Fai th is, in so rn e ways, ve ry intang ibl e.
A nd yet, fo r many, it is actually quite palpab le. At the sa rn e tim e, there are certain as pects offa ith that do not lend
themse lves to th e sc ientifi c method. For Catho li cs, fo r exa mple, th e beli ef that Chri st is trul y present in the Eucha-
rist is di ffic ult to quantify. It does not le nd itse lfvery we ll to scientifi c in vesti gati on w here pa lpa bl e numbers and
too Is of stati stica l signifi cance can be used fo r eva luation . A nd yet, it is important to note that, there has never been,
to my kn owl edge, a ny pe rso n w ho has ever w ished to impose that beliefon a nothe r. lt is a be li ef that trul y must
come from within . Thi s is the nature offa ith.
On the other hand , there are othe r iss ues to wh ich re li gion and fait h have made comme nt suc h as the issue of
abo rtio n. The Catho li c Church and rna ny evange li cal Christians, 0 1t hodox Jews and othe r religio us denominati ons
ha ve been severely critic ized for ex pressi ng the view that abortion is wro ng . Th ey ha ve been told , " We do n ' t want
your reli g io us va lu es im posed upon us. " And yet, the abortion procedure does le nd itse lf to scientifi c evaluati o n.
The grow th a nd deve lo pme nt of the emb ryo and fe tus can be scientifi ca lly in ves tigated. Whe n li fe begin s lends
itse lf to obj ecti ve observa tio n a nd measure ment. A bo1t io n is not a q uesti on or arti c le offaith. One 's oppos itio n to
aborti o n is based o n reason a nd va lues . Reason tell s us that a n a bo rtio n destroys (v io lentl y and viciously) a new
hum an li fe. With that in fo rmati on o ne's va lue in the respect fo r li fe demands, out of reason, that a bortion be
o pposed. More a nd mo re, o ne also can reason (and thu s see) the da mag ing effect a bo rtio n has o n th e indi vi dual , th e
fa mil y, society a nd the cu lture. T here is not a Chri sti an in th e world w ho needs to apologize fo r the Chri st-drive n
New Testa ment comm andment: " You shall love the Lo rd yo ur God, w ith ali yo ur healt, w ith ali yo ur so ul , and w ith
ali your m ind. Thi s is the greatest and th e first comrn andment. T he second is like it: You sha ll !ove yo ur ne ig hbor
as yourse lf. Th e who le law and th e pro phets depend o n these two comm andments. " 15 These ultimately are the
reli g ious precepts th at he lp fo rmul ate these va lu es- va lues that can be understood by ali , even non-Chri sti ans.
The phys ica l rea liti es w hi c h a re measurab le by science ca n be docume nted, and th e des ire to be a person of love for
both the unbo rn child and the wo man pregna nt wi th that c hild is generated by va lues . These sa me va lues led to the
deve lopment of many maj or medi ca! instituti o ns in the U ni ted States and in oth er countri es. The sa me conv ictions
have deve lo ped orphanages a nd ha ve reached o ut to fee d the poo r a nd malno uri shed of the world . These are tbe
same va lues that info rm parents to love th eir children as " supreme gifts of marri age." They a re not va lues for whi ch
o ne mu st apologize and they sho uld not be suppressed or ke pt on ly pri vate. They trul y drive the li ves - both pri vate
and public - ofth ose who bel ieve .
As we begin to present the new wome n 's hea lth sc ience of NaProTECHNOLOGY, keep in mind that o ne can
scie ntifically determine the time of ovul ati o n; o ne ca n sc ienti fica ll y determin e if an ovul atio n di sorder ex ists by
eva luating th e gro wth and deve lopm ent of the fo ll ic le wi th the use of ultraso und techno logy ; one can scie ntifica lly
esta bli sh the presence and no rm ality o r abnorma li ty ofcerta in hormone indi cators w ith the use ofradi oimmunoas-
say; o ne can sc ientifi ca ll y assess the use-etfecti veness ofa natu ra l meth od offa mil y pl anning. A li of the questio ns
that can be ra ised abo ut Catho li c teac hing in the area of huma n rep roducti o n can be submi tted to th e scientific
method . A n obj ecti ve data set can be deve loped; thi s textbook and its 28 yea rs of suppo rti ve research is a bout th e
extent to w hi ch we have been ab le to deve lop such data.
Aga in, in the encyc li ca l, Fides et Ratio Pope Jo hn Pa ul 11 continues :
Chri stian phi losophy ... has two aspects. The first is subjective, in the sense that fai th purifies reason. As a
theo logical virtue, fa ith liberates reason from presum ption, the typica l temptation of the ph ilosopher . .. The
philosopher who learns hum il ity wi ll also fi nd courage to tackle questions whi ch are diffícul t to resolve if
the data of Revelati on are ignored - for example, the problem of evi l and sufferin g, the personal nature of
God and the question of the meaning of life, or mo re di rectly, the radica l metaphysica l questi on , "Wh y is
there someth ing rather than noth ing?"
xxxii
The second aspect of Christian philosophy is objective, in the sense that it concerns content. Revelation
clearly proposes certain truths which might never have been discovered by reason unaided, although they
are not of themselves inaccessible to reason. Among these truths is the notion of a free and personal God
who is the Creator of the world, a truth which has been so crucial for the development of philosophical
thinking, especially the philosophy ofbeing. There is also the reality ofsin. as it appears in the li ght offaith.
which helps to shape an adequate philosophical formulation ofthe problem of evil. The notion ofthe person
as a spirinial being is another of faith 's specific contributions: The Christian proclamation ofhuman dignity,
equality and freedom has undoubtedly influenced modern philosophical thought. ln more recent times, there
has been the discovery that history as event - so central to Christian revelation - is important for philosophy
as well. lt is no accident that this has become pivota! for a philosophy of history which stakes its claim as a
new chapter in the human search for truth. 16
Pope John Paul TI points out that Scripture allows us "a vision ofman as imago Dei" (in the image ofGod). "Th is
vis ion ," he points out, "offers indications regarding man 's life, his freedom, and the immortality of the human
spirit. Since the created world is not self-sufficient, every illusion of autonomy which would deny the essential
dependence on God ofevery creature- the human being included- leads to dramatic situations which subvert the
rational search for the harmony in the meaning ofhuman life .. .The problem of moral evil- the most tragic of evils'
forms- is also addressed (in Scripture) , which tells us that such evi l stems not from any material deficiency, but is
a wound inflicted by the di sordered exercise of human freedom." 17
"One of the most significant aspects of our current situation ," he points out, " is the ' Crisis of Meaning.' Perspec-
tives on life in the world, often ofa scientific temper, have so proliferated that we face an increasing fragmentation
of knowledge. " 18 He points out the Second Vatican Council 's reaffirmation that "[i]nte lli gence is not confined to
observable data alone. lt can , with genuine certitude, attain to reality itselfas knowable, though in consequence of
sin that certitude is partially obscured and weakened." 19
[n the Pastoral Directives of Humanae Vitae , Pope Paul VI says :
Mastery of Self
The honest practice of regulation of birth demands first of ali that husband and wife acquire and possess
sol id convictions concerning the true values of life and of the fami ly, and that they tend toward securing
perfect self-mastery. To dominate instinct by means of one 's reason and free will undoubtedly requires
ascetical practices, so that the affective manifestations of conjuga! life may observe the correct order, in
particular with regard to the observance of periodic continence. Yet this discipline which is proper to the
purity of married couples, far from harming conjuga! !ove, rather confers on ita higher human value. lt
demands continua! effort yet, thanks to its beneficent inlluence, husband and wife will fully develop
their personalities, being enriched with spiritual values. Such discipline bestows upon family life fruits
of serenity and peace, and facilita tes the solution of other problems; it favors attention for one's part-
ner, helps both parties to drive out selfishness, the enemy oftrue !ove; and deepens their sense of respon-
sibility. By its means, parents acquire the capacity ofhaving deeper and more efficacious influence in the
education of their offspring; little children and youths grow up with a just appraisal of human va lues, and
in the serene and harmonious development of their spiritual and sensitive faculties w (Emphasis applied)
He also points out that there is a " ... need for creating an atmosphere favorable to education in chastity, that is, to the
triumph ofhealthy liberty over license by means ofrespect for the moral order." 21
These are legitimate challenges of the obstetrician-gynecologist and the family physician. We are, or at least we
should be, primarily educators. We must help foster a value andan ethic that supports family life, su pports mar-
riage, and ultimately supports the children that result from that marriage. Indeed, while difficult times and
problems can arise, the physician should be an instrument towards their so luti on rather than the suppression oftheir
very existence and the ultimate inability to find solutions.
Pope John Paul TI discusses another threat which needs to be reckoned with which he calls "scientism. " 22 He says
that:
xxxii i
This is th e philosophica l notion which refuses to admit the va lidity offorrns of kn owledge other than those
ofthe positi ve sci ences; and it relegates re ligio us, th eological, ethi cal an d aesth eti c knowledge to the realm
of mere fantasy. In the past, the same idea emerged in positivism and neo-positi vism, which considered
metaphys ical staternents to be meaningless. Criti ca! epi stemology has discredited such a claim, but now we
see it revived in the new guise of scienti sm , whi ch dismisses values as mere products of the emotions and
rejects the notion of being in order to clear the way for pure and simple facticity. Science would thus be
poised to dominare a li aspects of hum an life through technological progress. The und eni abl e triumphs of
scientific research and co ntemporary technology have helped to propagate a scienti stic outlook, which now
seems boundless, given its inroads to different cultures and the radical changes it has brought.
Regrettably, it must be noted, scientism consigns ali that has to do with the qu estion ofthe meanin g oflife to
the realm of the irrational or imagi nary. No Jess disappointin g is the way in which it approaches the other
great problems ofph il osoph y which, if they are not ignored, are subjected to analyses based on superficial
analogies, Jacking a li rational founda ti on . Thi s leads to the impoverishment of human thought, which no
longer addresses th e ultimate problem s which the hum an being, as th e animal rationale, has pondered
constan ti y from the beginning of time. And since it leaves no space for the critique offered by ethical judg-
ment, the scientistic mentality has succeeded in leadi ng many to think that if something is tech ni call y pos-
sible, it is thereby morally admissable.22
lt cannot be deni ed that over the last 40 years or more, scie ntific involvement in issues related to h uman reproduc-
tion has led to th e push for s perm ba nks, the storage of froze n human ova, freezing of embryos and experimentati on
on them, postmenopausa l mothe rhoo d , s urrogacy, s uperovulation with its attendant exorbitant risk of mu ltiple
preg nancies and premature birth , "se lective reduction", embryon ic stem cel l research , discuss ions on h uman clon-
ing, a nd the list continues. [t does no t take much to rea lize that we ha ve been abo ut the deve lopment of a cu lture of
dea th. lndeed, it seems un e qui voca l that those original dec is ions regard ing the deve lopment of art ificia l mea ns of
contracepti o n, which relega tes the mea nin g of a sex ua l rel at ion ship to a pure ly phys ica l and emotiona l na tu re, ha ve
depri ved the sexual re lat io nship ofthe significance of its ultimate mean ing. W hen these meanings a re smothered,
it leads to more a nd m o re s uppress io n a nd destruction . There is a need as we begin the 2 1st century to take a
renewed look at this a nd hopefull y be open-minded e noug h to look at new so lutions .
Pope John Paul ll , aga in in Fides et Ratio, a lso speaks very pos itively about science and sc ie ntists in general. He
says:
1 cannot fa il to address a word to scientists, whose research offers an eve r greater knowledge of the universe
as a whole and ofthe incredibl y rich arra y of its component parts, animate and inanimate, with th eir complex
atomic and molecul ar structures. So fa r has science come, especiall y in this century, that its achievements
never cease to amaze us. In expressi ng rn y admirati on and offerin g encouragernent to these brave pioneers of
scientifi c researc h, to whom hum anity owes so mu ch of its current development, l wo uld urge them to
continue their efforts without ever abandoning the sapiential horizon within which scientific and techno-
logica l achi evements are wedded to the philosophical and ethical va lues which are the distinctive and indel-
ible mark ofthe hum an person . Scientists are we ll aware that ' the search fo r truth, even when it concems a
finite reality ofthe world or ofman, is never-ending, but always points beyond to something hi gher in the
imrnedi ate object of study, to the questi ons which give access to Mystery.' 23
In his teachings during his pontificate, he has developed what is now referred to as the " The ology of th e Body."
This was presented as a series of reflections on the meaning of human sexua li ty a nd Humanae Vitae du ri ng his
Wednesday audiences in the early l 980s. It has subsequently been publis hed in its entirety and allows for a number
of further reflections to be made with regard to the very s ignificant application of understanding one 's body and the
mea ning ofsexuality.24
The " T h eology ofthe Body" begi ns directly wi th the Genesis account where God te ll s us that we are created " in
His image and likeness." Thus, as we unde rsta nd how our bodies work and function andas we furthe r understan d
how God created them, we then understand God Himself in a way which we ha ve never understood H im in the past.
Putting this understanding into the context of His Son , Jesus Christ and His m issio n, and putting th is into the
context ofthe New Testament call to !ove, it is profound and revolutionary.
xxxiv
Pope John Paul ll talks about understanding the natural methods for the regulation of human fertility by realizing
that it challenges us to:
Respect the bodies of the spouses
Encourage tenderness between spouses
• Favor the education of an authentic freedom
Is an innate language that expresses the total reciproca! self-giving of husband and wife.
Furthermore, he teaches in a very profound and understandable fashion that "contraception :

Is an objectively contradictory language (not giving one's selftota lly to the other)
• Leads to a positive refusal to be open to li fe
And , is a falsification ofthe inner truth of conjuga! !ove.
He goes on to teach us that the differences "both anthropological and moral , between contraception and recourse to
the rhythm of the cycle ... involves, in the final analysis, two irreconcilable concepts of the human person and
human sexuality." 25 (emphasis applied)
This is a significantly meaningful teaching. lt allows us to understandjust how different the C hurch approaches the
whole concept ofhuman sexuality. Like oil and water, the "modem" concepts and th e C hurch 's concepts simp ly do
not mix. Contraception , sterilization and abortion are a li part ofone view ofhuman sex uality while !ove, responsi-
bility, a better understanding of ourselves and how our bodies work, and a respect for one 's se lf and for one 's
spouse are another view ofhuman sexuality taught singularly by the Catho li c Ch urch at the present time.
Pope John Paul ll, in his exhortation to families entitled Familiaris Consortio, introduced the concept ofthe " inner
soul" ofhuman sexuality. He wrote that:
''The choice of the natural rh ythm s in vol ves acceptin g the cycle of the person, that is the woman , and
thereby accepting
• Dialogue
• Reciproca ! Respect
• Shared Responsibility and
• Sel f-control
To accept the cycle and to enter into dialogue means to recognized both the spiritual and the corporal
character of conjuga ! communion, and to live personal !ove with its requirement of fidelity. In this context,
the couple comes to experience how conjuga! communion is enriched with those va lu es of tenderness and
affection which constitutes the inn er soul of human sexua lity, in its physical dimensions also . In this way
sexuality is respected and promoted in its truly and fully human dimension and is never ' used' asan 'object'
that, by breaking the personal unity of soul and body, strikes at God 's creation itself at the leve! of the
deepest interaction ofnature and person." 26 (Emphasis applied)
This contribution by Pope John Paul 11 in language and concept is extraord inary. As one reflects upon the discus-
sions of human sexual ity that ha ve occurred over the last 40 or 50 years, the one thing missing is a better under-
standing of its meaning in human relationships, its meaning to the very nature of lo ve and, asa n extension of that
meaning, a discovery of its "inner soul. " Thus, those who are involved in teaching the natural means to regulate
fertility and , in particular, the CREIGHTON MODEL FertilityCare™ System and NaProTECHNOLOGY (whi ch
has within its very fabric these concepts ofhuman sexuality) become experts in the very fundamental meaning and
significance ofhuman sexuality and, in particular, the discovery ofits " inn er soul. "
The approach presented in this textbook does not see genital contactas an evil but rather a fo rm of sex ual contact
to be placed in to the whole or total perspective o.f human sexuality. lt is a part of human sexuality that, to be best
expressed, must be kept in its proper balance. Some would call this a cha llenge to develop a balanced sexual
ecology. In many ways, this view allows for the couple to see their human sexual ity in the w holeness of its ex istence
XXXV
and not take any component of it out of context or put it out of balance. lt is a challenge towards the development
ofsex ual friendship. With the development ofthis friendship , a couple develops and fosters sexual maturity and
a discovery of its "inner soul."
There will be sorne who will reject this work because ofits close association with Catholic philosophical concepts.
They wi ll say that the Church has no platform on which to speak because of past and certainly present sexual
abuses. For my part, l can understand that. Those within the Church ha ve definitely not practiced ali of what the
Church preaches. But having said that, l ftrmly believe that the Church and Her teachings are divinely inspired.
Unfortunately, the Church , like all other earthly groups , is administered by human beings who are frail and imper-
fect. As Vicki Thorn , cofounder of " Project Rache!" has often said (1 think it is worth repeating here), " the Church
is not a hotel for sa ints but, rather, it is a hospital for s inn ers ." We need to keep these things in perspective and not
let it prejudice our observations.
In NaProTECHNOLOGY, individua Is are called to submit their sexual passions to their reason and to their will.
We are not asking them to do this as ifthey hada " robot-like constitution." But rather, we are asking for them to see
their sexua lity within the context of the wholeness of the human sexual person and to incorporate these concepts
and ideas- through their understanding- into the wholeness oftheir own lives . We do this to help create a para-
digm shift. lt moves peoplefrom a contemporary "sexual license" toan authentic sexualfreedom.
If we ha ve been created " in His image and likeness," then an individual human person can grow closer to God and
better understand Him by understanding and listening to how our bodies work- by understanding the language of
s
the body. The CREIGHTON MODEL System is an authentic language of a woman health andfertility. We have
been called to build a civilization of love.27 As physicians , there is no reason on earth that we should not respond
to this call.
And so this is the stimu lus for the work of the last 28 years that has led to the development of The Medica/ and
Surgical Practice ofNaProTECHNOLOGY. How far NaProTECHNOLOGY will go in the future ofmedicine is yet
to be determined. C learly, it must overcome the resistance people will ha ve to its paradigm shifts. In fact, there may
be no new science that challenges the current paradigms more so than NaProTECHNOLOGY. For it to become
successful, it must overcome not one paradigm shift but multiple shifts in the paradigm (see Chapter 2). This will
be difficult, complex, and perhaps seemingly unyielding. But, in order for us to go beyond the pain and suffering
that our c urrent science has developed, we must make that effort.
In concludin g the preface to this work, it may seem somewhat surprising to the reader that 1 might quote from a
song ftrst sung by El vis Presley. In December 1968, the very month that 1 began my first research in the natural
means to regulate fertility, El vis Pres ley sang a very special song at the conclusion ofhis Comeback Special. While
Elvis Presley's li fe was not always a paragon of vitiue, his music and his talent touched millions. One of those
milli ons was me. From December 1968 up until the present time, the words from lfl Can Dream ha ve echoed in my
mind over and over again. These words ha ve been, to sorne extent, a spiritual anthem to the work presented in this
textbook and 1 wish to share them with you:
~1...e.i-e "'""·Jt !:e Pe..i-c:e

~and understanding sometime
Strong w inds of pro mise
that will blow away
Ali doubt and fear.
'J¡ 'J C-"l-I\. di,e.-"i,ll\.
of a warmer sun
where hope keeps shining
on everyone
Tell me why, oh why
won ' t that sun appear.
xxxvi
We ' re lost in a cloud

with too much rain.
We ' re trapped in a world
that 's troubled with pain.
But as long as a man
has the strength to dream
he can redeem bis soul and fly.
Deep in my heart
there's a trembling question.
Sti 11 l am sure
that the answer is going to come somehow.
Out there in the dark
there 's a beckoning candle.
And while [can think

while l can talk
while 1 can stand
while 1 can walk
while 1 can dream ...
Please let my dream

come true right now
Thomas W. Hilgers, M .D.

Senior Medica! Consultant
Obstetrics, Gynecology, Reproductive Medicine and Surgery
Director
Pope Paul VI lnstitute for the Study of Human Reproduction
Clinical Professor
Department of Obstetrics and Gynecology
Creighton University School ofMedicine
Omaha, Nebraska
xxxvii
References
l. Paul VL encyclical H11111 l11we Vitae, Jul y 25, 1968. NC Ne\\S 15. e\\' American Bible, MallhCI\ 22:36-40.
Service Translation, Pauline Books and Media, 1968. iJ7.
16. Op. Cit., Fides et Ratio, iJ 76.
2. !bid., iJ8.
17. lbid ., iJ80.
3. !bid' iJ9.
18. lbid ., iJ81.
4. !bid., iJIO.
19 . lbid ., iJ82.
5. !bid., iJI 1.
20. Op. Cit., H11111 a11ae Vitae, iJ2 I.
6. !bid., 12.
21. lbid., iJ22.
7. lbid., iJ24.
22. Op. Cit.. Fides et Ratio, iJ88.
8. Op. Cit., iJ27.
23. lbid. , iJI06.
9. Hilgers TW: The Medica! Applications ofNatural Family Plan-
24. Pope John Paul 11: The Theology ofthe Body: Human Love in
ning: A Physician 's Guide to NaProTECHNOLOGY, Pope Paul
the Divine Plan. Pauline Books and Media. Boston, MA. 1997.
VI Instilule Press, Omaha, 1991.
25. Pope John Pau l 11 : Apostolic Exhortation on the Ro le ofU1e
10. John Paul 11 , encyclical leuer Fides et Ratio, Seplember 14,
Christian Family in the Modern World (Fam ili ari s Consort10).
1998.
Daughters of St. Paul. Boston, MA. ov. 22, 1981 , iJ 32.
11. lbid., iJl3.
26. lbid.
12 . lbid., iJ43.
27. Pope John Paul 11. Ew111geli11111 Vitae. An encyclical Ieuer on
13. lbid .. iJ46. the Gospel of Life. March 25, 1995. Libreria Edifrice Vaticana.
Vatican City.
14. lbid ., iJ48.
xxxviii
xxxix
Acknowledgements
The author wishes to acknowledge with gratitude the invaluable role that a number of people have
played in seeing that this project has come to completion.
First and foremost are those research assistants who ha ve provided in valuable aid to the completion of
the data presented in this book. These people include, first of ali , Pamela Yaksich, BS ; Jeremy
Kalamarides, BS; and Paula Maslonka, BS . Additional research assistance was also provided by
Jennifer Davis, Kristina Garnett, Stephen Hilgers, Michael Hi lgers, Paul Houser, Amanda Mafilika
Austin , Anh Nguyen, Rae Nguyen , Jennifer Pavela, Teresa Sobie, Brian Tullius, and Patrick Yeung. In
addition, Nelson Fong, PhD, assisted with sorne of our biostatistical analyses and John Vasiliades,
PhD, served as a consultant in biochemistry. Ken Oyer, librarian at the Dr. John Hartigan Memorial
Library at Bergan Merey Medica] Center, and the librarians at Creighton University and Univers ity of
Nebraska Schools ofMedicine are also acknowledged for their professional support.
The in va luable, expert layout and design services ofVictoria Sage, BSc, and the secretaria! ass istance
of Terri Green along with her assistants, Jean Packard, Anne Au lner and Faith Evans, is gratefu lly
acknowledged.
The work could not have been accomp li shed without the development ofthe CREIGHTON MODEL
FertilityCare™ System and the great assistance of its co-deve lopers, K. Diane Daly, RN , CFCE;
Susan Hilgers , BS, CFCE; and Ann Prebil , RN , BSN , CFCE.
The medica! technicians in the National Hormone Laboratory ofthe Pope Paul V I lnstitute ha ve also
provided invaluable assistance: Barbara Gentrup , Deborah Frahm, and Janice McAlp in e. Our
ultrasonographers, Sandra Keck and Jeanine Johnson are also grateful ly acknowledged.
Our nursing staffheaded by Linda Cady, RN , along with Barbara Schimerdla, RN ; Marlene Beckman,
RN; and Teresa Kenney, APRN, and the assistance ofthe directors ofthe FertilityCare™ Center of
Omaha, Kathy Cherovsky, CFCS , and Jeanice Vinduska, CFCP, FCE, are also gratefu lly acknowl-
edged.
The author wishes to thank Mary Pat Wilson for her artistic skil ls in assisting with the production of
xi
the CREIGHTON MODEL FertilityCare™charts that are included in this book.
In addition , Stacee Mi lan , compu ter graphi cs ass ista nt at Creighto n Uni vers ity 's Bi ocommuni cations
Center is acknow ledged for assisting in the production ofma ny ofthe gra ph s presented in thi s text-
book.
Also recognized are those nur es and technicians from the operating room staff of the Creighton
University Medica! Center and Berga n Merey Medical Cente r who have been most helpful in assist-
ing the surgica l procedures discussed in this te xtbook. The nur es in la bor and delivery and the nurses
on the postpartum and post-surgical recovery floor are also recognized.
Dorothy Dugandzic, Dr. Robert Pi erson , and Dr. Anthony Pi va runus are thanked fo r th eir special
assistance.
The au th or also recogni zes the A merican Academy of FertilityCare Professionals who, over the
last 15 years, ha ve given a forum to the presentation of the ideas presented in this textbook so that they
could be publicly presented , discussed and implemented. Their col leg ial support has been deepl y
appreciated and the development of NaProTECHNOLOGY co uld not ha ve occurred without their
assistance .
Finally, this work also cou ld not have been accomp li shed wit ho ut the financia] support ofthose who
have so deeply believed in this work. This includes many indi vidual and institutiona l donors who
have been extraordinari ly generous in supportin g this effort.
A specia l note ofapprec iat ion , too, to L. Pau l Comea u for hi s su pport and friends hip and to the entire
staff ofthe Pope Pa ul VI ln stitute.
For a ll ofthe above, the au th o r ex presses his deep and s incere appreciati on and gratefu lly acknow l-
edges their ass istance and support .
xli
List of Abbreviations
AAFCP American Academy ofFertilityCare Professiona ls

ACOG American College of Obstetricians and Gynecologists
ACTH adrenocorticotropic hom1one
AJOS acquired immune deficiency syndrome
APGO Association of Professors of Gynecology and Obstetrics
AR+ argon
ART artificial reproductive technologies
ASRM American Society for Reproductive Medicine
ATM atmospheres
BBT basal body temperature

beta-HCG beta human chorionic gonadotropin (or ~-HCG)
BID two times a day
CERT cooperative estrogen replacement therapy

CHO carbohydrates
cm centimeter
CO- negative cumulus oophorus
CO+ positive cumulus oophorus
co 2
carbon dioxide (laser)
CPRT cooperative progesterone replacement therapy
CrMS CREIGHTON MODEL FertilityCare™ System
DES diethylstilbestrol
DHEA dehydroepiandrosterone
DHEAs dehydroepiandrosterone sulfate
DPC Oiagnostic Products Corporation
DSM-IV Diagnostic and Statistical Manual ofMental Disorders (4th Edition)
DUB dysfunctional uterine bleeding
D&C dilatation and curettage
xlii
E1 estro ne
Ez estradiol-17~
E3 estriol
EDC estimated date of confinement
ETA estimated time of arrival
ETC estimated time ofconception
FCCA FertilityCare™ Centers of America

FCCI FertilityCare™ Centers lnternational
FCE FertilityCare™ Educator
FCI FertilityCare™ Instructor
FCMC FertilityCare™ Medical Consu ltant
FCP FertilityCarerM Practitioner
FCS FertilityCareTM Supervisor
FIGO Federation lnternationale de Gynecologie et Obstetrique
FP fami ly physician
FPD follicular phase deficiency
FSH fo llicl e-stimulating hormone
GABA gamma am ino butyric acid

GIFT gamete intrafal lopi an transfer
GnRH gonadotropin-re leasi ng hormone
Hb hemoglobin
HCG human chori on ic gonadotropin
HDL-C high-density lipoprotein cho lestero l
Hg mercury
HIV human immune deficiency virus
HMG human menopausal gonadotropi n
HPV human papilloma virus
hs at bedtime
HSG hysterosa 1pi ngogram
ICD-10 lnternational Classification Of Diseases- 1Oth Edition

ICSI intracytoplasmic spenn injection
IIRRM lnternational lnstih1te ofRestorative Reproductive Medicine
IL-1 interleukin-1
IM intramuscular
IN intake
IS introductory session
ITP intratubal pressure
lU international units
IUGR intrauterine growth retardation (or restriction)
lVF in vitro fertilization
K+3 three days past the last day of clear

KTP potassium titanyl phosphate (laser)
LDL-C low-density lipoprotein cholesterol

LEEP loop electrosurgical excision procedure
LH luteinizing hormone
LMP last menstrual period
LPD luteal phase deficiency
LUF luteinized unruptured fo lli cle
xliii
LUNA laser uterosacral nerve ablation
MCS mucus cycle score

MDQ menstrual distress questionnaire
MFD mean follicular diameter
MPA medroxyprogesterone acetate
µg micrograms
NCL near contact laparoscopy

Nd:YAG neodynium yttrium-aluminum gamet (laser)
NFP natural family planning
NFPMC Natural Family Planning Medica) Consultant
ng/dL nanograms per deci liter
ng/mL nanograms per milliliter
NK (ce lls) natural killer cells
NPT NaProTECHNOLOGY
NS A ID non-steroidal anti-inflamrnatory drugs
NST non-stress test
08/GYN obstetrician/gynecologist
P Peak Day
P+ 7 7 days after the Peak Day
PAS Pontifical Academy ofSciences
PCO polycystic ovaries
PCO D polycystic ovarían disease
PCOS polycystic ovarían syndrome
Peak+ 3- P+ 12 From 3rd through the 12th day post-Peak Day
PEA RS pelvic excision and repa ir surgery
pg/mL picograms per mi lliliter
PID pelvic inflammatory disease
PMD D premenstrua l dysphoric disorder
PMS premenstrual syndrome
PO by mouth
POC po int of change
PP D postpartum depression
PP P postpartum psychosis
PROM premature rupture ofthe membranes
p-va lue probability value
QD every day
Q ID four times a day
QOD every other day
Re retained (cumulus oophorus)

r-HCG recombinant-human chorionic gonadotropin
RI A radioimmunoassay
RR re lative risk
rT 3 reverse triiodothyronine
SAB spontaneous abortion

SHSG selecti ve hysterosal pingogram
SIN salpingitis isthmica nodosa
SP ICE spiritual , physical, intellectual , creative, emotional interaction
xliv
SQ subcutaneous
SSRl selective seroton in re-uptake inhibitor
STD sex ually-transmitted di sease(s)
T3 tri iodothyro nine

T4 thyrox ine
TCFT transcerv ica l catheteri zation of the fallopian tu bes
TID three times a day
TNF-a tumor necrosis factor-alph a
TRH thyrotropin-releasing Hormone
TSH thyroid stimul ating horm one
u-HCG urinary-h uman chorioni c gonadotropin
VDRS vagin al di scharge recordi ng system
ZfFT zygote intrafa ll opian transfer
170HP-C 17 hydroxyprogesterone caproate

170HP-H 17 hydroxyprogesterone hexonate
2W wet without lubri cation
xlv
Special Note
Medicine is an ever-changing field. Standard safety precautions must be followed but, as new re-
search and clinical experience broaden our knowledge, changes in treatment and drug therapy be-
come necessary or appropriate. Readers are advised to check the product information currently pro-
vided by the manufacturer of each drug to be administered to verify the recommended dose, the
method and duration of administration , and the contraindications. lt is the responsibility ofthe treat-
ing physician , relying on experience and knowledge ofthe patient, to determine dosages and the best
treatment for the patient. either the publisher nor the authors assume any responsibility for any
injury and/or damage to persons or property.
The Publisher
xlvi
Disturbing Trends in the Health Care of
Women , Children and Familias
t is truly an honor to be an obstetrician-gynecologist While there continues to be sorne progress made in ali
I and to work in the field ofreproductive medicine. Phy-
sicians in this specialty attend to the unique healthcare
of these areas, sorne truly disturbing trends observed
in the health care ofwomen, children and fami lies have
needs ofwomen. They deliver babies in a way which is developed, over the last 40+ years. lt is vital that these
safe for both the mother and the child. They perform trends be examined and reflected upon so that actions
surgical procedures and correct underlying abnormali- can be taken to reverse them.
ties and difficulties, and they provide medications that
can also cure certain problems or diseases. This is an
exceptiona l privilege. In fact, being a physician, no mat- The Divorce Rate --------~
ter what the specialty might be, is itself a remarkable
opportunity. ln the United States, beginn ing in the early l 960s, a
signi ficant increase in the divorce rate and in the num -
In reproductive medicine, over the last severa! centu- ber ofchildren who have been involved in divorce de-
ries, an incredible amount of progress has been made.
One of the most obvious advances is the reduction in
maternal mortality (Figure l-1). 1 Over the past 200 years,
chi ldbirth-related maternal death has declined signi fi-
cantly, and , at the present time, pregnancy and child-
birth can be considered a very safe experience. Along
with this, there has been an accompanying decrease in
both infant and neonatal mortality rates. 2 Much of the
decline in these areas ofmedicine has resulted from the
introduction ofantibiotics and anesthesia, the ability to
perform certain types of surgical procedures and blood
.01 %
transfusions, and the introduction of other medications ms 1890 1930 1956 1980
Year
that can assist in providing support to critically ill pa-
Figure 1-1: The matern al mortality in deaths per 100,000 live
tients. births over the period 1775 through 1980.1
1
2 The Medical and Surgical Practice of NaProTECHNOLOGY
1,400,000
1,200,000
Number ol children involved in divorces .·
1,000,000
800,000
;;;
.o
E
::¡
z
600 ,000
400,000
200 ,000
1950 1955 1960 1965 1970 1975 1980 1985 1990

Year
Figure 1-2: The number of divorces and children involved in divorces in the United States, 1950-
1990.3
veloped (Figure l-2). Divorce adversely affects adult sion, and somewhat sharp increases fallowing World
relationships, and it also has a generally negative im- Wars l and II. 4 Each ofthese increases were fallowed by
pact on the physical , emotional , and economic well-be- a decline (a lthough the overall trend continued to in-
in g ofthe children involved. 3 crease slowly). These changes in patterns far divorce
are sma ll in comparison to the exponen tia! increase that
In the past, there have been sorne variations in the di- occurred beginning in the early l 960s. lt is legitimate to
vorce rate in the United States. There was a short epi - ask why such a trend occu1Ted.
sode of variation , far example, during the Great Depres-
M ichael 4 has reported a sizable and robust statistical
analys is far the various potential causes ofthis increase
Table 1-1: Why has the
in divorce. He faund that the standard responses such
Divorce Rate lncreased? 1
as change in the divorce laws, unemployment, involve-
ment in the military, or publi c assistance variabl es were
Potential Cause % Responsible'
not majar forces in this increase. Even such th ings as
Changes in divorce laws NPR' income variab les or variables in age composition be-
Unemployment NPR tween the spouses contri buted only moderately. The
Military manpower NPR majar variable that accounted far the increase in di-
Public assistance variables 10 vorce was the introduction, on a widespread sea/e, of
lncome variables 23 the various contraceptive technologies, which inc luded
Age composition variables 25 mostly the ora l contraceptive and intrauterine device,
Contraception diffusion variable' >50 and then fema le and male steri lization (Tab le 1-1 ).
Unaccounted for 6
1. Michael RT: Why Did the U.S. Divorce Rate Double Within a Decade? This rise in the divorce rate has had an enormous im-
Research in Population Eoonomics.6:367-399. 1988. · pact on the living arrangements ofthe children affected
2. Adds up to greater !han 100 percent beca use of overlap of sorne of the
variables. by divorce. The number of children living with both
3. NPR; Not Positively Related biological parents has signi ficantly decreased over the
4. The introduction of technological forms of birth oontrol, especially the last 40 years (F igure 1-3) whi le the number of children
oral contraceptive, and intrauterine device and then. a little later. female
and male sterilization. li ving with their mother on/y has significantly increased
during this same period ofti me (Figure 1-4). This breakup
Chapter 1: Disturbing Trends in the Health Care of Women, Children and Families 3
90.0% ~---------------------..,
ofthe family was bou nd to have a significan! sociolog i-
cal impact. Forexam pl e, it is we ll recogn ized that chi l-
dren have the best chance for bo th psycho logical,
physica l and economic success ift hey are ra ised in fami-
lies where both parents are present and have shown
affirmation and !ove to th e chi ldren .
Percent of Chlldren under Age 18 The rise in the divorce rate since the l 960s parallels the
65.0% Living with Both Biologlc1I Parents > - - - - - - - - - -----<
u.s. 1960-2000 increase in the use oftechnologica l contraceptives (F ig-
60.0% ~-~-~-.......--"--~-~-~-~~-,,,___,
ure 1-5) suggesti ng a close association, as prev iously
1~ 1~ 1~ 1~ 1~ 1~ 1~ 1~ 1~2~ discussed between the two . While sorne have argued
Figure 1-3: Th e percentage of chi ldren under !he age of 18
that the change in the divorce laws in the early l 960s
living with both biological parents, United States -1960-2000.5 led to the increase in th e d ivorce rate, evidence sug-
gests that the changes in the laws followed and codi -
fied social change in stead of preceding and ca using
30.0% ~------------------~ these social changes.4
25.0%
Abortion in the United States ---~

20.0%
15.0% Beginning in the late I 960s, with changes in abo1tion

legislation in various states, the number of abortions
10.0%
began to increase. There was a majo r increase in the
Percent of Chlldren under Age 18 number of abortions perfonned fo llowing the implemen-
5.0% ------------------------------·- Living with thelr Mother Only
u.s. 1960-2000 tation ofthe 1973 Supreme Court dec ision, Roe v. Wade
0.0% --..--....--~-~--.---.----.---.-~-' (Figure 1-6). lt can also be shown that there was a par-
1~1~1~1m1~1~1~1m1~2~
a/le/ increase in the use of contraceptives whi ch oc-
Source: U.S. Bureau of the Census, Internet Release date· June 29, 2001
curred in advance of the rise in ind uced abortion (Fig-
Figure 1-4: Perce nt of chi ldren under the age of 18 living
with their mother only, United States - 1960-2000. 5
90
1,400,000
80
1,200,000
70
1,000,000
60
"
<I>
~
800,000 50 ;:!
o
¡;¡
,,;;;
E ~
z" 40 -<
600,000 ~
~·
30
Percent Using Technological
400,000 Contraceptives 1960-1995
• • 20
Number of Divorces
200,000 United States: 1950-1990
10
1950 1955 1960 1965 1970 1975 1980 1985 1990 1995
Figure 1-5: The percentage of women aged 15 to 45 using technological forms of contraceptives, 1960-
1995, and the number of divorces in the United States, 1950-1990.3·6-10
ure 1-7). While there has been a tendency, over the last in obstetrics, the number of illegal abortions observed
1O to 15 years, to look at small declines in the abortion was low. Fu11hermore, those who argue that we need
rate and view it positively, when looking at abortion contraception in order to reduce the number of abor-
rates one should view the data in perspective by go ing tions sim pl y have no evidence that this occurs, and in
back to the early l 960s. At that time, there were very few fact, the ev idence is to the contrary. Figure 1- 7 strong ly
abortions performed. Since then, however, the in crease suggests that the introduction of widespread techn o-
in abortion has been monumental. logical contraception positively influenced the num ber
of abortions being performed in the United States. The
Some would say that prior to the legalization of abor- exp /osion of contracepti ve avai/ab ility and use has
tion there were large numbers of illega l abortions per- had only one impact- to increase the number ofabor-
fom1ed in the United States with a large numberofwomen tions. lt is al so we ll recognized that those organ izations
dying. However, the author spent six months work ing which are most suppo11ive of contraception are also in
at Cook County Hospital in Chicago prior to the Su- support of abortion.
preme Court decision. During his experience, completely
1800
1600
1400
1200
1000
800
600
400 > - - - - - - - -+----------< Number of Legal Abortions per Year

in Thousands
200 u.s. 1975-1997
o
1960 1965 1970 1975 1980 1985 1990 1995 2000
Figure 1-6: The number of legal abortions per year in the thousands , United
States, 1975-1997-" ·13
1200 ~--------,f------+---------------+60 ~
1000+-- - - ---l' - - - ---,P.,..C-- - - - - - - - -- - - - --+50

.a
"
ñ
e
Number of Legal ;a
aoo+-- - --+- - - --Jc-- - - - - - - Abortions per Year ·40 ª'
"<
e
in Thousands, !!l.
30 ,a
u.s. 1975-1997
400+-- -/--- - - -+--- - - - - - - ---;_.,_ Percenl using lechnologlcal · 20
contraceptives, 1960-1995
200+ -•0--- - - ---.1. - - - - - - - - ---;--.- ~ut7~r 1o~~~~~s 10
+o11.,..:ir-.....-..........,..............,.........,.............,..........,....,....,...,,....,.....,....,,....,.....,....,,....,.....,....,....,....,......-+ o
o -l-.-.-+"!......
1960 1965 1970 1975 1980 1985 1990 1995 2000
Year
Figure 1-7: The number of legal abortions per year in the United States and the
percentage of women age 15-44 using technological contraceptives , 1960-1995.6 · 13
Chapter 1: Disturbing Trends in the Health Care of Women, Children and Fami lies 5
Unmarried Parenthood _ _ _ _ _ _--. Drug Use and Crime Rates- - - - --.
Since the early l 960s, there has also been a six- to seven- During this same period of time, the estimated violent
fold increase in the num ber of unmarried women who crime rate has also increased dramatically (Figure 1-1 1)
have given birth (Figure 1-8). While the widespread a long with the percentage of juveniles who ha ve been
ava ilability of contracepti on and abortion promised to taken into police custody and referred to either a crimi-
reduce thi s trend, it is notewo1ihy that the only impact nal or adu lt court (Figure 1-1 2). Concomitant with these
observed has been to increase the number of births to increases has been the in crease in drug use among teen-
unmarried women. ln fact, the pregnancy rates (which agers. In Figme 1-13, the increase in the number ofteen-
differ from the birth rates), among teenage women age agers between 12 and 17 that became new cocaine us-
15 to 19, has increased significa ntl y during this same ers is shown.
period oftime (Figure 1-9).
Child Abuse and
Neglec1
1,000.000
Child Abuse and Neglect -----~
930,001
1996
790,526
Child abuse and neglect figures are difficult to obtain 1990
669,000
because, over the years, there has not been an orga- 1976
500.000
ni zed effort to coll ect thi s data in a universally accept-
able form. Nonetheless, it seems quite clear that the
number of children who are in vo lved in both chi ld abuse
and neglect situati ons has increased along with the in -
1975 1980 1985 1990 1995 2000
creased di vorce rate, the increase of children born to Vea•
unmatTied women , the increased use ofcontraceptives, Figure 1-1 O: The number of children affected by child abuse
and the increase in abortion (Figure 1-1 O) . and neglect in th e United States from 1976 through 1996. 16·17
Percent of Births to
30 Unmarried Women USA
1960-1997
25
20
1
....
10·
Estimated Vlolent Crlme Rate (per 100,000 lnhabitants)

100 1- - - - - - - j of Offenses Known to Pollee
u.s. 1960-2000
o .___..___..___ ..___ ...__ _.__ _.__ _..__ _..__
""
_.__~
Vea•
1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005
Figure 1-8: The percentage of births to unmarried women in Figure 1-11: The estimated violen! crime rate (per 100,000
the United States, 1960-1997.14 inhabitants) , of offenses known to police, in the United States
from 1960-2000.1ª
Pregnancy Rates
9% t-- - - - - - - - - - - - - - - - - - --1
12s Teenagers Age 15- 19
1972- 1999
8% t-- - - - - - - - - - - - - - - - - - --1
3% E--:::;;J->.rF=------ - - - - - --=- -- --1

2% l=-----1-~----<0.
pe~rc~en~truo¡~stn~
·b~ut~
lo~
n o~rO.
Ju~ve~nlli
ile~s~takhe~
n~lnt~ol
Pollee Custody by Method of Disposition
25 u.s. 1972-2000
0% ~--~---'-----'-------'-----'----'--'
1970 1975 1980 1985 1990 1995 2000
1970 1975 1980 1985 1990 1995 2000
Figure 1-12: The percent distribution of juveniles taken into
Figure 1-9: The pregnancy rates in teenagers age 15-19 in police custody and referred to criminal or adult cou rt in the
the United States , 1972-1999.1s.•6 United States, 1972-2000. 18
6 The Medica! and Surgica l Practice of NaProTECHNOLOGY
35 20.0
Suicide Rate (per 100,000 Persons In
- . - 12to11 Rates for New Cocalne Users 18.0 Age Group) for Persons 15-19 Years of Age
12-17 Years of Age per 1000 Persons
30
Years of Exposure 1965-1998 16.0
_.,_ A111--...1s-t1
25 14.0 ~ ...... . - 1s-11 - - - - ---.t'-- - - --\-- -- 1
20
10.0 t-----------,---~,,C---'lc------l
15 8.0 t---------T----7"~----------l
6.0 E-- - - --:::11""-- -:;;11""-- - - - - - - - - --t

10
4 .0 ~-!:~~~--=::::::::::;;;;¡¡~~---1
2.0
o.o c;__ _. J . __ __ . __ __ . __ __ . __ __ . __ __ . __ __ ,
0 L·- -.._...::::.._.1..-_--''----'----'---.i..---'----'
1940 1950 1960 1970 1980 1990 2000 2010
1960 1965 1970 1975 1980 1985 1990 1995 2000
Figure 1-13: The rates for new cocaine users in young people Figure 1-14: The suicide rate (per 100,000 persons in the
age 12-17 per 1000 persons by year of exposure , 1965- age group) for persons age 15-19.18
1998.19
Suicide and Depression ____ _ _~ more prevalent.
The suicide rates for young people aged 15 to 19 has Depression and sexual activity have been evaluated in
also increased signifi cantly. Suicide is now the third teenage boys and girls. Sexua lly active teenagers de-
leading cause of death among teenagers in the United scribe themselves as " depressed somet im es ," " de-
States .20 ·2 1 In crease in the su icide rate has been signifi- pressed a lot" or " depressed most/all ofthe time" more
cantly higher for you ng teenage boys than it has been frequently than teenage rs who are not sexuall y active
for teenage girls (F igure 1-14). (Table 1-2). This finding is stronger among teenage gi rl s.
In fact, when surveyed , the majority ofsexually active
Depression is we ll-recognized as the major cause ofsui- teens indicated that they wished they had waited longer
cide. With the extraord inary socio logica l changes that befare beginning their sex ual activi ty (Tab le 1-3). This
have occurred over the last 40 years w ith the disinte- finding is, aga in , more prominent among teenage g irl s
gration ofthe fam il y and the fragmentat ion ofparental than it is in teenage boys .
support, it is not difficult to see why depression is now
Table 1-2: Depression and Se;\.'Ual Activity
Never/Rarely Oépréssed Depressed Oépressed Most

Depressed Sometimes A Lot Ali of the Time
Boys 14-17
Sexually active 63.3% 28.4% 5.0% 3.3%
Not sexually active 76 .2% 20.3% 2.6% 0.8%
Girls 14-17
Sexually active 36 .8% 37.9% 15.5% 9.8%
Not sexua lly active 60.2% 32.1% 4.9% 2.8%
1. Source: National Long~udinal Survey of Adolescent Health, Wave 11, 1996. Cited in: A Report ofthe Heritage
Center far DataAnalysis . Recker RE , John son KA, Noyes LR: Sexually Active Tee nagers are More Likely to
be Depressed and to Attempt Suicide. The Heritage Foundation, June 2, 2003.
Table 1-3: The Majority of Sexually Active Teens Wish They Had
Waited Longer before Beginning Sexual Activity 1
Wish They Had Wa ited Longer Ali Sexua.lly Sexually Sexually

before Starting Sexual Activity Active Teens Active Boys Active Girl s
Ye s 63% 55% 72%

No 32% 39% 25%
1. Source: National Campaign to Preven! Teen Pregnancy. June 2000. NOTE: Survey covers sexually active teens
aged 12 to 17. Cited in : A Report of the Heritage Center far Data Analysis. Recker RE , Johnson KA, Noyes
LR: SexuallyActive Teenagers are More Like/y to be Depressed and toAttempt Suicide. The Heritage Foundation,
June 2, 2003.
Chapter 1: Disturbing Trends in the Health Care of Women , Children and Families 7
Teenage SexualitY --------~ what is referred to as an "atonement pregnancy" fol -

lowing the abortion (usua lly within the next year).
Pl ann ed Parenthood 's call is that teenagers "are going
to have sex anyway no matter what we do" so contra- There is a striking relationship between the use of alco-
cepti ves should be widely available to them. However, hol and subseq uent sexual activity rates. For those
data suggests that thi s is incorrect. There is a distinct teenages who have used alcohol recently, there is a
relationship between sex ual va lues and sexual activity greater than six-fold increase in the percentage engag-
rates. The sex ual activity rate was nearly 1O times less ing in sexual activity (F igure 1-16). Thus, there is a strong
(7 .8 percent) for those who strong ly agreed with the link between the use of alcohol and subsequent sexual
statement, "lt is against my values for me to have sex activity. Although television advertisements speak
while 1aman unmarried teen" than those who strongly strongly against the use of drugs and alcohol , few, if
di sagreed with that statement (72.4 percent) (F igure 1- any, have made the connection to their associated
15). This type of data suggests that if teenagers are moreas in premature sexual activity.
adequately trained in a va lue forrnation setting that wi ll
allow them to understand th e potential harm that can
come from sexual activity at that age, they will see to it Prematurity and Low Birth Weight _~
that their sexual activ ity significantly decreases. Fur-
therm ore, it has been shown that the recidivism rate There has been anear doubling in the prematurity rate
following the use of contraceptives (with regard to sub- (births at less than 37.0 weeks gestation) in the United
sequent pregnancy) is very hi gh. The same is true for Sta tes sin ce 1967, and the prematurity rate continues to
yo ung women who have abo1iions. They often have increase (Figure 1-1 7). This is extraordinary given the
relatively widespread avai lab ility ofperinato logists who
are specifica ll y trained in the management ofhigh-risk
pregnancies. Their presence has made no identifiable
Relationship Between Sexual 724
70 Values and Sexual
impacton the prematurity rate in the United States. The
Activity Rates hi gh prematurity rate is a nationa/ tragedy and is linked
60-1--- - - - - - 58.5
"lt is agalnst my values lor me to have
sex while 1am an unrnamed teen •
to a variety of different problems that ha ve been dis-
.~ 50 cussed (including the increased rate of teenage preg-
ll e
~ ~40 - nancies and, as wi ll be poi nted out later, the increased
~a.
"' 30-
use ofartificial reproductive technologies with their in-
crease in multiple pregnancies and the increase in sexu-
ally-transmitted diseases).
In Figure 1-1 8, the increasing number of babies born

S1rongly Agree Agree Not Sure Oisagree Strongly Disagree
with what is considered low birth weight (less than 2500
Figure 1-15: The relationship between sexual values and grams) and those born with very low birth weigh t (less
sexual activity rates . The response to the statement, "lt is th an 1500 grams) are also shown over the last 20 years.
against my val ues forme to have sex while 1 aman unmarried
leen" compared to involvement in sexual activity. Based on a This increase significantl y damages the health ofthese
survey of 1537 students , 15 to 17 years old. 22 neonates.
Alcohol Use and Multiple Pregnancies -------~

_ Sexual Activity Rates _ _ _ __
70
Percent Who Have Ever
Had Sexual lntercourse
60 -- - - - - - - - - - - - There has been a large in crease in the number of mul-
tiple pregnancies over the last 20 years. The number of
h
~a.
50 - - -
40- - - - - - - - - - -
- - - - - - -·
triplets and other high-order multiples has increased
more than four-fo ld during this period oftime (Figure 1-
30- - - 19). This is undoubtedly related to the number of artifi -
cia l reproductive technology cycles that have been
started for the treatment of infertility (Figure 1-20). These
approaches to treatment are associated with very high
No Orinking Used Alcohol Been Orunk Drunk Recently
rates of multiple pregnancy ranging from 25 to 50 per-
(20.4%) (30.4%) (25.2%) (24.1 %)
cent.
Figure 1-16: Comparison of the use of alcohol with sexual
activity rates (p<.001 , chi-square analysis). 22
8 The Medical and Surgical Practi ce of NaProTECHNOLOGY
Prematurity Rates In the

12.0 - United States: Births < 37 11 .s - 11 .9 -
11 .6 11.6
Weeks Gestation 1967-2001 11.4
11 .0
11 .0 11 .0,1.0 11.0 ..____
10.6 10.6 10.8 10.7
10.2 10.2
- 10 .0 9.8
10.0 ..____
e:
Q) 9.4 9.5 9.6
~ 9.4
Q)
o._ 9.0
8.3
8.0
7.0
6 .7
6 .0 1
rfi-
' ' ' ' '~ ~ ~ ~ ~ '~ ~ ~ ~ ~ ~ ~ 'D ~ ~ ~ ~ ~ ~ ~ '~ ' '
~ ~~~~~~~~~ ~ ~~~~~~~~~ ~&
' ~ ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ~ ~
Year
Figure 1-17: The prematurity rate in the United States (births less than 37 .0 weeks gestation) 1967-
2001 .23-26
8 . 5 ~----------------------------
Percent of Births Low Birth Weight
(<2,500 gms)
B.O+-- - -
_. ____¡
7. 5 +----------------------~........~==-
e
¡'¡
7.0-1- - - - - - - -
;;; 6.5+-- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 1
a.
-----------
Percent of Births Very Low Birth Weight
(<1,500 gms)
1.5+-- - - - - - - - - - - - - - - - - - - - - - - - - - - --l
1.0-1-- - - - - - - - - - - - - - - - - - - - - - - - - - - - - '
1980 1985 1990 1995 2000
Year
Figure 1-18: The percentage of births by low birth weight (less than 2500
grams) and very low birth weight (less than 1500 grams ) in the United States
1980-2000.27
70000
35.0 ~------------------~ 250.0 ~ TotalcyclH peryear
...,.._ nwini'-per1 ,000 1tv1 bltth1
65000
30.0 - ~ TrlplM,.t1per lOO.OOOllY1blrth& - - - - - - -=,----- --1
200.0
~ 60000
:3
20.0 -l----,--;=--........-.=c:._-----+-- - - ---1 150.0 t
! 55000
15.0 -1-- - - - - - - - - - -- - - - - - ---1 100.0 l s
~ 50000
Birth Rates of Twln and Triplet or 50.0
Higher Order Pregnancies Total Assisted Reproductlve Technology
u.s. 1980·2000 45000 ! -- - - - ' ' - - - - - - - - - - Cycles Started per Year
O.O 1--- -...,..-- ---.-- --...-- -....-- --,-- ---1 O.O u.s. 1995-1999
1975 1980 1985 1990 1995 2000 2005
40000
1994 1995 1996 1997 1998 1999 2000
Figure 1-19: The birth rate of twin and triple! or high-order Figure 1-20 : The total number of assisted reproductive tech-
pregnancies in the United States, 1980-2000.28 ·29 nology cycles that were started per year, 1995-1999 in the
United States.30
This is tragic! The infant mo11ality rate fortriplets of all birth). 32 At the same time, modern medicine offers these
gestational ages is 10 .9 times greater than for singleton women the artificial reproductive technologies such as
live births (Tab le 1-4). Babies from high-order multiple in vitro fert ilization. However, in a one-year period of
pregnancies are born ata much lower birth weight (Fig- time, 30,000 babies are born as a result of IVF. Thus,
ure 1-21 ). What is not reflected here is the significant these most "technologically advanced" programs as-
increase in neonatal morbidity among those babies who sist only 0.5 percent of a li women in the Un ited States
survive their prematurity. lt is wel l recognized that such who have impaired fecundity. These programs a lso come
morbidity is significantly increased and thus the health with multiple pregnancies, frozen embryos, surrogacy
ofthese children is compromised . programs, postmenopausal motherhood, embryo experi -
mentation and so forth.
lnfertility Rates ---------~

Sexually-transmitted Diseases ---~
There has been an increase in the number of women
who have experienced both childlessness and infertil - There has also been a sign ificant increase in the occur-
ity. These increases in the infertility rates have been rence of sexua ll y-transmitted diseases. While the re-
well documented at this point in time. It is estimated ported rates of gonorrhea (F igure l-22) ha ve decreased
that there are 6.2 milfion women in the United States over the last 30 years (preceded by a marked increase),
who have impaired fecundity (this includes not only there has been a significant increase in human papil-
infertility but also previous abnormal reproductive out- loma virus (genita l warts) (Figure 1-23) and Chlamydia
comes such as miscarriage, ectopic pregnancy, and still - infection ( especially among women) (Figure 1-24). In
addition , the number of ectopic pregnancies in the
United States as measured by both inpatient and out-
Table 1-4: Infant Mortality Rates by Plurality

and Age of Mother:
500
United States, 1995-1997 1
400
Age of Mothe.r Twin Triplet/+ Síngleton
¡
lnfant deaths per 1,000 live bírths
t 300
~-
Ali ages 32 .0 71 .8 6.6
U nder 20 years 63 .1 172.2 9.8
20-24 years 42 .1 133.8 7.4
! 200
25-29 years 30 .1 96.4 5.5 ~

30-34 years 25.2 60 .7 5.2 100
35-39 years 22 .6 46 .7 6.2
40-44 years 20.4 38 .5 8.1
1. lncl udes quadruplets and oth er higher arder multiple births. From: 1970 72 74 76 78 80 82 84 86 88 90 92 94
Trends in Twin and Triple! Births:1980-1997. National Vital Statistics
Reports. 47:4. 1999. Figure 1-22: The reported rates of gonorrhea in the United
States, 1970-1994 and the year 2000 objective.33
360
320
40 Singletons
"'" "'
280
Triplets
30 /
e:
Ql
e
Ql
20 / \
Cl.
10
\
80
.,,,,,,,.
o
Less 2,000- 4,000
than 500 2,499 ormore 1966 69 72 75 78 81 84 87 90 93
Grams Figure 1-23: The number of initial visits to physicians' offices
Figure 1-21 : The birth weight distribution for triple! and other for human papilloma virus (genital warts) in the United States
high order mu/tiple births and singleton births, 1992-1994.31 from 1976-1993.33
patient estimates (Figure 1-25) has also increased sig-

nificantly. These increases are directly attributable Table 1-5: Estim.ated Annual New Cases of
to the sexual promiscuity that has accompanied the epi- STDs in the U nited States
demic increase in these diseases.
Estimated number
STO of new cases
lt has been estim ated that there are over 15 mi Ilion new
cases of sexually-transm itted diseases (STDs) in the Human papilloma virus 5,500 ,000
United States each year (Tab le 1-5). Furthem1ore, there Trichomoniasis 5,000 ,000
are well over 50 miL/ion total cases of viral STDs in the Chlamydia 3,000 ,000
United States (Table 1-6). The direct medica! costs for Herpes 1,000,000
caring for this epidemic is $8.4 bi//ion p er year (Table Gonorrhea 550 ,000
1-7). Hepatitis B 77 ,000
Syphilis 70 ,000
Women who have used oral contraceptive are now HIV 20 ,000
shown to be at an increased risk of invasive cervical 1. From: Sexually-Transmitted Diseases in American: How many cases
cancer (F igure 1-26). This is related to the epidemic in and at what cost? American Social Health Association. Kaiser Family
Foundation. December, 1998.
human papilloma virus infection ofthe cervix, which is a
sex uall y-transmitted disease. Odds ratios of the effect
of oral contraceptives on the risk of cervical cancer and
cervical neoplasia (not just invasive cervica l cancer)
are shown in Figure 1-27.
While some have argued that there are health benefits Table 1-6: Total Number of Cases of
to the use of oral contraceptives and that the ovarian Viral STDs in the United States
and endometrial cancer rates have been shown to de-
Estimated total
STO number of cases
300
Herpes 45,000,000
Women
250 Human papilloma virus 20 ,000 ,000
1~ Hepatitis B
HIV
750 ,000
560 ,000
I· 150 1. From: Sexually-Transmitted Diseases in American: Howmany cases

and at what cost? American Social Health Association. Kaiser Family
! 100 Foundation. December, 1998.
j
so
- - - - - - - - - - - Mtn
19M as 86 &7 aa 89 90 91 92 93 94
Figure 1-24: The rates of Chlamydia infection by gender in

the Un ited States, 1984-1994.33
Table 1-7: Estimated A nnual Medica! Costs for
Treatment of Sexually-trans mitted Diseases
in the United States 1
120
- 1970-1992 lnpatlent Estlmates
, _.
100
• 1992 lnpatient 1nd Outpatient Estlmate ,, Estimated
l
annual cost
80
The major curable STDs $1 ,974 ,600,000
60 in the United States
.R 40 The major vira l STDs $6,422 ,200 ,000
§
z in the United States
20
Estimated total cost $8 ,396,800,000
o....,......,..""T"..,.....,......,.............,_,......,..""T"..,......-.,....,,.........-..........-.--.-..-...-~
1m ~~ 1m 1m~ oo 1™ 1~ 1~ 1m 1m 1. From: Sexually·Transmitted Diseases in American: How manycases
Year and at what cost? American Social Health Association. Kaiser Family
Foundation. December, 1998.
Figure 1-25: Number of ectopic pregnancies in the United
States, 1970-1992. This includes inpatient estimates and 1992
outpatient estimates. 34.35
10.0
crease with the ir use, the increase in cervical cancer and
also the increased relative risk ofbreast cancer in women
~
who have long-term oral contraceptive use seems to be 1 -

incontrove1tible at this point in time (Figures 1-28 and
1-29). There is also a well-recognized association be-
1
¡ ¡ 1
1t ¡
tween induced abortion and the development of breast
canceras well. --
The issues related to cancer and contraception also point 0.1

out the shift that has occurred in medicine over the last ~ TI ~ U U U V W W W W WH
few decades from one whose focus is on the individual Summary RR= 1.4 (95% CI, 1.3-1.6)
patient to one whose focus is more generic. This is il- Fi gure 1-28 : The relative risk of breas! cancer in women
lustrated by the focus provided in a recent review ofthe under the age of 45 with long-term use of oral contracep-
net effect of oral contraceptive use on the risk of cancer tives :A summary of the results of 12 case-controlled stud-
ies.38
in women in the United States. 40 After recognizing the
net increase in the number ofbreast, cervical, and liver
10.0
!
.-
...
.
¡¡¡
1.0
. .. .
- ·:·
~
o;
"'
0. 1~--,---.--....--.---....---,---r-....---.---r~
0.1~--,.-..----r-..---r---.-..,..---..-....---.--,---,---,..--~ 10 11
10 11 12 13
Years of OC Use Total Years of OC Use befare first·Term Pregnancy
Figure 1-26 : The relative risk for the development of invasive Fig ure 1-29 : The incidence of breas! cancer in women
cervical cancer in women under the age of 60 years by how younger !han the age of 45 years : The relative risk compared
long they use the oral contraceptive.A summary of eight sepa- to the total number of years of oral contraceptive use befare
rate studies.36 a first-term pregnancy in nine different studies .39
Effect of Oral Contraceptivas

On Risk of Cervical Canear
In Women With HPV 4.01 4.03
4.0 -
,g
~ 2.92
~ 3.0 2.82
-
2.0
1.67
1.29 1T.3 8 1T
.42
~ T
1.0 1--..-.....,......;;;m;;.....,.._..11.._,.,......a..,....,......a.......,.--11-...,..-&.......................................-1.._.,.................
Figure 1-27: The effect of oral contraceptives on the risk of cervical neoplasia and cervical
cancer in women with human papilloma virus, expressed in odds ratios .37
12 The Medica! and Surgical Practice of NaProTECHNOLOGY
Men
65 HIV lnfection
60
55 !1i~~~i~a~ ~juries
50 Heart Disease
.,,'2o 45
.
:; Suicide
Q. 40
&. Cancer
§ 35
Homicide
ª.
30
25
!
~ 20
Liver Disease
Stroke
"' 15
10 Diabetes
5
o
1982 1984 1986 1988 1990 1992 1994
Year
Women
30 ~~.-
..-..-..-..-••-..-.-.. -.. -••-..-••-..-••-.-.. -..-..-..-.-.. -..-..-. -.. -. .-..-..-.-.. -. .-. .~~~~
. ..... . ' •,
Cancer
~i~~~°!!'.'~juries
25
HIV lnfection
!.. 20 Heart Disease
l§ ............. .... ._ ......... Homicide
~f
15
-·-·-·-·--·--· ............. Suicide
! 10
-··-··-··-··-··-··-··-··--··-·· Stroke
~ ...... Liver Disease
... .:: ::::;:=::::-: :-::-:,.. ..... __ _
------
---------- Diabetes
1982 1984 1986 1988 1990 1992 1994

Year
Figure 1-30: The leading causes of death among men (upper gra ph) and women
(lower graph) 25 to 44 yea rs of age in the Un ited States 1982-1994.The rising
incidence of mortality from HIV infection is shown .41
20 20
- Percent
- Number
15 15
~
-o
...
e:
:; ....
~
o
¿ 10 10 ;:;
~
~
a
~
u
5 5
o 1989 1990 1991 1992 ¡993• 1994

o
1985 1986 1987 1988
Year
Figure 1-31 : The number and percentage of HIV/AIDS cases among women aged ~ 13 years of
age: United States, 1985-1994.42
cancer victims amongst oral contraceptive users and a women greater than 13 years of age has also increased
net decrease in endometrial and ovarian cancer victims significantly over the years (Figure l -31 ).
in simil ar users, the conclusion is reached that, "from a
population perspective, there are on ly sma ll cancer-re- Condom distribution is usually proposed to eventually
lated risks and ben efits associated with oral contracep- decrease the spread of the Al DS virus. However, data
tive use and, on balance, the net effect is negligible." now strongly suggests that there is a parallel increase
Thi s approach depersonal izes health care and places it in condom distribution and spread of the HIV/AIDS
on ly in aggregate terms. Medicine should be at the ser- virus (Figure 1-32).
vice ofthe human person. For the woman who has fallen
victim to a breast, cervical, or liver canceras the result
of her use of ora l contraceptives, the effect on her health Federal FundinQ --------~
is not we ll served by being described as "negligible."
Many people wou ld argue that while these trends have
The AIDS virus has al so increased significantly. Whi le occurred, they can be reversed by increasing the dol-
sorne of these infections are related to blood transfu- lars that are spent both on research and distribution of
sions and unclean needle use, the overwhelming major- technological contraceptive service and abortion. How-
ity are related to sexual promiscuity in both men and ever, there has been a significant increase in the federal
women. Acqu ired imm une deficiency syndrome is a fa- dollars given to support AIDS research and also a sig-
tal illness and the increased mortality rate for both men nifi cant increase in the federal funding of Planned Par-
and women has been well documented (Figure 1-30). enthood over this same period of time (Figure 1-33).
The number and percentage of AIDS cases among The incidence and prevalence of all of the conditions
mentioned ha ve increased sign ifi cantly, in spite of, the
increase in the number of dollars spent for programs
that largely continue to support sexual promiscuity, the
use of contraceptive agents, steri1ization, abo1tion , and
the artificial approaches to reproduction.
Summary and Conclusions -----~
This chapter opens The Medica/ ami Surgical Prac-

tice of NaProTECHNOLOGY for a good reason. Over
the last 40 years, there has been a we ll-documented
disintegration ofthe family and with ita we ll-docurnented
increase in adverse sociological and medica! outcomes.
1984 ·2003 There is evidence to suggest that this is, at least in part,
Figure 1-32: Th e global increase in HIV/AIDS infections com- related to the widespread ava ilability of contraceptive
pared to the number of condoms distributed abroad by the agents, which have clearly increased sexua l promiscu-
United States Agency for lnternational Development (USAID).43 ity.
25
º·º - Total taxpayer money to PPFA via
government grants and contracts
from 1987-June 2002
200.0 $2,454,900,000
.
~
'¡¡ 150.0
"O
"'e:
~ 100.0
:i
so.o
o . o~-~...._-. _ ____.______._ __._____..___.__.___.._. -__._

1987 1988 1989 1990 1991 1992 93-94 94-95 95-96 96-97 97-98 98-99 99-00 00-01 01-02
Figure 1-33: The federal funding of Planned Parenthood from 1987 through
2002. 44
14 The Medical and Surgical Practice of NaProTEC HNOLOGY
This chapter has not addressed the influence of pomo- pregnancy problem. It is referred to as " selective reduc-
graphic literature or the widespread availability ofsexu- tion. " In this procedure, one or two or more of the ba-
ally alluring content oftelevision programs, movies, and bi es are aborted so that the pregnancy is "reduced" to
so forth. Beginning in 1956, there was a well-documented one or two infants, thus reducing sorne of these risks.
increase in the sexual explicitness ofthat literature. 45 It And yet, this is an ethical and service principie which is
has been said that this was the beginning of the sexual based on the development or protection of life through
revolution. Few can deny that it was the beginning of a its destruction . In a society which generally prides it-
shift in sexual behavior. While many would call it revo- self on the respect for life, this is ultimately incompat-
lutionary, one could argue that the "sexual revolution" ible.
has stifled human growth and development, trivialized
sex and produced an epidemic of victims. Instead of it There are severa! reasons why prematurity rates and
being sexually revolutionizing, it has really been sexu- the occurrence of low-birth weight infants have in-
ally retarding. creased. As will be discussed later in this textbook on
the prevention ofprematurity, there is a strong sugges-
The health ofwomen, children and families has distinctly tion that there is a microbial explanation for sorne ofthe
been harmed by these changes of the last 40 years . premature births that occur. This also may be related to
Many have argued that these are victimless trends. And the fallout from the widespread sexual promiscuity that
yet, the data shown in this chapter and well-documented has occurred in this nation and much of Western cul-
demographic analyses clearly indicate the opposite. The ture.
tragedy is that this is a revolution whose majar victims
hove been innocent children, although adult men and The widespread increase in sexually-transmitted dis-
women have also been significantly victimized. eases affects mostly women. Menare often not affected
(with the one exception of AIDS). Women need to be-
There is evidence to suggest and a strong trend analy- come more sexually savvy. That is to say, they need to
sis to show that the increase in divorce, which leads to become more assertive with regard to the protection of
an increase in children being affected by divorce and their own sexuality, their own bodies and their own self-
no longer living in a family unit, is connected to the respect. To continue submitting themselves to the harm
increase in sexual promiscuity, which has been fueled of abortion , sexually-transmitted d iseases , multiple
by the widespread infusion oftechnologically-oriented births, premature biI1h, the delivery ofa low-birth weight
contraception , and ultimately the increase in abortion infant and the risk ofmarriage dissolution is foolhardy.
rates. Contrary to what many have suggested, there is This needs to be reversed and women mus/ take the
simply no data to support the use of contraception as lead in seeing that this is accomplished'
the answer to abortion. In fact, the data clearly shows
the close correlation between the rise in technological They do not need to do this out ofresentment, although
forms of contraception and the subsequent rise in abor- their resentment would be very understandable . Wornen
ti on . Furthermore , it is becoming clear that should approach it by challenging society to respect
p erinidational abortion has become an emphasis. Oral thern as human persons who have dignity and integ-
contraceptives are, to sorne extent, aborti facient. Intrau- rity; to respect their bodies as the nurturers oflife, and
terine devices are abortifacient (at times). Embryo ex- to respect the offspring that may be created in the un ion
perimentation, the frozen embryos that are stored in between man and wornan. While I do not in any way
freezers throughout the United States and in other for-
eign countries, the push towards cloning, and other
forms of experimentation are the fall-out from this same
"revolution." Table 1-8: Trends lnvolving the
Endangerment of Women: 1956-2004
A woman with the problem of infertility, vulnerable in
Physical Endangerment Emotion al Endangerment
the position she finds herself, goes to her phys ician to
seek care for that problem and is offered artificial repro- • Breas! cancer • All physical endangerments
• Cervical cancer • Divorce
ductive technologies. She does not expect to be deliv- • HPV • Teenage suicide
ering triplets, quadruplets or quintuplets. Superficially, • Abortion • Teenage pregnancy
• Ectopic pregnancy • Abortion
it may even be enticing. And yet, the data is clear that • Multiple pregnancy • Child abuse and neglect
these pregnancies and the children resulting from them • HIV/AIDS • Prematurity
• Chlamydia • Low birth weight infants
suffer enormously. Those who promote contraception
and abortion ha vean abortive solution to the multiple-
The Domino Etfect of Seismic Shifts In Trends

That Endanger Women , Children and Families
Sexually Explicit Literature -t-- - - - - - - - - - - - - - - - - - - - - - - - - -

Children lnvolved In Divorce
Technological Contraceptives
Teenage Suicide
Divorce
Violent Crime Ratas
Gonorrhea
Taenage Pregnancy Rates
Births To Unmarried Women
New Cocaine Users Age 12-17
Human Papilloma Virus
Prematurity Ratas
Living Arrangamants of Children
Abortion
Ectopic Pregnancy
Juveniles In Court
Child Abuse & Neglect
Multiple Pregnancy Rates
Frozen Embryos
HIV Deaths - Men
HIV Deaths - Women
Chlamydia lnfection
AIDS In Women
Landmark Events - Expansion of Birth IVF

Sexually Expfictt Control Legalization
Literature Pill of Abortion
Figure 1-34: The domino effect of seismic shifts in trends that endanger women , children and families .
believe that men are " hopeless" in this endeavor, the

author's more-than 30 years ofwork with both men and
women has indicated that women have a far more sensi-
Table 1-9: T rends lnvolving the tive, intuitive and palpable connection to these events.
Endangermen t of Children: 1956-2004 Men are often concerned with other issues. That does
not make them bad by nature. They can be educated
Physical Endangerment Em otional Endan germent and then will often respond positivel y. In fact, one of
• Teenage suicide • Divorce
the reasons the author has been invol ved in this work
• Violent crime • Depression (suicide) so mu ch over the years, is because of the positive and
• HPV • Teenage pregnancy
• Prematurity • Unmarried mothers
liberating impact it can ha ve on men .
• Low birth weight • Living arrangements
• Abortion • Abortion
The major story in health care over the last 40 years or
• Cocaine use • Child abuse and neglect
• Juveniles in court more has been the epidemic increase infamily violence
• Child abuse and neglect that have been brought with us from the 20th century
• Multiple pregnancy
• Chlamydia into the 21 st. The very way in which medicine is prac-
ticed has endangered the health of women (Table 1-8),
children (Table 1-9) and families (Table 1-1 O). The evi-
dence cited here is from nationally recognized data col-
lection systems. !t tells the story of a society that has
los! its fundamental moorings by sacrificing its most
importan! resources. Our priorities have undergone a
16 The Medi cal and Surgical Practice of NaProTECHNOLOGY
seismic shift and with il, /eft a lrai/ of viclims (F igure 1-

34). One would need to be incredib/y insensilive 110110 Table 1·10: Trends lnvolving the
be able to see the conneclions and lhese victims. Endangennent of Families: 1956-2004
This book does not prom ote the notion of go in g back-

wa rds to the l 950s. There has also been a good dea l of • Divo rce • Living arrangement of child ren
• Children affected by divorce • Abortion
positi ve progress that has been made over th ese same • Teenage suicide • Juveniles in court
40 years. But, at the same time, the data shows that it is • Teenage drug use • Child abuse and neglect
our curren! culture and its priorities and beha viors • Premature bi rth • Sexually explicit literature
• Low birth weight
that have created these dangers . The data also shows
that fa mil y vio lence, to thi s great extent, need 1101 ex ist.
Ultim atel y, th ere needs to be another response. The

portian of that response being proposed in thi s text- tive techno log ies that ha ve been used over the last 40
book is a new wome n's hea lth science referred to as to 50 yea rs. What has been happening over the last 40
NaProTECHNOLOGY (Natural Procreati ve Technology) . years is a national , and to sorn e extent, international
This w ill be described furth er in the next chapter and tragedy. lt must now be take n seriously and programs
the who le sc ience will be outlined in thi s textbook . It is, must be de ve loped to reverse these trends. The author
trul y, 180 degrees d ifferent from the current artifici al, believes that it ca n begin now!
suppress ive and destructi ve approach of the reproduc-
1. Gibbs RS:lmp ac r of ln fec ti o us Di seases on Women·s 11 . Hil ge rs TW, O'Hare D:Aborti on-rela ted Materna l Mortal-
Hea lth: 1776-2026, Obstel Gynecol 97: 1O19 -1 023, 200 1. ity:An ln-D epth Analysis. ln :Hil gers TW, Hora n DJ, Mali
D: (E ds) New Perspecti ves on Hum an Abortio n.A lethe ia
2. O'Dowd MJ , Philipp EE:The Hi sto ry of Obstetrics and
Books, Unive rsity Publications of America, 1981.
Gyneco logy. Parth enon Publi shin g Group, New York, 1994.
12. Syska BJ, l-lil gers TW, O'Hare D:An Objective Model for
3. Vital and Hea lth Stat isti cs:S uppl ements to th e Monthly Vi-
Estim atin g Criminal Abort ions and its lmpl ications for Pub-
tal Sta ti sti cs Repon.Series 24, No. 9, Apr il 2003.
lic Policy. ln: Hil gers TW, Horan DJ , Ma li D: (Eds) New Per-
4. Michae l RT:Why Did the U.S. Divorce Rale Double Within spectives on Hum an Abortion.A leth e ia Books, Un iversity
a Deca de? Resea rch in Popul ati on Economics 6 :367-3 99, Publications of America, 198 1.
1988 .
13. U.S . Census Bureau Data for 1975- 1997.Statistical Abstrae!
5. U.S. Bureau of the Census, Internet Release Date:June 29, of the United States ( 121 " Edi tion), Washington DC, 200 1.
200 1. 14. Ventura SJ , Bachrach CA:Non-M arita l Ch ildbea ri ng in the
6. Abma J, Chandra A, Mosher W, el al:Fertili ty, Fa mil y Plan- Unit ed States , 1940- 1999.Na tiona l Vital Statistics Re-
nin g and Women's Hea lth: New Data from th e 1995 Na - porrs.Center for Di sease Con trol and Prevention.4 8: 1-40,
tional Survey of Family Growlh.U.S. Deparlmenl of Health October 18, 2000.
and Human Se rvices.Ce nter for Di sease Co ntrol and Pre-
15. Ventura SJ, Mosher WD, Henshaw S:Revised Pregnancy Rates,
ven tion , May 1997.
1990- 1997 and New Rate s for l 998- 199 9 :Unit ed
7. Mosher WD, Pratt WF:Conlraceptive Use in th e Unit ed States. ati ona l Vital Sta ti stics Report s, Center for Di sease
States, 19 73 -19 88.A dv anced Data from Vita l and Health Co ntrol and Preven tion : 52: 1- 16, October 3 1, 2003 .
Statisti cs; No. 182 . Hya llsv ill e, Maryla nd:Nationa l Cente r 16. Benn ett WJ:The ln dex of Leading Cultural lnd ica tors .The
for Health Statistics, Washington DC, 1990. Heritage Foundat ion and Empower America.Washington,
8. Pete rson LS :Contraceptive Use in the Un it ed Sta tes: 1982- 1993.
1990 .Advanced Data from Vital and Hea lth Statisti cs; No.
17. Orr S:National Data on Child Abuse an d Neg lect.Adoption
260. Hyattsvi ll e, Maryland: Nationa l Center for Health Sta- Factbook 111. Marshn er C, Pierce WC (Eds) .National Co un-
tistics , Washington DC, 1995. ci l fo r Adoption, 1999.
9. Mosher WD, Bachrach CA :Contracepti ve Use:Un ited States, 18. Federal lnterage ncy Forum on Child and Fami ly Statistics.
1980.Vita l and Hea lth Statis ti cs.Series 23, No. 12. DHHS America's Children: Key National lndi cato rs of Well-Bei ng,
Pub No (PHS ) 86, 1988. 2003. Washington OC: US Government Printin g Office.
1O. Ford K:Contracepti ve Utili zatio n. Un ited Stales.Vital and 19. SAM HASA Office of App li ed Studies, Nationa l Househo ld
Hea lth Statistics.Se ri es 23 , No. 2. DHl-I S Pub No (PI-IS) 79,
Survey on Drug Abuse, 1999.
1978. Publi c Hea lth Se rvice .Wash in gton.Office of Hea lth
Resea rch , Statistics and Techno logy, Na ti onal Center for
Hea lth Sta ti stic s, Hyattsvi ll e, Maryland , September 1979.
20. Rector RE:Johnso n KA, Noyes LR:R e port:Sexua ll y Acti ve 3 3 . Sex ua l ly-Tra nsmitted Di sea se Surve i ll anee, 1994. Div is ion
Tcenagers are Mo re Likely to be Depressed and to Attempt of STD/ H IV Preve nti o n .U .S . Departmen l of Hea lth and
Suicide.A Re po n o f a He ritage Cen ter fo r Data A na ly- Hum an Servi ces, Pub lic Hea lth Serv ice. Atl anta: Center for
sis. Was hi ngton, DC, 2003. Disea se Contro l, September 1995.
2 1. Se lIs C W, Blum RW :Mo rbidi ty and Mo rta lity Among U.S. 34. Ce rne r fo r Di sease Co nt ro l a nd Preve nti o n. Ec to pic Pre g-
Ado lescen ts :An Ove rv iew of Dat a a nd Trends.Am J Pub nancy - United States, 1990- 1992.MMW R 44:46-48 , 1995.
Hea lth . 86:5 13-5 19, 1996.
35. Grimes DA , Wa ll ach M:Modern Co ntracepti on:Updates from
22. Weed S:Research Upda te on Promo tin g Chas tit y Amon g the Conl racep ti on Repo rt. Emron , To towa, N J 1997 .
Ado lescents. 16'h A nnu al Meeting, American Acade my of Fer-
36. Schlesselm an JJ:Cancer of the Breast and Reproduct ive Tract
tility Ca re Pro fess io nals, Jul y 18, 1997.
in Re lat io n lo Use of O ra l Co nlrace pti ves.Co ntracepti o n
23. C reasy RK :Preterm Labor and De livery. ln: Materna l-Fe ta l 40: 1-38 , 1989.
Medi c ine: Principl es a nd Prac ti ces.Creasy RK , Re snik R
3 7. Moreno V, Bosch X, Munoz N, et al:Effect of O ra l Contra-
(Eds). W.B. Saunders Co., Phil ade lphi a, 1984.
ceptives on Ri sk of Ce rvica l Cancer in Women wi th Hum an
24. Nati o nal Ce nter fo r Vita l Statisti cs Report , Vo lum e 50, o. Papi ll oma Virus lnfecti o n: The IARC Mu lt icentric Case-Con-
5, Fe bruary 12, 2002 . tro l Stud y. La ncet 359: 1085- 1092 , 2002.
25. Rates of Prema ture Birth by Sta te, 200 1:Na ti o nal Ce nt c r 38. Th o ma s DB :Ora l Contracept ives and Breas t Ca ncer:Review
fo r Vita l Sta tisti cs, F ina l Na talit y Dat a, Pre pared by th c of the Epidemiologica l Lite rature. ln :Ora l Co ntrace pt ives
March o f Dime s Perinata l Dat a Ce nter, 2003. and Breas! Ca nce r.Comm itt ee o n th e Re lati o nship Between
Ora l Con tra cepti ves and Breast Ca ncer. lnstitute o f Medi-
26. Trend s in " Prematurit y" Un ited Sta tes: 1950-1967. ational
cine , Division of Hea lth Promo ti o n and Di sease Pre ve n-
Center fo r Hea lth Stati sti cs, .S. Department of H EW, Pub-
tion. Was hington, DC:Nat iona l Academy Press ; 199 1.
licatio n No. ( HSM ) 72- 1030, Rockv ill e, Maryland, January
1972.No. 15 , Se ri es 3. 39. Sc hl esse lman JJ :Ora l Contrace pt ives in Breast Ca nce r.A m J
Obstct Gyneco l 163: 13 79- 1387 , 1990.
2 7. lnfan t Mo rta lity and Low Birth We ig ht A mo ng Black a nd
Whit e lnfant s - United S tates , 1980-2000.Morbi dit y and 40. Schlesse lm an JJ : Nel Effec t of O ra l Co ntrac e pti ve Use o n
Mo rta lity Weekl y Report , 5 1 (27): 589-592 , Jul y 12, 2002 . th e Risk of Ca nce r in Wo rn en in th e United States. Obstel
Gyneco l 85: 793-80 1, 1995.
28. Martin JA, Hami lto n BE, Ventura SJ , et. a l:Births:Fi nal Data
fo r 2000, Na ti ona l Ce nter fo r Hea lth Stati sti cs Vol. 50, No . 4 1. Cente r for Disease Co nt rol and Preve nti o n :Mo n a lity Al-
5, 2002. tribu tab le lo HI V lnfection Among Persons Aged 25-44 Years
- Un it ed States 1994 .MMWR 45: 12 1-1 25 , 1996.
29. Martin JA, Park MM :Trends in Twin and Trip let Birth s: 1980-
1997, at io nal Vita l Stati sti cs Report ; Vo l. 4 7, No. 24 , Na- 42. Cenlcr for Disease Co ntrol and Preve nli on.Up date: A IDS
tiona l Ce nter for Hea lth Sta tisti cs , Hya ttsv ill e , Mary land , Amo ng Wornen - United Sta tes , 1994. MMWR 44: 8 1- 84,
1999. 1995.
30. Ce nte r for Di sease Contro l and Preventi on.Ass isted Repro- 43. Mosher SW: The Uncon tro ll ed A IDS Ep ide rni c. Po pul ati o n
ducti ve Techn o logy Success Rates, 1995- 1999. Research ln stitu le Rev iew. 13:3 , 2003.
3 1. Vita l and Hea lth Stati sti cs. ati o na l Center for Hea lth Sta- 44. Gigant K:Your Tax Do ll ars at Work for Pl an ned Paren l-
t istic s. Trip le t B irths:Trends and Outcome s, 197 1- 1994. hood.Ce lebrate Li fe.25 :42-45 , 2003.
Ja nu a ry 1997.
45 . Bogacrt AF, Turkovich DA , Hafer CL:A Con tenl Analysis
32. C handra A, Steph en EH:lmpa ired Fecundi ty in the United of Pl ayboy Ce nte rfo ld s frorn 1953 throu g h 1990.C han ges
States : 1982 -1 995.Fa m Plan Persp 30:34-42 , 1998. in Exp lic itness, Object ifica ti o n and Mode ls Age. J Sex Res
30 :1 35 -1 39, 1993.
What is NaProTECHNOLOGY?
N aProTECHNOLOGY - NPT (Natural Procreative

Techno logy) can be defi ned as a new wo men 's
hea lth science which has, as its main princip ie, the abi l-
ily planning with reproductive and gynecologic health
monitoring and maintenance. lts use has application s
in fam i ly pl anning, the evaluati on and treatment of in-
ity to work coopera ti ve/y with a woman 's menstrual and fert il ity and other reproducti ve di sorders , abnonn al
fe rtility cycles. lt uses th e CREIGHTON MODEL bleeding, abnonn al honnone conditions ofthe menstrual
FertilityCare™ System, 1-4 which is a prospective and cyc le including premenstrual syndrome and recurrent
standardized means of monitoring the menstrual and ovarian cysts, the dating of the beginning of a pregnancy,
fert ili ty cycle. It has multiple appli cations to wome n of and postpaitum depress ion. NaProTECHNOLOGY has
reproductive age. The spectrum of thi s new science is medica! , surgical and peri natal ap plicati ons.
shown in Figure 2-1 .
Yarious applications ofthe CREIGHTON MODEL Sys·
NaProTECHNOLOGY is thefirst system to networkfam- tem (CrMS) are illustrated in Fi gures 2-2 through 2-6.
Spectrum of the Women 's Health Science

of NaProTECHNOLOGY
Preconception
1
Periconception Postconception
Figure 2-1: The spectrum of the women 's health science of NaProTECHNOLOGY.
19
20 The Medica! and Surgical Pra ctice of NaProTECHNOLOGY
o 21 22
Progesterone
40.0 ng/dl -r-t-+-t-t-+-+-t-+-+-.......l-+-~+--+--l~+-'-~+--+--l~+--+-~-+- 2 0 . 0 ng/ml
30.0 ng/dl -r-t-+-t-t-+-+-~+-+-.......H•~+--+--1~+-t:t--+ t--1-T--t--1-1--t--1- 15.0 ng/ml
Figure 2-2 : The application of the CREIGHTON MODEL System in a regular menstrual cycle . The menstrual period , pre-Peak
dry days , mucus cycle, Peak Day (P) and post-Peak phase are shown. The cycle is shown with correlating est radio l -17~ (E2 )
(black bars) and progesteron e (red bars) levels .
15 16 17 18 19
¡001( IOKL.. lOKL '1C se

L AO AD IC 1 KI
"º PE fOD
Figure 2-3: The application of the CrMS in long cycles. In th is 51-day cycle, the Peak Day (P) occurred on day 38 . The post-Peak
phase wa s 13 days in duration .
Chapter 2: What is NaProTECHNOLOGY? 21
Figure 2-4 : The application of the CrMS in breas! feeding . "Patches" of mucus occur sporadically, dry days usually predomi-
nate , and as ferti lity returns , the mucus cycle and fertil ity return .
Figure 2-5: In this case, a woman of normal fertility, the CrMS is used to achieve pregnancy. Th e acts of intercourse in the
midst of the mucus cycle (days 16 and 18) should be expected to result in pregnancy as they did in this example.
22 The Medical and Surgical Practice of NaProTECHNO LOGY
lnfertility
Low
progesterone
Abnormal
OAO OAO CIAD Clo'D CIAD
bleeding
NaProTRACKING for a Woman's Health
Figure 2-6 : The monitoring (NaProTRACKING ) of the biomarkers of the CrMS for a woman 's health . In the first cyc/e , a limited
mucus cycle is observed . This is common in infertility. In the second cycle, a short post-Peak phase of 5 days is present. In th is
cycle , miscarriage would be a very high risk if pregnancy occurred . In the third cyc/e, low luteal phase progesterone is
expected from the premenstrual spotting that is present. And in the fourth cycle , the unusual bleeding would demand more
evaluation .
The Union of Procreative Education and While education is one of its foundations,
Medical Technology _ _ _ _ _ _ _~ NaProTECHNOLOGY also relies on developments in
medica/ technofogy. This is best exemp lified by its use
NaProTECHNOLOGY is a medica! sc ience whi ch has of largeted hormone surveys, expert uftrasound evafu-
the education ofpatients as its fo undation. Specifically, ation, and variou s surgicaf approaches that uti lize la-
it educa tes women in the objective parameters of their ser technology, microsurgicaf applications and anti-
menstrual and fe1tility cycle in such a way that they adhesion strategies.
can develop a partnership with the physician in the
eva luation and eventual treatment ofwhatever gyneco-
logic and reproductive problem they may encounter. Approaching Women as Whole Persons
This education is standardized o that it can be used One of the obstacles in the current approaches domi-
throughout the United States and in other foreign coun- nating obstetrics, gyneco logy and reproductive medi-
tries. Beca use of its standardi zation , it is objective. It is cine over the last 40 years or more is the view that women
also reproducible so that the information that the women are tarnished by the presence oftheir procreati ve abili-
gather can be interpreted and it can be used for both ties. In sorne ways, the menstrual cycle is still viewed as
medica/ evaluation and treatment purposes. a "curse" 5 and the fertility cycle is viewed as a burden
and an obstac le to be suppressed or destroyed . These
Ali ofthe above featu res of NaProTECHNOLOGY are mindsets have so ingra ined themselves within the pro-
unique at this point in history in obstetrics, gyneco l- fessio n that when one approaches obstetrics, gyneco l-
ogy and reproductive medicine. They are incredibly ogy, and reproductive medicine from a different per-
important to being able to identify the underlying spective or point of view, it rai es significa nt antago-
cause(s) of a particular medica! problem(s), and then nisms.
establish a form oftreatment.
Chapter 2: What is NaProTECHNOLOGY? 23
In NaProTECHNOLOGY, however, fertility is not con- and clients are accepted as ind ividuals who are quite
sidered a disease. The menstrual flow and the menstrual capab le of li ving in a positi ve way with the normal func-
cycle are thought of as normal biological and phys i- tion offertility.
ological processes wh ich can, of course, become dys-
functional and abnormal. Nonetheless, the cyclic physi-
olog ica l process ofmenstruation and fertility is a nor- Selective lntercourse vs. Spontaneous
ma l process. A pregnancy that results from that phys i- lntercourse ~~~~~~~~~~~---.
olog ical event is also norma l. While abnormalities of
pregnancy can occur and result from diseases, the fun- Current approaches to the management of fertility re-
damental process ofpregnancy, childbirth and delivery quire that spontaneous intercourse be protected at ali
is considered normal. costs. In NaProTECHNOLOGY and with the CrMS , the
"principie of selective intercourse" is introd uced.
Approach ing women with the educational principies of
their menstrual and fertility cycles and helping women This principie is one that applies uniquel y to a natural
to di scover the power that exists within the ir cycle al- mea ns to regul a te ferti lity and spec ificall y to the CrMS .
lows the phys ician to approach women as total human Whil e many natural systems over the yea rs have relied
persons. This is a medica! science that is at the service on the concept of "periodic abstinence" to describe
ofthe human person. lt not onl y encourages the fema le what is involved in the implementation of these sys-
patient to become a partner in the eva luation and treat- tems, "periodi c abstinence" is not at ali specific to their
ment of her reproducti ve health , but such participation use . Those who use contracepti ves also practice peri-
is an actual component of the approach. odic abstinence since they do abstain from genital in-
tercourse between one sex ual contact and the next. So,
th e idea of "peri odic abstinence" is not a concept that
Achieving and Avoiding Pregnancy==l appli es exclu sively to a natura l mea n to regul ate fe rtil-
ity.
In the CrMS, the foundational fam il y plannin g system
of NaProTECHNOLOGY, it is acceptable for a coup le The decision to either have or not have interco urse is
either to achieve or to avoid pregnancy. The achieve- dependent upon actual choices one makes to either
ment ofpregnancy is not considered a "sex ually tran s- achi eve or avoid pregnancy. The use ofthe term "selec-
mitted disease" as sorne have expressed it in the past. 6 tive" specificall y implies th e decision-making choices
Achieving a pregnancy is not co nsidered a violation of that couples implement while acti vat ing the fu llness of
the demographic ecology but, rather, an event that ca lIs the system. In their deci sion making, they are selecting,
ali ofus to support and care. The deve loping child within in a responsible way, the ve1y bes! time to have inter-
the mother 's womb is neither viewed as a parasite nor course . Perhaps even more importantl y they are mutu-
as a potential human being. Rath er, the chi ld is viewed al/y selecting that time. Thus, spontaneous intercourse
as a human being with potentia/. in vo lves a submi ss ion to emotional impulses whi le se-
/ecti ve intercourse submils itse/f to choices evaluated
In modern reproductive medicine, the approach to fam - and implemented through the incorpora/ion of the in-
ily planni ng is one ultimate ly of either suppression or tellecl, the wi// and the va/ues that the coup/e shares.
destruction . There are no current contracepti ve sys- The sharing that is in vo lved in the impl ementation of
tems that work cooperative ly with the reproductive sys- any natura l system including the CREIGHTON MODEL
tem. Oral contraceptives, for example, suppress the func- is also different from contraceptive approaches. These
tion of the pituitary gland so as to suppress ovulati on. systems do not work unl ess the co upl e cooperates with
When an ovulation is not suppressed and a pregnancy each other. Technological systems are built upon the
deve lops, then the contraceptive works by destroyin g noti on that such cooperati on does not or may not exist.
the new ly deve loping embryo at the time of nidation. 7 In thi s latter approach, the a priori premise precludes
the development of cooperation in this important as-
In current approaches to contraception, sterilization has pect of the married coup le's li fe. That preclusion can
become one ofthe maj or technologies. One of the prin- lead to distress, tension , rese ntm ent and eve ntuall y
cip ies behi nd sterili zati on is that it requires no moti va- destruction of the relationship.
tion. Steri lization relies on the principie th at human be-
ings are unabl e to deve lop any leve! of se lf-mastery
when it comes to their expression of genital sex uality. In
NaProTECHNOLOGY and with the CrMS , the patients
Cerebrocentric vs. Genitocentric harmed and so mu ch pain and agon y has been created.
SexualitY -----------~
Thi s "sex ual freedom " has fos tered a signi fican t di s-
Thi s cooperation of the inte llect and the wi ll is some- ruption in human re lationships over th e fo ur decades of
tim es referred to as cerebrocentric sexuality. The fo cus its ex istence. lt is difficult to believe th at true freedom
is primarily personal and intern a!. lt mainta ins the con- wo uld genuinely generate such di srupti on.
necti ons between !ove and li fe, and it leads to persona l-
izati on, humani zati on and phys io logica l and spiritu al Thi s " sex ua l freedom" has been phys ically vio lent as
affirmation. In the CrMS, we use the acronym SPICE to we ll . Thi s vio lence is well documented in C hapter 1 of
refer to the multidimensional nature of human sexual- thi s tex tbook. Thi s " sex ua l freedom" has spec ifica lly
ity, which is spiritual, physical, intellectual, creativel harmed countless numbers of wo men under the gui se
commu ni cative a nd em otio nal/psyc hologica f. of their liberati on. One could hardl y consider that ha v-
Cerebrocentric sexuali ty is at the fo undation of the coming a woman seek an aborti on and having the embryo or
m itment to support the natural means to regul ate fe rtil - fe tus di smembered by surg ica l instrum ents is the prod-
ity and to marital bonding . lt respects the di gni ty of uct of true freedom. It is difficult to be lieve that true
both men and wo men and the integri ty of marri age . It is freedom wou ld be so destructi ve.
geni ta lly affirm ing but not extreme in geni ta l fu ncti on-
ing (it is ecofogically ba fanced), and it should be ex- A more appropri ate term would be a revolution w hich
pected to lead to a decrease in fa mil y violence. has been establi shed to promete sexual license. Thi s
license is different fro m true freedom . lt is self-centered
C urrent contraceptive approaches to fa mil y pl anning and not other ori ented. It is pleasure-seeking rather than
invo lve a genitocentric focus in sexuali ty. As a natural joy and fu lfillm ent seeking. It is not nearly so concerned
extension of thi s genitocentric foc us there is a separa- about others as its proponents would make one think.
tion oflove fro m life and ofli fe fro m !ove . Thi s deper- Indeed, this "sex ual freedom" is not freedom at a li , but
sonali zati on leads to dehumanizati on and psycholog i- rather it has produced a kind oftyranny in which people
ca l and spiritual depri vati on. Contrace pti on, sterili za- are often trapped . Thi s is because it results from sexual
tion , aborti on, artifi cia l reproducti ve techno logies and li cense and not true freedom.
po rn ographi c ex press io n are natural res ults of a
geni tocentric view. As a result of genitocentri sm, as pre- In the CREIGHTON MODEL FertilityCare™ System and
vious ly po in ted out in C hapter 1, it is absolutely cl ea r in other natural methods offamil y planning, Iegi timate
that famify violence has increased to epidemi c propor- ch oices are made relati ve to the ac hi evement o r avoid-
ti ons. ance of pregnancy, commun ication exi sts between the
spouses , and th e virtue of chasti ty is resp ected . Thi s
pro motes a deep and profo und respect, not onl y fo r the
Sexual Freedom vs. Sexual License=l indi vidua l person who holds these principies but also
toward those indi viduals w ith w hom he or she shares
O ver the past 40 years, there has been a movement some- them . There is a w illingness to reach out to others and
ti mes referred to as the "sexual revo luti on." The clari on trul y care fo r them and w ith them. It is ne ither se lf-cen-
call of thi s movement has been "sexual freedom. " But, as tered no r pl eas ure-seekin g as its primary obj ective.
we have now looked at thi s over the last fo ur decades, it Rather, it is mutual. lt prom otes growth over a period of
is hard to su pport the notion that what has occurred is time and not in stant gratificati on. It is notan arrested,
the result of an authenti ca lly deve loped freedom. ado lescent approach but a full and mature and loving
app roach that respects the value and di gnity of each
Those peop le who are sex uall y free are abl e to say both and every human life, the di gni ty of women and the
" yes and no" to the genital ex press ion. With a natural integrity of marri age . Thi s can be argued to be an au-
means to regul ate fe1i ili ty, thi s expression ofsexual free- thentic sexual freedom and carries with it the possibili ty
dom is in-buil t withLn the system. However, the modern of estab li shing a legitimate sex ual revo lution.
contracepti ve culture a ll ows peopl e to say " yes" w hil e
g iving onl y token expression to their abili ty to say " no ."
Prospective vs. Retrospective
The "sex ual freedom" of the contracep ti ve movement Data Collection _ _ _ _ _ __ _ _~
has harmed many peopl e over its ex istence. Lt clearl y
has not been victiml ess. lt is di ffic ult to ap prec iate a As a new medica! sc ience, NaProTECHNOLOGY relies
concept of freedom where so ma ny peopl e ha ve been on the prospecti ve acc umul ati on of obj ecti ve and stan-
Chapter 2: Wh at is NaProTECHNOLOGY? 25
dardized data on the menstrual and fertility cyc les. In tives. A woman has an infe rti li ty pro blem and the doctor
reproducti ve medicine, th is has neve r occ urred befare. places her on medication to sti mul ate ovulation without
Far the most part, physicians do not kn ow yet what to look ing far the underlying cause. lf she <loes not get
do with th e infa rmati on. That is one ofthe reasons fa r pregnant in one to three cyc les, she is referred to the
this textbook. artificia l re producti ve technologist. Those doctors ha ve
not been in terested in look ing far the underl ying ca uses.
At th e same time, one can see that reprod uctive medi -
cine has been entrenched fa r at least a century in the In NaProTECHNOLOGY, the fac us is on looking fa rthe
retrospecti ve coll ecti on of data. A survey of textbooks underl yi ng pathophys iologic event whi ch all ows fa r a
in obstetrics, gynecology and reproducti ve medi cin e rational approac h to treatment. lt is not claimed here
from 19 15 un ti1the present time shows clearly that the that in NaProTECHNOLOGY ali of th e ca uses or ali of
emphasis has been on the relatively unreliab/e retro- the abnorma l events ca n be determined. However, it is a
spective collection of data on the menstrual andferti/- phil osophi ca l approach, a co ncept used in many oth er
ity cycles. 3-39 med ica! specialties except reproducti ve medi cine, that
all ows fa r the phys ician to look far and in vesti gate those
The CrMS changes al! of that. Far the first ti me, women underlying causes and then deve lop or impl emen t ef-
are in structed in the functi on of th e menstrual cyc le and fective treatments fa r th ese condi tions.
the observation of its va ri ous parameters. These pa-
rameters are often referred to as biomarkers (bi ologica l 1n NaProTECHNOLOGY, as more and more research is
markers). The research th at has been done over the last undertaken, more ca uses wi ll be fa und and eventually
28 years shows that these bi omarkers allow the wo man better treatments emp loyed. lt is a system th at will onl y
and the phys ic ian to make pro per eva luati ons and find improve over ti me.
th e eventual treatm ent. Furthermore, abnorm aliti es in
these bi omarkers are close ly assoc iated with underly-
ing pathophysiol og ic abnormaliti es . Since these bi o- Cooperative Approaches vs. Suppressive
logical markers ha ve mostl y been ignored over the last and Destructive Approaches ----~
century, many important in sights on reproducti ve med i-
cine have been mi ssed. Physicians who are in terested A fu ndamental princip ie in NaProTECHNOLOGY is to
in working with NaProTECHNOLOGY must become thor- work cooperatively with the menstru al and fe rti lity
oughly fa miliar with this pros pecti ve data co ll ection (the cyc les. O n th e oth er ha nd , modern re produ cti ve
CrMS) so they can begin to lea rn and interpret these technology 's fu ndamental principie is to overcome them
bi ologica l markers based on th e resea rch to date and by eith er suppress ing or destroying them. These two
future research . Over the many yea rs th e author has approaches are at polar ex tremes. Bu t befare indi vidu-
been in volved in this, he is constan tly reminded how als criti cize or di sregard NaProTECHNOLOGY, they
incredibl e this system rea lly is. shoul d think about it, attempt to implement it and evalu-
ate it fu rther because there is very much in thi s new
med ica ! sc ience which is extremely good and pos iti ve
Band-Aid Approaches vs. Getting to the for one 's patients. It so lves many pro blems that we have
Underlying Causes _ __ _ _ _ _~ not been abl e to sa lve in the past and all ows fa r ap-
proac hes to be taken whi ch are di ffe rent than current
The current approaches taken in reproducti ve medi cin e approaches. At th e same tim e, it all ows fa r th e imp le-
approach prob lem so lving from what could easi ly be mentation of treatments that hold great promi se. lf th e
ca lled a "Band-Aid approach." A wo man comes to the phys ician elects to imp lem ent it, a word of caution: Do
phys ician with dysmenorrhea and she is placed on birth not do so haphazardly or superfi ciall y. Do it to the very
contro l pills rather th an findin g out why she has dys- best ofyour ability!
menorrhea. A woman comes with irregul ar menstrual
cycles and, instead offind ing out why she has irregul ar
cyc les, she is placed on birth contro l pill s. A woman What NaProTECHNOLOGY Is Not _~
comes to the phys ician because of irregul ar bleeding,
and she is placed on birth contro l pil ls so that she can Wide criticism is anticipated fa r this approach to medi-
artifi cially bleed regularl y without looking fa r th e un- ca ! ca re. lt will be criti cized mostly beca use it is differ-
derlying causes. A woman who is being in vesti gated ent. lt will not be criti cized, fa r th e most part, on its
fa r recurrent ovari an cysts, instead of being in vesigated merits. For example:
fa r th e underlyin g causes, is pl aced on ora l co ntracep-
26 The Medical and Surgical Practice of NaProTECHNOLOG Y
NaProTECHNOLOGY is no/ non-technological. lt is This Textbook __________~

not opposed to techn ology. In fact, it in corporates
the very best technological developments whil e This textbook is the first definitiv e prese nta tion
servin g the human person in total. of The Medi c a / and Surgical Practi ce of
NaProTECHNOLOGY. It is the author 's attempt to present
NaProTECHNOLOGY is not ineffective. There is no thi s in great detai l so that ali aspects of it can be stud-
question that this approach to medica! care is effec- ied, evaluated, and further understood and implemented.
ti ve in those areas to which its promises are made. In thi s textbook, we will describe for the reader, the fu ll
dimensions ofthe CREIGHTON MODEL FertilityCare™
NaProTECHNOLOGY is not unscientifíc. Much of System. We will discuss th e vari ous aspects of labora-
thi s new sc ience has already been subjected to very tory assistance in the practice of NaProTECHNOLOGY.
carefu l evaluation and scientifí c scru ti ny. We will look at the medica! appli cations for using thi s
approach in the treatment of pati ents, in cluding those
So me may say that NaProTECHNOLOGY is not for every- issues such as recurrent ova rian cysts, premenstrual
one. In response, it can be said that NaProTECHNOLOGY syndro me, postpartum depression and abnormal bleed-
is a women 's health science that can be app lied to every mg.
person. The author does reali ze that it will not be ap-
plied to every person for a whole va ri ety of different In add ition, it will detai l th e approaches to the treatment
reasons , most ofwhi ch cannot even be anticipated. But, of reproducti ve abnorma lities such as infertil ity an d re-
it can be sa id th at NaProTECHNOLOGY will attract current spontan eous aborti on. The textbook wi ll out-
those individuals who are serious about having strong line its perinata l appli cati ons, including th e work th at
marriages and healthy families and it will atlract has been done to reduce premature births. An extensive
healthcare providers who want to be a par/ of the so- description ofthe various surgica l approaches and pro-
lution to family violence and nota par/ ofthe problem. cedures in NaProTECHNOLOGY is presented in great
lt will attract those indi viduals who have a wi llingness detail to form the fo undati on for the eventual train ing of
to become co-partners in eva luation and treatment and physicians in the surgica l techniques in this area. Some
who have a des ire to look for the underl ying causes. of the resea rch approaches th at have bee n taken in
NaProTECHNOLOGY places a val ue upon treatm ents NaProTECHNOLOGY wil l also be described and some
that coopera/e with the natura l procreative processes further look at its future will be presen ted.
and do not suppress or destroy them.
This textbook hopes to offer as ful l a descri pti on of
NaProTECHNOLOGY as is possib le at this time. There
The Paradigm Shifts of will certa inly be advances made in the years ahead. This
NaProTECHNOLOGY_ _ _ _ __ book does not descr ib e the e ntire potentia l of
NaProTECHNOLOGY, on ly the beginning of it. It pre-
There may not be a new sc ience introduced into medi- sents the first phase of 28 years of fo undational re-
cine that carries with it so many shifts in the accepted search. Hope full y, it will lay the groundwork fo r its fu-
paradigm as NaProTECHNOLOGY addresses. These ture development and imp lementation .
paradigm sh ifts are li sted in Table 2-1. 1n fact, these
shifts in the paradi gm will make it very diffí cult fo r
Table 2-1: The Paradigms Shifts
NaProTECHNOLOGY to become instantly accepted.
of NaProTechnology
On the other hand, it is also the sh ift in these paradigms
th at make it very attractive for many people and many
physicians. These individuals will fi ght to see that • Achieving and avoiding pregnancy
NaProTECHNOLOGY becomes ava il able to any indi - • Selective intercourse vs . spontaneous intercourse
vid ua l who wishes its approach. • Cerebrocentric vs . genitocentric sexuality

• Sexual freedom vs. sexual license
While it is a polar opposi te to current app roac hes in • Prospective vs . retrospective data collection
reproductive medicine, it is not aja/se approach; it is • Band-Aid approaches vs. getting to the underlyi ng
causes
not inept; it is not un scientific; and, it is not aga in st th e
• Cooperative approaches vs . suppressive and
princ ipi es of good medicine. In fact, it takes into ac- destru ctive approaches
count the most signifícant basi c princip ies ofmedici ne
and wi ll , therefore, be worth the struggle .
Ch apte r 2: W hat is NaProTECHNOLOGY? 27
1. Hil gers TW, Prebil AM , Daly KD , Hil gers S K: Tbe Picture 19 . Nova k ER, Janes GS, Ja nes HW: Novak' s Tcx tbook of Gy-
Dictionary o f th e CREIGHTON MOD EL Fertili cyCare™ Sys· neco logy. 9•h Ed. Wil liarn s and Wilkin s Co .. Baltirn ore, 1975.
cem . Second Edition . Pope Paul VI ln stitute Press, Ornaha ,
20. Ki stn er RW: Gyneco logy: Prin c ip ies in Prac ti ce, 2"' Ed .
NE, 1999.
Yearboo k Medi ca ) Pub li sbers, Chi cago, 197 1.
2. Hil gcrs TW, Dal y KD, Hil gers SK , Prebi l AM: CREIGH TON
2 1. Benson RC: Current Obstetri c and Gyncco log ic Di agnosis
MODEL Fertilicy Care™ System : A Standardi zed Case Manage-
and Treaunent. Lange Medi ca l Publi ca ti ons. Los Altos. 1976.
rnent Approach to Teachin g - Boo k 1: Basic Teacbing Skill s.
Seco nd Ed it ion, Pope Paul VI ln stitutc Press, Ornaha, NE . 22. Li chtrn a n R, Papera S : Gyneco logy: We ll - Wornan Care .
200 2 . App lcton and Lange. Norwalk , 1990.
3. Hilgers TW, Hil gers SK, Prebil AM , Daly KD: CREIGHTON 23 . Scott JR . Di sa ia PJ , Harnrn ond C B, Spc ll acy WN ( Ed s) :
MODEL FertilicyCare™ System: A Standard ized Case Managc- Danfo rtb 's Obstetri cs and Gy neco logy. JB Lip pincott Co. ,
rnent Approacb to Teac bing - Boo k 11: Adva nced Teac bin g Phil ade lpbi a, 1994
Ski ll s. Pope Paul VI lnstitutc Press, Orn aba, NE, 2003 .
24. Danfo rtb D , Dignarn WJ. Hcndri cks CH, Maech JVS ( Eds):
4. Hilgers TW: CREIGHTON MODEL FertilityCare™ Syscem : A Obstctrics and Gynecology. 4•h Ed. Harper and Rowe, Phila-
Conternpo rary Approach to Wornen's Hca ltb ca re. Pope Paul de lpbi a, 1982 .
VI lnsti tute Pre ss, Orn aba, NE, 200 1.
25 . Droege muellcr W, 1-J erbst AL, Misbell DR, tencbever MA:
5 . Delaney J, Lupton MJ , Toth E: Th e Curse: A Cultu ra l Hi s- CV Mosby Co .. St. Loui s, 1987.
tory o f Men struati on. EP Dutton and Co., ew York , 1976.
26. Rya n KJ , Berkow itz R, Barbieri RL: Ki stn er's Gyneco logy:
6. Cat es W, Gr im es DA , Smith JC: Aborti on as a Trea trn cnt Prin cip ies and Practi ce. 5'h Ed. Yea rboo k Medi ca ) Publi sb-
for Unwa nted Pregna ncy: Th e Nurnber Two Sexually Trans- ers, Cbi cago, 1990.
mittcd " Disease". Presented at: l 4t h An nual Scientifi c Meet-
2 7. Rosc nwaks Z, Benjarnin F. Stone M L: Gy neco logy : Prin-
in g, Association of Planned Parenth ood Pb ysici ans, M iarni
c ipi e and Practi ce . McMill an Publishing Co. , ew York,
Beach, FI. Nove mber 1 1, 1976.
198 7.
7 . Larirnore WL, Stanford JB: Postfertili zat ion Effects of Ora l
28 . Tinda ll VR : Je ffcoate's Prin cipi es of Gynaeco logy. S'h Ed.
Cont raceptives and th e ir Re lati onship to ln fo rrned Co n-
Butterwo rth s, Lond on, 198 7.
sent. Arch Fa rn Med 9: 126-13 3, 2000.
29. Mi sbell DR, Stenchever MA , Droegcmucller W, Herbst AL:
8 . Berkely C, Bonney : A Guid e to Gynaeco logy in Ge neral
Co mp rebensive Gynecology. Mos by, St. Loui s, 1997.
Practice. FA Davi s Co. , Pbil ade lpbi a, 19 15.
30 . Edgc V, Mill cr M: Women's Hea lthcare. Mos by, St. Loui s,
9 . Asht on WE: A Te xt-boo k o f" th e Pra cti ce o f Gyneco logy
1994.
for Practitioners and Students. WB Sa un ders Co., Pbiladcl-
phia , 19 16. 3 1. Herbst AL, Mi shell DR, Stenchever MA , Droegemuell er W:
Co mprehensive Gynecology. 2"" Ed . Mos by Yearboo k, St.
1O. Bandler SW: Medi ca ) Gynecology : WB Sa nd ers Co., Pbil a-
Loui s, 1992.
de lphi a, 1924.
32. Du enb oe lt er JH : Gree nbill 's Office Gyncco logy. Yearboo k
1 1. Bland PB: Gyneco logy: Medi ca ) and Surgica l. FA Davi s Co.,
Medi ca ) Publisbers. Chi cago, 1983.
Pbiladelpbia, 1926.
3 3 . Benso n RC: Current Obstetri c and Gyncco log ic Dia gnos is
12 . Curti s AH: A Tex t-boo k of Gyneco logy. WB Saund ers Co.,
and T rea tm ent. 5•h Ed. Lange Medi ca ) Pu bli ca ti ons. Los
Pbiladelphia , 1930.
Alt os , 198 4.
13 . Cooke WR: Esscn ti als o f Gynecology. JB Lippin co tt Co.,
34 . Ledgc r WJ. Wi llson JR, Ca rrington ER (Eds) : Obstetrics and
Pbi lad e lphia, 1943.
Gyncco logy. S•h Ed. CV Mosby Co .. St. Loui s, t 987.
14. Curti s AH , 1-luffman JW: A Tex tboo k of Gyneco logy. WB
35 . Berek JS, Ad ashi EY, 1-l ill ard PA : ova k's Gynecology. 12•h
aun ders Co., Phi ladclphi a, 195 0.
Ed. Willi ams and Wi lkin s, Baltirn orc, 1988.
15. Bebrrnan , Gos lin g JRG : Fundamentals of Gyneco logy. Scc-
36 . Will son .IR , Ca rrin gton ER ( Eds): Obstctri cs and Gyneco l-
ond Ed. Oxford Un iversit y Press. Ncw York , 1966.
ogy. Mosby Yea rboo k, 9'" Ed. St. Loui s, 199 1.
16. Will so n JR , Ca rri ngton: Obstetric s and Gynecology. C V
3 7. DeC hern ey AH, Pern oll ML : Current Obstetri c and Gy ne-
Mosby Co., St. Loui s, 1983.
co logic Di agnosis and Trcatrn ent. s •h Ed. Appl cton and Lange.
17. Greenbi ll JP : Office Gyneco logy. Ycarb oo k Medic al Pub- No rwa lk , 1994.
li shers. Chicago, 197 1.
3 8 . Sten cbever MA: Office Gynecology: 2"" Ed. Mosby, St. Loui s,
18 . Ja nes HW, Went z AC, Burn ett LS : Nova k' s Tex tboo k o f 1996.
Gyncco logy. J J•h Ed . Willi arn s and Wi lkin s Co., Balti more.
39 . Beck mann CRB , Lin g FW, Herbert W P, Laube DW, Srnitb
1988 .
RP, Barzansky BM: Obstctri cs and Gyneco logy. 3'' Ed. Wil-
li ams and Wilkin s, Ba lt im ore, 1998.
NaProTECHNOLOGY
and the New Humanism
Renée Mirkes, OSF, PhD
1 had originally in tended in this chapter of The Medica/

I t is a co mbination of mystery and serendipity when
what yo u read, sometimes a single statement, changes
yo ur li fe o r- more modest ly- changes the way yo u
and Surgical Praclice ofNa ProTECHNOLOGY to dem-
o nstrate why NPT re presents sound medica! science,
thin k abo ut so mething. lt's as if that s imple sentence that is, science as it should be; sc ience with a conscience;
ma nages to stop you from fixatin g on the individual tree sc ience th at nei ther deifies itself nor defies fa ith. But
so you can, fina ll y, survey the whole fores t. then 1 read that simpl e PAS statement and realized that
my orig ina l thesis was en tire ly too narrow and even
T he latter precise ly describes a recent ex pe rience of naively myopic.
m ine. A statement issued by the Pontifical Academy of
Sciences (PAS) in June of2003 1 revo lutionized the way 1 A deepe ned appreci ation ofthe PAS statement un veiled
had fo rmerl y been thinking abo ut N aProTECHNOLOGY the breathtaking hori zo ns of the "ex panded" thesi s l
(NPT). 2 The Academy (comprised of di stingui shed sci- needed to ex plore: N PT is a prol eps is of the positi ve
entists fro m aro und the world appointed by the Pope) soc ieta l impact ofa hum anistic sc ie nce . In oth er words,
echoed a plea and a challe nge that John Paul 11 has re- it is an already existing mocle l of re producti ve hea lth
peatedly extended to scientists a nd peop le of fa ith . care that anlicipates biomedicine 's ro le in the new hu-
" What is required more now than ever befare," the PAS manism env is io ned by th e Po pe and PAS membership .
urged , is "a new humani sm," a new yste m ofthinking, N PT was and is and w ill be a part of a much large r
be li ev ing and acting that evo lves from and is nurtured movement, ofa more fo rmidab le objective th an that of
by dia logue, rather than opposition, betwee n science, merely being an examp le of how faith and reproductive
ethi cs and fa ith. This, l imag in e, is the apparition that med icine ca n be in harmon y. With its neo-humani st cul-
fo rms the backdrop ofthe PAS state me nt: The " breath" ture, NPT is, in my opini on, the fla gship ofnatural pro-
of a coo p erative ly ho ned, inte g rated scientific crea ti ve initiatives that are, even a yo u read, produc-
worldview- best known for safeguarding " what is hu- ing the "good fruit" ofa trul y human cu lture where knowl-
man in people" and for a llowing us huma ns to ""be" edge, belief and behavior will be ordered to the good of
more 3 - wou ld be capable ofresuscitating our mora ll y present and future generations of the fami ly ofmankind .
ex ha usted world.
29
30 The Medical and Surg ical Practice of NaProTECHNOLOGY
To prove my thesis 1 want to exp lore with you the cul- PersonalVirtues _________~
ture of NPT from five perspectives: the vision of its
pioneer, the vision ofits cience, the vision of its ethi cs, Man of Wisdom
the vis ion of its fa ith, and the vis ion of its eccles ial sup-
porters. Taken together, these perspecti ves share one John Paul 11 maintain s that scienti sts do a good or bad
feature in commo n: They attest, from different poi nts job of deciding on th e ultim ate meaning and value of
ofview, how the cu lture ofN PT is a robust response to their li ves depe nding on whether th ey do so with or
the call for science, ethic , and faith to bui ld a new hu- without "the reflective depth" of"theological wisdom."4
mamsm.
But why wou ld John Paul make wisdom the pivota! vir-
tue for a good scienti st? The answer is found in the fact
l. NPT: The Vision of lts Pioneer_ _ _~ that wisdom is "the intellectual virtue whi ch considers
the highest ca uses" ofthings and above ali focuse on
Since the perspective ofth is section could be constru ed th e ultimate cause or God. 5 For that very rea on,
as gratu itous flattery on my part or a kind of blatant Ari stotle call ed wisdom the "fi rst sc ience" or the pre-
self-serv ice on the part ofthe textbook 's author, 1 have mi er way ofknow ing and understanding everything that
a suggestio n for the reader. Be clear from the outset exists.
why neither construa l wou ld be justified. First, the man y
who know and work with Dr. Hil gers would agree with Being wise and acting wise ly is part ofthe gen ius ofT.
me that it is fact not ílattery to argue that the positive W. Hilgers. He is, in Aq uinas 's definition of things, a
humanistic impact of NaProTECHNOLOGY is ali ofa wise man because he "systemati ca ll y relates ali things
piece with his character. Second, that Hil gers never di- to God." This is to say that Hil gers is a "consumm ate
rected me to approac h the subject from a bi ographi ca l realist" ; he
perspective- and even obj ected to it for fear it appear
sees that as a matter of fact ali things are related to
se lf- prom otional or ob cure the co llegial nature of hi s
God, and therefore he is but acknowledging the ba-
research- definitively disproves any sort of se lf-service
sic truth of things. The wise man sees that nothing
on his part.
ca n be adequately ex plained unl ess it is related to
the first cause of ali that is. He sees that nothing can
Like every other human being, Thomas W. Hilgers has
even be understood in itself unl ess it first is under-
had to decide what it is that gives ultimate meaning to
stood in terms ofthe Bei ng to whom it owes its be-
his life. And ,just as impottantly, he must then behave-
ing.6
that is, make choices- accordingly. And, as with every
other clini cian in vo lved in research, Hil gers has had to
adjudge, and then act on, what gives meani ng and va lue l ca n say, based on exchanges with him , that he con-
to his work . sciously works off the premise that he will never under-
stand the mea ning and th e workings of the human re-
Relying on many prívate discussions with him over the productive system and of th e menstrual and ovulatory
years as well as on his published articles and Iectures, 1 cycles unless and until he reverences the mystery of the
would like to reconstruct what, in my mind , constitute who le person, the whole patient. And, in the final analy-
this man's vision- the goa ls and principies by which sis, he recogni zes that apprec iating the worth of the
he lives and works . And the best way to do that, it seems whole patient will only come when he views her aga inst
to me, is to highlight, first, orne ofhis more prominent the person ofGod and hi li fe-givi ng !ove.
personal virtues and characteristics (those habits and
attitudes that make him a good man) and , second, his
inte llectua l ski ll s (those hab its that make him a good Man of Humility
medica! researcher) . Not surprisingly, these mora l and
intellectual vi 1tues frequent ly overlap and fert il ize one Dr. Hil gers' unassuming ways make you feel he'sjust a
another and, together, recapitulate the genuine human- regul ar guy. And , to my mind, that impress ion is di -
ism ofhis person and ofh is brainchild. PT. rectly con nected to the truth that he's someone who is
comfortab le in hi s own ski n. He neither grossly exag-
gerates nor severely underestim ates hi s abi liti es. He
avo ids the ex tremes of pride7 and immoderate self- de-
preciation. Describing him as a man of humil ity, then,
is the same thing as defi nin g him as a man ofGod. For,
Cha pter 3: NaProTECHNOLOGY and t he New Huma nism 31
as John Paul notes, " whoever labors to penetrate the by parli ament [substitute medica ! community] a nd
secrets ofreal ity with a humbl e and steady mind is, even the press. He has to prove that his every step is well
unawares, being led by the hand ofGod , who holds ali fou nded and abso lutely fl aw less. lndeed, an out-
things in existence and g ives them their ident ity." 8 o standing, tru ly grea t perso n who has unusual a nd
wonder, then , that th e co rrect definition of humility is un ex pected initi atives in mind does not get any
knowing the truth abo ut o ne 's se l f, knowing one 's " true c ha nce to asse rt himse lf; dozens oftraps w ill be set
position with respect to God and ... neighbo ur. " 9 for him from the beg inning . 14
Ofthe many ways that Hi lgers demonstrates honest self- There is a res urrection s ide to long-s uffe ring, of course.
estimation, none is more strikin g than when he refers to As So lzhe nitsyn also attests, peopl e who are no stranger
himse lfas the pioneerofNPT, as a trai lblazer who looks to sorrow and rejection are, for that same reason, per-
forward to the contributions ofhis conte mporari es and sons who ofte ntimes achieve " a spiritua l deve lo pment
those who come after him . In other words, he know hi s of such inte nsity" that they're eminently a ble to stay the
work of ploughing, planting, a nd wateri ng represe nts co urse over the lo ng ha ul. What el se but a strong spiri-
the springtime ofNPT and th at it will be fo r oth ers to tual rudder acco unts for the fact that, amidst ali sorts of
bring in its autumn ha rvest. Justas Hilgers' findings are adversities, Hilgers is crui s ing into hi s 28th yea r of re-
a n integral part of the research that is precedent to hi s search and still counting?
own, so his work will be "a n integra l part ofthe future
as one whose thoughts have fertilized science." 1º One
hi storian of sc ience astutely observes that it is entirely Man of Faith
appropriate " to prai se the first initiator not only for what
he had actua lly put in hi s [researc h] but also fo r what he Dr. Hilgers' fai th is uni versa l (small-c catholic) because
had left there in potency." 11 it is concrete and particular (capi ta l-e eatholi c). 15 l n
the first place, th e uni versal sense (or sma ll-c catholi c)
A pe1tinent example: Nothing pl eases the pioneer of that permeates hi s faith and , thu s, the sc ientifi c culture
NaProTECHNOLOGY more than the thought that, down of N PT, comprises these importa nt facts: ma n has a
the li ne, researchers other th an him will conduct the delegated dominion over the wo rld, and God has do-
do uble-bli nd randomized clini ca l trial s that could we ll mini on overman. Second, he directly links hi s concrete
be critica! in winning over doubting Thomases to the and parti cul ar sense of those (small -c) uni ve rsa l facts
merit ofNPT. of stewardship and divine pro vidence to the greatest
(cap ital-e eatho li c) fact ofhistory: the lncarnation , and
the 1ife-g iving !ove that Jesus e hri st ca rne to reveal. 16
Man of Long-suffering
So, as a speciali st in reproducti ve medicine, Hilgers gets
Every time I read the passage from lsa iah that describes it; he takes th e uni ve rsal/paroc hi al nature ofthe lncar-
the Servant ofthe Lo rd as a man acc usto med to suffe r- nation as the touc hsto ne fact of hi s life and hi s work.
ing and infirmity (Is. 53:3), 1think of Dr. Hilgers. e hoose Practica lly speakin g, th is seminal insight in spires obe-
any negati ve respo nse 12 yo u ca n think of- rejection, dience in him. He is fa ithful to w hat is uni versa lly true
a pathy, ridicule- and be rest ass ured that he a nd those a nd good by asse ntin g to (a nd g uiding hi s research by
associated with hi s work ha ve fe lt its sting . 13 The ob- the light of) the paiti cularizati o n ofthat truth and good-
servations of Solzhenitsyn give credence to the impor- ness ta ught by the concrete successors to Jesus e hrist,
tance ofbearing up under such adversity. In describing the magisterium.
the inequa li ty between the freedom for exce ll ence and
the freedom for evil that ty pifi es Western soc iety, the Thi s, to my mind , is Hil gers' modus operandi- even if
politi ca l di ss ident makes a case for th e long-sufferi ng sometim es ata sub-conscious leve!. He thinks through
and strength ofsoul that will be needed by people w ho, th e myriad of unanswered questions a nd ye t-to-be-ex-
like Hi lgers, are intent o n the excell ence ofa ne w hu- plored ave nues of hi s clinica l research in a mannerthat
manism. "A statesma n [substitute medi ca! researcher] ," can o nly be described as thinking w ith asse nt. 17 Rooted
So lzhenitsyn says, in those universally true principies of the Roman eatho-
li c e hurch, he is firml y convinced that " eatho li c an-
who wants to achieve something hi gh ly construc-
swers can be give n to such question s. " 18 With Marconi
tive for his country [substitute hi s profess ion and
( 1874-1 93 7), one of the great sc ienti sts ofthe 20th cen-
hi s c hurch] has to move cauti ous ly and even tim-
tury, Hil gers knows that sc ience can not exp la in many
id ly ; thousa nds of hasty (and irres pons ibl e) critics
things, espec iall y, th e greatest of mysteri es, huma n ex-
clin g to him at ali times; he is constant ly rebuffed
32 The Medi cal an d Surgical Practice of NaProTECHNOLOGY
istence. For th at reason, he resonates w ith Marconi 's is directl y re lated to hi s inte rna! freedo m. He is neither
profess ion : " I be lieve, not o nl y as a Cathol ic but a lso as a s lave to medi ca! fas hion nora cava li e r iconoclast of
a sc ie nti st. " 19 w hat is wo1thy in trad itional contemporary obstetric and
gyneco logica l medicine.25 He refuses to be a sychophant
And that 's precisely why, moved as he is by a co mbin a- to dominant menta liti es ofthe medica! comm unity, par-
tion of a fe isty inde pendence and re li g ious conviction, ticularl y to the someti mes nox io us tenets of so-ca ll ed
Hilgersjoined the sma ll coterie ofCatho li c profess ion- " sta ndard of ca re" in earl y 21 st century OB/Gyn. He
als who respo nded to Pope Paul VI 's plea for the deve l- has demonstrated repeated ly that, first, he sees thro ug h
opment ofa sc ience-based, moral method offamil y pl an- the thin fac;:a de of a politic ized science and medici ne
ning.20 That 's a lso w hy, in hi s infertili ty research , he pro motin g so-ca ll ed reproductive freedom and pro-
responded to the ca ll of Donum Vitae. He resisted " the c ho ice wo me n 's hea lth ca re , seco nd , res ists what
temptation to go beyond the limits ofa reasonable do- So lz henitsyn ca lled " the censorship of fashion ," and,
minion over natu re" and made " service ofpersons and third, has the temerity to announce that the emperor of
ofhu man procreation" 21 the cachet ofthe medica ! and so-call ed ass isted re produ ctive techno logy is stark na-
surgical components ofhis reproductive technology. He ked! 26
understands and believes that e ither the a nthropologi-
ca l vis ion behind NaP ro confo rms to the natura l truth Note we ll : Hil gers' freedom to seek the truth without
about the huma n person and hum an procreation en - encumb ra nce from ideology is an inte llectua l ramifica-
shri ned in magisterial teaching, or N PT is simp ly bad ti o n following from hi s un ion w ith the truth of C hri st
medici ne a nd bogus science. and bi s Churc h. An d, by the way, thi s stance explains
w hy he is not shy a bout defending the right of other
o one should dou bt that it was his Roman Cath oli cism physicians and hea lth care workers to invoke conscience
that suggested " lines of sc ie ntific investigation that clauses. He has championed their right to free exerc ise
would not otherw ise have occurred to him ." 22 H e real- ofre li gion, particularly in s ituati ons that wo uld require
izes that the ultim ate tou chstone of the va lidi ty of hi s the ir pa1ticipation in mora ll y offensive practices such
cl ini cal research is its conformi ty w ith the Truth , Jesus as contracepti o n, sterilizati o n or aborti o nn
Christ, and the C hurch that he fo unded .23 A nd it is pre-
cisely because ofthe truth and validity ofNPT that Hilgers
is ab le to offer women 's health care that is small-c catho- Energy and Care
li c, that is, uni versall y applicab le to women everyw here.
Give me the name of the company that produces hi s
vitamins beca use they, together w ith what must be a large
Man of Piety dose of actual graces, produce ene rgy levels th at rival
those of the old "Energizer Bunny" himself. lt makes
Piety su ms up the " ful! circ le effect" in whi ch Hil gers sense to say that the cause of the actual graces is the
lives the C hristia n life w ith ali its dema nd s. Hi s is a fact th at Hil gers expends as mu ch energy and care on
piety that renders God hi s due and then radiates o ut- the humanistic s ide of hi s researc h and medica! p rac-
ward toward neighbor, re nderin g others their due. The tice- w hat JP ll calls " the huma n potentia liti es" 28 of
fait hful obedience and loving wors hip that he renders sc ience- as he does o n the techni ca l.
to God anim ate, a nd find their perfection in , hi s frater-
nal !ove for others. As he makes " an honest a nd res po n-
sib le use of [hi s] own ingenui ty and of the great and Rigor and lntelfectua/ Honesty
sma ll achi evements which sprin g fro m it," 24 Hil gers'
service ofGod is of-a-pi ece w ith hi s service of patients I could not give a more concise acco unt of the intellec-
and profess ional co ll eagues. tu ally rigorous way he conducts research than the o ne
outlined by the Pope for the academic commu nity of
the Uni vers ity of Fribo urg. " For hi s work to be w ho lly
Research Skills - - - - - - - - - - . credib le," the Pope says,
the researcher mu st for hi s part respect those req uire-

lndependence ments w hi c h genera ll y derive from the logic ofsci-
ence itse lf. lt means fid e li ty to the rea lity which has
You do n ' t need to speak to T. W. Hil gers fo r any great to be exam in ed [for Hil gers, the human pe rson and
length befare you realize that hi s abili ty to think things the huma n reproducti ve syste m] , constant self-di s-
throug h- to pinpoint problem s and to find soluti ons- cipline and freedom from se lf-seeking interest, read i-
Chapter 3: NaProTECHNOLOGY and the New Humanism 33
ness to cooperate, wh ich leads to compari son of two facts protects Hil gers from the hubri s of many sci-
one's own res ults with th ose of co ll eagues, eventu- entists who den y, at th eir own peri 1, so me very impor-
all y even to bring them into questi on if they meet ta nt truth s about th e effects ofsin: e.g., th e human intel-
with competent critici sm. 29 lect is handi capped in its search for the truth; the hu-
man will is hindered from consistentl y choosing the
The same ri gorous standards that must be consistently genu ine good, and human freedom is tilted toward li-
appli ed in sc ient ifi c researc h are upheld in hi s work, cense. 32
especially in respect to: th e co ll ection, collation, and
interpretation of data; the experim enta l design of the Putting love of truth as bis first pri ori ty, he knows that,
research proj ect, and the ethical rules that govern bio- rather than viewing themselves and others as beings who
medica l research and its app li cations to clini ca l medi- are somehow beyond history or beyond the Fa ll, medi-
cine. ca! researchers ought to look to the Source of truth ,
goodn ess and beauty as a Font of enli ghtenment that is
beyond th eir puny human intellects.
Originality and Creativity
Dr. Hilgers is the first to ad mi t that he is etern ally in- Sense of Mission
debted to th e work of Drs. John and Lyn Billings whose
prodigious research on th e Ovulation Method began in Dr. Hilgers is a man with a mi ss ion. More precisely, he
1953 , and to Dr. Erik Odeblad whose research efforts is a man with a mi ssion within a mi ssion. His over-arch-
had a doubl e foci: th e biophysica l characteri stics of ing respons ibility is that which is given every human
cervical mucu s throughout the menstrual cyc le and the being in the book of Genes is: to ha ve dom in ion over
mapping of the endocerv ix. 30 Hilgers' origin ality be- the earth. As the acronym NaPro reveals, the heart of
gan with the in sight th at standardi zation (uni fo rmity of hi s secondary mission is to pursue clinical research and
service de livery) of the Billings Ovulation Method of medicine that work cooperati ve ly wi th a woman 's natu-
fami ly plann ing would greatly enhance its precision and ral procreative system.
flexibility and, hence, its effectiveness in helping couples
achieve or avo id a pregnancy. H is ori ginali ty continued Hi s most basic miss ion is not N ietzchean in character.
as he tran sformed what was initially know n as the He does not share the view that the human being and
CREIGHTON MODEL ofNatura l Family Pl anning into, human procreation are things that must be overcome
tirst, the CREIGHTON MODEL FertilityCare™ System but, rather, someone and somethin g, respecti ve ly, that
and , second, into N PT. can be understood and revered. Nor is bis mission post-
hum ani st. He neither rejects obj ective truth nor the in -
trinsic goodness of th e human "biological fo rm" 33 nor
Love of Truth nature 's "normati ve pointings." 34 He is not willing to
enter into a Faustian bargai n that would remodel the
As a clin ica l resea rcher, he is keenly awa re that he has a human being in man 's image rather than in God's. No,
vocation in common with every other human being: to he clearly understands the di stincti on between domin-
be a philosopher, a seeker or lover of (phi/-) wisdom ion and domination over nature, between respect for
(sophia) . Which is to say that, in reference to the truth and cooperation with , rather than the suppression , re-
of the natural world, Hil gers does not limi t bis under- placement and/or total contro l of the procreative ardo
stand ing of existing things to their phys ica l facticity. rerum (order of things).
For to limit know ledge of the hum an person and the
hum an reproductive system to physical facts and only Hilgers ' secondary and more specific mi ss ion is to have
phys ica l facts wo uld denigrate th e truth of th e repro- dominion over (as in hav ing a full er understanding ot)
ducti ve matters under consideration and diminish bi s the comp lex workings of the menstrual and ovulati on
sc ience. He recogni zes that genuine science will sim - cycles. With this knowledge, th e med ica! and surgica l
ply not be had un less and until it is open to correlation services of NPT will, ever more surely, work toward
and confirmation from meta-physical or super-natura l the integral procreative good of hi s patients. In the end,
facticity.31 we ha ve hi s authentic sense of mi ss ion to thank for a
blue-ribbon guarantee that natura l procreative medicine
Whether by the li ght of fa ith or com monsense, he un- is and will be a technology that serves, rather than be-
derstands that people willfully choose ev il and that those trays,35 those who use it.
bad choices ha ve consequences. Knowledge of these
11. NPT: The Vision of lts Science _ _~ nature teaches (and psychological and sociological stud-
ies attest) that, first, ch ildre n find a much-needed secu-
Undergirding and permeating mainstream reproductive rity in the knowledge that they were conce ived w ithin
technology is a scientific theory about the human per- acts of their parents ' committed sex ual !ove. Second,
son and human procreation. lt is a view freighted with for chi ldren to be conce ived, gestated and brought into
materialism, pragmatism, progressivism 36 and individu- and w ith in marriage is impo rtant not just for the
alism. The science ofNPT, in contradistinction, avoids we ll be ing ofthose children but also for a hea lthil y func-
ali of these reductionistic errors. As a result, it distin- tioning fam ili a! and socia l o rder. Third, it is critica! to a
guishes itse lf as a technology that is in dialogue with , sound society that parents who conceive their c hildren
not divorced from , ethics and faith. within a permanent monogamous marriage are also sup-
ported by public laws that o utline parental respons ibili-
The resultant contrasts between mainstream reproduc- ties for those ch ildren.
tive science and NPT are, theoretically and practically
speaking, stark. The science behind contraception and Many infe1tile couples resort to ART because they see
assisted reproductive technologies (A RTs) constitutes it is a quick-fix science. lt provides w hat looks like the
scientism ; the body ofknowledge that grounds NPT is most pragmatically effective way for them to ha ve their
genuine science. Logically, then , the culture of ARTs own biological child. Moral considerations within this
and contraception promotes the " isms" that coll ectively schematic are predictable. The c hoi ce of IVF, o r o ne of
constitute the o ld reductionist humanism . The cu lture its variatio ns, is presented as the "right" choice for two
of NPT, in contrast, advances the new integrated hu- reasons : it wo rks (it's pragmatic) and it's ostens ibl y the
manism envis ioned by the PAS. Let me unpack these most expeditious way of conce ivi ng (i t's useful or uti li-
rather sweeping conclusions. tarian). And, since a "good" choice is one that produces
" good" consequences and maximizes " human happi-
The principal assumption grounding ARTs is that of a ness," the pragmatic c hoice is thought to be necessarily
value-free or morally neutral science. Mora l norms and " ethical."
ethical va lues arise not from an objective source- the
nature of the human person and human dignity- but What 's behind a couple 's choice ofNPT, in contrast, is
from societa l consensus: the culturally acceptable, ever- the convictio n that there are such things as objective
shifting indi v iduali st ic preferences that surface at a ny truth and obj ective ly good a nd bad choices. To choose
given point in time .37 Value-free science views human we ll in the arena of reproductive medicine is , first, to
beings as "the by-products of an evo lutionary process" choose a treatment or method that fu lly respects what is
that ha s no intrinsic finality. 38 Peopl e are, by nature, objective ly true abo ut personhood a nd human fe rtili ty
nothing but material beings, material entities which lack and , second, to c hoose w hat fu lly respects the couple's
not onl y a moral or spiritual dimension but that also dignity and the ir procreative capaciti es.
lack a nature " deeply desirous of knowing the truth " 39
and of choosing the good. 1 suppose, by way of sum mary, yo u co uld say that the
science of NPT is a both/and sc ien ce. The science of
The main premise behind the reproductive science of ARTs, on the other hand, is a reductionistic, either/or
NPT, on the other hand , is rooted in the imago dei doc- science. Proponents of ART a rg ue that, fo r ART to be a
trine ofScripture and Tradition (human bein gs are cre- reason-based sc ience,41 it mu st necessaril y exclude a n
ated in the image ofGod) and the comprehensive psy- appea l to faith. ART's designers in s ist that the empiri-
chosomatic vision ofthe human person to whic h it gives cal observations of reason and experience are the so le
shape. Accord ing ly, God's purposes for male and fe- criteria for finding so lutions to the problem of inferti l-
male sexuality are connatural. Human sexuality is meant ity.
to foster a covenantal life-gi ving love between a mar-
ried man anda woman , who " by a mutual personal gift, But NPT tries to get at the objective rea lity ofwhat is
proper and exc lusive to themsel ves,".¡ 0 mirror God 's being studied- female fert ility, the complexities of the
own inner, tri-personal , love-giv ing life. menstrual cycle and conception- through " a subtle com-
bi nation of faith and experience, intuition and reason,
Moreover, the anthropologica l vision ofNPT- the di- imagination and deduction , persona l insight and com-
v ine p lan for our sexual ly bifurcated human race- is munal w isdom." 42 Stated differently, while the radical
not only discernible by human reason and our human empi ri cist science beh ind ARTs refuses to admit facts
ex peri en ce of natural (moral) law but is al so supported other than those observati ona ll y verifi ab le, the science
by the best availab le scientific data. The law ofhuman of NPT admits metaph ys ical truths. The latter truths,
Chapter 3: NaProTECHNOLOGY and the New Humanism 35
what John Paul calis the " realities ofthe spirit," though a science divorced from ethics and fa ith . Consequently,
notable to be viewed under a microscope, are rea l none- although the scienti sm of ARTs deifi es itse lf, this se lf-
theless and form "part of the whole truth" 43 about hu- proclaim ed science-god 48 has no answers to those im-
man fertility and fertility treatments. In short, the sc i- portant ex istenti al questions that intelii gent people ask,
ence ofN PT necess itates th e march of human reason as such as, " Why are we here?" and " What moral in struc-
it ought to be: "wi th [its] eyes fixed on divine revela- tions do yo u give us?"49 In th e marketpl ace of ideas,
tion. " 44 the fa ilure of a truncated rational ism to provide answers
to li fe 's importan t questions turns out to be an absur-
di ty squared. Such a philosophy directs the designers
111. NPT: The Vision of lts Ethics --~ and provid ers of ART to fl ee not only from "the tran-
scendent mystery ofGod," 50 but also from the mystery
Since ethics and sc ience are wedded in NPT, you have and truth of the human person and human procreation
probably noted that l cannot describe its science with-
out, at the same time, exp lai nin g the vis ion of its ethi cs. So-called "ass isted" reprodu ctive techniques, th en, are
But, beca use 1 now want to concentrate on that moral part of a rationali stic biomedicine that el oses off reason
vis ion , 1 need to probe further. What is the ground of "to the existence of ultimate and obj ecti ve truth. " 51
those already discussed human goods and norms hon- Despair and irrat ionality, the flotsam and jetsam ofthe
ored by NPT? old humanism in general , typifi es the mindset ofmany
infe11ile coupl es in particul ar. After ali , if there is no
Neil Postman provides an innovative way of answeri ng way that human reflection and intelii gent thought can
that question .45 The author and Cha ir of the Depart- di scern the deeper meaning of procreating a new hu-
ment ofCu lture and Communi cation at ew York Uni- man being, or the meaning of hurnan sex uality, or ofthe
versity avers that what our hyper-techno/sc ientifi c age marital act, why bother deri ving moral norms to protect
most desperate ly needs is the " loom" of a story ornar- these human va lues? And if that's the case, how can
rative that helps hum an beings to weave or connect the one find moral direction in matters of fam ily planning
(i nformati o na l) dots of our li ves. So , borrowing and infertility treatments? Why should a coupl e even
Postman 's imagery, the applied science of a reproduc- try?
tive technol ogy would also stand in need ofa transcen-
dent narrati ve. Without this " loo m," the myriad of Given that proponents of ART answer these questions
med ico-techno logical facts of in fertility and in fert ili ty negati ve ly, you can readi ly see why the worldview or
treatments are just "strands" or "dots" of un connected culture of NPT is poles apart from that of ART. NPT
data that have no integrated meani ng. 46 With this 100 111 , recogn izes that the onl y way to understand marriage,
the human interface of that data emerges. In short, it human sex uality, and procreation is to do so within the
takes a transcendent story to show the human signifi- "horizon oftruth" found in the personhood ofGod, the
cance of sc ientific and technological facts ; it takes a divine prototype for understanding ali things human.
story-l oo m to weave them into a whole piece of cloth . Never abandoning the "sapi ential hori zon" of an in-
for med conscience, th e devel opers ofNPT reali ze that
Let me be clear. I am not arguing that NaPro is the only its scientifi c and medi ca! achi evements are inextricabl y
reproductive techno logy whose ethi ca l sens ibilities are wedded to ethi cs and, in turn , to moral theology. The
grounded in a story. Quite the opposite. ART also has persons responsible for the ethical culture ofNPT tru st
its story-loom, the difference being that it's nota tran- " in the power ofhuman reason" to grasp a total view of
scendent narrati ve. The philosophical in frastructure of the human person: "body and sp irit, indi vidual and com-
ART is a finite, secul ar, narrow, partial, prov isional, munity, a rationa l being and one ennobl ed by love." 52
subjecti ve and reducti onist story. To apprecia te the con-
trast, consider this: th e narrati ve gro unding NPT is a In sum , NPT acknowl edges that our hum an reason is
transcendent one- infinite, superna tu ral , ex pansive, a ble to grasp the prim ordi al truth of the di gnity of the
compl ete, comprehensive, and objective. These respec- human person which, in turn, is explained and confirmed
tive narratives dictate drasticaliy contrasting agendas: by Divine Reve lati on. Every hum an being, created in
NPT links sc ience to ethi cs and fait h; ART severs its God 's image, is di gni fied by sharing not on ly in the di-
sc ience from theology or natural moral philosophy, cre- vine spiritu al powers of intell ect and free wili but also
ating a "cri sis of mea ning." 4 7 in th e divine capac ity for life-giving cornmuni on. As
Humanae Vitae points out andas NPT recogni zes, to
As I ha ve already poi nted out, the worldview or cul ture understand responsibl e parenthood is to understand that
of ART hawks a va lue-free, moraliy indifferent science, husbands and wives bear the image of th e Creator in
their w ho le being and are ca ll ed to mirro r God 's gen- deeper meaning of procreation] derive from the sa me
erati ve love in the mutua l self-g ift of the ir sexua l " one- God."62
fl esh" uni on.53 Based on human di gni ty, every hum an
bein g has a right to li fe and a ri ght to be conceived , In sum , the fa ith vision ofN PT, full y admitting that sc i-
gestated, bom into and born w ithin a fa mil y. Hence, th e ence must wo rk in harmony with fa ith , makes an in-
sc ience of NPT also ful fil Is the mora l prin cipies la id va luab le contributi on to hum an culture and parti cipates
down by Donum Vitae: " ... re produ cti ve techno logy fu ll y in th e new humani sm .
that ass ists the conj uga ! act to ac hi eve its natura l end of
pregnancy could be morally li c it . Reproducti ve tech -
nology that does not destroy newly deve lop ing human
life and th at does not di spense with a persona l act of V. NPT: The Vision of lts Ecclesial
inte rcourse betwee n husband and wife is mora ll y lic it, Supporters ----------~
a li other things being equal. " 54
Whil e there is a small coteri e63 of bi shop-, archbishop-,
and cardin al-advocates of N PT, there is no doubt in my
IV. NPT: The Vision of lts Faith - - - - mind that the cu1Tent bi shop of Rome, John Paul Il , is
and has been NaProTECHNOLOGY's most serious and
O ut of the gate, the sing le most impo1tant thi ng 1 coul d si ncere supporter. Tclose thi s arti cle w ith a montage of
say about the fa ith vis ion behind N PT is w hat it is not. se lected publ ic 64 statements of the Pope that app ly to
[t is not fideis m. 55 That is, the fa ith which gro unds PT and confirm my th es is that NaProTECHNOLOGY an-
does not pit " fa ith against reason, beli ef aga inst know l- ticipates biomedi cine's ro le in the new human ism env i-
edge, or re li g ious exp eri ence aga in st criti ca! intelli - sioned by John Paul and the Pontifical Academy ofSci-
gence."56 The sc ience of NPT recogni zes that fa ith is ences membership.
the " great fr iend of intelligence." 57 The R oman Catho-
lic fa ith that inspires NaPro guarantees that the knowl- In respect to the vis ion of the pioneer of NPT:
edge base ofthi s reproducti ve techno logy maintain s the " A li of us w ho bear in our hearts the treasure ofa reli-
ri ght re lati onship between fa ith and human reaso n as it gious fa ith , must share in the common work of man 's
honors their "autonomy and mutuality." 58 The fa ith v i- developm ent, and we must do it with clearsightedness
s ion of N PT admits that, although "science and fa ith and courage."65
re present two di ffe rent orders of kn ow ledge, autono-
mous in their processes," they conve rge, in the end, upon In re5pect to the vis ion of the science andfaith back of
" the di scovery ofrea li ty in ali its as pects, w hi ch has its NPT:
ori g ins in God. " 59 The vision ofth e fa ith behind NPT " Is the commun ity of world reli gions, includi ng the
links "sc ientific thought with ma n 's power in fa ith to Church, ready to ente r in to a more th orough-go ing di a-
seek truth " and " to bring th e whole fu lln ess of human logue with the scientific community, a di alogue in w hi ch
º
capa biliti es to rea li zati on." 6 th e in tegrity of both reli g ion and science is suppo rted
and th e adva nce of each is fos tered? Is th e sc ientific
As a resul t, the Cath oli cism beh ind N PT has confi dence communi ty now prepared to open itselfto Chri stiani ty,
in reason and its human intellectual component is open and indeed to ali the great wo rld re ligions, worki ng w ith
to Catholi c theo logy. The vision of its fa ith puts reaso n us ali to build a culture that is more hum ane and in that
and fai th at the service of the human fa mil y. Hence, it is way more di v ine? We mu st as k ourselves w hether both
a fa ith that will not deteri orate into the truncated rati o- sc ience and reli gion will contribute to the integra ti on
nali sm typi cal ofscienti sm . Wh at's more, N PT is not at of hum an culture orto its fragmentati on. lt is a si ng le
risk fo r the tempta ti on th at pl agues a fu ncti ona l sc ience choice and it confro nts us ali. ... Yet the uni ty that we
like A RT: to serve ideo logy (rather than hum anity). 61 seek . .. is not identity. The church does not propose
that sc ience should become reli g ion or relig ion science .
In short, the fa ith behind N PT stands in the ri ght rela- . . . We are asked to beco me one. We are not asked to
tionshi p w ith reason envis ioned by the Second Yati can become eac h other. " 66
Counc il: " lf meth odo log ica l investigation w ithin every
branch of lea ming [s ubstitute reproducti ve medi cine] In respect to the vis ion of the et/ú es behind NPT:
is ca1Tied o ut in a genuinely sc ientific manner and in " For sc ience develops best when its co ncepts and con-
accord with mora l norms, it never tru ly confli cts with c lusions are integrated into the broader hum an culture
fa ith . For earthl y matters [substitute fa mily planning and and its concerns fo r ultimate meaning and va lue. Sc ien-
in fe rtility] an d th e concern s of fa ith [su bstitute th e ti sts cannot, th erefore, ho ld themselves entirely a loof
Chapter 3: NaProTECHNOLOGY and !he New Humanism 37
from the sorts of iss ues dealt with by phil osophers a nd just fa ilure in relation to fert ili zati o n, but w ith regard to
theologians . .. ." 67 " You w ill always find an al ly in the the subsequent deve lo pment of the embryo, whi ch is
c hurc h, each time that yo u stri ve to promote ma n and ex posed to the risk of death , generally w ithin a very
hi s authentic development." 68 sho rt space of time. Furtherrnore, the nurnber of em-
bryos produced is often greater than that needed for
In respect to the vis ion of the ecclesial supporters of impl antation in the woman 's womb, a nd these so-call ed
NPT: 'spare embryos ' are then destroyed or used for research
"The concept of a morally correct reg ulation offerti lity w hi c h, under the pretext of scientific o r medica!
is nothing other than the rereading of the lang uage of progress, in fact reduces human li fe to the leve! ofsimple
the body in truth ... . A li efforts directed to an ever ' bi o logica l materia l' to be freely disposed of. " 7 º
more precise knowledge ofthose natural rhythms which
are ma ni fested in rel ation to human procreation , ali ef-
forts offam ily counselors and indeed ofthe coupl e them- Codici1 ------------~
selves, are not aimed at making the language ofthe body
merely biological (at reducing ethi cs to biology, as sorne Asan old maxi m points out, ' The wh isper oftruth can
ha ve mi stake nl y held) . But they are ai med exclusive ly ha vean amazing resonance. ' Proof positi ve is that, within
at ensuring the integral truth ofthat language ofthe body the neo-humani st spheres of NaProTECHNOLOGY, our
in which husband and w ife sho uld express themse lves national a nd international communiti es have access to
in a mature way befare the dema nds ofrespons ible par- a proc reati ve cu lture that ce lebrates the priority of eth-
enthood. " 69 ics over medica! techno logy, the primacy of the person
over things, and the supe riority of the spirit over mat-
" The va rious techniques of artificial reproduction, ter. ln shoti, the hallrn ark ofthe new humani sm- seiz-
which wo uld seem to be at the service of li fe and wh ich ing the hidden dynamic behind reality- is interchange-
are frequently used w ith thi s intention , actua lly open ab le wi th t he sc ient ifi c a nd c ultura l c ha ri sms of
the door to new threats agai nst li fe . Apart from th e fac t NaProTECHNOLOGY. What an ac hievement for our
that they are mora lly unacceptable s ince they separate generation and those to co me! What a bold , versatil e,
procreation from the fully human context ofthe conju - and kinetic model ofprocreative medicine! Whata bless-
ga! act, these techniques ha ve a hi g h rate offa ilure : not ing for society and the fa mil y ofhumankind!
1. "Statement of the Pontifi cal Academy of Sciences on the Cul- 4. Lener " To the Reverend George V. Coyne, SJ, Director of th e
tura l Va lues of the Natural Sciences," Zen it, 6117/2003 (ava il- Vatican Observatory," in John Paul /J On Science and Re/i-
able at zeniteng lish@zeni t.org). gion: Rejlection on 1he New Víew from Rome, ed. Robert J.
Russell , Will iam R. Stoeger, SJ and George V. Coyne (Rome:
2. Natural Procreative Technology, an emerg ing science of women 's
Vatican Observatory Publication s, 1990), M 13.
health care, is a compl ex of medica! and surgical interventions
promoting gyneco logical hea lth that obviates the need for ei- 5. D. Q. Mclnerny, A Course in Thomislic E1hics (E lmhurst, PA:
ther reproductive techniques that exclude marital intercourse or Privately printed, 1997), 158.
the prescription of oral contraceptive for therapeutic or contra-
6. lbid.
ceptive purposes . First, it is reprod uctive hea lth care that ass ists
and optimizes, rather than obviates and/or suppresses, the natu- 7. Wendell Berry describes the dangerous hubris ofa reductionist
ra l procreative system. lt allows a woman to mai ntain her ob- sc ient ist: " His humility is on ly etiquette, not a conviction or
stetric and gyneco logical hea lth and he lps coup les to under- even an attitude." (3 1) "Wav ing aside ignorance and mystery
stand and respect the full psychosomati c truth of their fertility. and human li mitation as rnerely illusory or irrelevant, he clairns
Second, it is obstetri c and gynecologica l medic ine that acc u- not only ali knowledge but ali future know ledge and everythin g
rately eva luates and effectively treats a host of abnormal ities unknown as the property of sc ience." (3 1) (Lije is a Mi rae/e:
(whether on an endocrine or anatomi c leve!) wh ich could be the An Essay Againsl Modern Superstilion (Was hington, D.C.:
causes of infertility or, in the case of a pregnant woman, the Counterpoint, 2000.)
cause of miscarriage. Third, it promotes fertility awareness that
8. "The Co llaboration ofSc ience and Religion," Origins 21 (Oct.
enables couples to avoid and ach ieve a pregnancy in a way con-
10, 1991): 283.
sonant w ith the cornprehensive mean ing oftheir conjuga! un ion.
9. Dona ld Attwater, ed., A Catholic Dictionmy, 3rd ed. (New York:
3. John Paul LI , " Moral Cho ices of the Future," Origins 1O (Mar
The Macrnillan Co, 196 1), 239.
12, 198 1): 622 .
1O. Stanley L. Jaki , Sciemist and Catholic: An Essay 011 Pierre consistent with the meaning and integrity of human sexua lity"
Duhem (Front Roya l, VA: Chri stendo111 Press, 199 1), 223. and "with ali three of the ethica l principi es" proposed by DV
regarding the meanin g of human life and human procreati on.
11. Jbid.
(Assisted !-fuman Reproduction: Fa cts and Ethical lss ues
12 . Stan ley L. Jaki offers sound advice to Hilgers and researchers [Dublin: Veritas Publi cations, 2000], 27.)
of his vintage: " ... the Catholi c intell ectua l 111 ust not tum the
22. Avery Dulles, SJ, "Science and Theo logy" in John Paul 11 On
truth of those answers [glea ned fro111 research] in to a function
Science and Religion, 12.
of the 111easure of their acceptance by secular academia, whi ch
is well nigh zero in most cases." 23 . However, to di spel any notion of a fa ith that demands blind
obedi ence to irrational dogma, Father John Neuhaus poi nts out
13. Fro111 the side ofthe medical com111unity and so111e ofth e U.S.
(a nd Hil gers would agree), ''to think with the Church begins
Catholic bishops, Hilgers experiences th e un varnished truth of
with thinking." (Firs t Things, "The Public Square: Pass ion fo r
Pascal 's dicn1111, "S ilence is the greatest persecution."
Truth : the Way or Faith and Reason," 88 [December, 1998]:
14. Aleksandr l. Sozhenitsyn, "A World Split Apart,'' 1978 com- 73 .)
mence ment address at Harva rd Uni ve rsity, (reprint ed at
24. John Paul 11 , 'The Links Between Science and Fa ith,'' Origins
www.nationalrev iew.com, 6/7/2003 on its 25 th anniversary).
19 (Oct. 26, 1989): 340.
15. Stan ley L. Jaki , "The Cat holi c lntell ectu al," availab le at
25. 1 would defin e ·'traditi onal contemporary obstetric and gyneco-
www.ca th o lic.net /rc c/ Pe riodi ca ls/ Dos ie r/ J a n-F ebOO/
logica l medici ne'' as the non-contracepti ve and non-abortive
lntro2.html , 1- 12.
OB/Gyn that had been known, practi ced, and tau ght from
16. Rav i Zacharias, a convert to Chri stianity who grew up in India rough ly the l 940s until the l 960s.
and practiced Hinduism, is one of the first Christian apo logists
26. As Steve Conner, sc ience editor fo r the lndependent News has
to come out of the Third World. His ex pertise on comparative
noted, "Almost every day a sc ientific or medica! deve lopment
reli gions has put him be fo re audiences from Ca pitol Hill to
seems to bring new promise and controversy to mankind; none
Harvard . When asked " How can Chri stian ity meet the needs of
more so, perhaps, than in the field of human fert ility." ("Era of
a place li ke India?" he replied with an answer that confirm s
' unborn 111other ' looms as sc ienti sts use aboned fetu ses to grow
why it behooves Christian sc ientists and intellectuals to take
hum an eg gs," Jul y 1, 200 3 ava ila bl e a t http ://
the ln carnation seriously: "The first thin g Chri stianity does is
n e w s. i nd epe nden t .co . uk / worl d/ s c i en ce 111 e d i ca 1/
rai se the leve! of every indi vidual. There 's an essenti al di gnity.
storv.jsp?storv=420607.) In other words, IVF and it s stem cell
Every human being is of essential worth. The second thing it
and clonin g spin-offs are the bioethics crises du jour.
does is give the i111petus to love and reach out in a way that
rescues the person , not just the functi on.... Fro111 where ca111e 27 . See Thomas W. Hil gers, " Reproductive Medicine and Viola-
the i111petus? lt ca rne fro111 the love ofChrist. " (Jnterview conti on ofthe ' Free Exercise' Clause ofth e United States Constitu-
ducted by Juli a Duin, "Christi an Worldview," The Washington tion,'' Linacre Quarterly 69 (February, 2002): 79-86.
Times, July 4, 2003, avai lable at www.washingtonti111es.co111.)
28 . Letter "To th e Reverend George V. Coyne; · M 13.
l111portantl y, Dom11n Vitae al so states that the Church intervenes
in the area of infertili ty "on th e basis of her duty to protect and 29. " Add ress at the Universi ty of Fribourg," Origins 14 (June 28,
defend the human person and out of love fo r human ity and each 1984): 108.
human bei ng, a love th at has its sou rce in Ch ri st, the lncamate
30. T. W. Hil gers, Th e Scientiflc Foundations o/ the Ovulation
Word." (Joseph Card inal Ratzinger, Doman Vitae. [Et/úes &
Method (Omaha: Pope Paul VI ln stitute Press, 1995), 1; 16-32.
Medies edit ion of DV(Pope John Center: Bra intree, MA , 1987)]:
7.) 3 1. Stephen M. BaiT points out that what many people re fer to as
the conflict bet:ween fa ith and sc ience is reall y a conflict be-
17. John Paul JI , Fieles et Rafia,# 79. Dr. Hil gers looks fmward to
tween materi ali sm and religion. ·' Materia lism regard s itsel f as
the day when the majority of the U.S. Cat holi c bishops encou r-
sc ientific, and indeed is oft en ca ll ed 'sc ientific materi ali sm,'
age and act ively support Catholi c sc ientists and phys icians who
even by its opponents, but it has no leg it imate claim to be part
are courageous enough to take up the Church's chall enge to
of science. lt is, rather, a school of philosoph y, one defi ned by
uphold Catho lic principies in their research and clinical prac-
the belief that nothing exists except matter, or, as Democritus
tice. He expectantl y awa its the day when the bishops respond
pul it, 'atoms and the vo id."' (" Retelling the Story ofScience,"
with heartfelt gratitude to hi s announcements about a system of
Firsl Things 131 [March, 2003]: 16.)
wo111en's hea lth care that responds to ( 1) the pleas of Pope Pau l
VI for a syste111 offam ily plann ing that is 111ora l and (2) to Doman 32. Gilbert Meil aender suggests that human beings, including sc i-
Vitae fo r a system of reproductive technologies that (a) truly entists and researchers, ought to keep cruc ial questions in mind:
ass ist the conjuga! act rather than replace it, that confom1s to Is there ··any limit to such free self- tran scendence;" are we '\vise
the digni ty of the couple and their uni on and (b) intervene in enough and good enough to be free self-creators," or ought we
developing human li fe onl y in ways that respect the in violabi l- "acknowledge destructi ve poss ibilities in a freedom that refuses
ity ofhu111an life in 11/ero. any lim it?" (" Bioethi cs and the Character of Human Life ," The
Neiv Atlan tis, 1 [Sprin g, 2003] avai la ble at
18. Jaki , "The Catho li c lnte ll ectual,'' 9.
www. thenewatlanti s.com/arch ive/ l/meliaenderprint.htm , p. 2.)
19. The premise of Gug lielmo Marcon i's profess ion is that fo und
33 . C. Christopher Hook, " In Whose lmage?: The Remaking of Man
in an oft-quoted insight offellow-sc ientist, Albert Einstei n ( 1879-
with Cybemetics and Nanotechnology," (Mayo Clin ic Founda-
1955): "Science without reli gion is lame, religion without sci-
ti on, written sometime after late spring of 2000): 5.
ence is blind." (See " People of Faith- Famous Sc ienti sts" at
http://www.godandscience.org/apologetics/sc iencefa ith.html.) 34. Richard John Neuhaus (quoting Leon Kass in ), 'T he Public
Square: A World of Our Own Making," Firsl Things 87 (No-
20. See !-!umanae Vitae, #24.
vember 1998): 72. In the sa me article (74), Neuhaus points to
2 1. Ratzinger, Dom11n Vitae (ln troduction , # 1 and Part 11 , B, #7), 7 the deleterious results of a revo lution that swept aside the "nor-
and 19. The lrish Bishops' Co111mittee on Bioethi cs mora ll y as- mati ve pointings" ofhum an sex uality: "Sex seemed such a pretty
sessed the various techniques of ART and declared: "Na Pro is tinkertoy, and so 111addeningly complex. Telling oursel ves that
Chapter 3: NaProTECHNOLOGY and the New Human ism 39
we did not know what it was fo r, we took it apart to find out 37. 1 was reminded ofjust how vacuous and downright se lfi sh hu-
how it works, and could be made to work in different and exc it- man preferences can be when 1 read th e fo llow in g repon re-
ing ways. After the deconstructi on, thi s part ofth e anatomy was counti ng a woman 's reasons for using one of 1VF 's spin-ofTs,
stuck into that part, and thi s kind substituted for that kind, un til prenata l geneti c diagnos is: "' Em bryo gender se lection is per-
ali memory of design was lost in the immeasurable ex panse of mitted in Spain for fa mil y balancing, as we ll as fo r medica!
desire. ' Sex is fu n,' it was sa id ever more insistently, ever more reasons. Ms Chenery, who is now 17 weeks pregna nl, under-
desperately. Ofcourse there were the spoil sports among us. They 1venl a previous unsuccessfi.il a//empr to conce ive a baby girl at
remembered, and they mumbled about 1he nalure of !he lhing , the Span ish clinic in Jan uary. She is now reported to be 'de-
and how it was somehow and in separab ly tied up with the nali ghted ' and cann ot understand why the procedure is banned in
ture of us. ' 01110/ogy' they ca ll ed it. They were tolerated, so Britain. ' I ha ve always wanted lo ex perience the mother-daugh-
long as they didn 't get in the way of our doing what we wanted ter relationship, which is totally difTerenl to the mother-son re-
to do, even though we had grown tired ofwantin g to do nothing Jationship, and 1 feel as 1 can, then why not?', she sa id." 1 would
more than what we wa nted to do. '' (emphasis mine) wager that the phrase in itali cs is a c1y pt ic way to desc ribe th e
abortion of a prev iously prod uced embryo whose ticket to ex-
35. " Betrays" (as in betrays the parents, the surrogate and the child)
tincti on or cryo prese rvati on was bei ng of the wro ng sex.
sums up the sad commentary of the mindset ex pressed in "sur-
(BioNews 2 14 ava il able at http://www.progress.org. uk/News/
rogacy facts" published in Parems magaz ine: "' lf you' re con-
BioNewsSearch.htm l 6/23/2003-6/29/2003, p. 6.)
sidering surrogacy, here are sorne things you shou ld know. A
surrogate ca n become pregnant in one of two ways: She can 38. Luke Gonnally, "Luke Gorma ll y on Hum an Dignity and Bioet-
have her ow n eggs artifi cia ll y inse minated by the fat her 's sperm, hics- Pa rt I," Ze nit , Jul y 11 , 2003 (ava ilab le at
or she can have another woman's artifi ciall y inseminated eggs zenitengli sh@zenit.org).
implanted in her uterus. Th e Jatter, which is ca lled gestational
39. Joh n Pau l 11 , " Raising the Leve! of Philosophi ca l and Theologi-
surrogacy and invo lves in vitro fe rtil izat ion, costs aro und
ca l Retlecti on," Origins 28 (November 19, 1998): 404.
$ 10,000 per attempt. Arti fic ial insemination of the surrogate's
eggs costs abo ut $5,000. Most insurance poli cies do not cover 40. Joseph Cardinal Ratzinger, Congregation fo r the Doctrine of
eith er. Wh en surrogacy is arranged through an agency, the sur- the Fa ith, "Considerati ons Regarding Proposa ls to Give Legal
rogate is genera lly paid for her services. She might undergo Recogniti on to Uni ons Between Homosex ual Persons," # 2
psychologica l screening to determ ine her mot ivation and whether (ava ilable at www.vatican. va).
she can cope with being pregnant and giving up the baby. Laws
41. C. S. Lewis ( 1898-1963) understood that, although sc ient ific
regardi ng surrogacy vary from state to state. Some req uire par-
reason is va lid, it is not the only kind of reasoning. He poi nted
ents to lega lly adopt the child , even if it 's biologica ll y theirs.
out that, although "[N]oncontrad iction, va lidity, truth , va lue,
Others ban for-a-fee surrogate arrangements completely. Con-
meanin g, purpose, and ob li gat ion" are "'necessary presuppos i-
sult an attorney for the laws in your state." (Melba Newsome,
tions of the scientifi c method" they are "'not themselves scien-
" Meet a mom, Debbie, who vo lunteered to be a surrogate fo r
ti fi c pheno mena." (M . D. Aesch lirnan, "C. S. Lewis on Mere
her pal, Stacey, an d gave birth to quads." March, 2003 : 15 1.)
Science," Firsr Things 86 [October, 1998]: 17.)
The ba ldly mercenary theme of ARTs sin gs loud and clear-
42. Du ll es, "Science and Theo logy," 13.
seemingly without anyone's protest- in thi s descripti on of"egg
givi ng." 'The UK's Human Fertilisati on and Embryology Au- 43. "A Papa l Address on the Church and Science," Origins 13 (Ju ne
thority (HF EA) has announced th at it has started a review of th e 2, 1983): 52.
practice of 'egg giving'. Egg giving is a ty pe of egg donati on
44. Jaki , Scienris1 and Ca1holic, 278.
where patients wa iting fo r 1VF treatment undergo one cycle of
egg retrieva l and al i the egg col lected in that cyc le are donated 45. Ne il Postman, "Science and th e Story that We Need ," Firs r
for use by another woman. The woman then receives a second Things 69 (January, 1997): 3 1.
cyc le at a reduced cost, keeping ali the eggs retrieved for her-
46. Edna St. Vincent Millay's poem, "Huntsman, What Quarry?"
self This differs fro m 'egg sharing', a more common ly oper-
describes the "crisis of mean ing" amidst th e glut of our in for-
ated scheme, where halfthe eggs co ll ected in one cycle are do-
mation age and the need fo r a story- loom:
nated and the other half used by the patient, agai n in retum for
Upon this gifted age, in its dark hou r,
a redu ct ion in th e usua l pri ce of IVF." (ava il a bl e at
Rains from the sky a meteori c shower
BioNews@progress.org.uk: "Egg Giv ing Schernes Under Re-
Of facts . .. they líe unquesti oned, uncombined.
view," BioNews (7/2 1/2003): 4.)
Wi sdom enough to Jeech us of our ill
36. ' Progress al any cost' an d ' the objectifi cation ofhuman be ings' Is daily spun , but there ex ists no 100111
are the best ways to sum up the mora l sensibilities of the fo l- To weave it into fa bri c
low ing rosy report marking the 25th an ni versary of th e birth of
47. The presc ience of Rev. John Cowtney Murray, the Jesuit author
the first IVF baby, Loui se Brown. "Most infertility problems
of the Second Vatican Council 's teaching on religious freedom
could be eradicated in ten years, accordi ng to Alan Troun son,
who wrote nearly a half century ago, is stri king. He prophesied
from the Monash lnstitute of Reproduction and development,
that contemporary soc iety would be "a technical order ofthe most
in Victoria, Australi a. Troun son, one of the early pioneers of
marvelous intricacy, which will have been const:ructed and which
IVF, said that the key to many infertility related problems may
will operate without true política! ends: and this technologica l or-
be found by undertaking research 011 stem cell s and combining
der will hang, as it were, suspended overa mora l confusion; and
stem cell technologies with ex isting fertili ty treatments ... . Roger
this moral confusion will itself be suspended overa spiritual
Pederson, a stem ce ll researcher at the Uni versity ofCambridge,
vacuum." (John F. Cul linan, "Godless in Brussels," Narional Re-
UK, said the enormous potenti al of ES cel Is, for treatments for
view Online, 611612003 [http://ww·w.nationalreview.com] : 4.)
both in fertili ty and disease, is 'ali a Jegacy of2 5 years of IVF',
addin g that 'eve1:y single emb1yo 111hich can be srudied is a 48. Ne il Postman labels this stand-in fo r reli gion as "a fa lse god." lt
resu/1 of I VF". " (it a lics min e . Ava il ab le al is a god that "speaks to us of power, not limits; speaks to us of
BioNews@progress.org. uk, "Scientist Predicts Soluti on to ln- ownership, not stewardship; spea ks to us onl y of rights, not re-
fertility," BioNews (7/21 /2003]: 3.) sponsibili ties; speaks to us of se lf-aggrand ize ment, not humi l-
ity." ("Sc ience and the Story that We Need," 3 1).
49 . lb id. bi sho ps (e.g., Archbi shop Chaput of Den ver, Bi shop Stei nbock
ofFresno, and Bi shop Galeone o fSt. Augustine to name a few).
50 . John Paul 11 , " Raising the Leve l,'' 403.
Bi shop Ga leone was especially candid regarding the etiology of
5 1. !bid. the cris is of the past fo ur decades in respect to marriage. In hi s
35th anni versary letter, " Marriage: A Communion of Life and
52. John Paul 11 , " Mora l Choices of the Future," 622.
Love," he adm its, " beca use of our sil ence we bishops and pri ests
53. See Humanae Vitae, especially nos. 8-10. are to blame." (# 12) He compares the w idespread use of con-
traception as a "spiritual cancer" and laments, " [c] onfronted
54. Ratzi nger, Do11111n Vitae, 9.
w ith the spiritual cancer attacki ng the fa mil y today, how can
55. More complete ci tations ex plain the danger of depreciating rea- one ex pl ain the reluctance of us bishops and priests in spread-
son. The first iffrom John Paul 11 : " lfreason cann ot atta in ult i- ing the good news of the Ch urch 's fu ll teaching on married love
mate truth s, fa ith loses its reasonable and inte lli gible character and li fe?" (# 15) Hi s fi ve concrete prescriptions for correcti ve
and is reduced to the realm of th e nondefin abl e, th e sentim enta l acl ion are wonhy of duplicati on in eve1y U.S. diocese. (see #
and the irrational. The o utcome is fideism. Detached from its 15)
relat ionship to human reason, faith loses its public and uni ver-
64. Personal letters fro m John Paul 11 to Dr. Hil gers and the staffof
sal va li dity and is lim ited to the subjecti ve and private sphere.
the Pope Paul VI ln stitute always " make our day.'· Hi thor-
l.n the end, theo logical fa ith is destroyed." (" Raising the Level
oughgoing suppon is as heanenin g as it is genuine. E.g : " ! am
of Philosophi ca l and Theo log ica l Re íl ection," 404). The sec-
grateful for the contribution that the ln stitute makes in pro mot-
ond is fro m M. D. Aesch liman:" ... there is an oppos ite temp-
ing faithful observance of the Church's teachings regarding mar-
tati on that [C. S.] Lew is also criticized-the temptation to deji-
riage and the fa mil y. In a special way l wish to recognize and
sc ience, from the standpoint of either romantic/panthei stic Gnos-
encourage th e ln stitu le 's continuing effons intent on bui lding
ti cism or theological fidei sm .. . Th e appeal of pantheisti c G nos-
that cu lture of life whi ch is so vita ll y imponant for today 's soci-
tici sm was so mething that Lewis understood and withstood ; it
ety. As 1 wrote in the Encyclical Letter Evange lium Vitae, cen-
lies at the hean of occult ' ew Age ' spirituali ty, ' deep Eco logy, ·
tres for natural methods of regul ating fertility need to be pro-
and a good deal of ' eco-fem in ism' today.'· ("C. S. Lewi s o n
moted ' as a va luable help to responsible parenthood, in which
Mere Science," 17).
all indi viduals, and in the first place the child, are recognized
56. Neuh aus, "The Na ked Publi c Square: The Pass ion for Truth: and respected in their own right, and where every decision is
the Way of Faith and Reason," 73. gu ided by the ideal ofthe sincere g ift o f self (No. 88)."' ( Letter
sent on the tenth anni versaiy of the Pope Paul V I ln stitute 's
57. Joh n Paul 11 , "Address to Ponti fical Academy o f Sciences; ·
fou nd ing: " From the Vatican, 24 August 1995." )
Origins 13 (Nov. 12, 1984): 542.
65. " Mora l Cho ices ofthe Future," 623 . Elsewhere John Pau l refers
58 . Neuhaus, " Pass ion for Truth ," 70.
to the miss ion of a scienti st as the ''practice ofthe ir own spec ial
59. John Paul 11 , ·'A Papal Address on the Chu rch and Science,'' 51. pri esthood. " ("The Links Between Scien ce and Faith ," 340 .)
60. John Paul 11, ·'Sc ience and the Church : A Di alogue,'· Origins 1O 66. Letter "To the Reverend George V. Coyne,' · M7.
(Dec. 4, 1980): 397.
67 . lbid ., Ml 3.
6 1. lbid. , 396.
68. " A Papal Add ress on the Church and Science," 52 .
62 . Gaudium et spes, # 36 (c ited in ''The Co llaborati on ofScience
69. Lije According to the Spirit: Rejlecrions on "Hwnanae Vitae,"
an d Religion," Origins 2 1 [Oct. 1O, 1991]: 283).
in The Theology of rhe Body: Human Lave in rhe Divine Plan ,
63. The accen t is on the word smal/. Getting support, sp irirual or wi th a Foreword by Joh.n S. Grabowski ( Boston, MA : Pauline
fin anc ia! from the U.S. Catho lic bishops is one of the greatest Books & Media), 402.
challenges to the Catho lic acceptance ofN PT, as noted in foot-
70. Evangelium Vitae in The Encyclicals ofJohn Pau/ 11 , ed. w ith
note # 15. Pascal 's reminder, "Si lence is the greatest persecu-
Lntrod uctio ns by J. Mi chae l Mill er, CS B, (Huntington , IN: Our
tion," is germane to this discouraging situati on. However, change
Sunday Vi silor Publi shing Di v, 1996), 804.
is in rhe air. The 30th ( 1998) and 35th (2003) anni versaries of
H V ha ve precipitated sorne outstanding pastora l letters from
Part 1:
?~Jc,&llcff, te tA,e
CREIGHTON MODEL System
Thomas Hilgers, M.O . "Woven into the fabric of the Creighton Model System is a
Chapter4
Catholic understanding of the personal nature of our
human sexuality and the challenge to respect one 's
spouse, to respect the workings of one 's body, and to try
to understand and further allow far two people to relate in
a way that God intended. ..[The CrMS] contribut[es] to
counteracting the extraordinary crisis that exists in our
modern society."
41
42
lntroduction to the
power by mandating fertility contro l. 3 Each of these

R es e a rc h le adin g to th e d eve lopm en t o f th e
CREIGHTON MODEL FertilityCare™ System
(CrMS) began in 1976 and the system was first full y
prophetic in sights ha ve come true in our modern soci-
ety.
described in 1980. 1 It is a full y in tegrated educational
system whi ch has an extrao rdinary degree of sc ientific Humanae Vitae was met with great di ssent by the theo-
understanding and va lidi ty. logians and the Cathol ic lay popul ati on who fo ll owed
those theo logians. The Churc h 's pri ests or bi shops gave
Woven into the ve ry fa bric of the CREIGHTON MODEL little leadershi p to help guide the fa ithful out of th at
System is a Catholic understanding of the personal na- abyss. Along with thi s dissent to the fund amental teach-
ture of our human sexuali ty and the chall enge to re- ings, there has been alm ost compl ete neglect of what
spect one's spouse, to respect the workings of one 's are referred to as the " pasto ral directi ves" of Humanae
body, and to try to understand and fu11her all ow fo r two Vitae, 4 or w hat could be referred to as the "challenges
people to rel ate in a way that God intended. T hus, thi s of Humanae Vitae."
makes a contributi on to counteracting the extrao rdinary
cri sis that ex ists in our modem soc iety. Pope Paul V I, in seeking aid and protection for marri ed
coupl es and the fa mil y in the third part ofth is encyc li-
In 1968 , Pope Paul V I iss ued the now-fa mous encyc lica l letter, made a perso na l appea l to seven d ifferent
ca l letter, Humanae Vitae.2 In that letter, he outlined th e gro ups of peopl e to carry on thi s work, meet the cha l-
longstanding teaching ofthe Cath oli c Church with re- lenge, and develop the p rogram s necessary to see that
ga rd to contracepti o n, s te rili za ti o n a nd abo rt io n. the teachings of the C hurch could become viable. He
lncredib ily, he was abl e to predi ct th e co nseq uences of appea led to pub lic authoriti es, men of sc ience, Chr is-
co ntraception. The Ho ly Father predi cted that mari ta l ti an spouses, the a posto late of spouses, doctors and
infidelity would increase, th at there wo uld be a weak- hea lth care profess iona ls, priests and bishops. The re-
ening of moral d iscipl ine, that hu sbands wo uld lose response to thi s cha ll enge has been deafe ning ly silent.
spect fo r the ir wives and th at they wo uld begin using
the ir w ives (and others) as instruments fo r serving their No compari son can be made between th e response to
own des ires, and that publi c authority wo uld exercise these specific chall enges given by the leader ofth e larg-
43
est religious force in the world and the response that Planning) was first established in 1982 and is no w the
has been given to the scientifi c investigation into the official national certifying and acc rediting body for the
methods of contraception, sterili zation , abortion , the CrMS . FertilityCare™ Centers of America and
artificia l reproductive technologies, and so forth. Those FertilityCare™ Centers lnternational lin k a li of the
who believe in contraception , sterili zation and abortion CREIGHTON MODEL programs through a network of
ha ve far outstripped the formation ofprograms and de- FertilityCare™ Centers throughout the United States,
ve lopments that would lead to the widespread use of a Canada and in many other areas ofthe worl d. In 1985,
natural means to regulate human ferti lity orto a better the Pope Paul VI lnstitute fo r the Study of Human Re-
understanding ofwhat Pope John Paul 11 calls the " lan- production , the home of the CrMS and the new repro-
guage ofthe body." 5 ductive science of NaProTECHNOLOGY, was estab-
li shed for ongoi ng research and education program de-
ve lopment.
The Need to Aid and Support Couples=l The first vo lu me ed ition of the CREIGHTON MODEL
training manua l was pub lished in 1982 .9 It presented a
The Catholic Church, coming out ofthe second Vatican program capable of making advances in this field in a
Council, presented the follow ing teaching, "Human be- way no other program had been ab le to do up to this
ings shou ld also be judicious ly informed of sc ientifi c point. Now, the CREIGHTON MODEL FertilityCare™
advances in the exp loration of methods by w hi ch System has we ll-estab lished effectiveness stud ies which
spouses can be helped in arranging the number oftheir se rve as its foundation, and the CrMS forms the very
ch ildren. The re li ab ility of these methods should be hub of the new medica! and surgical women's health
adequately proven and their harmony with the moral science of NaProTECHNOLOGY. This training manual
order be clear. " 6 was completely updated in 2002 10 and its companion
vo lume, Book Il, on advanced teach in g ski li s was pub-
At about the same time in 1969, Pope John Paul II, who li shed in 2003. 11
was then Card in al Karol Wojtyola, proclaimed that,
"abandoned to their own li ghts, most married co upl es Thus, it is a system that not on ly establi shes a very strong
will remain stuck with their difficulties and , without scientifí c foundation and serv ice de livery program but
competent help, they will run the risk oflosing fa ith in has also responded to the ap pea ls of the popes of the
God and rema in the prisoners of inextricable and des- last 35 years and respo nd s to the Catholi c C hurch 's cal!
perate moral conflicts." for a view of human sexua l ity that goes beyond what
our current society seems to accept.
After he became Pope John Paul II , he wrote in bis ap-
ostolic exhortation to famil ies, Familiaris Consortio ,
that, " .. .the necessary co nditi ons also include knowl- The CREIGHTON MODEL
edge of the bod il y aspect and the body 's rhythms of FertilityCare™ System - - - - - - - - - - .
fertil ity. Accord ingly, every effort must be made to ren-
der such know ledge acceptable to ali married people The CrMS is a standardized modification of the Bill-
and also to young adults before marriage, through clear, ings Ovulation Method. [t is a leg itimate offspri ng of
timely and serious instruction and education given by that system which is built on research , education, and
married coup les, doctors and experts ." 7 service (the "triangle of support" for th e CrMS user -
see Figure 4- l) and is an integrated educational system
Since that time, the Holy Father has continued to write designed to ass ure the highest quality service de li very
in this area. He has developed what is now called the possible for the FertilityCare™ Educator, Practitioner,
"Theology of the Body." 5 And , in his encyclical letter and the client coup le.
Evangelium Vitae (the Gospel of Life), 11 he specifically
called upon institutions and individuals to develop aca- In the CrMS , fertility is observed as a part ofhealth, not
demic centers for research and education in the field of disease. It is a system that is specificall y nota natural
natural fami ly planning and also to develop service pro- contraceptive. Rather, it is a true method of family
grams for such. planning ... a method that can be used in two ways -
to ac hi eve as well as to avo id pregnancy. These prin-
The CrMS has responded to ali of these calls. The cipies make this system distinctly different from con-
American Academy of FertilityCare Professionals traception (artificia l or natural).
(formerl y the American Academy of atura! Family
Chapter 4: lntroduction to the CrMS 45
e mphas is on the achievement of pregnancy in couples

CLIENT COUPLE of completely normal fert ili ty. While an emphasis has
been placed on assisting couples with in fert ili ty (and
the CrMS has a very special capab ili ty ofhe lping coupl es
with those types of problems), these two systems are
unique in their abil ity to assist coup les of compl etel y
normal fertility to use th em throughout the course of
their reproductive life for both the achievement and
avoidance of pregnancy. Therefore, it is, by definition
and application , a lifelong system not to be reduced to
a fract ion ofone 's procreative life.
Fertility Appreciation _ _ _ _ _ _~
RESEARCH Fertility a ppreciation is a term that is used in the CrMS.

Figure 4-1 : The "triangle of support" for the CREIGHTON lt can be defined as the abiliry to mutual/y value, re-
MODEL user. s
spect, and understand one fertility. Such a va lue, re-
spect and understanding should befoundationa/ to the
teaching and use ofthe CrMS .
The CrMS is based upon a couple's knowledge and
understanding oftheir naturally occurring phases offer-
tility and infertility. Through this understanding, the Background of the System ----~
co uple is ab le to make decisions (choices) regarding
the ach ievement or avo idance of pregnancy. lt is the The fundamental principies of the CrMS have been
onl y system (besides the Bi lli ngs Method) that provides known to phys ic ians for many years and we ll docu-
information dealing with the comp lete dimensions of mented a lthough, as Cohen, et al 12 observed, "They have
the procreative ab ility. In addit ion, it provides women been almost disregarded by gynecologi ts ." In 1952,
the added benefit ofbeing ab le to monitor and maintain this group published a schemata ofthe events that oc-
their procreative and gynecologic health overa li fetime. cur relative to the changes in the cervical mucus as ovu-
CrMS teac hers are trained a llied health professionals, lation approaches. In retrospect, this schemata a lso de-
and physicians are trained to incorporate the CrMS into fined the basic principies ofthe not yet described Bill-
their medica! practice. ings Ovulation Method and the CrMS (Figure 4-2) .
lt is a system that is comp lete ly integrated in its educa- 1t was noted that as ovulation approached, the stretch-
tion , research and service orientation. It meets the de- abi lity and clarity of the mucus increa ed along with its
ma nds of the al li ed hea lth and med ica! professions in quantity ofproduction. At the same time, the v iscosity
the fie ld ofthe natural means to regulate ferti li ty. [t is and its content of leukocytes decreased. The most per-
bui lt to accomplish accountability and competency tinent observation, however, was the indication that th e
throug h a strong profess ional infrastructure (see Chap- survival of the spermatozoa was directly re lated to the
ter 18) and it works within
the context of a Cathol ic
l /l
e thical and m ora l serv ice
de l ive ry framework . The
CrMS a ll ows rnarried
couples the opportunity to
consciously cooperate in the
CERVICAL l(UCUS ~-::7
SPI MM LUltEll' 1 Ol
i & GIL IS CM. 12 CM.
C'íf:::7
3 CM .
ach ievernent of a pregnancy TMIN THI .. TMIC:K
VISCOSITY THICk lotOOERAT!
as a cornponent of the use ®AHflTY + ~ .... +
of a natura l system . At the LlUCOCVU$
* o o
-+++t-
*-t- *
present time, the Billings Sl'UM $4MNIVAl. o -lltt' !l+t +
Ovulation Method is the Figure 4-2: Cohen's original schemata far the events that occur in the cervical mucus around
o nl y other systern ofwhich the time of ovulation . Of special note is the depiction of the sperm survival and the , de facto ,
we are awa re that puts such recognition of the role of the cervical mucus as a biological va lve (From : Cohen MR , Stein IF
and Kaye BM : Spinnbarkeit: A Characteristic of Cervical Mucus. Fertil Steril , 3: 201 , 1952).
14
20
Figure 4-3 : Three cycles charted for the CrMS showing the occurrence of menstruation , the pre-Peak dry days, the mucu s cycle,
the Peak Day (P), and the post-Peak dry days. The pre-Peak phases are va riable in length (14, 9, and 20 days) but the post-Peak
phases are consisten! (14, 15, 13 days).
19 20 21 22
Progesterone
40.0 ng/dl -+--ll-+--+-+-+-+--ll-+-+--11-. .1-1---ll-+-+--ll-.f-4-~-l-4-~-l--+-+--+--20 . 0 ng/ml
30.0 ng/dl -+-t-+;~-+--+--+-t--+--+-6-_.....,._t--+--+-t-..a-...,_.1--+--+-1-•-1-+--+- 15.0 ng/ml
5.0 ng/ml
Figure 4-4: Th e relati onship of serum levels of estradiol-17 ~ and progesterone during the course of the menstrual cycle and the
occurrence of the mucus sign and the Peak Day (P) in one cycle of a woman with normal fertility.
Figure 4-5: The application of the CrMS in long cycles. In this 51-day cycle , the Peak Day (P) occurred on day 38 . The post-
Peak phase was 13 days in duration . During the pre-Peak phase, "patches" of mucus are apparent.
presence or the absence ofan ovu latory or periovulatory The same principies appl y in anovu latory conditions
type ofmucus produced form the cervix . such as breast feeding (Figure 4-6). lnfant suckling may
suppress ovulation and ferti lity for a number ofmonth s.
In the CrMS, externa! vu lvar observations of the dis- The presence or abse nce of the characteristic cervical
charge ofthe cervica l mucus, the presence ofbleeding mucus discharge associated with ovu lation is then de-
and the days w hen no discharge is present (dry days) layed until fertil ity retums and predicts the onset ofthe
are ali used to obtain pertinent information on the phases first menstrual period.
offerti li ty and infertility and the state ofthe woman 's
procreative and gynecologic hea lth . The versatility of the system, clearly one of its stron-
gest features , is fo und in its fundamenta l bi ology. Be-
In the woman with regular cycles, the cyc le begins with cause it relies on events leading up to ovulation , it de-
the onset of menstruation (see the first cyc le of F igure fines the times offerti li ty and infertility in a definitive,
4-3). As menstruation tapers there is genera lly no dis- day-by-day, prospective fashion. Previously difficult
charge and the woman observes this as dry. As ovu la- cases, such as long and irregular cycles, breast feeding,
tion approaches, there becomes apparent a cervical com ing off of contraceptive pi lis, anovulatory states and
mucus di scharge which often begins as sticky, c!oudy the premenopause, ali can now be dealt with in a posi-
or tacky, cloudy discharge and eventua lly becomes c!ear, tive fashion without delay.
stretchy or lubricati ve. The last day of the mucus dis-
charge that is clear, stretchy or lubricative is identified Even a woman with a continuous mucus discharge (Fig-
as the Peak Day. ures 4-7 and 4-8) can properly identi fy th e days offer-
tility by using a base infertile pattern (BIP) which is
The presence of the cervical mucus discharge corre- identified with the presence ofan unchangi ng discharge.
lates well with the rising leve Is of estrogen (Figure 4-4) When fert ili ty begins, there will be a change in the pat-
and the occurrence of the Peak Day is correlated we ll tern , which is easil y identified by the woman who has
with the timing of ovulation. been properly instructed . Thus, ferti lity is identified .
Because the production of the periovulatory cervical The CrMS is not a contraceptive system. lt is a system
mucus is an estrogen dependent effect and is produced of true family planning (see Figure 4-9). The informa-
at the ti me offollicular deve lopment, when estrogen is tion obtained from monitoring the phases offertility and
increasing and ovulation approaching, the cervical mu- infertility can be used to either achieve or avoid preg-
cus is produced and will be di scharged before and dur- nancy. Users of the CrMS know their fertility status on
ing the time of ovu lation . In long cycles (Figure 4-5) any parti cu lar day and are given the freedom to utilize
there may be occasional "patches" of mucus prior to that information as they so choose. Those who use a
the onset ofthe mucus associated with ovulation. What day of ferti lity to achieve a pregnancy are successfu l
is prolonged in these cycles is the pre-Peak (or preovu- users and not failures . A pregnancy can legitmately be
latory) phase of the cycle and what rema ins relatively observed as the result of the system 's successful use.
consistent is the post-Peak (postovulatory) phase ofthe
cyc le. At the same time, it can also be used by couples, with a
Figure 4-6 : The application of the CrMS in breas! feeding . "Patches" of mucus occur sporadically, dry days usually predominate,
and as fertility returns , the mucus pattern and fertility return .
7 9 11 1- .;o :?_,, 29 lo 15
2 5 11 27
"'
1 1 ó X 15 ~J 24 32 3.l 14
4 10 12 14 I~
'' 19 21 " :?_) .1 /
,., - - -
~ ·p 'l
u li
l i
V
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,,
óC 6 C 6GC f/6f
,, 6C 6 C 6C l'C li'C. ve 6C
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'iC. \IC. yc,, •" "º ~ 101< tpC o AD
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.e;~ .:-..~ ....,. ..- '"., ."•. ."'

l
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tpC
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'ik
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f =POINT OF CHANGE :
110
~F -t
Figure 4-7 : The example shows the use of the CrMS in a breast-feeding woman with a continuous mucus discharge . The plain
yellow stamps indicate a discharge pattern which is the same from one day to the next. The arrows indicate th e points of change
and the baby stamps indicate days of fertility.
Chapter 4 : lntroduction to the CrMS 49
hi gh degree of securi ty, as a means of avoiding preg- has been done in thi s area has been completed at the
nancy. The data not only suppo11 this but our own expe- Pope Paul VI Institute fo r the Stud y of Human Repro-
rience with thi s system shows th at even those coupl es duction in Omaha, Nebraska. Th is reflects the Institute's
who have very strong medi ca! reasons to avo id preg- bac kgro und and experi ence in obstetr ics and gynecol-
nancy can use it effecti vely so long as they are con- ogy and in reproducti ve medicine and surgery. As thi s
nected to a quality education system for pro per tra ining system has been used over the years, it has become an
and support. ideal toolfor any gynecologist.
Because the CrMS is based upon biological markers After ma ny yea rs of ex te ns ive eva lu ation , th ese
that include not only the cerv ica l mucus but also the bi omarkers hve been shown to revea! the presence or
absence and the presence of va ri ous types of bl eeding, absence of certain types of pathologic or phys io log ic
it can be used as a means of monitoring and maintain- abnorma liti es. They g ive the phys ician and the pati ent
ing reproductive and gynecologic health. In vestigati on a "handle" on the menstrual cycle and allow fo r its proper
of thi s has given birth to the whole new re producti ve eva luati on. lt allows one to treat abnormalities ofth e
science ofNaProTECHNOLOGY. Most ofthe work that menstrual cycle in cooperati on w ith its fun cti on .
2 .1 5 6 7 X 9 111 11 12 11 14 ló 17 IX 19 20 2 1 n 2.1 14 25 2h 21 2x 29 30 11 32 .11 .14 .\.1

1 4
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l .,_, ... " ···'. < .Q ",.,
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fo(
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H !-/ l'1 ,.v¡ /.....
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/..... VL 9k ~e
r.:t
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Figure 4-8 : In a woman with regular menstrual cycles and continuous mucus discharge, the base infertile pattern is shown up to
the point of the change. The Peak Day is identified and the pre- and post-ovulatory days of infertility are shown with plain yellow
stamps .
OAO 04.0 00.0 OAO OAO O.A.O OAD OAO OAD CIAD OAO OAO OAO OAD
r I r I
Figure 4-9: In th is case, a woman of normal ferti lity, the system is used to achieve pregna ncy. The acts of intercourse in the
midst of the mucus cycle (days 16 and 18) should be expected to result in pregnancy as they did in this example .
The CrMS and the Use of Criteria --~ questions and answers, and allows the system to be " tai -
lor-made" to the individual couple.
In studying the biomarkers of the menstrual cycle as
observed througb the eyes of the standardized CrMS, lt is a lso built upon a case management concept. T hi s
one recognizes that the CrMS is a criteria-driven sys- is an approac h to client care that allows fo r complex
tem. ln other words, the phys ic ian, the FertilityCare™ problems to be so lved. The case management approach
Practitioner (FCP) and the woman who is charting her allows for a comprehensive and prioritized approach to
cycles can identi fy certain bi ological events that are oc- the management of difficult cases. lt is truly a benefit of
curring by the objective presence ofa biomarker. Such standardi zation and it is completely holi stic in its ap-
biomarkers have been associated, with a hi gh degree of proach.
clini ca l corre lation , w ith either one or more abnorma l
physio log ic para meters of e ither reproductive fun ction CREIGHTON MODEL services are delivered by edu-
or woman 's hea lth. cating couples about thei r fe rtility. This is accomplish.ed
through a network of service program s developed and
The health care provider must recogni ze the importance operated by spec ialists in CrMS educati on.
of criteria. These criteria are obj ecti ve signs that ha ve
been studied in such a fas hion so th at when they are
observed in the CREIGHTON MODEL charting system
they can be eva luated in an obj ecti ve fashion. The di s- Curriculum Concepts _______~
covery ofthese vari ous obj ecti ve markers (the presence
of certain criteria) will indicate where evaluation should The ed ucati on ofteachers in the CrMS is built upon an
begin and what type of evaluation should be conducted . alli ed health educati ona l model. The FertilityCare™
Furthermore, w ith a high degree of probability, it will Practitioner (FCP) program is a 13-month core cur-
give an in sight into the potential underl yi ng ca uses of rí culum built upon two theoretical phases (nine and
the clíni ca! abnormali ty. seven days in duration) and two supervised practica
(five and eight month s long). During the second super-
Although the biomarkers ofthe CrMS are not 100 per- vised practicum, the student undergoes an on-site visit
cent correct, th ey are strongly suggestive of a specifi c so that the fac ul ty supervisor can personally witness the
probl em or set ofunderl ying probl ems. When th ese ob- Practiti oner 's teach ing skill s. At the conc lusion of the
jecti ve parameters - these bi omarkers - are identifi ed , progra m, a final exam must be completed in order to
the hea lth care provider and the woman who is making receive the certifi cate.
the observations will be abl e to understand more fully
the nature ofthe underlying problem, the type ofeva lu- During the supervised practicum, the indi vidual practi -
ati on that needs to be done and eventually the treatment ti oner intems are supervised by indi vidua ls who are
that would be best impl emented. Furtherm ore, it needs themse lves trained to provide that superv ision. These
to be stressed that these bi omarkers can onl y be identi - supervisors are the FertilityCare™ Educator (FCE) and
fied w ith the use of the CrMS . FertilityCare™ Supervisor (FCS). The currí culum is
managed, directed and carried out by the advanced leve!
The CrMS is trul y un ique. lt is not onl y a standard ized FCE . There are many such programs throug hout the
system but an enormous amount of research has gone United States and in other countri es. Th ey have the as-
into the basic understandin g and correlati on of these sistance of FCSs, Natural Family Planning Medica! Con-
various biomarkers to underl ying physiologic and patho- sultants, and certain special faculty who are invited to
physio log ic events. Thus, nobody should be confused partic ipate in these programs.
that any oth er system can prov ide the same info rrna-
tion. Perhaps it may be possi bl e, sorn e time in the fu-
ture, fo r other approaches to approximate what the CrMS An lntegrated Allied Health System ==J
does in this regard. However, significant research needs
to be done prior to that being accompli shed. T h e teachers of th e CrMS a r e referred to as
FertilityCar e™ Practitioners (FCP) (a program de-
signed to ass ist coupl es w ith ali difficu lties or problems
The Teaching System - - -- - - - - . that they mi ght face) and FertilityCare™ lnstructors
(FCI) (a seven-month program designed to provide only
The CrMS is based upon individual fo llow- up of cl ient the very basics in CREIGHTON MODEL educati on).
coupl es. This ass ures indi vidual attenti on, all ows for
Chapter 4: lntroducti o n to the CrMS 51
Comprehensive Research Programs= l dardization of teaching from one teacher to the

next and an arder/y transfer of knowledge pro-
Throughout the hi story of the CrMS, there has been a vidin g "egua! access" to the vital inforrnatio n to
significant, comprehensive comm itment to research and utilize the systern properly
ed ucation program development in the fie ld of better
understand ing the natural means to regulate ferti lity. 4. a Vagi na l Disc harge Recording System 5 M
(VDRS) wh ich allows for a standardized ter-
In the basic sc iences, this has in vo lved hormone corre- minology to be used. Standardized observations
lation studi es of ovu lation, endocervical mucus corre- and standardized charting have also been de-
lations, use effecti veness stud ies, ultrasound eva luations veloped.
of ovu lation , and so forth. Many years of research in
education led to the development of the core curricu- 5. a pregnancy evaluation form
lum of th e CREIGHTON MODEL program and the
American Academy of FertilityCare Professionals for 6. ongoing assessment ami evaluation tools.
the certification of teachers and accreditation of pro-
grams.
Advantages of the CrMS - - - - - - - .
From a cl inica l point ofview, the new medica! and sur-
gical women 's health science of NaProTECHNOLOGY The advantages ofthe CrMS are nurnerous . First ofa ll ,
has been a fruit of the commitment to CREIGHTON it is saje! There are no known medica! side effects as-
MODEL research obj ectives and the development ofthe sociated with its use. lt is inexp ensive! The cost of
Pope Paul VI lnstitute for the Study of Human Repro- FertilityCare™ services is consid erably less than th at
duction to carry it out. Because it is a comp letely sta n- of contraceptives. Fi na ll y, it is highly reliable and it is
dardized system, information has been built into the sys- natural. The CrMS cooperates with the coup le 's own
tem as it has been learned through this com mitment to natural ferti lity process.
research . The very science of NaProTECHNOLOGY
could not have been developed without the standard- Another important advantage to the system is that it is a
ization inherent to th e CrMS . The CrMS, as a result, shared method off ertility regulation . The responsibil-
offers suppo1i to client coup les that is based on educa- ity for its use is placed eq uall y upon both spouses. To
tion, service and resea rch. This three-pronged etfort pro- use th e systern successfu ll y, it is necessary to make ac-
vides the couple a cutting-edge teaching session, which curate observation and to chart them correctl y. In ad-
is in constant evo lution in terms of its signi ficance and dition, one must fo ll ow the instructions of the system
meaning to their practica! everyday lives. wh ich depend upon the couple's decision to either
achieve or avo id pregnancy. Also, the coup le sho uld be
mutually rnotivated in its use and enter into it with a
NaProEDUCATION Technology _ _~ loving and cooperative sp irit.
NaProEDUCATION Technology (Natural Procreative As the couple learns more abo ut their natural pilases of
Education) is a techn ology that has developed as the fertility and infert ility, they will begin to realize how
result of the commitment to education research in the irnpo1iant and vital these gifts rea ll y are. Un like contra-
CrMS . It is an advanced educational technology, the ceptives, the CrMS treats fertility as a normal and
princip ies of which have not been previously used in healthy process. It does not treat ferti lity as a disease!
ei ther medica! or patient education. The allied health The chall enge to li ve in harrnony with one's fertility is
education rnodel and standardized educational content often one of th e rnost exciting and meaningfu l aspects
previously mentioned are a part of this in the use of this system. Most coup les find that the
NaProEDUCATION Technology. It also involves: love and respect each holds for the other grows as their
understanding and app rec iation of their fe rtility in-
1. objective and measurable standards that are increases. lt is a system that is firrnly based in a respect
corporated into the system for human life, human di gnity, and the integrity ofmar-
riage . Indeed, it is the co up les who use this system and
2. the use of a Picture Dictionary which objectively their fami li es that benefit from this experience.
presents the rnucus observations
3. a Follmv-up Form whi ch all ows for the stan-

Education of Teachers _ _ _ _ _ _~ An addi ti onal program that ex ists is the Natural Family
Planning Med ica! Consu ltant Program. This program
The Pope Paul VI lnstitute for the Study ofHuman Re- tra ins physicians, physician ass istants, nurse practiti o-
prod uction has developed a currícu lum for the educa- ners, and nurse midwives who are committed to the
tion ofnew FertilityCare™ teachers. At the present time, natural methods offertili ty regulation to enhance their
five different programs fo r educationa l traini ng exist. expertise in this field . It is a six -month program which
requires extens ive theoretica l input, a supervised
There are two programs that are designed to train indi- practicum , and other ass ignments specificall y geared
viduals to teach the CrMS to new cl ient coup les. T hese toward their specia l area of expertise. Additionally, they
programs, in affi liation with the Continuing Medica! are exposed to the foun dations and app l ications of
Education Division ofCreighton University Schoo l of NaProTECHNOLOGY.
Medic ine, educate FertilityCare™ Practitioners (FCP)
and FertilityCare™ lnstructors (FCI). The education
programs are ali designed to provide teachers with an
adequ ate theoretical background and clinical exposure Certification and Accreditation Standards
to teaching the CrMS so that an adequate development
ofteaching sk ill s can occur. The c lini cal phases are ali Each new CrMS ed ucation program must submi t itse lf
conducted under supervision. The FCP program trains to the review of the Commission on Accredi tation
teachers to be ab le to perform both basic and advanced (COA) of the American Academy of FertilityCare
teaching ski li s and educationa l serv ices. This program Professionals (AAFCP). This review is mandatory and
educates new teachers so that they can provide educa- assures the public that the highest standards for CrMS
tional services to ali coup les. The FCI program is de- education are being met. Once the review has been com-
signed to train teachers to be capa ble of performing basic pleted and the program meets those standards the COA
teach ing skili s and educationa l services. This program forma ll y accredits the p rogram. Such accreditation is a
trains teachers to provide educationa l services to ama- great ach ievement. Sim ilarl y, oncean FCP, FC I, FCE,
jority, but not ali, new client coupl es. While FCPs can FCS or NFPMC has comp leted the ed ucation program ,
work independently, a li FCl s must work in association then he or she may app ly for forma l certification thro ugh
with an FCP . the Comm iss ion on Certifi cation (COC) oftheAAFCP.
At the present time, such certification is opti ona l but,
The Practitioner and In structor programs are not de- when accomp lished, ass ures the public that the indi-
signed to train teachers to train other new teachers. The vidua l is providing serv ices that meet the hi ghest stan-
educationa l ski ll s necessary to educate FCPs and FCls dards and that he or she has successfu ll y completed a
are different from those necessary to ed ucate new c li - peer rev1ew process.
ents. Thus, spec ifi c programs have been deve loped to
train FCPs to educate other FCPs and FCl s. The two For a program to be identified as a FertilityCare™ Cen·
programs that have been developed for th is are the ter, the program m ust be forma lly affiliated with etiher
FertilityCare™ Educator (FCE) and FertilityCare™ FertilityCare™ Centers of America or FertilityCare™
Supervisor (FCS) programs. New education programs Centers lnternational. This reinforces the standards set
can on ly be developed under the auspices of an FCE . by the AAFCP.
FCEs are e ither registered nurses or have the equiva-
lent of a bachelor 's degree in anothe r field. T hey are
FCP s with one addi tional year ofteach ing experience.
Their currículum involves additional, in-depth exposure Awareness, Acquisition, and
to the theoretical and clinical aspects of educating and lnternalization ---------~
superv ising FCPs and FCls. FertilityCare™ Supervi·
sors are also FCPs with one additiona l year ofteaching As one stud ies the CrMS and learns the sk ill s that are
service. However, the other educational requirements necessary to impart the knowledge required for proper
are unnecessary. FCSs work in conjunction w ith FCEs use, it is helpfu l to draw a distinction between the edu-
and are trained to be particularly ski lled in the clinical cational concepts of awareness, acquisition, and inter-
supervisory aspects ofthe CrMS . Many other indepen- nalization. These concepts will help a new teacher bet-
dent education programs for FCPs and FCls are now ter understand his or her own educational needs. In ad-
active at other sites around the United States and in sev- dition, it wi ll be very helpful to the new teacher in un-
era! other countries. derstanding the process involved in educati ng a new
client. These three terms represent three di stinct levels
of the educational process. Understanding them is es- John and Lyn Billings have li sted the fo ll owing quali-
sential to understanding the teacher 's and th e user 's re- ties ofa good teacher of the Billings Ovulati on Method
sponsibilities. The teacher should read these concepts to whi ch we can concur:
carefull y and, rather than be fo rgotten, they should be
internalized. 1. They must ha vean adequate know ledge.
2. They must ha ve the abili ty to impait confidence.

Awareness : A leve! of simpl e recogni tion: I am
aware that a fac t, con cept or body of know ledge 3. They must be compass ionate and fr iendl y, and
exists and can be sensibl y understood. thi s should be based upon their respect fo r hu-
man li fe and human di gni ty.
• Acquisition : A leve! of more complete lea ming:
4. They should be tactful and sensitive, and respect-
I have the capaci ty, acquired through dril! and
ful of the confidenti al nature of the teac her-user
practice, to use a fa ct, concept or body ofknow l-
interaction.
edge. 1 understand how it operates in re lati on to
other fa cts, concepts or bodies of know ledge, 5. They must be pati ent, have a willingness to li s-
and J am abl e to bring other indi v iduals to an ten, and ha ve a respect fo r the clients and an ac-
awareness ofthe same. ceptance of th em. Co mbined w ith thi s, they
should have th e capaci ty to give advice based
• Internalization : A leve! of unity with certain upon a philosophy in w hi ch the teacher recog-
knowledge and skill s: J possess a leve! of uni ty nizes his or her own prin cipies.
with certain facts, concepts or bodi es of know l-
6 . They rnu st have the abili ty to teach with sim-
edge that allows me to clearl y, confi dently and
plicity in ali cases and to impart knowledge at a
spontaneou sly expl ain these and help others ac-
leve! appropri ate to the client 's education and
quire a greater knowledge and skill with the
intelli gence.
same.
7. They must have the ability to help the husband
and the w ife to beco me ind ep end ent of th e
lnformation Versus Education ---~ teacher.
In educating new teachers in the CrMS , it is important

to recognize that there has been a tendency, hi storica ll y, It is a lso very important that teachers be users of the
in thi s general field to simply provide info rmati on. Such CrMS . By being a user of the system, the teacher can
informati onal session s do an injustice to the challenge better deve lop a keen sensiti vity to the needs inherent
of education programs in thi s fi eld. Thus, it is helpful to in its use. In additi on the teacher can better deve lop an
understand the di stinctions. appreciation fo r the va lues th at the use of the CrMS
upholds and proj ects. Thi s ass ists the teacher in being
When informa/ion is p rovided, facts are given. How- committed to the successful use of the CrMS fo r al! in-
ever, informati on is onl y at the leve! of awareness and dividuals who co me to thern fo r assistance . No case
is, by its na ture, superfi cial. lnfo rmati onal programs are should ever be looked upon as too di ffic uJt or impos-
not suffi cient fo r the development of good judgment. sibl e to so lve . Beca use the use-dynamics of the CrMS
are substantiall y different from the use of contraceptive
Education programs are des igned to impart know ledge methods, th e teacher 's use ofth e CrMS is a very impor-
and require using the process of internalization. By their ta nt component of quali ty service w here support and
nature, they are substanti ve and are better able to in still ass istance fo r those use-dynami cs must be mea ningful
in the new teacher the ability to make goodj udgmen ts. and credibl e.
If th e teacher is sing le or celi bate, then it is vital that

Qualities of Good Teachers ----~ that indi vidual be a credible philosophical acceptor of
the CrMS . Being a credible phil osophi cal acceptor of
Teaching the CrMS is both a sc ience and an art. lndeed, the CrMS means that the teacher is committed to the
the sc ience reflects an adequate know ledge of ali as- inherent value that thi s approac h to fami ly planning has
pects of the system. The art deal s w ith th e teacher's fo r human re lati onships. lfthe teacher is a wo man, it is
abili ty to communicate with new cli ent coupl es, w ho important th at she chatt the signs of her fert ili ty so that
come from a lJ walks of li fe and a li backgro unds. Drs. she has an a pprec iation fo r this aspect of its use .
54 The Medica l an d Surgical Practi ce of NaProTECHNOLOGY
Qual ity Assurance in the CREIGHTON Qualities of Being A Professional --~

MODEL FertilityCare™ System ---~
Teaching the CrMS can be considered an emerging a l-
The system ofteaching has been des igned to prov ide a lied hea lth profess ion. It is exc iting to see the potentia l
fra mework for the monitoring of quality control in the that CREIGHTON MODEL services has fo r married
CrMS . The development of quality control meas ures in coupl es. For tb e CREIGHTON MODEL teacher, an op-
the CrMS programs is critica! to its appli cation to use rs portunity ex ists to be a part of that growth and develop-
and its future deve lopment. ment. However, as with ali new profess ions, there is a
need to be ex posed to those qualities which elevate the
When one discusses quality control in the CrMS , it is activity to th e leve! ofprofessional. It should be po inted
first ofa ll important to ask the question , " lf quali ty con- out that professiona li sm is not determined by fin ancia!
trol measures are developed, who wou ld be the benefi- reimbursement for the services. A person can be a pro-
ciary ofthose meas ures?" It seems like such an obvio us fessio nal whether or not he or she is paid for the act iv-
question that it need not be asked . lt is prec ise ly be- ity. Thus, the fo llow ing qua liti es make up profession-
cause ofthe obv ious nature ofthe question that it should als:
be asked and , of course, answered.
Th ey possess a speciali zed knowledge.
Quality contro l procedures in the CrMS shou ld ha ve as • They di splay experti se with the too ls necessary
their goal the user's improved utili zati on ofthe system. to transfe r knowl edge properly.
When one talks abo ut the utilizati on ofthe CrMS, it is
They maintain a high standard of achievement
important to keep in mind th at it is used both as a sys-
and conduct.
tem to ac hieve as we ll as a system to avo id pregnancy.
Therefore, improved utili zation does not simply mean, They are committed to continued study.
as is so often stated, the use to avoid pregnancy. Any They render a publi c service.
quality contro l measures in the CrMS th at are oriented They are responding to "a calling."
onl y to the avo idance of pregnancy are inappropriate.
• They have the ability to love .
Since deli very ofq uality serv ices is one ofthe ultimate • They possess qualities ofpoise, confidence, self-
goa ls, it is obv ious that the delivery system must be respect and reliability.
adequate ly eva luated on an ongoing bas is. Howeve r, They respect another 's value system but are a ble
the delivery systems are onl y as good as the people who to challenge it in a constructive way without be-
deliver the services. Therefore, quality control begin s ing judgmental.
with the tratning and education ofthose individuals who They respect the client's confidentiality.
actua lly provi de the services to interested couples. Qual-
• They are both accountable and responsible to
ity contro l measures need to be implemented at the leve!
themselves, their clients, the ir profession and
of the ed ucation programs to whi ch new teachers are
th eir va lues.
exposed. This requires an ongoing eva luation ofthe cur-
riculum , the training personnel , and the goa ls and ob- Th ey respond rather than react.
jectives of the educati onal needs of the CrMS . When- They are well-groomed, punctual and organized.
ever such goa ls or obj ectives are neglected or di scarded, They possess good co mmunication techniques,
it is the user of the CrMS w ho is shortchanged. both ve rba l and non- ve rbal.
• They have the ability to guide the couple toward
Quality control is an ongo in g process in vo lv in g vari-
independence.
ous measures that can constantly bring to the attention
of the program personnel probl ems that ma y be cor- • They look beyo nd their own perso nal needs .
rectable. Ali programs require constant monitori ng in They possess the skills to li sten as well as to
order to ach ieve a leve! of hi gh quality. Quality contro l present c learly and succinctly.
is, in essence, an ongoing process of se lf-eva lu ati on They are emotionally stable and sensitive to the
wh ich assures the de li very of quality services. needs of others.
• They are open to comment and critici sm .
• They are capable of adequately handling con-
fl icts and stress.
They are reasonabl y predicab le to those who
work with them .
• They are both approachable and yet assertive . As the new student ofthe CrMS begins his or her stud-
• They are capable offo llowing through with their ies, a conscious reappraisal of attitudes and the words
commitments. used should be conducted. Often , while new teachers
may not hold such negative attitudes themselves, they
They are aware of the need to use good judg-
oft:en convey these attitudes without thinking. In sorne
ment and are conscious ly engaged in develop-
ways, the use of certain words and phrases are so deeply
ing that quality.
ingrained in our social comm unication that even indi-
viduals w ith positive attitudes may find they are using
them without their awa reness.
Words Convey Attitudes _ _ _ _ ___,
The words we use convey attitudes so new teachers must
The natural methods have " grown up" with a rhetoric
become diligent in their use ofwords and phrases that
of their own. Many times, the words that are curren ti y
properl y convey the true dimensions of the CrMS.
used to describe certain events, actions, or behavior in
Through this process , att itudes can eventua ll y be
teaching or using these methods convey truly negative
changed on a wider scale.
attitudes. For examp le, the days of fertility are oft:en
referred to as "unsafe" or "dangerous" days. Indeed ,
there is nothing unsafe or dangerous about those days.
Final Note ----------~
Couples who use the days offertility are oft:en charged
with " taking a chance . . . (that they wi ll not get preg-
A comp lete and total presentation of the CrMS can be
nant)" w hen, in fact, they have used the method to
found in the training manuals fo r teachers 7•8 and wh il e a
achieve a pregnancy. These methods are often deroga-
good summary ofthe system is present in this textbook,
torily referred to as " Vatican roulette" and user couples
a comp lete discussion of it can on ly be found in those
are often ridiculed . E ven the word abstinence negatively
manuals .
portrays what is in fact a positive experience and one of
the true advantages ofthese systems.
l. Hilg e rs TW, Prebil AM , Dal y KD , Hil ge rs SK : T h e 8. Pope .l o hn Paul JI. Evangelium Vitae. An Encyclical Letter on
CREIGHTON MODEL fo r the Deve lo pment o f Na tura l Fa m- the Gospe l of Life. March 25, 1995. Libreri a Editrice Vaticana.
ily Pl anning Educati on and Service Programs. Creighton Uni - Vatican C ity.
versity Natural Family Pl anning Educatio n and Research Cen-
9. Hilgers TW, Da ly KD , Hilgers SK, Prebil AM. Th e Ovulation
ter, Di vision o f All ied Hea lth , Departme nt of O bstetri cs and Gy-
Meth od of atura! Famil y Pl annin g: A Standardized Case Man-
necology, Creighton University Sch ool ofM edic ine, Omaha, Ne-
agement A pproach to Teaching - Book 1: Bas ic Teach ing Ski lis.
braska. April 1980.
Creighton Uni versity Natu ra l Famil y Planning Educati on and
2. Po pe Paul VI: Hwnanae Vitae (Of Human Life). An encyc lica l Resea rch Center, Ornaba , Nebraska, 1982.
letter o f His Holiness Pope Paul VI on the regul ati on of birth.
10. Hil gers TW, Daly KD, Hilgers S K, Pre bil AM : CREIGHTON
lssued July 25, 1968. NC News Serv ice Tran slatio n.
MODEL FertilityCare™ System : A Standardized, Case Man-
3. !bid , parag raph 17. agement Approach to Teaching-Boo k 1: Bas ic Teaching Sk i lis .
Second Editi on. Pope Paul VI ln stitute Press, Omaha, Nebraska,
4. !bid, paragraph s 19-3 1.
2002.
5. Pope John Paul JI : The Th eo logy o fth e Body: Human Love in
11. Hil gers TW, Hilgers SK, Prebil AM , Daly KD: CREIGHTON
the Divin e Pl an. Pauline Books and Medi a. Bosto n, MA, 1997.
MODEL FertilityCare'" System: A Standardized, Case Man-
6. Pastoral Con stitutio n o n the Church in the Modem World . Pope agement Approach to Teachin g-Book 11: Ad va nced Teaching
Paul VI. December 7, 1965 . Daughters of St. Paul , Jama ica Ski li s. Pope Paul VI lnstitute Press, Oma ha, ebraska, 2003.
Plains, MA , Paragraph 87.
12. Cohen MR, Stein IF, and Ka ye BM: Spinnbarkeit : A C haracter-
7. Pope John Paul l 1: Aposto lic Ex hortati on on thc Ro le ofth e Chri s- isti c o f Cervical Mucus. Fenil Steril , 3: 201 , 1952 .
tian Famil y in the Modern Wo rld (Fami/iaris Consorrio). Daug h-
ters o f St. Paul , Bosto n, MA, November 22 , 198 1, Paragra ph
33.
---~ ~tu,S
Standardization of Teaching
without the standardization built into the CrMS.

T he natural ferti lity process is unique to each indi-
vidua l couple. It is composed of certain biological
components, sorne that are well known and understood, Natural methods of fertility regulation ha ve reached a
sorne that are less known and understood , and sorne point in their development where most people would
that are tota ll y unknown . [n delivering CREIGHTON agree that the contemporary methods are biologically
MODEL services, the teacher deals with these factors very effective as a means of avoiding pregnancy ifused
on a couple-by-coup le basis realizing that the total body properly and according to instruction. However, many
of know ledge may not yet be comp lete . A number of questions continue to be left unanswered. lt is impor-
practica! teaching aids or systems ha ve been deve loped tant, for example, to identify the versatility of different
based u pon the concepts that are understood about the natural methods offerti1ity regu lation and the precision
natura l fertil ity process. with which they identify the phases of fertility and in-
ferti lity. lt is also important that successful use be mea-
The method of teaching the CREIGHTON MODEL sured not only in terms of avoiding pregnancy but also
FertilityCare™ System (CrMS) is completely standard- in terms ofachieving pregnancy. Since a principie goal
ized . Stand ardization can be defined as the process in teaching a natural method offertility regu lation is to
through which a system of teaching is brought to a uni- teach couples to use it for the remainder of their repro-
form standard or quality. Such standardization has a ductive lives, it is important to generate information
number of advantages. First of ali , it assures that equal regarding their long-tenn use. These questions can on ly
access to the knowledge and understanding of the sys- be answered i f adequate preparation of the teaching
tem is provided to each new couple who learns it. In system through a standardization of the educational
addition, it ass ures an accurate transf er (duplication or delivery system is deve loped . To ask such questions and
replication) ofthe knowledge ofthis system. Standard- attempt to find answers is vital to the future ofthe natu-
ization provides a solidfoundation upon which future ral methods offerti lity regulation . For those of us who
development can be built. It is critically important to have faith in the abi lity of natural methods to accom-
the advancement of knowledge in this field. An excel- plish what we say they wi ll , answers to such questions
lent examp le of this is the development of are simply forerunners to new insights and new devel-
NaProTECHNOLOGY, which would not have occurred opments which allow us to realize these goals more fully.
57
Tools of Standardization _ _ _ _ _~ 11. The Pregnancy Evaluation Forms
12 . The SPICE lndex

The process through which standardization is accom-
plished is made up of two components. The first com- 13. Other basic organ ization forms (such as the Gen-
ponent is education of the teachers who deliver era l Intake Form)
CREIGHTON MODEL services. Such education must
be thorough and conducted accord ing to a developed With th e use ofthese materials and the teaching skills
currículum to provide the teacher with adequate theo- that must be developed in orde r to use them properl y, a
retical and el inical ex pos ure necessary for the develop- standardized teaching system is assured . A "clothes tree"
ment ofthe basic and advanced teaching ski lis essenti al has now been deve loped upon which future progress
to the development of quality educational services. Such within this system can be made. In fact, it is this "clothes
an educational process for teachers implies that they tree" effect that has allowed for the development of
are provided with an adequate fo undation in the prin- NaProTECHNOLOGY.
cipies ofstandardization and ongoing supervision in the
development of clinical ski ll . The second com ponent A few important items should be pointed out at this time.
revolves around the delivery of the information in a First of ali, the on ly materia Is that are publicly avail-
standardizedfashion so that equal access to new cli- able are the fol lowi ng: Th e CREIGHTON MODEL
ent couples can be assured. This educational service FertilityCare™ System: A Standardized Case Manage-
must also allow for an as essment of the user's effec- ment Approach to Teaching- Books 1 and 11, Repro-
tive retainment and application ofthe knowledge they ductive Anatomy and Phys iology : A Prim er far
are learning. FertilityCare™ Professionals, and Th e Picture Dictio-
nary of the CREIGHTON MODEL FertilityCare™ Sys-
The first component can be satisfied through the de ve l- tem . Ali of the other materi als are made available only
opment ofeducational programs with the eventual cer- to certified or in-training FCPs and FCl s for use directly
tification of teachers. The second component is sati s- with their client couples in the ir FertilityCare™ Cen-
fied through the thorough development of educati ona l ters .
tools coordinated and integrated into a completely stan-
dardized teaching system. The tools of CrMS educa- Secondl y, it is essential to point out that this teachi ng
tion can be listed as follows: system is one complete system, and it should not be
conji1sed or mixed with other methods of teachingfer-
1. Th e CREIGHTON MODEL FertilityCare™ Sys- tility regulation. The scientific data which is presented
tem : A Standardized Case Management Ap- to support this system do not apply to its mixing with
proach to Teaching. Book l for FertilityCare™ other methods .
lnstructors ( FCI ) and B ooks I and lJ fo r
FertilityCare™ Practitioners (FCP). 1•2 In order to better understand the standardization of the
CrMS and to beg in to integrate its concepts, a basic re-
2. Th e Picture Dictionary of the CREIGHTON
view of the following teaching- and system-related com-
MODEL FertilityCare™ System3
ponents will now be undertaken :
3. The CREIGHTON MODEL FertilityCare™ Sys-
tem : An Jntroductory Bookletfor New Users. 4 • The Teaching Schedule
This is an introductory booklet designed for use The Picture Dictionary ofthe CrMS
by the new client couple. • Making Good Observations
• The CrMS Follow-up Form
4. The introductory sli de presentation and its con-
• The Basic Principies ofFollow-up
tents
5. The CREIGHTON MODEL System chart

Teaching Schedule -------~
6. The CREIGHTON MODEL System stamps
7. The CREIGHTON MODEL Fo llow-up Form A system for teaching a natural method offertility regu-
lation should be designed with the educational needs
8. The Observational Review
of the clients in mind . Without that perspective, it is
9. The Reproducti ve Category Specific Cycle Re- easy fo r a program to bypass important areas of new
views learning orto ignore an approach oriented toward the
new learner. The educationa l needs ofthe new user are
1O. The samp le teaching charts
Chapter 5: Stan dardization of Teac hing 59
immediate and, when the educational process delays low-up that the principie teaching in the CrMS is ac-
meeting those needs , the client 's learning becomes complished. Users who are unwilling to attend follow-
strained. The education , because of its sensitive nature, ups must have explained to them that they have chosen
demands that each client couple recei ve individual at- a less efficient means of leaming the system and that
tention in a system of organizedfo llow-up. When indi- they are receiving an inferior education and service.
vidual questions are left unanswered, frustration and Programs that do not provide for adequate follow-up
anxiety tends to build. Users of the CrMS never lose teaching must be identified as delivering less than opti-
the need to have access to a FertilityCare™ teacher. ma! services.
While clients clearly reach a leve! of autonomy in the
early instruction, it is impossible to address ali oftheir The follow-up educational program is most intensive
potential needs for the next twenty to thirty years. A during the first three months of learning with five fol-
good teaching system allows for continued leaming in low-ups scheduled (see Figure 5-2). Three additional
a program oflong-term follow-up . The teaching sched- follow-ups are scheduled for the last nine months ofthe
ule of the C rMS is presented in Figure 5-1. first year of use. These later follow-ups are helpful to
new users since they reinforce their own successful use
The intake ofa new client into a CREIGHTON MODEL ofthe system. The long-term follow-ups are also valu-
program is a form ofregistration where the teacher col- able to the teacher. They assist the teacher in putting
lects intake information. By doing this, the teacher will the actual use of the CrMS into perspective and bal-
obtain background on the new el ients prior to the Intro- ance. The teacher is provided the opportunity to ob-
ductory Session, thereby helping him or her prepare serve the behavioral pattems which develop in the ac-
for the beginning ofthe prospective user 's instructional tual use ofthe system .
program. This Introductory Session is specifically de-
signed to introduce people to be users of the system. In understanding this teaching schedule, it is important
The introductory slide presentation usually lasts approxi- to understand the flexibility within it. What has been
mately one hour. With the scheduling of appointments presented is a bas ic follow-up schedule for the teaching
following the Introductory Session, the entire session ofthe CrMS . However, at times it is necessary to devi-
will take approximately 90 minutes (see Chapter 6). ate from such a follow-up schedule depending on the
needs of clients. The FertilityCare™ teacher, using good
The follo w-up is the cornerstone to the delivery ofqual- judgment, will understand that such tlexibility is built
ity FertilityCar e™ Services . lt is at the time ofthe fo!- into this schedule.
The Teaching Schedule
lntake lntroductory Flrst FU FU-2 FU-3 FU-4 FU-5 FU-6 FU-7 FU-8 FU-9, 1O, 11, etc .
Sesslon 2 Weeks 4 wks 6 wks 8 wks 12 wks 24 wks 9 mos 12 mos Every 6- 12 month s
Figure 5-1: An overview of the teaching schedule (FU = Follow-up)
Follow-up Schedule
IN IS 1 2 3 4 5 6 7 8 9, 10, 11 , etc.
1
o 3 mos . 6 mos. 9 mos . 12 mos. Eve ry
6-12 mos .
Figure 5-2: A dateline far conduct of the teaching schedule (IN = lntake; IS = lntroductory Session ; mas = months}
60 The Med ical and Surg ical Practice of NaProTECHNOLOGY
The Picture Dictionary of the CREIGHTON wo men can relate extre mely we ll to the examples pre-
MODEL System - -- - - - - - - - , sented. In addi tion, men fi nd th e pictures valuabl e be-
cause the pictures help them understand the system bet-
Th e Picture Dictionmy of the CREIGHTON MODEL ter. It is important to note, however, th at not ali women
FertilityCare™ System 3 is a teaching a id that has been will relate to al! th e examples shown because not ali
deve loped to assist both the teacher and the client couple women observe ali that is shown. oneth eless, women
in understanding the termi no logy used to describe the w ill be abl e to re late theirobservati ons to the examples
muc us observations. The pictu res contained in the dic- which apply to them .
tionary have been systematically se lected thro ugh care-
fu l gyneco logic eva luation of users of the CrMS . Thi s lt is criti ca lly important to remember that, in using thi s
research process in vo lved 157 women fro m ali repro- di cti onary, a picture cannot be taken of the sensati on
d ucti ve categories thro ugh 444 mucus ob ervations which the mucus creates. Therefore, the sensation must
taken at rando m. In each case, the mucus was directl y be descri bed verball y to users. T he di ctionary should
observed and then immedi ately fo ll owed up by gyne- be used as a teaching aid only by teachers who have a
co logic examinati on, visualizati on of the cervix, and thorough grasp of its proper use
testing of the fe m and chann el characteri stics of cerv i-
ca l mucus. This researc h process all owed for the direct T here are sixteen photograph s of vul var observations
visualization of the actual mucus observations of women that are included in The Picture Dictionary. Each of the
using the CrMS . T hro ugh thi s eva luati on, a system of photographs have been specifi cally selected as the re-
standardized terminology fo r the mucus observati ons sult of the research to describe the essenti al components
has been deve loped and is used by new users and teach- ofthe mucus observations. It now has over 25 yea rs of
ers alike . The dictionary vis uall y depicts that sy tem of c linical experience as a fo undati on fo r its use. Each of
standardi zed termi no logy. these photograph s and its descripti ons are now pre-
sented:
A second research process was also involved in the de-
ve lopment of The P icture Dictionary. Thi s process in-
vo lved the very carefu l ongo ing evaluation of the ac- Picture One-Dr y (O)
tua l use of these pi ctures in the c lini ca l teaching set-
ting. It was with thi s process that th e actua l use and
appli cation ofthese pictures in a teaching enviro nm ent
was refi ned.
Presentation of The Picture Dictionary=i
The Picture Dictionary is presented to the c li ent co upl e

by the teacher duri ng the course of at least the firs t two
fo llow-ups. ln order for thi s to be accompli shed, the
teacher deve lops a ski ll in its presen tati on.
lt is important to keep in mind th at the new cli ents are

leaming an en tire system and notj ust bits and pi eces of 1. When you wi pe w ith this tissue yo u w ill feel a sen-
it. ln order fo r them to learn the entire system, the whole sati on of dryness. This w ill be a very obvious sensa-
system is presented in its entirety, fro m the beginning to tion.
end , so that they understand it and are not confused 2. As yo u observe the tissue yo u can see th at it is dry
thro ugh an inadequate or incomplete presentati on. and that it wrinkles eas ily.
3. othing can be fi nger tested from the tissue.
The di ctionary visually depicts a system of standard- 4 . Dryness is generally not a pro bl em fo r most women
ized te nni no logy to be used by teacher, user and health since it is such an obvious sensation.
ca re provider. It must be kept in mind that the pi ctures
are examples of what women w ill observe while mak-
ing the mucus observati ons used in the CrMS . As such,
the actual observations of the women may vary fro m
the exampl es. Nevertheless, investigation has shown that
Chapter 5: Standardization of Teaching 61
Picture Two-Damp Without Lubrication, Picture Three--Shiny Without Lubrication,

Damp With Lubrication (2 or lODL) Shiny With Lubrication (4 or IOSL)
l. When yo u wipe with this tissue yo u mayor may not l. When yo u w ipe with thi s ti ssue yo u may or may not
observe a sensati on of lubri cati on. observe a sensati on of lubri cati on.
2. When yo u observe the ti ssue yo u wi ll see an area of 2. When yo u observe the ti ssue yo u will observe a
dampness on the ti ssue . damp area with small areas in the center that are
3. Nothing can be li fted off of thi s ti ss ue to be fin ger shiny.
tested. 3. Nothing can be lifted off of thi s ti ssue to be fin ger
4. The key to your fe rtility is in thi s observation is the tested.
p resence or absence of lubricati on. 4 . The key to yo ur fertili ty in thi s observati on is the
5. The observation of damp without lubrication has the presence or absence of lubrication .
same significance as a dry observati on. 5. The observati on ofshin y without lubrication has the
6. The observati on of damp with lubri cation is Peak- same signi fica nce as a dry observati on.
type mucus. 6. The observation of shiny with lubri cation is Peak-
type mucus .
Explanatory Note
The dampness without lu brication observati on is due Explanatory Note
to perspiration which coll ects or a small amo un t ofvagi- The observati on shin y without Jub rication is due to the
nal fluid w hich is normall y produced. Neither of these w iping away ofsome ofth e superfi cia l squamous cells
are lubricati ve. While techni call y nota " dry" observa- present on the mucus membranes at the opening ofth e
tion , it correlates perfec tl y with the concepts of dry ob- vagina. These cell s are very similar to the cell s that make
servations in the CrMS. The observation da mp with lu- up the pasty di scharge and, on occasion, may in fac t be
brication represents a small amount of cervical mucus a small amount of the pasty di scharge itse lf. However,
that has a relative ly high water content, loses its stre tch- the discharge is prese nt in very small amounts and, w ith
ability, and becomes more absorbable. However, it <loes the wip ing process, is smeared o ve r the surface of th e
not lose its ab ility to be lubricati ve. Such an observa- tissue so that when observed it a ppears di stinctl y as
ti on is a Peak-type mucus observation and correlates shi ny. Such a d ischarge cannot be fin ger tested and it
we ll with the effects of in creasi ng estrogen levels on rubs easi ly away. When such an observation is present
the cervix. in the absence of lubricati on, it correlates w ith th e dry
observations although it is not tec hni ca ll y " dry." The
shiny with lubrication is a co mbinati on of sorne small
amou nt of cervica l mucus, which has a hi gh wa ter con-
tent simil ar to the damp observation, and shiny ce llul ar
materi al. The presence of lubricatio n indi cates a cervi-
cal mucus discharge. When shin y with lubrication is
present, it is a Peak-type mucus observati on and corre-
lates with the estrogen changes.
When observing the mucus discharge after uri-
nation, there w ill be wetness on the ti ssue fro m the urine.
lt is easy fo r a wo man to di stingui sh thi s urine from ali
62 The Medical and Surgica l Practice of NaProTECHNOLOGY
other observations. However, it may confuse the client 1. This photograph demonstrates the sticky consistency
with regard to what observation should be recorded on that may be present in the discharge.
her chart. As a matter of convention, the observation 2. In this example, the woman is stretching the pasty
observed prior to urination should be the one which is discharge by finger testing it between her thumb and
recorded on the chart if the observation after urination index finger.
does not change th is. For example, ifthe observation is 3. As she stretches it, you can see that it only stretches
dry before urination and only the wetness of urination approximately Y. inch.
is observed afterwards, then the recorded observation 4. When the mucus stretches up to ~ inch, we call it
is dry. However, ifthe observation changes to sh iny with- sticky.
out lubrication after urination , then that takes precedent 5. lnterestingly enough, the pasty discharge never
and is recorded on the chart. stretches more than Y. inch .
Explanatory Note
Picture Fo ur- Pasty (C reamy), Cloudy (PC) The pasty discharge originates from the wall ofthe va-
gina . lt is not cervical mucus. It is a very characteristic
discharge, which is easily understood by the client and
the teacher with the help of The Picture Dictionary. It
should be pointed out, however, that the pasty discharge
may be mixedw ith cervical mucus, and any number of
combinations can be obtained as the result of this. For
example, an observation of pasty, cloudy, lubricative
would be a legitimate observation and would be a Peak-
type mucus observation. ln addition , many stretchy,
cloudy observations around the time of the Peak Day
are due to the mixing of the stretchy, clear mucus that
originates from the cervix at that time with the pasty,
cloudy vaginal discharge, which is also present in a large
amount at that time. When the two are mixed together,
1. When you wipe with this tissue you mayor may no! one actually observes a stretchy, cloudy, observation .
observe a sensation of lubrication .
2. When you observe the tissue you will observe a dis-
charge wh ich has the characteristics of hand lotion Picture Six-Cervical Mucu s on Tiss ue
or flour paste. lt may even be milky in appearance if
the water content is high.
3. This discharge orig inates from the vagina and is
characteristically different from the cervical mucus
discharge.
4. We ca ll this a pasty or creamy discharge. oaen , this
d ischarge is present in a smaller amount than what
is picture here .
Picture Five-Sticky, Pasty (Crea my), Cloudy (6PC)
1. This is what cervical mucus looks like . U pon obser-

vation , you can see the cervical mucus raised on the
surface ofthe tissue.
2. lt does not absorb into the tissue and can be lifted
offthe tissue for finger testing.
3. We recommend that flat layers ofwhite toi let tissue
be used in making the observations . The blue tissue
in this picture has been used for photographic pur-
poses only.
Chapter 5: Standardization of Teach ing 63
Picture Seven-Tacky, C loudy (8C) 1. It is best to finger test the mucus between the thumb
and index finger.
2. This example shows a fine thread of mucus which
is tacky (Yi inch stretch) in consistency and cloudy
in color.
3. On occasion, the cervical mucus will stretch only Y4
inch (sticky).
4. When it does so, it will stretch into a fine thread , as
in this example, thereby being distinguishable from
the sticky, pasty type of discharge.
Explanatory Note
Cervical mucus has the tendency to stretch, when
present in small amounts, in to a very fine thread whereas
the sticky, pasty discharge tends to be more clumpy or
mounds up on the finger. When a client has a sticky,
1. When you wipe with this tissue, you may or may cloudy observation recorded, using this picture in The
not observe a sensation of lubrication. Picture Dictionary will be helpful in clarifying whether
2. When you observe this tissue, you will observe the or not it is a sticky, cloudy cervical mucus observation
presence ofmucus. or a sticky, pasty, cloudy vaginal dis charge observa-
3. When you finger test this mucus it stretches Yi to :Y. tion. It is important to know how to distinguish the two
inch. observations because it may be important in case man-
4. With this degree ofstretch, we cal! the mucus tacky. agement.
5. lt obviously has a cloudy color to it. Do not give
the mucus discharge a color unless it can be finger
tested with the color observed directly at eye level. Picture Nine-Stretchy, Cloudy/Clear, Lubricative
6. When the mucus is present in small amounts , it can (lOC/KL)
be finger tested by lifting it from the tissue as in this
example.
Explanatory Note
lt is preferable to finger test the mucus between the
thumb and the index finger. On occasion, the mucus
may be present in such a small amount that an observa-
tional technique would be difficult. Under those situa-
tions, it is legitimate to finger test the mucus by lifting
it offthe tissue. When the mucus is stretched, it should
be lifted up to eye leve! so that it can be looked through
directly to determine the color.
Picture E ight-Tacky, Cloudy (8C)

1. When you wipe with this tissue you may or may not
observe a sensation oflubrication although it is usu-
ally lubricative.
2. Upon observation of the tissue, you will observe
that there is mucus present.
3. With finger testing ofthe mucus, you can observe
the stretchy nature of the mucus and observe the
color which in this case is clear and cloudy
4. As the estrogen increases in the body, the cervical
mucus begins to show Peak-type mucus character-
istics (clear, stretchy, ar lubricative).
5. This example demonstrates the stretchy consistency
(one in ch or more of stretch) of the mucus.
Picture Ten-Stretchy, Cloudy/Clear, Lubricative Picture Eleven-Stretchy, Clear, Lubricative (lOKL)

(JOC/KL)
1. When you wipe w ith thi s tissue yo u mayor may not

1. When fin ger tested between the thumb and index observe a sensati on of lubrication although, with this
fi nger, th e stretch y consistency and cloud y/c lea r observati on, you are usually lubricati ve.
co lor are easily identifi ed . 2. Upon observati on of the ti ssue, you will observe that
2. It is important to note here that, when the term clear there is mucus present.
is used to describe the mucus, thi s means th at there 3. With finger testing, the beginning stretchy appear-
is at least sorne ofthe mucus that is crystal clear in ance is visibl e.
its a ppearance . 4 . Often, the Peak-type mucus will be crystal clear in
3. In this case, there is sorn e cloud y and sorne crystal co lor.
clear, thus the des ignation cl oud y/clear. 5. While it is impossible to take a photograph oflubri-
4 . T hi s type of mucus can usuall y be stretched severa! cation (which is a sensation), one can appreciate how
ti mes before los ing its stretchabili ty. th is parti cular ty pe of mucus, w hich is spread out
on thi s ti ssue, would create a g lid ing effect w hen a
Explanatory Note wo man w ipes w ith the ti ssue.
As ovul ati o n approac hes and the estrogen leve ls ri se in 6. Th e sensati on is what wo men know as lubri cati on.
the body, the cervix is stimul ated to increase its pro-
duction of ce rv ica l mucus. lt is thi s increased produc-
tion of cervical mucus that lend s to its di scharge in the Picture Twelve-Stretchy, Clear, Lubricative (lOKL)
preovul atory phase of the cyc le. ln additi on, the mucu s
contains more water at thi s time, and thi s increases its
ab il ity to stretch. Sometimes the stretch of the mucus is
considerable, go ing fo ur to fi ve inches or more. A t other
times, the stretch bare ly reaches one inch. Thi s is re-
flecti ve of the overa ll amo unt of mucus producti on.
The sensati on of lubri cati on is an obvious one.
Perhaps the best wo rd to describe the sensation (a lthough
not th e most aestheti c) is the wo rd slimy. Th e wo men in
Fiji who fi sh in wa ist deep wa ter ali day relate the sen-
sation to the slipperiness of the f:i sh as they slip out o f
one 's hand. A more useabl e visuali zati on ofthe sensa-
tio n is attempting to w ipe up a raw egg w hi te that has 1. The previous example has now been stretched into
been dropped on the fl oo r. T his exampl e re lates to an a thread-like stra nd of about two inches.
activity in whi ch nearl y ali wo men (and most men) ha ve 2. In thi s case, ali three characteri stics ( c lear, stretchy,
engaged at least once. With the observati on of lubrica- lubri cati ve) of Peak-type mucu s are present.
tion , there is a need to wipe more than once . It is not ali 3. However, yo u need only one of these characteri s-
removed with th e first w ipe. tics to identi fy the mucus as Peak- type.
Explanatory Note
C lear, stretchy mucus may not always be lubricati ve.
The exact exp lanation far thi s is not entirely understood. tion is present random ly throughout the menstrual cycle
Undoubtedly, it relates to the amount of water present and with no association to the timing of ovu lation. A
in the protein structure of the mucus. lf the mucus is second explanation has been observed in patients who
clear and stretchy but not lubricative, this would be an have infertility. In these patients, the re may be a wet
indicati on that the water content is decreased. At this without lubrication observation on occasio n, which ap-
time, it is not known what effect this has on one 's fertil- pears to be assoc iated w ith the timing of ovulation. The
ity. best explanation for this would be the presence of a
vaginal transudate produced in response to increased
blood flow to the pelvic organs which occurs asan es-
Picture Thirteen-Wet Without Lubrication, Wet trogen effect, in the immediate preovulatory phase of
With Lubrication (2W or lOWL) the cycle. In such a circumstance, it is possible to have
a wet without lubrication observation appearing around
the time when ovu lati on could be occurring. However,
experience has shown that such an observation still cor-
relates with one's fertility as a true dry observation wou ld
correlate. A third possibility is the wet discharge that
occurs following injury to the cerv ix through
cryosurgery or cervica l cauterization.
The observation of wet with lubrication is ex-
plained on the basis of a copious amount of cervical
mucus production that is high in its water content. When
the cervical mucus increases its water content, it loses
its ability to stretch and tends to abso rb deeply into sev-
Recordlng = 2W or 1OWL
era! layers of tissue, but does not loose its lubri cative
qualiti es.
1. When you wipe with this tissue you may or may not
observe a sensation oflubrication. Picture Fourteen-Gummy (Gluey) Yellow (GY)
2. When you observe the tissue, the tissue is very wet.
The wetness often has a glary appearance to it that
is different from the previous use ofthe term shiny.
3. Nothing can be lifted off of the tissue to be finger
tested.
4. Tbe critica! sign ofyour fertility in this observation,
as w itb damp and sh iny, is the presence or absence
of lubrication.
5. The observati on ofwet without lubrication has the
same significance as a dry observation .
6. The observation ofwet with lubri cation is Peak-type
mucus.
7. Remember, you need only one ofthree signs (c lear,
stretchy, or lubricative), alone or in any combina-
tion, to make the s ign Peak-type mucu s. 1. This discharge is characteristic. lt is thick in its con-
s istency, similar to half-dried airplane glue or rub-
Explanatory Note ber cement.
The observation ofwet without lubrication is dueto the 2. Beca use ofthis, it is given the name gummy or gluey.
copious production of a vaginal or cervical fluid , which 3. The ye//ow discoloration is typcial ofthis discharge
is not cervical mucus. The exact cause for the produc- although not always present.
tion of this vaginal fluid is not entirely understood. 4. lt is a discharge that is often associated with an in-
However, it is thought that there may be two or three flammation of the cervix (for example, cervicitis,
possible explanations. In recent studies, it has been erosion , ectropion , eversion).
shown to represent a subtle vaginal or cervical infec-
tion especially when not observed at times of fe11ility.
In this instance, the wet without lubricati on observa-
Picture Fifteen-Tacky, Gummy (Gluey), Cloudy on identifying cervical inflammations from the CrMS
(8GC) chart (see Chapter 24).
Remember
As the final portion of the presentation of The Picture
DictionOJy, there is a section that reviews for the client
the definition of certain words used during the course
ofthe presentation and the special categories whi ch have
been identified.
1. The word sticky refers to the stretch of the mucus

up to V. inch.
2. The word tacky refers to the stretch of the mucus

from Y2to % inch.
3 . The word stretchy refers to the stretch ofthe m ucus

1. ln this picture, a gummy discharge can be seen show- 1 inch or more.
ing its tacky (Y2 - % inch stretch) consistency.
4. A ruler is not needed to make these observations.
2. This is a characteristic type of discharge that is eas-
ily identifiable by women. 5. These schematic diagrams illustrate the definition
3. The terms gummy and gluey are interchangeable. of these terms.
6 . Remember the special categories of Peak-type mu-

cus : damp, shiny, and wet with lubrication.
Picture Sixteen-Tacky, Gummy (Gluey), Cloudy 7. Remember the special categories of"dry" observa-
(8GC) tions: damp, shiny, and wet without lubrication.
r ·~~
8. l n ea ch of these, no m ucus can be fi nger tested. Your
fertility is determined by the sensation w hich is cre-
ated during the wiping process.
. jt Making Good Mucus Observations==l
~~. ~ .......::,·}~ The CrMS is recognized for its estab lished standard-
.
.
ized and reproducible system of observing the various
~"""''!''· discharges (or dryness) at the opening ofthe vagina (the
introitus). The Billings Ovu lation Method does not teach
Recording = 8GC a standardized system. This identifies one of the main
differences between these two approaches. Other sys-
l. ln this picture, a gummy discharge exhibits a slightly tems ofnatural fertility regulation use other variations
different tacky consistency as it is finger tested be- of observations but none of them use the app roach of
tween the thurnb and index finger. the CrMS .
Explanat01y Note When the CrMS research program began in 1976, a non-
This type of discharge is also characteristic. lt is easily standardized approach was used and extensively eva lu-
identified by wornen once they have seen these pictures. ated. The conclusion was reached that such an approach
lt is an inflammatory type of cervical mucus discharge did not offer a system that could be uniformly du p li-
that is often observed in the presence of a cervical in- cated for the same woman observer or with between-
flammation. lt is not, however, the only type of cervical woman observation. Furthermore, it was discovered,
mucus discharge which is observed in the presence of through extensive survey analysis, that the m uc us was
an inflammation. What is most important is the timing observed at certain times better than at other times but
during the course of the menstrual cycle. This can be that those times were unpredictab le. Thus, the way to
more appreciated by studying the section of this book solve this was to establish a standardized routine for
making vulvar observations of the various discharges help the user in making good observations. An easy way
and through such a system introduce both the reliability to remember the three steps is to remember the word
ofthe observations as well as their reproducibility. The SOFT:
development of The Picture Dictionary anda standard-
ized terminology to describe the observation had already S = Sensation
changed the mucus sign from a subjective toan objec- O = Observation
tive sign. F = Finger
T = Test
This system of observation was then refined and pilot
tested prior to its introduction on a wider scale. It now It is very important to make a decision regarding the
has over 25 years of clinical experience and scientific sensation that the mucus creates when the woman is wip-
investigation behind it, and it has served the CrMS ex- ing with the tissue prior to looking at the tissue. The
tremely well. lts major disadvantage would appear to sensation is extreme/y importan!. lt is something that
be one of perception rather than reality. While it takes the womanfeels. lt is not something she can see.
sorne degree oftime to describe the system, thus mak-
ing it appear rather complicated and difficult, in ach1al The second step in checking for the mucus is a visual
fact it takes only 20 to 30 seconds to do and is well observa/ion of the tissue to see if mucus is present. lf
integrated usually by the second follow-up. This sys- mucus is present, then she moves to step three.
tem , which has been immeasurably useful to the stan-
dardization of the CrMS, its subsequent development In the third step, mucus that is present on the tissue is
and the development of NaProTECHNOLOGY, is now lifted offthe tissue andfinger testedbetween the thumb
described: and the index finger. In this step, the "stretchability"
and consistency ofthe mucus are tested, and the color
ofthe mucus can be determined . Whenever any mucus
Three Steps in Checking the Mucus is present on the tissue, it mus! be finger tested . In addi-
tion , ali areas of the mucus that are present on the tis-
There are three steps in observing for the mucus: sue must be finger tested. By finger testing ali areas of
mucus, errors in observing wi ll be avoided. When de-
termining the color of the mucus at the time of finger
Step 1: Wipe the opening of the vagina with toilet
testing, the mucus sho uld be raised to eye leve/ so that
tissue paying attention to the sensation which this
the woman can " look through" the mucus.
produces.
Step 2: Observe the tissue for the presence or ab-
sence of mucus. How to Check for the Mucus
Step 3: lf mucus is present on the tissue, finger test
A. Use flat layers of tissue.
the mucus between the thumb and index finger.
B. Do not use crumpled tissue.
In observ ing for the mucus, a few layers of white
There are three components to making any one good toilet tissue should be folded into a flat, rectangular
mucus observation. The woman needs to determine the shape of about 3x5 inches. Using flat layers of tis-
sensation that the mucus creates, she needs to deter- sue makes the observation much easier. When
mine its stretchability and consistency, and she needs crumpled tissue is used , it is easy to "lose" the mu-
to determine its color. The basic principie behind teach- cus in the creases ofthe tissue.
ing three steps in checking for the mucus is that no one
part of making a good observation is either forgotten or C. Wipe from front to back.
ignored. It is very easy for a woman who has not been
taught the step-wise pattern of observation to wipe with D. Wipe from the urethra through the perineal body.
the tissue not paying attention to the sensation and later, In Figure 5-3, a diagram ofthe anatomy ofthe vulva
when looking at the mucus, to ask " Was l lubricative or is presented. lt shows where the mucus should be
not?" Obviously, the time to determine sensation is di- observed. The wiping process should begin just in
rectly at the time ofwip ing with the tissue and not later. front ofthe urethra, proceed between the labia over
the opening of the vagina through to the back por-
Application ofthis step-wise system of observing will tion of the vaginal opening, and half way over the
perineal body toward the rectum. The entire obser- F. Do not do intern a! examinations.
vation is referred to in teaching as " wiping from the Interna! exam inations are not a part of the CrMS .
urethra through the perineal body. " The method is based upon observi ng the mucus ex -
The mucus can be present at any place a long tema lly. lnterna l examinations create confus ion and
this area. lt has a tendency to collect near the back wi ll provide mislead ing info nn ati on fo r thi s system.
portian of the vagina just in front of the perineal
body (posterior fourchette) . Thus , wiping from the G Do not ch eck directly with the fin gers.
urethra through the perinea l body is necessary so ali This standardized system of observing the mucus is
ofthe mucus will be observed. In addition , wiping based upon us ing toi let tissue to make th e observa-
over the skin ofthe perineal body is important in a tions . Using the fingers di rectly at the opening of
proper determination ofthe sensation. Th e decision the vagina will create confus ion w ith thi s system.
regarding the sensation should be made based upan
the observation ofthe sensation as the tissue pass es H. Do not base the observations on what is observed
over the p erineal body . on the underwear.
It is common to see sorne discharge present on the
E. Wi pe un til th e mu cus is gon e. underwear. However, the presence ofthi s di scharge
The woman is instructed to wipe until the mucus is genera lly does not corre late with the phases of fer-
gone. lt has been observed frequently that non-Peak- tility and infertility. Therefore, the woman should
type mucus is observed on the first wipe on ly to ob- not base her observati ons on what is in the under-
serve Peak-type mucus on a second or even a third wear. A user 's good j udgment is someti mes neces-
wipe. If the decision on the mucus observation is sary with th is instructi on. For example, iffor sorne
made on only one wipe, then an important mucus reason a mucus d ischarge w ith Peak-type character-
observation can be missed. Apparently, the w ip ing istics is observed in the underwear and at no other
process has the ability to "pul!" mucus down toward time, then it should be reco rded and assessed.
the opening of the vagina. ln effect, the woman
should wipe until dry .
Figure 5-3 : A diagram of the vulvar anatomy. The arrow indicates the direction of the
observation for mucus and the area from the urethra through the perineal body which is
wiped when observing the mucus.
When to Check for the Mucus O. Bear down every time before bedtime.
At the last observation prior to bedtime, the woman
l. Check for the mucus every time before urination. should also be instructed to urinate and then bear
down with a mild pushing simi lar to a bowel move-
J . Check for the mucus every time after urination ment. This allows far any mucus that may be present
It is important in observ ing the mucus to observe to be pushed down to where it can be observed by
be/ore and after urination. The mucus may be seen externa! observation. lt is a part ofthe observational
only befare urination and not after, and then again it routine because many wo men will not have a bowel
may be seen only after and not befare. lt cannot be movement every day. This bearing down simp ly
pred icted in advance when the mucus will be ob- mimicks the pressure of a bowel mo vement far one
served so, in order to make reliable observations, fin a l observation at the end of the day.
they should always be made both be/ore and after
urination . P. Make a decision at each observation.
K. Check fo r the mucus every time before a bowel Q. Register each observation.
movement. The woman is taught to make a definitive decision
regarding what she is ob erving at the time she makes
L. C heck fo r th e mucus every time after a bowel her observation. She shou ld then make a mental note
movement. of that observation so that it can be recorded at the
lt is important in observing the mucus to observe end ofthe day. This in struction becomes even more
both be/ore and after a bowel movement. The mu- important as the woman becomes an experienced
cus may be seen only befare a bowel movement and user of the system. Once the observationa l ro uti ne
not after and, then again, it ma y be seen only after a becomes a routine, the observations can be done so
bowel movement and not befare. lt cannot be pre- qui ckly that, unless a conscious dec ision is made at
dicted in advance when the mucus observation will the time, the observation can be lost. Therefore, en-
be observed so, in order to make reliab le observa- couragement at the later follow-ups is provided.
tions, they should always be made both befare and This process of making a mental note of the
after a bowel movement. observation is referred to as registering the obser-
vation. Registering is important if observations are
M. Check every time you go to th e bathroom. not to be lost. In addition , the observation must be
lt is important that the mucus observation be made taken as is. There ca n be a tendency to negotiate an
every time that the woman goes to the bathroom . observation. The process of negotiating is the pro-
She does not have to make special trips to observe cess whereby the actual observation is mentall y
the mucus but, when she goes to the bathroom , an "talked away" and replaced with aja/se observa-
observation should be made. This becomes part of tion . Us uall y, this occurs because the client thinks
her normal hygiene. While there wi ll be variati ons that the actual observation just "couldn 't be. " There-
from one woman to the next in the number oftimes fare , it is vitally important far the teacher to make
she goes to the bathroom in a given day, nearly 97 the importance of registering actual observations
percent of women will go to the bathroom four or clear to the elient.
more times. The mucus is afien seen only once dur-
ing the day and, ifthe woman is not in the routine of R. Never discon tinu e observations.
observing every time she goes to the bathroom, she In teaching, it shou ld be stressed that the cli ent must
can miss an important observation. adhere to the observationa l routine 100 percent of
the time. Therefare, di scontinuing observations will
N. Check for the mucus every tim e before going to make the system less effective.
bed.
A last observation of the mucus should be made at S. Do not become complacent about making the ob-
the end of the day just prior to going to bed. Occa- servations.
sionally, this wi ll be the only time that the mucus is As the woman becomes more confident in the use
present for the day and, if an observation is not made ofthe system and the observations become easy far
at that time, the mucus will be missed. In teaching her, she needs to be reminded th at she should not
this instruction, the teacher and user should be aware become complacent or " lazy" in checking for the
that this observation should be made within 15 min- mucus . Again, this is discussed in the early fa llow-
utes of going to bed to go to sleep. ups but becomes especia ll y important at the later
follow-ups and in long-term follow-up because mak- 3. Do you generally take baths, showers, or both?
ing these observations is so very easy once leamed At the time ofbathing or showering, the mucus can
and intemalized that it is easier to become compla- be washed away when the vulva is washed. There-
cent the longer one does them. fore, the client is instructed to observe far the mu-
cus prior to taking a bath or shower and, as a gen-
eral rule, to observe far the mucus whenever the
Additional lmportant Considerations in vulva is wiped.
Checking Sorne women also do an interna! washing of
the vagina while bathing. While this is nota com-
In addition to teaching the woman the basic observa- mon practice, it could lead to sorne difficulties in
tional routine, which has been presented above, there mucus observation and should be discouraged.
are a number of miscellaneous items that are al so cov-
ered with each new c li ent. 4. How often do you go swimming?
Those women who swim freque ntly have a unique
l. How often do you have a bowel movement? concem regarding the mucus. Again, when towel-
Most women wi ll have a bowel movement at least ing, the mucus may be wiped away. They should be
every day or every other day. However, sorne women made aware of this possibility so that a mucus ob-
move their bowels less frequently than that. E licit- serva/ion is not missed.
ing the bowel habits of the client is important so
that the teacher can stress the importance ofthe in- Many women wi ll have a retroflexed or "tipped" uterus.
struction to bear down at the end of the day. There is no known association between a tipped uterus
and any diffic ulty observing the mucus.
2. How often do yo u get up at night to urinate?
Over 40 percent ofwomen will get up at least once
in the middle of the night to urinate. They are in-
structed to be sure to observe the mucus at that time
as we/l.
Remember
Sticky = up to 114"
Tacky = Vi to %"
Stretchy = 1" or more
1
i
/4 inch
1 1
l 1
'h -31• inch 1 inch 1 1/z inches 2 inches 21/z inches 3 inches, etc.
Sticky Tacky Stretchy

Figure 5-4: Words used to describe stretchability (diagram is to exact size) .
Words That Are Used in Describing Words used to describe two other variations:
the Mucus ~-----------~ There are two other types of discharge that a woma n
might observe while using the CrMS . These two types
In order for a common language to be developed , the of discharge are very characteristic in their consistency.
words that are used in describing the mucus are stan-
dardized. With this in mind, the following definitions
VARIATIONS
for words used in describing the mucus are used:
Pasty (creamy) = The pasty discharge is very simi-
lar to the consistency of flour
Words to describe " stretchability" ( Figure 5-4): paste or hand lotion . lt may be
sticky, but it is never tacky or
stretchy (by itself). lt is usually
STRETCHABILITY cloudy or white in color, although
Sticky = the mucus stretches up to '.!.. inch . on occasion it may be yellow
Tacky = the mucus stretches from Y, to :Y. inch . Gummy (gluey) = Sorne women may observe a very
Stretchy = the mucus stretches 1 inch or more.
thick discharge which looks like
half-dried airplane glue or rubber
cernen!. lt will often (but not al-
ways) have a yellowish discolora-
The words sticky, tacky, or stretchy refer to the stretch- tion to it. lt may be sticky, tacky, or
abil ity of the discharge. Once these words ha ve spe- stretchy.
cific definitions they take on sorne meaning. lt is im-
portant to note that the woman does not require a ruler
to make these determinations: she can easily estimate
them.
A Note about Sensation _ _ _ _ _ __
Words to describe color: The sensation the mucus creates is extreme/y importan/
to the proper use ofthe CrMS . There are basically three
COLOR sensations that a woman will observe: dry, smooth, and
lubricati ve. Ali three of these sensations are obvious.
Clea r = The mucus is crystal c/ear However, it is common to have a woman who confuses
Cloudy (white) = The mucus has cloudy or white ap- the smooth sensation for the lubricative one. This hap-
pearance to it. lt may be opaque pens particularl y in women who are not experiencing
(that is you cannot see through it) or true lubrication and, therefore, think that the smooth-
it may be translucen! (somewhat
ness they feel is lubrication. Actually, the d1y and smooth
"foggy" in its appearance
sensations be long to a broad category of nonlubricative
Cloudy/clear= The mucus is partly cloudy and partly sensations while lubrication is separate from those (Fig-
clear. When this designation is used ,
ure 5-5) lt is very important for the woman to develop
the clear means crystal clear.
confidence in her ability to detect sensation , and this is
Yellow = The mucus has a yellowish discol-
acco mpli shed with good teaching.
oration to it. This may indicate a
small amount of blood present in the
discharge ora low-grade infection. The decision regarding the sensation should be made
al the time the woman wipes o ver the perineal body. In
Red = This indicates that there is fresh
blood in the discharge. addition, she should make her decision regarding the
Brown (black) = This indicates that there is old blood
in the discharge.
The Three Sensations
l. Dry - - - - -
nth ________... Nonlubricative
2. Smooth
3. Lubricative
Figure 5-5: The three sensations.

sensation prior to looking at the tissue and finger test- A basic understanding of these two types of discharge
ing the mucus . The sensations are obvious. When dry- is important in the overall understanding of the CrMS
ness is present, the woman will feel definitely dry and and espec ially in case management.
the tissue will drag and develop a "scratchy" type of
sensation. When the woman is lubricative, the tissue 1t shou ld be noted that a third type of discharge may be
will " g lide" easily over the perineal body. When the rel at ively in distinguishable from the type of mucus
woman has a smooth sensation, she will feel a smooth- which comes from the cervix. This discharge is thought
ness as the tissue pas es over the mucus membranes at to originate from the lining of the uterus (the endo-
the opening of the vagina but, then when the tissue metrium). lt is a discharge most usually observed im-
reaches the perineal body, it will have a " halting" ten- mediately premenstruum. lt is nota common discharge
dency and move more roughly. That " halting" tells the but, when observed, it may be sticky, tacky, or stretchy
woman that this is a smooth sensation, belonging to the in nature and cloudy, cloudy/clear, or clear in color.
nonlubricative category, and that it is not true lubrication.
Observation of the Mucus during

Two Types of Discharge Menstruation ___________-.
There are essentially two types of discharge that a The menstrual period is a unique time for mucu obser-
woman will observe. These discharges are characteri - vation. There are severa! important factors to be kept in
tically different. One type of discharge has its origin in mind . First ofall , it is common to observe a mucus-like
the vagina. The other has its origin from the cervix. discharge that occur at the same time as the heavy days
of menstruation and even on the moderate days. This
The pasty (creamy) discharge has its origin from the mucus discharge is endometria l fluid if it is observed
lining cells ofthe vagina. It is a very characteristic di s- during a true menstrua/ion (a bleeding episode which
charge which has the appearance of flour paste, hand follows an ovulatory event). As the menstrual period
lotion or, on occasion , may be thinner than this and be becomes light and very light, the presence or absence
milky in appearance. The different variations in the con- of mucus is as easy to detect as if there were no men -
sistency of the pasty discharge depend u pon its water strual period.
content. The true pasty discharge will never stretch more
than Y. inch. Therefore, it will never have more than a In using the CrMS , the recommendation to the client
sticky consistency to it. 1t does not stretch into a fine should be to use mini-pads during the light and very
thread. li ght days so th at normal mucus observations can be
made. Therefore, tampons should be avoided if pos-
The discharge from the cerv ix is characteristically dif- sible. However, tampons can be used during the heavy
ferent than the discharge from the vagina. Al i discharges and moderate days so long as they are changed fre-
that come from the cervix are cervical mucus discharges. quentl y, at least every four to six hours, and are not used
The cervical mucus discharges may be sticky, tacky, or during prolonged sleeping intervals. These latter rec-
stretchy in consistency. They also may be cloudy, cloudy/ ommendations are preventative measures against toxic
clear, or clear in co lor. On occasion , they may have a shock syndrome.
yellow or red discoloration. Any discharge that stretches
at least Y2 to :Y. inch (tacky consistency) is, by defini- Sorne women will wish to use tampons during the en-
tion, a cervical mucus discharge with its origin from the tire course of their menstrual periods. Those women
cervix. On occasion , the cerv ical mucus discharge wi ll can rely u pon the sensation that is created by the inser-
only stretch Y. inch similar to the pasty discharge . The tion or removal ofthe tampon. This will create a defi-
cervical mucus discharge will stretch into a very fine nite dry or pulling sensation, w hich is very characteris-
thread, and this is different from the pasty discharge. tic . Those observations can be observed as dry. The ob-
This can be verified by communicating this to a user servations of mucus, then , shou Id continue throughout
through the use of The Picture Dictionary. When the the course ofthe menstrual flow.
description is sticky and cloudy, it is important to dif-
ferentiate whether this is the vaginal or cervical dis-
charge. Incidentally, the cloudy nature ofthe mucus dis- General Hygiene _ _ _ __ __ _~
charge which comes from the cervix may be due, on
occasion , to the mixture ofthi s pasty discharge with the The vagina is a self-cleansing organ. There is no need
cervical mucus. to douche. Regular bathing or showeri ng is adeq uate
for norm al hyg ien e. Sorne women who come to a introduced at that time was somewhat modified based
CREIGHTON MODEL FertilityCare™ program may on the experiences of the pilot study and was th e sec-
have been taught that douching is important. In using ond general ion form.
the CrMS, women should not douche sin ce it may wash
away the mucus. Therefore, educati on in thi s area is In l 980, the third generation Follow-up Fo rm was in-
important. troduced and it served the CrMS extremely we ll for 22
years. In 2002, afourth generationfol/ow-up form was
Many women continue to prefer to use tampons for their introduced after three years ofpi lot testing. Thi s form
menstrual hygiene. However, their mi suse can lead to takes into account the major advances that have occurred
toxic shock syndrome, a potentiall y severe infection . in the deve lopment of the CrMS . In particular, it takes
But, there is little danger in the use of tampons so long into account the di verse popul ation to whom CrMS ser-
as proper precautions are taken. It is recommended that vi ces a nd the new wo men's hea lth scie nce of
the tampon be changed evety four to six hours and never NaProTECHNOLOGY are provided.
any longer than that. The prol onged presence of a tam-
pon is the major ri sk for the deve lopment of problems. The Fo ll ow-up Fom1 is, on the one hand, an educa-
Thus, specific instructi on on the pro per use oftam pons tional too! designed to be of service to both the teacher
should be given to each cli ent who uses them. ln addi- and the cl ient. On the other hand, it is a vehicl e whereby
tion, we would recommend that tampons be used only the teaching of a natural means to regu late ferti li ty is
during the heavy and moderate days of menstrual flow. standardized. This form and its proper use in the edu-
Once the light and very light days of menstruation are cational process are integral to the importan/ capabil-
present, we would recommend th e use ofa mini-pad or ity of monitoring a system s teaching effectiveness. Be-
panty shield. ca use of this, it becomes an essential ingredient in the
ongoing assessment of the quality control of a service
A number oftoi let products have perfumes in them . As delivery program.
a general rule, scented hygiene items should not be used.
Those items that may contain such perfumes include The CrMS Follow-up Fonn serves three basic functions:
tampons, pads, mini-pads, toilet ti ssue, fabric softeners
(especia lly those that are used in the dryer), bubble bath, l. The fo nn serves as a cltecklist so that no item which
and bath oi l). Even dyed toilet ti ssue can be irritating. is essential to effective learning is inadvertently omit-
In sorne women, the perfumes and dyes can stimulate a ted. In this case, the form serves as a reminder to the
chem ical irritation, which resembl es the symptoms ofa teacher that certain items must be presented to each
vaginal infection. Only with di scontinuation ofthe prod- new user in a standard fas hi on. This assures that ali
uct do the symptoms di sappear. new users ofthe CrMS have equal access to ali of
the pertinent informati on whi ch is necessary to the
Fina lly, it is preferrabl e that women using the CrMS successfu l use ofthe system.
wear underwear made of all-cotton materia l or with a
2. The Fo ll ow- up Form allows the teacher to monitor
cotton crotch. Undergarments th at are manufactured
tite clients ' new learning and growtlt toward a fuller
from synthetic materi als repel moisture whereas those
understanding ofthe system and its appli cations. Thi s
of cotton material absorb it. With the synthetic fibers ,
process is accompli shed through the teacher's fol-
moi sture tends to co ll ect at the vulva and can be irritat-
low-up by fo ll ow-up assessment and valülation of
ing and , in sorne cases, can lead to confus ion in making
spec ific learning areas. In essence, the Fo llow-up
good mucus observations.
Form outlines the measurable instructional goa ls and
objectives of a learning progra m. This ro le of the
Follow-up Form allows the teacher th e opportunity
CREIGHTON MODEL Follow-up Form=l
to identi fy the specific needs of each new user cli-
ent.
In l 977, a new and unique teaching instrument deve l-
oped through CRElGHTON MODEL ed ucationa l re- 3. Finally, the form serves as a dev ice whereby the edu-
search was introduced into the teaching of the natural cational content of fo llow-up can be carefully docu-
methods forthe regulati on offertili ty. This was theflrst mente d. Such a docum entation is essenti al to qual-
generation Follow-up Form and, after a one year pilot ity assurance monitoring.
eva lu ation , it was introdu ced to th e fir t class of
FertilityCare™ Practitioners (then call ed Natura l Fam- The CrMS Fo ll ow-up Form is di vided into a face sheet
ily Planning Practitioners) in November l 978. The fonn and 21 sections. Of the va ri ous secti ons, 16 ections
74 The Med ical and Surgical Practice of NaProTECHNOLOGY
are related specifically to teaching the system while 5 deed, the material is so familiar that the teacher needs
sections contain various bookkeeping items. The form only to glance at the form on occasion as a simp le re-
is designed in such a way so that one form is used for minder of items that need to be d iscussed. The form
each client-coup le through the course oftheir first eight can easily and unobtrusively be marked as the fo llow-
follow-ups or the first one yea r of use. up progresses. lt has been spec ifica lly des igned so that
such record keeping can proceed witho ut d ifficulty.
The Follow-up Form is an official document and per-
manent record of the FertilityCare™ program that is As the follow-up sess ions progress, the form is used to
kept during the regular course of providing services. assist the cl ients in monitoring their own learning pro-
Ali documentation , written, checked and asse sed, must cess. For example, the assessments which are recorded
accurately reflect what occurred during the course of in Section 4 on observations become a flow chart to the
the follow-up session(s). By answering data on the el ient 's progress in learning how to make the observa-
record and recording his or her teacher code, the FCP is tions and apply them. Another example would be the
representing the information as being true and accurate. use ofthe assessments ofthe client 's satisfaction, con-
fidence and receptiv ity w hich become, in Section 15, a
At the first follow-up , one ofthe first items ofbusiness flow chart as the follow-up sess ions progress. Under-
is to introduce theform to the couple. The teacher shows standing this role of the Fo ll ow-up Form, that is, to
the form directly to the client and explains its three ba- monitor the learni ng progress of the client, allows the
sic functions. As the form is used during the course of teacher to use the form to its fullest potential. When
the follow-up, it should be placed flat on the teaching such monitoring is being performed, it is helpful to turn
surface and it should not be held up in such a way as to the form around so that the client can actually see the
form a barrier between the teacher and the client. In- progress that is being made . In this regard, it shou ld be
.._......,.............._.__. Form t: _/_

Woman's Name: fm41 [t,'unt Age.~ MantaJStatus:._~---
Man'sName: ~'-'-(1 ,;,,...,-r_ _ _ _ _ _~Age.~ MantaJSlatus:~~---

"",..
'-/W - ;J,;J.:J;J
Address:-----1l.L,LLc...t::1~ Tele (H) :Z.:Jd- '''' (W) 3- -oooi m
33
State~ Zip...a:Jo;u.l_ Woman'se-mail -J~~~---
11 marned, lengthof presenl marnage. 3 t!J' º "º Number of marnage '°' each Woman __L__Man
WOMAN'S REPRODUCTIVE HISTORY:
1) #o! Pregnancies C!:) 2) # ol hve b1rths GJ 3) # of children now living [ ! ] 4) Dale ol las1 PAP:~
5) Shortest to longest menstrual cycle {1n days} ~ _ ...3.L_ Pap Recommended· Y or N !E)
6) Mostreoen1 me1hod ol lamilyplanning ~~""------
~
7) Reproduct1ve Ca1egory at 1si F-up
l c Regular Cycles (21 · 38 days)
~ 8) Change in reproduct1ve category 10
6:P1emenopause (40 years or okler) :::_ Figure 5-6 : The face sheet
l s:i: Aegular Cycles - steniized 7:Postpartum - Not Breaa1teed1ng date _ __
2: loog Cycles (generalty > 38 days) 8=Post·abort1on (induced or spootaneous)
3 =8reastfeedmg·Total 9=1nfertilify date._ __
of the Follow-up Form .
4=Breastfeed1ng-Weaning llPPregnant
date _ __
Sz::Posl·P1ll (w1th1n past year)
(lnctudes Oepo Provera, Norplanl)
9} Names &Agesol Ch11dren: _ _,1TJ>"ID-""''J

'i-=-
- --LL
' "--4L<""'--- - - - -
COMMENTS ON GENERAL HEALTH'
1) Commen1sonWoman'sGeneraJ Health: __J"""'" " ' - - - - - - - - - - - - - - -
2) CommentsonMan'sGeneral Health: --"- - " - -- - - - - - - - - - - - - - -
v... . . 2 3 • 5 6 7 8
1) DATE OF FOLLOW-UP 1 •,¡¡.

2) TEACHEA COOE 2 o
3) ADDITIONAL PEASONS al FOLLOW-UP 3 1~
(M=Man C=Ch1ldren e.g. 1C. 2C . etc., 11 no one else is present , pul a ·-·) RTC ,.¡
kept in mind that the Fo llow-up Form is not simply a Section 16: lntention: Use Assessment (IUA) (F ig-
pri vate fo rm fo r use onl y by the teac her but it is a fo rm ure 5- l 3)
w hi ch is to be used to its fu llest capabili ty in th e inter- Section 17: Bi omarkers of NaProTECHNOLOGY
acti ve teaching process. (F igure 5- 14)
Section 18: Summaiy and P lan ofCase Management
The CrMS Fo ll ow- up Form is made up ofthe fo llowi ng
components: Section 19: Assessments and Ass ignments
Secti on 20 : C hange of Status
Face sheet (Fi gure 5-6) Secti on 2 1: A uthorization fo r Re lease of Records
Section 1: Date of Fo ll ow-up
Secti on 2: Teacher Code There are ten reproducti ve categories recogni zed cur-
rentl y in the CrMS . T hese are identi fied and recorded
Secti on 3: Addi tiona l Persons at Fo ll ow-u p
on the face sheet ofth e CrMS Fo llow-up Form and they
Secti on 4 : O bservations (F igure 5-7) are important to th e manage ment of the instructions for
Section 5: Hea lth and Hygiene Rev iew the use of the system. These reproductive categori es
Section 6: Picture Di ctionary Presented are :
Secti on 7: Defi niti ons (Figure 5-8)

1 = Reg ul ar C ycles (2 1-38 d ays) : The c lient is catego-
Secti on 8 : Charting (NaProTRACKING) rized as hav ing regular cycl es if her predominant cycle
(Figure 5-9) pattern has been within the range of2 1-38 days over
Secti on 9: Special Di sc harges the past six months and she has not been on any medi-
A. Aro usal fl uid cation w hi ch might artifici a ll y alter the length of the
B. Sem ina l flu id cycles. T he reproductive category is classifi ed as l S if
Section 1O: C harting (NaProTRACKING) Patterns th e wo man has regular cycles but has been ste ri lized . If
Identifi ed the man has been sterilized, then the category remains a
" l ."
Section 11: Special C irc umstances
A. Earl y Ovul ation
2 = Lon g C ycles (genera lly >38 d ays): A wo man is
B. "Doubl e" Peak
categorized as ha ving long cycles if her predominant
Secti on 12: Spec ial Applications cyc le pattern over the past six months has been >38
A. Post-pill days in du ration and has not been infl ue nced by medi -
B . Breastfeeding cations whi ch might a lter the length of the menstrual
C. Postpartum - not breastfeed ing cycle.
D. Post-abortion
E. Ado lescen t ( 17 and under) - not 3 = Breastfeeding - Total: A wo man is class ifi ed as
genitall y active bei ng tota lly breastfeeding so long as her in fa nt 's tota l
F. Sing le ( 18 and over) - not genita lly nutritiona l needs are being rn et by the breast (w ith the
active so le excepti on ofoccas ional sips ofwater). This defini-
G. Premenopause (40 years and o lder) tion appli es regard less of the presence or abse nce of
H. Post-steril ization menstrual bl eeding.
l. Premenstrua l Synd rome
J. Infertili ty(F igures 5-1 Oand 5- 11 ) 4 = Brea stfeedin g - Wea nin g : O nce any fo rm of
Secti on 13: System In structions supp lementati on is ad ded to breastfee ding then, at that
I. Bas ic Princ ipi es po int, the c lass ification changes to "Breastfeeding -
ll . Sp ice lntegration (Figure 5-1 2) Wean ing. " T his class ifica ti on system continues through
[[ l. Mutua l Dec ision- making three complete menstrual cycles fo ll owi ng the complete
Secti on 14: ln structi ons cessation of breastfeeding.
I. Li st
II. In structi on 1ntegra ti on 5 = Post-pill (within p ast yea r): A wo man is in thi s
re prod uctive category, rega rd less of cyc le pattem , if
Secti on 15 : Personal Evaluatio ns
there is a hi story of birth contro l pill usage w ithin the
A. Satisfaction w ith the CrMS
past 12 months. Rec lassifi cation to another reproduc-
B. Confidence in Use of th e CrMS
tive category occurs after one fu l! yea r has passed with-
C. Rece pt iv ity to Unpl anned Preg-
o ut the use of the birth contro l pi ll. T hi s reproductive
nancy
category is a lso used fo r other chemi ca l fo rms of con- 7 = Postpartum - Not Breastfeeding: A woman is clas-
traception such as DepoProvera, Norpl ant, and the skin sifi ed in thi s reproductive category when she has re-
patch. cently given birth but has not breast fed her infant. This
c lass ifi cation continues through three complete men-
6 = Premenopause (40 years or older): Regardl ess of strual cycles regardless of how long a time it rn ay take
cyc le pattern th e woman is changed to thi s reprodu c- fo r those cyc les to be cornpl eted.
tive category at the time of her 40th birthday. Thi s defi -
niti on is des igned for basic sirnpli city of record keep- 8 = Post-abortio n (sponta neous, ectopic or induced):
ing with the full recogniti on that phys iologicall y ali Thi s reproducti ve category is utili zed for wornen who
women are not prern enopausa l at age 40 and so rn e ha ve experienced a recent spontaneous abortion, ectopic
women rnay be prernenopausa l pri or to the age of 40. pregnancy or induced abortion . The reproducti ve cat-
Nonetheless, it pro vides a reasonabl e marke r for the ego ry continues through the first comp lete menstrual
beg inning of the premenopause and thus is helpfu l 111 cyc le.
teaching.
4) OBSERVATIONS - REVIEW & ASSESSMENT

(Code for this section: 1=Unsatisfactory Application 2=Satisfactory Application ..J=Reviewed • assessment not indlcated
- =Not applicable)
How do you check for t he mucus? 4 7
:; wI~ I ~ 1 1 1 1 1 1
5 6 8
A . Do you use llat layers of tissue?
B. Do you ever use crumpled tissue?
C. Do you wipe from back to front (1) ar
from front to back (2) 4C
'""'--1=-F"-<-+-_.____..._..._....
O. Do you check from the urethra thru the perin eal body?
40 '-'---="-""--'-+-........-..1.-1---....
E. Do you always wipe until the mucus is gane ? Until dry?
4E l'--'-i<-'"-l'~i<---.jo<.-~-l<'-lL-....1
F. Do you ever do interna! exam inations to check for the mucus? 4F =--=_...,,_,_+-_.____..._...__.
G. Do you ever check directly with your fingers? 4G "'illllliíÍI. .. _ . _ . _. . ._ . _ . _ .
H. Do you ever base your observations on what you may
see on your underwear?
4) OBSERVATIONS - Cont"d
When d o yo u chec k for the muc us?

3 4 5 6
~
. ' ~ .:< .;¡
l. Do you check every time belore urinatlon ? ~ I
UJ -
~ il J¿ J. Do you check every time alter urination ? 4J ~ :J
"
;;
o
-~
> K ..\<'.'.'. K. Do you check every time before a bowel movement? •K
"1 .;¡ Figure 5-7 : Observation s - review
a:~
L JL L. Do you check every time after a bowel movement? 4L ~ ;¡ lc:J and assessment (from Section 4
!~ M _¡¿'. M. Is there ever a time when you go to the bathroom but do not check? <lM 1 I ¿;¡ of the Follow-up Form).
~ ·-:- NL N. Do you check every time before going to bed ? ~ .;¡
~ ~ oµ¿ O. Do you bear down every time before go1ng to bed ? (wl! hm 15 min.)
"' I
,;;¡
o¡;; 'º 1
"
E~ p l.L P. Do you make a dec1s1on at each observation ? 4P ;; ¿;¡ :;;
ªl.L O. Do you register that observalion?
'ª ;2 ,;;¡ .l
~
a:
A[.,¿: A. Do you ever d1scontinue your observat1ons?
"" 1 I
1 .) .;¡
,;)
s ~ S. Do you ever gel complacen! about your obse rvat1ons ? •S
4) OBSERVATIONS - Cont'd
The Three Steps 4 5 7 8
T íA
~
T. Can you tell me what are the three steps in check1ng
for the mucus?
•T I / 1-< l 1 1 1
Í."/1 U. Do you always determine the sensation when wip1ng
~
:~ I', I ~ 1: 1 1 1 1 1 1
befare observing the tissue?
v 0 V. Do you always finger test anything you see on the tissue?

(lncluding 2, 2W, 4)
w~ W. What observations do you make when finger test ing? 1

X. SPECIAL INSTRUCTIONS
x,fl) 1. How often do you have a bowel movement?

(# ol times/# ol days )
4X1 IYvVVVVVl/VI
x2 [2} 2. How often do you get up at night to urinate? (#o! times)
Do you observe at that time? (Y or N)
4X2 \YvVVVVVl/VI
X3 0 3. Do you generally take batl1s(1). showers(2) , or both(3)?
Do you check befare and alter? (Y or N)
4X3 ~
x• [Z) 4. How often do you go swi mming? (# ot times)

Do you check before and atter? (Y or N)
•x• WVVVVWI
Y. SECT10N4: ISMANAGEMENTOFOBSERVATIONS
NECESSARY? (Y or N)
1
Figure 5-8 : Review and

assessment of definitions 7) DEFINITIONS - REVIEW & ASSESSMENT
(Code for this section: 1=Unsatisfactory Knowledge 2=Satisfactory Knowledge -V=Reviewed - assessment not indicated
(Section 7 ofthe Follow-up
- =Not applicable)
Form ).
A . What is Peak Type mucus? 7A f .;J ;>. ;¡
B. What is non- Peak Type mucus? 78 I ,;¡ ,;¡ .;(
C . What is the Peak Day? 7C 1 ;¡ ;¡ .;¡
D . What is the pre-peak phase of the cycle? 70 1 I ,;¡ .J.
E . What is the post-peak phase of the cycle ? 7E 1 I ;¡ ;;¡
8) CHARTING (NaProTRACKING™}- REVIEW & ASSESSMENT

(Code far this section: 1=U nsatisfactory Application 2=Satisfactory Application ..J=Reviewed - assessment not indicated
- = Not applicab1e)
A. CHART REVIEWED WITH FCP/FCI ( ../ )
B. Peak Days correctly identified (1, 2, V)

The Peak Day confidently identified (Y, N, V) 88 0 ~ ~1
31 / 1/ / /
C. Correctly charts stamps se 1 .;¡ ;J. ;;¡
O. Correctly charts recording system eo 1 ,;¡ ,:¡ ;;¡
RECORDING SYSTEM (VDRS) REVIEWED (V) y y
E. Charts at the end of the day • Who does the charting? (M, W, B) lf" 1% Ys 1% X 1/1/ / /
F. Charts the most fertile sign of the day 8F 1 .;;¡ ;¡ ;;¡
G. Charts the menstrual flow - H, M, L, VL, B 8G ;;¡ ;;¡ ;;¡ ;;¡ Figure 5-9 : Review and assessment
H. Charts brown/black bleeding as B 8H 1 1 ¡;¡ ;;¡ of client's charting (Section 8 of the
t. Charts bleeding other than the period 81 v ;;¡ ;¡ Follow-up Form).
-"
J. Charts dry/mucus on L, VL, and B days SJ 1 - ...< ¡;¡
K. Charts all acts of intercourse - 1 8K
v j ;;¡ :;
L. Charts discharge after intercourse on its merits 8L ,/ ,; ;l. d.
M. Are barrier methods being used? (Y or N) !t.1 N N
N. Is coitu s interruptus or withdrawal being used? (Y or N) 8N
N
O. Discuss concomitant use of barrier methods, coitus interruptus 80
"
v ./
and withdrawal ('<)
P. SECTION 8: IS MANAGEMENT OF CHARTING NECESSARY? (f or N)
•
12) SPECIAL APPLICATIONS - Cont'd
J . INFERTILITY
1. Clrcumstance not appllcable O 6 7
2. Avoid genital contact 1st complete cycle 12J2
3. Length of time trying to achieve pregnancy ,,,,
4. Name of physician conducting evaluation 12J4
5. Diagnosis to date (be medicaUy specific) 12J5
6. Explain CrMS regarding subfertility or infertility 12J6
7. HISTORY OF TESTS, PROCEDURES, TREATMENTS:
A. TESTS :
Diagnosis of Ovulatlon TESTS Dates & Results
a. BBTUsed
b. Endometrial Biopsy
c. LH Testing (urine)
d . Ultrasound Series (for ovulation
:~;::, ._.
12J7Ad
¡,_,_.=;l.==____________
~=....=="====b=;=p="•~'~+;":!"
• 1.. : : ""''" - ha-6= ·~=======::1
.....-
assessment}
1
Hormone Studles
e . Complete Hormona Profile y ®
f. Hormona Testing, Other (describe) y® 12J7Ael
12J7AI
g. Serum Progesterone y ®
12J7Ag ~::::::::::::::::::::::::
Male Fertlllty Teetlng
h . Post·Coital test (Huhner test)
l. Seminal fluid analysis
y ®
('j) N 12J7Ah l 4/o -,. _ 1
----------
12J7Ai . ogr"n")o.I _
J. Sperm Antibodies y @ 12J7Aj 1---~~~~-----
Mlscellaneous
k. Thyroid Testing
1. Beta-endorphins
m .Other
:~;=~1
12J7Am f-.
1
- - - - - - - - - -.....
_____________ ---11
B. PROCEDURES: PROCEDURES Dates & Resutts
a. Hysterosalpingogram 12J7Ba l-."1,l.lU:C....::
- :..I+1.1.1><. ~ ....,-,____
............J:lf _.
h. Selective Hysterosalplngogram 12J7Bb
c. Hysteroscopy 12J7Bc l - - - - - - - - - - --11
d . Laparoscopy 12J7Bd
e. Transcervical Catheterization of Fallopian 12J7Be 1 - - - - - - - - - - --11
Figure 5-10 : Special Applications - lnfertility

T.-
1. Other 12J7Bl
(from Section 12 of the Follow-up Form)
78 The Medical and Surgical Practice of Na ProTECH NO LOGY
Figure 5-11: Special Appli cations -

12) SPECIAL APPLICATIONS - lnlertility cont 'd lnfertility (from Section 12 of the
C. TREATMENTS: Follow-up Form)
Medleal Treatments TREATMENTS AND DATES
a. Birth Control Pills (for endometriosis) 12J 7Ca
b. GNRH Analogs (lupron, Syneral, etc.) 12J7Cb
c. Serum Progesterone 12J7Cc
d. Clomid 12J7Cd
e. HMG - HCG (Pergonal-like drugs) 12J7Ce
t. Mucus enhancers 12J7Ct
g. Progesterone (lf so. what kind ?) 12J7Cg
h. HCG 12J7Ch
l. Glucophage 12J7CI
j . Thyroid Rx 12J7Cj
Surgical Treatments
k. Cauterization of Endometrial lmplants 12J7Ck
l. Laser Laparoscopy 12J7C1
m. la ser Laparotomy 12J7Cm
n. Myomectomy 12J7Cn
o. Ovarian Drilling 12J7Co
p. Ovarian Wedge Resection 12J7Cp
q . Tubal Surgery 12J7Cq
r. D&C 12J7Cr
ART Treatments
s. IVF 12J7Cs
t. GIFT 12J7Ct
u. ICSI 12J7Cu
v. ZIFT 12J7Cv
w . Artificial lnsemination
lntrauterine (IUI)
Husband (AIH) 12J7Cw
Donor(AID)
Male
x. Variocele Repair 12J7Cx
y. Male on Medication
z. Other Male lnfertility Treatment
12J7Cy
t2J7Cz 1
CrMS
aa. Fertility-Focused lntercourse t 2J7Caa
bb. Other _ _ _ _ _ _ _ _ __ 12J7Cbb
11. SPICE INTEGRATION (v )

(Dialogue between teacher and couple)
A. What is genital contact? (Assess 1 or 2) 1311A
B. What is a contact pregnancy? (Assess 1 or 2) 13118
C. What is sexual contact? (Assess 1 or 2) 13llC
o. What is SPICE? (Assess 1 or 2) 13110

1 .;¡, ~ ;;¡
E. Discovering the "lnner Soul' of your Human Sexuality:
1. Dialogue between the spouses (comm unication) 1311E1 1/ v v' v
2. Mutual respect for each other 1311E2 v V' v v'
3. Shared fam ily planning responsi bility 1311E3 v v' v' v
4. Self-control and self-mastery in the area of your sexual 1311E4 ./ V' .,.-- V
relationship
5. Planned avoidance of genital contact 1311E5 v v v v
. ,---··v-·-v-..·-..v
-.---
.
6. Development of new patterns of non-genital sexual interaction I I / 1 . / 1 ./ I · / 1
(arousal touch vs. affirming touch) 1311E6
7. Tenderness and affection are what constitute the "inner soul'
1~1~1r1~11 1
of human sexuality
8. CrMS asan 'investment in the future"
,~I
1311E8
Fig ure 5-1 2: SPICE lnt-
egration (from Section 12
9. Discussed SP ICE lndex "'e
F. Other (record in comments section) 1311F
of the Follow-up Form).
Chapter 5: Standardization of Teach ing 79
Figu re 5-13: lntention : Use

16) INTENTION : USE ASSESSMENT (IUA) Assessment (from Section
A. Are yo u (your spouse) c urrently using the CrMS as a system to achleve 16 of the Follow-up Form ).
pregnancy (1) to avold pregnancy (2) orto monitor lertillty (3)? 1 2 3 4 s 6 e
:~1~
1 ~ 111~m111
1. Woman's self·evaluation
2. Woman's evaluation of man
3. Man's self·evaluation
4. Oiscussed (Y or N)
B. How wo uld yo u rate yo ur (your spouse's) strength ol convictlon

regard lng your curren! lntention in using the CrMS?
1 ; Definitely not strong 2;Not strong 3;Not sure (undecided) 4;Strong 5; Very strong
:~11~111~1~11 1
1. Woman's self-evaluation
2. Wom an's evaluation of man
3. Man's self·evaluation
4. Discussed (Y or N)
C. lntention : UseAssessment(IUA)
1. Observations (Section 4)
2. Charting (Section 8)
3. Application of lnstructions according to users expressed intention
lnterpretatlo n of lntentlon: Use Assessment (IUA)

::1
Excellent;15; Very Good;14; Good;13; Fair;12; Poor;_s 11 IUA . . . . _ I_ _ _ _.1_1s_.l_16""'1-""'_.
17) BIOMARKERS OF NaProTECHNOLOGY REVIEW ANO ASSESSMENT
A. CYCLE LENGTH (>/)

1. Regular length cycle (25-31 days)
2. Short cycle (s 24 days)
3. lntermedlate long cycle (32-38 days)
4. Long cycle (> 38 days)
B. POST-PEAK PHASE
~ "'' 1i
1. Range of length
2. Short post-Peak phases (~ B days) (.../)
3. Long post-Peak phases (~ 16 days) (V)
4. Variable length post-Peak phases (> 3 days) (../)
1· 1 · 1· 1
C. MUCUS CYCLE
1. Aange of Mucus Cycte Seores (MCS)
2. Type of mucus cycte
1 = Dry (O.O); 2 = Umited (0.1 - 5.6) ;
3 = lntermediate Umited (5.7 - 7.5);
4 = Jntermedlate Regular (7.6 - 9.0) ; 5 = Regular {9.1 - 16.0)
3. Length of mucus cycle
1 = 1·8 days 2 = 9 days or more
D. BLEEDING
111
1. Tail-end brown (2: 2 days)
2. Premenstrual spottlng (2. 3 days)
3 . lntermenstruar bleeding
1 = Earty in Mucus Buildup 2 :e Late In Mucus Buifdup
4. Prolongad menses (8 or more days)
S. Very heavy menses
E. OTHEA MEDICAL SYMPTOMS (Y or N)

1. Bad menstrual cramps
F.
2. Pelvic pain
BIOMARKERS MEET THE CAITERIA FOR:

1 1 1 1 I= 1 1 1 1
1. Alsk of cervical inflammation
2.
3.
"'"' Risk of low progesterone
Miscarriage risk
4.
5.
"'
"'
Sublertility risk
Aisk far PCOO
6.
7.
"'"' Risk for hypothalamic amenorrhea
Risk for ovarian cyst
8. "' Risk for endometriosis
"'
9. Unusual bleeding
10. Other Nor '!"'P-1
Figure 5-14: Guidelines of NaProTECHNOLOGY
- Review and Assessment (Section 17 of the G. SECTION 17: IS ..-TECHNOLOGY MANAGEMENT
NECESSARY ? (Y or N)
Follow-up Form ).
9 = l nfertility: A couple is classified in th is re prod uc- B. The teacher deve lops the abi lity to use each of
tive category if no pregnancy has occurred w ith in the the education too ls a long with the abili ty to do
previous l 2 months whi le no contrace pti ve measures proper assessments, use good judgment, under-
have been used and acts of intercourse have occ urred stand th e organization and fl ow of the fo ll ow-
at random or if no preg nancy has occurred with in 6 up, and do pro bl em so lving and case manage-
cyc les in co uples who have used the ti me offertili ty as ment.
defi ned by th e CrMS (fertili ty foc used intercourse).
C. Every FertilityCare™ teacher develops the abil-
ity to teach clearl y and concise ly.
10 = Pregnant: Thi s reproducti ve category is used fo r
any woman who is pregnant. Thi s category wo uld be
utili zed when a woman becomes pregnant and is li sted
Physical Environment
as a change in reproducti ve category. l n other in stances,
it may be used fo r a pregnant woman w ho is in for a
ln order for a fo llow-up sess ion to be educationally re-
fo ll ow-up and review of the system pri or to the time of
warding, certai n ite ms in the phys ica l enviro nrnent are
her deli very (for appli cati on after de li very).
helpfu l.
A. The fo ll ow-up teaching roo m, which faci litates

Basic Principies of Follow-up _ _ _~
the interacti ve teaching process, is prí vate and
functio nal yet comfo rtable and access ibl e. The
A CrMS fo ll ow-up can be defined as a one-on-one edu-
teacher avoi ds schedul ing confli cts and sharing
cation sess ion. The fo ll ow-up teachi ng sess ion is con-
offices simultaneously with other programs or
ducted fo r the primary purpose of educating the new
ind ividuals.
CrMS client co upl e. Such sessions are conducted sev-
era! times, over a period of month s and years, with the B. The fo llow-up teaching room provides a seating
edu cational conte nt evo lving and the support expand- arrangement that maintains an equal distance be-
ing as the process continues. The provis ion of the fo l- tween the FertilityCare™ teacher and the users.
low-up serv ices requi res a caring, organized, and ac- For exampl e, the teac her <loes not sit next to the
cessible center where the client's confi dentiality is ma in- woman w ith the man on the other side of th e
tained. room. The teacher allows the coup le to sit to-
gether and the interaction is between both mem-
The FertilityCare™ teacher leads the fo ll ow-up. How- bers of the coupl e.
ever, the fo ll ow-up is not a lecture; it is a dynami c pro-
C. T he teaching room contain s comfo rtable chairs
cess requiring a thorough understanding of the util iza-
and a small desk. These items are not to be a
ti on of the education tools used in fo ll ow-up , a refined
barrier to the conduct of the teaching session.
ability to use CrMS-specifi c teaching ski li s, an adequate
The room should have direct li ghting and proper
phys ical and menta l env ironment, and an effective and
venti lation .
professional delivery.
D . Accesso ri es s hould be ava i la bl e in eac h
At each fo ll ow-up sess ion, the appropriate standard- FertilityCar e™ progra m that adds to the teach-
ize d for m s and e du ca ti o n too ls are use d . Th e ing model. For examp le, toys should be ava il-
FertilityCare™ teacher has immedi ate access to appro- abl e to enterta in sma ll chi ldren, a clock should
pri ate refe rence materials. be available fo r ali to see, and posters can be
hung on the walls to brighten them .
E . At each follow-up session, the teacher must ha ve

CrMS-Specific Teaching Ski/Is
immediate access to office supplies that are used
during the fo ll ow-up process.
A number ofskill s are necessary in teaching th e CrMS .
Wh ile a complete list of these cannot be made, th e fo l-
lowing are the most important:
Effective and Professional Delivery
A. The teacher develops communication skills w ith
To assure that the del ivery of services are effective and
special refe rence to hi s or her ability to listen to
professional , a number of other basic principies shou ld
clients and be sensiti ve to their needs.
be fo ll owed .
A. The teacher exhibits an attitude of respect for Summary ____________- .

each new client. He or she mainta ins confidenti-
a lity and <loes not co un se l o r refer inappropri- This cha pter has presented th e basic concepts of stan-
ate ly. dardized teaching. Many in education ha ve fe lt over the
yea rs that such standardization is not possible. How-
B. The teacher prepares him se lf or herse lf for the
ever, w ith o ve r 25 years of cl ini cal teaching ex peri en ce
fo ll ow-up. Thi s type of preparation begins dur-
now behind the CREIGHTON MODEL service delivery
ing his or her early training as a teacher but con-
program, it has clearly been shown that it can be done
tinues through an indi vi dual preparation fo r each
whi le also maintaining a ve ry personable relationship
fo ll ow-up. He o r she sho uld be dressed appro-
w ith the client coupl es. In fact, in a survey of CrMS
priately, assume a profess io nal posture, main-
client coupl es , it was the pe rsona l a nd indi vidual atten-
tain equal eye contact between both the husband
ti o n ofthe CrMS that made the most s ignificant impres-
a nd the wife, and allow the educatio n tools to
s ion.5
work rather than laboring for the sake ofthe edu-
cation tools .
This standardi zati o n has bee n made poss ibl e through
C. The teacher has a working theoretica l knowledge the creative deve lopment a nd th e ed ucational and sci-
and is ab le to dem onstrate a ppro pri ate clinical entifi c research of the CrMS . lt is the lntroductory Ses-
skili s. The teacher understands case management sion, the teaching schedule, the Pi cture Dictionary, the
concepts and makes a speci fic attem pt to meet observatio nal routine, the CrMS Follow-up Form and
the needs ofthe client. the CrMS follow-up itself - where a li of thi s is inte-
g rated - that ha s a ll owed thi s to develop. And,
D. The teacher is always wi lling and capab le ofwit-
NaProTECHNOLOGY has become the fru it ofthis ef-
ness ing to the va lues inherent in the deli very of
fort.
quality FertilityCare™ Services. The teacher
should never be afraid to cha ll enge a client's
thought process, especia ll y if it is viewed as det-
rimenta l to their learning and successful use of
the system.
1. Hil gers TW, Daly KD , Hil gers SK, Preb il AM : CREIGHTON 3. Hil gers TW, Prebil AM, Dal y KD, Hilgers SK: The Picture Dic-
MODEL FertilicyCare'" System : A Sta ndard ized, Case Manage- ti onary of the CREIGHTON MODEL FertilicyCare' " System. Sec-
ment Approach to Teaching- Book 1: Basic Teaching Ski lis. Sec- ond edition. Pope Paul VI lnstitute Press, Omaha, Nebraska, 1999.
ond Edition. Pope Pau l VI lnstitute Press, Omaha, Nebraska,
4. Hilger TW: CREIGHTON MODEL Fenilicyü ire'" System: A Con-
2002.
temporary Approach to Women's Hea lth Care. Pope Pau l VI ln-
2. Hil gers TW, Hilgers SK, Prebil AM , Dal y KD: CREIGHTON stitute Press, Omaha, ebraska, 200 l.
MODEL FertilicyCare'" System : A Standardized, Case Manage-
5. Hil gers TW: Couples Eva luation ofCrMS Teaching System. Sur-
ment Approach to Teaching-Book 11: Advanced Teaching Skills.
vey conducted at th e Pope Paul VI ln stitute, Omaha, Nebraska,
Pope Paul VI lnstitute Press, Omaha, Nebraska. 2003 .
1999.
lntroductory Presentation
of the CrMS
T he lntroductory Sess ion is the point ofentry into a

FertilityCare™ program. lt is cons ide red the first
step toward a coupl e's life-lo ng use ofthe CREIGHTON
The slide presentation , deve loped for use in the lntro-
ductory Session, has been des igned to address these d if-
ferent needs. However, it has been deve loped only to
MODEL FertilityCare™ System (CrMS). lt is usual ly introduce clients to the use of the CrMS, not to teach
p resented ata spec ified time and by appointment. lt is the system. While they w ill certainly learn a great deal
encouraged that coup les attend the presentation together. about the system during this introduction, it is impor-
However, it is also recognized that at times this may not tant to keep in mind that the actual teaching and indi-
be poss ible and that no one shou ld be excluded because vidual app lication ofthe system is accomplished at the
fo r sorne reason one member of the couple cannot at- individualized fo ll ow-up teaching sessions.
tend . While recognizing that thi s may occur, it is stressed
that the successful use ofthe system depends upon edu- The CREIGHTON MODEL chart, stamps and basic in-
cating the couple. T he mo re one involves coup les in structional materials are not provided to any coup le fol-
the educati on process, the more successful the overall lowing the introductory s lide presentation unless they
teac hi ng progra m. Co nti nued enco uragement of coup le have made an appointment for follow-up. The quality
invo lve ment in the ed ucatio n process is a foundat ion of of fertilityCar e™teach ing is eliminated when follow-
a l1 FertilityCare™programs. up teaching is not cond ucted. lt is unfa ir to the potential
user to give them an introduction to the system and then
Couples atte nd the introductory presentation for a vari- send them home w ithout any further assistance. In or-
ety of di ffere nt reasons. Most of them will come to the der to assure a qua lity ed ucation program , instructional
sess ion hav ing a lready decided to use the CREIGHTON materia Is are d istributed only when the first follow-up
MODEL. However, there wi ll be others who will simply appointment is schedu led.
be coming fo r info rn1ational purposes . For those who
w ill be using the system, some wil l be attending the For this to be properly accomp lished , it is announced to
session to learn abo ut it as a means of avoiding and the couples, at the beginning of the lntroductory Ses-
achi ev ing p regnancy wh il e others wi ll learn it to moni- sion , that they should be making a decision , as they par-
tor their cyc les for med ica! reasons. ticipate in the sess ion , regarding their intention to use
the CrMS . By the time the s lide presentation is com -
83
84 The Medi cal and Surgical Practice of NaProTE CHNO LOG Y
pleted , most couples will have made a decision to use up teaching sessions and the teacher's performance.
the CREIGHTON MODEL. Therefore, following the pre- These eva luations are one aspect of the CrMS qua lity
sentation , the presenting couple will conduct the sched- control monitoring.
uling ofindividual follow-up appointrnents and provide
basic instructional materials (a CREIGHTON MODEL Following this session , ifthe couple makes an appo int-
chart, book of stamps, and the lntroductory Booklet to ment for follow-up , they w ill then be provided with the
the CREIGHTON MODEL FertilityCare™ System 1). lf materials needed far reading furt her abo ut the system
the couple cannot reach a final decision on the use of and to staii charti ng. They wi ll be instructed to:
the system at that time, they may call the FertilityCare™
• begin charting immedi ate ly
System when they have decided to schedule an appoint-
ment. At that time, the basic instructional materia Is are • read the Jntroductory Booklet befare the first fol-
made available. As a general rule, ifthree months pass low-up
prior to the couple's decision , then the couple would be bri ng the chart to each fo ll ow-up
required to attend the lntroductory Session again so that • attend fo ll ow-ups together if poss ibl e
their new leaming can begin under the best of circum-
• review the follow-up schedu le .
stances.
For the reader ofthis textbook who is not fa mil iar with
the basic principies and concepts ofthe CrMS it wo ul d
Priority ltems in Presenting the
be helpful toread the follow ing commentary which is
lntroductory Session _______~
used by FertilityCare™ Practitioner for the ln trod uc-
tory Session sl ide presentation. 2
The following priority items help to develop a good
impression of your overall teaching program . lt is es-
sentia l for the teacher to be so familiar with the mate-
rial being presented that the presentation can be deliv-
Commentary for lntroductory Slides ==l
ered thoroughly, accurately and with poise. To do this
properly, the teacher must be well organized and pre-
pared in the presentation ofthe material. As the presen-
tation commences, it is impo1iant that the teacher de-
velop an atmosphere which allows the participants to
feel comfortable in asking questions. Such aclimate for
free and open exchange of information during the ln-
troductory Session is a quality which ali new teachers
should develop.
The lntroductory Session is usually given to a group

wh ich is no larger than 6 to 1O couples in size. A group
this size allows for an adequate amount of interchange
throughout the presentation without any person in the
group feeling that they cannot ask questions . The lntro-
ductory Session slide presentation is presented only by
individuals who are thoroughly trained in its content. Slide l: 1 (we) would like to we lcome yo u to th is lntro-
ductory Session for the CREIGHTON MODEL System .
During the course ofthe presentation , questions are in- This presentation shall be made up offo ur parts: a few
vited and, after the session , those in attendance will introductory remarks, a basic rev iew of anatomy and
complete an evaluation form so that input can be con- physiology, a review ofthe CREIGHTON MODEL Sys-
stantly gained on the educational quality and relevance tem anda few concluding remarks .
ofthe presentation. In fact, such evaluations have been
a constant component of CrMS service delivery since
its inception. Evaluation forms are also completed later
in the follow-up program to further assess the follow-
Chapter 6: lntroductory Presentation of the CrM S 85
S lide 2: This system has been built upon an advanced Slide 4: The system provides information to ass ist yo u
educational technology called CREIGHTON MODEL in two areas of your life: FertiliCARE and
NaProEDUCATION Technology . Through this unique NaProTECHNOLOGY. In FertiliCARE, we will teach
technology, thi s system can be provided to you with the you how to appreciate your fertility and how to take
highest quality of an alli ed health profession. care ofit. NaProTECHNOLOGY is a new reproductive
science that works cooperative(y with the natural pro-
creative cycle.
S lide 3: Thi s is a service program designed to give you

the important information yo u will need to make natu- Slide 5: In FertiliCARE, we will provide responsible
ral procreative choices and monitor, maintain and evalu- parenthood instruction for achieving and avoiding preg-
ate your procreative and gynecologic health. nancy, timing conception, pregnancy evaluat ion ,
NaProTRACKING the procreative cycle, SPICE in-
struction , and marital bonding .
Slide 6: With NaProTECHNOLOGY, women are able Slide 8: The advantages ofthis system include its medi-
to monitor, maintain and evaluate their own health for ca! safety and proven reliabi li ty (l w il l disc uss this fu r-
the first time. This will include such conditions as in- ther later in this presentation). Tn addition, it is com-
fertility, miscarriage, maintaining pregnancy, irregular paratively inexpensive, natural and cooperative, and
cycles , hormone problems, premenstrual syndrome shared between the spouses. lt res pects the d ign ity of
(PMS), ovarian cysts , un usual bleeding, and the effects women and marriage and it is standard ized. This is a
of stress. national (and international) program where, ifyou move
you can transfer to another serv ice program in your new
location.
And ...
lt's "Tailor Made" for YOU!
Can be Used with:
Regular Cycles Breastfeeding

Irregular Cycies Premenopause
Anovulatory States Post-Pill
Or Any Other Situation
For Your Entire Procreative Lite
Slid e 7: And it is "tailor made" for you! lt is a system

that can be used with regular or irregular cycles, anovu-
latory states, breastfeeding, premenopause, post-pi!! or Slide 9: The system is based on so lid scientific and edu-
any other situation. lt can be used for your entire pro- cationa l research, the observation and tracking ofvari -
creative life. ous biological markers, and it is easy to learn and easy
to interpret.
Chapter 6: lntroductory Presentation of the CrMS 87
A BASIC REVIEW
OF
ANA TOMY AND PHYSIOLOGY
Slide 10: We wou ld now like to review for you some Slide 12: The cell ofhuman reproduction which is con-
bas ic a nato my and physiology so that everyone in at- tributed by the male is ca ll ed the perm. This sl ide shows
tendance can deve lop a common understanding oftheir an actual microscopic photograph of severa! d ifferent
fertility. sperm. The genetic material for reproduction is con-
tained in the head ofthe perm (point to the head ofthe
sperm) and the ability of the sperm to move from one
place to the next comes from the motion of its tail (point
to the tail ofthe sperm).
Slide 11: We begi n this section by stating that menare

always fe1ii le. A man 's fe1i ility begins at the age of 12
or 13 years and continues for the remainder of his life.
lt is a very important rea lization formen to apprec iate
the natu re oftheir ferti lity. Men must understand their Slide 13: The sperm are produced in two g lands called
ro le in the fe rtility process ifthe CREIGHTON MODEL the testes or testicles. The testicles (po int to the tes-
is to be successful. It should be recognized at th is point ticles) are located on the outs ide ofthe man 's body. They
that, on occasion , me n may not be fe11ile or may be are located there primarily because the sperm are highly
subferti le w ithin the context of a couple with infertility sensitive to heat and , if the testes were located inside
but, in general , menare always fertile . the man 's body, the body temperature would destroy
the sperm. On occasion, that may be a cause of male
infertility. After the sperm are produced in the testicles
they are then transported upa tu be called the vas defer-
ens (point to the vas deferens). From the vas deferens,
the sperm go to the urethra and are transported to the
outside of the male's body. The urethra (point to the
urethra) is the channel which normally connects the blad-
der to the outside of the body.
88 The Medical and Surgical Practice of Na ProTE CH NOLOGY
Slide 14: While menare always fert ile, wo men are, for Slide 16: Thi s is a di agram ofthe uterus, tubes and ova-
the most part, infert ile. Women are fertil e for onl y a ri es (po int to the uterus, tu bes and ovaries). The ova ries
short period of time du ring each menstrual cyc le. Of are almond-shaped organs located on each side of the
course, it is not entirely proper to ta lk about the man 's uterus (po int). The uterus is basically a muscle (point
fertility and the woman 's ferti li ty separate ly. The on ly to the muscle) . There is a cav ity w ithin the uterus and ,
meaningful point of discussion is the comb ined ferti l ity at the open ing ofthe uteru s, there is an organ ca lled the
ofthe couple. Since women are for the most part in fer- cervix. Lining the canal ofthe cerv ix are cervical crypts.
tile, this means that the couple for the most part is also lt is with in the cervical crypts that the cervical mucus is
infertile. Since men are always " fertil e" and women are produced (po int to the cervical crypts). The mucus is
for the most part " in fertile," the understanding of the di scharged then to the outside of the woman 's body
couple 's fert ili ty is focused by necessity upon the cy- whe re ali of the observations in the CRE IGHTON
c lic variations of fertili ty and infertil ity that occu r in MODEL are made. There are no interna! examinations
the woman. in vo lved in using the CREIGHTON MODEL. lnciden-
tally, the location at the opening ofthe cervix where a
pap smear is taken is also shown on this slide (po int) .
PREOVULATORY POSTOVULATORY
SHOllT
CYClE
<YV 1 • 17 DA'f'S
~&f'
<YV 13.t .. DAY9
VARIABLE LENGTH <YV STABLE LENGTH
Slide 15: ln this slide, the location ofthe reproductive

organs- the uterus, tu bes, and ovaries- are shown as they
exist in the pelvis. Un li ke the man , the reprod uctive or-
gans in th e woman are located inside ofher body. Slide 17: The menstrual cycle begins w ith the first day
of menstrual bleeding and ends w ith the last day prior
to the beginning of the next menstrual period. Most
people are aware of the fact that the menstrual cycle is
not exactl y regular. However, many people wonder what
the difference is between a short cycle, a regular length
cycle and a long cycle (point to those words on the slide).
In this slide, the phases ofthe menstrual cycle
are expl ai ned . There are basically two phases that are
important, the preovulatory phase and the postovulatory lation cycle." There are severa! hundred thousand indi-
phase. The preovulatory phase of the cycle is counted vidua l, undeveloped eggs in the ovary (point to the sma ll
from the first day ofmenstrual bleeding until the day of blue dots in the upper ri ght hand area of the ovary).
ovu lation (point) . The postovulatory phase ofthe cycle Early in the menstrua l cyc le, one or two ofthese eggs is
is counted from the day after ovu lation until the day se lected to deve lop toward ovu latio n. These eggs de-
before the beginning of the next men strual period ve lop within a fo llicle. A fo lli cle is a small cyst- li ke
(po int). structure. The fo llicle begins to grow and develop and ,
It is the preovulatory phase ofthe cycle which just prior to ovulation , is one inch or more in diameter.
is high ly variable. The postovulatory phase ofthe cycle At that time we call it a mature fo lli cle (point to the
is quite stable in its length. From the time of ovulation fo lli cles). With the rupture ofthe fo lli cle, the egg is re-
until the beginn ing of the next menstrual period aver- leased from the ovary in a process ca ll ed ovulation
ages about 13 days although a range of9 to 17 days can (point). The same tissue, which was the mature follicle ,
be expected in a population ofwomen. However, in the now becomes what is ca ll ed the corpus luteum . That
individua l woman , there is great consistency in the means "ye llow body" because it appears yell ow on the
length ofthe postovulatory phase ofthe cyc le. It is the ovary.
preovulatory phase of the cyc le which is highly vari - Now the developing fo lli cle (point) produces
ab le in length. a hormone that is the predominant preovulatory hor-
This fact has plagued methods of natural fer- mone and the one which stimul ates the production of
tility regulation for many years. Ifthe preovulatory phase mucus. After ovul ation the corpus luteum produces a
of the cyc le was stab le, then a li one wou ld have to do hormone call ed progesterone. The progesterone hor-
wo uld be to ca lcu late so many days from the first day mone is the dominant postovulatory hormone. lt stops
of the menstrua l cycle in order to determine one 's fer- mucus production and is essentia l to the hormonal sup-
tility. However, the variability of this phase dictates port to the lining cells ofthe uterus preparing them for
against doing that. The CREIGHTON MODEL has fi- a pregnancy. lnfertility or frequent spontaneous abor-
nally allowed us to so lve this problem. As yo u can see tions (miscarriages) may be caused by an inadequate
by the lightly shaded areas wh ich are present in the preo- corpus luteum whi ch <loes not produce enough proges-
vulatory phase of these cycles (po int) the mucus ap- terone.
pears prior to ovulation and gives advance indication
that ovulation is approaching. Incidentally, as you learn
the sign of ovu lation whi ch is assoc iated w ith the cerv i-
cal mucus observation, the information in this slide be-
comes highly practica!. In fact, a woman wi ll be ab le to
predict the onset of her next menstrual period wel l in
advance of its occurrence.
Slide 19: In this slide, the changes in the lining ofthe

uterus which occur during the course of the menstrua l
cycle are shown ( orient the audience at this point to the
slide by pointing to the far left edge as being the first
day of the menstrual cycle and at the end of the secre-
tory phase as being the end ofthe menstrual cycle). lt is
the lining cells ofthe uterus w hi ch slough at th e time of
menstruation. The menstrual phase is shown on this dia-
Slide 18: During the course ofthe menstrual cycle, there gram (po int). Foll owing menstruation , under the influ-
is a cyc lic event occurring in the ovary call ed "the ovu- ence of the estrogen hormone, the lining ce ll s of the
uterus again begin to grow and develop in what is called late in response to sexual stimulation, but humans do
the "proliferating phase" ofthe menstrual cycle (point). not.
The ovulation cycle is shown on this diagramas well.
The phase of follicular development coincides in the
ovary with the proliferating phase in the lining of the
uterus. Once ovulation has occurred and luteal devel-
opment begins with the production ofprogesterone, the
lining ce li s ofthe uterus begin to secrete a highly nutri-
tious fluid. This is called the secretory phase of the
menstrual cycle (point) . lt is during this phase of the
cycle that implantation of the new human life occurs
following conception. Again , ifthis phase is not prop-
erly supported by the hormone progesterone it can be a
cause of infertility or frequent miscarriage. When the
progesterone hormone leve! fa lis, removing its hormonal
support to the lining ofthe uterus, the lining cells once
again slough and a menstrual period occurs .
Slide 21: Once ovulation does occur, the egg li ves for
only 12-24 hours ifit is not fert ilized . Ifanything, the
life span ofthe egg is closer to 12 hours than it is to 24.
This life span ofthe egg is so short that, ifour fertility
depended upon this fact, most likely very few people
would become pregnant during their entire reproduc-
tive life. But the length ofthe fertile period is extended
by another vital factor. This vital factor is the cervica l
mucus. lt is the cervical muc us that allows the sperm to
survive long enough to be ava il able when an egg is re-
leased and, of course, it is the cervical mucus that is
involved in learning and understanding your fert ility
through the CREIGHTON MODEL System.
Slide 20: It is important to understand that ovulation

occurs on on ly one day during the course of a given
menstrual cycle. Ovulation does not occur today and
then again sometime next week. Ifthi s form of double
ovulation did occur, of course, a natural system would
not work. This form of double ovulation is one of the
old myths that needs to be dispelled when discussing
natural fami ly planning. Ovulation can , of course, oc-
cur twice or even three times in one cyc le as non-iden-
tical twins and triplets would prove. However, when ovu-
lation occurs twice in a menstrual cycle, it occurs within
the same 24-hour time period. From a practica! point of
view, this fom1 of double ovulation does not pose a prob-
lem for users of a natural system . As an addendum to
this discussion, sorne people have felt that women ovu- Slide 22: So, therefore, the sperm need mucus to sur-
late in response to sexual stimulation . This is another v1ve.
myth which needs to be dispelled. The evidence for such
sexually stimulated ovulation comes from experiments
that have been done in rabbits. lndeed , rabbits do ovu-
SPERM WITHOUT MUCUS

DIE WITHIN HOURS
SPERM WITH GOOD MUCUS

MAY LIVE 3-5 DAYS
Slide 23: Sperm, in the absence of good mucus, will Slide 25: This graph shows the pattem ofthe two ova-
die within hours or even minutes when placed into the rian hormones , estrogen and progesterone, as they
vag ina. However, in the presence of good cervical mu- change throughout the menstrual cycle. To orient you ,
cus, the spem1 may li ve for 3 to 5 days. Sperm survival the first day ofthe menstrual cycle would be in the lower
is directly dependent upon the presence of good cervi- left hand comer of this graph (point). The last day of
cal mucus. the menstrual cyc le wou ld be at the lower right hand
comer of the graph. The day of ovulation is shown by
the vertical dotted line in the middle. lfyou follow the
estrogen curve, here shown in red , you will note that
the estro gen leve! rises to a very high leve! , a peak, j ust
prior to the time of ovulation. lt is this rise in the estro-
gen hormone w hi ch stim ul ates the production of the
cervical mucus . After ovulation, the predominant hor-
mone is progesterone. This hormone rises to very high
levels following ovulation as exhibited by the green por-
tian of the graph . The progesterone hormone inhibits
the effects of the estrogen hormone on the production
of cervica l mucus. It a lso he lps prepare the lining cells
ofthe uterus, as mentioned earlier for the implantation
of a new human life .
Slide 24: The hormone estrogen , to which we ha ve re-

ferred earlier, is extremely important in mucus produc-
tion. This hormone reaches a very high leve! or a peak
approx imately one day before ovulation .
Slide 26: So, you should keep in mind that it is the hor-
mone estrogen that stimulates the cervical crypts to pro-
duce the good quality cervica l mucus which is so im-
portant to your ferti li ty.
Slide 27: Thi s slide reveals a very important fun cti on Slide 28: These are actual microscopic photographs of
of the cerv ica l mucu s in human fe rtility. lt illustrates the type E and type G cerv ical mucus. You can see the
the map of the cervix that has been deve loped through chann els present in the type E mucus, in thi s case run-
the important research efforts of Dr. Erik Odebl ad in ning fro m the lower ri ght to the upper left portian of the
Sweden. To ori ent yo u, thi s is the cerv ix (po int to the pi cture (po int to channe ls). The type G mucus, on th e
cerv ix) and above the cervix (point to the area above oth er hand, is thi ck and dense. You can im agine thi s
th e sli de) wo uld be the uterus. Below the cerv ix are the pi cture to be a stone wa ll barrier to sperm penetrati on.
wa ll s of th e vagina (po int) . On the left si de of th e d ia-
gram is a very characteri stic type of cervica l mucus that
is only produced when the estroge n leve ls are ri sing or
are very hi gh. Thi s type ofmu cus arra nges itse lf in par-
all el stra nds (point to the para ll e l strands), fo rming, lit-
era ll y, sw imming channels fo r the spem1 so th at they
can penetrate thro ugh the cerv ix and go up to the fa ll o-
pi an tubes where concepti on will occur. Thi s type of
cervica l mucus is call ed type E mucus. On the ri ght side
is the ty pe ofmu cus that is produced w hen the estrogen
levels are very low or when the progesterone levels are
ri sing and ve ry hi gh. Thi s ty pe ofmu cus is ca lled type
G mucus and is very thick and dense and , in fact, acts as
a barrier to sperm penetrati on.
T hese two types of cerv ica l mucus act, in ef-
fec t, li ke a bi o logica l va lve. The valve is open, all ow-
ing sperm to penetrate through the cerv ix, when the type
E or estrogen stimul ated mucus is prese nt. The va lve is
closed to sperm penetration when the mu cus is type G. SHde 29: These are actual photos of the cervi x and the
Thi s bi o logica l valve is essenti al to human fertili ty an d changes it goes through during the time of fertil ity. You
ass ures that fresh sperm and fres h eggs are avail abl e at can see the fl ow of mucus (point to seco nd photo fro m
th e tim e of con ce ption. The CREIGHTON MODEL left) that is prominent under the influen ce of estrogen
teaches yo u when the bi olog ica l va lve is open and when (the type E mucus) . After ovulation , under th e influ-
it is closed. Generall y, the bi ologica l va lve is open when ence of progesterone thi s fl ow of mucus is absent (type
the wo man observes mucus (po int to the phrase " mucus G mucus). Do keep in mind that ali ofthe observations
days") and the bi o log ica l va lve is c losed when the in the CREIGHTON MODEL are made externall y and
woman observes dry days (po in t to the phrase " dry interna! exams are not a part ofthi s system. The exter-
days"). na! observati ons have been shown to be an excell ent
monitor of these intern a! events.
Ch apter 6: lntroductory Presentation of t he CrMS 93
Slid e 30: In thi s s lide, sc ientifi c ev idence fo r the exist- Slide 32: W hen a n egg and spe1111 uni te is ca ll ed co n-
e nce of th is bi o logic va lve is shown. The actual num- ception and it marks the beginni ng ofa new huma n li fe.
ber of channels increases s ignifi cantly d uring the tim e Each huma n li fe created in thi s fas hi on is uni que. And,
offertili ty (point to the fo ur vertica l bars that go above we mig ht po in t o ut, th is is w hen we ali began o ur li fe's
the dotted line). During days of infertil ity these c han- JOU rney.
nels are sharpl y reduced and sperm wi ll not penetrate.
Here the bi ologic valve is o pe n (po int agai n to the bars
as they go a bove the dotted lin e) and here the bi o logic
va lve is closed (point aga in to th ose bars that are be low
the dotted line).
FERTILITY DEPENDS ON:
• Good Sperm
• Good Eggs
Slide 33: Conception occurs in the o uter porti o n of th e
• Good Mucus fa ll o pian tube (po int). In the few days fo ll ow ing con-
ceptio n the early process of hum an deve lo pment be-
g in s w ith cell div isio n. Abo ut six to nin e days fo llow-
ing conception, a process ca lled impl antati on occurs
Slide 31: Our fe rti lity depend s upon the presence of (po int). T his is th e process w hereby the new human
good sperm , good eggs a nd good cervica l mucus. There bei ng nestles itself into the s id e wa ll of the ute ru s es-
are, of course, ma ny othe r fac to rs in vo lved in the fe rtil- tab li shing its lo ng-te rm suppo rt system fo r its 9-mo nth
ity process. Howeve r, the presence of good quality cer- journey toward birth .
vica l mucus is nearly as im porta nt to the fe rtili ty pro-
cess as the presence of good sperm and good eggs. We
a re only beginni ng to appreciate the ro le of cerv ica l mu -
c us as it re lates to the overa ll reprod uctive process .
However, w hen any one of these three factors is absent,
th e coupl e w ill not become pregnant.
Slide 34: This slide shows an unborn child at 16 weeks Slide 36: One fina l note for those who wish to use the
of age. The placenta is in the upper left (point), and the CREIGHTON MODEL as a means of avoiding preg-
child is connected to that support system by his or her nancy. You need to know that pregnancy can result from
umbilical cord (point). any genital contact on days offertility even without pen-
etration or ejaculation . There is a fluid produced by the
male which is called pre-ejaculatory fluid and thi s fluid
has a very high concentration of sperm. If that fluid
(which can be present without ejacu lation) comes into
contact with the cervical mucus, which is present at the
opening of the vagina, the sperm can find the ir way to
the fallopian tu bes anda pregnancy can resu lt. So, it is
very important in using the CrMS that a li genita l con-
tact be avoided during the times offerti lity ifit is your
intention to avo id pregnancy.
Slid e 35: This slide shows the sloughing ofthe lining

cells ofthe uterus at the time ofmenstruation. This hap-
pens when pregnancy does not occur. The menstrua l
period is reasonab ly good evidence that pregnancy has
not occurred in that given menstrual cycle. At this point,
the cycle is prepared to begin once again.
Slide 37: ow we will proceed to look ata few details

of the NaProTRACKING used in the CREIGHTON
MODEL System.
follow menstruation an d from the fo urth day fo ll owing

the Peak until the beginning ofthe next menstrual tlow
(point to the days offertility and the days ofinfertil ity).
At this point, there are usually two questions
that come up regarding the CREIGHTON MODEL. The
first question is: Why is the menstrual flow cons idered
to be fertile? Menstruation is considered fert ile because,
on occasion, a li wo men wi ll experience a short men-
strual cycle and therefore an early ovulation. This can-
not be predicted at the beginning ofthe menstrual cycle.
When this occurs, there will be no pre-Peak dry days
and an overlap of the mucus with the light and very
1ight days of the menstrual flow wi 11 occur. The men-
Slide 38: This circle diagram indicates both the days of strual flow does not inhibit the migration or penetration
fertility and infertility as well as the essential events that of the sperm a nd therefore is in no way contraceptive.
occur during the course of the CREIGHTON MODEL The presence of the mucus in this stage of the men-
cycle. The menstrual period is shown here (point to the strual cycle (that is, the days of menstruation) will al-
menstrual tlow) and its normal length is usually three to low for sperm survival and penetration and pregnancy
seven days in duration. Following the cessation ofmen- may therefore occur. From a practica! point ofview we
strual flow, a woman will generally observe the absence observe menstruation as a time offertil ity as primarily
of any type of vaginal discharge or the sensation of dry- a beginner's instruction. We would ask that during the
ness (point to the dry days). After the dry days, she will first three months ofcharting, while the woman learns
begin to notice the beginning of a very characteristic to observe for the presence or absence of the mucus
discharge (point to the mucus cycle). This discharge discharge during the lighter days ofthe menstrual tlow,
usually begins with sticky, cloudy or tacky, cloudy char- that you observe this time as fert il e. At the end ofthese
acteristics and progresses to become clear, stretchy or three months, when the woman can confidently detect
lubricative in one or two days. The clear, stretchy or the presence or absence of discharge during the li ghter
lubricative mucus discharge lasts usually for three to days of menstruation , these days (that is, the 1ight days
four days. However, this will be variable from woman ofmenstrual flow) can be determined to be days ofin-
to woman and from cycle to cycle. In any regard , the fertility on the same basis as the pre-Peak dry days. ln-
last day in which the mucus is clear, stretchy or lubrica- fe1tility, in this situation, is defined accord ing to the pres-
tive is ca ll ed the Peak Day (point to the Peak Day) . Af- ence or absence of the mucus discharge.
ter the Peak, the remainder ofthe cycle is generally dry The second question that is usually asked is:
(point) . Later, when we look at charts, this process will Why do you ha ve to count three days following the Peak
appear in a horizontal line like this (point) . We have day? Research has shown that the reasons for this re-
menses, dry days, mucus and dry days again. volve around the fact that ovulation can occur up until
You will notice that on this circle diagram the the third day after the Peak. There has, however, never
days are not numbered from the first day of menstrua- been an ovulation detected on the fou1th day after the
tion un til the day ofthe Peak. However, the numbers 1 Peak.
through 12 do appear from the day following the Peak
until the beginning ofthe next menstrual cycle. lfyou
will remember the previous discussion regarding the tim-
ing of ovulation within the menstrual cycle, then the
reason for this becomes apparent. lt is the preovulatory
phase ofthe menstrual cycle that is highly variable in
duration. Once ovulation occurs, menstruation usually
follows 13 days later (with a normal range of 9 to 17
days). When a woman begins her period approximately
12 days after identification ofher Peak , she wi ll quickly
develop confidence in her ob ervations. The days of
fertility whi le using the CREIGHTON MODEL include
the days ofthe menstrual tlow and from the beginning
ofthe mucus discharge until three full days past the Peak
Day. The days of infettility include the dry days that
C'S are consistency, co/01; change and sensation. T he

consistency ofthe mucus refers to its stretchabi li ty and
quality. The co lor of the mucus discharge refers , for
exampl e, to the cloudy or the c lear characteristics of
the di scharge . The change in the mucu s discharge re-
fers to the day-by-day change in the qualities or charac-
teristics ofthe mucus discharge. The sensation refers to
either the sensation of dryness or lubri cation.
Slide 39: There are essenti a ll y three steps in checking

for the bi o log ic markers. The first step is to wipe the
opening ofthe vag ina w ith wh ite toil et tissue. This step
is extreme ly important since it is during the wiping pro-
cess that a woman shou ld identify the sensation of dry-
ness or lubri cation , which is vita l to her successfu l u e
ofthe CREIGHTON MODEL. After she has made a de-
term ination on the sensation , then the second step i to
observe the tissue for any rnucus which may be present.
Ifmucus is present, then she shou ld finger test the mu-
cus between the thumb and index finger to test for the
stretchabili ty ofthe mucus. While doing this, she should
a lso observe for the color of the mucus . Slide 41: When charting is begun we adv ise that al i
In add iti on, it is extremely important that a coup les avoid genital contact for at least one cyc le or
woman check for the mucus routinely, every time she one month, whichever is shorter. This instruction is im-
goes to the bathroom. She shou ld check both before portant to your rapid development of confidence in the
and after she urinates and before and after a bowel move- use of the method . For the beginner, the seminal fluid
ment. The who le proces takes less than 30 second . discharge which occurs fo llowing intercourse may prove
However, successful use of the method depend u pon to be confus in g. The semina l fluid may look very much
accurate observations so you shou ld adapt your lifesty le like the characteristic mucus discharge. As a result, it is
to include the few extra seconds that it takes to acc u- good to ha ve the opportunity to observe the mucus dis-
rately monitor your fertil ity. charge in its " pure state" without the confusion of the
sem inal fluid. Sem inal fluid wi ll prove to be of li ttle
difficulty ata later time to the woman who has a clear
understanding ofher mucus sign .
ln this sl ide, we a lso have the opportunity to
help you to begin understandi ng the difference between
sexual contact and genital contact. Gen ital contact can
be simply defined as any contact of the gen ital organs.
Sex ual contact is to be specifica ll y d istinguished from
gen ital contact. Sexual contact involves the total per-
son. lt is sp iritual , phys ica l, inte llectua l, creative and
emotional. While ali genita l contact is to be avo ided
during the days offerti li ty if it is the intenti on to avoid
pregnancy, sexua l contact i never to be avoided.
Slide 40: In charting, you should chart on a daily basis

what we cal! the "3 C 'S " (with a capital S) . The three
Chapter 6: lntroductory Presentation of t he CrMS 97
!ID MU=~~
IIJ PEAK
ril [)] [)] co~~T THREE
DRYN ESS
1+ DESCRIPTION 1
Slide 42 : We wi ll now show yo u sorne details that are S lide 44: These are the differe nt stamps that we use in
involved in NaProTRACKING your fert ili ty. In this slide, NaProTRACKING the CREIGHTON MODEL. These
yo u see the front of the chart that we use here at o ur sta mp s provide a uni ve rsa l la ng u age for the
center. CREIGHTON MODEL and are used ali over the world .
The red stamp is used when bleeding is present. The
pl ai n gree n stamp is used when dryness is observed.
The white, baby stamps are used w hen the mucus di s-
charge is apparent. The baby is there, of course, to re-
' .. ....' ,, tJ ll u tj I• 1•" 1• • )1 J: ll :.o¡' Z., l' ZI
" . •1 ·~ )) .. " mind yo u ofyour fe rt il ity. The white, baby sta mp with
a " P" written o n it is used fo r c ha rting the Peak Day.
Now, we do not furnish stamps that already ha ve a little
" P" on them. You must write yo ur own " P" on the stamps
o n the day which yo u judge to be the Peak. During the
three days fo ll ow ing the Peak there may be white, baby
CHART AT THE END OF YOUR DAY
THE MOST FERTILE SICiN OF THE DAY sta mps or green baby stamps. The green baby stamps
STAM PS + DESCRIPTION 1
are used ifthese days are dry and the white, baby stamps
1
are used ifnon-Peak mucus ( i.e. mucus that is not clear,
stretch y or lubricative) is present. Aga in , yo u must pro-
•I·• r NAF'l<o1RACKING THE PRCCREA11VE C'ICL.E
1
1-
vide in your own ha ndwriting the numbers 1, 2 and 3.
Afte r the three days fo llowing the Peak day, the p lain
g reen stamps are again used to indi cate the retum to
Slide 43: In this s lide, yo u see the ins ide of o ur chart. In dryness. Remember, yo u always record the most ferti le
thi s chart, there is room for essentiall y six month s of s ign of the day and yo ur charting at the end of th e day
reco rdi ng. Across the top of the chart you will see th e includes stamps plus descriptions .
numbers from 1 throug h 35. This all ows for 35 days to
be charted horizontally across the chart (point to the
numbers along the top of the chart). Under each day,
there are two compartme nts (point to the two compart-
me nts). The first compartment g ives yo u room to place
the ap propriate ly colored stamp for the day and the sec-
ond compartment, directl y underneath it, provides room
for yo u to write a descripti on ofwhat yo u have observed
fo r that day. You should c hart a stamp and descripti o n
every day and the best time to c hart is at the end ofyou r
day. You need on ly to c hart the most fertile sign ofthe
day and re membe r to always chart a stamp plus descrip-
tion of that s ign.
98 The Medical and Surg ical Pract ice of NaProTECH NOLOGY
liiiifi ti_: ¡ f f i " ~ ~ n " " » H U D .. U > " > • » H n D M D
BLEEDING
rrrnrr ~ -
BLEEDING
-~
DRYNESS
~ 'Muciis
~ PEAK
111
1-l-"l
1N H
' ¡c.:_
• '-'
o:l>f: NP ICJ • sljl.""''
"¡:::'":¡c".¡:1<:.i-"c+'---l":.="'
' ¡::c.¡..:.
N
'"-+-+~ NAPRolRACKlNG THE PROCREAlTV'E OCLE t
S lide 45: We would now like to explain to you a sample Slid e 47: Following the pre-Peak dry days in this ex-
chart indicating the use of the stamps and the descrip- amp le, there is the beginn ing of the mucus discharge
tions . In this chart, the cycle begins with five days of and the buildup ofthat disc harge to the Peak Day. T he
menstrual flow and these are charted with five plain red discharge in this example begins as a sticky, cloudy d is-
stamps to indicate bleeding (menstrual bleeding). U n- charge and progresses to become tacky, cloudy and then
der the red stamps, there is a description which has a clear, stretchy and lubricative. Remember that the last
H,H,M,M and L. These letters indicate whether or not day of any mucus which is clear, stretchy or lubricative
the menstrual flow was heavy (H), moderate (M) or light is called the Peak Day. In this chart this is the day ofthe
(L) in intensity. Peak (point to the Peak Day). The day of Peak is usu-
ally not determined until one or two days after the last
day ofthe Peak-type mucus. T here is a dramatic change
in the qual ities or characteristics of the discharge fol -
lowing the Peak Day. So, when the woma n determines
that she has observed her Peak, she then marks a " P" on
the white, baby stamp for that day. You wi ll notice that
BLEEDING
these days have been charted with wh ite, baby stamps
and the description ofthe mucus is written in daily dur-
1 DRYNESS
ing the cou rse ofthe mucus cyc le.
•l •.i t•
1-+•:.¡_:¡l-
O O!
::¡::::
"'W O< • '1
'"¡..::":¡::"'-t-.:".:¡:'c:¡:
M)
'":::¡
"~
NI
::.:¡.::
"'+-+-H NAPRolRACKING ll'iE PRCX:REATTVE CYCLE ~
,,,, J l,l s • l .. .. 11 rl 1Jj1' IS
. .
" u 1•
" """ " . .. . " " " .
" "
H~ f H
H H MM L
~
~ ~~ ,... -
BLEEDING
Slide 46: Following the five days ofmenstruation , there
are four dry days that are charted with plain green stamps
DRYNESS
and the description of dry under each day.
f HUCUS
PEAK
"" ...' ... .."' "' "'

.. o o • ~ 1 <>
· 1"
.... "f f 11COUNT THREE
NAPRolRACKING THE PRCX:REATIVE ClCLE r
'
Slide 48: In this example, we now have charted the three

days following the Peak. On the first day after the Peak,
there was a disc harge wh ich had sticky, cloudy charac-
teristics to it and the next two days were dry. The change
from the day ofthe Peak unti l the day after the Peak is a
dramatic change, which a woman will easi ly learn to
Chapter 6: lntrod ucto ry Presentati on of t he CrMS 99
identify. lt is this dramatic change following the Peak

Day that w ill identify for the woman her Peak Day and
the time to begin her count ofthree.
STAMPS
/ +
. . . ". DESCRI moN 1+-+-+-l-+-!-+-+-+-+4--1-+--l
l l lf
11 BLEEDING
m
' ~
11
H
1: u ..
u
~~ ·
"
~f~
11 .. 1•• Jll
il""
~ J!
-·
• In
'
" "" "
/ 1
/ Ll.l.il..UJ..l.LL.ll.l.l.::DII:D::O:I:D::IJ:ID::IJ:r:I...J
1 DRYNESS Slide 50: In this sl ide, we see the examples of three

menstrual cycles charted. These could be three consecu-
f MUCUS
tive cycles from the same woman. The first cycle is iden-
tical to the one that we ha ve just shown you . The sec-
f pfü ond cycle, however, is a short cycle. Jt is only 24 days
H f COUNT THREE
11
.
IN
~·.:
M
•N M
N
. ...
.,.. ~ ·~.
~· "'
• • DRYNESS 1
in length. As you can see, there are no pre-Peak dry
day and there is an overlap of the mucus present dur-
ing the menstrual tlow. The time of fertility in a short
Slide 49: Finally, the remainder of the cycle is com- cycle like this is from the beginning of menstruation
pleted with plain green stamps indicating dryness. Again, until three ful! days past the Peak and the time ofinfer-
you wi ll notice that a stamp and description has been tility is from the fourth day past the Peak until the be-
placed daily thro ughout the cycle. In essence, we have ginn ing ofthe next menstrual period . In the third cycle,
just taken you through one men trua] cyc le in the way a the cycle length is longer at 33 days. In cyc les such as
woman could chart the CREIGHTON MODEL. In th is this, there may be " patches" of mucus which occur on
cyc le, the menstrual period and from the beginning of occasion befare the beginning ofthe mucus buildup to
the mucus discharge until three ful! days past the Peak the Peak Day (point to the mucus patches). These two
Day is considered fertile (point to these areas on the patches ofmucus would be considered individual days
chart). As the beginner becomes more experienced in offertility but, since the quality ofthe discharge on these
her observations, usually after three month s of use, the days does not have Peak-type characteristics to it (they
li ght days at the end ofmenstruation wi ll be identified are not clear, stretchy or lubri cative), there is no need
as either fert il e or infertile based u pon the presence or to count three followi ng them . lfwe were to look ata
abse nce of the mucus discharge (po int to the light day cyc le like this third cycle in retrospect, the e days (days
ofthe menstrual tlow in this cyc le) . This instruction is 8 and 9 and day 13) would probably not be fertile. How-
not for beginners, however. They shou ld consider the ever, you must remember that the CREIGHTON MODEL
menstrual period as ferti le. is a prospective method identifying days offerti li ty and
infertility as they occur. So on any day like this (point
to day 9 and to day 13), we wi ll not know really ifwe
are at the beginning ofthe mucus buildup (point to day
15). The quality and characteristics are the same. How-
ever, the instructions ofthe CREIGHTON MODEL take
these variations into account and the existence of such
" patches" ofmucus do not usually pose a problem.
You will also notice on this chart that a long
the ri ght hand side there are the numbers 14, 15 and 13.
These numbers refer to the relatively stable length of
the post-Peak phase ofthe cycle (point to the post-Peak
phase of the cycle). The numbers a long the left hand
side ( 14, 9 and 20) are the relatively variable lengths of
the pre-Peak phase of these cycles (point to the pre-
Peak days ofthe cycle). Remember, it is the preovula-
tory phase ofthe menstrual cyc le which is the most vari-
able, whereas, the postovulatory phase of the cycle is
rather stab le in length.
l JUTlA.O IOl -17& • ,.OGUTUONl l
~ . ¡..·+--.+--+-~~~......++-1~-R-+-i
. -+-+-H-t..1...,. ~
~ "h ·'+-+-+-+-i-tl-tl-tl:-tli........91 . 1-1-1-t •.•• ;..
W-++-Wl ~
1 111111 1
Slide 51: In thi s slide the dail y estrogen and progester- Slide 53: In thi s slide, we show yo u an examp le of a
one leve ls have been moni to red . As ov ul ati on ap- chart fro m a woman who is breastfeeding. Breastfeeding
proac hes, the estroge n rises and muc us is observed (the serves to suppress ovulati on and a woman may go on
bi o logic va lve is open). When the estrogen leve ls are fo r a pro longed peri od of time w ithout ovulati on and
low or the proges terone levels are increasi ng, there is without menstruati on occurring. In thi s example, th e
no mucus fl ow and dry days are observed. These hor- green stamps ali indicate times of infe rti lity. The occa-
mone changes - ofwhich now thousa nds of cycles ha ve sional occurrence of the " patches" of mucus are rather
been eva lu ated - show the correlati ons in the monitor- comm on in th e breastfeeding situati on. In thi s exampl e
in g of the CREIGHTON MODEL System 's bi o log ic ( days 18, 19 and 20 of the second lin e of the chart) yo u
marke rs and their corre lation wi th the hormona l events will see three days of non-Peak-type mucus in a row.
ofthe fert ili ty cycle. T he in structions of the CREIGHTON MODEL indi cate
that when yo u see three days or more of this type of
di scharge yo u are advised to count three days of co n-
tinued fertility fo ll ow ing the cessati on of that type of
mucus. In thi s exampl e, yo u w ill noti ce that the woman
has marked two Peak days (po int to the " two" Peaks).
Thi s va ri abl e return ofthe Peak-type mucus pri or to the
onset of th e first menstruati on is not unu sual in the
breastfeeding wo man. However, the in structions fo r the
breastfeedi ng wo man take th ese occurrences into ac-
count, and these couples find very little difficulty in navi-
gating the return of th eir fertili ty.
Slide 52: In this exampl e, we show a wo man who has

long cyc les. The first is 40 days in du rati on and the
second is 42 days . The onl y majo r di ffe rences between
these cyc les and the other cycles that we have shown
yo u are in the num bers of pre- Peak dry days. As yo u
can see, wi th longer menstrual cycles, th e num ber of
the pre-Peak dry days increase rather rema rkably. A lso,
in the second cyc le, the descripti ons are shown in the
Vaginal Di scharge Recording System. Thi s system will
be explained to yo u at fo ll ow-up. It make charting
easier and more accurate.
' >I•
' •I· .. U I! 111• "1• n 11 lt • 11 :l JI
"" • :1 » .. JljJJ
~
" ."
1 H H H H H f
H H M M L L
. .., •1 -
CONTINUOUS DISCHARGE • YELLOW STAHPS
•I
. ;: .. . .
IN
; ~ ~~ ~· 'b• '
V
: i'W'RolRACKJNG lHE PROCREAllVE CtClE
HORHONE STUDY • CONSECUTIVE OVULATORY CYCLES
Slide 54 : Some wo men have a conti nuo us di scharge. Slide 56: In thi s s lide, we present th ree consecuti ve
The method can be effecti ve ly used in th ese s ituatio ns. me nstrual cycles in w hich the ide ntifi cati on of the tim e
Thi s s li de shows how, w ith the use of ye ll ow sta rnps, of ovul ati o n was dete rm in ed by do ing ho rmone stud-
your instructor can help yo u ide ntify th e days offertil- ies . In the first cycle, we sho uld po int o ut the act of
ity and infe rtili ty. T he rnu cus assoc iated w ith ovul ati o n interco urse that occurred o n the l 2th day of the cyc le at
is very characteristic and di ffe rent fro m other discharges. the end of the day. Thi s act of in tercourse occurred ap-
lncidentally, wo me n using the CREIGHTON MODEL proximate ly 36 ho urs pri o r to the tim e of ovulation and
te nd to identify ab no rmal di sc ha rges earl ier and have th ere was no e vidence that pregnancy occurred . Yo u
the m treated. wi ll notice that on day l 3 ofthe cyc le Peak-type muc us
was present. Man y people as k w hat ha ppens if a coup le
has inte rcourse on a dry day w hich is then fo ll owed the
next day by the appearance of the Peak-type mucus. lt
has been o ur ex perience that these days are hi ghl y re li-
able ind icators ofi nfe rtili ty.
T he next cycle is a relative ly normal cycle w ith
th e normal type of muc us di scha rge present.
T he third cyc le, the wo man observed dry ness
1 1 1
th ro ughout the entire cyc le as indi cated by the presence
ACHIEVlNG PREGNANCY of the plain g reen stamps a nd the descripti o ns of dry
th ro ug ho ut the cycle. Thi s coupl e had inte rcourse on
th e l 4th and the l 6th day of the cyc le a nd , by hormonal
eva luati on, ovulation was estimated to ha ve occurred
o n day 15 of the cycle. In spi te of inte rcourse occurri ng
very c losely to the time of ov ulatio n, pregnancy d id not
occ ur. Thi s type of dry cycle is very unu sual in the nor-
ma lly fe rtil e wo man. However, it is a quite commo n
Slid e 55 : We mu st a lways kee p in mi nd th at th e occurrence in couples w ho have had di ffi c ul ty achiev-
CREIGHTON MOD EL is a method of both ac hi ev ing as in g preg nancy. The absence of th e mu cus discharge in
we ll as a vo idin g p reg na ncy. In thi s exa mpl e , th e these cases is re lated to the cause of the infe rtili ty prob-
CREIG HTON MOD EL has been used successfull y by a lem. T hi s cycle is an examp le ofw hat we wo uld ca ll an
coup le of no nnal fe rti lity to ac hieve a pregnancy. Thi s infe rtile ovulatio n. Ovu latio n occurred during thi s cycle,
has been accompli shed by hav ing intercourse on the days but the cyc le was still an inferti le o ne. Asa n adde ndum,
offertili ty as defin ed by the method (po int to th e acts of thi s partic ular wo man di d not have an infe rti li ty prob-
interco urse on days 16 a nd 18). lt has been o ur ex peri - lem. T hree cyc les afte r completing he r invo lve ment in
ence that w hen the time o f ferti li ty is used, the likeli - thi s stud y, she had a cyc le that loo ked like her second
hood of pregnancy occ urring is extre mely high. cyc le in thi s s lide, and they used th e meth od success-
full y to ac hi eve pregnancy.
NaProTRACKING For Monitoring A REVIEW

Maintaining and Evaluating
Procreative Health THE CERVICAL FLUID:
Begins as a sticky or tacky, cloudy mucus

Limited Mucus Cydes • Tail-end Brown Bleeding Progresses to clear, stretchy OR Lubricative
DryCydes ·• Length of the Cyde THE PEAK DAY:
Premenstrual Spotting • Length of the The LAST DAY of Clear, Stretchy OR Lubricative Mucus
Post-Peak Phase
AFTER THE PEAK:
+ And Many Others
A DRAMATIC CHANGE
+ For a Lifetime of Procreative and Gynecologic Health
Sticky or Tacky, Cloudy Again, or Dry
Slide 57: NaProTRACKING the menstrual cycle is Slide 59: And now for a short review. The cervical fluid
something that shou ld be done over the life time of your genera lly begins as a sticky or tacky, cloudy mucus and
procreative and gynecologic health. While we cannot progresses to become clear, stretchy or lubricative. The
go into ali ofthe details that the system can do to help Peak Day is the last day of clear, stretchy or lubricative
you understand various health problems, we can say mucus. After the Peak Day, there is a dramatic change.
that such observations as limited mucus cycles, dry The mucus reverts back to a sticky or tacky, cloudy
cycles , premenstrual spotting, tail-end brown bleeding, mucus again or the woman wi ll experience dryness.
the length of the cycle, the length ofthe post-Peak phase
and many, many others are ali cl inically very relevant.
DA YS OF FERTILITY AND INFERTILITY
FERTILE
Days of the Menstrual Flow
The Mucus Days through 3 Full Days Past Peak
INFERTILE
The Dry Days Following the Menstrual Flow
From the 4th Oay Post-Peak until the Next Menses

-------------·-··-···· ·---
Slide 60: T he days of fertility inc lude the days of the

Slide 58: This slide demonstrates how va luable this menstrual flow and the mucus days until three full days
system is in reproductive and gynecologic hea lth main- past the Peak . The days of infertility are the dry days
tenance showing severa! different examples. In the first fol low ing the menstrual flow and from the fourth day
cycle, the very limited mucus cyc le is often seen in in- past Peak until the beginning ofthe next mensn-ua l pe-
fertility. The second cycle shows a short post-Peak phase riod.
(5 days) and is associated with a very high risk ofmis-
carriage. ln the third cycle, the premenstrual spotting is
associated with very low progesterone levels. And in
the fourth cycle, abnorma l bleeding is observed. This
can be associated with hormone problems or even can-
cer. This information , w hich is easy to collect and moni-
tor, can only be obtained through using the CREIGHTON
MODEL System. lt is an incredible system for self-moni-
toring a woman 's reproductive and gyneco logic health.
Slide 61: A lways keep in mind that the CREIGHTON Slide 63: Since the system is nota contraceptive, it is
MODEL can be used in two ways. lt can be used to also used by coup les of normal fertility to ach ieve a
ac hi eve pregnancy as well as to avo id pregnancy. ln- pregnancy. This sli de shows that, on an individual cyc le-
deed, it is a true method offami ly planning, nota method by-cycle basis, w hen the days of ferti li ty are se lected
of contraception . for use, the pregnancy rate is 76 percent in the first cycle,
90 percent by the third cycle and 98 percent by the sixth
cycle. lf one looks at a population of 100 users who
come into the system to avoid pregnancy, 21 users (21
percent) will se lect days offe11ility to use at sorne point
during the first year and successfu lly achieve a preg-
nancy (see page 64 for fu11her discussion).
THE EFFECTIVENESS OF THE CREIGHTON MODEL

TO ACHIEVE PREGNANCY
IN COUPLES
WITH INFERTILITY
WITH USE OF CrMS ONLY ....................... 20.0 • .-0.0% •

Slid e 62: The first effec ti ve ness study of th e
WITH CrMS ANO MEDICAL TREATMENT ... UP TO 80.0%1
CREIGHTON MODEL System was comp leted in 1980.
In 1999, the Journal of Reproductive Medicine pub-
lished the resu lts of five different studies. This study
involved 1,876 coup les over 17, 130 couple months of
use. The method effectiveness to avoid pregnancy was
99.5 percent and the use-effectiveness to avoid preg- Slid e 64: The system adds a completely new dimen-
nancy was 96.8 percent. These effectiveness measures sion to the successful ach ievement of pregnancy in
are as good as ora l contraceptives and better than any couples with infertility and other reproductive problems.
other drug or device on the market. With the use ofthe CrMS on ly, success rates between
20 and 40 percent can be expected. With a cooperat ive
med ica! approach to treatment, success rates of up to
80 percent ha ve been observed (the actua l success rate
will vary, ofcourse, w ith different medica! conditions).
104 The Med ical and Surgica l Practice of NaProTECHNOLOGY
WHEN USING THE METHOD TO

A VOID PREGNANCY
Using Days of Fertility ABANDONS

the Method as a Means of AVOIDING Pregnancy
and
ADOPTS the Method as a Means
of ACHIEVING Pregnancy
Slide 65 : lt is important to point out to those of yo u Slide 67: This brings thi s (evening's, afternoon 's or
who wish to use the system to avoid pregnancy that us- morning's) presentation nearly to a c lose. You will find
ing days offertility aba ndons the system as a means of that it will req uire sorne time, energy and pati ence to
avo iding pregnancy and ado pts it as a mea ns of ac hi ev- lea rn the CREIGHTON MODEL. However, we must
mg pregnancy. point out that thi s will be an in vestm ent in yo ur fu ture.
FOLLOW UP SESSIONS
ARE VERY IMPORT ANT TO YOU
• So that the System can be "Tailor Made•

to You and Your Situation
and
• So that You may Qulckly Gain Confidenoe
in the System
Slid e 66: That is to say: there are no "taking chances"

with the CREIGHTON MODEL. You wi ll know when Slide 68: And the fo llow-up sessions are very impor-
yo u are ferti le and when yo u are not fertile on any g iven tant to yo u so the system ca n be "ta ilor made" to yo u
day. The CREIGHTON MODEL has made the concept and yo ur situati on and so that yo u ma y quickl y ga in
of " taking a chance" o ld and archaic. confidence in the system . There are five fo ll ow-up ses-
sions in the first three months and three more over the
next nine months.
Slide 69: lfyou wish to be successful in the use ofthe Slide 71: The CREIGHTON MODEL System wi ll teach
system, you must make accurate observations, accurately yo u to appreciate your ferti 1ity and the chi ldren that may
chart those observations and follow the instructions of result from its use. lt is a system that challenges that
the system depending upon your intentions to either every child is not just wanted , but loved.
achieve or avoid pregnancy. In addition , your mutual Jt is also a system which asks women to be
motivation and loving cooperation are al so essential in active participants in the monitoring and maintaining
its successful use. oftheir procreative and gynecologic health.
Slide 70: In the CREIGHTON MODEL System, the Slide 72: Thank you very much for your attention.
woman makes the observations, the man supports her,
but the couple uses it.
Discussion on Slide 63:

The statistic of 2 1.O percen t is often diffi cul t fo r new users tic. In the use-effectiveness study ofthe CrMS which in volved
and new teachers to understand. Technically, it represents the 17, 130 coupl e months o fu se with 1876 coupl es, 2 1.0 of 100.0
" use effectiveness to achieve pregnancy" or the achi eving- couples w ho joined the progra m with the intenti on to avoid
related pregnancy rate. 1 Thi s stati stic applies only to a popu- pregnancy became achievers within the first year of use ami
lat ion of users and not specifi ca ll y to the indi vidu al user. were successful at achi eving pregnancy (see Chapter 27, use-
Therefore, it is a demographic statistic. lt is also a stati stic effectiveness) .
that applies on ly to coupl es of nom1al fe rtili ty an d not coupl es
with infertility. Boiled down toan everyday statistic, this ca n be stated (a p-
proximately) that " one o ut of every five cou ples w ho enter
The statisti c applies to a group of 100 users of norma l fert il- the program to avoid pregnancy will become ac hievers an d
ity who come into the CrMS with the intenti on to avo id preg- wi ll be successful at achi evin g pregnancy within the firs t year
nancy. Whil e most will co ntinue to avoid pregnancy during of use." Of course, because ali of the decis ion making is in
the first year ofuse, a small percentage of th em w ill begin to the hands of the cou ples who use the systern , the system can
select days of ferti lity (know ing ly and consciously) and will be used to both avo id as well as to ach ieve pregna ncy. lt is
subsequentl y be successfu l at achieving pregnanc y. T hese not possib le to predict whi ch coupl es w ill be represented in
couples are successful users of the system as a system to th e " one-in-fi ve" when they begin usi ng the system.
achieve pregnancy and are measured as suc h w ith this statis-
References
I. Hil gers TW: The Statistical Eva luat ion ofNatura l Methods of
Family Planning. lnt Rev at Fam Pl an. 9: 168, 1985.
Basic Charting and Chart Reading
3. The Peak Day = The last day of any mucus di s-

C harting con-ectly the sig ns of fe rtili ty is very im-
po rtant to the successfu l use of th e CrMS . In addi-
tio n, it is of great assistance to the user in developing
charge that is clear, stretchy , o r lubricative.
confidence. The chart is also the outstanding health

record which documents in a pro pective fas hio n the
important biomarkers that a re the foundat ion of
NaProTECHNOLOGY . This c hapter outlin es the basic
princ ipies of good charting and chart reading. CREIGHTON MODEL
FertilityCare"' System
Definitions
AN AVTHENTIC LANGUAGE OF A WOMAN 'S
HEALTH ANO FERTIUTY •
The fo ll ow ing definitions are important during this dis-

cuss ion.
1. Peak-type M ucus = Any mucus discharge that is

clear, stretchy, or lubricative. A ny one of these
Creighton Modal
three characteristics, alone or in any combination
~-
res ults in the muc us di scharge bein g defined as
Peak-type mucus. FertilltyCare"' and NaProTECHNOLOGY"'
A Contemporary Approach to Women 's Health Care
2. Non-Peak-type M ucus = Any mucus di scharge that
Use lh•chllrt to record \Nl.l"JoTAACK ¡ lh8blolnar1<..noltho Nllurtllyoccumng pta.sesol your lerti11ty
is no/ clear, stretc hy, ar lubri cative. Ali three of •nd inletllltty Thue urne bton\arbrs wil •leo alow you to mootlOr and mu\laln 'fOIN r.productiw and
gynecologic heallh The Cr1ighton Modsl Syuem c 110en11hcally aound acc:urale and precise and ettoc-
these c haracte ri sti cs mus/ be absent in order to es- twe lt can be uud to actueve or aYOid pt9grl.locy or m the lurui.t 9VahAtlOn of mlerbhly rep9bbve mis·
caJMge abnotm.llbl9.cil'IQ.rKU1TentOYanancysts, polvlepain ~lruatayndrome etc ltdoet;al
ol In 1n a way wtuc:h cooperale:s wrth your fertiltly respoct& !he dignlty ol women and the inte;n¡y of
tabli sh the ide nti ty of non- Peak-type mucus . m111m1109 ~ a bonua 11 helps m.1med c.ooples dilCO\ler ltta "inner IOUI" o! tho1r human sexuahty Fot
mora lnlormation log:onto - c~htonmodel com 0t www galu:ymalLcomlhuttMcca
Figure 7-1 : Front of chart
107
108 The Med ical and Surg ic al Practice of NaProTECHNOLOGY
Front of the Chart the Peak Day . Secondly, the vaginal discharge record-
ing system is also on the back of the chart. Th is is for
The front of the CrMS chart identifies the name of ready reference to assist the user in charting. Finally, an
the system being taught and contains the important instructions list is provided . Here the teacher documents
words f ertility apprec iation , FertilityCare™, and the reproductive category specific instructions that have
NaProTECHNOLOGY . In addition, the family logo of been given to the client couple.
the CrMS is present. (F igu re 7-1)
lnside of the Chart

Back of the Chart
On the inside ofthe chart (Figure 7-3), there are num-
The back ofthe chart is shown in Figure 7-2. There is bers across the top from 1 through 35. This tells the day
room for the name of the client couple (and it is sug- ofthe menstrual cycle. For each day, there is a box pro-
gested that both the man and woman 's na me appear sin ce vided for the placement of the proper stamp and an-
it is their chart). In addition , there is a place fo r the other box prov ided for writing the proper description.
client's identification number, the number of the chart In addition , there is a place provi ded to write in the
(first, second , etc.), the teacher code (TC), and the cen- date. The user should chart each new menstrua l cycle
ter code (CC) . The name ofthe instructor is put into the beginning at the left marg in ofthe chart and continuing
appropriate place and, ifnecessary, the telephone num- it horizontally. There is room for six months of chart-
ber of the instructor (this is optional depending u pon ing. The following are considered the basic principies
the needs ofthe client). The back ofthe chart also con- of good chartin g:
tains a place for writing dates and times for each ofthe
follow-up appointments. l. The client begins charting immediately after re-
ceiving the initial instruction.
In addition to the above items, a number of vety impor-
tant bookkeeping items are placed on the back of the 2. During the first month of charting or during the
chart. First of ali , there is a section entitled Definitions. first complete cycle (which ever is shorther), the
This section makes readily accessible the definition s of client shou ld avoid genital contact so that the
the terms Peak-type mucus, non-Peak-type mucus, and mucus can be seen in its natural state without
being intluenced by the presence of seminal fluid.
'- - - - """"' , _ _ >e_ cc_
NAME Of tN8TAUCTOAo_ _ _ _ _ _ _ _ _ _ __
3. The client should chart the proper stamp and de-
TIIOl~MOCMllHOULOHOT8El.EARNEOWll\Olll.,..,..nlr\ICtlOfl-~lromnr.o~
..
W..-IO
scription at the end of each day during the cycle
¡;.;:,~Tl~T i'-¡~·rrn AL... ':a~~C*RT including the days ofmenstruation.
"''"""°"'
l"Ul(..TYP'l MUCU1 •N('(MIJCUI01!CHAAGE TMAT 18 Q..IAft, IT'MT'CHY, OR LUeAICAT'IVL
HOH-PU.IC TYl>I MUCU8 • AHY MUCUI ~ TiiATIS NOT CUAI\ STAETCHY OR WBAICATIVE
Tllf. P"-K OA'I' • TtfE L.AIT DAY Of' AHY MUCUI DllCHAROE lliAT IS CUAl'l, STllln'CHY, Ofll LU8RiCATIVL
4. The client should chart the most fertile sign of
__
· ·~(Ollllllc:k)BIMdillg
C•~(-.)
"", ""'°""""'"'
O •~(~
the day.
..
IC •C....
,. • JIMty(clffl'llt)
101$L a8"irly WrTM ~

Y.Y..,,.(-plll9yellooi(J 5. The cli ent should chait the 3 C'S of the mucus
x1 ..... ~--119y
10WL a
lnldcllon.1-.t,_ol'l*l~NdlfyllWIJOU_h...,.
Wel wtTH ~
112 .. ._.....,..,,...,
tilQnOll_..,..,.._ •AO •a...MO..
.....
u .. a- ...... _ _ ..,
.,_loloiollng!MlliDn:
dail y.
~-------- INSTAUCTIONS _ _ _ _ _ _ _ __ ,
YOUR INSTRUCTIONS FOR USlNO THE SYSTEM Wlll BE OIVEN TO YOU BY YOVR TEACHER, FFIOM THE LIST OF
INSTRUCTIONS BELOW. 3 C 'S
A. ~llMCllOIM-.oon.I'°"""
• . Clwlllh-Oll)'(M"!My, ....,.,., _ _ I A"'llidg9f!UICllll'Udlll'llilpdll>UO&Mil~
C = Consistency
. . . . . . . . . . . ol . . dsy
... _.,..n..-.d
i.~~no.-,n
C.
a.
••
__
A-~canlael
D. ~~~199.:.,,_PI~
,
:l.From~olrnuc:ut~3Ud9Y1'pt1911M Pt.lll
11112.-or -..- ...- pr~
3!1'"'°'9_,.ol -..... - ~
a. Ñ"Vlifigledlyol PMll: mucw - p1u. eo.on13

J . ~hlmOllrllol...edtolN....._
.. \~l~~::i?.,.....~ ¡~
mldi.fl~-(LAl'),(...--,.Pll*Uar'lfl
" · =~ ;;,,,~...,.........., IN
C = Color
C = Change*
1. Mf~~ - pl.- eo.onll 11 . Ylllow ~ lnllnnoN
t:. ~ ol..,..,. IO-*!¡. - PN9WtCYI ~ =::;:.¡;::.,';y,~=---~ ....... .,. S = S ensation
--
l . Oiym,. pr~ - erlllol ... lilf. ....... ,_,..
:t. o.ym.,. pr.....- - endotlledly, ~de!y
3, "4Jldly po.l-pNll - 8twr(9 -ofhdly t ~i~:=..~~;"mv
---
L'=-'""*'f*IOCl._iV>
•. Oiym.,. po."11Nk (.,.., 40l~ - -olhMJ,
* The change is the day-by-day change in the consis-

--
L ~~ 1..,...ii ¡.n.1tt11dlly) - -oth . . l . •IOl!lly~h5em.,.lltllfr.thol
t. Dlym.,. ~ t1111ertu1~-~olNdly
r. ~~:Jm~"'"'*"._,°' .. . E.ndoldly~lllOl'lf'll-.qi- . . l!OfftW
tency, color and sensation. Watching for obvious day-
... ,,.,...AuodlMINCllOll(--....1)
o.
H C:W- l•.f __...luld-.__.._ .... NT. •q
'ODuDl9" ......
l . OnP•3 . . 'doubWplllll~ by-day changes is important in understanding the na-
l. ·~--.--- lldly.r....aon
=.:"-.::..~':,,,,i-:~-
l. wt_. 9'111c...,.. • ....._. pMll. k9'PIO IN ture of the mucus.
Md ollhe ...... . , . . . . . . . "*'OOM!Vlillanf
1(.
_,
WhMlndola. eonlllditr)'Cll>l'MllolP9911~..0
POPE P"Ul VI IM5TTTVTEfOff TME ITUOYOFHUMAH AEPl'ICIOt.ICTIO
Fig ure 7-2: Back of chart

Chapter 7: Basic Charting and Chart Rea ding 109
1 2 3 4 5 6 7 8 9 10 u 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
STAMP
/ "'
/ "'
CHART AT THE END OF YOUR DAY

THE MOST FERTILE SIGN OF THE DAY
/ ... STAMPS + DESCRIPTION
/ "'
/ ... -
~EM NDE IR: 1DRD 'R r EW 111 RT, STA ~ P S AN[
11AK ~ A~ POI HM ~ NT f OI FO LO V·U ~ NAPRoTRACKING THE PROC REATIVE CYCLE
-
/ "'
USE THESE SIGNS : P =PEAK • 1.2.3 • FERTtLE DAYS FOLLOWING PEAK • l • INTERCOURSE BSE = BREAST SELF· EXAM
1
Figu re 7-3: lnside of chart
Stamps lsTAMPS I
Starnps have been deve loped for use with the CrMS (F ig- BLEEDING
ure 7-4) . These stamps are used throughout the world :
DRYNESS
STAMPS
[l] MUCUS
= For days of bleeding
Pla in Red Stamps
Plain Green Stamps = For infertile dry days [I] PEAK
White, Baby Stamps = For mucus days
Green, Baby Stamps = For dry days that are fer- !Il [)] [l] co~~T THREE
tile (within the count of 3)
DRYNESS
In additi on to the above stam ps, yel/ow stamps are also 1 + DESCRIPTION 1
at times used w ith th e CrMS (F igure 7-5). ln thi s teac h-
ing system, ye l low stamps are only used upon speci.flc Figure 7-4: Basic stamps used in cha rting the CREIGHTON
MODE L System . The "P" and "1,2 ,3" are written on the chart
indication and then only wi th the ad vice of the teacher. by the client co uple.
Therefore, a new client com ing into a teaching program
is not given yell ow stamps in the introductory packet of
stamps. A discuss ion of the use ofyell ow stamps is pre-
se nted l at er (C hapter 8) and is t he subject of
extensi vediscuss ion in Book Two ofthe CrMS tra in ing
YELLOW STAMPS
1
manual on Advanced Teaching Ski/Is .
USED ONLY UPON INDICATION
ANO WITH TEACHER'S ASSISTANCE
Fig ure 7-5: Ye llow stamps are used only fa r special situations,
and th en only with the assi stance of the teacher. Complete
discussion of their use is in Book 11.
Descriptions stretchy and lubri cati ve . Far each day, a written descrip-
ti on is pl aced in th e descripti on box. In additi on, each
Fa r each day of chartin g, a descri pti on is written in the of these days takes on a white stamp wi th a baby im-
descripti on box. A standardi zed means fo r recording print on it. That last day of the mucus di scharge that is
these has been deve loped and is di scussed later in thi s c lear, stretchy, or lubri cati ve is ca ll ed the Peak Day
chapter (see Vag ina l Di scharge R ecordin g System). In and a "P " is pl aced on that stamp . O f course, th is can-
addi tion, the fa ll ow ing signs are placed on the chart at not be pl aced until at least the day afte r the Peak. Wh en
a ppropriate times : the change in the mucus occurs fo llowing the Peak Day,
then a " P" can be pl aced on th e chart fo r the Peak Day.
P = Placed on a white, baby In thi s case, on the day after the Peak, the mucus has
stamp on the Peak Day changed to a sticky, cloudy type of discharge. No n-Peak-
1, 2, 3 = Place on the three stamps type mucus days that fa llow the Peak Day in the coun t
following the Peak Day of tbree take a w hite, baby stamp .
1 = An act of intercourse
In Figure 7-9, two additi onal days have been added to
the prev ious chart . These next two days are dry days
T he descripti ons are extremely importan t. The user or and ta ke on a green baby stamp . In addition, the num-
users should record the most fert il e sign of th e day in bers 1, 2 and 3 ha ve been pl aced on the stamps fa r these
th e box prov ided. The CrMS story is told in the day -by- three days indi catin g the three additi onal days offertil-
day descriptions of !he mucus palterns. ity fo ll ow ing the Peak Day.
In the fin al chart of thi s sequence, F igure 7-1 O, the 28-

A Charting Example day cyc le is compl eted. T he remainder of the cycl e is
dry, and thi s is recorded in the descripti on box. In add i-
ln Figure 7-6 through 7- 1O, one co mpl ete menstrual ti on, the wo man has pl aced a pla in green stamp in the
cycle is charted as it progresses. The first chart of thi s stamp box fa r eac h of the days.
sequence is in Fi gure 7-6 . In thi s case, five red stamps
have been pl aced fo r the des ignati on of th e fi ve days of The charting is done da ily , and it should be done at the
menstruation. The symbo l " H" means heavy menstrua l end of each day . The chart should be kepl in a conve-
fl ow, " M " means moderate menstrual fl ow, and " L" nient and readiLy accessibLe Location .
means light menstrual fl ow. On the day of li ght men-
strual fl ow, the woman has also recorded dry . With ex-
perience, most wom en, if not all , can identi fy the pres-
ence or absence of mucus on the li ght and very li ght
days at the end of the menstrua l
fl ow.
' ' 3 ' ' ' 7 8 • ro 11 12 13 14
" " 17 18 19 20 21 22 23 24 25 26 27 28 29 )() 31 32 J] 34 JS
In Figure 7-7, th e coupl e has

now reco rd ed th e nex t fo ur ~ '
days of dry ness . T he written
desc ripti o n dry is pl aced in
1 BLEEDING
each box and, far these infe r-
ti le dry da ys occ urrin g pre-
P eak, a pla in g ree n stamp is
pl aced in pos iti on. The wo man
has not recorded ali of th ese
fo ur days at one time . She has
recorded each of these days at 1
the end of the particular day. ln

F igure 7-8, the woman is now
oº' ~ N :. CH A• S t!..N 'S NI
f
Rll IN PER
recording the observation of the "
1"A1 PP )IN MC NT F( R Fflll OYI UP
: NAPRoTRACKING THE PROCREAlNE Cl'CLE
mucus di scharge . It begins as a
1 1 1 1 1 1 1 1
stick y, cloudy di scharge and
Figure 7-6 : First five days of charting showi ng th e use of red stamps for charting the
p rog resses to beco me c lea r,
menstrual flow.
Chapter 7: Basic Charting and Chart Reading 111
Figure 7-7: The next four days are

l s
' •
1.5 26 27 211 JO JI 32 33 ~ JS
2 J
' 6 7 10 11 12 IJ 14 16 17 18 19 20 21 22 2J
" " 29
-
1
charted with plain green stamps. The
L
~I days are pre-Peak dry days.
'
1 BLEEDING
1 DRYNESS 1
f(.' p u OVI ••
RE I IN •• o ROE N W CH " R Sl AM NI
~
~ Al ' pp PIN Mf N T UF
: NAPRoTRACKING THE PROCREA11VE CYCLE
1 1 1 1 1 1 1 1 1 1 1
1 2 J . s 6 1 1' • 10 11 12 13 14 IS 16 17 18 19 '" 21 22 2J
" " 26 27
" 29
JO JI 32 JJ ... JS
~~ .....~~..... .~.. f... ....f r""'l
11(BLEEDING
Figure 7-8 : With the beginning of the
mucus, white baby stamps are used.
l 1DRYNESS1
The Peak is marked with a "P." The
day following the Peak is a dramatic
change and is a day "1" in the three- ~ MUCUSI
day cou nt.
f PEAK
,. P,,••
REI IN O RDE ~ N W CH I>• s AM ?S NI
P" O VI ·UF
~
PP ) IN Mf Nl fC • f
: NAPRoTRACKING THE PROCREA11VE CYCLE
1 1 1 1 1 1 1 1 1 1
' 11 12 ll 14 15 16 17 18 19 '"21 22 23
"" 26 27 JO JI 32 )) " 3S
•
' 10
" 29
y
~ ~ ~ ~ ~ ~ f f f f.,
"" .., ..,=: :::~ :i, "'
~ ::r "4l utt
.
l 1BLEEDING1
i 1DRYNESS1
f IMUCUSI
f PEAK
f f Jf COUNT THREE Figure 7-9: Da y 2 and 3 after th e
Peak are dry days. They are charted
~ IN ,. o 1 1 1 1 1
"" ~· !DE NW C H ~R
"""'•· S NI
El pp P IN Ml ~•H F( R F OLI p UP
: NAPRoTRACKJNG THE PROCREA11VE CYCLE
1 1 1 1 1 1
f with green baby stamps and "2" and
"3" are written on them to complete
the three-day count.
112 The Medica l and Surgical Pra ctice of NaProTECHNOLOGY
Figure 7-10: The cycle is now 1 6 11 12 13 14 15 16 17 18 19 20 21 l2 2J 24 25 26 27 28 29 JO JI J2 JJ J4 JS

J ' ' 10
•
complete. The remaining days
of this cycle are dry and
charted with plain green
1 .i., ..::.
r
,,.
Df:I OlT DOY
l f ~ ~ f f f f fll ll O~Y
I•
!y !ll~
r
stamps. In this example , the
H L
y -~ :o .::,,~ = ...... Z2 D•Y DlT DRY UI l""Y DlY u.Y u•T
length of the cycle is 28 days

in duration . The length of the 1 BLEEDING 1
menstrual flow is five days and

the mucus cycle is five days
as well.The length of the pre-
Peak pase of the cycle is 14
11 DRYNESS 1
days and the post-Peak phase
14 days . Each of these
documents certain of the ~ IMUCUSI
biomarkers that are present.
f 1 PEAK I
fff COUNT THREE
RfJ IN ER
•A
O DE N W CH !<IR ·l•M ~ s NI
f J PP >IN MCNT F( R Fpu -UP
º"' 1 1DRYNESS1
Vaginal Discharge Recording System 5 M (VDRS) B = brown (or black) are used. During the light and
very light days ofthe menstrual flow, an observation of
The descriptions are the most importan/ par! of charl- the mucus should always be recorded.
ing. They must accurate ly reflect the observations that
the woman makes so that a true picture of the mucus The numbers O, 2, 2W, and 4 ali re late to observations
patterns can evolve. The vaginal discharge recording that have the same sign ificance as dry observations. In
system (VDRS) has been developed o that charting can these cases, when the client wonders which would be
be done more easily and its accuracy improved. Every the "most ferti le sign ofthe day," she records the higher
client is encouraged to use the vaginal discharge record- number. This is merely a convention for recording pur-
ing system from the very first follow-up. The language poses and for accuracy of recordi ng. Ali four of these
of the body that is incorporated in the VDRS is based recordings are thought of as dry observations re lative
upon the research that was conducted on the vulvar to stamp placement and the use of the instructions for
mucus observations and is incorporated in the Picture the system.
Dictionary which was previously presented in Chapter
5. Experience has shown that it is veryemyto learn and When the numbers 6, 8, and 1O are used , a letter from
use and, with its ready accessibility on the back ofthe the right hand column must always be used. Either a
chart, the client always has it for quick reference. color ora consistency or both must be present when the
mucus is stretchable.
The recording system is outlined in Figure 7-11. While
this recording system uses numbers, it should not be The special categories of Peak-type mucus are recorded
called a scoring system. 1n effect, any form of symbol- as 1ODL (damp with lubrication), 1OSL (shiny with lu-
ism could be u ed in the same fashion , but a sy tem of brication), and 1OWL (wet with lubrication). Since lu-
numbers and letters was chosen for this particular sys- brication is present in ali of these observations, the
tem. While there is a general tendency for the higher mucus is therefore of the Peak-type and would be of a
numbers to be a sociated with higher fertility, this shou/d hi gh degree offerti lity, the number 1Ohas been used in
no/ be used in that way. The series of numbers and let- combination with the letters. The number 10 in this case
ters are simply a mea ns of recording accurately the ob- does no! mean slretchy. lt is simply a means of record-
servation that the woman is making. When one becomes ing these specia l categories of Peak-type mucus.
fam iliar with the recording system, it also makes chart
reading much easier. In add ition to the above record ings, it is also important
to record how often the most fertile sign of the doy is
During the menstrual flow, the symbo ls H = heavy, M = observed. This is done by using X 1 = seen only once
moderate, L = light, VL = very light (or spotting), and that day, X2 = seen twice that day, X3 = seen three times
Chapte r 7: Basic Charting and Chart Reading 113
Vaginal Discharge Recording SystemsM

(VDRS)
H = Heavy Flow O= Dry

M = Moderate Flow 2 = Damp witho ut Lubrication B = Brown (or Black) Bleed ing
L = Light Flow 2W = Wet without Lubrication C = C loudy (Whi te)
VL = Very Light Flow (s potting) 4 = Shiny without Lubrication C/K = C loudy/C lear
B = Brown (or black) Bl eeding 6 = Sticky CI. inch) G = Gummy (G luey)
8 = Tacky ( Yi - % inch) K = C lear
Always record the presence or ab- 10 = Stretchy ( 1 inch or more) L = Lubricative
sence of mucus during the light and
lODL = Damp with Lubrication P = Pasty (Creamy)
very light days of th e menstrual
flo w. lOSL = Shiny with Lubrication Y = Yel low (even pale ye ll ow)
JOWL = Wet with Lubrication
In addition, record how often during the day that yo u see the most ferti le sign ofthe day in the following fashion:
XI = Seen onl y once that day

X2 = Seen twice that day
X3 = Seen three times that day
AD = Seen A li Day
Figure 7-1 1: The vaginal discharge record ing system (VDRS)
that day, and A D = seen a li day. The latter des ignation Examples of the Recording System in Use
means that the mucus has been observedfour or more
times du rin g the day. Once it has been observed fo ur 1. Dry- observed al i day = O AD
times, th e wo man no longer needs to keep a count of 2. Damp witho ut lubri cat io n- o bserved a ll d ay
the number oftimes she has observed that most fe 11ile = 2AD
sign . lt automatically becomes an all-day (A D) obser- 3. Stretchy, c lea r, lubri ca ti ve- o bse rve d a li day
vation . = JOKLAD
4. Sticky, clo ud y- observed once = 6C X l
10 11 l2 13 14 15 16 29 30 31 32 33 34 35
B
L VL. OltO
a a
AO AO
Figure 7-12: In cycle A, the descriptions are written out. In cycle B, th e same descriptions are recorded using the vag inal discharge
recording system .
5. Tacky, gummy, yellow - observed twice B. Large amounts of writing squeezed into the
= 8GYX2 small description box may indicate user 's anxi-
6. Sticky, pasty, white-observed twice = 6PC X2 ety.
C. Extraneous notes written on the chart may give

In Figure 7-12, the use of the vaginal discharge re-
the teacher insights into various aspects ofthe
cording system is shown. In cycle A, a 27-day cycle is
user's behavior. For examp le, we observed a
presented with the mucus discharge beginning as sticky,
chart obtained from a yo ung woman that had
pasty and cloudy. It then progresses to tacky and cloudy;
the words "who cares" written undemeath a
stretchy, cloudy and lubricative; and then stretchy, clear
series of post-Peak green stamps. Th is gave
and lubricative. The abrupt change after the Peak Day
an insight into the couple 's attitude toward the
is to tacky, cloudy and then shiny without lubrication.
use ofthe system.
CycleA contains the written descriptions while cycle B
contains the conversion of the same cycle to the vagi-
nal discharge recording system (VDRS). 2. Read each description day by day.
lt is very importan! that the chart be read on a
day-by-day basis. lt is very easy to miss the chart-
ing errors if a casual or disorganized approach to
Basic Chart Reading -------~ the chart is taken. A teacher cannot short-circuit
this process. There are no short cuts. In order to
In teaching the CrMS, the chart becomes the hub ofthe know what the chart says, each descriptioo needs
system-related communication between the teacher, the to be read , usually silently, so an understanding of
user and the health care provider. It is through careful the chart and its pattems can be obtaioed .
eva luation of the chart that errors related to charting,
knowledge, and application ofthe instructions, and even 3. Read the properplacement ofstamps day by day.
observations will often come to light. Reading a When reading each description day by day, it is
CREIGHTON MODEL chart is one of the most impor- equa lly important to note the placement of the
tan/ basic teaching skills that teachers develop and in- stamps at that time, checking that they have been
ternalize. Such ski ll s are developed when the teacher correctly placed. For the new teacher, this process
adheres to certa in basic principies of chart reading and of reading the chart day by day is slow. However,
has a firm grasp of the concepts of the system. It is as the teacher ga ins more experience, he or she
through a careful reading ofthe user 's chart at the time wi ll find that it is an easy task and one wh ich can
offollow-up that teachers identify errors in the user 's be done quickl y. To develop the skill s necessary
application ofthe system. With the identification ofsuch to accurate ly read a chart quickly and easil y, the
errors, specific recommendations can be made to man- new teachers in the CrMS must go through the pro-
age and correct them . cess of read ing chart after chart on a day-by-day
basis.
Principies of Chart Reading for Teachers 4. Develop a consistent pattern which is concise but
complete.
The following could be considered the genera l prin- Each teacher wi ll approach a chart in a somewhat
cip ies of reading a CrMS chart for CrMS teachers: different fas hi on. However, the general principies
still apply. What is most important is that each
l. Take a general look at the chart. teacher develop a consisten! pattern which is simi-
It is important to begin chart read ing by taking an lar for each chart that they read. If the pattem is
overall, general look at the chart, looking for gross consistent and becomes habitual , then important
accuracies and inaccuracies and also any informa- items wi ll not be forgotten or missed and the chart
tion which might be helpful to the teacher in rereading will be complete .
gard to the user 's application of the system . Ex-
amples of what might be found upon a general
observance ofthe chart would be the following : Specific ltems in Chart Reading
A. The teacher may find large gaps in charting
After having taken a general look at the chart and hav-
either in the descriptions, the dates or the place-
ing read the chart oo a day-by-day basis , the teacher
ment ofthe stamps.
mo ves toward the evaluation of certain specific items
Chapter 7: Basic Charting and Chart Read ing 115
that are important in chart reading and chart interpreta- reading begins in the upper left comer progress ing in
tion. The fo ll owing li st coi ncides with Section 8 ofthe diagona ls for the remainder ofthe chart. Figure 7-1 4 is
fo ll ow-up fo rm . an examp le ofa breast-feedin g chart that begi ns in the
upper left comer and p rog resses in a sp ira l fas hi on to
B. Has the Peak Day been correctly identified? the ri ght, down the bottom of the chart and aro und, even-
C. Have ali the stamps been correctly charted? tuall y endi ng in the center.
D. Has the recordi ng system been charted correctly?
A fter now havi ng read the charts in these figu res, the
E. Is the charting done at the end ofthe day? following comments are provided for each ofthe three
F. Is the most fe rtile sign ofthe day being charted? charts:
G. Is the menstrual flow being properly charted (H , M,
L, VL, B)? Figure 7-13 : Th is is a 29-day cyc le in whi ch the length
of the menstrual tlow is six days and the length of the
H. Is brown/black bleedi ng being charted?
mucus cyc le is five days. There are four pre- Peak dry
l. Is bleeding other than the period being charted? days and two additional dry days on the light and very
J. Is dry/mu cus on L, VL, and B days being charted? light days ofmenstruation. There is an abrupt change in
K. Are ali acts of intercourse being charted (I)? the mucus pattem fo ll ow ing the Peak Day. The length
of the post- Peak phase is 14 days. The student should
L. Is the di scharge after intercourse being charted on
have read through thi s chart on a day-by-day basis and
its merits?
been able to make these observations.
Figure 7-14 : Thi s is a breast-feedi ng chart that shows

Working Examples the time when the mother began weaning her child . There
are severa ! days of Peak-type mucus present indicating
In Figures 7-1 3 and 7- 14, two charts are prov ided that a va riab le retum of Peak- ty pe mu cus. The length ofth e
have been des igned to ass ist the new teacher in devel- post-Peak phase is 13 days and there is ev idence ofpre-
op ing the skill s ofbasic chart readi ng. Figure 7-13 re- menstrua l mucu .
vea ls a normal 29-day men trua ! cyc le and the chart
1 2 3 4 5 6 7 8 9 IO u 12 13 14 IS 16 17 18 19 20 21 22 23 25 26 27 28 29 30
-
24 31 32 33 34 35
VL
~ OAD
DAD """ 10'1<
•I ""ª
- ~
H ioAD IOKL aAD DAD
""
r
H ... , f
IOSI
x3
k·" DAD
- 1 I~ 1
M DAD ~e
<I
DAD ... ,
- 1
~
f f
L ~PC ~e
""ª
OAD
"" KI
- ~se f
VL
OAD K1 """ aAD
Figure 7-13: A normal 29-day cycle designed as a cha rt reading exercise. Begin chart reading, day by day, in the upper left-hand
co mer an d read the chart in a diagonal fashion.
116 The Medical and Surgical Practice of NaProTECHN OLOGY
22 23 24 25 26
f
IOK
f t
aAD OAD
XI
f
;;AD
~ f
t
OAD
~
....
~e VL H M
ª"ª
aAD
f
aAD OAD
~
~e
xi
tBK
XI
Fig ure 7-14: A breast-feeding chart designed as a chart readi ng exercise. Beg in readi ng, day by day, in the upper left- hand
comer and move rig ht - in a spiral fash ion - until the chart ends in the center.
Principies of Chart Reading fo r the The Jength of the pre- and post-Peak p hase .
Medica/ Consultan t
The occurrence of the P ea k Day (with in th e
cyc le) .
The techniques used by a CREIGHTON MODEL med i-
ca! consultant to read a CrMS cha11 are somewhat dif- • The intensity and length of the mucus fl ow .
fe rent than those of the teacher. Th e teacher 's ro le is to
The presence of a continuo us d ischarge and its
see that the user understands charting and can do it ac-
characte ri sti cs .
cura te ly. The health care prov ider loo ks more global/y
at the chart so that it can be viewed fro m the medi ca! or And the presence of abnorn1al or irregular bleed-
NaProTECHNOLOGY perspecti ve. mg.
In do ing thi s, the medi ca! consulta nt must: As one reads furth er into this textbook, one w ill be-
co me mo re fa m il iar w ith a w hol e host of vario us
• Lea m to trust the record ings and the teacher cli- biomarkers that w ill be an ind ication of or target one 's
ent role in making the chart.
medi ca! evaluation to a va riety of di fferent p athologic
• Read th e chart "globally" not " day by day" a l- or pathophysiologic processes. These will become easier
though the message of the chart is still in the to identi fy as the medica! consulta nt learns more and
da ily descri ptions. deve lops confid ence. But looking globa lly at the C rM S
cha11 and eva luating it in an organ ized fas hi on will al-
• Learn to look f or patterns that are ex hibi ted in low fo r these situati ons to become very obv ious.
th e chart.
• And look for th ose that meet speciflc criteria

Basic Chart Correcting
In looking " g lobally" at the CrMS chart, th e medi ca!
consultant should assess : After th e chart has been comp lete ly read and reviewed
with the cl ient, the teacher will then be involved in mak-
The cyc le length and regu larity.
ing chart correcti ons. Thi s is an important fu nction of
Chapter 7: Basic Charting and Chart Reading 117
the fo llow-up teach ing process and it is through this the box as in cycle B . lf no recollection can be
process that the new user learns how to keep the CrMS made, a red " ?" is placed.
chart. The fo ll ow ing principi es app ly to making chart
corrections. 2. On day 6 and 7 of the cyc le A, the number of
times that shiny without lubrication was observed
1. A red pen or pencil is always used. is not recorded. The user is as ked whether or not
she remembers how many times the observation
2. lf stamps require changing, the corrections are placed was observed. Ifs he can reca ll , then that is re-
at an ang le. corded as a correction.
3. Corrections are made together with the c lient and 3. On day 8, the obse rvat ion of PC X 1 (pasty,
the teacher. c loudy seen once) is recorded in the description
box but with a green sta mp. The pasty, c loudy
A red penci l is used during chart correcting so that ali discharge requires a white, baby sta mp . This cor-
corrections made at the time ofthe follow-up are eas ily rection is then appli ed on cycle 8 by pl ac ing the
identified. The same holds for placin g the sta mps at an stam p at an angle.
angle. When stamps appear on a chart at an angle, it
mea ns that those were corrections wh ich we re applied 4. On day l l and 12, two observa tions appear in
at the time of follow-up . the written descripti on box. C learl y, the user has
not recorded " the most ferti le sign. " Since 1OCL
In Figure 7-1 5, an examp le of chart correcting is pro- (stretchy, cloudy, lubricative) wo uld be consid-
vided . Cyc le A is a 27-day cyc le, which is an example ered more ferti le than 8C/K. (tacky, cloudy/c lear)
ofa cli ent's chart early in learn ing. There are a number or se (tacky, cloudy), a red line is drawn through
of errors in this chart and the student, by covering over the observati ons of lower fertility.
cycle 8 , should attempt to read the chart and identi fy
the errors and the corrections that may be made. Cyc le 5. In additi on, on day 12, the number oftimes that
B is the same cyc le but no w the chart corrections have the most fe rtil e sign was observed is not re-
been applied. corded. T he client is asked whether or not she
can recall how many times she observed it. If
The fo llowi ng is an outl ine of the errors foun d in cycle she can, then that number is recorded. lf she can-
A and correc ted in cyc le 8 : not, then a question mark is recorded in the fash -
ion of " X?".
1. There is no recording ofm ucus on the light and
ve ry light days ofthe men strua l tlow. The cli ent 6. O n day 14, the number of tim es is also not re-
should be first asked if mucus was observed on corded . The teacher uses the sa me process for
those days. lfthe answer is yes, then a question days 6, 7, and 12.
shou ld be asked rega rding whether or not th e
client can reco ll ect th e observations. lfthat can 7. O n day 15, the observa ti on 8L (tac ky, lubrica-
be done, then those observat ions are written in tive) is an incomplete one . Whenever the mucus
9 10 11 12 13 14 15 16 29 30 31 32 33 34 35
B
"' Pe 'H. t Ck '~ t e 10KL 10.KL ..er ..JG- a
•I 0 ;¡ 1a. ':f" IOU. AO •I •I AP
Figure 7-15: An example of applying chart corrections . Cycle A is a client's first cycle of charting . Cycle B illustrates the
co rrections and the manner in which they were made at follow-up.
118 The Med ica! and Surgical Practice of NaProTECHNOLOGY
can be stretched, a co lor shoul d be observed and 1O. S ince the Peak Day was mi sidentifi ed by one
reco rd ed . T he teac her wo ul d ask the c li ent day, a green baby stamp needs to be placed on
whether or not she recall s what the co lor of the day 18 since the 3-day count is extended by one
mucus was. lfs he <loes reca ll , then that co lor is day.
recorded. In th is case, th e 8L is crossed out and
8CL added because she could reca ll that the co lor 11 . As th e chart continues, a PC (past, cl oudy) di s-
was c loudy (tacky, cloudy, lubricati ve). O n day charge was observed and recorded on days 2 1
16, the same applies. The observation 8G (tacky, and 22. However, in cycleA, the client has placed
gummy) is incomp lete. It req uires a co lor. Since green sta mps fo r those days. ln the early leam-
she ca n reca ll that the co lor was cloud y, th e 8G ing process, pasty, cloud y da ys during the post-
is crossed out and 8CG is replaced (tacky, cloudy, Peak phase of the cyc le should be charted w ith
gum my). white, baby stamps.
8 . As thi s process draws to a comp letion, it also With the above corrections app lied, cycle A has now
beco mes obv io us that, w ith lubri catio n sti ll been corrected (cycl e 8 ) and th e cli ent has a record of
present on day 15, th e client has inaccurate ly these correcti ons on the chart so that future reference
identified the Peak Day. The refore, the Peak Day can be made to them .
marked on day 14 is crossed out and a new Peak
Day is marked on day 15 in red pencil.
Special Note
9. In cycle A, green baby stamps have been pl aced
for days l and 2 after the identified Peak . Since For the medi ca! consul ta nt, cycle B can also be evalu-
these days a re days in w hic h mu c us is still ated. The cycle is 27 days long with the pre-Peak phase
prese nt, the white, baby stamps should be used. be ing 15 days and the post-Peak phase 12 days in du ra-
In cyc le B, those have been pl aced at an angle tion. The menstrual tl ow is 5 days long and the mucus
sbow ing the correction. cycle, whi ch is of good intensity, is 8 days in length .
----~6u-8
Charting Continuous Discharges
po st- Peak phases of the cycle from d ifferent

W he n sorne women chart their cycles using th e
CREIGHTON MODEL FertilityCare™ System,
the charting pattem will revea! a continuous mucus pat-
perspecitves. They will a lso look at the type of mucus
discharge that is present during those phases: non-Peak-
tern. Such a pattem is di stinctl y ditferent from the more ty pe ve rsus Peak-type mucus.
standard pattem in which there are pre- and post-Peak
dry days anda mucus cyc le associated with a Peak Day. The teacherwill begin by looking at the post-Peak phase
At first g lance, it wou ld appear that the CREIGHTON first. This is because the instructi ons fo r the use ofyel-
MODEL System (CrMS) would not work in situati ons low stamps can be more qu ickly advanced during that
such as thi s. Howeve r, the true mucus cycle tends to be phase of the cycle. Infertili ty is determined on the basis
disti nctly ditferent than the genera l pattem of continu- ofthe woman 's confidenl identifica/ion ofthe Peak Day
ous mucus observed in these cyc les and, with the use of which determines that ovulation has passed and, thus,
certain teach ing techniques, the true mucus cycle ca n infert ili ty exists.
be identified and utilized in much the same fashion a
in otherwise normal cycles. In order to di stinguish the In the pre-Peak phase of the cycle, yellow stamps are
days of infe1ti lity from the days of fertility in cycles used in the presence ofvery specific criteria. The woman
with a contin uous discharge, y ellow stamps are used is taught to assess the mucus di scharge on its essenti al
instead of green stamps. Certa in teaching techniques same ness fro m day to day (estab li s h an essential
are emp loyed to deve lop these patterns. sameness pallern, ESP) and to look for the presence of
a change from that pattem (identi fying a poinl of change,
The orig ina l use of ye ll ow stamps was introduced by POC ). The ESP indicates that the ovary is not acti vely
Drs. Jo hn and Lyn Bi ll ings and publi shed in the ea rl y progress ing toward ovulation (ovarian quiescence) and
l 970s. 1 The work with yellow stamps in the CrMS be- that the natura l state of inferti lity exists as the result.
gan in 1976. The CrMS now has over 25 years of expe- When the POC is identi fied , it indicares that the ovary
rience in the use of ye ll ow stamps. is now active ly moving toward ovulation (the fo llicle is
beginni ng to develop) . With the deve loping follicle
In approach ing the use ofyellow stamps, the FCP will comes increasing leve Is of estro gen, w hi ch changes the
assess the necess ity oftheir use in the pre-Peak and the quality and quantity ofthe mucus being produced, and
119
120 The Medica l a nd Surgical Pract ice o f NaProTECHNOLOG Y
the vu lvar observation signals thi POC w ith a mucus

observation that is d istinctly different from th e ESP. Table 8-1: The U se of Yellow Sta m ps Post-Peak
When the FCP approache the teaching ofa woman with

a continuo us di scharge, these concepts are addressed 1. Can be used with both Pea k-type and non-Peak-
type mucus
early in the fo ll ow-up sequence and rapid progress in
2. Post-Peak use requires confi dent identification of
their impl ementation can generall y be made. T he teach- th e Peak Day
ing approach is modifi ed to sorne ex tent depending upon 3. Post-Peak use does not involve the essential
when the mucus is of the non-Peak type or Peak type . sameness criteria (is a pre- Peak tech nique only)
In add iti on , there are different variations of non-Peak- 4. lnfertility post-Peak is dueto ovulati o n having
type mucus and that w ill a lso influence the teaching and passed
charting approac h to sorne extent. Whil e it is critica !

for the teacher ofth e CrMS to be we ll trained in these
approaches because th ey will see all of the va ri ations
over time, it is much eas ier for wo men lea rning th e
syste m fo r themse lves because they onl y need to Iearn cervical infl am mation. Thus, while th is is being man-
the variati on that appli e to them . aged with yell ow stamps, it i an option to have the cer-
vix checked by a phys ic ian and treated.
A further e laboration of these management concepts
a long with sorne charting exampl es are now presented. In sorne women, there may be a regular (or irregular)
appearance of a mucus discharge just prior to the be-
ginning of menstruation. Th is condition, referred to as
The Use ofYellow Stamps: Post-Peak, Non- prem enstru a l mucu s, has been shown to occur (in a
Peak-type Mucus _ _ __ _ _ _ _~ stud y of600 cycles) 12 .3 percent ofthe time (Chapter
15). Thi s can be a regular occurrence in sorne wo men,
A common area of teaching applies to women who have thus, the actual inc idence is lower than 12.3 percent
a post-Peak, non-Peak type mucus discharge. The non- when appl ied to the popul atio n ofwomen.
Peak-type mu cus may be cervical mucus, a vaginal dis-
charge or endometrial mucus discharge (genera ll y pre- Th is premen strual mucus disc harge is thought to occur
menstrual in location). The presence ofnon-Peak-type as the result ofthe secretory fluid from the endometrium
mucus post-Peak can generall y be identitied thrnugh being di scharged through the cervix during the imme-
the tirst cyc le of good observations and charting. So diate premen strua l phase of the cyc le. The di scharge
long as the woman has confidentially identifted the Peak may be non-Pea k- type or Peak-type.
Day, ye ll ow stamps can be g iven for use in the second
cyc le (Tabl e 8- 1 and Figure 8-1 ). In Figure 8-2, th e occurrence ofpremenstrua l mucus is
shown . In thi s exa mple, the tacky, c loudy mucus in the
The presence of non-Peak-type mucus discharge occ ur- first cyc le is observed as fe rtile beca use it is the first
ring during th e post-Peak phase ofthe cycle (excluding cycle of charting. However, with good observati ons and
any pasty type of di scharge) is often associated w ith a charting and con fídent identitication of the Pea k Day,
29 .JO 31 32 33 34 35
Figure 8-1 : Post-Peak, non-Peak mucus shown on a CrMS cha rt with evolution of the use of post-Peak yellow stamps.
Chapter 8: Charting Continuous Discharges 121
thi s no n-Peak, post-Peak mucus can be charted with In other women , a continuous discharge of pasty, cloudy
yellow stamps during the second cycle and used accord- mucus may be observed. Because the pasty, cloudy dis-
ingly. However, in the th ird cyc le (cycle C), the pre- charge comes from the vagina and is not cervica l mu-
menstrual mucus is stretch y, clear and 011 that basis is cus, it can be managed differently than the more typical
agai n observed as a day offertility. Ifpremenstrual mu- 11on-Peak-type cerv ical mucus discharge that occurs dur-
cus is persistently of the Peak-type, the days mayal so ing the post-Peak phase ofthe cycle (Figure 8-3).
be cons idered to be infertile.
The i11structions for post-Peak , pasty discharge during
27 28 9 30 31 32 33 3 35
.~ A
e
I :r:
D
1-1 M M oAO
L VL
.l..AD
I
Figure 8-2: Preme nstru al mucus charted with the CrMS .
25 26 27 28 29 30 J I 32 33 34 35
.9
~
Q
~
.o'.': A
P<
AP
I :r
e
D
,. L 'L '1'40 {,Pe '/AD ..... ~"" <.Pe 'Pe 'I~ """ ec.e l """ 16/L
H H r( ~ .. .1 il AD (~ ~D
~
" 'P,,C r :r :r :r ::r :r .r :r r :r
Figure 8-3: Post-Peak, pasty discharge charted with the CrMS and the use of yellow stamps progressing to green stamps
because the pasty cloudy discharge is vaginal , not cervical in origin.
the post-Pea k phase of the cyc le are the sa me as fo r any cycles of charting po t-Pea k ye ll ow stamps fo r the pasty
non-Peak-type mucus di scharge during th e first three c loudy discharge, green stamps are impl emented.
cyc les of charting. lf the presence of the pasty, cloudy
di scharge is identifi ed during the first cycle of chartin g,
then ye llow stamps can be used fo r thi s non-Peak-type Post-Peak, Peak-type Mucus ----~
mucus di scharge after one cyc le of good observati ons,
good charting and the confident identifica/ion of the The di scharge pattern in the post-Peak phase can a lso
Peak Day . The ye ll ow stamps are then used fo r a mini - be a continuous di scharge of Peak-type muc us. W hile it
mum oftwo additi ona l cyc les. During thi s time, confi- may seem to be an oxymoron to ha ve Peak-type mucus
dence is establi shed that thi s is the pasty, cloudy type of during the post-Peak phase ofthe cycle, in actual prac-
di scharge. Such confidence is obtained by using The ti ce the woman can determine the Peak Day (and do o
Picture Dictionary to c larify with the client that the confi dently) by the change in the mucus pattern that
observati on is indeed the pasty ty pe of di scharge, which occurs as th e res ult of an increase in progesterone im-
ori gina tes from th e vagin a. ln the fo urth cyc le of chart- medi ately fo ll ow ing ovul ation. Thi s impacts the mucus
ing, th e yell ow stamps used fo r the pasty, cloudy di s- pattern so that the Peak Day can be confidentl y identi-
charge durin g th e post-Peak ph ase of the cycle can be fied regardless of the type ofmucu s observed post-Peak.
conve rted to green stamps. In additi on, the instru cti ons
that apply to post- Peak green tamps- any tim e of day
for intercourse--can be used regardless ofthe post-Peak, Use of Pre-Peak Yellow Stamps:
pasty type of di scharge . The use of green stam ps for a General Guidelines _ _ _ _ _ _ _~
non-Peak-type mucus di scharge durin g the post-Peak
phase of the cyc le is limited to the presence of a pasty, Good judgment is critica! in the use of pre-Peak ye l-
c loud y di scharge only. lt does not apply to an y other low stamps (Table 8-2). Th e teacher leam s to recog-
fo rm of non-Peak-type mucus di scharge . In addi tion, ni ze the good candidate fo r the use of ye llow stamps.
these instructions do not apply to the presence of a pasty, Ye llow stamps are not automatically issued w ith the
cloudy di scharge during the pre-Peak phase of the cyc le. stamp packets th at are g iven to cli ents at the beginnin g
Standard in structi ons fo r continuous mucus during the of their use of the CrMS. Yellow stamps should be g iven
pre-Peak phase need to be introduced to manage thi onl y at the spec ifi c recommendati on of the CrMS and
situati on (see be low) . th en onl y after spec ific criteri a have been met.
S ince the pasty, c loud y di scharge i a specia l type of With the use of pre-Peak yell ow stamps, the questio n
di scharge ori g ina ting fro m the vagi na and no t fro m the has long been as ked, " What is the pregnancy rate wi th
cerv ix, the fo ll owing spec ia l instructi ons appl y: th eir use?" A large group ofwomen who are using pre-
Pea k ye ll ow stamps has, as a subj ect of spec ific stud y,
Special In stru ctio ns never been eva luated fro m the po int ofview ofth e ef-
fec ti veness of the infertili ty of these days . However,
1. The in structi on fo r post-Peak, non-Pea k- type women who have used pre-Peak yell ow stamps have
mucus appl y until two cyc les ofye ll ow stamps been inc luded in ali five use-effecti ve ness studi es that
bave been successfull y compl eted. have been conducted w ith the CrMS.2 In those studi es,
there was nothing to suggest that the use of pre-Peak
2. After two cyc les of ye llow stamps and confir-
ye ll ow stamps adver ely affects the overall effecti ve-
mation at fo llow-up with The Picture Dictionary
ness ofthe system in any way. In other words, the effec-
that thi s is indeed the pasty, cloudy discharge,
ti ve ness of pre-Peak yell ow stamps does appear to be,
green stamps can be used during the post-Peak
over a 25-yea r experi ence, ve ry good and in line with
phase of the cyc le.
the effecti ven ess one would normally see with the use
3. The bas ic in structions appl y including any time of green stamps by those women who bave pre-Peak
of the day fo r intercour e once the green stamps dry days. We can conclude from the effecti veness stud-
are impl emented during the post-Peak phase of ie tbat have been compl eted th at the use ofpre-Peak
the cyc le (see C hapter 9). yellow stamps should carry with them the same effec-
tiveness rating as tite use ofgreen stamps for the iden-
tification of pre-Peak dry days and pre-Peak days of
In cyc les A, B, and C of the example (Fi gure 8-3), the inferti/ity. In other words, the use of pre-Peak ye ll ow
in structions that are used fo r post-Peak, non-Peak mu- stamps should be a ve ry re liabl e indi cator of the pre-
cus in genera l ha ve been fo ll owed. However, after two Pea k days of infe rtility.
Chapter 8: Charting Continuous Discha rges 123
C. Breast feeding- prior to the beginning of the

Table 8-2: The Use of Pre-Peak Yellow Stamps: first menstrua l period
General Guidelines
The use of ye ll ow stamps in these situations is illus-
trated in Figures 8-4, 8-5 and 8-6.
Good judgment is critica!
FCP must learn to recognize the good candidate far Figure 8-4 hows the use of pre-Peak ye ll ow stamps in
yellow stamps
a regu lar length cyc le in wh ich the mucus cycles are
Yellow stamps are given only al the specific
recommendation of the FCP and only alter specific greater than eight days in duration. In Figure 8-5, the
criteria have been met use of pre-Peak ye ll ow sta mps in a woman with long
cycles is shown and, in Figure 8-6, the use of pre-Peak
ye llow stam ps in a woman who is currently breast feed -
ing is shown.
Use of Yellow Stamps: 1n Figures 8-7 and 8-8, an exa mpl e ofthe hormone pat-
Specific Guidelines _ _ _ _ _ _ _~ tern in a woman with a prolonged mucus cycle but oth-
erwise regular length cycle has been measured and iden-
The essentia l sameness criteria, which is based upon tified. In Figure 8-7A, the overa ll length of the men-
the essential sameness question, is a criterio that is uti- strua l cyc le is 33 days. The Peak Day occurs on day 22
lized during the pre-Peak use of yel/ow stamps far a and the length of the mucus cyc le is 13 days. In the
mucus discharge which is essentially the same from day early pre-Peak phase ofthe mucus cyc le, the mucus is
to day. The inferti li ty of these days is based upon the determined to be essenti all y the same and a point of
fact that the sa meness ofthe mucus pattern is indicative change is identifi ed on day 16 of the cyc le. Thus, in
of ovarian quiescence. There will be a point of change Figure 8- 78 , the days that wou ld be con idered infer-
(POC) in the pre-Peak mucus pattern which is obvious tile are charted with ye ll ow stamps. These days are days
and is dueto rising levels ofestrogen a the deve loping 1Othrough 15 ofthat cyc le (thi s includes only the days
fo lli cle progresses toward ovu lation (Tab le 8- 3). of infertility in w hi ch a mucus discharge is
present. .. days 5 through 9 are also infertil e based upon
The use of pre-Peak ye ll ow sta mps fo r the identifica- the basic dryness of the pattern).
tion of pre-Peak days of in ferti lity is limited to three
categories: The cycle shown in Figure 8- 78 is the sa me cyc le as
that shown in Figure 8-7A except it has now been charted
A. Regu lar length cycles when mucus cycle is
with ye llow stamps.
greater than eight days in length
B. Long cycles- greater th an 38 days in durati on In Figure 8-8, the pattern ofthi s same cycle is now shown
with the estrogen and proge terone leve! measured in
Table 8-3: The Use of Pre-Peak Yellow Stamps:

Specific G uidelines
Can be used with both Peak-type and non-Peak-type mucus

The essential sameness pattern (ESP ) of the mucus indicates
ovarian quiescence
The pre-Peak change in the mucus pattern is obvious and is dueto
rising estrogen levels
Pre-Peak use is limited to :
Regular length cycles when mucus cycles
are greater than eight days in length
Long cycles (g reater than 38 days)
Breast feedi ng - prior to the first menses
lnfertility pre-Peak is dueto the follicle not yet being in develop-
ment
124 The Medical and Su rgical Practice of NaProTECHNOLOGY
1 2 J 4 5 6 7 8 9 10 11 12 IJ 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 J3 34 35
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Figure 8-4 : The use of pre- and post-Peak yellow stamps in a wom an who has a continuous mucus discharge, regular length
menstural cycles and a mucus cycle wh ose length is greater !han eight days in duration.
1 2 J 4 5 6 7 8 9 IO u 12 13 14 IS 16 17 18 19 20 21 22 23 24 25 26 27 28 29 JO 31 32 33 34 35
~" ~~~~ t se ... ... ~~~

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Figu re 8-5: The use of pre-Peak yellow stamps in a woman with a long cycle .
"I " ·i
1 2 3 4 5 (> 7 8 9 10 14 15 16 17 18 19 20 21 22 2.1 24 25 26 27 28 29 30 .1 1 32 33 34 .15
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Figure 8-6: The use of pre-Peak yellow stamps in a woman who is breas! feed ing .
Chapter 8: Charting Continuous Discharges 125
1 2 3 4 s 6 7 8 9 10 11 12 13 14 IS 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
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Figure 8-7 A and B: In cycle A, a regular length menstrual cycle with a prolonged mucus cycle (13 days). In cycle B, the same
cycle with pre-Peak yellow stamps for mucus that is essentially the same.
association with it. As can be seen, the estrogen levels thermore, whe n this was further eva luated, the slope of
during the earl y pre-Peak phase of the cycle are very the estrogen curve was quite low from POC - 1 to the
low but, as the mucus cycle changes (shown by the es- POC . Between these points, the slope was 1.34. How-
trogen levels on days 17 and 20), there is evidence for ever the slope in the estrogen curve in creased dramati -
fo lli cu lar growth and deve lopment. Ovulation occurs ca ll y from the day ofthe POC to POC + 1. In this case,
w ith the rise in progesterone identified on day 20 ofthe the slope was 4.46 (Figure 8- 1O).
cycle. This example ofhormones being measured dur-
ing the course of the cycle and of the use of yellow E sentia/ sameness is a pre-Peak technique only. ln-
stamps to detect a patte rn of mucus discharge that is ferti li ty during the post-Peak phase ofthe cyc le is due
essenti ally the same (indicating ovarian quiescence) to the fact that ovulation has passed.
revea Is the point of change in the mucus discharge. The
mucus pattem identifies act ive foll icu lar growth and
development toward ovulation and this is confirmed Final Note -----------~
by th e ri sing level s of estrogen.
This chapter on ly introduces the reader to the concepts
In the onl y study that has ever been conducted on the that are helpful toan understanding ofthe physiologic
hormonal parameters ofwomen using pre-Peak ye ll ow basis and teaching principi es for the implementation of
stamps, Cvetkovich7 showed that, in a composite often yellow stamps in women with a continuous mucus dis-
menstrua l cycles, the point of change coinc ided with charge the CrMS . The compl ete details are published
the break in the estrogen curve towards the active phase in the teacher training manuals for the CrMS .4·5
offo llicular growth and development (Figure 8-9). Fur-
1 2 3 4 5 6 7 8 9 IO 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 1ls 29 30 31 34 35
•-
32 33
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·~
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E«<1 OGI N' ~' 1 l. 11 - 1 PR bG8 ;n:¡ ONI

N~ ML
Figure 8-8: The same cycle as in 8-7A and 8-78 but with the estrogen and progesterone leve Is identified . The estrogen levels are
low during the essential sameness pattern (ESP) where pre-Peak yellow stamps are used . The estrogen levels are much higher
when the mucus changes at the time of fertility. The rise in progesterone occurs at Peak - 2 days.
22
20
20
18
18
16
'O 16
......
Ol 14
e
~
t- 14 u
....
UJ O> 12
ID e:
,__ o
u +1
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o u;
UJ
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~en 10 8
UJ P.O.C.
6 P.O.C. -1
8
4
Day of Cycle
-2 -1 +1 +2 +3 +4 +5 +6 +7
Figure 8-10: Th e mean estradiol level and its standard error
Oay of Cycle the day befare , the day of and the day after the point of change
Figure 8-9 : A composi te estradiol curve in 1O menstrual cycles (POC) in the mucus pattern (a composite of 1O cycles) . The
and its correlation to the point of change (POC) in the mucus rate of increase is demonstrated by th e measurement of the
pattern ' (From : Cvetkovi ch LC , Hilgers TW, Gentrup B: slope of the curve' (From: Cvetkovich LC, Hilgers TW, Gentrup
Continuous Mucus : Correlation of Point of Change with B: Continuous Mucus: Correlation of Point of Change with
Preovulatory Rise in Estrad io l-17 ~ . lnt Rev Nat Fam Plan . 12: Preovulatory Ri se in Estradiol - 17 ~. lnt Rev Nat Fam Plan . 12:
340-352 , 1988). 340-352 , 1988).
Chapter 8: Chartin g Continuous Discharges 127
1. Billings EL, Billings JJ and Catarinich M: At las ofthe Ovulation 4. Hil gers TW, Daly KD , Hil gers SK, Prebil AM: CREIGHTON
Met hod: Th e Safe Period Based on the Mucus Symptom. Advo- MODEL FertilityCare™ System : A Standa rdi zed, Case Manage-
ca te Press PTY Ltd. Melbourn e, Austrailia, 1973. ment Approach to Teac hin g- Book 1: Basic Teach in g Skilis. Sec-
ond Edition. Pope Paul VI lnstitute Press, Omaha, Neb raska,
2. Hilgers TW and Stanford JB: The Use-Effectiveness to Avoid
2002.
Pregnancy of CREIGHTON MODEL NaProEDUCATION Technol -
ogy : A Meta-An alysis of Prospecti ve Trials. J Repro Med 43: 5. Hilgers TW, Hil gers SK, Prebil AM, Dal y KD : CREIGHTON
495-502, 1998 . MODEL FertilityCare™ System : A Standa rdizcd, Ca e Man-
ageme nt Approach to Teac hing-Boo k 11: Adva nced Teaching
3. Cvetkovich LC, Hil gers TW and Gentrup B: Continuous Mucus:
Ski li s. Pope Paul VI ln stirute Press, Omaha, Ne braska, 2003.
Correlation of Point of Change with Preovulatory Ri se in Estra-
di o l-1 7~. lnt Rev al Fam Plan. 12: 340-352, 1988.
Basic CrMS lnstructions
nderstandin g the instructi o ns of th e 4. lt is the client co uple's responsibility to use the

U CREIGHTON MODEL System (CrMS) is obvi-
ously fundamenta l to its proper use. The FertilityCare™
CrMS .
5. lt is the teacher 's responsibility to teach the

Practitioner (FCP) will thoroughly know the instruc-
CrMS .
tions as they apply to different situation s. This chapter
wi ll present those basic in struction s. 6. To achieve pregnancy the days of ferti lity are
se lected for use.
7. To avoid a pregnancy the days ofinfertility only
Basic Principies ---------~
are se lected for use.
There are a number ofbasic principies that lay the foun- 8. Us ing days offerti li ty abandons the system as a
dati on for the proper teaching of the system in struc- system to avo id pregnancy and adopts the sys-
tions. These includ e th e fo ll ow ing: tem as a system to acbieve pregnan cy.
9. There are no "taking chances" with the CrMS . lt
1. The CrMS is a system of both achi ev ing and
is either used as a system to achieve pregnancy
avo iding pregnancy. lt is nota system of contra-
oras a system to avo id pregnancy. This concept
ception. It is true fa mi/y p/anning .
is taught from the very first exposure ofthe cli-
2. Users of the CrMS are free to use the system to ent to the learning process.
either ach ieve or avo id a pregnancy as they so
1O. The instructions ofthe CrMS include instructions
choose.
rega rding observations and charting, as wel l as
3. While the FCP will assist the client couple in the application of the instructions related to geni-
using it accord ing to their intentions, the teacher tal contact.
will not be prejudicia l in conveying the instruc-
11 . The instructions related to genital contact evolve
tion s to the user. Specifically, a teacher's bias
from one fo llow-up to the next before the full
toward using the system to achieve a pregnancy
instructions of the system are avai lable to the
or towa rd using the system to avo id a pregnancy
user. This evo luti on of instructions is conducted
is avo ided.
129
under the superv ision ofthe FCP . Non-Pea k-type M ucus:

A ny mucus di scharge th at is no/ clear, stretchy, ar
12. The instruction related to genita l contact change
lubri cati ve.
from one re producti ve category to th e next re-
quiring additi ona l teachin g input at the time of a
Pea k Day :
change in reprod ucti ve category.
T he las / day of any mucus di scharge that is clear,
13. The in structi ons to avo id preg nancy as they re- stretchy, or lubricative.
late to observati ons, charting and geni ta l con-
tact have been developed so that, w hen used cor- Pre-Peak Phase :
rectl y, th e CrMS is over 99 percent effective as a The phase of the menstrua l cyc le from the first day
system ofavoi di ng pregnancy. T hé client couple of menstruatio n up to and including the Peak Day.
must be info rm ed th at w hen they choose to de- The length of the pre- Peak phase is the number of
viate from these in struct ions they ha ve chosen a days fro m the firs t day of menstruation through the
less effective means to avo id pregnancy and have Peak Day.
adopted a more effective means of ac hi eving a
pregnancy. Post-Pea k Ph ase :
T he phase ofthe menstrual cycle from the day after
14. At ali times the teacher must exercisegoodjudg-
the Peak Day th ro ug h th e last day pri or to the be-
ment based upon sound princ ipi es and a thor-
g inn ing of the next menstruation. The length of the
ough understand ing of the CrMS whe n recom-
post-Peak phase is the number of days from the da y
mending in structi ons to the client.
after the Peak Day th rough the last day prior to th e
beginning ofthe next menstruati on. The total length
of th e menstrua l cyc le shou ld equa l the sum of the
Definitions ------------~ lengths ofthe pre- and post-Peak phases of the cyc le.
There are a number of defi niti ons that are important so Genital Contact:
th e in structi ons can be thoroughl y un derstood. These Any phys ica l contact of the male and fe ma le genital
defini tions fo ll ow : organs. Thi s includes the act of complete intercourse,
an incompl ete act of intercour e, c lose contact of
l nstruction s: the genita l orga ns w ithout intercourse, ej aculation
The instructions of the CrMS are those concept or with in the vicini ty of the fe ma le genital organs, and
statements th at govern the practica ] use of it. T hese any hand-to-genital contact. A li genital contact must
are w hat make it work. They cannot be changed be avo ided on the days of fe rt ili ty if it is the inten-
without additi ona l resea rch. The latter ta k is not tion to avo id pregnancy.
w it hi n t he d o m a i n of ex p e rti se fo r m os t
FertilityCa re™ teachers or medica! consul ta nts . Sex ual Contact:
Sex ual contact is to be spec ifi ca lly di sti ngui shed
G uidelin es: from genita l contac t beca use sex ua l contact is th e
T he guideli nes of the CrMS are certa in concept or " contact'' of the total person one to the othe r. Such
statements that a lso govern the practica ! use of it. contact incl udes genital contact but is much more
T hey should be viewed as be ing nea rl y as important than genital contact. In fac t, most ofthe ti me, since
as instructi ons, but they have an addi tiona l degree it is a much broader concept, the ph ys ica l act of in-
of tl ex ibili ty whi ch, w ith serious reason and consid- terco urse is not in vo lved. Sex ual contact invo lves
erati on can be modi fied by the teac he r. However, true sexual interaction and is therefore multi-dimen-
such mod ifi cation must onl y be done w ith the most sional. lt is creative, intellectual, emotional, spiri-
seri ous of reason and then always w ithin the frame- tual and physical. Whil e genital contact is to be
wo rk of the exercise of good j udgment. avo ided during the days offertili ty ifit is the inten-
tion to avo id pregnancy, sex ual contact is never to
Pea k- type M ucus: be avoided.
A ny mucus di scharge that is clear, stretchy, or lu-
bricative. Unu sual Bleedin g:
T hi s is bl eed ing that is interpreted by the woman as
any bleed ing other than a norm al (usual) menstru al
tlow.
Chapter 9: Basic CrMS lnstruction s 131
Va ria ble Return of Pea k-type M ucus: Women can very eas ily identify the last day of Peak-
Thi s refers to a condition in wh ich the Peak-type type mucus and this dramatic change, whi ch occurs in
mucus tends to come and go dueto rising and fal l- the days that fo ll ow. When these changes, conjirmed by
ing leve Is of estrogen. It is most common ly observed the woman 5· observations ofmenslruationfollowing at
in the breastfeeding woman who is in the weaning the appropriate time, ha ve been tracked fo r one or two
process and in women who are either anovulatory cycles, the woman wi ll convey to the teacher her confi-
or oligoovulatory. dence in her identification of the Peak Day. Using the
instructions of the CrMS that app ly to the post-Peak
End of the Day: phase of the cycle requires conjident identifica/ion of
The end of the day is cons idered to be that time of the Peak Day. Such confidence is elicited through dia-
the day when the woman goes to bed to go to sleep . logue with the woman re lative to her observation and
recording of the Peak Day. Her development of confi-
Alternate Days: dence in this observation genera ll y takes onl y one or
Alternate days refers to every other day. In the in- two cycles.
structions related to genital contact, this instruction
recom mends gen ital intercourse on one day, a day lt must be kept in mind that the identificat ion of the
is then skipped where no gen ital contact occurs, and Peak Day is not based on the amount of mucus. The
then the next day genital contact may be resumed. Peak Day is the last day of any mucus that is clear,
stretchy, or lubricative. This mea ns that any one ofthese
Seminal F luid Elimin ated : three signs, afane or in any combina/ion or amount,
A di scharge is not observed the day fo ll owing inter- determines the presence of Peak-type mucus. Although
course after use ofthe semi nal fluid in struction (see the amount ofm ucus might be relatively sma ll , the char-
Chapter 9). acteristics ofthe mucus are still present all ow ing for a
proper identifi cation of Peak-type mucus and the Peak
M ucus Patch : Day.
A series of one or more consecuti ve days of non-
Peak-type mucus. Generally, if the mucus patch is Of ali the cli nical signs currentl y avai lab le for the de-
greater than seven days in duration , it is referred to tection of ovulation, the Peak Day has been the most
as a continuous discharge ofnon-Peak-type mucus. closely eva luated. At thi s time, five studies in four coun-
A pattern ofmucus that has Peak-type mucus is gen- tries have independentl y eva luated the corre lation of
era ll y referred to as a Peak-type mucus buildup . the Peak Day with the e timated time of ovu lation. These
five studies have confirmed the accuracy of the Peak
Contact Pregnancy: Day as a sign indicating ovu lation. In our studies of 65
Any pregnancy that occurs as a result of genita l con- hormona lly normal menstrua l cycles, ovulation occurred
tact exc luding the comp lete act of genital intercourse. on average on the Peak Day and, with in the population
of women, occu1Ted from three days befo re to three days
Mucus Cycle: after the Peak Day. In over 95 percent of the cycles,
The mucus cyc le is the number of days from the ovulation occurred from two days before to two days
tírst day of mucu s counted continuously through to after the Peak Day (see Chapter 14). These studi es ali
and including the Peak Day. used indirect hormone param eters to identify the tim-
ing of ovu lation. Recentl y, the direct observations of
fo lli cul ar rupture by ultraso und has further established
A Note on the Peak DaY - - - - - - - - . the range ofovulation as P- 3 to P+3.
The Peak Day is the last day of any mucus that is clear, In certain situatio ns, espec iall y in women who are
stretchy, or lubricative. The Peak Day is determined in breast-feeding- wea ning and in women who are anovu-
retrospect. Only after the Peak Day has passed can it be latory or oli goovul atory, the woman will ex peri ence a
identified. One ofthe most important factors that goes variable return ofPeak-type mucus . In a situation such
into identification of the Peak Day is the abrupt and as this, the woman may experi ence severa! different days
dramatic change in the pattern of mucus that occurs that fit the definition ofthe last day of any mucus which
after the Peak Day. This abrupt change in the mucus is clear, stretchy, or lubri cative. In situations such as
pattern is due to the effects of the progesterone hor- this, ovu lation , if it occurs at ali , is associated with the
mone (which increases after ovul ation) on the produc- last Peak Day. This last Peak Day should be referred to
tion of cerv ical mucus from the endocervical crypts. as the Peak Day. Ali ofthe other " Peak days" should be
132 The Medical and Surg ical Practi ce of NaProTECHNOLOGY
referred to as a Peak day. Having a Peak day simpl y B. Chart at the End of Your Day, Every Day and
allows conveyance ofthe message that Peak-type mu- Record the Most Fertile Sign of the Day
cus was present but thought not to be associated with
ovulation. Having the Peak Day implies that the buildup Charting is begun immediate/y (no later than the next
ofthe mucus and the abrupt change following the Peak day) after the lntrod uctory Session. It, too, shoul d be
Day was typical ofthat associated with ovulation. This viewed as an extremely important element in the suc-
has practica! importance in charting and in knowing and ce sful use ofthe CrMS . lt should also be kept in mind
understanding the instructions. In the early months of that the chart ofthe CrMS is an excellent heolth record.
learning, a "P" hould be placed on any Peak day. lt is Occasionally, a user will be disappointed at the thought
optional, however, in later charting to put a " P" on a of having to chart for the rest of her reproductive life.
Peak day whereas a "P" should alway be placed on the However, the charting routine is basically a simple one
Peak Day. In addition , it i necessary for the Peak Day and the long-term benefits are outstanding, not only in
to have passed in order for the instructions that apply to the successful use ofthe system but also in the identifi-
the post-Peak phase of the cycle to be applicable. lf cation ofprocreative and gynecologic health problems.
on ly a Peak day has passed, the user continues to be
pre-Peak and the pre-Peak instructions continue to ap- Charting should be done at the end of the doy, and the
ply. chart should be kept in a convenient location, which is
readily accessible to both the husband and the wife.
Charting can be done by either spouse. Good charting
Basic lnstructions of the CrMS _ _ _~ habits include charting every doy and not leaving sev-
era! days ata time to cha1t. One's recollection of obser-
In most situations where the CrMS is used , there is a set vations decrea es propo1tionately with the time that tran-
of basic instructions that apply. While there are times, spires after the observations are made. And finally, the
especially related to specific reproductive categories, charting requires on ly the recording ofthe mostfertile
where special instructions apply temporari ly prior to sign of the day. A record of every spec ific observation
instituting the basic instructions, the basic instructions is unnecessary and not recommended .
provide the foundation ofthe system . The following dis-
cussion explains the basic instructions. The letter and
number associated with the instruction refer to its loca- C. A void Genital Con ta et
tion in the CREIGHTON MODEL FertilityCare™ Sys·
tem Follow-up Form (see Chapter 5). The initial instruction regarding the use of the CrMS
provided at the time ofthe lntroductory Session is for
the couple to avoid genital contact for either one month
A. Always Keep to the Observation Routine or one cycle, whichever is shorter. The instruction al -
lows the woma n an opportunity to observe the mucus
lt is important to realize that making 100-percent ob- discharge without confusion from semina l fluid. The in-
servations in accordance with the routine previously struction is extremely imporlont to deve lop her confi-
discussed is an instruction ofthe CrMS . One's ability to dence in the observations. There are no exceptions to
define the time offe1tility and infertility depends upon it. Those couples who choose to have intercourse dur-
the adequacy ofthe observations that are made. There- ing this time should anticipate delays in leaming and
fore , clients are made aware ofthe importance ofthis at the deve lopment of confidence as well as a higher preg-
the leve! of an instruction. It should also be empha- nancy rate .
sized that this instruction is as important for those who
wish to use the CrMS to avoid a pregnancy as it is for Special instructions regarding the avoidance of genital
those who wish to achieve a pregnancy or who are moni- contact apply to the infertility couple and to totally
toring their cycles for purposes of health maintenance. breastfeeding. In infe1tility, the recommendation is to
There is a tendency to eliminate sorne of the observa- avo id genital contact through the first complete cycle.
tions when using the system to achieve a pregnancy. In a total/y breastfeeding situation, no avoidance of
This is a throwback to the contraceptive idea that in genital contact is necessary during the first 56 days af-
order to achieve a pregnancy one "stop using the ter the birth of the baby. Both of these instructions are
method." When usin g the CrMS , good observations expanded upan in detail under the specia\ application
should be used and encouraged whichever way it is be- for those two reproductive categories (see Chapter 1O).
ing used.
Instructions A, B and C should be provided to the client
Chapter 9: Bas ic CrMS lnstructions 133
at the lntroductory Session and the first follow-up (with bility of confusing a true menstrual period for
the spec ial variation for avoiding genital contact in in- bleeding that occas ionall y occ urs at the time of
fertility and breastfeeding). Instructions A and B apply ovulation (so ca ll ed "ovulation bleeding"). In a
from the lntroductory Session on and are a uni versal in- small percentage of women, bleeding will occu r
struction ofthe CrMS to be applied at ali times. around the time of ovulation as the result of th e
hormonal changes occurring at that time. This
bleeding, of course, wou ld be occurring at the time
D. Days of Fertility ofpeak fertility. lfovulation bleeding were thought
(Select to Achieve Pregnancy) to be inferti le and intercourse occurred on those
days, a pregnancy wou ld be expected to result.
Usually at the second follow-up , the days of fertili ty
and infe rtility are explained to the user. The days of Some degree of modifícation of this instruction
ferti lity are those days when , if used, the potential for has been developed (see E-7 below). When this
pregnancy ex ists. The client should be informed that modifícation is instituted, the li ght and very light
they should expect to become pregnant when these days days of menstrual bleeding take precedence over
are selected for use (Figure 9-1 and 9-2) . D-1.
D-1. The Menstru al Flow D-2. From the Beginning of th e Mucus Until Three
The menstrual flow is considered fertile for two Full Days Past the Peak Day
reasons. First of ali , every woman will experience Fertility starts at the beginning ofthe mucus di s-
a short menstrual cycle as the result of an early charge and is presentas it builds up to the Peak
ovulation sometime through her reproductive life. Day. Fertility continues through three full days past
When this happens, the beginning of mucus oc- the Peak Day (i nferti lity begins at the end ofthe
curs during the tail end days ofthe menstrual flow fourth day) . This instructi on app lies whether it is
and ovulation follows shortly thereafter. In this a Peak Day or the Peak Day.
situati on, intercourse during this time could re-
sult in a pregnancy. The second reason for con- The mucus is presentas an effect ofthe preovula-
sidering the menstrual period fertile is the possi- tory estrogen rise on the production of cervical
,2 ,1,1 ,4 .15
D
L t'1 H .L.
o AD
Figure 9-1 : The basic system instructions are completed in the above chart.
134 The Medical and Surgical Pra cti ce of NaProTECHNOLOGY
.--~~~~~~~~~~~~~~~ INSTRUCTIONS ~~~~~~~~~~~~~~~----,

YOUR INST RUCTION S FOR USING THE SYSTEM WILL BE GIVEN TO YOU BY YOUR TE ACHER, FROM THE LIST OF
INSTRUCTIONS BELOW.
A. Always keep lo lho observatlonal roullne 1. Speclel Fertlllly lnstrucllons
B . Chart al !he end ol your day, every day, and record 1. Avold genital con1ac1 unlll good mucus Is presonl
lhe mosl lertllo slgn ol the doy (sublortlllly r•llenlS only)
2. Use days o grealesl quanllly and quellty end
c . Avold genital conlacl
flrst two days alterward
D. Daya ol lertlllly (use 10 echleve pregnancy) 3. Record the emount ol stretch ol lhe mucus
1. The menstrual llow ( 1·, 2", 3" etc.), (sublertlllly pallents only)
2. From beglnnlng ol mucus unlll 3 lull days pesl lhe PEAK 4. Record abdominal peln (AP), nghl abdominal paln (RAP),
3. 1 or 2 deys ol non-peak mucus pre-peak end lefl abdominal peln (LAP), (sublertll lly patlents only)
4.. 3 or more days ol non .. peak mucus pre-peak -
plu1 count3 J . Essenllal sameness quesllon - " la 1od1y oaaontl1lly tht
5. Any single day ol pe1k mucus - plu a coun1 3 11me 11 ye1t1rd1y?" - yes or no.
6. Any unueuel bleedlng - plua coun1 3 K . Yellow Stamp lnslrucllons
E. Deys ol lnlertlllly (use 10 evold pregnency) 1. Pro-peok - end ol lhe day. allernele deys
1. Dry deys pre-peek - end ol lhe day, alterna le daya 2. Po11-pe1k (alter 41h dey) - ond ol lhe doy, ellorneto daya
2. Dry deys pre-peak - end ol lhe day, every day 3. Poat·pHk (&flor 41h doy\ - ond ol lhe doy, every doy
3. 41h doy poat-peak - alw1y1 end ol the dey 4. Po1 t-pe1k (a lter 41h day - any11me ol tho day
(Predomlnont P1ttem Dry)
4. Dry deya poat-peek (alter 4th dey) - end ol the dey,
alternate daya 5. blsconllnuo use whon perlod atarts (BF)
5. Dry deys poa1-peek (alter 41h dey) - end ol the dey. L . 11 101ally breeel1eedlng, flrsl 56 deys eflor blrth ol
every day baby ero lnlortlle.
6. Dry days poet·peak (alter 4th day) - anytlme ol lhe day
8
7. ~'ln~TX.ªa?ílo'w ~ ~~9 .,'J~ri, ~ ~1eedlng at end ol M . End ol dey lnstrucllons epply through lhe flrsl normal
menstrual cycle.
F. Seminal Fluid lnstrucllon (seo manual)
N . Olhor (o.g. seminal lluld test, aecond wlpo 1011, BBT, ole.)
G. "Double" Peak
1. On P + 3 esk "doublo" peak quesllons
2. 11 post-peak phase greater !han 16 da ya In duratlon
and system used properfy 10 evold pregnancy.
anllclpele "mlssod" perlod lorT)1 ol "dooble" peak Figure 9-2 : Basic system instru ctions given to
3. Whon entlclpatlng "double' peak, keep lo the
end ol lhe lnlertlle deys end continua good observellons client on the back of the CrMS chart that is
H. When In doubl, conslder yoursell ol peak lertlllly end u sed .
count 3
mucus from the endocervica l crypts. As the e - during the pre- Peak phase of the cycle prior to
trogen rises, the estrogen stimul ates the crypts to the mucus fl ow.
produce cervical mucu s and , wi th that produc-
tion, there is a di scharge ofthe mucus to the open- D-3. Any One or Two days of Non-Peak M ucus Pre-
ing of the vagina . Because the mucus is associ - Pea k
ated with the preovul ato ry estrogen rise, it is also The CrMS is a prospective system by which the
associated w ith the timing of ovu lati on. Ovula- time offertility can be identifi ed. lt does no t rely
tion has been shown to occur from three days u pon past cycles or prev ious calcul ations. When
before the Peak Day through three days after it, one day ofnon-Peak mucus appears, it isj udged
thus the need to count a full three da ys after the to be fertile because it could be the beginning of
Peak Day. the mucus buildup to the Peak Day. Ifthere is one
day or two consec uti ve days ofnon-Peak mucus
Sorne have wondered why, when the three days during the pre- Peak phase of the cycle and dry
after Peak are dry, concepti on can occur. The an- days follow thi s pattern , experience has shown
swer to this question , outside of the occurrence that these days are infe rtile .
of ovulation during these days, is not com plete ly
understood at the present time. One theory re- One is considered to be pre-Peak until one has
volves around the effect ofthe cervical mucus.flow confldently identified the Peak Day. Confident
on the acidity ofthe vagina and , tbus, sperm sur- identifi cati on ofthe Peak Day usually takes at least
vival. The vagina is normally acidic (pH 3.8-4.2). one cycle. Therefore, non-Peak-type mucus that
When the cervical mucus fl ows through the va- occurs in the post-Peak phase ofthe first cycle is
gina, it tends to neutrali ze thi s acidity (the cervi- usually charted as fertile with white, baby stamps.
cal mucus has a pH of7.8-8.2). The seminal fluid
is also alka line . Thi s neutrali zation is undoubt- D-4. W hen There are Three or Mo re Days ofNon-
edly important in sperm survival. After the mu- Pea k Mucus Pre-Pea k, th ese Days are Fertile
cus flow stops, the vagina must go through a " re- Plus An Additional T hree F ull Days
covery phase" where its norm al acidity is recov- When three or more consecutive days of non-
ered after having been neutralized. How long this Peak-type mucus occur during the pre-Peak phase
takes, no one knows. But theoretically, the three ofthe cycle, the poss ibili ty that ovu lation has been
days after Peak could represent th at time . As a associated with thi s pattern increases anda count
result, sperm survival is still increased during thi s of three days fo ll ows the last day in which the
period oftime. No such ph enomenon would exi t non-Peak-type mucus occurs. It should be noted
Chapter 9: Basic CrMS lnstructions 135
here that if, for examp le, there are three days of E. Days of /nfertility
non-Peak-type mucus, a dry day and then three (Select to A voíd Pregnancy)
addi tiona l days ofnon-Peak-type mucus, the sec-
ond three-day mucu s patch should be considered Th e following days are used if it is the couple's inten-
separate ly. Thus, the count of three starts on the tion to use the CrMS as a means ofavoiding pregnancy.
dry day but is interrupted by the second non-Peak These instructions can be considered to be highly reli-
mucus patch, anda second three-day count must able indicators ofinfertility (Figure 9-2).
follow the last day ofthe second three-day mucus
patch. E-1. Dry Days Pre-Peak: End of the Day, Alternate
Days
D-5. Any Single Day of Peak-type Mucus is Fertile The dry days during the pre-Peak phase of the
Plus an Additional Count ofThree Days cycle are considered infertile (ifthey are not within
When the mucus is ofthe Peak-type, only one day a co unt of three) because they are an indication
ofmucus is necessary to stimulate a count ofthree that the ovary has not yet begun its progression
days. That one day would be considered fertile as toward ovulation . The infe1tility ofthe pre-Peak
would the next three days. This applies whether dry days, however, is always an end of the day
the woman is pre- or post-Peak unless she is on instruction. lt is necessary for the woman to ob-
special instructions for post-Peak Peak-type mu- serve the mucus throughout the entire course of
cus. It is common for the Peak Day to be a si ngle the day to be certain ofthe infertility ofthat day.
day of Peak-type mucus. There is the occasional
tendency on the part ofthe cli ent to think that the In the early phases of leaming, the client coup le
mucus, because it is limited in this situation, <loes is also instructed to use alternate days. This in-
not necessitate a three-day count. Therefore, the struction allows the user to gain confidence in her
presence of thi s specific instruction is necessary understanding of the seminal fluid. This means
to help users clarify that potential misunderstand- the utilization ofthe sem inal fluid instruction with
ing. the elimination of a seminal fluid discharge the
day following intercourse. However, ifa di scharge
D-6. Any Unusual Bleeding is Considered Fertile is observed the day fo llowing intercourse it should
Plus an Additional Three Days be observed on its merits as a discharge. The "al-
Bleeding that is thought to be other than a normal temate days" instruction is temporary, usually last-
menstrual period (unusual bfeeding) is considered ing only the first one or two cycles of use and is
in this system to be of Peak fertility andan addi- specifically designed to assist the woman to gain
tional three days offerti lity should be added after confidence in her observations without making
the last day of un usual bleeding. In addition , to errors in the early days of leaming.
the best ofthe user 's ability, whatever dryness or
mucus discharge is observed during this unusual E-2. Dry Days Pre-Peak: End ofthe Day, Every Day
bleeding episode should also be recorded. The The pre-Peak dry days are considered infertile but
reason that unusual bleeding is considered fertile only at the end ofthe day. Once the woman devel-
is because its occasional association with the tim- ops confidence in the use ofthe seminal fluid in-
ing of ovu lation. struction and the day fol lowing intercourse is con-
sistently dry (see discussion on semi nal fluid in-
The identification of unusual bleeding is left to struction), then the coup le can be moved to an
the woman s discretion and is meade with spe- every-day instruction. Intercourse can occur dur-
cific reference to a normal menstrual period. The ing each ofthe pre-Peak dry days at the end ofthe
menstrual period has typical flow characteristics day with this instruction.
to it that a woman quickly leams to identify. Bleed-
ing other than the normal menstrual period is dif- With pre-Peak dry days, the cli ent should be made
fe rent and is easily distinguished by the woman. aware that to use any other time of the day than
However, the teacher must teach the woman that the end ofthe day is to use the CrMS in a less effec-
this is to be her decision based upon her knowl- tive means to avoid pregnancy and a more effec-
edge of her menstrual periods . tive means ofachievi ng pregnancy. Having mom-
ing, aftemoon, early evening, or middle ofthe night
intercourse during these days should be considered
achieving-related behavior or use since the preg-
nancy rate wi ll be higher (see Chapter 12 and 13).
E-3. Fourth Day Post-Peak: Always End ofthe Day ab nom1a lities that may show up only during this
ln fertility begins after the Peak Day on the fourth period oftime. Secondl y, the mucus observatio ns
day post-Peak always at the end of the day. Thi s should be part of normal hyg iene beca use a stop-
instruction a ll ows an adeq uate time for the ovum and-start routine can lead to compl acency. Thirdl y,
to di sintegrate so that in fe rtili ty is indeed present. there is an occas ional time when a " double" Peak
lt also a ll ows the coupl e additi ona l time to ob- mi ght occur, and continued identifícation of the
serve the occasional res ump tion of Peak-type mucus all ows fo r that to be identified and the days
mucus which may occur on the fo urth day. observed as fertile in the appropriate fas hion.
E-4. Dry Days Post-PeakAfter the Fourth Day: En d E-7. Dry Days on the Light, Very Light or Brown
of the Day, Alternate Days (Black) Days ofBleeding at the E nd ofthe Men-
The dry days during the post-Peak phase of the strual Flow: E nd of the Day
cycle after the fourth day are considered in fertil e. When the woman has entered into the li ght, very
In the initial learn ing stages, because the woman light or brown (black) days of menstrua l tlow, she
needs to develop confidence in her identifi cation can identi fy the presence or absence of mucus with
ofthe Peak Day, an essentiall y pre-Peak instruc- confidence after a short peri od of time. If dry, those
tion is continued throughout the cyc le including days can then be used in the same fas hi on as any
post-Peak. Within thi s context, the end of the day other pre-Peak day. Ifthe days have mucus, they
and a ltem ate day instructi ons are present for the wo uld be days offertili ty. In other words, the fer-
same reasons as in E-1. tility or infertility ofthe these days at the tail end
of menstruation can be identified in the same way
E-5. Dry Days Post-PeakAfter the Fourth Day: End as the other pre-Peak days, by the presence or ab-
of the Day, Every Day sence of the mucus di scharge. Thus, the in struc-
As learning progresses and understanding of semi- tion fo r avo iding pregnancy on these days is a lso
nal fluid advances, the couple can quickly progress the same as any of the other pre-Peak dry days:
toan end of the day, every day instruction. This intercourse should occur at the end of the day.
means that ali of the dry days during the post-Peak
phase ofthe cycle are considered infertile (exclud- As a genera l guideline, thi s instruction should not
ing the three-day count) for an end of the day act be implemented until at least three menstrual fl ows
of intercourse. Thi s instructi on is considered an have been consistently, accurately, and confidentl y
interim , temporary instructi on as the coupl e de- charted.
velops an understanding of the sem inal fluid and
confidence in the Peak Day. In the woman who
cannot de ve lop confidence in the Peak D ay, this F. Seminal Fluid lnstruction
instruction wou ld be continued until such confí -
dence deve lops. Seminal fluid wi ll be di scharged follow ing intercourse
and may continue for up to 72 hours. Frequently, this
E-6. Dry Days Post-PeakAfter the Fourth Day: Any discharge has the visual and sensual characteristics of
Time ofDay Peak-type mucus. As a result, a wo man may experience
Once the woman has developed confidence in her confusion relati ve to the interpretation of her observa-
identification of the Peak Day (usually after two tions. Therefore, such observations may limit access to
or three cycles), the couple can be mo ved on to the CrMS as a system of avoiding pregnancy. In order
an instruction that allows intercourse any time of to solve these problems, the seminal fluid instruction
the day after the fourth day post-Peak. Such an has been deve loped.
instruction is based upon the concept that once
the Peak Day has passed so, too, has ovul ation .
SEMINAL FLUID INSTRUCTION (SFI)
Sorne have asked why observations should be con- 1. Urinate after intercourse (within one hour) .
tinued during this phase ofthe cycle if the woman
2. Bear down and do severa! Kegel 's exercises in
is confident that she is post-Peak . The answer re-
an alternating fashion .
volves around three concepts. First of ali there is
at times a di scharge during the post-Peak phase 3. Wipe until the seminal fluid is gone.
ofthe cycle which , ifrecorded, can give sorne in- 4. Observe ali discharge after the SFI on its mer-
sight into the presence of certa in gyneco logica l its.
1fa woman urinates following intercourse, bears down sperm have an opportunity to migrate throu gh the cer-
and does severa! (3-5) Kegel exerci es in an a ltemating vica l cana l to the fallopian tubes w here conception can
fas hi on, and wipes until the seminal fluid is gone, she occur.
wi ll usually not observe seminal fluid on the day fo l-
lowing interco urse. In this way, whatever is observed T he se minal fluid instructio n should not be viewed as
the fo ll owin g day (or, technically, anything after the contraceptive. The teacher shou ld know that once the
implementation ofthis in struction) ca n be observed on sem in al fluid has been depos ited in the vagina, there is
its merits as a discharge. Thus, if Peak-type mucus is no phy ical means of removing the semina l fluid that
observed , it is observed as Peak-type mucus and the would prevent a pregnancy. The instruction to wait thirty
appropriate instructions are followed. lf the discharge minutes before emp loying the SF I during the time of
is a non-Peak-type mucus di charge, the same can be fertility is an additiona l assurance that the in struction is
sa id . The basic principie is that whatever is observed is not contraceptive.
never assumed to be seminal fluid. 1t is always assumed
to be a cerv ica l mucus discharge and, then , can be The semina l fluid instru ction was developed, at least in
co unted on for the a ppropriate adm ini stration ofthe in- part, through a study of our own patients. Man y women
structio ns. In addition , if the discharge is absent, the ha ve a natural tendency to urinate fo llow ing intercourse
dry observation s which fo llow can be used accordingly. most like ly because ofa natural irritati o n ofthe urethra,
which occurs as the result of intercourse (see Chapte r
There are a number of features of this instruction that 15). Thus, the implementation ofthe SF I is a sta ndard-
require additiona l clarification. First of ali , the instruc- ized action whi ch many women a lready undertake.
tion is to urinate following intercourse within one hour.
The one hour time limit is given for two reasons. The There are a number of advantages to employ ing the
instruction specifica ll y attempts to avoid teaching seminal fluid instruction. First of ali , it prevents confu-
coup les to interrupt the act of intercourse immediately s ion developing in the observation ofthe mucus. In ad-
after its comp letion . A couple sho uld be encouraged to dition , it may ha ve the positive effect of decreasing the
use an approp riate time following intercourse to expe- incidence of bladder infect ion s. A nd fina ll y, many
rience the peace which can come at that point. How- women have reported that it eliminates the discomfort
ever, afte r one hour has passed, the seminal fluid in- of an additional discharge the day fo llowing intercourse.
struction is less effective. Second ly, the Kegel 's exer-
cise, which is used in this instruction , is a contracting
and relaxing of the muscles at the opening of the va- G. "Doub/e" Peak
g in a. The woman can detect these muscles by using the
muscles that stop and start the flow of urine. A fter uri- ln structions related to a " double" Peak sho uld be con-
nation , four or five of the Kegel exercises should be s ide red a basic system instructi o n. There may be times
performed and then the woman should gen ti y bear down . when such in struct ion wi ll be delayed beca use of the
This shou ld be done in an alternatingfashion . Exactly reprod uctive category in wh ich the client finds herself.
how often this exercise needs to be repeated is depen- For examp le, if a woman is breastfeedi ng totally, she
dent upon the indi vidua l woman and each woman must may not ha ve immediate use for the " double" Peak in-
" test" her own needs. Finally, the woman shou ld be instructi ons. In these s ituations, it is approp riate to delay
structed to wipe until the seminal fluid is go ne . Thi s the instructions until the approp ri ate time . Ho wever,
may require severa! wipes since the seminal fluid is very teaching ofthe " double" Peak instruction is fundamen-
si milar to Peak-type mucus. This process, however, as- tal to good teaching of the CrMS.
sures that the excess seminal fluid will be eliminated
with the use ofthi s in struction.
H. When in Doubt, Consider Yourse/f of Peak
The instruction should be used for coup les of normal Fertility and Count Three
and ab normal fertility. The coup le with an infertility
problem shou ld use this instruction so that confusion Whenever the coup le has doubt in regard to the use of
does not exist regarding observations that mark their the CrMS, they shou ld consi de r themselves of Peak fer-
true fertility. Because ofthis, it is a very important in- tility during the time of the doubtful period and count
struction for them. lt should a lso be pointed out that, three days of additio na l fert ility fo ll owi ng the si ngle
whenever the in struction is used during the time offer- day or last day of doubt. Th is is an important instruc-
tility, the coupl e should specifically wait thirty minutes tion that covers any unu sual happeni ng whi ch may cre-
prior to employi ng the instruction. Thi s assures that the ate confus io n in the clients' minds. Perhaps observa-
138 The Med ic a! and Surgical Pra ctice of NaProTECHNOLOGY
tions have been mi ssed or fo rgotten ; perhaps an un usua l In cycle E, the instruction related to a single day of Peak-
set of circumstances occurs that crea tes confusion. W hen type mucus is shown. T hree additiona l days offerti lity
doubt ex ists and the co uple intends to avoi d pregnancy, are added to any single day of Peak-type mucus that is
th ey should consider that time Peak fert il ity. ln add i- observed.
ti on, when such con fus ion ex ists, they should be in -
fo m1 ed to contact the ir FertilityCare™ Center so that In cycle F, the occurrence ofu nusual bleeding is shown.
the questi ons th ey ha ve ca n be answered and the doubt W hen unu sual bleeding is identifi ed, it should be con-
can be re lieved. sidered Peak-type fert ili ty and three additional days of
fert ili ty are added afte r the last day. Both cyc le E and
cyc le Fa lso show th e occurrence of a " doub le" Peak.
Examples of Basic lnstructions ---~
ln F igure 9- 1, six cyc les are used to portray the basic Achieving PregnanCY- -- - -------.
instructi ons of the CrMS. To interpret thi s chart, as well
as others, the mucus observations ha ve to be performed Figure 9-3 demonstrates the use of the CrMS to achieve
correctl y and then charted properl y. Good observations a pregnancy in a co uple of normalfertility. As a gen-
and charting are theflrst two of the basic instructions eral rul e, when a coup le uses the days of Peak fertility,
ofthe CrMS. the chances that th ey w ill achieve a pregnancy are ex-
tremely hi gh. A pre limin ary survey of 50 pregnancies
In cycle A, a typical cycle is shown. The menstrual pe- indi cated that over 75 percent ofth e couples (of norma l
ri od and fro m th e begirming of the rnucus until three fert i1ity) became pregnant in the very flrst cycle in which
fu ll days past the Peak Day are considered fertil e. The they used the days offertility.2 M ore stud y w ill be done
pre-Peak dry days and from the end of the fo urth day in this area to help us understand it better. This rein-
post-Peak until the next menstrual peri od are cons id- fo rces th e long-recogni zed preciseness of the CrMS fo r
ered infe rti le. A fter three months of good charting and identify ing fe rtili ty. Because ofthis, the concept of" tak-
observations and pro per reco rdi ng of such, the dry day ing a chance" has been made archaic.
on the fifth day of cycle A is a lso considered a pre- Peak
dry day and co nsidered in fert il e. If it is the coupl e's Wh ile the days off ertility li sted in the bas ic system in-
intention to avo id pregnancy, interco urse could occur structions have been deve loped to provide a system that
at the end of the day durin g the pre- Peak dry days and is highl y reli abl e to avoid pregnancy, sorne of the in-
at the end of the day on the fo urth day post-Peak or any structions are less effective when used to achieve a preg-
ti me ofth e day thereafter once the in teri m instructions na ncy. Thus, a specialfe rtility instruction has been de-
have been properly fo ll owed. veloped. It is (the lettering co1Tesponds to the fo ll ow-
up fo rm):
In cyc le 8 , the instructi on is shown rega rding one or
two days of non-Peak mucus. Any one or two days of l-2. Use th e Days of Greatest Q uantity a nd Q ual-
non-Peak mucus during the pre-Peak phase of the cyc le ity and First Two Days Afterward
are co nsidered fert ile and charted w ith w hite, baby Thi s ins tructi on was developed upon the asser-
stamps. However, th ey do not necess itate a count of ti on th at these days wo uld be th e days of hi ghest
three. Such occurrences of mucus are referred to as fert ility during the course of a menstrual cycle. ln
" rnucus patches." additi on, it is based upon experience in viewing
the CrMS in actu al appli cation and the scientifi c
In cyc le C, a non-Peak mucus patch of three days is data that suggests that ovulation occurs in 95 per-
shown. When three or more days of non-Peak muc us cent of cycles fro m two days before to two days
occur consecutive ly, three add itiona l days of ferti lity after the Peak Day. However, it should be made
are added after the las t day. c lear that, at the present ti me, there is no orga-
ni zed set of data which spec ifica lly proves thi s
In cycle D, the occun-ence ofan early ovulation is shown . in structi on. No netheless, ex perience shows that
With an earl y ovulati on, the pre-Peak phase of the cyc le an instruction such as thi s is worth whil e in ass ist-
is considerably shorter than usua l. In add ition, the mu- ing the coup le to focus their efforts in achieving
cus buildup to the Peak D ay beg ins earli er in the cycle, pregnancy at this particular time ofthe cycl e. Cau-
in thi s case on day 4 . With the appearance of mucus, tion should be exercised when providing thi s in-
fe rtili ty beg ins and the usual instructio ns are fo ll owed. structi on to couples who are using the CrMS to
avo id pregnancy. They must not be led to believe
that sorne of the da ys that are listed as da ys of A basic principie in teac hi ng the CrMS is that the op-
fertility can be observed as in fe rtil e. If the client tion to achieve a pregnancy is repeatedl y open to the
makes such an assumption, then the effectiveness couple and that their freedom to select the use of the
of the system will be considerabl y lowered as a system in thi s fashion should always be preserved. The
means ofavo iding pregnancy. This special ferti l- couple can use the CrMS effective ly, according to their
ity instruction is designed to augment the system 's intentions, only if they ha ve full knowledge of its use
effectiveness as a means of ac hieving pregnancy both as a system to achi eve as well as a system to avoid
and is ofspecial importance to cli ent couples w ho pregnancy. Thus, the statement is made that a good
may be experi encing infertility. achiever knows well how to use the CrMS to avoid a
pregnancy and a good avoider kno ws well how to use
the CrMS to achieve apregnancy.
-
~I -
..o -
AO OJllP oAo OAO 0..40 OAD º""º º""º IOAD OAO oAo OAD II
OAO oAo OA/) OAO o.qo OAD OAO
TI
PREGNANCY
TEST
+
OAD OAD ~o o;io º""" oAO oAD oAD OAO OAt> o.q.o
Figure 9-3: A chart depicting an achieving-related pregnancy.
References
1. Hil gers TW, Daly KD, Hil gers SK, Prebil AM: CREJGHTON 2. Hilgers TW, Daly KD, Preb il AM: C umu lative Pregnancy Rates
MODEL FertilityCare'" System : A Standard ized, Case Manage- in Pati ents with Apparently Normal Fert il ity and Fertility-Fo-
ment Approach to Teaching-Boo k 1: Basic Teaching Sk ill s. Sec- cused ln terco urse. J Reprod Med 1O: 864-866, J 996.
ond Edition. Pope Pau l V I ln sti tute Press, Omaha , Nebraska,
2002 .
---------~~6u,,10
Special lnstructions and Applications
T he instructions of the CrMS va ry from one repro-

ducti ve category to another. These variati ons are
used temporarily until the bas ic system instructi ons are
hav ior, whi ch becomes necessary with the institution
of a natura l means fo r fe rtili ty regul ati on. Generally,
th i di ffic ul ty sa lves itse lf as the c li ents begin to use
resta rted. The in structions fo r these va rious situatio ns and prac tice the system.
are referred to as special system instructions. They ap-
pl y to a group of special appli cati ons of the system. A The fo llow ing special considerati ons should be applied
thorough understanding of these instructions and ap- to those wo men and coupl es who are coming off birth
pli cations, is considered basic to the teaching of the contro l pill s.
system. Thi s chapter detail s th ese di ffe rent instructions
and appl icati ons. 1. T hey should stop th e pill imm ediately after the In-
troductory Sess ion . They should be ad vised at that
time that withd rawa l bleeding should be anticipated
within a few days a fter stopping th e pill .
Coming Off Birth Control Pills _ __ ~
2. The co upl e should avo id geni ta l contact fo r one
month or one cycle, whi chever is shorter, so confi-
A la rge perc e nt age of wo m e n co min g into a
dence may be establi shed.
CREIGHTON MODEL progra m will be coming offb irth
control pi li s or other hormone suppress ion (e.g ., Depo 3. The interva l between th e time of the withdra wal
Provera, orplant) large ly because of their di ssatisfac- bleeding and the first normal menses may be longer
tion with them. Generall y, little pro bl em is encountered than the wo man 's usual cycle interva l. In addition ,
in teaching them the system. Howeve r, a continuous the first norma l peri od will usua lly be heavi er than
di scharge coming fro m a cervical eversion can be ob- pill " peri ods. "
served . In additi on, sorne wom en coming off birth con-
4. The first ovul ati on fo llowing cessation of the pill
tro l pills will have prol onged peri ods of anovulation
may be more painful than usual.
fo llow ing the cessati on of the pi li s. But, the system can
be leam ed and used during thi s peri od of time. Perhaps 5. These couples should be advised to avo id achiev-
of most importance is th e modification of geni ta l being a pregnancy during the first th ree to six cycles
141
fo llow ing cessation of the pill. The reason for this infertile days through the first normal men-
is the poss ible increase in the freq uency of sponta- strual cycle.
neous abortion during thi s time. B. The basic pre-Peak system instructions ap-
6. The woman may be temporarily (or even perma- ply through thefirst normal menstrual cycle.
nentl y) anovulatory after stoppi ng the pill resu lting C. After the jirst normal menstrual cycle, the
in a long period of time in whi ch ovul ation and basic pre- and post-Peak system instructions
menses do not occur. Such an occurrence poses little apply.
difficulty in using the CrMS as a system to avo id D. lf anovulation occurs ora continuous dis-
pregnancy. The instructions relative to anovulatory charge is present, manage as for those two
states such as breast feeding shou ld be fo ll owed in conditions.
thi s circumstance. However, persistent post-pill ano-
vulation can be a cause of inferti lity and , if it per-
sists longer than six month s after cessati on of th e A Note About "Normal Cycles'_' ---~
pil l, the woman shou ld be referred to her physician.
7. Once the wo man begins cyc les, the pre-Peak phase When there is a retum of fertility afte r situations in
of the cyc le may be more variab le in length than which it has been suppressed (coming off birth contro l
usual. pi li s, depo provera, Norp lant, postpartum , breast feed-
ing, other anovul atory or o li goovulato ry conditions) , a
8. The post-Peak ph ase of the cycle may also be more period of time is genera lly necessary fo r the retum of
variab le in length during the initi a l months of chart- norma l fe rtil ity to occur. In most of these circumstances,
111g. normal ferti li ty will return w ithin three menstrual cycles.
9. If there is a de lay in the retum of ovul ation , the During this return, however, "double" Peaks and the
woman may experience a variable return of Peak- variable return of Peak-type mucus occur more com-
type mucus, typical of oli goovu latory and anovul a- monly. Thus, it is good to wait until norma l fe rtili ty
tory conditi ons. retu m s befare impl ementin g the full instructions of the
system.
1O. The usual fo ll ow-up sched ul e is genera lly adequate
for cou pl es coming off birth control pill s. The return of norm al fe rtility can be determined by the
11 . S ince avo iding genita l contact after topp ing birth presence ofa normal cycle. Following the pre-Peak in-
control pi li s may be initi ally diffi cult, it is often nec- structions (end of inferti le days for intercourse) through
essary to be particul arly supportive ofthese couples one normal cycle is a marker for adva nc ing the instruc-
and to assist them in the creation of other non-geni- tions. To do this , the teacher and user must know what
tal expressions of their love. is meant by a " normal cyc le. " A normal cycle is one in
wh ich the wo man has confidently identi.fied the Peak
12. Sorne post-pi ll coupl es w ill be anx ious about the Day and a usual menstrual flow has occurred 8 to 16
effectiveness of the CrMS and their ab ili ty to rec- days later.
ogni ze and interpret the mucus sign . Therefore, re-
assurance at thi s time may be necessary.
13. Tt should a lso be kept in mind that most ofthe prob- A Note on the
lems whi ch occur in this population of women re- Pre-Peak lnstructions -------~
late to the prev iou s use ofthe birth contro l pill and
are, in effect, due to aftereffects of its use (e.g. ir- Wben one refers to the use of the pre-Peak instruc-
regular ovulation and cervical erosion). It may be tions , it means that intercourse is limited to the end of
necessary to point out to the cli ent that the prob- the inferti le days and that the instructions related to both
lems are not specifically related to the CrMS so Peak-type and non-Peak-type mucus are recommended .
much as they are to the previous use of birth con- Ifthe couple has not passed the Peak Day and the couple
trol pills. As the couple progresses wi th the system intends to avo id pregnancy, the couple is still pre-Peak
and extends the time after cessation ofthe pill, these and intercourse should occur on inferti le dry days only
problems tend to correct themselves. and then on ly at the end ofthe day. Any mucus which
is observed is considered fertile and the instructions
14. Spec ial Instructi ons are fo ll owed as they wo uld apply to tbat type of dis-
A. If it is the intention to avo id pregnancy, in- charge.
tercourse should always be at the end of the
Chapter 1O: Special lnstructions and Applications 143
Breast Feeding ---------~ prepared to provide the mother with helpful hints that
will assist her in the establ ishm ent of a good milk sup-
Breast milk is the best nutritional source for the new- ply.
bom chi ld . Generally, total breast feeding can continue
for the first six month s after childbirth at which time A number of questions may be helpfu l in assess in g the
suppl ementation becomes necessary. At that po int, how- mother 's current breast-feeding status. Sorne of these
ever, partial breast freeding can continue for severa! questions have been incorporated into the Follow-up
months or even years. Prior to the ava ilability of the Form so that changes in the breast-feeding pattem can
Billin gs Ovulation Method and the CrMS, the breast- be documented from fo ll ow-up to fo llow-up.
feeding peri od posed cons iderab le difficulty for natu-
ra l methods of fert ili ty regulation . With the advent of 1. Have ni ght feedings been discontinued?
these systems, most cases can be handled w ith relative 2. Has milk or formu la been introduced?
ease . lmportant in understand ing the CrMS instructions 3. Have so lids been introduced?
as they ap ply to breast feeding is a clear understandin g
4 . Has there been any alteration in the baby 's nurs-
of the difference between total and partial breast feed-
ing pattern ?
ing .
5. Ha the mother been sick, on vacation, or under
Total Breast Feeding: stress?
Ali ofthe infant 's nutritiona l sustenance excepting
6. Is a pacifier being used?
occasional sips ofwater is received from the breast.
Partial Breast Feeding: The best time for the breast-feeding couple to be intro-
When supplemental f eeding is begun , as an addi- duced to the CrMS is during the tasi three months aj
tion to breast feedi ng, the woman is defined to be pregnancy. At that time, they should atte nd an lntro-
partially breast feed ing. Once this process begins, ductory Session and be provided a booklet, stamps, and
then weaning has begun. It should be noted, how- chart. In thi s way, they wi ll be prepared for th e post-
ever, that the wean ing process may occur rapidly partum period and they can proceed directly to a sched-
(overa few days) or slowly (over severa! months) . ule of follow-up appointments.
lndeed, th e beginning of weaning is not synony-
mous with the cessati on of breast feeding. Once the lochia decreases or disappears, the general
pattern for the CrMS in breast feeding is one of dryness
Suckling an in fa nt at the breast produces a physiolog i- associated wit h an occas ional patc h of either Peak-type
cal suppression of ovulation, w hich may continue for or non-Peak-type mucus. Once weaning begins, the
an exten ded period of time . The return of fert ility can woman should anticipate observing a variabl e return
occur before the return of menstruation. About one out of Peak-type mucus prior to the onset ofher first men-
of three women will ovul ate before menses retums. 1 struation. Normal ovul atory function returns over the
first three menstrua l cyc les. During these cyc les, sorne
Much of the success with the CrMS in breast-feed in g add itional variations in cyc lic function may be observed.
women is dependent upon the ab ility of the mother to As a ge neral rule, the basic system instruclions can be
estab li sh a good milk suppl y. With an erratic milk sup- used after the third menstrua l cycle has been compl eted.
p ly, the signs offertility may become more difficu lt to Occasionally, they can be introduced earli er. However,
interpret. A wo man should never be advised to stop there are certai n special instructions w hich apply to the
breast feeding so that her menstrual period can be al- breast-feeding woman and the instructions depend upon
lowed to retum . A good FertilityCare™ teacher will be whether she is totally or partially breast feed ing. A typi-
cal charting example can be fo und in Figure 10-1 .
Hints on lncreasing the Milk Supply
1. Get plenty of re st. If Breast Feeding:
l . The couple shou ld begin charting when the lochia
2. Drink extra fluid.
decreases (usua lly three weeks postpartum).
3. Nurse the child under restful and relax-
ing conditions . 2. The first fo ll ow-up scheduled should be at five
4. lncrease the frequency of nursing . weeks postpartum at wh ich time the couple will have
5. Nurse the child on demand . two weeks of charti ng to di scuss.
6. Nurse at night. 3. The usual fo ll ow-up schedu le shou ld be fo ll owed
7. Use the breast as a pacifier. through the first fo ur fo ll ow-ups and even further if
necessary. However, at th e fourth follow-up a spe- weeks to establi sh confidence in their obser-
cia l breast-feedingfollow-up schedule hould be re- vations. This is aguideline left to the teacher 's
viewed with the client. Generally, by the fo urth fo l- a nd use r ' s goo d judg ment. It s ho u ld be
low-up the principi es and concepts of the system , stressed that thi s in struction applies only ifthe
the observations and the chaiting are understood woman is totally breast feed ing. Once that pat-
we ll. At that time, the couple should be instructed tem is broken, this in structi on no longe r ap-
to return far fo llow-up 011 an eve1y -six-week basis pli es.
through the first three complete menstrual cycles .
B. lfthe couple does not come in to the program
4. Specia l 1nstruction s: Breast feed ing is essenti all y a until after the eighth-week postpartum, then
preovulatory condition. The fo ll ow ing spec ial 111- genital contact must be avoidedfor nvo weeks
structi ons app ly: (if complete/y dry during this time) or four
weeks (if mucus is apparent).
lfTotally Breast Feeding
A. Th e couple should consider the jirst eight C. lntercourse should always occur at the end
weeks (the first 56 tlays after the birth date ofthe tiay through the first normal menstrual
of the baby) infertile. cycle.
During this tim e, they should learn the
D. Th e basic pre-Peak instructions are appli-
CrMS o that at the eight-week point they can
cable during this period of time.
re ly u pon it. During these 56 days, the couple
should consider themse lves in ferti le regard- If Partially Breast Feeding
less ofwhat pattern of mucus is observed. The A . Th e first eight weeks after the birth date of
avo idance of genita l contact is necessary on ly the baby are not considered infertile.
at the time of th e postpartum bleeding (usu-
B. This couple should avoid genital contactfor
a ll y the first three to fo ur weeks) but, after
one month to learn the 11wc11s sign with con-
that time, the coup le does not have to avo id
fidence.
genital contact. Once the coupl e reaches th e
56th-day postpartum it may be necessary fo r C. If the couple is avoiding pregnancy, inter-
them to avo id genital contact fo r one or two course should occur a/ways at the end of the
H H l'1 l'1
Figure 10-1 : CrMS chart showing a postpartum , breast-feeding pattern .

Chapter 1O: Special lnstru ction s and Applications 145
day through the jirst normal menstrua/ cyc/e. The instructi ons ofthe CrMS allow the coupl e
to navigate th is pe ri od usually w itho ut great
D. Th e basic pre-Peak instructions apply.
di ffic ulty.
Sorne wo men w ho are breast fee ding w ill
Once Menses Returns have a conti nuous discharge. In cases such as
The re are specia l in structio n fo r th e breast-feeding that, yellow stamps may be appli cabl e. Ye l-
woma n o nce the menstrual peri ods ren1rn . She sho uld low stamps used during breast feeding are only
be informed of these in structio ns well in advance of a pplicable up to the return of the first men-
the return of menstruatio n so th at she can a ntic ípate strua /ion. T hey s ho uld not be used o nce
the m during this pe ri od of time. menses returns w ith out redefining their appli-
cati on.
1. Ovul ation usuall y returns w ithin the first three men-
strua l cycles.
Postpartum-Not Breast Feeding _ _ ---.
2 . The initia l cycles may be irregul a r a nd/or a novula-
tory. As a result, " doubl e" Peaks can be anticipated .
The ea rli est ovul ati on repo rted in the med ica! litera-
Th is is a fo rm of the variable return of Peak-type
ture fo ll owing c hildbirth in the abse nce of breast feed-
mucus .
ing has been at 27 days. 1 Therefore, no a uto mati c time
3. The pre-Peak ph ase ofthe cycle may be va ri able in of infe1i il ity can be presupposed in thi s gro up o f wo men.
le ngth. These coupl es sho uld cons ide r themse lves fe rtil e from
the tim e of the c hild 's birth . In additi on, these wo me n
4 . The post-Peak phase of the cyc le may be shorter in
may have rece ived a drug to suppress lactati on.
length.
5. Specia l Instructio ns The best time fo r the coup le to rece ive their introduc-
A. Th e basic pre-Peak instru ctions apply ti o n to the CrMS is durin g the las/ three months ofpreg-
through the jirst normal menstrual cycle. nancy. At thi s time, they rece ive their booklet, stamps,
The breast-feed ing coupl e sho uld be notifi ed, and chart with th e anti cipati o n of beg inn ing fo llow-up
well in ad vanee of its occurrence, that when in the ea rl y postpartum period. The fo ll owing instruc-
wean ing co mm e nces , a variable return of ti o ns are used fo r thi s reproducti ve category (a typica l
Peak-type mucus may be experienced. Thi s is c harting exampl e ca n be fo und in Fi gure l 0-2):
due to the ri sing and fa lling leve ls ofestrogen
w hich occur during thi s peri od of time w ith 1. Charting sho uld begin when th e lochi a decreases,
the return of ovul ato ry fun cti on. As th e estro- usually three to fo ur weeks fo ll ow ing deli very.
gen le ve ls rise, Peak-type mucus is produced .
2 . The coupl e sho uld avo id geni ta l contact fo r the first
As they fa ll , thi s type of mucu di sappears.
L H H /11. .L
OA O 2AD
Figure 10-2: A CrMS chart depicting a postpartum , no! breast-feeding pattern .

four weeks of charting so the woman can develop B. The basic pre-Peak instruction s apply
confidence in her observations. through thefirst normal menstrual cycle.
3. The firs t fo ll ow-up should be schedul ed for two C. After the first normal menstrual cycle, the
weeks after charting has begun. basic pre- ami post-Peak instructions apply.
4. The us ua l fo llow- up schedul e should be fo ll owed .
Whenever a wo man suffers a miscarriage, ectopic preg-
5. Specia l Instructions nancy, or induced abortion, there is a sense of loss that
A. If it is the intention to avoid pregnancy, info ll ows. For each of the situati ons, the woman, her hus-
tercourse should a/ways be at the end of the band and even mem ber ofthe fa mil y wi ll go thro ugh
infertile days through thefirst normal men- a grieving process . With the FertilityCare™ teacher
strua/ cycle. bei ng aware of that process, support is prov ided to th e
couple during thi s period of ti me.
B. The basic pre-Peak instru ction s apply
through the first normal menstrual cy cle.
C. A/ter the jirst normal menstrual cycle, the Single - Not Genitally Active _ _ _ _~
basic pre- and post-Peak instructions apply.
FertilityCare™ Centers often see yo ung women who
In th is re productive category, ovulation may occur ap- are not genita lly acti ve w ho come to learn the CrMS .
proxi mate ly 35 percent of the time prior to the onset T here can be a va ri ety ofreasons w hy they wo uld li ke
of the first me nstruatio n. T hu s, one cannot simp ly wa it to chart thei r cyc les. lt could be fo r medi ca! reasons
until the return of the first menstrua l period to beg in such as dys menorrhea , irregul ar cycles, premenstrual
mon itoring one 's fert ili ty. syndro me or recurrent ovari an cysts. Someti mes, they
have been placed on birth control pill s fo r the treat-
A continuous m ucus di charge can beco me apparent ment of a medica! conditi on and they want a non-birth-
in the earl y postpartum peri od . [fit does, the user may contro l-pill eva lu ati on and treatment. In other cases,
be a candid ate fo r th e u e of th e pre-Peak ye ll ow they wo uld li ke to fos ter a respect and appreciation of
stamps. the ir fe rtility.
In such cases, the CrMS makes a di stinction between

Post-Abortion __________-, the adolescent w ho is not genita ll y acti ve and the single
woman who is not genita lly active. By convention, the
Women w ho have had a spontaneous abortion (m is- ado lescent wo uld be conside red 17 years of age and
carri age), ectopic pregnancy or induced abortion w ill under and th e sing le woman wo uld be considered 18
have very littl e suppress ion of ovu lation after the loss . yea rs of age and o ld er. 1n both situati ons, th e teac her 's
Ov ul ation can return within two weeks. Therefore, the responsibility is to ex pl a in the CrMS to the ir spec ifi c
fo ll ow ing in stru ctions a ppl y to thi s reproduct ive cat- appli cation. Discussin gfertiliry appreciation with them
egory: is important so that they understand how the system
fu rthers their understanding of how their body works
1. Charti ng should begin when the bleeding decreases, and fun ctions. The CrMS actua ll y speaks to wo men
usua lly w ithin one week fo ll owi ng th e inc ident. about how their body wo rks and fun ctions w ith spe-
ci fic re levance to fert ili ty and wo men 's hea lth. lt helps
2. The couple should avoid genital contact for the firs t
them develop a language of the body, w hi ch helps de-
four weeks of charting so the woma n can deve lop
velop self-esteem and se lf-respect.
confidence in her observations.
3. The first fo ll ow-up should be scheduled fo r two When working w ith wo men wh o are not genitally ac-
weeks afte r charting has begun . tive, it is th e CREIGHTON MODEL teac her 's and
physician 's responsibi 1ity to affirm and support their
4. The us ual fo ll ow-up schedule shou ld be fo ll owed .
chastity.
5. Specia l Instructions :
A. lf it is the intention to avoid pregnancy, in-
tercourse should abvays be at the end of the
infertile days through thefirst normal men-
strual cycle.
Chapter 10: Special ln structions and Applications 147
Premenopause practica! point of view.

(40 Years or Older) - - -- - - -- - - -
The CrMS is a great advance for co upl es in this age
The menopa use is defined as the cessation o.fthe men- group. lt wi ll give them the necessary ecurity th at they
strualflow. lt is dueto the normal aging process ofthe des ire in their fam il y pl anning. This group of women
ovaries that decreases their functioning capabil ity. The is , in fact, one ofthe easier group (from a system point
average age of the menopa use is around 49 years, but of view) to teach . Alth ough th e menstrual cyc les tend
the norma l ra nge can be from 37 to 56 years of age. 2 to become shorter and more irregular, the instructions
The time leading up to the menopause is cal led the pre- wi ll carry them through with out much difficulty. The
menopau se. greate t difficulties wi ll relate to the fear ofpregnancy
and developing confidence in the sy tem and in them-
The premenopause is a time of adjustment for many se lves.
women and the ir fam ili es. Not only is there a change in
hormones with the subsequent loss of fertility, but the The fo ll ow ing are important to teaching cons iderations
fami ly is usually undergo in g changes at the same time. for thi s reproductive category (a typical charting ex -
Thi s is a ti me when the children u ually begin to leave amp le can be fo und in Figure 10-3):
home. In add ition , a woman 's husband may be reach-
ing a point of frustration with his work knowing he is 1. The usual follow-up schedu le is genera JI y adequate.
reaching an age where changes are not easily made.
2. The cycle patterns may be irregul ar and/or anovu-
The many adjustments that are necessary at this period
latory.
of a woman's li fe may create ten sions and anxiety. In
add ition, fear of pregnan cy may add to the increasing 3. The mucus patterns may be more irregular with
anxiety. Not all women wi ll experience these tensions, more mucus "patches" anda variable return of Peak-
but it is a group that requires a special sensitivity to type mucus observed.
these needs.
4. The pre-Peak phase of th e cyc le may be shorter than
usual. Therefore, it is necessary to watch fo r early
For the purposes of definition, premenopause is defined
ovul at ion by being certai n to observe for the pres-
to appl y to any woman who is 40 years o.fage or ofder.
ence or absence of mucus during menses.
This is an arbitrary, working definition based on ly upon
age and not a specific physiological change. However, 5. The po t-Peak phase may be irregular in length from
it is a simple defin ition that has worked we ll from a cycle to cycle.
1.1 /4 15 16 17 IX 29 .10 .11 .12 .l.l .14 .15
oAO oAo o AO o AO OAO OAO o AP ,;i,.. ¡ OAO .;l..t :l. 040

OAO
I T
Figure 10-3: A premenopause pattern charti ng using the CrMS .

148 Th e Medical an d Surg ical Pract ice of NaProTECHNOLOGY
6. Unus ual bleeding may be more frequently ob erved Sometimes th ese women experience regrets fo r baving
so the in structions regarding unusual bleeding ma y had a steri li zation anda discussion as to w bether or not
be more applicab le. they wou ld ever consider having a reversa! can be he lp-
fu l in the teach ing situati on. Furthermore, it is impor-
7. The menopause has been reached when one year
tant to ex pl ain to them that the CrMS can be used as a
passes without a period .
means of fa mi ly plann ing because there is now a re-
8. Jn structions ported two percent fai lure rate fo r tuba! ligation over
A. Basic system instructions apply the first ten yea rs ofits use.3 lt may be difficult although
The premenopausal woman may experi- not impossib le for them to avoid genita l contact during
ence " hot tl ushe ." These tlushes are a sud- the time offerti lity, but su pport with instruction on non-
den fee ling ofwarmth, sometimes associated gen ital forms of sexua l interaction is often very help-
with sweating and tlushing ofthe skin , which ful.
begin in the head , neck and upper chest. They
last for onl y a few seconds (rarely longer than
one minute) and th ey may occur severa! times lnfertilitY- - - - - - - - - - - - - . .
a day or infrequentl y. Genera ll y, they run their
natural co urse, disappearing after severa ! FertilityCare™ teachers w ill see a number of cli ents
month s. Th e cause of"hot tlushes" is noten- who ha ve experienced difficulties in achiev ing a preg-
tirely under tood , but they are definitely re- nancy. The CrMS offers hope to coup les with infertil-
lated to decrea sed levels of estrogen hor- ity problems because it ass ists them in identifyi ng the
mones . Therefore, "hot tlushes" and dry days Peak time oftheir fertility. The CREIGHTON MODEL
tend to go together. is the most precise system currentl y ava il able for iden-
Physicians wi ll often prescribe an estro- tifying the Peak time offertility. The CrMS thus assists
gen supp leme nt to contro l the " hot flushes. " in the treatment of the infertility problem and can be
These estrogen hormones may stimul ate the very he lpful in the overa !! evaLuation of the in ferti lity
production of Peak-type mucus . problem itse lf.
IM PO RTANT
lf a woman in this age group develops un- When an infertility c li ent is undergoing an evaluation,
usual bfeeding, a continuous discharge, in- the CrMS can be used in a number of ways. It is ex -
termenstruaL bleeding, or a discharge that is tremely helpful at targeting the cycle properly so that
malodorous, the teacher will advise her to see various tests can be performed accurately and repro-
her physician. ducibly. The postcoitaL test should always be done w hen
the best mucus is observed. Jf this test is done at the
wro ng time ofthe menstrual cycle, th e information ob-
Post-Sterilization - Medica! Reasons::::¡ tained w ill be in error. Hysterosalpingography,proges-
terone LeveLs, and endometrial biopsies can ali be timed
As the CrMS has developed over the yea rs to become prope rl y by a n und ers ta ndin g of the CrMS . The
highly applicab le to a va riety ofwomen's health prob- hystersalpingogram should be done witbin the week
lems, women w ho have been steri lized w ill often come fo ll ow ing menstruation . The progesterone Leve/ should
to seek in struction . In th is case, they ma y have had a be drawn during the mid-luteal phase ofthe menstrual
tuba! ligation or they come after their husbands ha ve cycle. In order to do thi s in a way whi ch is reproduc-
had a vasectomy. In such cases, the basic system is ible from one cyc le to the next and fro m one wo man to
taught to them. the next, the progesterone leve! should be drawn on
the 3rd, 5th, 7th, 9th, and 11th day following the Peak
When teaching women such as this , post-tubaL liga- Day during the first cycle of eva luation and on the 7th
tion syndrome is discussed with them . This cond iti on , day fo llowing the Peak Day on a li subsequent eva lua-
wh ile continuing to be somewhat controversia!, inc ludes tion cycles. When the proges terone leve ] is drawn in
menorrhagia, premenstrual syndrome (PMS), and pe l- this fashion , it all ows for a simpl e and yet reproducib le
vic pain. lt is thought to occur in a fa irly large percent- means through w hi ch a mid-lutea l progesterone leve!
age of women who ha ve had previous tuba! ligations. can be obta ined . T he endometrial biopsy is genera lly
In many cases, we ha ve found that the abnormal bleed- done one or two days prior to the beginning of men-
in g is the result of hormonal dysfu nct ion and PMS struation. By having a know ledge of the length of the
symptoms can be associated with it. post-Peak phase , a properly timed premenstrual en -
dometria l bi opsy can be ca lculated in adva nce by count-
Chapter 1O: Speci al lnstructions and Appl ications 149
ing the appro pri ate num ber of days from the Peak Day. vix and thu s no cervical mucus production. At
the present time it woul d appear th at the latter
In additi on to the above, know ledge ofthe muc us sign reason is by far the mo t frequent cause of dry
is ex tremely helpful in further understanding the infe r- cyc les (Cycle C: Fi gure 10-4 ).
tility problem itself. Much research has now been com-
pl eted in thi s area. lt is our fee lin g th at th e CrMS repre- B. Lim ited M uc us C ycles : In limited mu cus
sents one ofthe greatest adva nces in th e study of infe r- cyc les, the amounl of the cervica l mucus di s-
til ity and the last 30 years and th at, as it beco mes more charge is signiflcanlly reduced. Lim ited mucus
ava il abl e, it will be the cornerstone to every in fe rtility cyc les are genera lly associated with inadequate
eva luati on. A number of pattern s ca n now be described ovarian functi on. The preovul atory leve! of es-
as a preliminary look at the use ofthe CrMS in the eva lu- trogen is low and , therefore, the stimul ation of
ati on of infertility. These patterns include dry cyc les, the cerv ix is reduced. Thi s mechani sm, at the
limited mucus cycles, and regul ar mucus cycles. (Typ i- present time, appears to best ex pl ain the reduc-
ca l charting examples ca n be fo und in Figure 10-4). tion in mucus producti on. Often, in these cycles,
the post-ovul atory progesterone leve! will be
A. Dry Cycles : A dry cyc le is one in whi ch th ere is markedl y reduced (Cyc les A and B: Fi gure 10-
no cervical mucus di scharge observed th ro ugh- 4).
out th e course of the menstrual cyc le. The ca use
of such a cyc le is not entirely understood. At C. Regular M ucu s Cycles : In reg ul ar mu cus
the present time, two potenti al ca uses appear to cycles, the cervica l mucus cyc le is more normal
ex ist. In the first, despite norma l preovu latory in its appearance (Cycles D and E: Figure 10-4)
estrogen levels, the cervix does not respond with A regular mucus cycle may be associated with
the producti on of cervica l mu cus. Thi s might a number of other probl ems. In cyc le D of Fig-
occur when the cervix has been previously dam- ure 13-4, a regular mucus cyc le is shown in as-
aged, such as fo ll owin g cryosurgery or cone bioc iation with a short post-Peak phase. Thi s par-
opsy. Dry cyc les mi ght also res ult from inad- ticular cycle was monitored with hormone eva lu-
equate production of estrogen from the fo il icle ation and the length of !he /u/ea/ phase was
resulting in inadequate stimulation of the cer- shown to be inadequately shorl. In cyc le E, a
30 31 32 33 34 35
Figure 10-4: A CrMS chart showing various infertility patterns.

regul ar mucus cycle is present in assoc iation B. Record the amount of stretch of the mucus
with a norm al length post-Peak phase. ln cyc les (one inch, two inches, three inches, etc.) .
such as thi s, the in fe rtili ty may be due to a low Every infertility client should record how
sperm count. much the mucus stretches when it is "stretchy."
Thi s g ives the teacher som e indication ofthe
T he limited mucus cycles are the most frequently ob- amount of mucus that is present. Obviously,
served. The second most comm onl y observed patterns more stretch means more mucus. However, a
are regul ar mucus cyc les. The least freq uentl y observed teacher sho uld know that eve n a ve ry small
pattern is the dry cyc le. These patients may become amount of mu cus may occas ionall y stretch 2
pregnant w ith a spontaneo usly occurring limited mu- or 3 inches. Thus, it is al so he lpful to as k the
cus cyc le. However, the prognos is is wo rse than fo r cl ient if the amount ofth e mucus was great or
those cli ents with limited mucus cyc les . Medica ! treat- small.
ment ho lds hope fo r success in those pati ents who do
C. Record abdominal pain (AP) , right abdomi-
not become pregnant. The mucus cyc le can be objec-
nal pain (RA P), and left abdominal pain
tively assessed w ith the use of the 3C' S Mucus C ycle
(LAP).
Scoring System (see C hapter 14).
Thi s guideline all ows for the record ing of
intennenstrual pain in these cli ents. There is
T he fo ll ow ing are important considerati ons fo r thi s re-
no c lear ev idence at the present time that this
producti ve category:
ass ists in achi ev ing pregnancy, but such a re-
cording does ho ld sorne hope fo r the future in
l . The usual fo ll ow-up schedule is generally adequate.
helping infe rtili ty cli ents.
2. The in fe rtility coupl e should avo id ali genita l con-
D. Use the days ofgreatest quantity and quality
tac t during the fi rst complete menstrual cycle. lt is
and the first two days a.fterward.
as important to the infe rtili ty co uple as it is to the
Clients will often ask whi ch days are " best
couple that w ishes to use the system to avo id preg-
to use." Thi s guideline is helpful in fo cusing
nancy to have confidence in the identifi cati on of
attention on those days which shoul d be the
the mucus. Thus, avoidance of genita l contact is nec-
most fe rtile . It is not yet known whether a
essary. lt is also he lpful to eva luate the mucus cyc le
coupl e who has intercourse at the exact time
itse lf. Unlike the in structi ons fo r other coupl es, the
that the mucus is observed has a greater chance
" month" of avoiding genita l contact begins at th e
of becoming pregnant.
start of the menstrual cyc le and goes th ro ugh one
compl ete cycle so that an adequ ate eva luati on of
lnfe rtility cli ents are ex peri enc ing a very difficult prob-
one mucus cycl e can be obtained. lfthe coupl e has
lem . It is important that the FertilityCar e™ Practitio-
infe rtili ty associated w ith long menstrual cycles, this
ner (FCP) and Instructor (FCI) be sensiti ve to their
does not appl y. ln such situ ati ons, one month of
needs and special situati on. Th e FertilityCare™ teacher
avo idin g genita l contact is reco mm ended and it ca n
is in an excell ent pos iti on to offer sound advice, wh ich
begin at any tim e.
is mora ll y and ethi ca ll y responsibl e, to cli ents in thi s
3. An ex pl anati on of the CrMS as it relates to in fe rtil- reproducti ve category. In additi on, the FertilityCare™
ity should be provided each cli ent in thi s reproduc- teacher is in an excell ent positi on to be a hea lth educa-
tive category. tor and consumer advocate fo r couples in thi s repro-
ducti ve category.
4. Spec ia l ln stru cti ons
A . Avoid genital contact until good mucus is
present.
Seminal Fluid lnstruction -----~
Thi s guideline is fo r co upl es w ho have
regular cyc les and its purpose is to build up
Semina l fluid will be di scharged followin g intercourse
the spenn co unt. In addi tion, it has th e advan-
and may continue fo r up to 72 hours. Frequently, thi s
tage oftakin g the pressure off the coupl e who
di scharge has the vi sual and sensual characteristi cs of
fee l as if they must " perfo rm" when th eir fer-
Peak- type mucus. As a result, a woman may experi-
tility arri ves. lfthe co uple avo id s geni tal co n-
ence confus ion with the interpreta tion of her observa-
tact during the pre-Peak days of in fe rtility,
tions. Tn addition , such observati ons may limi t access
their des ire to ha ve intercourse at the tim e of
to the CrMS as a system of avoiding pregnancy. ln or-
fertili ty will be in creased.
der to so lve these pro bl ems, the seminal fluid instruc-
Chapter 10: Special lnstructions and Applications 151
tion (SFI) has been deve loped.

Seminal Fluid lnstruction (SFI)
[fa woman urinates fo ll owing inte rcourse, bears down 1. Urinate after intercourse (within one hour).
a nd <loes severa! (3 to 5) Kege l exercises in an alternat- 2. Bear down and do severa! Kegel 's exer-
ing fas hi on, and wipes un til the semina l flu id is go ne, cises in an alternating fashion .
she w ill usually not observe seminal fluid the day fo l- 3. Wipe until the seminal fluid is gone .
low ing interco urse. In thi s way, whatever is observed 4. Observe ali discharge after the SFI on its
the fo llowing day (or, technica lly, anything after the merits.
impleme ntati on ofthi s instructio n) can be observed on
its merits as a di scharge. Thus, if Peak-type muc us is
observed , it is o bserved as Peak-type mucus and th e sperrn have an o ppo1t uni ty to migrate th ro ugh the cer-
appropriate in structions are fo llowed. lf the di scharge vical ca na l to the fa ll opi an tu bes w he re conceptio n ca n
is a no n-Peak-type mucus di scharge, then it is cons id- occ ur.
ered no n-Peak type. ln additi o n, ift he discha rge is ab-
sent, th e dry o bservations whi ch fo llow can be used The SFI sho uld not be viewed as contraceptive. The
acco rdingly. The basic principie is that w hateve r is ob- teacher shou ld know th at once the semina l fluid has
served is never assumed to be seminal fluid but a lways been depos ited in the vagina, the re is no phys ica l means
ass umed to be a cervica l mucus di scharge. ofremoving the seminal fluid that wo uld prevent a preg-
nancy. The in struction to wait thi rty minutes before
There a re a number of fe atures of this instructio n that employi ng the SFI during the time offertili ty is an ad-
require additio nal expl anati on. First of ali , the in struc- ditional ass urance that the instruction is not contracep-
tio n is to urinate fo llowi ng interco urse within one hour. ti ve .
The one hour tim e limi t is g iven for two reaso ns. The
in struction s pec ifi ca lly atte mpts to avo id teac hin g The teacher w ill be sensiti ve to those coupl es w ho may
couples to interrupt the act of inte rcourse imm ed iately react negatively to thi s in struction. ln o ur experi ence,
after its compl etio n. A coupl e shoul d be encouraged to thi s is an infrequent occurrence. The co uple has the
use an a ppropriate tim e fo ll ow ing intercourse to expe- cho ice not to use thi s in struction if they so des ire. How-
rience th e peace whi ch can come at th at po int. At the ever, if tbey choose not to use the SFl, then, acco rd ing
same time, afte r o ne ho ur has passed, the semi nal fl uid to instructio ns, whatever di scharge is observed after in-
instructi o n <loes not work. Secondl y, the Kege l 's exer- tercourse is o bserved on its me rits as a cerv ica l mucu s
cise, whi ch is used in thi s in stru ction, is a contracting d ischarge.
and rel ax ing of the musc les at the opening of the va-
gina. The woman can detect these muscles by usin g the T he SFI was deve loped, at least in part, throug h a stud y
muscles whic h sto p and start the fl ow of urine. After of o ur own patie nts . Man y wo men ha ve a natu ra l ten-
urinatio n, four or fi ve of the K ege l exerc ises shoul d be dency to urinate fo ll ow ing intercourse most likely be-
perfo rm ed a nd the n the wo ma n sho uld gentl y bear ca use of a natura l irritatio n of the urethra, w hi ch oc-
down . Thi s should be do ne in an alternating fas hion . curs as the res ul t of intercou rse (see C hapter 15). Thus,
Exactl y how often thi s exercise needs to be repeated is the impl ementatio n of the SFI is a standard izatio n of
dependent upon the ind iv idual wo man and each wo man an acti o n already performed by the maj o rity ofwomen.
needs to " test" her own needs. Lastly, the woma n shou ld
be instructed to w ipe until the semin al flui d is go ne. T here are a num ber of adva ntages to em ploying the
Thi s may require severa! w ipes s ince the semina l fl uid SFI. F irst of ali , it prevents confusio n with the obser-
is very sim ila r to Peak-type mucus. Thi s process, how- vatio n ofthe mucus. In additi on, it may have the pos i-
ever, ass ures that the excess semina l fluid w ill be elim i- tive effect of decreas ing the inci dence of bl adder in-
nated w ith the use of thi s in structi on. fect ions. And fi nall y, many women have reported that
it eliminates the d isco mfo rt ofan addi tiona l discharge
The instructi on sho uld be used for coupl es of norma l the day fo ll owing inte rcourse.
as well as abno rma l fertili ty. T he coupl e with an infer-
tility problem should use thi s in structi on to e liminate As previo us ly stated, the impl ementati on of the bas ic
confusio n regarding observa ti ons that mark thei r true system instructi ons evo lve over a period of time. As a
fe rtili ty. Whenever the instructi on is used d uring the general guideline, it requi res three to fi ve acts of inter-
time of fe rtility, the coupl e w ith an infertili ty proble m course with the successfu l empl oym ent of the S Fl to
should be spec ifica ll y in structed to wa it thirty minu tes recommend advancement of the system instructi ons.
pri or to e mploy ing the instruction. Thi s ass ures that the In cyc le A of Fig ure 10-5 , the couple has avoi ded geni-
Figure 10-5: The seminal flu id instruction charted with the CrMS .
tal contact. Beginning on day seven of cycle B, the in- Special Instructions
struction is employed as an end of the day, alternare 1. lf confident that fluid is aro usal fluid, then it may
day instruction (if it is the ir intention to avoid preg- be ignored.
nancy) and the SFI is impl emented. The d ischarge that
2. lf ever uncertain, consider itfertile and observe it
is observed the day fo llowing intercourse is observed
on its merits.
on its merits. Thus, the non-Peak mucus days, which
are seen on days 8 and 1O, are observed as fertile but
without a count of three. On day 12, a Peak-type mu- As a genera l rule, aro usal fluid poses very li ttle diffi-
cus discharge is observed and the co unt of three fol - culty for users ofthe CrMS. lt is a fluid wh ich is very
lows it. End -of-the-day intercourse continues . The cha racteristic in its appeara nce and it is classically as-
Peak-type mucus discharge observed on day 24 fol- soc iated with some form ofsex ua l stimul ation. The as-
lowing an act of intercour e is observed as Peak fertil- surance that a particular di scharge is arousa l fluid shou ld
ity with a count of three. Finally, on days 28, 30 and be verifi ed th rough di alogue between the teacher and
32, acts of intercourse emp loying the SFI are fou nd to the cl ient at the time of th e fo ll ow- up. This ass ists the
be successfu l in eliminating the excess seminal fluid client in developing confi dence in the observation of
and dry days are observed fo llowing it. In the next cycle arousal fluid. lfthere is ever any uncertainty, it should
w ith the successful implementation of the SF! , end of be observed on its merits and consi dered ferti le with
the day, every day intercourse du ring the pre-Peak phase the appro pri ate instructio ns fo llowed.
of th e cycle is used.
Some helpful hints which may assist the user in man-
aging arousal fluid: If such a discharge is observed in
Arousal Fluid lnstruction -----~ association with the stimulation of breast feeding, the
wo man can be instructed to observe for the mucus ap-
Arousal fluid is a lubricativejluid that comesfrom the prox imately one hour before or one hour fo ll owi ng an-
Bartholin s glands , which are located in the back por- ticipated breast feed ing. Also, ifsex ua l aro usal occurs,
tion of the opening of the vagina. This flu id is pro- mucus observation can be de layed for one or two hours
duced in response to e ither physical or mental sexual following the aro usa l. Genera ll y, by that time, the
stimulation. The fluid is designed to fac ilitate inter- arousa l fluid will have dissipated and wi ll not be ap-
course. Arousal fluid has different characteristics than parent wh ile cerv ical mucus di sc harge will still be
e ither sem inal fluid or cervical mucus discharge. First present. Such helpful hints can be used in cases w here
of ali , it has less substance to it. lt tends to dissipate this may pose a problem.
quick/y and disappear. lt loses its stretch quickly. lt tends
to di sappear by an hour or so following stimulation.
The fo llowin g instru ction is des igned for use in man-
aging arousal fluid.
Early Ovulation _________~ A variety of different physical or emotional stresses may

cause "double" Peaks. A complete list cannot be made,
Ovulation may occur early in the menstrual cycle and, however, the following are common examp les of acute
ifthis happens , the appearance ofthe mucus will occur stress : sickness, strenuous activity, change ofjob, mov-
earlier as well. This is a rare occurrence but becomes ing, bereavement, major decisions, holidays, visiting
more frequent as the woman becomes older. Thus, it is relatives, travel , weddings, exams, and so forth . It is a
particularly important in the premenopausal age group. situation that can happen to any woman , and the "sec-
However, it is viewed as a sp ecial circumstance with ond" Peak generally occurs after the stress is relieved.
wh ich ali couples leaming the CrMS should be thor- Actuall y, such a "double" Peak may be a protective
oughly familiar. mechanism at work, thus reducing the chances of be-
coming pregnant under stressful situations.
It is easy to manage an early ovulation. This is done by
making good observations of the presence or absence The use ofthe CrMS assists coup les in becoming more
of mucus during the light, very light and brown days at aware of their daily stresses. In American society, this
the end ofthe menstrual flow. When mucus is observed, is particularly important since many people are under
it is observed on its merits and appropriate in structions great degrees of stress often witho ut even realizing it.
are fo ll owed (a typical charting example is found in It is important that every couple realize how to antici-
cycle B, Figure 10-3). pate a " double" Peak. The signs are :
1. Current or approaching stress.

"Double" Peak----------~
2. The Peak buildup or Peak Day appears unusual.
A "double" Peak can be defined as the occurrence of 3. The woman is 16 days or more post-Peak
two Peak-type mucus buildups which occur in the sorne ("missed" period).
menstrual cycle. In addition, there is a gap greater than
4 days between the appearance of the first Peak Day If the couple beco mes aware of current or approaching
and the resumption of Peak-type mucus discharge. stress, then they may anticipate a "double" Peak. To do
this properly, the husband is given the task of monitor-
A " double" Peak will occur principally in response to ing stress awareness in his wife. In addition , whenever
acute stress. When a woman is under stress, especially the Peak bui ldup or the Peak Day appears unusual , then
during the time of the mucus buildup, the process of a " double" Peak can be anticipated . The wife's task is
ovulation may be temporarily halted. With this, there to monitor the Peak buildup or any un usual character-
may be a buildup of the mucus to the Peak-type with- istics ofthe Peak Day. Thus, on the third day following
out the occurrence of ovulation. Ata later time (usu- the Peak Day, the couple shou ld ask the fo ll owing two
ally severa! days later) , there will be a second buildup questions, referred to as the "double" Peak questions:
ofthe mucus to a "second" Peak. Ovulation will occur
in association with this second Peak. The word double l. The husband shou ld ask his wife, "Has your
is placed in quotation marks because, in actual fact, Peak buildup or Peak Day been unusual in any
there is still on ly one true Peak in the menstrual cycle. way?"
This true Peak is the last Peak Day in the cycle. In a
2. The wife should ask her husband , " Have I been
study of564 menstrual cycles, the incidence of" double"
under any unusual stress over the past ten days?"
Peak was 7.8 percent. The incidence was lower in
women with regular cycles and higher in women com-
ing off birth control pills, breast-feeding women, and Ifthe answer is yes to either ofthese two questions, the
women with irregular cycles. Cl ini cally, it would ap- couple should anticipate the approach of a " double"
pear that sorne women are more prone to ha v ing Peak. With this, the couple can implement the appro-
"double" Peaks than others. priate end of the day instructions.
The "double" Peak situation can be easily managed with If a woman goes 16 or more days post-Peak anda pe-
proper education. The basic principie in this situation riod does not begin but the proper instructions on ob-
is advance education . Indeed, this is a second special servations and use ofthe system ha ve been followed to
circumstance with which every couple should be thor- avoid a pregnancy, then the coup le shou ld anticipate a
oughly familiar whi le using the CrMS (Figure 10-6). special form of " double" Peak. This specia l situation is
called a "missed " period. In actua l fact, it is a prolonged
34 35
Figure 10-6: The "double" Peak and the effects of stress on a cycle.
" doubl e" Peak where ovulation has been delayed due "Split" Peak _ _ __________ _,
to stress and may not occur fo r severa! days or even
severa! weeks. lt is referred to as a "missed" period A " split" Pea k can be defin ed as the occurrence of a
because fro m a practica! po int ofv iew, the wo man iden- gap no greater than 4 days between observations of
tifies itas such. However, it techni ca lly is not a mi ssed Peak-type mucus. Instead ofthe Peak-ty pe mucus days
period. A true menstrua l peri od onl y occurs fo ll ow ing occurring consecuti ve ly in the mu cus buildup, the days
an ovul ati on or an ovu lato ry event. Since the first Pea k are " sp lit," genera ll y by dry days. So long as the re-
mucus bui ldup in thi s situation is not an ovulation event, sumpti on of the Peak-type mucus occurs on or befare
no menstrua l peri od should be phys iolog ically occur- the end ofthe fo urth day, it is not techni ca lly a " doub le"
rin g and , thus, is not tru ly mi ssed. Nonetheless, the ter- Peak but is cl ass ified as a "split" Peak. T he separate
mino logy is app licable from a practica! po in t of view class ifi cati on of thi s situati on is supported by the fac t
in teac hin g. In order to manage the " doubl e" Peak situ- that, whi le on the one hand thi s occurs quite often, on
ati on, eve1-y couple should be aware of th e spec ial in- the other hand it poses 1ittle difficulty to th e new user.
structi ons whi ch re late to this spec ial c ircum stance:
Specia l In structions
l . On P+3 ask "double" Peak questions. Long Cycles _ __ __ __ _ _ _~
2. If answer is "yes" to either question, anticipate
Long menstru a l cycles can genera lly be defi ned as
"double " Peak. cycles that are consistently longer than 38 days in du-
3. lfpo st-Peak phase greater than 16 days in dura- ration. Thi s is a defini tion which is used for class ifi ca-
tion and system is used proper/y to avoid preg- ti on purposes. For sorne women, long menstrual cycles
nancy, anticípate "missed " p eriod form of are a normal pattern. For th em, the basic instructions
"double" Peak. wi ll appl y. Th ese wo men w ill usua ll y experi ence a
longer peri od ofpre-Peak dry days. However, they may
4. If "double" Peak anticipated,follow pre-Peak end
also ex perience " patches" of non-Peak- type mucus in-
of the day instruction until the situation is clari-
te rspersed w ith the pre-Peak dry days. The bas ic in-
fied.
structions fo r these " patches" can also be fol lowed (Fig- Anovulation ___________~
ure 1O- 7).
Th e woman who is anovu latory or irregu larly ovu lat-
On occas ion , wornen w ith long cycles will have a pating can be either one of the eas iest or one of the most
tern w hich resernb les the variable return of Peak-type cha ll enging cases to ma nage with the CrMS . Usua lly
mucus. In situations such as thi s, the basic instructions two patterns are observed (see Figure 10-8 , examples
rnay still app ly but, on occasion , instruction s for con- A and B):
tinuo us mucus rna y be required .
1. Long pe riods of dryness with an occasional ovu la-
tory mucus buildup ora frequent va ri able return of
Peak-type mucus (Example A).
2. A variab le return of Peak -type mucus that is easily
15 16 17 IK 19 20 21 22 2:1 24 25 26 27 2K 29 .10 .11 J2 .1.1 .14 .15
.o•. •C] .Q
~
Q Q "
'ií ·,'·' .,
(~ ~ ·~ '·
r<
"
he
xi ,...
'"'"
10 </k lókl IOlcl.. 6C 'i'C.

_.t0 '4D .AO .t i •/
Figu re 10-7: Long cycle charted with !he CrMS .
A
8
"
\,I "
~~
' } '{t
,,
10<
Figure 10-8 : Anovulatory cycles illustrated by a CrMS chart.

navigated , ora difficult variab le return that is c lose a. During the second cyc le or until semina l fl uid
to or identical with a prolonged Peak-type mucus is learned: end of the day, a lte rna te days.
discharge (Examp le B). b. ln the third cyc le or after se mina l fl uid is
learned: end of the day, every day.
In either situation , the basic instructions should be ap- c. ln the fo urth cycle, after step b: any ti me of
plied with the understanding that it is an end-of-the- day.
day situati on. This situ at ion is simi lar to the one ob-
4. The basic system instructio11s apply.
served in breast feeding. lf an ongoing contin uous mu-
cus discharge is present, a pattern of fert ili ty and infer- 5. Check for cervical i11jlammation.
ti li ty can genera ll y be established and yellow stamps
can be used. The presence of a non-Peak-type mucus discharge oc-
curring during the post-Peak phase of the cycle (ex-
cluding any pasty type of discharge) is often assoc i-
Post-Peak, Non-Peak Mucus _ _ __ ~ ated with a cervical inflammation (see Chapter 24).
Thus, while this is bei ng managed with ye ll ow stamps,
Commonl y, women charting the CrMS have the occur- the teacher shou ld recommend having the cervix
rence of post-Peak, non-Peak-type mucus. While easy checked and treated by a phys icia n.
to manage, it should be aggressive ly managed by the
CrMS teacher in conjunction with the client. The pres- The management of a post-Peak, non-Peak-type mu-
ence of non-Peak-type mucu s post-Peak can generally cus discharge i shown in Figure 10-9. In cycle A, the
be identifi ed with the first cycle of good observations identiti cation of post-Peak , non-Peak-type mucus is
and charti ng. If the woman has confldent/y identified made by using good charting, good observations, and
the Peak Day, ye llow sta mps can be emp loyed in the the confiden t identification of the Peak Day. In cycle
second cycle. lnfertility on these days depends upon B, the use of yellow stamps during the post-Peak phase
the confident identification of the Peak Day and the ofthe cyc le is shown . Fo ll owing the Peak Day, ye ll ow
passing of ovu lation. The fo ll owing pecial instruction baby stamps are placed for those non-Pea k-type mu-
app ly (F igure l 0-9). cus days with in the count ofthree. Pl a in yell ow stamps
are used for the remaining non-Peak-type mucus days
Special Instructions during the post-Peak phase of the cyc le. Those days
1. May use yellow stamps for post-Peak, non-Peak- can be considered infertile accord ing to the instruction
type mucus after the first cycle of good observa- previously di scussed. Such an in struction does not ap-
tions and charting and the confident identifica- ply to the use of non-Peak-type mucus days during the
tion of the Peak Day. pre-Peak pha e of the cycle. When mucus is continu-
ous in the pre-Peak phase ofthe cycle, days ofinferti l-
2. Infertility abvays begins at the end of the fourth
ity can be identitied , but spec ial teaching strategies to
day post-Peak.
implement pre-Peak yellow stamps must be used.
3. On the remaining tlays ofthe post-Peak phase, the
following progression of instructions applies for
11011-Peak-type mucus:
27 28 29 JO .11 .12 J.1 .14 .15
·~ A
:r I
Figure 10-9: Post-Peak, non-Peak mucus shown on a CrMS chart.

Cha pter 10: Specia l lnstructio ns and Applicati ons 157
Premenstrual Mucus -------~ regard to premenstrual mucus:
1. lt is due to endometria l fluid.

In sorne women, there may be a regular (or irregular)
appearance of a mucus discharge jusi prior lo the be- 2. lt may be ofthe non-Peak type or Peak type.
ginning of menstrua/ion . Thi s condition , referred to as
3. lf non- Peak-type mucus, follow ye ll ow stamp in-
premenstru al mu cus, has been shown to occur (i n a
structions for post-Peak, non- Peak-type mucus .
study of600 cycles) 12 .3 percent of the time. Beca use
thi s is a regular occurrence in sorn e women , the actua l 4 . If Peak-type mucus, consider fert il e or develop a
incidence is lower than 12 .3 percent when app li ed to yellow stamp pattern for post-Peak, Peak-type mu-
the popu lation ofwomen. cus .
Thi s premenstrual mucus di sc harge is thought to occur

as the result ofthe secretory fluid from the endometri um Premenstrual Spotting ------~
being di scharged through the cervix during the imme-
diate premenstrua l phase of the cycle. The discharge Premenstrual spotting is a common occurrence most
may be non-Peak-type or Peak-type. frequent ly seen in women beyond the age of 30 or in
wo men with a history of mi scarri age, infert ility, or pre-
In Figure 10-1 O, the occurrence of premenstrual mu- menstrual syndro me . By definition, preme nst ru al
cus is shown. In this example, the tacky, cloudy mucus spotting means three ar more days of light, very light,
in the first cycle is observed as fertile because it is the ar brown bleeding that precedes the beginning ofa mod-
first cyc le of charting. However, with good observa- era te or heavy jlow. These days do not ha ve to be con-
tions and charting and confident identifi cation of the secutive. Premenstrual spotting shou ld be charted w ith
Peak Day, this non -Peak, post-Peak mucus ca n be the previous menstrual cycle and not with the next men-
charted with yellow stamps during the second cycle strual period . However, if on ly one or two days of spot-
and the days can be used accordingly. In the third cycle ting exist, it shou ld be considered to be long to the next
(Cycle C), the premenstrual mucu s is stretchy, clear and menstrual period.
on that basis is again observed as a day of fertility. lf
premenstrual mucus is persistentl y Peak-type, days of An ab nonnal fall-off ofthe horm one progesterone dur-
infe rtility can also be identifi ed . ing the postovulatory phase of the cycle is thought to
cause an irregular shedding ofthe endometrium , known
The following concepts should then be remembered in as premenstrual spotting. Abnorn1a l funct ion ofthe cor-
29 30 31 32 33 34 35
!-/ M M L VL
oAD 2.AD
I
Figure 10-10: Premenstrual mucus charted with the CrMS .

pus lu teu m is ev ide nt. T hi s bleeding can be easi ly man- ing. in such cases, the fe rtility or infertili ty of those
aged wi th the CrMS . T he fo ll owi ng specia l instructi ons days is determin ed by th e observed mucus pattern .
apply to premenstrua l spotting :
Spec ia l In structi ons Post-Peak, Pasty Discharge _ _ _ _.....,

1. Chart as fertile for three cycles.
ln some women, a continuous di scharge of pasty, cloudy
2. Chart the presence or absence of mucus.
mucus w ill be observed. Beca use the pas ty, c loudy di s-
3. After three cy cles, continue to chart the bleeding charge comes fro m the vagina and not the cervix, it can
but follow the basic instructions based upon the be managed differentl y than non-Peak-type cervical mu-
presence or absence of mucus. cus di scharge that occurs during the post-Peak ph ase
of the cyc le (F igure 10- 12).
4. A t flrst sight of increased bleeding, consider f er-
tility to be present.
The prese nce of the pasty, c loudy di scharge is ide nti -
5. Use green, white or yellow stamps (but not red) fi ed durin g the first cyc le of charting. The instructions
after three cycles on the basis of the mucus while fo r post-Peak , pasty di scharge during the post-Peak
still charting the description of the bleeding. phase of the cyc le are th e same as those for any non-
Peak-type mu cus di scharge during the first three cycles
Figure 10- 11 shows an exampl e of how premenstrua l of charting. A fte r one cycle of good observati ons, good
spotting is managed. In cycles A, B, and C, red stamps charting and th e confi dent identificati on of the Peak
are used to chart the bleeding. ln cyc le O, however, Day, ye ll ow stamps can be used fo r thi s non-Peak- ty pe,
green stamps are used because the days are dry. T he pasty di scharge. The yell ow stamps are used for a mini-
bas ic instructi ons are fo ll owed relative to that situa- mum of two additi onal cyc les. During thi s time, th e
tio n. lt should be po inted out that it is appropriate to c li ent deve lops confidence in identi fy in g thi s pasty,
continue charting pre menstrual spotting with red stamps cloud y ty pe of di scharge. Such confidence can be fa-
espec ia ll y if th ere are co ncern s abo ut the wo man 's cilitated by using The Picture Dictionmy to clari fy the
health. Thi s w ill hi ghli ght the occurrence of the bl eed- observati ons with the client. In the fo urth cycle of chart-
.11 .12 .1.1 34 .15
11 H Hl'1
Figure 10-11: Premenstrual spotti ng charted with the CrMS .

ing, the yell ow stamps used fo r the pasty, clo ud y di s- 3. The basic instructions apply including any time
charge during the post- Peak phase ofth e cycle can now of the day for intercourse once the green stamps
be converted to green stamps. In addi tion, the in struc- are implemented during the post-Peak phase of
ti o ns that appl y to green stamps can be used. T hus, al- the cycle.
tho ugh a post-peak, pasty ty pe of di scharge ex ists, a n
4. A pasty discharge occurring during tite pre-Peak
an y-tim e-of-day in stru c ti o n fo r inte rcourse ca n be
pitase of the cycle is consitlered fertile unless a
implem ented ifthese procedures are fo ll owed. The use
pattern of infertility is deve/oped with the use of
of g reen stamps for a non-Peak-type muc us di scha rge
the instructions in Book ll, Advanced Teaching
during the post-Peak ph ase of the cyc le is limited to th e
Skills.
presence of a pasty, clo udy di scharge. Jt does not a ppl y
to any othe r fo nn of no n-Peak- ty pe mucus di scharge.
A lso, these instructi ons do not appl y to the prese nce of ln cyc les A, B , a nd C of the exarnpl e (F ig ure 10-1 2),
a pas ty, cloudy di scharge during the pre-Peak phase of the instru ctions th at a re used fo r post-Peak, no n-Pea k
the cyc le. Those days are still conside red fe rtil e under mucus in general have been fo ll owed . However, afte r
thi s pa1iicul ar instructi on. two cyc les of charting post-Peak ye llo w stamps for the
pasty clo udy discharge, green sta mps are implemented .
Since the pasty, c lo udy discharge is a spec ia l type of
di scharge ori ginating fro m the vag ina and not from the
cervix, the fo ll ow ing spec ial instructio ns appl y: Dry Cycles ---------~
Special ln structi ons Dry cyc les a re unco mmo n in the norm ally fe rtil e popu-
lation. In a stud y of 357 cycles fro m normal wo men,
1. The instructions for post-Peak, non-Peak-type mu-
onl y 2.5 pe rcent had cycl es w ithout a Peak Day. Dry
cus apply until two cycles ofyellmv stamps have
cyc les are muc h mo re commo n in the in fe rtili ty popu-
been successfully completed.
latio n. Dry cycl es that are of regular length sho uld be
2. After two cycles ofcharting with yellow stamps and co ns idered ovul atory cyc les since hormo nal profil es
conjirmation at fo/low-up with The Picture Dic- o btained in such cycles indi cate ovul atory events. Th e
tionary that pasty, cloudy discharge is being ob- exact ca use of regula r length, d ry cyc les is unknow n,
served, green stamps can be used during the post- altho ugh th ey may re late to either abno rmal ovari an
Peak phase of the cycle. fun cti o n o r an inability of the cervix to p roduce cerv i-
28 29 JO J 1 32 JJ 34 .15
I :r
e
'º7'11:
.it /
10
:.•
AO
~~ ~ "P.f ~re "lF "~ ~t¡
6
"!,' '.tf ""Pf ~~
r
D
H H l'1 L vl '/AD ~'i '/AD .. "° ;¡.,, ~fe ';i': ~~ ...... ª,',
lóPC ~PC
•1 " r ::r:: r ::r:: :r :.r: r :.r: r ::r:
Figure 10-12: Post-Peak, pasty discharge charted with the CrMS .

cal mucus . Such medications as antihistamines (cold Special lnstructions:

tablets) may also reduce cervica l mucus .
1. The basic pre-Peak instructions apply.
lf good mucus observations are being made, the dry

Examples of dry cycles can be found in cycle C ofFig-
days through cycles such as this are considered infer-
ure 10-3 and cycle C of Figure 10-4.
ti le with a high degree of reliability. As a resu lt, the
following instructions app ly:
J. Hilgers TW: Reproducti ve Anatomy and Ph ysio logy: A Primer 4. Hilgers TW, Daly KD, Hilgers SK, Prebil AM: CREIGHTON
for FertilicyCare™ Profess ionals. Second Edition. Pope Paul V I MODEL FertilicyCare™ System: A Standardized, Case Manage-
ln stitute Press, Omaha, Nebraska, 2002. Chapter 6: Lactati on and ment Approach to Teaching-Book 1: Basic Teaching Skills. Sec-
lts Effects on Ovulation. ond Editi on. Pope Paul VI ln stitute Press, Omaha, Nebraska, 2002.
2. !bid, Chapter 4 - Stati stical Parameters of th e Menstrual Cyc le Chapter 2: Human Sexuality: Discovering lts " lnner Soul". Chap-
ter 23: Teaching SPI CE.
3. !bid, Chapter l 1 - Artifi cial Methods of Contraception
Case Management
C ase rnanagernent can be defined as the cornpre-

hensive identification, interpretation, and integra-
tion of ali situations or problems that might arise in
sented in this book, is one which <loes not look at al!
problems and solutions as occurring ata rnornent in time
but rather looks toward solutions that evolve overa pe-
teaching the CREIGHTON MODEL System (CrMS) with riod of time recognizing that new situations or prob-
the objective of subsequently developing a cornprehen- lems may develop during the period of time tbe solu-
sive situation- or problem-specific plan of action that tion is being implemented and that such can have an
meets the needs ofthe CrMS client. Inherent in this defi- effect on previous actions taken. Such effects may cre-
nition of case management is the use of the process of ate a need to alter one 's original plan of action and de-
dialogue, clarification, and refinement, which ultimately velop a new one. Such a long-terrn dimension is part of
leads to an integration of the plan of action by the cli- the dynamic of case management.
ent.
The ski lis to accomp lish case management are not de-
The concept of case management was first introduced veloped quickly. Like developing goodjudgment, they
with the CrMS twenty-six years ago, and the CrMS con- grow with experience and attention to the process. Case
tinues to be the only case management model that has management becomes easier as experience is gained. A
been developed . The concept ofproblem solving is not number of basic principies of case management have
new. Problem solving on its own takes an individual been outlined and tbeir integration will assist the teacher
situation or problem, regardless of its importance and with implementing basic case management objectives:
provides a solution . Case management, on the other
hand, takes a number of situations or problems and in- 1. The FCP should thoroughly understand the concept
tegrates them into a cornprehensive, prioritized plan of of case management and the importance of it in
action . Case management involves ali of the ski lis of teaching.
problem solving but conceptually differs from it in that
2. To implement proper case management, tbe teacher
a more holistic perception of the client's needs is de-
must always exercise goodjudgment.
veloped. As a resu lt, it is less static and more dynamic,
less oriented to "symptomatic relief' and more oriented 3. Teachers must consciously and continually work on
to identifying fundamental problems and providing a the development oftheir sensitivity to the individual
"cure." lndeed, the case management concept, as pre- needs oftheir client couples. This sensitivity should
161
162 Th e Med ical and Surgical Practice of NaProTECHNOLOGY
be deve loped within the framework of a bas ic re- 4 . Misa ppli cati on of stamps
spect fo r the human person . a. No sta mps on days 9, 11 , and 13.
b. Wro ngstampsondays 10, 14, 18, 19,20, 2 1,
4 . The teacher s hou ld use the dynamic, interpersonal
22 , 27 , 28 , 3 1, 32, 33 , and 34.
educati on mode l as hi s or her primary too ! fo r de-
c. " P" and 1, 2, 3 placed on wrong da ys.
veloping case management plans. 1 A conscious, con-
tinued effort at developing and refinin g one 's com- 5. Poss ibl e long post-Peak phase
muni cati on sk ill s (especiall y the art of li stening and
6. Poss ibl e short post-Peak phase
teaching) is necessary.
7. Poss ibl e overreading of lubricati on
5. The development of a case manage ment pl an re-
quires th e abil ity to th ink comprehensively and to 8. Poss ibl e premenstrual mucus
anticipa/e future probl ems that could affect, either
9. Poss ible ac hi ev ing-related behavior.
positively ar negatively, the manage ment pl an. S uch
anti cipation all ows fo r a refin ement in one's ski li s
to deve lop case management pl ans.
lnterpretation of ltems ldentified --~
6. Since a manage ment pl an takes into acco unt sev-
era/ situations or pro bl ems, it is necessary fo r the Th ro ugh dialogue and clarification, each ofthe identi-
teacher to deve lop the abi lity to prioritize them. fied item s is now interp reted.
There is a limit as to w hat can be so lved at any one
p oint in time. The c lient ca n absorb only so much. 1. A number of inadequate descriptions appea r on tbe
Wi th adequate prioritizati on, the teacher and the cli - chart. Th e client wo uld be asked about those de-
ent can develop a real is tic approac h to the situation scripti ons so that the FCP could e lic it the client's
or probl em . perspecti ve. From thi s di a logue, tbe teacher fo rmu-
lates a pl an of action, but discuss ing that p lan of
7. The bas ic teachi ng skill s of chart reading, probl em
acti on with the c lient is de layed until al! items have
identi fica ti on, and assessment are necessary prereq-
been properly clarified.
ui sites to case manage ment.
2. A compl ete assessment ofth e client's observati ona l

1n order to i Ilustra te the concept of case management, a
routine is a part of the nonnal fo ll ow-up. Th is should
hypothetical case is rev iewed. 1n Figure 10-1 , a 34-day
revea ! the poor observati ona l ro utine observed in
cycle, much like one a teac her may have presented to
her charting. However, onl y clarification w ill te ll
him or her at the time of fo ll ow-up, is shown.
the teacher w hether thi s was an iso lated in ci dent or
a regular occurrance . Such a review of the observa-
T he fo ll ow ing list of potenti al situations or pro bl ems
tions has impli cations fo r the use of the bas ic sys-
can be identified in F igure 10- 1.
te m instruction s. As in ali identified and interpreted
items, the teacher fo rmu lates a p lan ajaction, which
is di scussed at a later time with the client.
ldentification of Potential
Situations/Problems _ _ _ _ _ _ _~
3. lt is obvious fro m the charting that thi s client has
mi sid entifi ed the Pea k Day. Severa! items need to
1. lnadequate descriptions
be c larified so that a pro per interpretati on ca n be
a. No descriptions ofmucus on li ght days offl ow.
made . First of ali, the cli ent may have an improper
b. Inaccurate descripti ons (4K?).
understanding ofth e Peak Day. Second ly, she may
c. N umber of tim es observed is mi ss in g.
be mi sin terpreting the definiti on of Peak- type mu -
2. Poor observa tional routine cus (think ing that it must be stretc hy, fo r examp le) .
a. O n day 13, "forgot" observations. Aga in , th e proper inte rpretati on is important so that
the el ient can be taught the use of the basic system
3 . M isidentification of Pea k Day
instructions.
a. Peak marked on day 17 w hile Peak actually
on day 19 (from recorded observations).
4. lt is easy to recogni ze in this chart the mi sapp lica-
tion of at least sorne ofth e stamps since some of the
spaces have been left empty. A number of other ar-
eas a lso ha ve the mi sapp lication of stam ps, wh ich
L H H fa1
::r: I :r
(")
::;
Ol
"O
~
Figure 11 -1: This cycle is an example of what a teacher might see at fo llow-up. lt is used as an exercise to assist the teacher in developing case management skil ls.
2
LHH/I'/
l. H H 11
cY'º
Figure 11 -2: With proper identification , interpretation and integration using the skills of dialogue and cla rification, this chart reflects one possible chart correcting solution to th e cycle
which was illustrated in Figure 11-1 .
Chapter 11 : Case Management 165
requires c loser rev iew by the teacher and then clari- wo uld be di ffe rent from a norma l menstrua l peri od,
fi cation with the client. As the cycle is charted, green and it fol lows on the appearance of Peak-type mu-
baby stamps should be pl aced on days 27, 28, 3 1, cus. These types of interpretati ons come from good
32, and 33 because these days fo ll ow observations chart reading and the teacher 's th eoreti ca l back-
of Peak-type mucus. However, whil e reviewing the gro und in the system.
chart, the stamp pl acement on days 26, 29, and 30
are also a concern . Thi s is clari fied as the teacher 9. T here are severa! acts of intercourse w hi ch appea r
di scusses the question of overreadi ng lu brication on the cha11 that could be potential ac hiev ing-re-
with the cli ent. Mi sapplicati on of stamps also con- lated behav ior. The use of day 5 in the absence of a
cern s the a pplication of the " P" and the count of recorded observati on of mucus wo uld be considered
three on the Pea k Day and the three days fo llow ing. a time offertili ty. lntercourse on day 11 is occurring
In thi s chart, those have a lso been mi sappl ied and on a sticky, c loudy pre-Peak day that wo uld be con-
wo uld need to be rev iewed with a plan of action sidered a day offertility. lntercourse on day 14 oc-
then deve loped. curs one day fo llowi ng a day on w hi ch observations
we re fo rgotten. Under such ci rcum stances, day 13
5. The post-Peak phase in thi s cycle as it is charted is should be co nsidered a day of Peak fe rtility and a
17 days. Whenever the p ost-Pea k phase is longer count ofthree should fo ll ow it. Similarly, intercourse
than 16 days, it can be categori zed as long. There on days 24, 27 , and 32 co uld ali potenti all y fa ll
may be severa! expl anati ons for thi s, but one of the w ithin thi s rea lm. T he di stincti on between w hether
most obv ious is the mi sidentifi cation of the Peak thi s is the exerc ise of achi eving-related behavior or
Day. Thi s would be c larified with the cli ent and a not de pends u pon the adequacy of the client 's in-
pl an of acti on developed . struction prior to thi s time and , through the educa-
tion prog ress , the va lidati on of the c li ent 's know l-
6. In thi s cycle as charted, a short post-Peak phase may edge of the instructions. For exa mpl e, if the client
be present if thi s is a circum stance where a va ri ab le was taught that " w hen in doubt, consider yo urse lf
pattern of Peak-type mucus ex ists. For example, if of Peak fe rtili ty and count th ree" and the cli ent's
day 30 is the Peak Day, the post-Peak phase wo uld know ledge ofthat instructi on was verified th ro ugh
be onl y fo ur days lo ng . T hi s ass um es th at the assess ment durin g the educati on process, then in-
stretchy, clear day on day 34 wo ul d be premenstrual te rcourse on day 14 must be ass um ed to be a fo rm
mucus. lt is important to clarify and disc uss this with of ac hi ev in g-related behav io r regardl ess of th e
the cli ent because it has impli cati ons fo r her fu ture cli ent's stated intentions. Thus, a pl an ofaction de-
chartin g and th e maki ng of adequate obse rvations. signed to dea l with that circum stance wo uld be de-
ve loped .
7. The shin y with lubricati on days that are recorded
on days 26, 29, and 30 are occurring dur ing the mi d-
post-Peak phase of the menstrual cycle in what oth- lntegration of ldentified
erw ise appears to be a norma l mucus buildup to th e and lnterpreted ltems ------~
Peak Day and a norm al length post-Peak phase (thi s
impli es the reappli cation ofthe Peak Day to day 19). O nce the process of identifi cation and interpretati on has
Whenever lubri cation is observed ata time when it been made (or in practica! applicati on, during the time
wo uld be expected to be phys io logica lly imposs ible, of identi fication and interpretation), th e teacher ass imi-
the questi on of overreading lu brication is ra ised. The lates or integrales ali of the in fo rrnation so that a proper
teacher must keep in mind that it is the woman 5· series ofrecommendations, ca ll ed a plan of action, can
decision to determine lubricati on. Through di scus- be deve loped and prese nted in d ialogue to the cli ent. ln
sion and c lari ficati on, the teacher can help to de- so doin g, prioritization is also undertaken. The teacher
velop an adequ ate pl an of acti on fo r ass isting thi s and the cli ent must dec ide w hich items should be cor-
cli ent in clari fy ing these observations. rected at the current fo llow-up and whi ch, if any, should
be corrected at a later time. Most of the items can be
8. The stretchy, c lear day on day 34, whi ch occurs the wo rked on fro m the fo llow-up where they have been
day before the beginning of an apparently norm al identified. However, sorn e may be reocc urring prob-
menstrual period, is considred pre menstrua l mucus. lems which, rea li sti ca lly, w ill ta ke addi tional amounts
The other poss ibili ty fo r such a mucus observation oftime. Since the case presented here is a hypothetica l
assoc iated with bleeding is the occurrence of break- case in w hich the dia logue and c lari fi cati on cannot be
through bleeding. In thi s latter case, the bleedi ng eas ily presented, the plans ofaction are simply presented
in the order of the identifíed items. However, the stu- ent because a li are not re lated to the client's use of
dent should keep in mind that this plan of action ma y the CrMS .
take on a different priority ranking depending u pon the
interaction with the cli ent. 7. Consideration of a short post-Peak phase depends
upon a clarificati on of the overread ing of lubrica-
l. With the identificati on of inadequate descriptions tion. It cou ld be that no discussion ofthe short post-
and the interpretation of its causes, th e teacher rnust Peak phase would come up w ith thi s ift he discus-
teach the client first of a li about how to make ad- sion of overreading lubrication revealed that such
eq uate descriptions . Teaching in vo lves the rein force- was not occurring. With that condition removed, then
rnent of the importance of accurate descripti ons in it can also be determined that no short post-Peak
the use ofthe systern. So, in thi s case, direct teach- phase ex ists .
ing to the client at th e time of the fo ll ow-up is the
plan ofaction w ith assessme nt ofthe results ofthat 8. ln consideri ng the problem of overreadi ng lubrica-
teaching taking place at the next fo ll ow-up. tion, a management plan wo uld be impl emented. In
this case, questioning the cli ent regard ing the lubri-
2. At the sarne time, clarifi cation of the inadequate cation on days 26 , 29 and 30 in comparison to the
descriptions is also undertaken during the course of lubri cation observed on days 16 and 17 indi cated
the fo ll ow-up w ith chart co1Tecting being a part of an ob vious difference between the two observations.
the teaching exercise. With this, the teacher re inforces the lubri cation ob-
served on days 16 and 17 w ith the srnooth sensation
3. With poor observations, much the sarne type ofp lan (non-lubri cative) observed on days 26, 29 and 30.
of actio n is developed. The cli ent is taught the irn- T he teacher then reviews observationa l routine, the
portance of a good observationa l routine and the observation of sensation o ver the perineal body, etc.,
reasons why good observations are irnportant (in- so that such confusion does not exist in the future.
c luding specifi c portions of the observational ro u-
tine, ifn ecessary). The teaching then becomes a pa1t 9. A considerat ion of premenstrual mucus ex ists and
of the pl an of action a long with the assessme nt at is discussed with the client. lmportant here is cli ent
the next fo llow-up . ed ucation on the interpretation ofthe premenstrual
mu cus and its cause a long with the way in whi ch it
4. lt is clear that the Peak Day has been rnisinterpreted should be managed . That day shou ld be charted w ith
but, in interpretation , iterns may co me up that move a white, baby sta mp and observed as fert i le in this
the teacher to focus on specific areas of teaching . earl y stage of learn ing.
The p lan of action in volves direct chart correcting
at the time of the fo ll ow-up and adeq uate teaching 1O. Beca use of the poten ti al fo r achieving-related be-
regard ing the identification of the Peak Day. Assess- havior, the teacher wo uld discuss, most likely as one
ment of that teaching takes place at the subsequent of the late r item s, afte r a li other things ha ve been
fo llow-ups. disc ussed and integrated, the pe1tinent aspects of
avo iding and achi evi ng- related behavior (use). lt is
5 . The m isappli cation ofstamps requires teaching the vita l that the client coup le thorough ly unders tand
proper use of stamps and their placement. Sorne of those aspects that are go ing to be impo1tant to them.
the chart correcting or stamp placement requires Their acc urate use ofthe CrMS may come down to
further interpretation of other questions posed by a proper understa nding of such behavior. Clearl y, if
the chart, in this case, whether overread ing lu brica- it is their intention to avo id a pregnancy, the n they
tion is occurrin g ora sho1t post-Peak phase ex ists. must ha ve interna!ized the understanding of avoid-
S ubsequent interpretation ofthat during fo ll ow-up ing-related behavior.
wo uld dicta te the type of chart correctin g that wou ld
be acco mpli shed.
6. The long post-Peak phase is most like ly due, in thi s Recommendations _ _ _ ________,
case, to the misidentificati on ofthe Peak Day. 2 How-
ever, other causes for a long post-Peak phase may Once the above is integrated, the process ofrecommend-
be suggested by the teacher and , i f appropriate, dis- ing or presenting the pl an of action to the client is un -
cussed w ith the c lient. The teacher wou ld be aware dertaken. This is done th roug h a dia logue in whic h the
that not a li items need to be di scussed with the cli- cli ent a lso has input and together the pl an of acti on is
Chapter 11 : Case Management 167
adopted. lt is important that it be done together since Leve/ 11

simply dictating to a cli ent what one thinks is the proper 1. Post-pill
course ofaction wi ll not be integrated as we ll as ajoint 2. Breast feeding- weaning
decision to use a spec ifi c pl an of action. With this pro- 3. Premenopause
cess of dialogue, the cli ents are observed so th at the 4. Postpa1tum- not breast feeding
teacher fee ls confident that they have integrated the plan 5. Post-aborti on
of action properly. 1f th e teacher fee ls that the pl an of 6. lnfertility
action should be written down on a pi ece of paper, then 7. Variab le return of Peak-type mucus
such should occur to help them work on spec ific items 8. 1ntermenstrual bleeding
which would be ofva lue. 9. Leve! 1 difficulty with an added advanced issue
1O. Leve! 1difficulty with a med ica ! situation
One potential chart correcting so lution to the above situ-
ation is presented in Figure 11-2. Level/11
1. Pre-Peak: Breast feed ing with continuous mucus dis-
charge
The Case Management Sheet ---~ 2. Pre-Peak: Long cyc les with continuous mucus di s-
charge
In order to ass ist new student teachers in the CrMS to 3. Pre-Peak: Regul ar length cycles with greater th an
deve lop good case manage ment skili s, a case manage- 8-days post-Peak
ment sheet (CMS) has been deve loped . This form as- 4. Post-Peak, Peak-type mu cus
sists the FertilityCare™ Practitioner intern in the use 5. Leve! 11 di ffic ulty with an added adva nced issue.
of a systematic method of assessi ng the client 's needs 6. Leve! 11 difficu lty with a medica! situation
and developing a plan of acti on fo r the management of
th e case. Th e CMS is a too! that helps new teachers Leve/ I V
integrate their theoretical knowl edge with the ir clini ca l 1. Leve! 111 difficu lty with an added advanced iss ue
teaching experience. lt is also an aid in long term plan- 2. Leve! 111 difficulty with a medi ca! situation
ning. In addit ion, it acquaints the intern with a method
of comm unication that has been used extens ively over Under the section ofbackground info rmation is a doubl e
the years by health care practiti oners in providing con- row of boxes, the numbers 1-35 are in the upper row
ti nui ty of care. Fina lly, it provides the FertilityCare™ and the bottom row of boxe is empty. The FCPI uses
Educator or Supervisor with a too! to eva luate the these 35 boxes to record the 35 successive days ofchart-
intern 's preparation and abili ty to pl an ongo ing care. ing that are the most representative of th e situati on or
probl em whi ch is being identified. The recording ofon ly
The case management sheet has a place fo r the na me of the descriptions is written in each box .
the FCPI and the date for which it is completed. In ad-
dition , there is a space provided fo r the woman/coupl e's The CMS is then broken into fo ur co lumn s. From left
1D number, the woman 's age and marital status, and the to right, the co lumns should ex pl ain th e case manage-
man's age and mari ta l status. The woma n's reproduc- ment in a logical and concise fas hi on. The fo ur co lumns
ti ve hi story, current reproductive category and length and an exp lanation of their use fo ll ows. l-l and writing
of time using the CrMS are th en li sted. There is also a the CMS is satisfactory. However, the student should
place to record the degree of difficulty of the case and keep in mind that conciseness and c/arity are important
any other pertinent inforn1ation. The degree of difficul ty qualities in thi s type ofacti vity. lt is subsequentl y sent
is a general guidelin e for the superv isor in monitoring to the FertilityCare™ Educator or Supervisor fo r evalu-
the student's client load. At the present time, the fo l- ati on and comrnent.
low ing system is being used to monitor the degree of
difficu lty: Situation/Problem: This colu mn is fo r summari zing the
situatio n or prob lem th at th e client coupl e faces . Each
Leve/ J situation or problem is li sted in numerical order. In ad-
1. Regular cycles dition , they should have a correspond ing plan of ac-
1s. Regular cycles - steri li zed tion , rationa le and ex pected outcome written in the ap-
2. Long cycles propriate co lumns. The si tuati ons or problems must be
3. Breast feeding- total prioritized accord ing to the order of importance ( 1, 2,
4. Post-Peak pasty, conversion to green stamps 3, etc.). lft he situation or probl em re lates to the chart in
5. Premen strual spotting any way, the exact day or days which demonstrate that
6. Post-Peak, non-Peak mucus (ye ll ow stam ps)
168 The Medical and Surgical Practica of NaProTECHNOLOGY
situation or problem should be written in this column. abil ity to foresee the expected outcome is an important
finishing component of a specific plan of action .
Plan of Action : The plan of action describes the
teacher's actions that are currently being imp lemented With the completion ofthe case management sheet and
or will b e contingent upon the Fertility Care™ its submission to the supervi sor, the supervisor can as-
Supervisor's approva l. This section requi res the use of sess the teacher 's developing skills in this area . The
a verb to introduce each proposed plan of action. superv isor makes comm ent with regard to the case
management approach selected by the teacher intern
Rationale : The rationale is the CrMS 's defen se, rea- and grades his or her performance. This, then , makes
soning, or explanation for each specific plan of action . up one portion ofthe necessary superv ision in the edu-
Each plan of action must be supported by an adequate cation of FertilicyCare™ teachers . However, the foc us
rationale. This co lumn all ows the student teacher to is not on the grading ofthe case management but rather
refi ne his or her reasoning sk ili s. on the education of the new teacher in developi ng a
thorough process that can be used in hi s or her years
Expected Outcome: In this co lumn , the teacher intern ahead as a FertilityCare™ Practitioner. This approach
describes what wo uld be the expected outcome of the to educating and supervising FCP intems has provento
plan of action or, if an outcome has already occurred , be very constructi ve in the development of case man-
an eva luation of the actions undertaken . ln ali case agement ski lis over the many yea rs of experience that
managements, plans of action are developed based u pon has been gained in its use.
what the teacher expects to be the future outcome. The
l. Hil gers TW, Dal y KD, Hil gers S K, Prebil AM : CREIGHTON

MODEL FertilicyCare™ System: A Standardized, Case Manage-
ment Approach to Teaching-Book 1: Basic Teachin g Skills. Sec-
ond Editi on. Pope Paul VI lnstitute Press, Omaha, ebraska,
2002.
2 . !bid, Chapter 24 - Bas ic Problem So lving.
)
-----el~tu,12
Decision Making in the CrMS
H istorica ll y, the natura l means to regulate ferti lity

began as natural systems for avoiding pregnancy
on ly (natura l " contraception)." In fact, up to the devel-
serious reason" to avo id pregnancy. This res ul ts frorn
an interpretation of Humanae Vitae 2 w here such terrni-
nology is used (a lthough there are other tra nslations
opment of the Bil lings Ovulation Method 1, there was which wou ld use such terms as "good and serious" rea-
little ifany emphas is on the use ofa system to actually sons, " honest and seri ous reasons," "good and j ust rea-
ac hi eve a pregnan cy. With the development of the so ns") . Coupl es w ho uti lize th is interpretation use no
CREIGHTON MODEL System (CrMS) - a standardi zed systern - not even a natural systern - for "avoiding preg-
modification ofthe Bi llings System - special emphasis nancy" and they do not chart their cycles at ali. They
was g iven to its use as a system of "true" family plan- leave it up to w hat they refer to as " Di v ine Providence"
ning. That is to say, it can legilimately be used through- - oras it is often stated " How rnany chi ldren God wishes
out a couple s entire reproductive life to both achieve us to have." Unfortunate ly, such an approach accepts
and avoid pregnancy. The ac hievement of pregnancy, and institutionalizes the notion th at a natural rnethod 's
in this reference, applies to those coupl es of complete ly on ly purpose is for the avoidance of pregnancy. It is
normal ferti lity and is not referring here to the coup les perhaps better referred to as f ertility nihilism, which
w ho experience inferti li ty (wh ich has been somewhat denies access to a cognizant knowledge and use of natu-
of a foc us of other natural systems o ver the yea rs). ra l ferti li ty. In additi on, this co ncept <loes not keep
abreast with the developrnents in the field of natural
Thi s concept of natural " contraception" <loes continue birth regulation over the last 25 to 30 years.
today and brings up the need to discuss, in sorne detail ,
the context to w hich mature decision making is made With the CrMS, the emphasis is equally upon both
with the CrMS . achieving and avoiding pregnancy. Thus, the co uple is
given that inforrnation so that a dec ision can be made at
Over the years ofthe development ofthe natural means, each menstrual cycle-each fertility cycle - as to whether
the co ncept of what has often been referred to as or not pregnancy shou ld be atternpted.
" providentialisrn" has developed. In thi s approach ,
coupl es do not use any forrn of farni ly planning - in- The Catho li c Church teaches that the decision on how
clud ing a natural systern - until they have a " grave and many children to have is the decision of the spouses
169
alone. 3 Furthermore, the Church teaches that " in the view when coupl es elect to accept many children or decide
of the inali enable right to marry and beget children, the not to have another child fo r a defi ni te or indefi ni te
questi on of how many child ren shou ld be born be longs amoun t of time." 7
to the honest j udgment of parents. The question can in
no way be committed to the decision of government."4 There may be "serious" reaso ns fo r spacing offspring.
It should perhaps be noted here th at no other person or These seri ous reaso ns would revo lve around, as the
age ncy has the right to di ctate to a married coupl e, e i- C hurc h teaches, " the physica l or psycho logical condi-
ther directl y or indirectl y, how many childre n they tion of the spouses" and " externa! fac tors."
should or should not have. T hi s wou ld inc lude the ro le
of phys icians. ln this rega rd, Pope Paul VI teaches that "[T]n such cases,
the Church teaches that it is morally permi ss ibl e to ca l-
Pope Pau l Vl elaborated upon this in a very special way: culate natura l rh ythms inherent in the generati ve fac ul-
"F inall y, it is fo r parents to dec ide, with fu ll know l- ties and to reserve mari ta l intercourse fo r infe rtile times.
edge ofthe matter, on the number oftheir children, Thus, spouses are ab le to ' pl an thei r fa mili es without
ta king into acco un t the ir responsi biliti es toward: violating the moral teachings. "'8
• God
• themselves Dr. Janet Sm ith, in her cornmentary on the "seri ous con-
• the children they have a lready bro ught into siderati ons" fo r limiting famil y size in Humanae Vitae:
the wo rld A Generation later, indi cates that the encyc lica l letter
• the community to which they belong Humanae Vitae gives no explicit guideline in this re-
In ali thi s, they must fo ll ow the demands of their: gard but does indicate that phys ical, economic, psycho-
• own consc ience logical and soc ial conditions are suggested:
• enli ghtened by God 's law authentically in- • the hea lth of the spouses and other fa mi ly mem-
terpreted bers
• sustained by confi dence in Him ." 5 • the fi nancia] situation of the fa mily
• the emotional stabili ty of ali invo lved
Furthermore, Pope Paul VI reiterated this in Humanae • condi tions in the society in which one lives. 9
Vitae when he said :
"T his res ponsible parenthood is rooted in the ob-
j ective moral order establi shed by God. O nl y an up- The Natural Means and Contraceptive
right conscience can be a true interpreter of thi s Practices are Different - - - --------..
order. Spouses must recognize their duties . .. as they
maintai n a correct set of priorities: Humanae Vitae spec ifica lly addresses the questi on as
• toward God to whether the natu ra l means to regul ate fert il ity are the
• toward themselves same as or di ffere nt fro m contraceptive practices. 10 It
• toward the family outlines the fo llowing signi fica nt diffe rences between
• toward hu man soc iety. " 6 the two:
• in the natural means, the spouses legitimately use
Thi s section is often mi sin terpreted by others to sug- a fac ul ty that is given by nature.
gest that the dec ision regarding the use of a contracep- • in direct contrace pti on, the spouses im pede the
ti ve system can be one that is left up to one's own con- order of generati on fro m completing its own
sc ience. But such a consc ience mu st always be a true natura l processes.
conscience and not a fa lse one. Pope Paul VI makes • interco urse at the infe rtile times is fo r the sake
th is abunda ntl y clear when he says that ones " own con- of mani fest in g mut ua l love and ma intai nin g
sc ience" mu st be "enli ghtened by God 's law authenti- pro mi sed fide li ty.
cal/y interpreted." • users of natu ra l methods of fert ility regulati on
offer a w itness to trul y and complete ly upri ght
In Humanae Vitae, Pope Paul VI goes on to say that love.
responsibl e parenthood is exercised " looking to p hys i-
ca l, econom ic, psycholog ical and soc ial cond itions and In the teaching of th e CrMS , " the teac her must teach
when guided by: the bas ic principi es offertil ity and infe rtility and not be
• prudent considerations contracepti ve ly bi ased. " 11 In the introductory sess io n
• generosity fo r the CrMS , its princ ipi es of use are outlined:
• due respect for mora l pri nci pi es • using days of fertility abandons the system as a
Chapter 12: Decision Making in the CrMS 171
means ofavoiding pregnancy and adopts the sys- l ntercourse" defines appropri ate ly the use and behav-
tem as a means ofachi evi ng pregnancy iora l dimensions ofthe CrMS. The use ofthe term "se-
• you will know when you are fertile or infertile lective" specifica lly implies the decis ion-making choices
on any given day. the coup les implement while act ivatin g the fu lln ess of
th e system.
The freedom to use the CrMS is also put forward:
"The freedom to choose how to use the CREIGHTON
MODEL System as a means of achi ev ing or avoid- The Sacramental Moment of
ing pregnancy is the right of th e couple to impl e- Human Procreation -------~
ment. This decision, to achieve or avo id pregnancy,
sho uld be ajoint one between husband and wife." 11 Because the CrMS foc uses on the ability of couples to
know when th ey are fertil e and not fertil e in a given
cyc le, it opens upa who le new capab ili ty that has not
Decision MakinQ ---------~ been avai lab le to married coupl es really in the hi story
of the world . lt opens up the poss ibili ties that couples
In deciding whether or not to ha ve intercourse, a coup le can consciously se lect to achieve a pregnancy in a given
must consider the fundamental question as to whether menstrual cycle. Of co urse, in such a cycle, pregnancy
they wish or do not wish to have another chi ld . In that sti ll mayor may not occur. However, by using the days
regard , a couple should give consideration to the phys i- offertili ty, the couple clea rly chooses to have another
cal, economic, psycho logical and social conditions upon child and, in that, the couple can and should do so out
which responsib le parenthood is decided . This is part of !ove.
ofthe decision making invo lved in the use of a system
which truly identifies days that are fe rtile and days that Furthermore, they have the opportunity to co-create with
are not fertil e. In thi s fashion, the term "selective inter- Goda new, etern al human li fe. They can "physically"
course" is used and th is properly places the focus on touch God in the action of creating this new hu man life.
the choices the coupl e makes to have intercourse at a F'or Catholics, this can be likened, at least in sorne ways,
particul ar moment in time. Since the choices shou ld be to the receiving ofthe Euchari st. lt is a Trinitarian pro-
mutua l, the term mutualy selective intercourse (MSI) posal of: 1+1+1=1. A man , a woman and God ali come
app li es. together to create a new hum an person. The man and
woman come together to contribute the phys ical mate-
So the question is not "S hould we or should we not ha ve ri al that will contribute to the creation of this new hu-
intercourse?" But a preceding question should be asked man person while God, at the moment of conception,
"Should we or should we not have another child?" in stills in that new perso n hi s or her eternal soul. When
one thinks about this, it is an incredible event perhaps
The "Principie of Selective lntercourse" is one that beyond our true ab ility to comprehend. And yet, our
appli es uniquely to a natura l means to regulate fertility abili ty to experi ence j oy in that action is truly bound-
and spec ifi ca lly to the CrMS. While many systems over less.
the yea rs ha ve re li ed on the concept of"period ic absti-
nence" as a means by whi ch they can describe what is So with regard to the CrMS, th e decision making in us-
involved in the imp lementation of the natura l system ing the system is best left in th e hands of the coupl es
being used, in fact, "periodic abstinence " is not at ali who use it. The providers of the CrMS wi ll not be mak-
specijic to the use of a natural system. Those who use ing these decisions for the coupl es. lt is the ro le of the
contracepti ves also practice periodic abstin ence since officia l Church, that is, its pri ests, religious and hi erar-
they do absta in from genital intercourse between one chy to give spec ial guidance to Catholic married couples
sex ual contact and the next. So the concept of "peri- so that they can make these decisions with correct mora l
odic abstinence " is not a concept that applies exclu- insight.
sive/y to a natural means to regula te f ertility.12
With the CrMS, it is also to be recognized that the con-
Us ing the CrMS is concerned with both the achieve- tinued charting of the system has incredible health
ment and the avoidance of pregnancy. Ultim ate ly, benefits to the woman. Thus, not to chart and pay at-
whether one does or one does not have intercourse is tention to one's fertility and the biological markers of
dependent upon the actual choices one makes to either one's ferti lity and hea lth , is to miss out on an enormous
achieve or avoid pregnancy. Thi s is paramount and fun- amount ofvery va luabl e inform ation that cannot be ac-
damenta l to its use. Thus, the "Principie of Selective curate ly reconformed ata later time. Thus, for a couple
to say "we w ill leave it in God's hand ," they are say ing functions . Thus, to use this info rrnati on, to understand
in effect that they are not interested in becoming coop- it, and to practi ce it should bring us closer to God and
erators with God in these most important as pects of our allow us to grow in even deeper appreciation for Hi s
li ves. God has created thi s and has created our inte ll ect goodness.
and our abi lity to understand how the body works and
1. Billings EL and Westmore A: The Billings Method: Controlling 7. lbid.

Fertility Without Drugs or Devices. Random Ho use, New York,
ew York 1980.
8. !bid, § 16.
2. Pope Paul V I encyclica l, Humanae Vitae, Jul y 25 , 1968. 9. Smith J : Humanae Vitae: A Generation Later. Cathol ic Uni ver-
sity of America Press. Washingto n, DC, 1991.
3. Pastora l Co nstituti on Second Vatican Council. Gaudium et Spes .
December 7, 1965 . Section 50. Thi s secti o n was also ci ted by 1O. Humanae Vitae, op. cit. § 16.
Po pe Paul V I in hi s encycl ical letter Humanae Vitae.
11. Hil gers TW, Da ly KD , Hilgers SK, Prebi l AM: CR EIGHTON
4. !bid, § 87. MODEL Fertility Care™ System : A Standardized, Case Manage-
ment Approach to Teaching- Book 1: Basi c Teaching Sk ill s. Sec-
5. Pope Paul V I encyclica l,Popu/orum Progressio, March 26, 1967, ond Edition. Pope Pa ul V I ln stitute Press, Ornaba, Nebraska,
§ 10. 2002.
6. Po pe Paul VI encycli ca l, Humanae Vitae, Jul y 25, 1968, § 1O. 12. C remin s R: Se lective lntercourse: Towards a Defin it ion ofNFP.
lnt Rev Nat Fam Plan , 9 :33 7-33 8, Wi nter 1985.
Achieving- and Avoiding-
Related Behavior (Use)
he CREIGHTON MODEL System (CrMS) can be percent. Th e students where then asked, "Given the
T used to either achieve or avoid a pregnancy. This is
a use-related concept that is unique to the natural meth-
chances as you expressed them , do you think you would
' take the chance' in using those days if it was your in-
ods of fertility regulation and especially to the CrMS . tenti on to avo id a pregnancy?" Predi ctably, the student
This feature distinguishes this system from methods of who indicated that the chances wou ld be 75 to 100 per-
contraception. ln fact, natural methods are the only meth- cent to achi eve a pregnancy sa id they would not "take a
ods whose use does not have to be di scontinued in a r- chance." On the other hand, those students who thought
der to become pregnant. th eir chances of achieving a pregnancy would be O to
25 percent indicated that they would be more likely to
lfthe couple is using the CrMS according to its instruc- "take a chance." While thi s concept has never been thor-
tions as a system to avoid pregnancy, they are exhibit- oughly stud ied, this same experience has been repeated
ing avoiding-related behavior (or use). At the same time, severa! times with basically th e sa me results. The point
i fa couple turns around and knowingly uses days of ofthe di scuss ion is that people who come into a CrMS
fertility, thi s is clearly achieving-related behavior (or program, co me in with a variety of different opinions,
use) . These two examples would be reasonably obvi- usually un stated and perhaps even subconscious, that
ous to most people. The cha ll enge with th e CrMS is to refl ecta broad spectrum ofbeliefs regarding the fertil-
understand the more subtle aspects of avoiding- and ity potential ofthe defin ed days offerti lity. The broad
achieving-related behav ior (use). range of opinion reflects generalized ignorance amongst
the general population on such issues. In tum , this is
At a student conference for medi ca! students, a group also a reflection of the genera li zed ignorance that ex-
of students were asked what their cha nces would be of ists in those areas among experts in the field of human
achiev ing a pregnancy if they u ed days of fertility as reproducti on.
defined by the CrMS . Surprisingly, the students reflected
a spectrum of thought. Sorne sa id they th ought the We have conducted a preliminary survey of50 consecu-
chances wou ld be between Oand 25 percent, others from tive pregnancies occurring in couples of normal fertil-
25 to 50 percent, still others from 50 to 75 percent, and ity in users of the CrMS was conducted. 1 In 76 percent
finally others (only a small minority) from 75 to 100 of those couples, pregnancy occurred in the ve1y first
173
cycle in w hi ch days of fe rtili ty were used. ine out of ing pregnancy is desired ofany method when the coupl e
ten were pregnant by the third cycle, and nea rl y ali were has reached a point where there is a serious need to
preg nant by the sixth cyc le. Whil e thi s c lea rl y requires avo id a pregnancy. No less a marker should be accepted
furth er stud y, it <loes add support to the noti on that the fo r natura l methods offertility regul ation.
days of fe rti lity as de fin ed by the CrMS are very pre-
cise. In fac t, they are so prec ise that they have the po- In fact, then , any deviation fro m the bas ic in structions
tenti al of revo luti oni z ing our approach to th e who le to avo id a pregnancy should be expected to lower the
concept ofachi ev ing a pregnancy. effectiveness ofthe system as a means ofavo iding preg-
nancy. By lowering the effective ness to avoid pregnancy,
Thi s type of data , along with the experience of many s
these deviations increase the system ejfectiveness to
teachers th ro ughout th e coun try, lends support to the achieve a pregnancy. Thus, whenever ac ti ons are take n
notion whi ch is taught in th is system that there is no whi ch increase th e pregnancy rate above one percent,
such thing as " tak ing a chance" when using the CrMS . th ose actions can be defi ned as achieving-related be-
The CrMS makes archa ic th at notion which grew up havior (use). Achi ev ing-related behavior, however, tends
w ith the Ca lendar Rh ythm Method. ln additi on, there to be more subtl e than this and more d iffic ult to iden-
has been need to move away fro m contrace pti ve termi - ti fy. T hi s is in part due to o ur own lack of understand-
nology as it mi xes with th e CrMS . The concept of " taking and in part due to our c li ent 's inability to commu ni-
ing a chance" is contrace ptive in substance. Th e couple cate these behav iora l concepts to the teacher.
that " takes a chance" is taking the chance that they w ill
not become pregnant. T hey are not taki ng a chance that In spite ofthis, sorne achi eving-re lated behav ior can be
they will become pregnant. Such contrace ptive te m1 i- ide ntified. For exampl e, when a woman begins to drop
nology conveys contracepti ve psycho logy. T hi s has th e observati ons even though she is fu lly cogni zant of the
effect of convey ing inacc urate images ofthe pro per use importance ofthose observations, or when a couple uses
of the CrMS . As a resul t, there has been a clear need to beginning of the day in terco urse during th e pre-Peak
revise our images keeping in mind the truefa mily plan- ph ase of the cycle when they kn ow that the instructi on
ning nature of th e system. One ofthe goa ls in teac hing is fo r the en d of th e day, or when the coupl e uses the
the CrMS is to teach co upl es to be abl e to avo id preg- thi rd day post-Peak thinking that they " most li ke ly" will
nancy when they wish and achi eve pregnancy when they not become pregnant. These are forms of achi ev ing-
desi re. Such cannot be properl y accomplished if the re lated behavior. Even when a coupl e is in a state of
co up le grows up w ithin the menta li ty of " tak ing a ambivalence regardi ng their intentions on how to use
chance." ln actua l fac t, " taking a chance" is the use of the system they are in an achieving-re/ated state. T hi s
the days that carry with them a higher p reg nancy rate. i because the mutua l decis ion to avo id a pregnancy is a
Thus, such behav ior prope rl y belongs w ithin the c lass i- co mponen t of avo idi ng-re lated be hav io r. O nce the
fi cati on of achieving-related behavior (use). coupl e has dev iated away fro m the dec ision to avo id a
pregnancy and, even though they have not reac hed a
lt is re lative ly easy to identi fy avoiding-related behav- full conscious leve! of dec iding to ac hi eve a pregnancy,
ior (use) . T hi s can be identi fie d by studyi ng th ose th eir move away from avo iding- related intentions is a
coupl es w ho have th e seri ous desi re to avoi d a preg- form of achi evi ng-re lated behav ior (use).
nancy. The most typica l group are those in the premeno-
pause. Thei r fa mili es are now complete and they are lt is important to recogn ize that achi ev ing-related be-
very serious avoiders in the use ofthe system . For these havior (use) often run s ahead of"fu ll sca le" ac hi ev ing-
coupl es, the observations are fo llowed 100 percent, the re lated intention. No t to decide is to decide.
charting is acc urate ly accompli shed, and the instruc-
ti ons to avoid a pregnancy are fo llowed perfec tl y. lft he The criti ca! fea ture of understand avo iding- an d ac hi ev-
system is used in that fas hion, it can be antic ipated as ing-re lated behav ior is the importance of client educa-
hi ghl y reliable in avoiding pregnancy. Ifwe set our "ef- tion in these areas so that they can ful fi ll the intentions
fecti veness baro meter" to avo id pregnancy at 99+ per- they have in usi ng the system. lf it is the couple 's inten-
cent, then to achieve such effectiveness requ ires that tion to avo id a pregnancy, then th e teacher exp lai ns to
the observational routine, charting and instructions be them the importance of se lecting avoiding-related be-
fo ll owed as instructed. A couple who uses the system in havior (use) in their use ofthe system. At the same time,
th is fas hi on can then be deflned as ex hi biting avo id ing- as an understandin g of our fert il ity increases, the po-
related behavio r. T hi s becomes the hallmark of avo id- tentia l ex ists to assist coup les in engaging in truly con-
ing-re lated behav ior (use) because, from a practica ! ceptual acts . Rather than "sneak up" on a preg nancy,
point of v iew, a 99+ percent effective system ofavo id- the co uple can reach a leve! of bein g able to consciously
Chapter 13: Achieving- and Avoiding-Related Behavior (Use) 175
co-create with God a new hu ma n li fe. the cyc le should also know that that is an ac hieving form
of behav ior. Thus, such behavior merits the c lass ifica-
Ultimately, an understanding of avo id ing and ac hi ev- tion of an ac hiev ing-re lated pregnancy. Of co urse, the
ing-related behav ior (use) is vital to the classificat ion c lassificatio n w ill depend upon other fac tors such as
of pregnancies in coupl es w ho become pregnant whil e the cli ent hav ing been taught the basic princ ipi es of
using the CrMS.2 lndeed, the couple that know ingly uses ac hiev ing- and avoiding-related behavior (use) .
the begi nning of the day during the pre-Peak phase of
Footnote
In thi s chapter, the term " behavior" and " use" are used that thi s type of psycho logy may be very subtl e, per-
interchangeably because the actual use ofthe CrMS is haps subconsc ious and thu s very subjective. H owever,
a product of behavior. Thus, the two te rms, when used in the CrMS , th e actual use of the system is obj ective ly
in associati on with the concepts of " ac hi evi ng related" defined and measurabl e. This virtuall y eliminates the
and "avoiding related" can be used interchangeab ly. subj ectiv ism that sorne may sense w hen one uses tem1 s
However, sorne observers have mi sinterpreted thi s, such as " behav ior. " When properl y understood in thi s
thi nk ing that the term " behav ior" has more of a psycho- contex t, it is not problematic in its interpretation.
logica l connotation to it. There is a sense among so rne
1. Hi lgers TW, Daly KD, Preb il AM: Cumu lative Pregnancy Rates the scope of this textbook. However, a complete discussion of
in Patients with Apparently Normal Fertility and Fertility Fo- this can be found in: Hilgers TW, Hilgers SK, Prebil AM, and
cused lnterco urse. J Repro Med , 1O: 864-866, 1992. Daly KD : CREIGHTON MODEL FertilityCare'" System : A Stan-
dardi zed, Case Managemen t Approach to Teach ing-Book 11 :
2. A com plete and thorough discuss ion ofpregnancy ev latuion, preg-
Advanced Teachi ng Ski ll s. Pope Paul VI lnstitute Press, Omaha,
nan cy classi fication and the study of pregnancies goes beyond
Nebra ka, 2003 . Chapters 14, 15, 16, 17 and 18.
Objective Classification
of the Mucus Cycle
O ne of th e imp orta nt
NaProTECHNOLOGY is the ab ility to assess the
techniques
mucus cyc le in an objective fas hi on. This provides the

in C'S MCSS) has been deve loped to ass ist thi s process
(Table 14-1 ).
opportunity to interpret the phys iologic or pathophysi- Cervica l mucus scoring systems have been previously
ologic events ofthe menstrual cycle with greater clari ty developed using direct observations of the cervix and
and, yet, extraordinary simpli city. A consistency, color, the cerv ica l canal. Such a system , developed by Insler,
change, and sensation mucus cycle scoring system (3 et al1, assesses the amount of cervical mucus produc-
Table 14-1: The Color, Consistency, Change, and Sensation

Mucus Cycle Scoring System (3C'S MCSS)
Consistency Points Change' •· points Sensation'
Red (Brown) o Sticky (6) 2 D-D o Nonlubricative o

Cloudy (C) 2 Tacky (8) 2 D-NL 2 (O, 2, 2W, 4 )
Yellow(Y) 1 2 Gummy(G)3 2 D -L 4
Clea r (K)' 4 Pasty, cloudy 2 Lu bricative 4
(6 PC or PC )' NL-D O (10DL,10SL,10WL)
Stretchy (1 O) 4 NL - NL 2
NL - L 4
L- D o
L - NL 2
L- L 4
1. Use only when an isolated color observation .

2. Use also far C/K observations.
3. Use only when no color is recorded but gummy is recorded.
4. Score only 2 points far a PC or 6PC observation. Do not add 2 points far cloudy color.
5. D = Dry; NL =Nonlubricative; L = Lubricative.
6. Whenever lubrication is present, score an additional 4 points.
177
tion , the stretchability of the cerv ical mucus consistency ofthe mucus, the day-by-day change which
(spinnbarkeit), the ferning pattern ofthe mucus and the the mucus discharge undergoes and the sensation which
degree of open ing of the cervix observed at the time of is generated by the mucus discharge are the four com-
the cervical examination. This is a scoring system which ponents taken into account to generate the score.
is physician dependent.
Examples ofhow the 3 C'S MCSS is applied are found
In the 3 C ' S MCSS, point values are assigned to the in Table 14-2. In example A, a 5-day mucus cycle is
four major components of the woman 's vu lvar mucus shown . In exampl e B, a 1-day mucus cycle and, in Ex-
observations in such a fashion as to allow for an in- ample C, a 9-day mucus cycle (ora mucus cycle greater
creasing score as fertility increases. For each day 's ob- than six days in duration) are shown. Additionally, in
servations, the cumulative score from each of the four these three examples, the seores have been calcu lated
major components is calculated. These seores are then to be 9.3, 1.7 and 11.0 respectively for the three ex-
tallied for the six days of the mucus cycle beginning amples.
five days prior to the Peak Day and including the Peak
Day 's observations. The cervica l mucus score is then A random assortment of cycles were calculated, in a
obtained by totaling the daily points and dividing by blind fashion , comparing the subjective interpretation
six. In effect, the resu ltant mucus score is the average ofthe chart with the cervical mucus score as generated
daily mucus score for the total of the six days leading by the 3 C ' S MCSS . This study involved 197 cycles
up to and including the Peak Day. The 6-day time frame from 122 patients. 4
was specifically chosen because it approximates the av-
erage length of the mucus cycle as identified in previ- The mucus cycle was interpreted to be regular, lim-
ous studies.2.3 ited, or dry based upon the observation of a decreasing
amount ofmucus discharge . ln addition, subclassifica-
The 3 C' S MCSS is shown in Tab le 13- l. The color and tion ofthe regular and lim ited mucus cycles was devel -
Table 14-2: Calculation of the Basic Mucus Cycle Score
EXAMPLE A : Five-Day Mucus Cycle

-8 -7 -6 -5 -4 -3 -2 -1 PEAK
OAD 1 OAD 2AD OAD 6C/K

x1
8C/K
x2
l 10KL
x2
10KL
x3
l 10WL
x1
1 1 1 1
Total Cervical
Daily Points Points Mucus Score
-- -- -- o 8 8 16 16 1 8 56 56/6 =9.3
1 1 1 1 1 1
EXAMPLE B : One-Day Mucus Cycle
-8 -7 -6 -5 -4 -3 -2 -1 PEAK
OAD OAD 2x1 OAD 4x1 2AD 4x1 4x1 l 10C/K

x1
1 1 1 1 1 1
Total Cervical
-- -- -- o o o o o 10 10 10/6 =1.7
1 1 1 1 1 1 1
EXAMPLE C: Nine-Oay Mucus Cycle
-8 -7 -6 -5 -4 -3 -2 -1 PEAK
10C 10C/K 1
10K 10KL 10C 8C/K 10SL 10KL 10K
X1 X2 X1 AD X1 AD AD X2 X1
1 1 1 1 1 1
Total Cervical
-- -- -- 16 8 8 8 16 10 66 66/6 =11.0
1 1 1 1 1 1 1
Chapter 14: Objectiv e Class ificati o n o f t he Muc us Cyc le 179
Table 14-3: Blind Comparison of Chart Reading lnterpretation of Mucus Cycle with
3C'S Mucus Cycle Sco ring System (N = 197)
lnterpretation of Numberof Mean Mucus MucusScore Statistical

Muc.u s Cyc;l".s Cycles Seo re s.o. . S ig nifi can c~
Regular 73 11 .3 2.3
p<. 001
lntermediate regular 13 8.1 1.1
p<. 001
lntermediate limited 30 6.8 1.2
p <.001
Limited 59 3.8 1.9
p <. 001
Dry 22 O.O O.O
oped resulting in an intermediate regular and an in- a long with their respective mucus seores is outlined in
termediate li mited subc lassification . Fi g ures 14-1 through 14-5.
[n Table 14-3 , the results of this blind compari son of In order to use previously developed scoring systems,
the subj ective chart interpretation and the 3 C ' S MCSS an interna! vaginal and cervica l examination was nec-
is shown . The mean score for regular mucus cyc les was essary. With the standardi zation in vo lved with the
11 .3. Sim il ar mean seores for the other types ofmucus CREIGHTON MODEL, it is now possible to identi fy and
cycles were 8. 1 fo r intermediate regular; 6.8 for inter- classify the mucus cyc le in a given menstrual cyc le in
mediate limited ; 3.8 for limited; and O.O for dry. The women charting this system .
mean mucus cyc le seores were signi ficant ly different
for each of the five c lassificatio ns (with p-scores rang- With this approach , a new class ifi cation for the mucus
ing from <.001 to <.O 1). cycle has been developed and it is based upon the use
ofa vulvar mucus scoring system with no needfor in-
From this data, a classification ofthe mucus cycles ac- terna! examina/ion. This makes the system physician-
c.ording to the 3 C'S MCSS was developed. This is independent and gives CrMS users a greater opportu-
shown in Tab le 14-4. The type ofm ucus cyc le can thus nity to be health care participants.
be determ ined by calcu lation of the mucus cyc le score
using vulvar mucus observations in a relatively simple lt has been observed that the mucus cycles may vary
fas hi on. from one woman to the next and from one cycle to the
next. At the same time, it has a lso been observed that
A number of examples of the various types of cyc les there is a general consistency which exists in the ap-
pearance ofthe mucus cycle in a particular woma n. This
is especially true for the appearance of dry cyc les and
limited and intermed iate limited mucus cycles in women
Table 14-4: Classification of Mucus Cycles -
with infertility and repetitive miscarriage.
Mucus Cycle Scoring System
Range ·of Mucus lt is now possible to objectively assess the cerv ical
Type of Mucus Cycle Cycle Se.ore
mucus cycle based upon the woman 's vulvar observa-
A. Regular tions. The advantage ofsuch an objective system is that
Regular 9.1 - 16.0 it allows diffe rent observers to be objective in the means
lntermediate regular 7.6- 9.0
w ith wh ich they categori ze the type of mucus cycle ob-
B. Limited served in women charting their menstrual cycles through
lntermediate limited 5.7 - 7.5 the use of the CrMS . Such an objective means of as-
Limited 0.1 -5 .6
sess ing the mucus cyc le has been very helpful in assist-
c. Dry ing the growth in the know ledge ofreprod uctive func-
Dry 00 tion .
15 16 17 18 19 20 21 32 33 34 35
MCS = 10.3
H H M M
MCS = 10.3
H H H M M
MCS = 11 .0
M M IOC.K IO KL. IOCK loc.K IOCK
• I 11ól. •a. •& •:il.
se
xi
aAO o.o.o 4•3 OAO °"º OAO °"'º 4•;1. °"'° OAO
Type of Mucus Cycle

(MCSS)
Regular= 9.1 -16.0
Figure 14-1: Typ ica l examples of regular mucus cycles with their mucus cycle score (MCS) using the 3 C'S MCSS.
13 14 15 16 17 18 19 32 33 34 35
MCS • 8.3
Vl L H H M M L
;1.AO -.AD MO
MCS • 8.0
VL14HM
""º
MCS" 7.7
IOKI.. 4 11¡. c.K IK ICK 4AO C.P 4 1t.& 4. •il 4 •1

M M M l L VL 11 I 1111 • I ira IC 1
O.A.O OAO O.A.O
I
Type of Mucus Cycle
(MCSS)
lntermediate
Regular= 7.6 - 9.0
Figure 14-2: Typica l examples of intermediate regular mucus cycles with their mucus cycle score (MCS) using the 3C'S MCSS .
Chapter 14: Objective Classification of the Mucus Cycle 181
16 17 18 19 20 J2 J3 34 35
MCS = 6.0
M H
MCS = 7.0
H H
MCS = 7.3
M ~o ~ ~~ ~ aAO -...o 'iCK IOCX <.CK aw a.AD il.AO

H H M aAO v.o a.AD ~~ • I
KXJ(.
• I el • I AO
...
I
I I I
Type of Mucus Cycle

(MCSS)
lntermediate
=
Limited 5.7 - 7.5
Figure 14-3: Typical examples of intermediate limited mucus cycles with their mucus cycle score (MCS) using the 3C'S MCSS .
33 34 35
MCS = 3.7
L l
aAD OAO
MCS =4.6
MCS = 5.3
Type of Mucus Cycle

(MCS)
Limited = 0.1 - 5.6
Figure 14-4: Typical examples of limited mucus cycles with their mucus cycle score (MCS) using the 3C'S MCSS.
29 30 31 32 33 34 35
MCS =O.O
H M M
MCS=O.O
VL VL L M H M
OAO °"'º OAD
I I
Type of Mucus Cycle
(MCS)
Dry =O.O
Figure 14-5: Typica l examples of dry cycles with their mucus cycle score (MCS) using th e 3C'S MCSS .
l. ln s ler V, M e lmed H, Eichenbrenner l, et a l: Th e Ce rvica l 3. Hilgers TW, A braham GE and Cava nagh O: Natural Famil y
Score: A S imple Semiquantitati ve Meth od fo r Monitoring Pl annin g 1 - Th e Pea k Symptom and Estirnated Ti me o fO vu-
o f th e Menstru al Cycl e. lnt J Gynaec Obste! 10 :223, 1972. lati on. Obste! Gynec 52: 575, 1978.
2. Billin gs EL, Billings JJ , Brown JB , et al: Symptoms and 4. Hil ge rs T W: Th e Obj ecti ve Assess ment o f the Vul va r Mu-
Ho rm ona l Changes Acco mpanyin g O vul ati on. Lanctet 1:282, cus Cyc le. lnt Rev at Fa m Pl an 12:25 0-258, Fall 1988.
1972.
-----el~-6u-15
Scientific Foundations of the CrMS
D r. John Billings, in 1953 , bega n a search fo r a bio-

log ical marker offertility that wo men could them-
se lves easily recognize. To hi s surpri se- not being a
natu ra l fe rtili ty regulation .
ln 1976, a team of investi gators at St. Loui s University

gyneco logist- he fo und severa ! accounts of a stringy, Schoo l of Medic ine began a criti ca! independent inves-
lubri cati ve mucus produced at abo ut the ti me of ovu lati gation of the Billings Ovul ation Method. Out of that
tion by the ce ll s lining the cervix . 1•4 Indeed, as earl y as wo rk, the legiti mate, standardi zed offspring of the Bill -
1855, Smith 5 observed that conceptio n was most li kely ings Method, the CREIGHTON MODEL FertilityCare™
to occur w hen the mucus was " in its most fluid cond i- System (CrMS ), was developed .
tion." In 1868, the fa mous gyneco logist J. Marion Sim s6
also po inted out the importance of cervica l mucus to
human fe rti lity. Background of the System ----~
Although thi s mucus had been observed by doctors for T he fundam ental principi es of the CrMS ha ve been
many yea rs, gyneco logists never questioned wo men known to physicians fo r many yea rs and well docu-
abo ut their awareness of it. Dr. John Billings, a neu- mented although, as Cohen, et al4 observed, "They ha ve
rologist, began questioning a sma ll nu mber of wo men been almost dis regarded by gyneco logists ." In 1952,
with regard to the poss ibl e signi fica nce of the cervica l this group pub li shed a schemata of the events that oc-
mucus as a marker of ovu latio n. It became evident that cur relative to the changes in the cerv ica l mucus as ovu-
the occurrence of a mucus di scharge during the me n- lation ap proac hes. In retrospect, thi s schemata also de-
strua l cycle was a fa mili ar observati on. From 1953 to fi ned the basic prin cipies ofth e not yet described Ovu-
197 1, these pattem s were refin ed, the appli cati on of in- lation Method (F igure 15- 1).
structi ons was des igned, hormonal correlations were ac-
comp lished and the Ovulation Method carne in to ex ist- It was noted that as ovulation approac hed, the stretch-
ence. Dt: l yn Billings joined the effort in 1966.7 ab il ity and clarity of the mucus increased a long with its
qua ntity ofproduction. A t the same time, the viscos ity
The cervica l rn ucus and other bio logica l rnarkers have and its content of le ukocytes decreased. The most per-
now become the sing le rnost studied observations in tinent observation, however, was the indi cation that the
183
c ha rge th a t is c lear,
ll
stretchy or lubricati ve is
identified as the Peak Day.
CERVICAL MUCUS ~-::7 jL C <Jf:..7

The presence of the cervi -
cal mucus di scharge corre-
SPllllllUtm" 1 (ll. ',w. l ~CM. 12 Cll. 3 CM .
lates we ll with the ri sin g
~ITY TIUCk lolOOEU.n
....
T" lll Tl41 >1
...
TIW:'.k
levels of estrogen (F igure
QUANTITY
LEUCOCYTES
SPRM surtrvAL - +
o
*
*
+
Figure 15-1 : Cohen's orig inal schemata for the events th at occur in the cervical mucus around
~
o o
**
+
....
+
15-3) and the occ urrence
of the Peak Day is corre-
lated well wi th the timing
of ovulati on.
the time of ovulation Of special note is the depiction of th e sperm survival and the, de facto ,
recognition of the role of the cervicl mucus as a biological valve (From: Cohen MR, Stein IF, Because the production of
Kaye BM : Spinnbarkeit: A Characteri stic of Cervical Mucus. Fertil Steril , 3: 201 , 1952).
the periovulatory cervical
mucus is an estrogen de-
surv iva l of the spermatozoa was di rectly related to the pendent effect and is produced at the time of fo lli cular
presence or the absence of an ovulatory or periovulatory deve lopment, when estrogen is increas ing and ovul a-
type of mucus produced fo rm the cervix . tion approaching, the cervical mucus is produced and
will be di scharged before and during the time of ovula-
In the CrMS , externa! vulvar observations of the dis- tion. In long cycles (F igure 15-4) there may be occa-
charge ofthe cervical mucus, the presence ofbleeding, sional "patches" of mucus prior to the onset ofthe mu-
and the days when no discharge is present (dry days) cus associated with ovu lation. What is prolonged in these
are ali used to obtain pertinent information on the phases cyc les is the pre-Peak (or preovulatory) phase of the
offertility and inferti lity, and the state of the woman's cyc le and what remains relati ve ly consistent is the post-
procreati ve and gyneco log ic health the info rmati on is Peak (post-ovulatory) phase ofth e cycle.
obtained prospecti ve ly.
The same princ ipi es appl y in anovulatory conditi ons
While the fo ll ow ing paragraphs and fig ures were pre- such as breast feeding (F igure 15-5). In thi s ci rcum-
viously presented in Chapter 4, they are worth review- stance, infant suckling may suppress ovu lati on and fer-
ing at thi s time. tili ty fo r a number of months. The presence or absence
of the characteri sti c cervical mucus discharge assoc i-
In the woman with regular cycles, the cycle begins wi th ated with ovulation is then de layed until fe rtility retums
the onset of men struation (see the first cycle of Fi gure and predicts the onset of th e first menstrual peri od.
15-2). As menstruation tapers there is genera lly no di s-
charge and the woman observes this as dry. As ovul a- T he versatility of the system, clearl y one of its stron-
tion approaches, there becomes apparent a cerv ica l gest f eatures, is fo und in its fu ndamental biology. Be-
mucus di scharge w hich often begi ns as sti cky, cloud y
or tacky, cloudy discharge and eventually becomes clear,
stretchy, or lubricative . The last day ofthe mucus di s-
.. . . . . .. ..
.. "
1I JI ' d • I ti • I •I • " ni •l ni• 11 l zi ln (1t l!l ~.i nl• l n
IH IH.. f
" .!e -
lo ~
14 h4
H H f\
- ·-- Trr·-
- ~
..
Hf'\J1L
201Hl"I
H"
,_
'" IH ll lt
}'\t!r. VL
-
-- - - H u
-
· r-
-
..
-~~
h5
-
Figure 15-2: Three cycles charted for the CrMS showing the Figure 15-3: The relation ship of serum levels of e stra dio l - 17 ~
occurrence of menstruation, the pre-Peak dry days, the mucus and progesterone during the course of the menstrual cycle
cycle, the Peak Day (P), and the post-Peak dry days. Th e pre- and the occurrence of the mucus si gn and th e Peak Day (P) in
Peak phases are variabl e in length (1 4, 9, and 20 days) but one cycle of a wo man with normal fertility.60
the post-Peak phases are consisten! (14,15, and 13 days).60
Ch apter 15: Scientific Foundations of the CrMS 185
'I• • • ca use it relies on events !eading up to ovula/ion, it de-

••f
1 l J • J • 11 u u " u i. n 1.11 1t • 11 l u 1l u u ¡,, 11 :. n ! 1' ) J 1 Jl " ... ,.
i;,, " H M
11• •--f
i;,,~'·:--,,- - r1"
~!'f,~ ~f
_, _ _, _ _ _
H·. . . .....
·.~ """ \'i. • • • fines th e times offertility and infertility in a definitive,
day-by-day, prospective fashion. Previousl y diffi cult
f~ t ~ i 't ~
r•••• - -- - - - ---,. ~ •u
cases, such as long and irregu lar cyc les, breast feeding,
coming off of contraceptive pills, anovulatory states and
the premenopause, ali can now be dealt with in a posi -
Figure 15-4: The appli cation of the CrMS in long cycles. In tive fashio n without delay.
this 51-day cycle, the Peak Day (P) occurred on day 38 . Th e
post-Peak phase was 13 days in duration . During the pre-Peak Even in the case of a woman with a continuous mucus
phase, "patches" of mucus are apparent.60
discharge (Figures 15-6 and 15- 7), the days offerti lity
can be properly identi fied with the use of a base infer-
..
-··
, ¡, ,¡ . • .¡,, "l " l " l "I .. ¡ .... ¡. • " " . ¡,, " • I• l•I J1 JJ tile pattern (BIP) whi ch is identifi ed with the presence
' .11 :M .IJ
u u
-·-~
--
~ H ofan unchanging discharge. When fertility begins, there
1':';' ••
rl"I- - Ti-- -1T!\ "
wil/ be a change in the pattern, which is easi ly identi-
H uu ~ H u fied by the woman who has been properly instructed,
- 1-- T"' ~ ~~
;~ l l l~;; -il- --- , ,.- and with thi s change the beginning offerti lity is identi-
- I~ - ~
ft
--- 11 " '" '" .. - - - - ""º ""° """
- -- fied.
H m-! U-- --
~~ ~~ ~ . 'to< ':'i" """
- -nT The system is nota contraceptive one. lt is a system of
H M
.
M M
. ,.,. ~
H
.:
IH 81• • •f.. H
· ~"
u """""" O'oll....,,_,_ truefami!y planning (see Figure 15-8). Thus, the infor-
""PI':' ·• I~
~
·111 mation obta ined from monitoring th e phases offertility

.. M M
~""" """' """'"""-~ ~.J
H H lfli lf
..-;l"l"I - --rr - - TI and infertility can be used to either achieve or avoid
pregnancy. Users of th e CrMS know thei r fertility sta-
Figure 15-5: The application of the CrMS in breas! feeding .
"Patches" of mucus occur sporadically, dry days ususally tus on any particular day and are given the freedom to
predominate , and as ferti lity return s, the mucus pattern and utili ze th at informati on as they so choose. In addition ,
fertility return .60 the CrMS has now expanded its use as a reproductive
and gynecologic health maintenance system and is the
"hub" of the new women s health scien ce of
NaProTECHNOLOGY.
The Cervical Mucus as a

1 · -1~ 1~11, Biologic Valve - - -- - -- - -----.
1
'
j ~ POINT OF CHANG ~ ~
1 1 1 1 1 r1 The biophysical characteri stics of the cervical mucus,
1-+~__.._+-1-_., BREA STFEEDI NG
1
PRE -PEAK YEL LOW STAM PS
1 1 11 as they change throughout the menstrual cycle, have
1 1 111 1 1 1 1 11 received considerabl e attenti on over the years. 8· 11 In
Figure 15-6: The example shows the use of the CrMS in a 1972 , a World Hea lth Organizati o n co lloquium o n the
breast-feeding woman with a continuou s mucus discharge.
The plain yellow stamps indicate a discharge pattern which is
topic of "Cervica l Mucus and Hum an Reproduction "
the same from one day to !he next. Th e arrows indicate the likened the uterine cervi x to that ofa "biological valve"
poi nis of change and the baby stamps indicate days of fertility.60 which , "at ce1tain peri ods during the reproductive cycle
allows the entry of sperm into the uteru s, and at other
1 ! 1 • < o • J ,. Id !1 I! 1' I' 1• I• 1• I• 1'" 'r.1 ) 1 ·~ :' :• •• ~· '' '> "" 111 1 tt 1: 11 1 1..1 '' times bars their admi ss ion ." 12The CrMS basically pro-
vides the coupl e with the info miation on when that valve
J.( -'1 .,~f.<. ~~ !f!~ :f~j~ ':: :"::~~~c f,~~ ~~!j~~ !
,, .,. 1"
is open (a time offerti/ity) and when it is closed (a time
of inferti/ity) .
.1
1 1
H H "1 -~ t¡ ~ f; !~ ~ ~ ~ ~ ~ ~ :!t ~
1
l! ~ POINT OF CHANG Ej-¡- ~ An eva luation offem and channel patterns ofthe cervi-
" .~ , , ,. t 1 1 1 - 1
ca l mucus in women using the CrMS has also been un-
1 1 1
REGU LAR CYCLES PRE -PEAK YELLOW ST AMPS
I' i
dertaken.1 3 Cervica l mucu s was obtain ed from th e
' 1 1 111 1 1 11
Figure 15-7: In a woman with regular menstrual cycles and
endocervica l canal and assessed fo r the presence or
continuous mucus discharge, the base infertile pattern is shown absence of crysta l1ization ( fern ing) and dendritic chan-
up to the point of the change . The Peak Day is identified and nel formation in dri ed cervical mucus. These phys ical
!he pre- and post-ovulatory days of infertility are shown with characteristi cs of the cervical mucus were then corre-
plain yel low stamps .60
186 The Medical an d Surg ica l Practice of NaProTECHNOLOGY
lated with the vulvar observations of th e mu cus di s- the number of channe ls in th e cervica l mucus were al so
charge as observed by the women using the system (F ig- eva lu ated and corre lated w ith the wo man's vul var mu-
ures 15-9 to 15- 14). cus observa ti ons made th ro ughout the course o f the
menstrual cycle. 13 The fre quency of negative, poor pos i-
As the Peak Day approac hes, th e appearance of pos i- ti ve and good positive fern s was pl otted according to
ti ve fe rning become predominant and the negati ve fe rn s the obse rved s pectrum of fertility (Figure 15-1 3),
di sappear (Figure 15- 1O). The number of dendritic chan- through e ight prac tica! stages of th e CrMS cycle. Re-
ne ls present (per low power fi eld of the mi croscope) gress ion lines were then generated fo r these three groups
increases dramatica ll y beginning six days pri or to the and signifi cance testin g perfor med . The linear reg res
Peak Day. The largest number of channels was observed
on the Peak Day itse lf( Fi gure 15-11 ). The dail y increase 100
Nl C • 11 v 1s
in the number of chann els/ LPF as the Peak Day and

ov ul ati on approac h a long w ith the hormona l corre lates
are shown fo r one cycl e in Fi gure 15-1 2. Beca use the 50
mucu s cycle is an estrogen dependent and ov ul ation-

related eve nt, the data on th ese two estroge n-related
events, that is the deve lopment o f pos iti ve fernin g and
an increasin g number of dendriti c chann els, corre late 100
themse lves impress ive ly aro und the wo man 's observa-
ti o n of her Peak Day. These data show the ex istence of
a true bi o log ic va lve and corre lates w ith the observa-
ti ons of O de bl ad in hi s recent descripti on of P type
mucus.
COOO l'OS•ll YI S
100
Sim il ar data on the presence or absence offernin g and
1 1 J • t I• T l • l •I• 11 u l.J t• u i. IT 11 I' » ll u u u u :111 na :o,. JI JI» )f,. SO
l '"
'; '
111oll U •• 10 1 •• J • •• • l•• 1 p lto J , ,. , 1 .. 1 10 .. u l l t• ~
n n » o u 60 l9 20 11
Figure 15-1 O: The distribution of negative, peor positive, and

good positive ferns (n=301 ) ±. Peak Da y (P) at th ree-day
Figure 15-8: In this case, a woman of normal fertility, th e intervals .' 3 Negative and poor positive ferns are impenetrable
system is used to achieve preg nancy. Th e acts of interco urse to sperm . Only good positive fern s are associated with sperm
in the midst of the mucus cycl e (days 16 and 18) should be penetration (From : Hilgers TW, Prebil AM : Th e Ovulation
expected to result in pregnancy as they did in th is example . Method - Vulvar Observations asan lndex of Fertility/l nfertility.
Obste! Gynec 53 : 12-22, 1979).
Figure 15-9: Examples of a negative fern (A), channel formation when the fern is negative (B), a good positive fern (C), and
channel formation wh en the fe rn is positive (D) (1OOx) (From: Hilgers TW, Prebil AM : The Ovulation Method - Vulvar Observations
asan lndex of Fertility/lnfertility. Obste! Gynec, 53: 12-22m 1979) .' 3
Chapter 15: Scientific Foundations of the C rMS 187
125 sio n coeffic ient for th e negati ve f ern group was - 0.14
MEAN CHANNE L NUMBER/ LPF
and th e o bserved data fit thi s line at a hi g h degree of
u.. signifi ca nce (p.::;.0001 ). Th e regress ion coeffic ient for
Q.
-a:
...J 100
w
th e good pos iti ve f ern s was 0.13 and thi s aga i n indi-
cated a correlation t hat wa s stati st ica ll y hi g hl y signi fi -
co ca nt (p.::;.0002).
~
::::> 75
z Th e m ean channel number fo r th e sam e eig ht stages of
...J
w v ul va r mucus o bserv atio ns w as al so pl o tted in a sim il ar
z
z 50 fas hi o n (F ig ure 15-14). Th e regressio n lin e hada re-
< 12.95 and is hig hly significant
:e gress ion coeffi c ient of
(.)
z (p.::;.0008) (F ig ure l 5-14A). I n o rd er to test th e prec i-
<
w 25
sio n o fthi s sig nificance testin g, a natu ra l log tra nsfor-
~ m ati o n of th e m ea n channel number was done. I n Fig-
ure 15-14-B, the natu ra l log ofthe m ean chann el number
of these sam e eight stages is p lo tted . Th e regress io n
u . 'º '. ' • . ' p ,. · u
• 1 • 1J J . 1 l ' • • , •• 11 ll . 15
coe ffi c ient for th is li ne w as 0.42 and the fit of the ob-
Figure 15-11 : The mean number of channels/LPF ± Peak Day se r ve d d a t a was st a ti sti ca ll y hi g hl y si g nific ant
(P) at th ree-day interva ls (n = 294 ).13 No sperm penetration (p.::;.0001 ). Th ese data have lent eno rm o us support to
occurs (theoreticall y) when the channel number is below the the woman s vulvar mucus observations are
th e i dea th at
hash marked line (From : Hilgers TW, Prebil AM : Th e Ovulation
Method - Vulva r Observations asan lndex of Fertility/l nfertility. an extraordinary rejlection of the biophysical events the
Obste! Gynec 53: 12-22, 1979). mucus is undergoing at the leve/ of the endocervix.
PEAK SX.
.
A A
150
u..
Q.
...J
u; 100
Chs/LPF os •
.&;
o so
. o
...
o:>. 0 .5
B
~- 0 .2
: - 0 .4 ;
~-§, 03 Estradiol 1713
u;~ e 0.2 =0 5
~
w 0 .1 ;;
i'
f
e
25 0
LH o.o •
'E 200 ~ 10
:s] 150 ~
o
E 'ºº i
so
35
!o
., 30 o
2_ 25
Progesterone
.. -
.! E
& g>
20
15
o.o
-o2
e 10
STI CKY
Q.
º"'
P+4 TACKY º"'
Ptt -
STICKY
TACKY º"
P+ I
STICKY
TACKY
CLEAR
STRETCH Y
CLEAR
STRETCHY
to PASTY PEA K PAST Y PASTY lU8RICATIVE LUBRICATIVE
MENSES P+4 Pre - P+ J P+I Pre- PEAK
IO IS
" 'º
DAY OF CY C LE
30
MENSES
PEA K to
P+l
Figure 15-12: Individual cycle with (A) channel number per LPF, Figure 15-13: Frequency of (A) negative (b 0.14, p s .0001 ), =
(B) estradio l -17 ~ , (C) LH , and (D) progesterone .13 The largest (B) poor positive (b = 0.02, p s .333), and (C) good positive
number of cha nnels is consistently observed on the same day ferns (b = 0.13, p s .0002) by woman 's vu lvar observations
as the woman 's observation of her Peak Day (Peak Sx) (From: (From : Hilgers TW, Prebil AM : The Ovulation Method - Vulvar
Hilgers TW, Prebil AM : Th e Ovulation Meth od -Vulvar Observations as an lndex of Fertility/l nferti lity. Obste! Gynec
Observations as an lndex of Fertility/lnfertility. Obstet Gynec 53: 12-22, 1979).
53: 12-22, 1979).
188 The Medical and Surgical Pra ctice of NaProTECHNOLOGY
ln add iti on , with the definition of these stages of the This modelling of human ferti li ty, as observed in the
CrMS cycle, the system has become an excellent too! CrMS, was thus shown to have an objective, scientific
for the modeling and further stud y ofh uman ferti li ty. fou ndat ion and since the observations cou ld be easi ly
made and co l! ected from cyc le to cyc le and woman to
In looking at the fe rti lity cyc le based u pon the observa- woma n, a new way of look in g at human fert ility
tion ofthese bio logica l markers, the study ofan antici- emerged. This approach has all owed a who le new and
pated spectrum off ertility (Figure 15-16) could be com- dynamic way of look ing at human fert ili ty/infertility to
pared to an observed specturm offertility (F igure 15- come in to existence lending itself to widespread study
17) . In the antic ipated spectrum offerti li ty, eight stages and evaluation.
offertility/ infertility could be expected based on these
observations. These same e ight stages of the presence
200
or absence of ferning and the number of channels that 200
Max No Channel 100 x

were observed in the different stages, cou ld be objec-
tively ordered in a seq uence from ferti li ty to infertility. 150 150
T his could be subseq uently subdivided into two sepa-

rate stages based uon what was now known from sperm
100
penetration studies. Those stages offertility above the 100
hashed marked line in Figure 15-17 are objectively

shown to be ferti le and those beneath the line objec-
tivel y shown to be infertile.
A 1 1
1 21•
1 1 ,
_J
1 '1
•••••mnDDM•~"~-~~•a••~
1 1 1 1 11si1
••
1 1 1 1 1 1 1 1 1 1 1
50
• 500 16
- ..
Plasma 17 ~
Estrad iol Plasma Progesterone
pg/mL ng/ml
400 0--0
! 12
u.
o u. 300
¡
a: o..
Ll.J...J
ID -
:E '.'.]
::l Ll.J
zz
zZ • • 200
~~ "
:E u
100
• :1
• 1
-, . _ _. _. .. ... 1
• -· 1
• • 100 100
Plasma LH Plasma FSH
LL
a:
L/,J
~ 41
B 80
-
mUlmL mU/ml
0--- 80
o::> 60 60
e> z
o
...J
...J
...J
L/,J
z •
e( z ) 40 40
a: e(
::> :e
t- u
e( z
z ~ , 20 20
:E
• •
10-'--..---.-- ....---.-- -.-- -.-- --...- --.-__J
...°" ,..
STICllY
°" SllCU ., STICllY Clf A" Cl!A"
1
1
1
2
1
3
1
..
1
5
'
6
1
7
1
8
1 1 11' , 1 1 1
9 10 11 12 13 1• 15 16 17 18 19 20 21 22 23 2• 25 26
1 1 1 1 1 1 1
"
MUSES
TAC U
PASTY
P,. .
PtU
U.tal
,,.. ,.,
PASTY
l'+I u.cu
,.,
STJIHCHl
,,.. , ...
m1noo
PASTY WllUC AHVl WIJllCATIVE Cycledays
1
!
1
MUIS($
PU•ll.
,., PE.U. ~
OVULATION
Figure 15-14: (A) Mean number of channels/LPF (b=12.95, Figu re 15-15: Plasma levels of FSH , LH estradiol -17~ . and
ps.0008) (no sperm penetration occurs when the channel progesterone, maximum number of channels in the highest
number is below the hash marked line) and (B) natrual log of canalized mucus area during a 26-day menstrual cycle (From :
mean cha nnel number by woman 's vuvlar observation by stage Faccioli G, Cortesi S, Calderoni P: Structure of Human Cervical
of CrMS cycle (b=0.42 , ps.0001) (From : Hilgers TW, Prebil Mucus Correlation with Plasma Ovarian Hormone Levels . Acta
AM : The Ovulation Method -Vulvar Observations as an lndex Europaea Fertilitatis. 14: 41-50 , 1983).
of Fertility/lnfertility. Obste! Gynec 53 : 12-22, 1979).
Ch apter 15: Scientifi c Foundations of the CrMS 189
Anticipated Spectrum of Fertility
Fertile
Peak
Clear, Stretchy, Lubricative
+
Pre-Peak
Clear, Stretc hy, Lubricative
Pre-Peak P + 1 to P + 3 P + 1 to P + 3
Sticky, Tacky, Pasty Dry Sticky, Tacky, Pasty
Pre-Peak
+
P + 4 to Menses = P + 4 to Menses
Dry Dry Sticky, Tacky, Pasty
lnfertil e
Figure 15-16: The anticipated spectrum of fertiilty based upon the CREIGHTON MODEL System .
Us ing identical techniques fo r assess ing the channel for- and deserve spec ial atte nti o n a nd descripti on. A chro-
mation of cerv ica l mucus, Facc io li , et al 14 a nd Garc ía, no logy ofOdeb lad 's work is outl ined in Tab le 15-l.
et al 15 made s imi lar observatio ns (F ig ure 15- 15) and
ad va nced o ur know ledge. lt was clea rl y demonstrated 15 Odeblad has shown that th ere a re three gro ups of cell s
that as ovulation approached the leve ] of estradio l - 1 7~ in the mucus me mbran e of the cervix .
increased, a nd there was a coi ncidental inc rease in the
number of channels fo rmed in the cervica l mucus . Thus, 1. Cy lindri ca l (co lumna r) sec retory cells (the ma-
the estab li shment of channe l fo rmation asan event de- jority);
pendent upon estrogen stimul atio n of the e ndocervix
2. Cy lindri ca l (co lumna r) ciliated ce ll s; and
was furth er substantiated (F ig ure 15- 19).
3. " R eser ve" cel ls.
Asa n as ide, it was a lso shown that th e number of c ha n-
ne ls co ntin ued to inc rease whi le the good pos itive T he orig in of the secretory ce ll s is kn own but the mode
fe rning sta bi lized, indi cating the cha nnel fo rmati on was of developm ent of the othe r two gro ups of cell s has not
a more sensitive indica/ar of endocervica l function an d yet been deft ned . Th e ce lls ofthe muc us membrane are
estrogen stimulation . In additi o n, pregna ncy, in go na- s low ly detac hed and are di splaced with the muc us. New
dotropin-stimu lated cycles, was observed to occur more ce ll s are formed to repl ace the m.
frequently in patients who had ever-increasing dendritic
c hanne l formation (F ig ures 15-20 and 15-2 1). The molecular weight of the mucus is about 70,000
Daltons and it is believed to be severa! mi Il io n Da ltons
fo r ge ls. Acco rding to Odeb lad , the mu cus is nota nor-
The Work of Professor Erik Odeblad ==l ma l but an a bno rmal fluid and its viscos ity ca nnot be
measured us ing li qu id- fl ow tec hniq ues. lt is, therefore,
The lifetime work of Professor Erik Odeb lad is a clas- necessary to use other methods preferably nuclea r mag-
s ic and unique researc h effort in natura l ferti li ty regula- neti c resonance (NM R) techniques, whi ch do not in-
ti on and the biophys ica l characteri stics of the cervical vo lve fl ow but rather the use of the thermal moveme nts
muc us. 16 •20 Th is work, met ic ul o us ly eva lu atin g the of mo lecules in the fluid .
anatomy and physiology ofthe e nd ocerv ica l canal, the
biophysical characteristics of its cervica l mucus through- Odeblad gathered mucus sampl es by using two differ-
o ut the various phases of the me nstrua l cyc le and the e nt ap proaches:
mapping ofth e endocervix are s ign i fíca nt contributi ons
Observed Spectrum of Fertility
Fertile
Peak
Pre-Peak
P + 1 to P + 3
•
Sticky, Tacky, Pasty
P + 1 to P + 3
•
Dry
Pre- Peak
Pre-Peak
•
Dry
P + 4 to Menses
P + 4 to Menses
Dry
lnferti le
Figure 15-17: The observed spectrum of fertility using fern and channe l studies arranged according
to the various stages of the CrMS cycle (see Figures 15-13 and 15-14 ). Those observations above
the lineare assoicated with sperm penetration and !hose below the lineare assoicated with no sperm
penetration . This reveals two basic phases of the cycle: fertile and infertile (see text).
Figure 15-18 : This photograph of the endocervical canal shows the

ca nal (left} and four separate openings of the endocervical crypts into
the endocervical canal. In doing his studies, Odeblad microsampled
these individual crypts (From : Pope Paul VI lnstitute research , 2004).
Cha pter 15: Scie ntific Fou ndation s of the CrMS 191
JOO
T
IOO
100
T
mean 12 . 4 : mean 3 4 .6 : mean 6 5 38
•
''
T
'' '
1 ~·
'
200
r I '
,,1 1
' ),
-e -
1
1
fr -
""'
E '
'
1
50
,,
'1
,, T
1 e
"'
' I
1
-5"
. l/ <i"'
~
e
e
"'
.e
o
o
: 1¡ ,,:;;
J
E
e"
o
_, .,
o
-· -· o
da ys
+ + + + + +
days
fern ing
Figure 15-19: The rela tionship of rising levels of estradiol-17 ~ Figure 15-20: The mean number of channels according to the
(E 2 ) and the number of channels observed in dry cervical grade of the fern an the number of days that grade was
mucus .' 5 The shape of the two curves is nearly identical observed .15 The grade of ferning is divided into three (+ , ++ ,
al though the peak in channel formation precedes the peak in +++)overa period of eight days . Whi le ferning grade remai ns
E2 by about 24 hours (From : García N, Giacchi E, Campo S, the same, the number of channels continues to increase. This
et al. Canalization of Human Cervical Mucus. Obsert Gynec, confirms that the number of dendritic channels observed in
64 : 164-169, 1984 ). dried cervical mucus is a more sensitive indicator of
endocervical function and estrogen stimluation (From: García
N, Giacchi E, Campo S, et al. Canalization of Human Cervical
Mucus . Obsert Gynec, 64: 164-169, 1984) .
..__. p r egn a n t
- . no pregn an t
100 J
50
-7 -6 -5 -4 -3 -2 -1
Days
Figure 15-21: The mean number of channels in gonadotropin
stimulated menstrual cycles as ovulation approaches . Those
women who became pregnant versus !hose who did not
acheive pregnancy are separated in the inset graph (From :
Garcia N, Giacchi E, Campo S, et al. Canalization of Human
Cervical Mucus. Obsert Gynec, 64: 164-169, 1984).
192 The Medica! and Surgical Pract ice of NaProTECHNOLOGY
with the upward movement ofsperm in the cervica l ca-

Table 15-1: Chronology of Odeblad's Work nal. The mapping of the endocervical canal, worked
Mapping the Endocervical Canal out by Odeblad, is shown in Figure 15-22 .
Year Event
Over the years it has been shown that the S-typ e mucus
1959 First reported that different types of cervical is very fluid (Figure 15-23) and that the sperm cells move
mucus were produced by different crypts along the cana l very rapidly reaching the S crypts in 3-
(NM R)
1Ominutes . The L - ty pe mucus has a medium viscosity.
1966-1968 Two mucus types described :
Type G and Type E Un it structures of L type mucus attract maiformed sp erm
1977 First published G, L, S model ceffs or those which move slow ly in an efficacious "fil-
1983 Began working with Drs. Bill ings and Brown tration " of sperm cells . The G-typ e mu cus has high
1990 P-type mucus was characterized viscosity and forms an impenetrable plug.
1993 F-type mucus was characterized
In 1983 Odeblad began working with the Drs. Billings
and Professor James Brown in Melbourne, Austra lia. 19
The hormonal response of the G, L, and S mucus was
studied. ft was found that the L-type mucus was stimu-
lated by medium and increasing levels ofestrogen while
1. lnvestigations of intracanalicular mucus usin g the S-type mucus was stimulated by high levels of es-
macrosamples ofmucus. trogen. Later, it was also shown that S-type mucus was
stimulated by noradrenalin. T he G-type mucus was
2. l nvestigations ofm ucus obtained from individual
crypts using microsampfing techniques (a me-
ticulous gathering ofmucus and mapping ofthe
endocervix using micropipettes) (see Figure 15-
18). ISTHMUS
In 1959, he reported the results ofmicroscopic exami-

nations which showed that the cervical mucus was com-
posed of different types which were produced by dif-
ferent cervical crypts. In 1966, the existence of crypts
which responded differently to the same hormona l stimu-
lation was shown. Rudo lfsson ,21 a collaborator of
Odeblad's, showed in 1971 the ex istence of crypts which
could contain two types of mucus. These crypts are
thought to have two branches with a common opening
with the branches having different secretory functions .
By 1968, two types of cervical mucus had been identi-

fi ed and characterized. One of these types had a high
viscosity (G) and the other hada low viscosity (E). The
Type E mucus was stimulated by estrogens and the Typ e
G mucus by progesterone. The G type mucus was pro-
duced in G crypts and the E type mucus in E cr yp ts. /
EXTERNAL
CERVICAL
Research during the years 1970 to 1975 indicated that
os
the progression of spermatozoa in the Type E mucus
was complicated and this mucus was composed oftwo
different types ofmucus named Type S (S = sperm trans- VAGINA
mis ion mucus, E5 ) and Typ e L (L = locking-in mucus
Figure 15-22: A schematic drawing of the endocervica l canal
because ofthe capac ity ofthat mucus to attract anden- indicating the distribution in the cervix of the fo ur types of
close malformed sperm, EJ This allowed for the de- mucus: E5 , EL' EP,and G. Th e location of the production of the
velopment ofthe G, L, S m od el of cervical mucus pro- F mucus is identified (F) and the originating location of the Z
duction , and it explained the major factors associated granules (Z) (This schematic is adapted from Odeblad , 1977
and 1994 ).19
Chapter 15: Scientific Foundations of the CrMS 193
stimulated by progesterone In th e first infertile ph ase elevated , the G crypts are strongly stimul ated . This G
of the menstrual cyc le th e progesterone leve!, whi ch is mucus is very dense (G + mucus).
low at that time, is, acco rding to Odeblad, suffi cient to
feeb ly stimul ate the G crypts (G - mucus). A fter ovula- Whe n comparin g these types of muc us to the woma n 's
tion , when the progesterone leve ls are in creas in g and observations, no vul var mucus is usually assoc iated w ith
the G-type mucus and the days are dry during the infer-
til e ph ases. When estrogen levels inc rease, the L-type
muc u begins to be produced. Later, when estrogen lev-
e ls are high, the S-type muc us is also produced and there
deve lo ps a lubricative sensation a nd this generall y re-
mains until the Peak Day. On that day, estrogen leve ls
are a lready decreasing but the noradrenal in-like activ-
ity ofthe sympathetic nervo us system additionally stimu-
lates the S-type mucu s. After th e Peak Day, G-type mu-
cus is accompanied by a dry sensation dueto the abu n-
dant secretion of progesterone by th e corp us luteum .
The te mporal relationships of the diffe rent secretions
I~ aro und the timing of ovu lation are shown in Fi g ure 15-
1-0 1·5 2·0

IA
2·5 3·0
24.
The characte ri stics ofthe cervical mucus have also been

Log T 1(spin · lattice relaxation time , water protons) . - - . . .
studi ed rather ex tensively by oth er investigators using
100 30 10 sca nnin g electron microsco py techniques (SE M) 22 •24
. . . _ Viscosity of the water phase of mucus Pu re
water (F ig ures 15-25 to 15-27).
Figure 15-23: Viscosities of microsamples of the different types
of mucus (from Odeblad , 1994 ).19
Follicular Development
Q ~
d':;:
Ovulation Luteal Development
j~ ~~-...
-#<
"
100
81
64
- r- i--
G r- i--
r- r-
-\ 1\ . . .. ...
L /
/ -
,,.,,,.. ......
G
~ 49
~
.!! -..}
ca 36
u V
en
'C
25
... .• 1\ ~
r\
...ca
Cll
16
... ...
V \
KV-...... \....
::::1
.. ~.F ... - - V
C' L
.. .. ..F
9
"' ... -·s -- -·
- --
4
----
¡..- -; • • • • •
- lt •V, 11 i--
.- .--• • • • •• ~ ::;.. .:-:- ..- --.. ..• ...--...
p
F
1
~-
.:.....:.:.. ;.: ... ~ •..;
• • • • •p
- - s
• •• • • lt
o
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3
t
'°:1111
111'
6 7 8 9 10 11 12 13 14 15 16 17 18 19 1
24 25 26 27 28 29
~ ~ ~ ~~ .~ ,~ l~
Figure 15-24: The cycle of a high school student, a virgin of 15 years of age . She has been cha rting for severa! years. Analyses
of types of mucus (S , L, G, P, F) on a microscopic slide are given . Da y of ovulation was determined by repeated palpatation (from
Odeblad , 1994 ).' 9 The Ovulation Method chart (BOM ) is correlated with the graph and the Peak Day is marked (X) (adapted from
Odeblad),
194 The Medica! and Surg ical Practice of NaProTECHNOLOGY
Figure 15-25 : Scanning el ectron Figure 15-26: Scanni ng electron ic Figure 15-27 : Sca nn ing electro ni c
microscopic photograph of filamentous features of fil amentous mucus of the aspee! of fil amentous mucus of post-
mu cus of the middle preo vulato ry o v ulato ry ph ase . 22 ·23 Th ere is an ovu la tory phas e. 22 ·23 Sper m do not
phase.22 •23 Sperm do not penetrate th is opening of the spaces in the mucus penetrate th is type of mucus.
type of mucus. al lowing for sperm penetration .
(Fro m: Faccioi G: Preliminary Results on the Sca nning Electron Microscopic Sructure of the lnfertile Human Cervi ca l Mucus.
Acta Europaea Fertil itatis , 15: 38 1-382 , 1984)
Sperm Penetration --------~ zoa did not occur until the third day prior to the LH
surge (oran estimated 4 days pri o r to ovulati o n). Pri o r
One ofthe bi o logica l prin cipi es ofthe CrMS is th e con- to that time and o n the th ird day fo ll ow ing the LH surge
cept that the s urvi va l and penetra ti o n ofth e spe rmato- (or 2 days past the estimated time of ovulati o n), there
zoa a re directl y re lated to the presence of a good q ua l- was aga in no s ig ni fica n! perm penetra tion ide ntifi ed
ity, estrogen stimul ated cerv ica l muc us. A nd thi , too, (see Sperm Penetra ti o n F2 in Fi g ure 15-29-8). Thi s
may be re lated to the qua nti ty of that muc us produc- stud y, pe rhaps mo re tha n a ny other, shows the impact
tio n. T he pres umpti on ex ists tha t the penetration of of the cervica l mucus ac ti ng phys io log icall y as a bi o-
sperm th ro ugh the e ndoce rvica l canal is ant icipated logica l va lve w ith regard to spenn penetra ti on . These
w he n an estrogen-stimul ated cerv ica l mucus is present observati o ns have qua litative ly been made by othe rs.
at the vul va. lt a lso presum es th at w hen th ere is no d is-
cha rge of cerv ica l muc us o r during the base in fert il e An in vivo mode l was studi ed by lns ler. 27 By pretreat-
pattern o r during the post-Peak phase of the menstrua l ing the uterus a nd cervix w ith va ri o us estrogenic and
cyc le, there is a natural impenetra bility ofth e sperm . A t proges tageni c ho rmones fo ll owed by inseminati o n and
o ne po int in the cyc le, the biologica l va lve is open whil e subsequent hyste rectomy, the we re able to concl ude that
at other po ints the bi ologica l va lve is closed . These pre- th e amo unt, phys ica l qua lities and che mical composi-
sumpti ons a re built o n the extensive basic sc ience eva luti o n ofthe cervica l mucus determin e both the extent of
ati o n of the cerv ical muc us that has been just presented . cervica l invas io n by spe rm ce li s a nd the storage capac-
ity ofthe crypts. Furthermore, they observed that estro-
Good studi es o n sperm penetrati o n are di ffic ult to fi nd. gen enhances a nd progesterone and related compounds
One ofthe few pregnanc ies in w hi ch the timing of sexual significantly hinder the sperm s ability to penetra/e the
inte rcourse and th e timin g of ovul ation (by in direct hor- uterine cervix. Othe r studi es of penetra tio n of th e cer-
monal paramete rs) is known was publi shed by Ferin, et vica l muc us by the sperm suggest that the abili ty ofth e
al2 5 (F igure 15-28) . Whi le thi s appears to be a 5-d ay sperrn to survive and pe netrate the cervix may last only
sperm surviva l, th e ri se in proge tero ne suggests that between 24 a nd 4 8 ho urs. lndeed, prac ti ca ] experi ence
th e spe nn su rv iva l may ha ve been o nl y 4 days and cer- with the use of the CrMS over the pas t severa ! yea rs
tainl y no g reater tha n 5 days. continues to suppo rt the principi e that spenn surviva l
and penetratio n i direct ly re lated to the prod ucti o n of
Mogh issi, et al,26 eva luated sperm penetra tion in vitro an adequate q uality a nd q ua nti ty of good cervica l mu-
in a gro up of pati ents w hose cerv ica l muc us was al o c us.
bein g eva luated fo r a variety of other parameters. Sig-
nifi cant penetrati o n ofthe cervica l m ucus by permato-
1 . • ,. 700
400
37'C
•
300 BBT
I 200
20 ;g
oGl
--.
1
"'E 36'C m
"'"'
Q. "'....
m
o 120hours 1
,, 15 elz
..J
E
10oi SEXUAL
, m
3 90- INTERCOURSE ff :J
E 8 §-,....
c5 70 10 s.
:E
:e 60 "C
o;-
a.
Q; 50
40
."'3
"C
e
N
5 91
30 LH • HCG
>
·:; ~
.cr
:e
20
10
..J
o
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
Oays after last menstruation
Figure 15-28: Time re lationship between plasm a LH-HCG levels, plasma progesterone levels, basal body temperature (BBT),
sexual intercourse , and beginning pregnancy. Note time elapsed between intercourse and estimated date of ovulation 25 (From :
Ferin J, Thomas and Johansson EDB: Ovulation Detection . In Human Reproduction: Conception and Con traception (Hafez ESE
and Evans TN , Eds .) Harper and Row, Hagerstown, MD , 1973).
24
Sperm
:¡(+)A~ 18 Penetrotion
12 FI
o i ' ' ' 1----.---r- r- ~--,----,---,--,-
6
19
Sperm
12 Penetrot lon
6 F2
+,A/,
16
Spinnborkeit
12 (c m)
.f · : ~
1
+fo +14
0
-4 o +4 +8 +12 +16 f8'- 14 - 12 -1 0 -e - 6 - 4 - zo •4 +e
•6 •fo
+12
•14
•1e
Doys of Cycle \V Doys of Cycle
Figure 15-29 A&B : Changes in various properties of cervical mucus throughout the menstrual cycle. Day O= day of LH peak
(dotted line), F, and F2 indica te the number of sperm atozoa in first and second microscopic fields (x200), from interface in in vitro
sperm-cervical mucus penetration test. Vertical bars represen! one standard error of the mean26 (From : Moghissi KS , Syner FN ,
Eva ns TN : A Composite Picture of the Menstrual Cycle . Amer J Obstet Gynec. 114: 405-416, 1972).
Hormone Assessment and Correlationl mated time of ovulation did not resul t in pregnancy. Two
cyc les after th e conclusion ofthi s stud y, the patient had
A number of in vestigators ha ve eva lu ated the relati on- the resumpti on of a cerv ica l mucus pattern si milar to
shi p of the time of ovulation to the wo man 's observa- that fo und in Fi gure 15-32 8 and pregnancy occurred
ti on ofth e Peak Day. 28 · 33 The results of these observa- and proceeded w ithout diffi culty. Her actual CrMS chart
tions appear in Table 15-2. Taking into acco un t sorn e is shown in Fi gure 15-33.
vari ati ons in the structure of each ofthese stud ies, the re
is a striking relationship between the wo man 's observa- Extensive hormone evaluation of the mucus sign in hun-
ti on of the Peak Day and the occurre nce of ovulati on as dred s of me nstru a l cyc les ha s bee n do ne bo th in
determined by indirect honnonal para meters. Mori shita, Melbourne and in Omaha . Th ese pro.files continue to
et al,34 have described similar horm onal corre lates to show these exacting relationships.35
increas ing quantiti es of c lea r endocerv ica l mucus.
T he re lati onship of the reproducti ve hormones to the

woman 's observation of the Peak Day and the estimated
time of ovu lation are shown in Figure 15-30. 32 Hil gers,
et al3 2 publi shed a number of menstrua l cycles show-
....
...,_
ing, in additi on, the relati onship ofth e preov ulatory ri se
in estradi o l - 1 7 ~ and th e occurrence of ovulation (using
ind irect horm ona l parameters) with the presence or ab-
·-
sence of the mucus cyc le. These are shown in Figures
15-3 1 and 15-32. In Figure 15-3 l A, a norm al 32-day
menstrua l cycle is shown. T he mucus cyc le begins at
g
e-
-
the start of the preovulatory ri se in estradi ol and ovul a- ...CIC E. . .200
::: ~
tion occurred by Peak + 1. In F igure 15-3 1B, a longer ... .100
menstrual cycle is shown, 38 days in du ra ti on. Whi le

the preovu latory rise in estradi ol and ovul ati on are both
de layed in thi s cycle, a conco mitan! de lay in the ap- COMPOSITE
100
115 NORMAL CYCLES
pearance of the mucus sign and occu1Tence of the Peak
1• ' l'f•• ••
Day are a lso observed . There is an additi onal co inc id- e
ing of the Peak D ay w ith the time ofovu lation. F inally,
:e "3
-' ...E
so
: • 1 IT O
¡ ...
in F igure 15-3 1C, the di scharge score retl ects a con-
tinuous mucus discharge. Even in the presence ofsuch
a di scharge, the wo man was able to identi fy the preovu- ,.
latory change in the mucus pattem and the Peak Day a li
corre lating very we ll with the vari ous hormonal para m- 10
eters.
w
In F igure 15-32, the horn1one levels and di scharge seores z
in th ree consec uti ve cyc les fro m the sa me pati ent are ~
w-
"
.._e
shown. Th ere are a coup le of important fea tures in thi s "'~ ....g'
pattern . The first cycle shows a short 3-day mucus cyc le. o-
a: 10
Q.
lntercourse in th is normally fe rti le coup le occurred the
day befare the beginning of the Peak type mucus. No
pregnancy occurred and the correlati on of the mucus
13 ~,.,,..,,,,..,......_,,,.._,.,,.,,,"""",.,.,,,..,.,,,.,.,,¡f.......,,,..,,-,..,,,.,,,,,,,"""",,.,,,,..,,,,,"""
sign and the Peak Day correlated well with the hormonal _
10
:fú\::::·::: · -: : ;·: - ;::::::=:::-::bt .:V~//t
events. Fi gure l 5-32B shows a normal m ucus cyc le in o.o
the sa me patient with similar correlati on. In F igure l 5- DAY OF C YCLE
32C, no mu cus was observed in spite of the presence of

a perfect ly norm al hormona l patte rn of ovulati on. A n Figure 15-30: The mean serum progesterone, LH, estradiol-
1 7~ . an d BBT values for 65 hormonally normal cycles iwth the
exact expl anati on fo r thi s dry cyc le has not yet been
day of the estimated time of ovulati on (ETO) used as the center
fo rthcoming but a target (end) orga n fa ilure of the ce r- point. The Peak symptom and standard error are identified25
vix could expla in thi s particular set of ci rcum sta nces. (From : Hilgers TW, Ab raham GE, Cavanagh D: Natural Family
lnte rco urse that occurred both before and after the esti- Planning - l. The Peak Symptom and Estim ated Time of
Ovu lation. Obste! Gynec 52 :575-582, 1978).
Chapter 15: Scie ntific Foundatio ns of the CrMS 197
BBT
990
... 980
•10
~
16
DI SC HA RGE
SCORE
05
-'
E º'
g. 03
02
01
LH LH LH
250
-' 200
~ 150
E 100
50
35
PROGESTERONE PROG ESTERONE
30
25
-' 20
~ "
10
10
" 20 25 30 35 10
"DAYDF CYCLE
20 25 30 35 10
" 20 25 30 35
Figure 15-31 : Serum progesterone, LH , e stradio l -17~ , discharge seores, and BBT va lues fa r a norm al 32-day cycle (A) , a long
38-d ay cycle (B), anda cycle wi th continuous discha rge (C). The first vertical line indicates the Peak Day and the second ve rti cal
line ind icates the fourth day after the Peak or the beginning of post-Peak infertil ity32 (Fro m: Hilgers TW, Abraha m GE , Cavanagh
D: Natural Family Planning - 1. The Peak Symptom and Estim ated Time of Ovulation. Obste! Gynec 52 :575-582 , 1978).
DISCHARGE
SCORE
0.5
_,
.§
...
0.3
"'e:
LH
,,. LH
_,
200
~ "º
e 100
50
" PROGESTERDNE
PROGESTERONE
"'
_, "
.§ 20
"'e: "
10
25 30 35 10 15 20 25 30 35 10 15 20 25
"' 35
DAY OF CYCLE DAYOF CYCLE DAY OF CYCLE
Figure 15-32: Serum prog esterone, LH , estradio l- 17 ~ , discharg e seores, and BBT values in th ree con secutive cycles from th e
same palien!. The third cycle was "dry" with no Peak. Acts of intercourse are indcated (IC) and the estimated time of ovulation
was day 15 (cycle C)32 (From : Hilgers TW, Abraham GE , Cavanagh D: Natural Family Planning - l. Th e Peak Symptom an d
Estimated Time of Ovulation. Obste! Gynec 52 :575-582 , 1978).
Table 15-2: Relationsh ip to the Estimated Time of Ovulation Measu red by Vario us Hormonal Methods
and the Woman's Observation of the Peak Day, P u blished Evaluations
lnvestigat or a.nd Year of Study

BILLINGS• FLYNN• CASEY' HILGERS• CORTESl~.
Estimated nme of Australia" Eng land'º Australia'' USA" ltaly"
Ovul ation to 1972 1976 1978 1978 1981
Pea.k Oay n % n °/o n % n % n %
P-3 o O.O o o.o o o.o 1 1.5 o O.O
P-2 1 4.5 o O.O o O.O 12 18.5 1 3.1
P-1 1 4.5 3 10.3 o O.O 13 20 .0 4 12.5
PEAK DAY 5 22.7 10 34.5 3 30.0 24 36.9 21 65 .6
P+1 9 40.9 13 44 .8 7 70.0 9 13.8 6 18.8
P+2 4 18.2 3 10.3 o 00 4 6.2 o o.o
P+3 2 9.1 o O.O o O.O 1 1.5 o O.O
NO PEAK - - - - - - 1 1.5 - -
TOTAL 22 99.9 29 99.9 10 100.0 65 99.9 32 100.0
a. Used day alter LH surge as estimated day of ovulation : P-2 to P+2=90 .8 percent.
b. U sed maximal mucus grading (MMG) which was defined as the maximum amount of clear mucus . Where equal seores occurred on two days, the
second of these was taken as the maximum . Data has been recognlzed from th e original to co rrelate MMG with the estimated time of ovulation
as calculated as the day alter the LH surge: P-1 to P+2 =99 .9.
c. Used time between LH surge and rise in progeste rone to estimate time of ovulation : Peak to P+1=100 .0 percent.
d. Used midpoint in progesterone rise from 1.0-2 .3 ng/ml to estimated time of ovulation: P-2 to P+2=95.4 percent.
e. Used day alter LH Peak as estimated time of ovulation . P-2 to P+1=100.0 percent.
15 ló 17 29 30 31 32 33 34 35
D~Y O"!' DRf

:r T I
L H ¡V\ L L VL VL
VL Pl?Y º~"ce"( ORY º""
nRV Dfi'( Ofi'( DN ctl( oR'(
r I r·~
L L
Dt~ Pf!Y
I I I
m---+--+---+--+-1--+-..--+--+---+--+-r-
t
Ovulation -+---+-+-"t--........-+--+--+-+--1t--t-- -+--+---+--+-1--+--11
HORMONE STUDY - CONSECUTIVE OVULATORY CYCLES
Figure 15-33: The CrMS chart, th ree consecutive cycl es , of the woman shown in Figure 15-32 A, B, and C.
Chapter 15: Scientifi c Fo undations of th e CrMS 199
Correlation with Ultrasound ___ _ ~

Table 15-3: Mucus Sign s Related to Ovul atio n
and D etermined by U ltraso und Serial ultrasound examin atio n of th e ova rian fo ll icle is
(N = 9 and 12) the newest technology to be used to assess the correla-
Day n 'lo tion betwee n the changes in the biophys ica l prope1iies
Most abundan! -1 1 11 .1
of the cerv ical mucus and the events occurring at the
fertile-type mucus o 7 77.8 time of ovulati on. Leader, et al,36 showed the re lation-
+1 11 .1
ship between the increas ing diameter of the dominant
Las! day of -1 o 00 preovulatory fo lli cle and its subseq uent rupture w ith the
fertile-type mucus o 4 33.3 increas ing In sle r cerv ica l muc us score (F ig ure 15-34).
+1 7 58 .3
+2 1 8.3 S imil ar observat ions were made by Da il y, et al,37 and
1 Depares J, Ryder REJ , Walker SM and Scan lon MF : Ovarian
Nu lsen , et al. 38
ultrasonography highlights precision of symptoms of ovulation
as markers of ovula tion. British Medical Journal. 292 :1562,
1986. In looki ng at the relationship of the Peak Day to the
occurrence of ovulati o n by ultrasound, Depares, et al3 9
pub li shed the data fo und in Tab le 15-3.
Ultrasound assesses the anatom y offo lli cu lar de ve lop-

ment and subsequent rupture of th e fo lli cle (presump-
Table 15-4: The Creighto n Model System: tive ovu latio n). This stud y revea led the continuing, re-
Correlating the Peak Day with Ultrasound markably close assoc iati o n of th e timing of ovu lation
Parameters of O vulation (N=33), to the occurrence of the Peak Day. H ilgers has con·e-
Patients with lnfertility lated th e rupture of th e ovari an fo llic le relative to th e
Follicular Rupture wo man 's observa ti o n of her Peak Day in wo men with
Relative to the Peak Day' n 'lo infertili ty. The resu lts of this stud y are shown in Tab le
P-2 2 6.1 15-4. The ruptu re of the fo lli c le in this study (n=33)
P-1 5 15.2 revea led a close assoc iatio n, o nce aga in , w ith th e ob-
Peak 11 33 .3 servance of th e Peak day a nd a range cons iste nt w ith
P+1 9 27 .3 previo us hormonal eva luation ( P-2 to P+3). Thi s study
P+2 3 9.1
has now been expa nded to 43 2 cyc les w ith th e same
P+ 3 3 9.1
resu lts (see Chap ter 6 1).
Tota ls 33 100 .1
1. X ETO = Peak + 0.45 days; ETO ! days of Peak = 91 .0% A lso, Hil gers has fo ll owed 47 in fertile patients, by se-
Data from : Hilgers, Pope Paul VI lnstitute
rial ultraso und , in cycles in which the woman actually
became pregnant. In th ese pregnancy cycles, th e rup-
ture ofthe ovaria n fo lli cle was also assoc iated w ith th e
occurrence of the Peak day in a s imil ar fas hi o n. The
pregnanc ies occ urred fro m Peak -2 through Peak + 3
(Tab le 15-5) . Thi s is the first study of its kind associat-
Table 15-5: Follicular Rupture vs. Peak Day
ing ultrasound w ith the occurre nce of ovulation and
in Pregnancy, Same Cycle U ltrasound,
pregnancy w hil e at th e sam e tim e corre latin g th e
W omen with lnfertility (N=47)
wo man 's observation of th e Peak day. In the study of
Folli.cular Rupture
Relative to the Peak Day'
o ver 2,000 menstrual cycles by seria l ultrasound eva lu-
n 'lo
ati on of ovulatio n, no pregnanc ies have ever been ob-
P-2 2 4.2 served before P-2 or afte r P+ 3 (experience at Po pe Paul
P-1 7 14.9
V I ln stitute, Omaha, Nebraska, USA).
Peak 17 36.2
P+1 11 23.4
P+2 6 12.7
P+3 4 8.5 The Karyopyknotic lndex Correlation =l
Totals 47 99.9
Taylor, et a l,40 reported o n th e relation ship of th e Kary-
1. Pope Paul VI lnstitute Division of Reproductive Ultrasound.
2. No pregnancies have been observed befare P-2 or after P+3 in
opyknotic lndex ( KPI ) a nd th e wo man 's observation
e ighteen years of study with ultraso und . of her Peak day. The KPI is th e ratio of ce ll s with ma-
ture pyknotic nuclei (superfici al cell s) to cell s w ith im-
mature vesicu lar nuclei (intermediate cell s) . T he cel ls

were obtained from the vagina. Vaginal cell s mature
from basal to intermediate to superficial w ith estrogen
"'o...
.,.,
V ~ stimulation. These vaginal cytology smears, taken seri-
... ally throughout the menstrual cyc le, provide a relatively
"' ~
"'" simp le and reliable procedure for the eva luation of ova-
rian function , especially the estrogen status during the
preovu latory phase of the cyc le. The striking relation-
ship between the KPl and the Peak mucus day is shown
in Figure 15-35 (78 menstrual cycles, 67 women). The
Peak PI occurred on Peak ±3 days in 98.7 percent of
the cycles.
30
25
... Breast Feeding ---------~
!: zo
...~ 15
Women who are breast feeding or postpaitum , not breast
o
~
-¡ 10 feeding, have a lso been studi ed extens ively w ith hor-
V
monal corre lation. Brown, et a l,28 using week ly urinary
o... ; estrogen and pregnanediol assays in 24-hour urin e col-
o o
lections and daily mucus seores , found that the endo-
-5 -4 -3 -Z -1 o +1
crine relationships to the woman 's observation ofmu-
Fi g ure 15-34: The Modified lnsl er Score as ov ul ation cus and the Peak Day were related and the indi rect esti-
approaches corelated with the increasing size and subsequent mation of ovulation was we ll correlated. Examp les of
rupture of the ovarian follicle as detected by ultrasound (From :
Leader A, Wiseman D, Tayler PJ : The Prediction of Ovulation:
these studies are included in Figures 15-36, 15-37, and
A Comparison of the Basal Body Temperature Graph , Cervical 15-38 . This study included 42 women for periods ofup
Mucus Score and Real Time Pelvic Ultrasonograph. Fertil Steril , to ayear or more, ali with simi lar results.
43: 385-388, 1985).
CORRELA TION OF MEAN KARYOPYKNOTIC Mucus Obs e rvation St udY-----~

INDEX WITH PEAK MUCUS DAY IN 78 CYCLES
% O ne of the techniques used to assist us in the develop-

4 ment ofthe standard ized system for observing the mu-
cus was an anonymous survey with questions directed
at the woman 's mucus observation routine. T hi s survey
40
was answered by 130 women (70 .2 percent response)
using the system of observation described for use with
the CrMS.41 From this eva luation, a number of impor-
tant facts carne forward (Tab les l 5-6 throug h 15-9).
1. Of the population of women studied , 90.0 percent

indicated that they checked for the mucus every time
they went to the bathroom. This percentage was
lower for those women who indicated that they were
20 using the system to achieve a pregnancy and higher
for those who indi cated they were using it to avoid
- Karyopyknot1c lndea (l<PI) pregnancy.
15 P P.. k Mucua Oay
: H 1 Sundard Error
o TI 1 1 1 1 1 t
1
1 1 1 i 1 1 1 1
2. Over 96.0 percent of women observed the mucus
-7 -6 -5 -4 -3 -2 _, p +1 +2 +3 +4 +5 +il +7
w ith folded tissue and less than one percent did in-
DAYS
terna! exami nati ons.
Fi gure 15-35: The correlation of the mean Karyopyknotic lndex
(KPI ) with mean mucus days ± 7 days in 78 cycles (From :
Taylor, R.S., Woods, J.B. and Guapo, M.: Correlation ofVaginal 3. When asked to pick one time of the day in which
Hormonal Cytograms with Cervical Mucus Symptoms. The the mucus was thought to be the most obvious, no
Journal of Reproductive Medicine. 31 , 1986).
MRS. H. F. AGE 29 PARA 3 DELIVERED 8JULY1971 INFANT DIED

3 MONTHS POST PARTUM (11 MONTHS) 1stBLEED
cn "
::> .¡.
(.) .
z"L
i, ENDOFLDCHIA~~~~...._..........,...........~~...............................~.......~....IJIA.,."'4...,,,.,WIJl,,,,.,~,lll,JIJWlll,.,+.,,...L.,..-~~~..J
W ·
(.!) I! n BREAST FEEDING
o&;
~~ u
cn a,
UJ :)
o
.
lt
:f
• 1
11
l(f
'
u
1 ' 1
•
1
lllY
1
u i'
1411
"' "
.
M.U U " ..
4PllL .... "
lllU: JUL1" "'
. "
un
Figure 15-36: Weekly urinary estrogen and pregnanediol va lues and daily mucus seores during latation amenorrhea, first
ovulation and pregnancy. In th is study, the dotted vertical lines represen! the best estimate of the days of ovulation and the solid
vertical lines mark the first day of menstruation . The calculated lengths of th e luteal phases are shown . 1 = intercourse (From :
Brown JB, Harisson P, Smith MA, et al. : Correlations between the Mucus Symptoms and the Hormonal Markers of Fertility
throughout Reproductive Life. Ovulation Method Research and Referen ce Centre of Australia , Melbourne, Victoria , Australia ,
1981 ).
MRS. J. O'B AGE 31 PARA 5 DELIVERED 23 APRIL 1971 MRS . G.F. AGE 24 PARA 2 DELIVERED 16 DEC. 1971
1 MONTH POST PARTUM DIO NOT BREAST FEED 6 MONTHS POST PARTUM PREGNANT BEFORE WEANING
1
ffi !?. ..
(!)
..
o~"
""""
:¡;a
w"
u
o
PREGNANT
"
JUlfC
,.
" "
llllf U'
u
lf?2
•
SE rt
u
1st BLEED
OCT
u ...
11
Figure 15-37: Urinary estrogen and pregnanediol values and daily mucus seores postpatum in a subject who did not breas! feed
(Mrs. J. O'B. ) and another subject who conceived during breas! feeding (Mrs. G.F. ) (From : Brown JB , Harisson P, Smith MA, et
al. : Correlations between !he Mucus Symptoms and the Hormonal Markers of Fertility throughout Reprodu ctive Life. Ovulation
Method Research and Reference Centre of Austra lia , Melbourne , Victoria , Austra lia, 1981 ).
MRS. U O' H. AGE 25 PARA 3 DELIVERED

1st BLEED
14 MONTHS POST PARTUM (17 MONTHS) STILL BREAST FEEDING WEANED FEB. 1973 (JO MONTHS)
en " ~
::>
g '
:E
zw .
.
!?
(!)
o&; "
"""" "
1-
en e,
w"
N
o "
..J
o&;
f 1
0~4
a. a,
E '
zs
SErT " "
OCT
ZI
1971
11
"º' DCC
" ' "" 'º HI
17
197Z
2
MARU
IS JO 13
APRI L
Z1
Figure 15-38: Urinary estrogen and prenanediol values and daily mucus seores in a subject who brea stfed for 30 months. First
ovulation postpartum occurred 17 months after delivery (From : Brown JB, Harisson P, Smith MA, et al. : Correlations between the
Mucus Symptoms and !he Hormonal Markers of Fertility throug hout Reproductive Life. Ovulation Method Research and Reference
Centre of Australia , Melbourne, Victoria , Australia, 1981 ).
clear pattern developed. The mucus was seen in this 7. The women were also asked if they had ever ob-
population of women throughout the course of the served the mucus just once during the day and at
day, and there was no time during the day where it that time it was observed on ly after urination . For
was consistently more obvious. the 130 responders, 58.5 percent indicated this cir-
cumstance had occurred to them . The same ques-
4. The most difficult time during the day to observe tion was asked relative to the observation of the
the mucus discharge was in the early morning. Over mucus only after a bowel movement and 57.7 per-
5 7. 7 percent of the women marked that choice out cent indicated this had occurred to them. The data
of a list of six. This undoubtedly is related to the presented in item 5, 6 and 7 lend support to the
hectic events of this time of day. lf the teacher is importance of the 100-percent observational rou-
aware of this, he or she can provide helpful assis- tine.
tance to the client where this is a problem.
5. When asked whether the mucus was most obvious Table 15-7: Mucus Observation Study
before or after urination and before or afte r a bowel cont'd (N;l30)
movement, 57. 7 percent indicated before urination ,
ltem Percent
45.4 after urination , 20.0 before a bowel movement,
and 79.2 after a bowel movement. There was room Mucus was most obvious :
Before urination 57 .7
for multiple answers to these questions, thus the to- Alter urination 45.4
tals do not add to l 00.0. onetheless, it indicates Before bowel movement 20.0
Alter bowel movement 79.2
that the mucus was sometimes more obvious at any
Ever observed the mucus:
one of those observations. Of course, it cannot be Before urination , not alter 73 .1
predicted at any one ob ervation when the mucus Alter urination, not before 61 .5
Before a bowel movement, not alter 33.8
might be observed.
Alter a bowel movement, not before 73 .8
6. When asked if the mucus had ever been observed

befare urination but not after, 73.1 indicated it had.
When asked if the mucus had ever been observed
after urination but not before, 61.5 percent indicated
it had. When asked ifthe mucu had ever been ob- Table 15-8: Mucus Observation Study
cont'd (N;l30)
served befare a bowel movement but not after 33.8
percent indicated it had. When asked if the mucus ltem Percent
had ever been observed after a bowel movement Ever obvserved the mucus once during
but not before, 73.8 percent indicated that it had. the day and this was:
Alter urination 58 .5
Alter bowel movement 57 .7
Table 15-6: M ucus Observation Study

(N;130)
ltem Percent
Table 15-9: Mucus Observation Study
Checked every time 90.0
cont'd (N;l30)
Observed with folded tissue 96 .0
Did not do interna! exams 99 .0 ltem Percent
Most difficult time to observe : early morning 57 .7 How long does it take to make the
Observing the mucus was easy or very easy 93 .0 observation
0-1 O seconds 44.0
Observing the mucus alter a bowel 82 .0 10-20 seconds 39.0
movement was easy or very easy 20-30 seconds 11 .5
Seminal fiuid instruction: easy or very easy 85.4 30-40 seconds 3.1
>40 seconds 2.4
Seminal fluid instruction is helpful or very helpful 84 .6 30 seconds or less 94 .5
Bearing down al end of the day: helpful or 86 .9
very helpful Time of day mucus was most obvious No time more
obvious than
Kegel's exercise : helpful or very helpful 79.2 others
8. The women were asked , " When in the bathroom,

about how much time does it take you to check for Table 15-10: Statistical Parameters of the
the mucus?" About 44 percent ind icated Oto 1Osec- Mucus Cycle (N =600)
onds, 39 percent 1O to 20 second s, 11.5 percent 20 ltem Answer
to 30 second, and 3.1 percent 30 to 40 seconds. Only
Peak Day observed 1 94 .0
2.4 percent indi cated that it took longer than 40 sec-
Average lenglh of the mucus cycle 5.6 days
onds.
Average length of the post-Peak phase 12 .3 days
1- 7 days 7.7%
9. Over 93 percent of women studi ed indicated that 8-16 days 89.9%
observing the mucus was either easy or very easy to >16 days 2.4%
do. 1ncidence of premenstrual mucus 12.3%

lncidence of "double" Peak 7.8%
1O. Over 82 percent of th e women indicated that ob- 1. Only 2.5 percent in women with regular cycles.
serving the mucu s after a bowe l movement was ei-
ther easy or very easy.
11. Ofthe 130 women , 122 were in a position to answer in women with regular cycles. There was a tendency
the question , "Prior to coming to the FertilityCare™ for the mucus cycle to be somewhat longer in women
Center, did you empty your bl adder afler hav ing coming off birth control pills but shorter in breast
intercourse?" A large majority (76.2 percent) an- feed ing women and those approachi ng menopause.
swered yes to thi s question . Thus, we learned fro m
our patients that the practice of emptying the blad- 3. The average length ofthe post-Peak phase in women
der fo llowing intercourse was a customary event. with regular cyc les was 12.3 days. This was sl ightly
shorter in women co min g off birth contro l pills,
12. For those women who had used th e seminal fluid breast-feeding women , women with long cyc les, and
instruction, 84.6 percent found emptying the blad- women approaching men opause. In women with
der either helpfiil or definitely helpful. In 86.9 per- regular cycles, the post-Peak phase was 1-7 days in
cent, bearing down was fo und to be ei ther helpfiil duration in 7.7 percent and greater than 16 days in
or defin itely helpfiil and 79.2 percent found Kegel 's 2.4 percent. The short post-Peak phase was found
exercise helpful or definitely helpfiil. Overall, 85.4 to be higher in women coming offbirth control pi lis,
percent ofthe women indicated that the seminal fluid breast-feeding women, and those women approach-
instruction was either easy or ve1y easy to do. ing menopause. The post-Peak ph ase was found to
be longer more frequentl y in women comi ng off of
birth control pil ls and women who were breast feed-
Statistical Parameters of the Mucus Cycle mg.
A preliminary study of 600 menstrual cycles form 100 4. The overa ll incidence of premenstrual mucus was
women was undertaken to exam in e th e statistical pa- fo und to be 12.3 percent in women with regular
rameters ofthe mucus cyc le. This study in volved women cyc les but less than that in women coming off of
with regular cycles, those coming offb irth control pi li s, birth control pi li s and those approaching menopause.
those approaching menopause, those who are breast
feeding, and those with long and irregu lar cycles. 42 A 5. The overa ll incidence of"double" Peak was 7.8 per-
number of interesting findin gs were revea led. These data cent.
ca n be helpful in teaching, in review ing charts and in-
terpreting their mean ing (Table 15-1 O).
Evaluation of the Education System ==J
1. In 94.0 percent ofcycles, a Pea k Day was observed.
However, the absence of a Peak Day was observed Clients ' eva luations ofthis educational system have been
in only 2.5 percent of women with regular cycles tabulated for a large national ex peri ence. With the use
while the incidence was hi gher in women approach- of the ln troductory Session, teacher, and follow-up
ing menopause. This could be anticipated since ova- eva luation fo rms, a large vo lume ofc li ent response has
rian function tend s to decline with advanc ing age. been collected. In Tables 15-11 through 15-1 7, the In-
troductory Session evaluation is presented for 4, 136 ob-
2. The average length ofthe mucus cyc le was 5.6 days servers. In Tables 15-1 8 through 15-22, eva luations of
204 The Med ical and Surg ical Practice of NaProTECHNOLOGY
the fo llow-up sessions from 936 respondents are pre-

sented. In Table 15-23 and 15-24, the result of 925 Table 15-12: In trod uctory Session Evalu atio n :
teacher evaluations are presented . "The quality of material was ... " ( =4,136)
Fema le Male Totals
A tota l of97.3 percent ofthe cli ents fe lt that the amount n % n % n %
of material in the fntrodu ctory Session was appropri- Too advanced 18 0.7 9 0.6 27 0.6
ate and 96.4 percent fo und that the quality of material Appropriate 2,505 96 .8 1,482 95.7 3,987 96 .4
was appropriate. Very few felt that the amount ofmate- Too simple 65 2.5 57 3.7 122 2.9
rial was either too much or too little or that the qua lity
Totals 2,588 100.0 1,548 100.0 4 ,136 99 .9
of mater ia l was too advanced or too simple. The
teacher 's presentation was judged to be interesting by
80.7 percent ofthe clients and exciting by 12 .5 percent.
Explanations during the l ntroductory Sess ion were
found to be usually or always c/ear by 99 .8 percent.
The opportunity for questions was judged to be good Table 15-13: lntroductory Session Evaluatio n :
or exce/lent by 98.3 percent. "The teacher's presentation was ... " (N =4,136)
Fema le Male Totals
When asked to check words that descri be the Introduc- n % n % n %
tory Session, clients rated it (i n descending order) worth-
Exciting 365 14.1 153 9.9 518 12.5
while, enlightening, open to comment, comprehensive,
1nteresting 2,089 80.7 1,250 80 .7 3,339 80 .7
and enthusiastic. Less than 1O percent found it to be (in
Average 129 5.0 142 9.2 271 6.6
descendin g order) dull, c/osed to comment,frustrating,
Dull 5 0.2 3 0.2 8 0.2
discouraging, or threatening. The session overall was
rated excellent by 56 .6 percent and good by 42.1 per- Totals 2,588 100.0 1,548 100.0 4,136 100.0
cent ofthe cli ents. There was very li ttle d iffe rence be-
tween male and female responders.
The teacher is evaluated for ix different items (includ-

ing an overa ll eva luation) on rating score of 1 through 7
Table 15-14: lntroductory Session Evaluation :
with 7 being the best score. The overall evaluation of
"Explanation.s we re ... " (N=4,136)
the teachers was either a score of 6 or 7 fo r 9 1. 8 per-
cent ofthe cl ients. The teacher 's general presentation Female Mal e Totals
n % n % n %
was judged a 5, 6, or 7 by 92.3 percent. The teacher 's
use of teaching aids was judged a 5, 6, or 7 by 89.4 Always clear 1,527 59 .0 923 59 .6 2,450 59 .2
percent. Opportunity for questions was score a 6 or 7 Usually clear 1,053 40 .7 625 40.4 1,678 40 .6
by 92.2 percent. The teacher ' personal approach with Seldom clear 8 0.3 o O.O 8 0.2
regard to support of the el ient was j udged a 6 or 7 by Dull o O.O o O.O o O.O
88.9 percent. Finally, the importance of the teacher in
Totals 2,588 100.0 1,548 100.0 4,136 100.0
the develop ment of the client's confidence was j udged
a 5, 6 or 7 by 90.4 percent.
When asked to check words that would apply to the
Table 15-15: lntroductory Session Evaluatio n :

Table 15-11 : ln.troductory Session Evaluation: "Opportu nity q uestions for was ... " (N=4,136)
"The amou n.t of material was ... " ( =4,136) Female Male Totals
n % n % n %
Female Mal e Totals
n % n % n % Excellent 1,798 69.5 1,050 67 .8 2,848 68 .8
1.9 65 1.6 Good 748 28 .9 474 30 .6 1,222 29 .5

Too much 36 1.4 29
Fair 39 1.5 22 1.4 61 1.5
Appropriate 2,529 97 .7 1,497 96 .7 4,026 97 .3
Poor 3 0.1 2 0.1 5 0.1
Toolittle 23 0.9 22 1.4 45 1.1
Totals 2,588 100.0 1,548 99 .9 4,136 99 .9

Totals 2,588 100.0 1,548 100.0 4,136 100.0
teacher, th e cli ents recorded the fo ll owing words most trating, dominating, disatganized, discouraging, threat-
freque ntl y ( in descending o rder): interested, support- ening, closed to comment, hostile.
ive, thorough , open to comment, organized, enthusias-
tic and sensitive. Less than 2 percent ofthe clientsjudged With regard to thefo/low-ups, 92 .3 percent ofthe cli-
the ir teachers to be (in descending o rder): unclear,frus- ents judged the ir teacher 's presentati o n as either inter-
esting or exciting . Explanations were j udged to be usu-
al/y or always clear by 99.8 percent. Opportunity far
Table 15-16: lntroductory Sessio n Evaluation:
questions was judged to be good or excellent by 99.5
"Overall, how would yo u rate the
percent. The amount of material presented at the time
lntroductory Session?" ( =4,136)
of the follow-up was j udged to be appropriate by 94.5
Fema le Male Totals
percent and the quality ofthe material was judged to be
n % n % n %
appropriate by 97.9 pe rce nt. Very few clie nts judged
Excellent 1,507 58 .2 833 53 .8 2,340 56 .6 the amount ofmateri al to be either too much or too littl e
Good 1,053 40 .7 690 44 .6 1,743 42 .1 or the quality ofthe material to be too adva nced or too
Fair 28 1.1 25 1.6 53 1.3 sim pl e.
Poor o o.o o o.o o 0.2
Totals 2,588 100.0 1,548 99.9 4,136 100.0 The use of the introductory booklet was fo und to be
eithe r useful or ve1y usefu / by 96.6 percent ofthe cli-
ents . The Pie tu re Dictionary was j udged to be usefid or
very usefiil by 94.5 percent. The Sample Teaching
Charts were found useful or ve1y useful by 93 .3 per-
cent.
Table 15-17: lntrod uctory Sessio n Evaluation:
"Check an ywords that describe the
When asked to check the words that described the teach-
lntroductory Sessio n" (N=4,136)
ing(fol/ow-up sessions, the fo ll ow ing words were given
Female Male Totals the most frequent ly (in descendin g o rder): worthwhile,
n % n % n %
essential to learning, encouraging, supportive, open
Worthwhile 2,458 95.0 1,378 89 .0 3,836 92 .7 to comment, enlightening, comprehensive and enthusi-
Threatening 16 0.6 8 0.5 24 0.6 astic. Less tha n 7.0 pe rcent of the cli ents viewed the
Open to commen t 1,343 51 .9 61 3 39.6 1,956 47 .3 teaching/fo ll ow-up sess ions as ( in descending o rde r):
Frustrating 54 2.1 14 0.9 68 1.6 fru strating, anxiety-provoking, discouraging, conde-
Comprehensive 1,255 48 .5 672 43.4 1,927 46 .6 scending, dull, closed to comment, threatening o r hos-
Dull 13 0.5 22 1.4 35 8.5 tile.
Enthusiastic 1,090 42 .1 477 30.8 1,567 37 .9
Closed to co mment 5 0.2 2 0.1 7 1.7 F ina ll y, w he n asked to prov ided an overall rating of
Enlightening 1,918 74 .1 1,119 72 .3 3,037 73.4 the teachinglfollmv-up session, 7 1.6 percent of the cli-
Discouraging 34 1.3 15 1.0 49 1.2 ent judged them to be excellent w hil e 27.7 percent in-
dicated good. Only O. 7 pe rcent said they were fa ir, and
Totals 2,588 1,548 4,136
none ofthem indi cated they we re poor.
Table 15-18: Follow-up Evaluation: Teacher's Presentatio n ,

Explanatio n, and Üpportunity for Questions (N=936)
Teacher's Opportunity
Presentation n % Explanations n % for Questions n %
Exciting 119 12.7 Always clear 511 54.6 Excellent 779 83 .2

lnteresting 745 79 .6 Usual ly clear 423 45.2 Good 153 16.3
Average 72 7.7 Seldom clear 2 0.2 Fair 4 0.4
Dull o O.O crear o O.O Poor o o.o
Totals 936 100.0 936 100.0 936 99 .9
Table 15-19: Follow-up Evaluation: Table 15-21: Follow-up Evaluation:

Amount and Quality of Material (N=936) "Check an y words that apply to teaching/
Amountof Quality of fo llow-up sess io ns" (N=936)
Material n % Material n % n % n %
Too much 11 9 12.7 Too advanced 511 54 .6
Worthwhile 853 91 .1 Enthusiastic 422 45.1
Appropriate 745 79 .6 Appropriate 423 45.2
Threatening 3 0.3 Anxiety-provoking 48 5.1
Too little 72 7.7 Too simple 2 0.2
Supportive 755 80.7 Encou raging 726 77 .6
Totals 936 100.0 936 100.0 Frustrating 64 6.8 Closed to comment 4 0.4
Dull 7 0.7 Discouraging 15 1.6
Open to comment 653 69 .8 Essential to learning 808 86 .3
Hostile 0.1 Condescending 9 1.0
Enlightening 579 61 .8 Comprehensive 484 51 .7
Table 15-20: Follow-up Evaluatio n:

Use of Teaching Aids (N=936)
lniroductory Picture Sample
Booklet Dictionary Chart
n % n % n %
Table 15-22: Follow-up Evaluation:
Very useful 511 54 .6 655 70.0 608 65 .0
"Overall, how would yo u rate the teaching/
Useful 393 42.0 229 24.5 265 28.3 fo llow-u p session?" ( =936)
Somewhat useful 31 3.3 52 5.6 61 6.5
Rating n %
Not useful 0.1 o O.O 2 0.2
Excellent 670 71 .6
Totals 936 100.0 936 100.1 936 100.0
Good 259 27.7
Fair 7 0.7
Poor o O.O
Totals 936 100.0
Table 15-23 : Teacher Evaluatio n (N=925)
General Using Teaching Opportunity Personal Confidence Overall

Ratíng Presentation Aids for Question Approach Development Evaluation
Seo re n % n % n % n % n % n %
Poorly Organizeo Not usefu/ Poor Unsupportive Not lmportant Poor
o o O.O o o.o o o.o 1 0.1 3 0.3 o O.O
2 o o.o o O.O o O.O o O.O 7 0.8 1 0.1
3 6 0.6 8 0.9 1 0.1 5 0.5 9 1.0 1 0.1
Organized Useful Good Supportive lmportant Good

4 65 7.0 90 9.7 32 3.4 38 4.1 69 7.4 30 3.2
5 108 11 .7 121 13.1 39 4.2 59 6.4 77 8.3 44 4.8
6 275 29.7 244 26.4 126 13.6 145 15.7 241 26.0 259 28.0
Very Organized Very Usefu/ Excellent Very Supportive Very lmportant Excellent
7 47 1 50.9 462 49.9 727 78 .6 677 73.2 519 56.1 590 63.8
925 99 .9 925 100.0 925 99 .9 925 100.0 925 99 .9 925 100.0

percent indicated it had increased, 18.8 percent indi-

Table 15-24: Teacher Evaluation:
cated it had remained the same, and no one indicated it
"Check an y words that apply to your teacher"
had decreased (Table 15-25).
(N;925)
n,, % n % These patterns of cornrnunication were thought to be
Disorganized 4 0.4 Supportive 779 84 .2 revealing. Most teachers ofthe CrMS have fe lt that such
Sensitive 640 69 .2 Thorough 752 81 .3 patterns existed and these data support that contention.
Discouraging 4 0.4 Hostile 0.1
Threatening 3 0.3 Organized 724 78 .3 Over 81 percent ofwornen indicated that their h usbands
lnterested 840 90 .8 Dominating 9 1.0 showed interest in their charting or observations and
Frustrating 11 1.2 Enthusiastic 700 75 .7 over 95 percent ofthe husbands indicated that they like
Open to comment 729 78 .8 Closed to comment 3 0.3
of the CrMS (as opposed to disliking) (Tab le 15-26).
Unclear 14 1.5
When the wives were asked iftheir husbands had given
thern support in the use of the CrMS, 75 percent said
• Of 925 clients, this data refiects the number and percent of those who
checked each word . Many cli ents checked more than one wo rd. that their husbands we re very supportive and another
20.8 percent indicated they we re sornewhat supportive .
Data such as this, if co ll ected on a rnuch larger scale,
could dispel the old myth that natural methods offertil-
ity regulation are disliked by rnen .
Spousal Communication with the CrMS
Fi na lly, the coup les were asked whether they foun d that
A pi lot survey of 48 coupl es were interviewed regard- avoiding genital contact was very easy, reasonably easy,
ing the cornrnunication pattems that they observed or reasonably difficult or very difficult. For 70.8 percent
developed with the use ofthe CrMS .43 This survey, wh ich of coup les, avo iding genital contact was thought to be
is prelirninary in its findings , provides sorne initi al in- either reasonably easy or very easy. However 21.2 per-
sight into what can be expected of coup les that use the cent indicated that it was either reasonably difficult or
CrMS. very difficulty. That group was a lso asked ifthey fo und
that it does or does not interfere with the developrnent
When the couples were asked whether they had dis- ofthe ir overa ll relationship . The overwhelrning rnajor-
cussed their decision to either ach ieve or avoid preg- ity, 85 .7 percent, indicated it did not interfere with the
nancy whi le following the CrMS, 100 percent indi cated development ofthe ir overa!] re lationship.
they had . When asked whether the couple verba ll y dis-
cussed when they wo uld and wou ld not have genita l These data suggest that avo iding genita l contact is, in
intercourse, 89.6 percent indi cated they had . When general, not particularly difficult whe n us ing the CrMS.
asked whether the CrMS encouraged or discouraged ver- At the same ti me, it does not rul e out the possibility that
bal cornrn unication in the decision to have genita l in- sorne coupl es w ill have so rne degree of difficulty with
tercourse, 92.8 percent indicated that it encouraged corn- this. However, for those couples, one can gain confi -
rnunication. When asked w hether verbal cornrnunica- dence in the fact that avo iding genital contact is not
tion in deciding to have intercou rse had increased , re- deleterious to their overa ll relationship .
rnained the sarne or decreased since changing from their
previous rnethod of contraception to the CrMS, 72 .9 Fehring 44 -46 , in a cornparison of users in the CrMS with
couples using ora l contraceptives, adrnin istered psycho-
Table 15-25: Communication in
Creighton Model Users: Table 15-26: Communication in
Pilot Survey R esults (N;48 couples) Creighton Model Users:
Pilot Survey R esults (N;48 couples)
Couples discussed pregnancy intentions 100.0%

Husbands liked system 95 .0%
System encouraged verbal communication 92 .8%
re: intercourse Husbands showed interest in charting or observations 81 .0%
Couples verbally discussed having intercourse 89 .6% Husbands indicated support in use of the system 95 .0%
Verbal communication re : intercourse increased 72 .9% Avoiding genital contact was reasonably easy or 70.8%
alter using the system (from their previous method ) very easy
Table 15-27: A Comparison of Psychological/Spiritual Variables

Between the Creighton Model FertilityCare™ System (N=88) and
Couples Using Oral Contraceptives (Fehring) 46
Psychoinet ric Creighton Model Oral
Assessment FertiHtyCare™ System Contracepiives .
X so X so t-test p-values
Spiritual well-being 108.70 10.27 96.43 14.98 6.36 .001
Religious well-being 55 .33 6.36 46 .74 10.40 6.98 .001
Existential well-being 53 .37 5.31 49 .67 7.70 3.73 .01
Self-esteem 84 .16 11 .99 78 .13 17.26 2.70 .01
lntellectual intimacy 77 .72 14.22 71 .67 16.92 2.57 .01
Sexual intimacy 78 .23 13.42 72.82 16.00 2.43 .01
Recreational intimacy 72 .80 13.51 68 .29 14.99 2.09 .05
Emotional intimacy 72. 32 17.51 70 .35 19.79 0.70 NS
Social intimacy 73.44 15.11 73. 51 16.84 0.03 NS
metric assessments to both sets ofusers. In this assess- to ac hi eve a pregnancy gives on the one hand, cycle-
ment, statistica lly significantly improved seores were by-cycle success rates in the use offertility focused in-
fo und in the CrMS for spiritual well-being, religious tercourse fo r the ach ievement of pregnancy (method ef-
well-being, existential well-being, self-esteem, intellec- f ectiveness to achieve pregnancy ) and, on the other hand,
tual intimacy, sexual intimacy, and recreational inti- data on the use-dynamics ofthe system in a popu lation
macy. For emotional intimacy and socia l intimacy, there of couples (use-effectiveness to achieve pregnancy). The
was no statistica lly sign ifi cant difference between the total pregnancy rate is a comb ination of its use-effec-
two gro ups (see Table 15-27). tiveness to avo id pregnancy and its use-effectiveness to
achi eve pregnancy and is expressed as arate. The sum
of these two rates (subtracted from 100) gives an estí-
mate of its demographic effectiveness (or, as so me ha ve
Effectiveness of the System _ _ _ _~ called it, the extended use-effectiveness). The devel-
opment of data such as this gives insight into the use of
The effectiveness ofthe CRElGHTON MODEL System, the system , as co mp are d to co ntrace pti ve
because it is not a contraceptive, must take into ac- methods.Additionally, measurements of effectiveness
count its abi lity to be used both as a system to achieve wi ll reflect the abi lity ofthe system to be taught prop-
pregnancy as well as avoid pregnancy. 4 7 The normal erl y.
use of a system such as this, during the reproductive
years in coup les desiring a fam ily, is to use it for a wh il e The CrMS has been extensive ly studi ed and a meta-
to avoid pregnancy and then use it to achieve pregnancy a na lysis of the system has incorporated the data from
(or vice versa) . This cycle is then repeated on afreely five studi es into a composite including 1,876 couples
chosen bas is according to a married coup le 's ab ili ty to over 17,130 couple months of use. 49 - 53 These studies,
have and raise children. This is the only family plan- a li utili zing life-table analysis and an objective assess-
ning method (including other natural methods) that can ment ofpregnancies, reported the range ofthe method
be used consc iou sly and conscientiously in both ways effectiveness to avoid pregnancy at the 12th ordinal
(w ith the exception ofthe Billings Ovulation Method) . month to be 98.7 to 99.8 (w ith th e 5-study composite
99.5). The use effectiveness to avoid pregnancy for the
In considering these concepts of use, the method and same tim e period ranged from 94.6 to 97.9 and was
use effecti veness as a means ofavoiding pregnancy and shown to continually improve over the 14 years ofthe
the method and use effectiven ess as a means ajachiev- studi es (the 5-study composite was 96.8) (Table 15-28).
ing pregnancy can both be measured. The method and
use effectiveness as a mea ns of avo iding pregnancy can The use effectiveness of the CrMS to achi eve a preg-
then be compared to comparable data for artificial meth- nancy showed expectedly wide fluctuations. At the l 2th
ods of contraception . The method and use effectiveness ordinal month, the achi eving-related pregnancy rate
Chapter 15: Seientifie Foundations of the CrMS 209
Table 15-28: Creighton Model Method and Use Effectiveness to Avoid Pregnancy by Center,
5-Study Composite and Ordinal Month of Use
Creighton St. John 's Merey St. Francis stJosepp •·•·• MarqueJ.te .
>Uníversity Hospital Hospital . ··. • ••.• Hos}'lital Nursing Ce!Mr · $-Stuciy ·
omana St. Louis Witehita . Houstón Milwaukee Composi te
Year of Study 1980 1980 1985 1989 1994 1995

Number of Couples 286 273 378 697 242 1,876
Number of Couple-Months 2,224.0 ' 1,980.0' 2,471 .01 7,084.51 1,819.5 1 17,130.01
Method Effeetiveness 3
Ordinal Month
1 100.0 100.0 100.0 100.0 100.0 100.0
6 99.6 99 .6 99.4 100.0 99.6 99.8
12 99.6 99.6 99.1 99.8 98.7 99.5
18 n/a n/a n/a 99.8 n/a 99.5
Use Effeetiveness'
Ordinal Month
1 100.0 99.6 99.7 100.0 100.0 99.9
6 95.8 96.4 97.3 98.4 98.7 97.9
12 94.6 95.1 96.2 97.2 97.9 96.8
18 n/a n/a n/a 97.1 n/a 96.4
1. Through 12 ordinal months

2. Through 18 ordinal months
3. To avoid pregnancy
n/a = Not applicable
ranged from 14.2 to 28.0 (the 5-study cornposite was the stated reason of "dif.ficulty avoiding genital con-
2 J .O). The use-effectiveness to ach ieve pregnancy is a tact'' was less than one percent .
demographic statistic which applies to a population of
users and not individuals. Jt is the mathematical oppo- The estimated demographic effectiveness (extended
site ofthe demographic effectiveness to avoid pregnancy use-effectiveness) for the oral contraceptive and intrau-
(Table 15-29). terine device is shown in Table 15-31 at the 6th, l 2th,
and l 8th ordinal month. Only a few studies of the ex-
Discontinuation rates were the highes t (9. 4) in the first tended use effecti veness (demograph ic effecti veness) of
six months ofuse. The discontinuation rate after the first these or any other artificial method have been done. lt
six months of use was on ly 2.9. The study did not in- is not well known that these percentages are significantly
volve any learning phases as other studies have pro- lower than the effectiveness normally quoted . That is,
moted. At the 12th ordinal month the discontinuation or course, as it should be since these include pregnan-
rate was l l .3 and at the l 8th ordinal month 12. l (Table cies after the individuals discontinue the method as a
15-30). lt is notable that the discontinuation rate far means of avoiding pregnancy. Jt is the demographic ef-
Table 15-29: Creighton Model Method· and Use-Effectiveness to Achieve Pregnancy by Center,
5-Study Composite and Ordinal Month of Use
Creighton St. John's Merey. st. Francis St..Joseph Marquette

Uníversity Hospital ··Hospital Hospital Nursing Center 5-Study
Orna ha ·st..Louis Witehita ··• Houstón MiJwaukee Cornposíte
2.1 1.8 5.3 0.7 1.2 2.1

6 10.5 13.6 19.9 7.9 14.0 12.8
12 19.1 23.7 28.0 14.2 24.8 21.0
18 n/a n/a n/a 17.9 n/a 25.6
n/a = Not applicable

210 The Medica! and Su r g ic al Practice of NaPro T ECHNOLOGY
Table 15-30: Creighton Model Cumulative Discontinuation Rates by R eason and

Ordinal Month of Use, 5-Study Co mposite
Re.ason for d iscontinuation 1 3 6 12 ... 18
To use another natura l method O.O 0.3 0.3 0.7 0.7

To use an artificial method 0.2 2.5 3.9 4.5 4.9
Lack of confid ence 0.2 0.6 0.6 0.7 0.8
Diffi culty with avoiding genital contact 0.5 0.5 0.6 0.7 0.7
Personal reasons 0.8 2.6 3.8 4.4 4.6
Medically induced infertility O.O 0.2 0.2 0.3 0.4
Totals 1.4 6.7 1 9.4 ' 11 .3 12.1
1. 55.4 percent of all discontinuations occurred in the first three months

2. 77.7 percent of all discontinuations occurred during the first six months
The discontinuation rate after six months was 2.9.
fecti veness of these methods, however, that is the cor-

Table 15-31: Estimate D emographic Effectiveness
rect effecti veness ra te to be compared to the tota l preg-
(Extended U se-Effectiveness) for BCP and IU D,
nancy rates of methodologies whi ch are natura l fe rtili ty
6th, 12th and 18th Ordinal Month
regulators.
Method and Range of Estimated
Demographic Effectiveness
The extended use effectiveness of an arti fic ia l meth od Ordinal Month BCP 1 BCP"' ••• IUD'''
includes a significantly increased number of pregnan-
6 89 .9- 97 .0 94.4- 97. 5
cies because the aitifi cia l method may not be tolerated
12 75. 7 - 91.6 89.9 -95.2
fo r a vari ety of different reasons over the time peri od of
the study. Whi le sorn e pregnancies in the categori es 18 65.9 - 85 .4 82.8-95.8
wo uld be of a simil ar nature in the use of a natu ra l 1. Polaneczky M, Slap G, Forke C, et al. : The Use of Levonorgesterol
method offertili ty regul ati on, most pregnanc ies occur- lmplants (Norplant) for Contraception in Adolescent Mothers.
NEJM. 331: 1201 , 1994.
ring fro m a natu ra l method will be in those who know- 2. Tietze C and Liewit S.: The IUD and the Pill: Extended Use-Effec-
tiveness. Family Planning Perspectives 3: 53-55, 1971
ingly use it to achieve pregnancy.
3. Tietze C and Lewit S.: Use Effectiveness of Oral and lntrauterine
Contraception . Fertil Steril. 22: 508-513, 1971 .
Total pregnancy rates, in users of natural meth ods, are
often quoted with regard to the long-term "failure rate "
of these methods. However, to do so takes a group of
people who ha ve been successful users of the method
(to achieve pregnancy) and class ifi es them inappro pri -
ately as failures ofthe method. More appropriately, these
pregnancies belong in the abo ve category of extended
Table 15-32: R ate of Wanted and Unwanted
use-effectiveness, a concept deve loped by Tietze and Pregnancy - Creighton Model U sers who
Lewit and referred to orig ina ll y as demographic effec- B ecame Pregnant 1 (N =428)
tiveness. 4854- 56 The term demographic effectiveness is
probably more pertinent to the concept of tota l preg- Wanted Unwanted
Center n % n %
nancy rates because these data retlect the use of a method
in a populati on of peopl e over a peri od of time. Creighton 91 98 .9 1 1.1
St. John's Merey' 66.5 99.2 0.5* 0.7
St. Francis 3 109 97.3 3 2.7
What may appear to be di ffere nt between the natu ra l
St. Joseph 88 97.8 2 2.2
and artifi cial methods is in the answer to the questi on:
Marquette 67 100 .0 o O.O
"are the extended use pregnancies the result of suc-
cessfiil use or fa ilure of the methods?" lt can be prop- Totals 421 .5 98 .5 6.5 1.5
erly ass umed that fo r the arti ficia l methods these wo uld 1. Pope Paul VI lnstitute research, 2004 .
2. There were three in which no reply was recorded .
be conside red fa ilures. Table 15-32 lists th e rates of 3. There were eight in which no reply was recorded .
wanted and un wanted pregnancy in those couples who 0.5 is shown because for one spouse the pregnancy was unwanted while
for the other spouse the pregnancy was wanted.
became pregnant in the fi ve CrMS studies. Out of 428
total pregnancies, only 4.5 couples identified their preg- first cycle of use. By three cycles of use, 90.0 percent
nancies as unwanted at the time ofthe pregnancy evalu- were pregnant and by the sixth cycle, 98.0 percent (Fig-
ation which was usually conducted, in person, within ure 15-39).
the first three months ofthe pregnancy. Thus, the wanted
pregnancy rate was 98.5 percent. This has important These data suggest that the efficiency of the human re-
behavioral implications which will require further study. productive system is actually greater than previously
thought. In addition, by understanding normal fertility,
In other studies it has been shown that as the age ofthe it gives usa better opportun ity to understand conditions
woman increases, the pregnancy rate decreases in users of abnormal fertility.
ofnatural methods. 57 With the Ovulation Method, Bill-
ings7 studied 98 women who were judged to be ap-
proaching menopause. The women ranged in age from NaProEDUCATION Technology _ _~
38 to 54 years and each was followed for an average of
4 years. One pregnancy occurred in this group in a CREIG HTO N MODEL NaProEDUCATION Technology
woman who used the days of fertility for intercourse. has been extensively evaluated over the last 25 years. It
The method-related pregnancy rate was zero. In a simi- is an approach to natural procreative education which
lar study of 13 7 women, 40 years of age or older, Klaus 58 allows for the transfer of information to be conducted
revealed a total pregnancy rate of 0.98 (with the Bill- in a way which is standardized and the actual use ofthe
ings Ovulation Method) . system can be measure in an objective fashion (Table
15-34). lt is the only medica! model ofnatural fertility
The method effectiveness to achieve a pregnancy is a regulation currently in ex istence and it is a mode l that
pregnancy rate based on fertility-focus ed intercourse specifically provides instructions both for the achieve-
compi led in a cumu lative fashion from one cycle to the ment ofpregnancy (in couples ofnormal ferti lity) and
next. In one such study, 59 in which 50 consecutive pa- the avoidance ofpregnancy and allows, by its very de-
tients were fo llowed as they began using the method to sign, the ability to measure its effectiveness in a pro-
achieve pregnancy, 76.0 percent became pregnant in the spective fashion using life-table analysis.
In addition, because of its standardized and objective

format, it has been instrumental in the development of
a new reproductive science of NaProTECHNOLOGY.
980 980 100.0
100
940
90.0
Q)
(tj 86.0 End Note _ _ _ _ _ _ _ _ _ _~
a: 80
>.
u The CREIGHTON MODEL FertilityCare™ System, an
e
C'd authentic offspring of the Billings Ovulation Method,
e
Ol
60
is, like its parent system , unique among natural meth-
Q)
..... Cumulati ve Preg nancy Rate ods. Because it attends to the details ofthe cervical mu-
a. Fertil ity Focused lntercourse
Q)
Patients of Apparent Normal Ferti lity cus sign, it allows fertility lo be prospectively identified
> and the naturally occurring phases offertility and infer-
(tj (N=50) 53
40
:J tility to be identified on a day-by-day basis. lt is simple
E to use and easy to keep records. lts versatility is un-
:J
ü matched .
20
An extensive amount of research has been conducted

over the last 27 years. The cervical mucus plays an es-
sential role in human fertility and the ability ofthe cer-
o 2 3 4 5 6 7 vix to act as a biological valve has now been well es-
Cycle Pregnancy tablished. In the CrMS, a woman is simply being taught
Achi eved when that valve is open. (which allows for sperm pen-
etration and survival) and when it is closed (when the
Figure 15-39: Cumu lative pregnancy rate , fertility focused
interco urse, patients of apparent normal fertil ity (N=50) (From: cervix acts as a barrier to sperm penetration and sur-
Hilgers TW, Daly KD, Prebil AM : Cumulative Pregnancy Rates vival) . Studies on the role of the cervical mucus ha ve
in Patients with Apparently Normal Fertility and Fertility Focused been done from the points of view of nuclear magnetic
lntercourse. J Repro Med , 10: 864-866, 1992).
212 The Medical and Surgi cal Practice of NaProTECHNOLOGY
Table 15-33: Applications of NaProTechnology
Family planning The effects of stress Other reproductive disorders

Chronic discharges lnfertility • Prematurity prevention
Targeted hormone evaluation • Miscarriages Abnormal bleeding
• Targeted hormone replacement Premenstrual syndrome Dating pregnancy
ldentify ovarian cysts Chronic infections • Psychosexual understanding
resonance,ferning and channeling stud ies and scan- tificialforms of contraception when app lied to a popu-
ning electron microscopy. They ha ve been done by mu/- lati on of users .
tiple investigators and the same principies continue to
be verified. NaProTECHNOLOGY has expanded the uses of the
system in to the treatment of a variety of different gyne-
The system has been extensively evaluated hormonally. cology conditions and these uses wil l continue to ex-
The mucus cyc le has been shown to be associated with pand with further research (Tab le 15-33).
the preovulatory rise in estradiol-17~. The Peak Day is
associated with the timing of ovulation and these stud- There continues to be a need for research in the psy-
ies show reproducible results between different investi- chosex ual aspects of the use of natural methods. lt is
gators in various places in the world. New technolo- in this component of its use that we anticipate its most
gies such as ultrasound observation and timing of ovu- critica! successes. While periodic abstinence has always
lation are adding to this already existent body ofknowl- been considered to be a negative relative to nat ural
edge continua ll y lending suppo1t to the basic principies methods, in fact, ifproperly and maturely approached ,
of the system. E ven vaginal cytology has been u sed to it is believe that it can become one ofthe strongest build-
confirm these findings . ing blocks for a strong marriage relationship. Strong,
bonded and loving marriage relationships also have a
There is now no question that the method effectiveness very positive impact on the children in the family. Thus,
ofthe CREIGHTON MODEL to avo idpregnancy is com- the CrMS 's versati lity and its potential to further a llow
parable to any drug or device on the market. lts method the discovery ofthese psychosexual components- and
and use effectiveness to avoid pregnancy are compa- our ability to understand and com municate these to new
rable with artificia l methods and its demographic ef- users- will allow this work to be expanded indefinitely
fectiveness , because it is safe and has a high continuity into the future .
ofuse, actua ll y holds greater promise than current ar-
1. Pommerenke WT: America n Jouma l ofübstet Gynecol 52: 1023, 7. Billings EL and Westmore A: The Billings Method : controlling
1946. Fertility Without Drugs or Devices. Random House, New York,
New York , 1980.
2. Rydberg E: Acta. Obstet Gynec Scand 29 (fac. I ): 127, 1948.
8. Roland M: A Simple Test for the Detennination of Ovulation,
3. Breckenridge MA and Pommerenke WT: Anal ys is ofCa rbohy- Estrogen Activity and Earl y Pregnancy Us ing the Cervical Mu-
drates in Human Cerv ica l Mucus, Fertil Steril 2: 29, 1952. cus Secretion. Am J Obstel Gyneco l 63: 8 1-89, 1952.
4. Cohen MR , Stein IF and Kaye BM: Spinnbarkeit: A Character- 9. Zondek B and Rosen S: Cerv ica l Mucus Arbori zation: lts Use
istic ofCervical Mucus. Fertil Steri l 3: 201, 1952. in the Detennination of Co rpu s Luteum Function. Obste!
5. Smith WT: The Pat hology and Treatment of Leucorrhea, Gynecol 3: 463 -470, 1954.
Ch urchi ll , London, 1855. 1O. lnsler V, Melmed H, Eichenbrenn er l. , el al: The Cerv ical Score:
6. Sims JM : British Medical Journa l, 2: 465-492, 1868. A Simple Semiquantative Method for Monitoring of the Men-
strua l Cycle. lnt J Gynec Obstet 1O: 223-228, 1972.
Chapter 15: Scientific Foundations of !he CrMS 213
11. C li ft AF: Ea rly Studies on the Rheology ofCervical Mucus. Am 3 1. Casey JH: The Corre lat ion Between Midcycle Hormonal Pro-
J Obstet Gyneco l 134: 829-832, 1979. files , Cervica l Mucus and Ovulation in Norma l Women . In:
Human Love and Human Life. Santamaria, J. N. and Billings,
12. Cervica l Mucus: Present State of Knowledge, In: Cervica l Mu-
J.J ., Eds. The Polding Press, Melbourne A ustra li a, p68 , 1979.
cus in Human Reproduction. World Hea lth Organi zation-Col-
loquium, Pub lished Proceedings, Ge neva, Switzerland , 1972. 32. Hilgers TW, Abraham GE, and Cava nagh D: Natural Family
Planning-1. The Peak Symptom and Estimated Time of Ovula-
13. Hil gers TW and Prebil AM: The Ovulation Method- Vul var Ob-
tion. Obstet Gynecol 52: 575-582, 1978.
servati ons asan Index ofFerti lity/lnfertility. Obstet Gyneco l 53:
12-22, 1979. 33. Cortesi S, Rigoni G, Ze n F, et al : Corre lat io n of Plasma
Gonadatropins and Ovarían Stero id Pattern with Symptomat ic
14. Faccioli G, Cortesi S, and Calderoni P: Structure of Human Cer-
Changes in Cervica l Mucus During the Men strual Cyc le in Nor-
vica l Mucu s Corre lation with Plasma Ovarían Honnone Leve ls.
mal Cycl ing Women. Contraception. 23: 635-64 1, 198 1.
Acta Europaea Fertil itati s. 14:41-50, 1983.
34. Morishita H, Hash imoto T, Mitani H, et al: Cerv ical Mucus and
15 . García N, Giacchi E, Campo S, et al: Cana li zation of Human
Prediction ofthe Time ofOvu lati on. Gyn Obstet lnvest 1O: 157-
Cervica l Mucus. Obstet Gynecol 64: 164-169, 1984.
162, 1979.
16. Odeblad E: Cervical Factors . lnt Rev Nat Fam Plan 5: 153-162,
35. H il gers TW: Hormon a l Profi les in Users of the Ovulation
198 1.
Method. In : Human Love and Human Life. Santamari a, J.N.
17. Odeb lad E: The M ucus Symptoms Length and Subphases Dur- and Billings, J.J., Eds . The Po lding Press, Melbourne, A ustra-
ing the Ferti le Age . lnt Rev Nat Fam Plan 1O: 303 -313, 1986. lia, p59, 1979.
18. Odeblad E: The Biophysical Properties of the Cerv ica l- Vag in al 36. Leader A, Wiseman D, Tay lor PJ: The Prediction ofOvu lation:
Secret io ns. lnt Rev Nat Fam Plan 7: 1-56, 1983. A Comparison of the Basa l Body Temperature Graph, Cerv ica l
19 . Odeblad E.: The Di scovery ofDifferent Types ofCervica l Mu- Mucus Score and Realtime Pelvic Ultrasonography. Fertil Steril
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Pontifical Academy of Sciences, Vatican C ity, Italy, Nov. 16, Changes in Relationship to Urinary Luteinizin g Honnone. Fertil
lta ly, Nov. 16, 1994. Steri l 48: 783-786, 1987.
2 1. Rudo lfsso n C : Nuclear Magnetic Resonance and Cytometr ic 39. Depares J, Ryder, REJ , Walker SM , et al: Ova rí an Ultrasonog-
Stud ies on Mucus from Single Cerv ica l G lands . lnt J Fert 16: raphy High li ghts Preci sion ofSymptoms ofOvul ation as Mark-
147- 150, 197 1. ers of Ovu lation. Brit Med J 292: 1562, 1986.
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ca l Mucus. Acta Europaea Fert ilitatis, 15: 131- 136, 1984. Med 31, 1986.
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E.S.E, and Eva ns, T.N. , Eds.) Harper and Row, Hagerstown , ra l Fam il y Planning Ed ucati on and Research Center. Omaha ,
Maryland, 1973. Nebraska, 1978.
26. Moghi ss i KS, Syner FN , and Eva ns TN: A Composite Picture of 44. Fehring RJ , Lawrence DM , Sa uvage CM : Self-estee m, Spiri-
the Menstrua l Cyc le. Am J Obstet Gyneco l 114 : 405-416, 1972. tua l Well-being and lntimacy: A Comparison Among Co upl es
27. lns ler V, Glezennan M, Ze idel L, et al: Fert il Steril 33: 288-293, Using NFP and Oral Contracepti ves. lnt Rev Nat Fam Plan 13
1980. (3/4) : 227-236, 1989.
28. Brown JB , Hari sson P, Smith MA , et a l: Corre lations Between 45. Fehring RJ and Lawrence DM: Sp iritual We ll-being, Se lf-es-
the Mucus Symptoms and the Hormonal Markers of Fertility teem and ln timacy Among Coupl es Us in g Natura l Fami ly Pl an-
Throughout Reprod uctive Life. Ovulation Method Resea rch and ning. Linacre Qua rterly. pp. 18-29, August 1994.
Reference Centre of Australia, Melbourne, Victoria, Austral ia, 46. Fehring R: Persona l co mmuni cation, Jul y 1999.
198 1
47. Hilgers TW: The Stat istica l Eva luation ofNatural Methods of
29 . Bil lin gs EL, Bill ings JJ , Brown JB , et al: Symptoms and Hor- Fami ly Planning. lnt Rev Nat Fam Plan 8: 226-264, 1984.
mon al Changes Accompanying Ovulation. The Lancet, Febru-
ary 5, pp. 282-284, 1972. 48. T ietz C and Lewit S: Stati stical Evaluation of Contraceptive
Methods: Use-Effectiveness and Extended Use-Effect iveness.
30. Flynn AM , and Lynch SS: Cervical Mucus ldentificat ion ofthe Demography 5: 93 1, 1968.
Fe11ile Phase of the Menstrual Cyc le. Brit J Obstet Gynaecol
83:545, 1976. 49. Hi lgers TW and Stanfo rd JB: The Use-Effectiveness to Avoid
Pregnancy ofthe CREIGHTON MODEL NaProEDUCATION Tech-
nology: A Meta-Anal ys is of Prospective Tria ls. J Repro Med
43:495-502, June 1998.
50. Hilgers TW, Prebil AM , and Da ly KD: The Effecti veness oflhe 55. Tietze C and Lew it S: The !UD and the Pill: Extended Use-
Ovu lation Method as a Means of Achieving and Avo iding Preg- Effecti veness. Fam Plan Perspec 3: 53-55 , 197 1.
nancy. Paper presented at the Educalion Phase 111 Co ntinuing
Education Conference for Natural Fami ly Planning Practiti o- 56 . Tietze C and Lew it S: Use Effectiveness of Oral and lntrauter-
ners, Merey Fontenelle Center, Omaha, Nebraska, Jul y 1980. in e Contraception . Fertil Steril 22:508-513, 1971.
51. Doud J: Use Effectiveness of the Creighton Model of NF P. lnl
57. Marsha ll J: A Field Trial ofthe Basa l Body Temperature Method
Rev Nat Fam Plan 9:54-72, 1985.
of Regulation of Births. The Lancet, pp8- I O, Jul y 6, 1968.
52. Howa rd MP: Use Effect ivene ss of the Ovulation Method
(CREIGHTON MODEL) ofNatural Family Planning. Paper pre- 58. Klaus H: Natural Family Planning : A Rev iew. Obste! Gynecol
sented at lhe N inth Annua l Meeting of the American Academy Surv 37 : 128-1 50, 1982.
ofNatura l Family Plan ning, Milwaukee, Wi sconsin , Jul y 1990.
59. Hilgers TW, Daly KD, Prebil AM, et al: Cumulative Pregnancy
53. Fehrin g RJ , Lawrence D, and Philpot C: Use Effecti veness of Rates in Patients with Apparently Nonnal Fert ility and Ferti l-
the Creighton Mode l Ovulation Meth od ofNatural Fami ly Plan- ity-Focused lntercourse. J Reprod Med 1O: 864-866, 1992.
ning. J Obstet Gyneco l, and Neonat N urs 23: 303-309, 1994.
60. Hil gers TW, Prebi l AM, Daly KD, and Hil gers SK: The Pi cture
54. Tietze C: The C linical Effecti veness ofContraceptive Methods. Dicti onary ofthe CREIGHTON MODEL FertilityCare™ System.
Am J Obstet Gynecol 78: 650-656, 1959. Pope Paul VI !nstitute Press, Omaha, Nebraska, 1999.
Measuring Effectiveness and Pregnancy
Rates of the CrMS
Joseph B. Stanford , M.O.
U nderstand ing the outcomes of using the

(CrMS) to avoid or to achieve pregnancy is of central
infertility. Finally, the clinical and research implications
ofthis area ofresearch are summarized.
importance to users, Practitioners, and Medica! Con-

sultants. Because the meaning of statistical sumrnaries Terms Used to Describe Effectivness
of effectiveness or pregnancy is dependent on the way 4
in which they are derived, an understanding ofthe meth- A number ofterms ha ve been used in the contraceptive
ods involved is necessary. The purpose of this chapter literature to measure the effectiveness of methods of
is to describe the scientific measurement and under- contraception. These include "failure," efficacy, effec-
standing of the occurrence of pregnancy during use of tiveness, and pregnancy.
the CrMS . T his chapter describes an established ap-
proach to measuring the effectiveness of the CrMS in Experts in the field of contraceptive research have rec-
actua l use to avoid or achieve pregnancy, 1 including a ommended against the use ofthe term failure because it
critica! summary of published effectiveness studies of does not accurately distingu ish between pregnancies
the CrMS . Important principies for conducting and in- that would or would not have occurred without use of a
terpreting CREIGHTON MODEL studies are detailed. Ref- contraceptive.2 More fundamentally, the tenn failure is
erences for the detailed calculations are provided. In not appropriate for any method offamily planning be-
addition, th is chapter introduces a new approach for cause the normal functioning of the reprod uctive sys-
measuri ng pregnancy rates specific to different types tem and the development of a new human life is not a
of use of the CREIGHTON MODEL. Throughout the failure but a success ofthe natural process, even when
chapter, defin itions are given for essential terms and a pregnancy is not expected. This is espec ially true of
concepts, and comparisons are made with approaches the CrMS, which fully cooperates with normal function
used in contracept ive research , to facilitate appropriate of the reproductive system rather than seeking to sup-
comparison and understanding. A brief description is press or destroy it and which fully respects and sup-
given ofhow these approaches may apply to assessing ports the right and responsibility of couples to make
the use ofthe CrMS in infertility, including suggestions decisions in cooperation with normal reproductive func-
for future development of methods to assess use with tioning.
21 5
Efficacy and effectiveness are related but not identical defining actual use of the method, identification and
terms . Different authors use the te1ms effectiveness and inclusion of pregnancies, and statistical methods used.
efficacy with different definitions, causing confusion These categories and the indi vi dual items are meant to
about their meaning. Efficacy generally refers to the be representative, not ex hausitive. They are not neces-
maximum possible effectiveness ifa method offamily sari ly listed in order of priority. Each of the method-
planning is used perfectly. In this chapter, efficacy is ological issues described in Tab le 16-1 also has a note
synonymous with avoiding-related/method-related ef- as to whether it is necessary for effectiveness stud ies
fectiveness (described la ter in this chapter) . Effective- of ali fa mil y planning methods, has particular applica-
ness is a term that must be further defined befare it is tion to NFP studies, or is uniquely formulated for stud-
meaningful. Different types of effectiveness rates are ies ofthe CrMS . This should aid in understanding key
defined later in this chapter in connection with the es- simi larities and differences with studies of other FP
tablished approach for assess ing fertili ty outcomes of methods and family planning methods generally. A com-
the CrMS . parison of the "ideal" and "acceptable" approaches
gives an idea of the range of possible variation of ap-
An objective way of describing the results during use proaches within the limits ofwhat is ideal and what may
ofany method offami ly planning is simp ly to describe be more practica! for a given study. A general descrip-
pregnancy rates. Using pregnancy rates is an objective tion of the actual approach taken by CREIGHTON
approach that is currently recommended by experts in MODEL studies to date is al so given, with the hope that
family planning research. 2-4 Just as for effectiveness, future studies may be ab le to expand the methodologic
the conditions of use of the method must be described rigor in identified areas.
in order for a pregnancy rate to be meaningful. Later in
this chapter, different types of pregnancy rates are de- As detailed in Table 16-1 , it is important that a study's
scribed in connection with a new approach fo r assess- protocol be clearly described , and preferably prospec-
ing fertil ity outcomes ofthe CrMS . tively conducted. A minimum ofstudy participant infor-
mation should include the woman 's age and basic re-
Effectiveness and pregnancy rates are directly related. productive characteristics. It is helpfu l to also have in-
One can be derived from the other by subtracting from formation about th e men. Standardized approaches are
100 (assuming that the original rate is expressed in terms necessary for teaching, teacher training, and documen-
of a percentage). For example, a pregnancy rate of 5 tation of couple learning. Key issues are identify ing how
percent means an effectiveness rate of95 percent. Simi- the method is actually used by the couple, including
larly, an effectiveness rate of99 percent means a preg- the use of additional methods (such as barriers or with-
nancy rate of 1 percent. drawal), and information about use to avoid or achieve
pregnancy (discussed below). In connection with the
actua l use ofthe method , it is essential that ali pregnan-
Features of a Good Effectiveness Study cies be identified, reported, and appropriately catego-
rized. Preferab ly, each cyc le or month wi ll also be cat-
Tab le 16-1 li sts fea tu res of the methodologically ideal egorized in terms ofactual use, as discussed further in the
and sound effectiveness stud ies. Many ofthe elements next section. This invo lves information on the occur-
listed here come from scientific literature on contracep- rence of intercourse during the fertile days. Information
tive studies but app ly also to natural family planning on the overa ll frequency of intercourse is also val uable
(NFP). 23 ·5-8 Also indicated in the table are features re- to assure that ali cycles or months in the study actually
lated to natural family planning studies in general and relate to use of the method to either avoid or achi eve
to the CrMS in particular. 1•9 To date, no study has ali of pregnancy. It is further recommended that couples dis-
the features of an ideal study. But, each of the four covered to have infertili ty by virtue of consistent inter-
published effectiveness studies of the CrMS is among co urse without pregnancy during the fe rtile ti me for six
the most sol id effectiveness studies avai lab le in NFP, or cycles, be removed at that point from the analysis, on
family planning genera ll y. 9- 12 Hopefully, future studies the same grounds as the exc lusion of couples from the
will incorporate or strengthen sorne of these method- outset with known infertility. 13•14 (To improve compara-
ological elements. bility to stud ies that do not make this exclusion, the
ana lysis can be repeated with and without it. )
The methodologic featu res highlighted in Table 16-1
fall into six categories: genera l study characteristics, Appropri ate statistical methods should be utili zed for
characteristics of the study population (sample), char- the data. A variety of statistical techniques can be ap-
acteristics of the NFP method and teaching system, pl ied to each of the different pregnancy and effective-
Chapter 16: Measuring Effectiveness and Pregnancy Rates of the CrMS 217
ness rates. In particular, Pearl rates for a study group ied, such as its effects in managing gynecologic condi-
followed for just one year will usually (but not always) tions or the couple dynamics of using it, but these are
be similar to net (multiple decrement) life table rates. outside the scope of this chapter.) A complete assess-
Gross (single decrement) life-tab le rates are the most rnent of the effectiveness of the CrMS in couples of
accurate to compare between studies, but they are some- apparently normal fertility must include the rneasure-
what higher than net life-table rates, and cannot be comrnent of achieving pregnancy (in normal fertility) and of
pared directly to net life-table rates or Pearl rates. This avoiding pregnancy.
is important because only a few NFP studies have actu-
ally reported gross life-table rates . Sorne studies have
had their data reanalyzed in terms of gross life-table Distinguishing Between Use to Avoid and
rates. 3 In comparing rates between studies, it is also Use to Achieve Pregnancy _ _ _ _ _---.
essential to look at the categorization, inclusion, and
exclusion of pregnancies and cycles or months of ex po- In sorne overall rneasures of pregnancy rates, it is not
su re for the different pregnancy and effectiveness rates necessary to distingu ish whether the rnethod was used
(see Tab le l 6-3 , discussed below). to avoid orto achieve pregnancy (as described later in
this chapter under " tota l pregnancy rates" and " ex-
tended use effectiveness"). However, much ofwhat we
Assessing Use to Avoid and Achieve want to know depends upon distinguishing between
Pregnancy _ _ _ _ _ _ _ __ __ ~ use of the method to achieve pregnancy and use to
avoid pregnancy. This leads to the important question
By definition and design, contraception is used to avoid of how best to rnake this distinction . Fundarnentally,
pregnancy on ly. Accordingly, ali research on contra- there are two ways to do this: intentional and behav-
ception seeks to exclude any pregnancy that is sought ioral. The CrMS uses the behavioral approach. It is im-
by the couple, and to consider only pregnancies that portant to understand for comparative purposes that
occur in the context of avoiding pregnancy. Regretta- rnost other studies of NFP and contraception use the
bly, most studies of NFP rnethods have followed this intentional approach. Both approaches are described
convention and have excluded couples who stated that below, followed by a discussion of the advantages of
they were trying to achieve pregnancy, or have ended the behavioral approach .
their participation at a point in time that they stated
they wanted to conceive. Tn sorne studies, there is not The intentional approach asks a couple ( or sornetirnes,
even any sort of assessment of whether a couple rnay just the wornan) to state whether they intend( ed) to get
start to try to conceive. The result is that a critica! di- pregnant during a particular time period, such as ayear,
mension ofthe use ofNFP is excluded from study. This a rnonth, a cycle, or at the time of a pregnancy. A couple 's
approach is fundarnenta lly incompatible with the unstated intentions are taken at face value, regardless of
derlying p hilosophy ofthe CrMS . their underlying reasons or the strength of intention.
Usually, the intentional approach is applied prospec-
The CrMS is taught as a systern of natural procrea ti ve tively : couples are asked to state in advance whether
education. Couples are empowered and supported to they intend to conceive in the next cycle, month , year,
make decisions abo ut avoiding or achieving pregnancy or other time frarne . Sometimes additional criteria rnay
on a daily basis, in accordance with the privilege and be used in order to eliminate couples who are not suffi-
responsibility of understanding their combined repro- ciently "serious" about their stated intentions to avoid.
ductive potential. 12•15•16 No couple is taught only how to For example, sorne studies ha ve tried to distinguish be-
avoid or only how to achieve pregnancy: the two aspects tween couples who say they wish to space their next
of the rnethod are always taught together. Of course, pregnancy and those who wish to never again become
one aspect of use rnay be emphasized more than the other, pregnant (though this distinction has not usually made
according to the couple 's current needs and desires, any difference in NFP studies). 11- 19 Those couples who
but this is only meaningful in the context offull respect state they wish to conceive ( or who may be undecided)
for both aspects of a couples' reproductive potential. are then excluded and, among the remaining couples, ali
pregnancies that occur in the stated time frame are clas-
lt follows that any study which seeks to reflect preg- sified as " unintended" or "unp lanned" regardless of
nancy rates during the actual use of the CrMS must the behavior of the couples at the time of conception.
also respect that it can be used either to achieve or to (Sometimes, couples who wish to conceive are fo llowed
avoid pregnancy and incorporate this reality into its separately to assess the rates of" intended" or "planned"
evaluation. (Other aspects ofthe CrMS can also be stud- pregnancy.2º)
Table 16· l: Ideal and Acceptable Methodological Features of Effectiveness Studies
.... dénllralStatus in · ·· •· • .·
Methodologie·· •Question .·· Appllesto• Ideal Approaéh AeceptableApproach cfMS sil.l~ i~S t() Dat~t' }
General Study
What is the design of the All Prospective cohort Prospective or retrospec- Prospective cohort
study? tive cohort, weli-identified
and tracked
Was a learning phase used? NFP No separate learning lf learning phase is used , No separate learning phase ,
phase , on ly new users include it in the analysis only new users
Is the study protocol All Able to replicate study Reasonable description ; up Able to replicate study if use
clearly described , including from description, uni- to at leas! 1 year of follow- CREIG HTON MOD EL clinical
entrance and exit criteria , form extended follow- up far ali subjects , with at approach and method refer-
definitions, and procedures? up far ali subjects leas! 100 subjects left in ence ; 12-18 month follow-up.
active continuing in study Status at endpoint of study
Are the study investigators NFP Most investigators At leas! one investigator Ali investigators clinical ly ex-
competen! in the NFP clinicaliy experienced in with thorough clinical under- perienced in method
method studied? method standing of method
Where was the study Ali Peer reviewed journal Complete data consisten! Peer reviewed journals
published? with peer reviewed quality
Study Population
What were the demographic Ali Age , race , income, edu- Minimum of woman 's age Summary descriptive informa-
characteristics of !hose cation , race , marital sta- tion on age , religion , race , in-
studied? tus- socioeconomic vari- come, weighted towards afflu-
ability desirable ent white Catholics.
What were the reproductive All Describe parity, cycle Describe parity, cycle cha r- Parity known only pa rtialiy and
characteristics of !hose characteri stics, sexualiy acteristics , describe who is sexualiy transmitted disease
studied? transmitted disease his- excluded and exclude known history not given. lnfertility
tory, past/recent use of infertil ity. excluded. Ali other reproduc-
hormonal or other family tive categories included (un-
planning methods, breas!- usual among NFP studies) .
feeding . Exclude !hose Cycle characteristics , breas!-
with likely infertility, but feeding , and recen! hormonal
include ali other reproduc- contraceptive use known , and
tive status (categories) . independently evaluated far
impact on effectiveness (one
study) .
What is known about the All Age , prior fertility None None reported
men?
NFP Method and Teaching

Is the NFP method clearly NFP Standardized description Standardized description CREIGHTON MODEL teach-
described or referenced and of how times of fertility of how times of ferti lity ing materials give complete
standardized? and infertility determined, and infertility determined , standardized and detailed
and instructions far use and instructions far use instructions far use
What was the procedure and NFP Standardized teacher Description of teacher train- Standardized Practitioner train-
quality of teaching? training and supervision , ing and teaching procedures ing and supervision , protocols
protocols far teaching far teaching visits
visits
Is there an assessment of NFP Standardized assessment None Standardized assessment is
how well the couple learned of how weli couples done but has not been reported
the method? learned method in published studies
What are the details of days NFP Percentage and distribu- Non e Non e
of fertility and infertility? tion of days identified as
fertile or infertile
Use of Method
Is the use of withdrawal , NFP Use of other methods ex- Use of other methods ex- Use of other methods excluded
ba rrier methods or other cluded from analysis of cluded or minimal from analysis of the
contraceptives identified? NFP method; may be CR EIGHTON MODEL
analyzed separately
Is the moral autonomy of NFP Ali study procedures con- Couples choices respected Al i study procedures consis-
couples respected? sistent with freedom of and reported with reasonable tent with freedom of coup\es
couples to choose how to categories to choose how to manage their
manage their fertili ty, with fertility, with support for inte-
support far integration of gration of a fuliy cooperative
a fuliy cooperative ap- approach to fertility
proach to fertility
Continued on next a e
Table 16-1, cont' d: Ideal and Acceptbale Methodologic Fea tu res of Effectiveness Studies
·.· ', . •, '' •,,,, ' .·. ·........... ... . . . _._ .. ·
-
Generat stafüs in
•·•· M~thodÓlog ic .Ques~i<lll Appliesto• Ideal Approach ••• ••..· Acéepiablii~pproaé:h Ct MS Studies fo o .a te*'
Use of Method , cont'd

Is there an assessment of Ali Sorne indication of satis- Non e Satisfaction is assessed but
couple satisfaction? faction of all participating has not been reported in pub-
couples lished studies
Are continuation rates NFP Continuation rates re- Overall continuation rates Continuation rates reported ,
reported? ported , along with details (or total discontinuation along with details of different
of different reasons for rates) reported reasons for discontinuation ;
discontinuation; expected expected continuation rates
continuation rates after after pregnancy included
pregnancy included
Is information on frequency All Summary measures of None None
of inte rcou rse reported? frequency of intercourse
per cycle (or month); ex-
clusion of cycles or months
with no intercourse (except
!he first month for CrM)
What about discovered NFP lf couples exhibit 6 cycles Non e Non e
infe rtility? of intercourse during fer-
lile time without pregnancy,
they should be removed
from the study at that
point
Is actual use of the CrM Sufficient ascertainment Sufficient ascerta in ment to Sufficient ascertainment to
CREIGHTON MODEL to describe whether the describe whether the method describe whether the method
described in terms of method was used to was used to avoid or was used to avoid or achieve
achieving and avoid ing avoid or achieve preg- achieve pregnancy in preg- pregnancy in pregnancy
pregnancy?' .. nancy in each cycle (or nancy cycles (months), cycles (months), obtained dur-
month), based on stan- based on standardiized preg- ing standardized pregnancy
dardized repeated intention nancy eva luatio ns evaluations. Standa rdized use
use assessment and preg- assessment is conducted is
nancy evaluations done during follow-up visits, but
is not routinely used to assess
type of use of the method dur-
ing each cycle
Pregnancies
Are all pregnancies in- NFP lnclusion of all pregnan- Clear description of pregnan- lnclusion of all pregnancies
cluded in the study ana lysis? cíes during NFP use, in- cíes included and excluded during NFP use, including dur-
cluding during use to ing use to achieve and avoid
achieve and avoid preg- pregnancy
nancy
How are pregnancies iden- All Monthly assessment with Regular assessment with Routine assessment continues
tified? objective measures, such defined measures and fol- for one year, but frequency of
as charting or urine preg- low-up for uncertain cases assessment decreases with
nancy testing increased duration of use;
charting provides objective
assessment of pregnancy
Statistical Methods
What statistical method is All Gross lite-table (single Net lite-table (multiple Net lite-table rates (2 studies
used to de ri ve pregnancy decrement) analysis best decrement) or Pearl Rates have also reported Gross Lile
rates? for comparison between limited to 12 months or 13 Table rates)
studies cycles (less accurate)
What pregnancy rates CrM Total and pregnancies dur- Total , method related Total, achieving related ,
are reported?*" ing achieving-related use, method related , using related,
avoiding-related use, teaching related , unresolved'"
method consisten! and
method inconsistent, with
further information on using
and teaching related
Are co nfidence intervals All lnclusion of confidence Non e Non e
calculated? intervals
All= applies equally to all family planning studies; NFP=applies particularly to NFP studies, including CREIGHTON MODEL; CrM= applies particularly to CrM studies
•• There is sorne variability among published CREIGHTON MODEL studies. A general outline is given here of how each issue is handled in most (or all) published studies.
*** See Table 3 which describes the derivation of previousty established and new types of pregnancy rates.
[n contrast, the behavioral approach assesses the In contrast, the identification ofbehavior that is directed
couple's actual behavior or their actual use of a natura l towards avoid ing or achi evi ng pregnancy is obj ective
method. The basic question is: did the couple use the and comparable between different populations. Experi-
method correctly to avoid pregnancy? In the CrMS , thi s ence confinns that thi s approach is readily understood
is assessed during routine fo ll ow-ups and the pregnancy and accepted by CREIGHTON MODEL users. Most im-
evaluation. Th is is a fundamental ly objective approach. portantly, the behaviora l approach is fu lly consistent
Although making the behavior assessment relies on with the underlying philosophy ofthe CrMS : to respect
comp lete reporting of behavior by the couple (inc lud- and support the right and responsibility of the couple
ing accurately reporting observations of ferti lity signs to make choices in cooperation with their reproduc-
and occurrences of intercourse or genital contact), it tive potential. The behavioral approach measures these
does not rely upon their stated intention or desire for choices (and the subsequent outcomes of pregnancy)
pregnancy. objectively. lt shou ld be noted that the behavi oral ap-
proach on ly makes sense when it is used in a context of
Sorne NFP researchers have argued that the intention teaching both uses of the method (to ach ieve and to
approach should be used in NFP because it is the ap- avoid pregnancy) to ali couples and when the couple is
proach used in contraceptive and demographic re- deemed to be capable of assuming ful ! responsibility
search.3·2 1·22 However, a major weakness of the inten- for their reproductive behavior. This is exactly the con-
tional approach is that it oversimp li fies a complex sys- text ofthe CrMS .
tem of human motivations aro und fert ility, making it
unclear what is actually being measured and what it lt shou ld not be assumed that intentions are irrelevant
means. 23 -26 At least in sorne United States settings, in the use ofthe CrMS . In fact, they are highly relevant,
women do not consistently define or even relate to the because they lead to behavior. Intentions can and shou ld
idea of intended pregnancy, and their definitions of plan- be studied, but they do not define actual use. Inten-
ning do not directly coincide with the definitions used tions are routinely assessed during the fo ll ow-ups and
by contraceptive researchers and demographers. 21 -29 In pregnancy eval uations of the CrMS, and the assessed
a national survey in the Un ited States, many women intentions are combined with the behavioral assessment
who were using a method of contraception defined their to all ow the FertilityCare™ Practitioner (FCP) to tai-
pregnanc ies retrospectively as intended. 30 Given the lor the teaching of the method to the specific needs of
variation in cu ltural, soc ial, and psychological circum- each client couple. In one CrMS study, over half of ali
stances between population s, it is doubtfu l that the achieving-related pregnancies ( discussed below) that
concept of intended or unintended pregnancy provides occurred were considered "planned" by the couple. 10
a meani ngful comparison between populations. Currently, research is in process to describe better the
Table 16-2: Creighton Model Pregnancy C lassificatio n
Code pategory Descri·ptioi:l
Achieving-related pregnancy From the avai lable information, the method was used as a method of
avoiding pregnancy, and the woman became pregnant.
11 A Avoiding-method related pregnancy From the avai lable information , the method was used correctly as a
method of avoiding pregnancy, and the woman became pregnant.
11 B Avoiding-using related pregnancy From the avai lable information, the method was used incorrectly (but
taught correctl y) as a method of avoiding pregnancy, and the woman
became pregnant .
11 C Avoid ing-teaching related pregnancy From the available information , the method was taught incorrectly
(but used correctly according to instruction) as a method of avoiding
pregnancy, and the woman became pregnant.
11 D Avoiding-using /teaching related A combination of using related and teaching related.

pregnancy
111 Unresolved pregnancy From the available information, the circumstances of the pregnancy
cannot be placed into any of the above classifications.
NR Not related pregnancy Pregnancy did not occur during use ofthe CrMS , but rather during the
use of another method, such as condoms or withdrawal.
Table 16-3: Calculation of Different Effectiveness and Pregnancy Rates

during Use of the Creighton Model System
Pregnancies in Time in
Nüinerator"* Denomínator:•~~~~9.rte~}n•••• Comments
Method-related 11 A a+b+c+d 1,2,3,4 ,5

pregnancy rate
Use-related
pregnancy rate
11B+11C+11 D a+b+c+d 1,2,3,4 ,5 } Category 111 pregnancies are distributed
among these measures , as described un-
der "Unresolved Pregnancies" in the text.
Achieving-related
pregnancy rate a+b+c+d 1,2,3,5 This has also been called the "use effective-
ness to achieve pregnancy." Sorne category
111 pregnancies are included in this measure,
as described under "Unresolved Pregnan-
cies" in the text.
Total pregnancy rate l+llB+llC+llD a+b+c+d 1,2,3, 5
Extended-use 1+11 B + 11C+11 D + NR a+b+c+d+e 5 This has been estimated in one CREIGHTON
pregnancy rate MODEL study. Sorne non-CREIGHTON
MODEL studies exclude "unplanned" preg-
nancies from this statistic.
Pregnancy rate with 11 A b

avoiding-related ,
method-consistent use
Pregnancy rate with 11 B + 11 C + 11 D e These measures Category 111 pregnancies and use of the
avoiding-related , have not yet CREIGHTON MODEL with insufficient
method-inconsistent use been used in information ("d" time in Figure 1) are distrib-
CREIGHTON uted among these measures , as described
Pregnancy rate wi th 11 A + 11 B + 11 C + 11 D b+ c MODEL studies under "Unresolved Pregnancies" and "Unre-
avoid ing-related use solved Time Periods of Use" in the text.
Pregnancy rate with a

achieving-related use
Note that each of these calculations can be done with different time frames (such as 6, 12, or 18 ordinal months). Different statistical approaches could be used far each
measure, but the preferred statistical method used in ali studies to date is life table analysis. This table states ali measures in terrns of pregnancy rates. Effectiveness rates
are obtained by subtracting the respective pregnancy rate (expressed consisten! with a percentage) from 1OO.
~ As described in Table16- 2 and Figure 16-1 .
*** As described in Figure 1.

Published CREIGHTON MODEL studies and method papers referenced (in chronological arder):
1. Hilgers TW, The statistical evaluation of natural methods offami/y p/anning lnt Rev Nat Fam Plann 8(3)Fall p. 226-264, 1984.
2. Doud J, Use-effectiveness of the Creighton Model of NFP. lnt Rev Nat Fam Plann, 9(1 )Spring: p. 54-72, 1985.
3. Fehring RJ , D Lawrence, and C Philpot, Use effectiveness ofthe Creighton-Model Ovulation Method of naturalfamilyplanning. J Obstet Gynecol Neonat
Nurs, 23(4): p. 303-309, 1994.
4. Hilgers TW and JB Stanford, Creighton-Mode/ NaProEducation Technology for Avoiding Pregnancy. J Reprod Med , 43(6): p. 495-502, 1998.
5. Howard MP and JB Stanford, Pregnancy probabilities during use of the Creighton Model Fertility Care System. Arch Fam Med, 8: p. 391-402, 1999.
relationsh ips between a coupl e's designation ofa preg- bias towards a contraception-only approach (avoiding-
nancy as " planned," " unplanned," "wanted," or " un- on ly approach) than others, but none ofthem is consis-
wanted," and the objective behavioral class ification of tent with the understanding of sexual freedom and re-
the pregnancy, described further below. sponsibility that underlies the CrMS . However, it is im-
portant to distinguish those pregnancies that resu lt from
For the reasons discussed , the term " unintended preg- use of the CrMS to avo id pregnancy and its use to
nancy" is not used as a category in studies of CrMS achieve pregnancy. It is also important to understand
effectiveness or pregnancy. Consequently, a number of the impact ofthe quality ofteaching on pregnancy rates.
other terms that have been used in contraceptive and This leads us to a cons ideration ofthe pregnancy clas-
NFP stud ies are a lso not appropriate for studies of the sification system used in the CrMS . This system is used
CrMS . These include pregnancies resulting from " con- both clinically in actual teaching ofthe method and in
scio us departure from the rules," " informed choice," the CrMS effectiveness studies that have been con-
" user fail ure," " behavioral failure ," " ri sk taking," " im- ducted to date.
perfect use," or " occas ionally not following ali the
rules ."3 1- 34 Sorne of these terms include more inherent
222 The Medica l and Surgical Practice of NaProTECHNOLOGY
Pregnancy Classification -----~ a "

~
1
The pregnancy classification ofthe CrMS divides preg- b
" IIA
nancies into three categories: achieving related, avoid- e
ing related, and unresolved. 12 •16 Avoiding-related preg- r IIB
nancies are further subdivided , as described in Table e "
r
IIC
16-2.
e
"r IID
These categories of pregnancy are closely related, by b 1 e 1 e
1
r llI
definition, to corresponding categories of sexual be- 1
havior. During instruction in the CrMS , couples are e "

r NP
taught clearly that intercourse (or genital contact) on b
days of fertility abandons use of the rnethod to avoid r
X
pregnancy and adopts use of the rnethod to achieve e
"r X
pregnancy. 12· 15•16 This includes days that are consid- e b a
1 1
ered fertile by virtue of incornplete or absent observa- 1
"r T
1
tions of the fertility biornarkers at the vulva. This is e 1 b 1 a
1 1 "r l
called achieving-related behavior (or use), or achiev-
e 1 e
ing-consistent behavior, and it usually results rapidly 1
r
NP
in an achieving-related pregnancy. a 1 e 1 b
1 1
r TIA
In contrast, avoiding-related behavior occurs when a a 1 e 1 b
"
1 1 X
couple is using the rnethod to avoid. Ifthere is no error
in user understanding, application , or teaching, the
Figu re 16-1: The left-hand vertical line represents the begin-
avoiding-related behavior is subcategorized as rnethod
ning of CrMS instruction for each participan!. Each horizon-
consistent, and any pregnancies are categorized as tal line represents a couple who began CrMS instruction .
avoiding-related/rnethod-related. lf there is an error of The length of the line (and each segment of it) represents time
user understanding or application , and/or teaching, then of use .
the avoiding-related behavior is not rnethod consistent The lower case letters above each line represen! the type of
and any pregnancies that result can be categorized as objective use for a given segment of time for that couple. The
avoiding related and subcategorized based on the pres- types of use are:
ence or absence of errors in use, teaching, or both. Jf a: achieving-related use (objective use of the CrMS as a
method to achieve pregnancy)
there is insufficient information to categorize a preg- b: avoiding-related , method-consistent use (corree! use and
nancy, it is treated as unresolved (discussed in " Unre- corree! teaching of the CrMS as a method to avoid preg-
solved Pregnancies"). nancy)
e: avoiding related , method-i nconsistent use (incorrect use
of !he CrMS as a method to avoid pregnancy)
d: use of the CrMS with insufficient information to deter-
Effectiveness and Pregnancy Rates , mine whether !he use was as a method to achieve or to
Established Approach _ _ _ _ _ _----. avo id
e: non-use of the CrMS , with or without use of another
method of family planning (such as barriers at the fertile
The relationship between different types ofuse to avoid time, withdrawal , beginning oral contraceptives, etc.)
or achieve pregnancy, the resulting pregnancies, and
effectiveness or pregnancy rates are illustrated in Fig- The Roman numerals on the right hand of each horizontal line
represen! different outcomes of use at the endpoint of use
ure 16-1 and Table 16-3. Figure 16-1 illustrates different for a given couple . The outcomes are the same as the codes
hypothetical patterns of use of the CrMS by 14 differ- given for the pregnancy classifications in Table 16-1 (e .g., 1
ent users over different lengths oftirne. These patterns represents achieving related pregnancy, 11 A represents avoid-
ing-method-related pregnancy, and so on). There are two
are intended to be illustrative and not exhaustive of ali
additional outcomes: NR represents non-CrMS related preg-
possible patterns. Sorne ofthe use is achieving related, nancy (e.g., a pregnancy related to using barriers at the fer-
sorne is avoiding-related/rnethod-consistent, and sorne tile time or otherwise not using the CrMS), and "X" repre-
is avoiding-related/rnethod-inconsistent. In addition, sents exiting the study or being lost to follow-up observation .
there are periods ofuse with insufficient inforrnation to This figure is for illustrative purposes only and is not mean to
determine whether the use was as a rnethod to achieve be exhaustive or represesentative of CrMS studies or popu-
or to avoid, and periods of not using the CrMS. The lations using the CrMS .
pregnancies are categorized according to the scherne in
Table 16-2. Table 16-3 indicates wh ich pregnancies are idea of the "upper limit" of possible effectiveness (or
used in the numerator and which periods of use are in lower limit of possible pregnancy rates) . The value of
the denominator for each of a number of pregnancy the use-related pregnancy rate is for couples to under-
rates. As noted previously, the correspond ing effec- stand what pregnancy rate they are likely to achieve
tiveness rates are calculated by subtracting the preg- with "real world" consistent use ofthe method to avoid
nancy rate from 100. Note that the exact way of setting pregnancy, accou nting for user or teacher erro rs . 12·38
up the relationship ofthe numerator and the denomina-
tor in these statistics will vary according to the statisti-
cal approac h chosen ( ee Table 16-4). The standard Comparison of Method and
approach used for years in contraceptive efficacy stud- Use Effectiveness to Other Studies =l
ies has been the net life table (multipl e decrement), pro-
posed initial ly by Tietze and others. 35 This approach A careful review ofFigure 16-1 and Table 16-3 wi ll help
was adapted by Hilgers to include the assessment of in comparing the method effectiveness and use effec-
achiev ing pregnancy and this adaptation has been used tiveness reported in CrMS studies to other FP stud-
in ali CrMS studies conducted to date. 1 Sorne CrMS ies. A couple of points are critica!. First, o lder contra-
sh1dies have additionally reported rates from gross li fe ceptive efficacy stud ies that report "use effectiveness"
table (single decrement) , based on the description re- include as user pregnancies sorne pregnancies that in
ported by Trussell and others. 36·37 CrMS studies are considered achieving related (namely,
those that would be " unplanned" as measured by the
With in the net life table used in ali studies to date ofthe intention approach described ea rlier). Perhaps roughly
CrMS , the pregnancy rates reported include method- half of achieving-related pregnancies might ha ve been
related, use-re lated, achieving-related , and total preg- considered "unplanned" by the intentional approach
nancy rates (P.R. ). 1 From Table 16-3 , it can be ascer- described above (as inaccurate and problematic as that
tained that (method-related P.R.) + (use-related P.R.) + approach may be ). 10 Therefore, use-related pregnancies
(achieving-related P.R.) = (tota l P.R.). Thus, in the tradi- will be somewhat lower unde r the CrMS definition than
tiona l approach to measuring effectiveness ofthe CrMS , under the definition used by most older contraceptive
the component pregnancy rates simply add up to the efficacy studies, and most o lder FP studies. Second
total pregnancy rate. (and related), older studies of other methods of FP or
family planning have exc luded "i ntended" pregnancies
The value of the method-re lated pregnancy rate is as a from their total pregnancy rates, so total pregnancy rates
measure ofthe maximum possible effectiveness to avoid for CrMS studies will be higher than total pregnancy
pregnancy (a lso known as theoretical or biologic effi- rates for studies of other NFP or family planning meth-
cacy, or perfect-use effectiveness). This gives users an ods (again , perhaps ro ughly half of achieving-related
Table 16-4: Statistical Approaches for Measuring Pregnancy Rates
Approach Status Comments
Pearl rates Original standard approach, Is strongly influenced by length of followup ; longer followup
now in disfavor periods lower rates; gives reasonable approximation if length
of followup is limited to 1 year; rates are independent of
time point
Net life table Long-time standard Is significantly influenced by rate of discontinuation; rates
(multiple decrement) are specific to a given time point; if common denominator
used , then componen! rates add to total pregnancy rate
Gross life table Probably curren! standard Is independent ol rate ol discontinuation , making it com-
(single decrement) parable between studies ; rates are always somewhat higher
than the net life table ; rates are specific to a given time
point; componen! rates do not add directly to total preg
nancy rate
Kaplan-Meier Similar to net lile table Starting to be used; rates are specific to a given time point
Cox proportional Similar to net lile table Allows for sophisticated multivariate comparisons (such
hazards regression as adjusting for age, parity, etc.)
224 The Med ical an d Surgical Practice of NaProTEC HN OLOGY
pregnancies would be comparable to the " planned" preg- be corre lated wi th vario us externa ! factors th at wo uld
nancies in other studies by the intentional approach). 1 º influence a coup le 's motivations for avoiding or achiev-
Perhaps the most direct comparison between CrMS stud- ing pregnancy, such as the current economic environ-
ies and o lder fami ly planning studies wou ld be w ith the ment.40 The achieving-related pregna ncy rate can al so
extended-use effective ness statistic (a lso somet im es he lp new users understand what proportion of a gro up
called demographi c effectiveness). 6·7·3739 This statistic of coup les may be likely to successfully use th e CrMS
includes essentially a li time and ali pregnanc ies for a to ac hi eve pregnancy over a year or other follow-up
specified time period after starting a method offamily period (assum ing the coup les studied are in a simi lar
planning, regardless of whether the method continues demographic and economic situation as the new users).
to be used or not, or whether any other method is used.
However, even this comparison must be made tenta-
tively because no CrMS study has rigorously followed Effectiveness and Pregnancy Rates ,
pregnancy rates among those who discontinue use of New Approach _ _ _ _ _ _ _ _ _~
the CrMS and begin use of other methods and beca u e
many who have applied the statist ic to other methods Recentl y, researchers have proposed that it is more logi-
have excluded coupl es who state an intention for achiev- ca l to measure "perfect use" pregnancy only during
ing pregnancy. cycles or months whe n a contracepti ve method is used
perfectl y to avoid pregnancy. 2 ·8·38 .41.42 A!l other cyc le
or months of use and pregnancies that occur during
Achieving-Related Pregnancy Rate those cyc les are considered to be related to " imperfect
use." lmportantly, " perfect use" pregnancies andcycles
The achieving-re lated pregnancy rate deserves specia l are not counted w hen measuring " imperfect use," and
mention because it has been widel y misunderstood .9 "imperfect use" pregnancies and cycles are not cou nted
As noted , the concept of ac hi evin g-re lated pregnancy whe n measurin g " perfect use. " However, both " perfect
is objectivel y defi ned (arguabl y much more so than the use" and " imperfect use" pregnanci es and cycles (i.e. ,
concept of intended pregnancy) and easil y understood ali pregnancies and ali cyc les) are counted when mea-
by CrMS users. The confusion comes in two areas. First, suri ng "typica l use ." This approac h has become stan-
some contraceptive researchers who do not understand dard for newer contraceptive efficacy studies43 and has
the concept have erroneous ly attempted to equate also been used for some NF P studies. 3·44
achiev ing-re lated pregnancies with " planned" pregnan-
cies.38 Pregnanc ies are classified as achievi ng related This approach cannot be directly app lied to th e CrMS
based on behavioral measures . As previously dis- for at least two rea ons. Fi rst, it is inappropriate to call
cussed , if intentional " planning" questions are appl ied use ofthe method to achieve pregnancy " imperfect use. "
to achieving-related pregnancies, a heterogeneous set Second , as w ith past contracepti ve efficacy studies, the
of responses will be obta ined that is hard to interpret. inten ti ona l approach is used to di stingui sh between use
Second, there is confus ion about the denominato r. In to avo id and use to ac hieve, rather than the behav ioral
some CrMS studies, the achieving-related pregnancy approac h and " intended" pregnancies are excluded.
rate has been ca ll ed use effectiveness to achieve preg-
nancy, and this has been reported to be in the ran ge of However, this approach can be adapted to be compat-
24 to 28 percent at one year. 1º· 11 Sorne ha ve erroneous ly ible with the CrMS, just as previous contracepti ve meth-
interpreted this to mean that, of ali coup les trying to get odo logies were adapted to acco unt fo r the unique as-
pregnant with the CrMS, only about 25 percent will suc- pects of the CrMS . us The categories of avoiding-re-
ceed in getting pregnant with in one year. In fact, the lated and achieving-re lated pregnancies (and the su b-
denominator for the achievi ng-related pregnancy rate categories of avo iding related) can be adapted with the
includes many co upl es who never try to achieve preg- new denominators to be comparabl e with the approach
nancy. of " perfect" use ,"imperfect" use, and "typical" use that
is now standard for con traceptive effectivene s stud-
The achieving-related pregnancy rate does ha ve aspe- ies. The details of how this wou ld be done are given in
cific meaning and appl ication. lt is essentiall y ademo- Table 16-3. The pregnancies for the categories are the
graph ic measure. lt g ives a precise measure ofthe pro- same but the denominators are sma ller; the denom ina-
portion ofa given population ofcoup les using the CrMS tors in each case wou ld be the cycles for which the type
who choose to engage in behavior likely to result in ofuse is known to be occurring rather than ali cycles in
pregnancy a nd successfull y conceive. A s a demo- the study. As for the o ld approac h, the actual rates could
graphic measure of conscious ly engaged fert ili ty, it can be ca lculated using any of the statistical methods de-
Chapter 16: Measuring Effectiveness and Pregnancy Rates of the Cr MS 225
scribed later in Table 16-4, but the preferred approach engage in achieving-related behavior, how likely am 1 to
would be life-table analysis with gross and/or net rates. get pregnant? The rates will probably be on the order of
at lea t 50 percent and maybe higher. An essentially
lt is important to note that this approach will have the simi lar ana lysis ofa multinational study ofthe Billings
following properties in comparison to the older ap- Ovulation Method suggests that the rate would prob-
proach, for CrMS studies (as we ll as for contraceptive ably be 80 percent over one year. 33 Of course, it will
studies): depend on the " intensity" (relative to ferti li ty) of the
ach ieving-related behaviors.
• The pregnancy rates for ali subcategories wi ll
be hi gher for the new approach than the older Which approach is better, the old or th e new? Both
approach. Only the total pregnancy rate wil l be have their advantages and place, depending on th e
the same for the old and new approach. question being asked. We ha ve di scussed this above in
relation to the different meaning of the achievi ng-re-
• The total pregnancy rate is not the sum of the
lated meas ure under the old approach (demographic
component pregnancy rates. Rather, the total
meani ng) and the new approach (c linical meaning).
pregnancy rate is the weighted average of the
However, there are some distinct advantages with the
component pregnancy rates.
new approach:
• Because ofthi , the pregnancy rates ca lcul ated
• lt is more directly comparabl e with the new stan-
with the old approach cannot be compared across
dard approach for contraceptive effectiveness
the board with pregnancy rates ca lculated with
studies
the new approach.
• lt is conceptuall y more pure in that on ly cycles
More specifically, how would pregnancy rates look with of a certain kind ofuse are used to analyze preg-
the new approach as compared with the old? The total nancies from that kind of use.
pregnancy rates would be the sa me. Beyond that, we
• lt makes important di stinction s for describing
do not know exactly, as the new approach has not yet
how often the method is being used to avo id or
been applied in any CrMS study. However, some at-
to achieve pregnancy (i .e., how many months or
tempts ha ve been made to estímate this, anda few pre-
cyc les).
dictions could be made with reasonable confidence.12·38
First, the pregnancy rate with avoiding-related, method- • 1t emph as izes fo r couples the true likelihood of
consistent use wou ld be very comparable to the current pregnancy with achieving-related use.
method-related pregnancy (for which it is the ana lo-
gous category). This is because most ofthe time when 1t seems prudent for new stud ies of the CrMS to app ly
achi eving-re lated use takes place, achieving-related both approaches to ana lysis: the old one in order to
pregnancies rapidly result. Therefore, the largest part compare with previous studi es and the new one for the
ofthe denom inator fo r al i cycles wi ll still be avoiding- advantages noted.
related cycles (see category "b" in Figure 16-1 and see
Table l 6-3). Conversely, for the same reasons, there wil l The new approach has more data requirements than the
be far fewer cycles with achi eving-re lated use. This old approac h, but the basic concept is simpl e. As be-
means that th e achi eving-related pregnancy rate will be fare , each pregnancy is ca refu ll y class ifi ed; the preg-
much hi gher with th e new approach than with the old nancy class ifi cations and their criteria do not change
approach. When yo u think about this, it makes sense. 1f (Tab le 16-2). However, the new req uirement is that each
instead of putting ali cyc les in the denominator of the and every month (or cyc le) needs to be assigned to a
achieving-related pregnancy rate (including many cycles "use" status; in other words, during each month, was
where couples never tried to get pregnant), you put the method being used correct ly to avoid pregnancy
onl y those cycles in the denominator where achi ev ing- (avoiding-related, meth od-consistent use), incorrectl y
re lated behavior was happening, you will have few to avoid pregnancy (avo iding-re lated , method-incon-
cycles re lative to pregnancies because couples who are sistent use), orto achi eve pregnancy (achi ev ing-related
engaging in achieving-related behavior rapidly become use)? This determination must be made for each and
pregnant. As such, the pregnancy rate with achieving- every month or cycle so that the mon ths or cycles can
related use will have a different meaning than the old be divided accord ing to the schema shown in Figure 16-
achieving-related pregnancy rate. The new rate will have 1 and Table 16-3. Note that the same couple can contrib-
a meaning that is probably more intuitive for mo t ute to multiple types of use (as illustrated in Figure J 6-
coup les. That is, it wi ll directly answerthe question: 1f1 1). For example, the coup le cou ld , in the first month ,
have avoiding-related , method-inconsistent use. Then , method-incon sistent use. So, hypothetically, if a study
in the second month , th ey could ha ve avo idin g-related, showed a 10-percent pregnancy rate over one year for
method-consistent use. In the th ird cycl e, they co uld avo iding-related, method-inconsistent use (remember
ha ve achi ev ing-related use and become pregnant. Onl y there are fa r fewe r cycles in this class ifi cation and thi s
the third cycl e wou ld count towards the denominator rate will be much hi gher than if it were measured for ali
(by li fe tabl e or other tati stica l means) of pregnancy cyc le ), one could further break thi s down and say that,
duri ng achi ev in g-re lated use. The other two cyc le of those pregnancies, 50 percent we re using related, 25
wo uld count towards the ir respecti ve categori es of use percent were teaching related, and 25 percent were both
(w ithout the pregnan cy, because it occurred during the using and teaching related.
cyc le ofachiev ing-related use). Obv iously, it is critica!
to get accu rate info rmati on about th e use during each
cyc le. Alth oug h thi s is a lread y done to sorne degree Unresolved Pregnancies and
during ro uti ne CrMS fo ll ow-up teac hing se ions, the Time Periods of Use _ __ __ _ _~
assessment of thi s should pro babl y be strength ened
fo r the purposes of thi s type of stud y. Th e bas ic prin- The treatment of unresolved pregnancies is an impor-
c ipi e is thi s: each and every month (or cyc le) should tant i sue, regardl ess of whether old established or new
undergo th e same kind of scrutin y for type of use that proposed measures are used (see Category Ill in Tables
occurs durin g a pregnancy eva luation. Thi s is neces- 16-2 and 16-3 and see Fig ure 16-1 ). An ideal study will
sa ry in order to e limin ate any bi as that mi ght otherwi se coll ect enoug h informati on prospecti vely to have few
occur fro m class ify ing pregnancy eva luati on months or no unreso lved pregnanc ies. Still, unresol ved preg-
di ffe rently (beca use of hi gher scrutin y) th an non-pregnancies will occur due to incompletely ascertai nabl e in-
nancy months. formation . There are two ways that they can be hand led .
First, they can be di stributed among the pregnancy clas-
T he pregnancy evaluation is one of the great strength s sifi cati ons of a li other pregnancies in the same propor-
of the CrMS, both for Practitioners (FCP) and for us- tion s as the other pregnanc ies ( e.g., if 75 percent of ali
ers. lt allows both gro ups to gain an insight in to the use class ifi able pregnanci es are achieving related , then 75
dynami cs ofthe CrMS (and in theory, any FP meth od percent of ali unresolved pregnancies are as umed to
th at is taug ht with an o penness towa rd s its use to be achi ev ing related).1. 12 Thi s is a " best case" cenario
°
ac hi eve - see C hapter 17). 4 For the new approach , thi s and may be too optimi sti c when one compares unre-
strength could be incorporated mo re full y into the de- so lved pregnancies with couple 's stated intenti ons in
ta i led scrutiny of every month or cycle of use, at least in other pregnan cy categori es. 10 Alternati vel y, one can
the context of a research stud y. O f course, there is al- con struct a " worst case" scenario in which a li unre-
/ ready a lot of intenti on use assess ment that goes on in so lved pregnancies are ass umed to be avoiding related .9
teac hing the CrMS . Bu t fo r the reaso ns noted, th ere These two scenarios ca n represent a sensiti v ity anal y-
would need to be even more in the settin g of an effec- sis, with the actua l distribution ofthe unresol ved preg-
tive ness stud y. nancies probabl y lying somewhere in between.
A fin al comment is necessary regarding the new ap- The question of unreso lved time periods of u e (see
proach and th e establi shed categori es of using-rel ated category " d" in Fi gure 16-1 and see Table 16-3) would
and teaching- related pregnancy. You w ill note that in be reso lved in exactl y the same kind of proportional
the new approac h (Tabl e 16-3), these specifi c catego- di stribution with an app ro pri ate sensiti vity an alys is.
ri es are not suggested for pregnancy rates. Thi s does
not mean that measuring these types of pregnancy is As in the past, period s of non-u se of the CrMS and
not important. Pregnancies could still be pl aced in these pregnancies during those times would be excluded from
categories according to the pregnancy evaluation . How- the analysi s of the CrMS pregnancy rates, except for
ever, it wo uld probabl y not be feas ibl e to pl ace each the extended-u se pregnancy rate, where they sho uld be
month of use that is avo iding-re lated, method-incon- inc luded. (lt wo uld theoreti ca ll y be poss ibl e to analyze
sistent use into one ofthe subcategori es ofu sing, teach- these separate ly, if desired.)
ing, or using/teaching related. There is obvious overl ap
between these categori e . The im portant iss ue of iden-
ti fy ing the re lati ve contribution of these subcategori es Statistical Approaches ------~
of avoiding-re lated, method-inconsistent use could eas-
ily be accompli shed sim ply by g ivin g a percentage Table 16-5 li st the stati stica l approac hes that ha ve been
breakdown of the subcategori es of avo idin g-related, used or could be used in CREIGHTON MODEL studies.
lt is important to note that, at least in theory, the statis- review. 40 The results are sum mari zed in Table 16-5 . The
tical approach is independent of which pregnancy rate CrMS has exce ll ent method effectiveness and user ef-
is being measured , with which denominator. In other fect iveness. User effectiveness has improved over the
words, each ofthe pregnancy rates listed in Table 16-3 time of the five stud ies, suggesti ng an improved stan-
could be ca lcu lated with each ofthe stat istical methods dardization ofthe processes of FCP training a nd client
listed in Table 16-4. teaching. In this table, unreso lved pregnancies are re-
solved according to the " best case" scenario described
A detailed guide to the net life-table approach has been under "unresolved pregnancies" above.
published and used by ali CrMS studies to date. 1 A l-
though this a pproach was initi ally conceived of as be-
ing appli cab le to other NFP methods, in practice, only Discontinuation Rates ______~
the CrMS has embraced the approac hes described and
cond ucted these rigorous stud ies. As noted earlier, this Table 16-5 also illustrates another very important statis-
ap proach was adapted largely from that ofTietze. 35 Gross tic: continuation or discontinuation rates. Discontinua-
life tab les a re derived from net life tables. For the gross tion rates fo r the CrMS a re quite low com pared to most
life tables, good methodo logic references are also avai l- methods offam il y planning, even ifpregnancies are not
able.36.37 counted as discontinuations. Contraceptive studi es
have generally considered pregnancies to be a category
of discontinuation , but this is not appropri ate for the
Current Data _ _ _ _ _ _ __ _ _~ CrMS. While a study may not have suffic ient fo ll ow-up
time to ascertain the actua l continuatio n rates of the
The most current data ava il ab le on the CrMS were pub- CrMS after pregnancy, a continuatio n rate can be esti-
lished as a 5-study meta-analysis in 1998 . 12 A further mated by asking coupl es who are currently pregnant
ana lys is ofthe achieving-related pregnancies is still in whether they plan to use the CrMS afte r delivery.
Table 16-5: Summary of Pregnancy Rates from Meta-Analysis of Five Creighton Model Studies*
Creighton St. John's St. Francis St. Joseph Marquette 5·Study

University Merey Hospital Hospital University Composite
Parameter Omaha St. Lou is Wichita Houston Milwaukee
Year ot study 1980 1980 1985 1989 1994 1998

Number ot couples 286 273 378 697 242 1876
Number ot couple-months, 2224 .0 1980.0 2471 .0 5730 .5 1819.5 14,225 .0
12 months
Pregnancy rate
Method-related , 12 months 0.4 0.4 0.6 0.2 1.3 0.5
net lite table
Method-related , 12 months 0.6 0.7 1.0 0.2 1.8 0.7
gross lile table
Use-related , 12 months 5.4 4.9 2.1 2.8 2.1 3.2
net lile table
Use-related , 12 months 7.9 7.5 3.3 3.9 3.0 4 .7
gross lile table
Achieving related , 12 months 19.1 23 .7 30.4 14.3 24 .8 21 .0
net lite table
Achieving related , 12 months 26 .2 33. 0 42.0 18.8 31 .1 28.2
gross lite table
Total , 12 months 24 .5 28.6 32 .5 17.1 26 .9 24 .3
Total , 12 months 32 .7 38.8 44.4 22 .2 33.3 31 .9
gross lite table
Discontinuation rate, 11 .5 13.9 14.8 5.0 20.2 11 .2
net lite table , 12 months
Unresolved pregnancies are distributed according to assumption that they have the same distribution far dassification as the resolved pregnancies.
228 The Medical and Surgical Pract ice of NaProTECHNOLOGY
Achieving Pregnancy in lnfertility _ _ ~ Areas for Future Research _ ____~
Ma ny of the a me princ ipi es o utlined here can be ap- A num ber of area require furth er research. T hese in-
pli ed to a po pul ation of co upl es w ith in fe rtility. That is, c lude the foll ow ing :
months or cyc les of use to achie ve preg na ncy can be
fo llowed and pregnancy rates calculated at different time l. The effecti ve ness of the CrMS during breast feed-
poi nts. M o nth could be further subdi vid ed fo r th is ing needs furth e r exa minati on. 1n one stud y that ex-
spec ia l situatio n into e ffec ti ve and no n-effec ti ve cycles. a mined thi s g roup separa te ly, hi g her ach ieving-re-
An e ffecti ve cyc le is a cyc le in whi ch o vul ati o n occurs lated pregnancy rates we re found among couples
w ith a good mu cus pattern , inte rcourse is app ro pri ate ly breast feedin g. lt is impo rtant to understand whether
timed during the fertil e muc us days, the lutea l phase is thi s findin g may be repli cated .9
adequate by CrMS cha rtin g and ho rmo nal c rite ria, and
stress is ma naged .45 The ideal study wo uld ana lyze ef- 2. The studi es to date ha ve had very few wo me n in the
fec tive cyc les as a separate group ( i. e., in a separate li fe premenopau sa l age ran ge, and mo re data are needed
table). in thi s age g ro up.
lt is impo rta nt to keep in mind that the li fe tab le ap- 3. To date, no stud y has ana lyzed e parate ly wo me n
proach proba bl y g ives a hi g h estimate of effecti ve ness w ith continuo us vagina l di scharge, i.e., wo men who
in infertility, because it ass umes th at a ll persons who use yellow sta mps . Thi s is an important subg roup
sto p treatme nt have an equal proba bility of s uccess as that dese rves detail ed stud y for effective ness.
those who continue treatment, an ass umpti o n that is
pro bably not true.46 However, adjustments can be made 4. The dynami cs ofachiev ing-rel ated use are no t well
to estimate a mo re rea li sti c pregna ncy rate fo r ac hiev- understood and require much more stud y.
in g-re late d u e a m o ng co upl es w ith in fe rtility. A d-
ju s ting fo r concurrent m e dical trea tm e nt 5. Methods need to be deve loped to measure effec-
(NaProTECHNOLOGY) is essential. A deta iled treatment ti ve ness over multipl e segme nts of use ( i.e., over
of thi s is beyond the scope of thi chapter. and between multipl e pregna nc ies). Thi s is a com-
pl ex methodo logical pro ble m . Such methods have
no t yet been devel oped for any fami ly pl a nnin g
method.
1. Hil gers TW. T he Stati stica l Eva luati o n Of Na tura l Meth ods 7. Trusse ll J, Kost K. Co nt raceptive Fa ilure in th e United States :
Of Fa mi ly Pl a nni ng . lnt Rev Na t Fam Pl a nn 8:226 -264 , A Critica! Revi ew of th e Li tera lure. Stud Fam Plan n. 18:23 7-
198 4 . 283, 1987.
2. Ste iner M, el a l. Measuri ng Cont race ptive Effcc1i ve ness: A 8. Tru ssell J, el al. Co ntracepti ve Fa il ure in the United Sta tes:
Conceptual Framework . Obste! Gyneco l,. 88:24s-30s, 1996. An Update. St ud Fa m Plann. 2 1:5 1-54 , 1990.
3. La mprec hl V, Tru sse ll J. atu ra l Fa mil y Pl a nnin g Effec- 9. Howa rd MP, Sta nfo rd JB . Pregnan cy Probabi lit ies Durin g
1i veness : Eva luatin g Publi shed Repo rts. Adva nc Contra cept , Use of the CREIGHTON MODEL FertilityCare' " System. Arch
13 :1 55- 16 5, 199 7 . Fam Med . 8: 39 1-402, 1999.
4. Tru sse ll J, Kowa l D. Th e Esse ntia ls of Contrace pti on . In : 10. Do ud J . Use -effect iven ess o f th e CREIGHTON MODEL of
Co ntra cepti ve Techn o logy, Hatcher R., et a l., Editors. Ar- FP. lnt Rev at Fam Pl ann. 9: 54- 72, 1985.
de nt Med ia : ew Yo rk. p. 2 11-24 7, 1998.
1 1. Fe hrin g RJ , Law rence D, and Phil pol C . Use Effecti veness
5. T ietze C. T he Cl ini ca l Effectiveness o f Co nt raceptive Meth- o f the CREIGHTON MODEL Ov ul ati on Meth od o f Natu ra l
ods. Ameri ca n Jou m a l of Obstetrics and Gyneco logy. 78 :65 0- Famil y Planni ng . J Obstel G yneco l Neo nat Nurs. 23:303-
656, 1959. 309, 1994 .
6. T ietze C, Lewi t S. Sta ti stica l Eva lu atio n o f Cont raceptive 12. H i lge rs TW, Sta n fo rd JB . CREIGHTON MODEL
Me thods: Use-Effecti ve ne ss and Ex te nd ed se-Effec ti ve - NaProEDUCATION Technology fo r Avo idi ng Pregnancy. J
nes s. Dc mography 5:93 1-94 0, 1968. Reprod Med . 4 3: 49 5-502, 1998 .
Ch apter 16: Meas uring Effectiven ess and Pregnan cy Rates of the CrMS 229
13 . Hil gers TW. The Medical App licati ons Of atura l Famil y 30. Trussell J, Vaughan B, Sta nford J. Are Ali Co ntraceptive
Pl annin g: A Cont empo rary Approach To Wo111en 's Hea lth Fa ilures Unintended Pregnancies? Ev idence fro111 th e 1995
Ca re: A Ph ysic ian 's Guide To NaProTECHNO LOGY (N PT). Na tional Sur vey of Fa111il y Grow th . Fa111 Pl ann Perspect.
Pope Paul VI ln st itut e Press, Omaha, E, 1991. 3 1:246-247, 260, 1999.
14. tanford JB , White GL, Hatasaka H. Ti111in g lntercourse to 3 1. Bren nan JJ , Klaus H. Ter min ology and Co re Curr icu la in
Ac hi eve Preg nancy: Current Ev icl ence. Obstet Gynecol. Natural Fa111il y Plannin g. Fe rtil Ster il. 38 :11 7-11 8, 1982.
100: 1333- 1341 , 2002 .
32 . Kl aus H. Natural Famil y Pl ann in g: A Revi ew. Obstet Gynecol
15 . Hilgers TW. The CREIGHTON MODEL FertilicyCare™ Sys- Surv. 37: 128- 150, 1982.
tem : An lntrod uctory Booklet For New Use rs. 5 ed., Pope
33. Tru sse ll J, Grumm er-Strawn L. Furthcr Analys is o f Co ntra-
Paul VI ln stitute Press, Omaha, NE , 200 l.
ceptive Failure o f th e Ovulation Met hod. Am J Obstet
16. Hil gers TW, et al. The CREIGH TON MODE L FertilicyCare'" Gyneco l. 165:205 4-2059 , 199 J.
System : A Standardi zed, Case Mana ge ment Appproach To
34. Trussell J. Natural Famil y Pl an ning. Effecti ve Onl y lf Used
Teachin g, Book 1: Pope Paul VI ln stitute Press, Omaha,
Perfectl y (Letter). Br Med J. 30 1: 1003, 1993.
NE, 2002.
35. Tietze C, Lcwit S. Stati sti ca l Eva lu at ion of Con trace pti ve
17. Labbok M H, Klau s H, Perez A. Emcacy Studies in Natura l
Mcthods. C lin Obstet Gyneco l. 17: 12 1- 138, 1974.
Fa mil y Plannin g: lss ues and Mana ge ment J111pli ca ti ons 11-
lu strated with Data fro111 Five Studi es. A111 J Obstet Gyneco l 36. Tru sse ll J, Menken J. Life Tab le Anal ys is of Contraceptive
165 :204 8-205 1, 199 1. Use-Effecti ve ness, C.f. t. A.o.F. P.P. lntern ati onal Un ion fo r
th e cien tifi c Stud y of Pop ul ati on, Ed it or. 19 O, Bogota:
18 . Ka111 bic RT, et al. Use- Effec ti ve ness Among Use rs of the
[U npubli shed) 1980 . Presented at th e lntern ati onal Uni on
Symptothermal Method of Famil y Plannin g lnt Fam Pl ann
fo r the Scienti fic Study o f Popul ati on Se minar on Th e Use
Perspect 17:96-99 , 199 1.
of Surveys fo r the Analysi s of Fa mil y Pl annin g Prograrnrnes .
19. Labbok, MH, Klaus H, Barker D. Factors Related to Ovula- p. 1-35.
ti o n Met hod Efficacy in Three Prog ram s: Ba nglad es h,
37. Tru sse ll J, Menken J. Life Tab le Analysis of Co ntracepti ve
Kenya, And Korea . Contrace pti on, 37: 577-5 89, 1988.
Fai lure. In : The Role of Surveys in th e Analysi s of Fa rnil y
20 . Gnoth C, et al. Time to Pregnancy: Result s of the German Pl annin g Progra ms. Herma lin A l and En twisle B, Editors.
Prospecti ve Study and lm pact on the Manageme nt of ln fer- Ordi na Ed iti ons, Liege, Belgi um p. 537-57 1, 1982.
tility. Hu111 Reprod . 18: 1959-66, 2003.
38. Tru sse ll J, et al. Analyzi ng Co ntracept ive Fa ilure [Lette rs] .
2 1. Ka111bi c RT. The Effecti veness of Nat ural Famil y Pl annin g J Reprod Mecl . 44:478-48 1, 1999.
Methods for Birth Spac in g: A Co mprehensive Rev iew. In :
39. Trussel l J, et al. A Guide to lnterpretin g Contraceptive Effi-
Hum an Ferti lity Reg ul at ion Demog rap hi c and Statistica l
cacy Studies. Obstet Gyneco l 76:558-567, 1990 .
Aspects. Girotto S, Bressan F, Ed itor . Verona ltaly. p. 63-
90, 1999. 40 . Hil gers TW, Stanford JB . Ac hieving-Related Pregnancy Rate
and Ev idence to its Ab ility to be Nat ura ll y Adaptab le. In :
22. Ca mpbell AA, Mosher WD. A Hi story of th e Measurement
Hil ge rs TW: T/1e M edica / ami Surgical Pra ctice of
of nintended Pregnancies and Births. Matern Child Hea lth
NaProTE CHNOLOGY. Chapter 17. Pope Paul VI ln stitute
J. 4:163-9, 2000 .
Press. Omaha, NE 2004.
23. Miller W. Reprod ucti ve De cisions: How We Make Th em
41. Dominik R, Trusse ll J, Wal sh T. Failure Rates Among Per-
an d How They Mak e Us. Advanc Population. 2: 1-27, 1994.
fec t Users and During Perfect Use: A Di stincti on That Mat-
24. Peterse n R, Moos M. Defi nin g and Meas urin g Unintended ters. Co ntra ce pti on . 60:3 15-20, 1999.
Pregnancy: lss ues and Co nce rn Women's Hea lth lss ues.
4 2. Trusse ll J, Grumm er-Strawn L. Co ntraceptive Fa ilure of the
6:234-240 , 1997.
Ovu lation Meth od of Pe ri od ic Ab tinence. Farn Pl a n
25. Luker K, et al. Contraceptive Failure and Unintended Preg- Pers pect. 22:65-75, 1990.
nancy. Fa111 Pl ann Pers pec t. 3 1:248-253, 1999.
4 3. Hatcher RA , et al. Con trace pti ve Techn ology. l 7th revised
26. Kl erm an LV. The lntendedness of Pregnancy : A Concept in edition , New York: Ardent Media, lnc. 85 1, 1998.
Transi ti on. Matern Child Health J. 4: 155-62, 2000 .
44. Karnbic RT. atura ! Farnily Planning Use-Effectiveness and
2 7. Moos M, et a l. Pregnant Women 's Perspective on ln tend- Continuation . Am J Obstet Gyneco l. 165:2046-2048, 199 J.
edne ss of Pregnancy. Women's Hca lth lssues. 7(385-392)
45. Bo y le PC, Parn e ll TA , Stanfo rd J B. atura l Procrea ti ve
1997.
Techno logy: A ew Approach to ln fertility. In Review, 2003.
28. Fisc her RC, et al. Ex pl or in g the Co ncep ts of lntend ed ,
46 . Stolwijk AM, et al. A More Rea li stic Approac h to the Cu mu-
Plann ed, and Wanted Pregnancy. J Fam Prac t. 48: 11 7-22,
lative Pregnancy Rate After ln -Vitro Fe rtili zati on. Hu111
1999 .
Reprod . 1 1:660-3, 1996.
29. Stanford JB , et al. Definin g Di111 ens ions of Pregnancy ln-
tendedn es Mate rn C hil d Hea lth J. 4: 183 -9, 2000.
Achieving-Related Pregnancy Rate and
lts Naturally Adaptability
Thomas W. Hilgers, M.O. and Joseph B. Stanford , M.O.
he CREIGHTON MODEL FertilityCare™ System (o r use effectiveness to achi eve pregnancy) and to
T (CrMS) is a standardi zed medi ca l model of natura l
procreati ve educati on (NaProEDUCATION) that uses an
eva luate its abili ty to be naturall y adaptabl e.
advanced educational technology deve loped at the Pope

Paul VI In stitute for the Study of Human Reproduction How Study was Done - - - - - - ---.
and the Creighton Uni versity choo l ofMed icine in the
Department ofüb stetri cs and Gynecology and is ava il- Pros pective tria ls to eva luate the method- and use-ef-
able as an allied health profess ional education and ser- fect iveness of the CrMS fo r avoiding pregnancy and its
vice deli very progra m in Fertility Care™ Centers achi eving-related pregnancy rate were conducted at fi ve
throughout the United States and severa! other coun- di ffe rent in stituti ons over different time periods. These
tri es. The CrMS informs a coupl e of the fertil e and infer- included: Creighton Un iversity Schoo l of Medicine,
til e phases ofthe menstrual cyc le so they can choose to Omaha, Nebraska;2 St. John 's Merey Medi ca! Center,
u e thi s info rm ati on to either ac hi eve or avoid a preg- St. Loui s, Missouri;2 St. Francis Regional Medica! Cen-
nancy. ter, Wi chita, Kansas; 3 St. Joseph Hospital, Houston ,
Texas;4·5 and Marquette Uni versity Schoo l of ursmg,
Since its introducti on, in 1980, five pros pective trials of Mil waukee, Wisconsin. 6
th e CrMS ha ve been conducted.1•6 These tri als give sig-
nificant insight into the system 's effecti veness and use In ali fi ve pros pective trial s, identi ca l life-tabl e tech-
dynami cs. A meta-analys is of these tria Is relati ve to the niques were used as th e stati sti ca l too! th rough which
system 's method- and use-effecti ve ness to avo id preg- effectiveness was measured. The li fe-ta bl e technique
nancy has been previ ously publi shed . 1 Beca use th e used in thi s study was first described by Hil gers7 ( 1984)
CrMS can be used by couples to achi eve as well as to as adapted fro m Ti etze and Lewit8 ( 1974). The CrMS is
avo id pregnancy, it is clearly of in terest to eva luate its nota meth od of contracepti on, but rath er it is a means
use to achieve pregnancy in co upl es of norm al fe rtili ty. by whi ch a coupl e knows and understands their fe rtility
and makes avoi ding- and achi ev ing-pregnancy dec i-
The purpose ofthi s chapter is to eva luate the stati sti ca l sions with regard to it. lt is taught by FertilityCare™
parameter ofthe CrMS achi eving-related pregnancy rate Practitioners (FCP) who are certified through the Ameri-
231
232 Th e Med ical and Su rgi cal Practi ce of NaProTECHNOLOG Y
can Academy of Fertili tyCare Profess iona ls. A sche- infertile. In thi s fashion , decisio ns ca n be made relative
mati c ofits application is presented in Fi gure 17-1 . lt i to one 's fertil ity on any g ive n day. The coup les are
used by couples of normal fe rtili ty as a means of achiev- taught that, de fac to, w hen they begin using days of
ing pregnancy as well as avoi din g pregnancy. In the ferti li ty for gen ita l contact, th ey have abandoned the
des ign of the li fe-table technique, the unique fea tu res system as a means of avoiding pregn ancy and have
of thi s system were taken in to acco unt and it was pos- adopted it as a mea ns of ac hi ev in g pregnancy (bas i-
sibl e to measure its ac hi eving-related use as we ll as its ca lly two methods incorporated into one, unlike contra-
avo iding-re lated use. 7 In thi s fas hi on, those w ho u e ceptives, which onl y have the fun ction ofavoiding preg-
the system to ac hi eve pregnan cy coul d be prospec- nancy). In this fas hi on, those who used the system to
tively identified and separated out of the pregnancy achieve pregnancy (tho e w ho had in tercourse on days
avo idance phase of the stud y. 1 they knew to be fe rtil e) cou ld be p ros pectively identi-
fi ed and separated out to become th e subject of thi s
The raw data fo r ea ch of the fi ve prospecti ve tria Is we re eva luation.
obtained from the original investigators. These data were
then compi led into a 5-study composite, allow ing a large A pregnancy classification system was established and
seri es of couples and couple-months of use to be fur- has been detail ed e lsewhere.1.1 However, it is wo rth re-
ther eva luated. The present analys is includes onl y those peating that an ac hi ev in g-re lated pregnancy was cat-
pregnancies occurring among user coupl es w ho chose egorized ifthe fo llowing definiti on was met: from the
to use the system to ac hieve a pregnancy, as defi ned avai lab le information , the system was used as a system
below. Only coup les of apparentl y normal fert ili ty were of ach iev ing pregnancy and the wo man became preg-
inc luded in the study. Couples with known in fe 11ility nant. The determination of thi s class ifi cation was ac-
we re identifi ed at entry into the stud y with the use of a compli shed following a standardi zed pregnancy eva lu-
fo ll ow-up form designed to esta bli sh various reproduc- ation interview, usuall y w ithin the first three month s of
ti ve categori es and, w hen identified, they were excluded . the pregnancy.
One of the key e lements in the c lass ification of preg- In additi on to the above, the exact dates ofpartic ipation
nanc ies in the CrMS is instructing the coupl es (w hi ch ofthe subjects in each ofthe fi ve studi es were obtained.
begins at the po int of entry, the introductory session) These dates we re as fo ll ows : Omaha- July l , 1977 to
that the system is not a method of contracepti on but Jul y 1, 1980; St. Lo ui s- Jul y 1, 1977 to Jul y 1, 1980 ;
rather a true mea ns of fa mil y planning. In thi s context, Wichi ta-Octobe r 1, 1980 to December 3 1, 1982; Hous-
the c li ents are info rmed that the system can be used in ton- August 1, 19 3 toJuly 14, 1989; Milwaukee-Octo-
two different ways and that the goa l of instructi on will ber 1, 1984 toMay 1, 1992.
be to educate them a to wheth er they are fertile or
Menstruation Pre-Peak Dry Days Vulvar Mucus Cycle Post-Peak Dry Days
1 1 1
/ \/ \/ \
Peak
Day
\ /\ /\ /
1 1
Days of lnfertility Days of Fertility Days of lnfertility
11
Avoiding-related Use Achieving-related Use Avoiding-related Use
Figure 17-1 : A schematic of the days of fertility (its achieving-related use) and the days of infertility (its avoiding-related use)
as identified by the CrMS .
Chapter 17: Achieving -Related Pregnancy Rate and lts Natural Adaptability 233
With these dates in mind, Bureau of Labor statistics Evaluation of Data --------~
we re used to obtain s ite-specific data re lative to un em-
ployment ra tes. Th ese were obtained for each of the T he ac hi ev ing-re lated pregnancy rates (use-effective-
five areas des ignated as Metropo litan Statistical Areas ness to achi eve pregna ncy) fo r the CrMS for each of
(MSA) directl y co rrespond ing to each ofthese five cit- the centers and the 5-stud y compos ite by ordinal month
ies. An MSA is a geographic area used as a unit fo r data of use (per 100 coupl es) are g ive n in Tabl e 17-1 . The
co llectio n and stati sti ca l presentation. lt is often used compos ite achi ev ing-related pregnancy rate was 2 1.0 at
by govern me nt age ncies as units for variables such as o ne year. H owever, th ere was a signifi cant range ob-
unemployment rates a nd calcul atio n of the consumer served in the vario us centers represented in thi s stud y.
price index. These unemployment measures are provided The St. Josep h Hospital Program in Ho uston had an
mo nthl y by the bureau of la bo r statistics thro ugh the ach ievi ng-re lated pregna ncy ra te of 14.2 w hil e th e
Uni ted States Departme nt of Labor. 9 Wi c hi ta study had an ac hi ev ing-related pregnancy rate
of28.0 (both at the l 2th ordin al month). Onl y the Hous-
T he un empl oyme nt rate is the percentage of the tota l to n study hada suffi c ie nt sampl e size to all ow thi s sta-
labo r fo rce that is une mpl oyed and the labor fo rce itse lf tistic to be meas ured th ro ugh the l 8th ordinal month
is defined as the sum ofthe emp loyed and une mployed . and at that point it was 17.9. The 5-site compos ite at the
Unempl oyment co un ts the number of persons w itho ut l 8th ord ina l month was 25.6. For fu rther co mpari sons,
jobs who are avail abl e fo r and ac ti ve ly seeki ng work. lt rates from the l 2th ord inal month were used because ali
covers ali persons 16 yea rs and o lder w ho lose o r q ui t fi ve cente rs were represented indi vidually at th at point
prev io us j o bs as we ll as hi g h schoo l grad uates, stu- in ti me.
dents and o the rs wi th no work experience who re-enter
the wo rk pl ace. As a relati ve measure of addi tional work- T he com pa ri so n of th e ac hiev in g-re lated pregnancy
ers avail abl e fo r empl oyment, the unem pl oyment rate is rates ofthe CrMS w ith the un empl oyment rates fo r ali
a key indi cator of econom ic conditions fiv e si tes are listed by di ffere nt variab les in Tabl e 17-2.
These une m ployment ra tes a re spec ific to the s ite loca-
Unempl oyment rates were recorded at monthl y inter- tion and the achi eving-related pregnancy rate at the
va ls fo r each geogra phi c area and tabu lated . Site-spe- l 2th ordina l mo nth of use (as seen in Tabl e 17-1 ). Thi s
cifi c une mpl oyment rates fro m differe nt time interva ls was eva luated for a variety of di ffe rent time sequences
were co mp a red to th e co rres po ndin g site-s pec ific fo r the une mpl oy me nt rates and thi s is presented in
ac hi ev ing-re lated pregnancy rates by li near correlat ion Tab le 17-2. ln additi on, the linear correlati on coeffi cient
coefficients usi ng NCSS 2000 1º. (r) was calcul ated fo r each of these comparisons. These
tre nd analyses, comparing th e achi ev ing-re lated preg-
nancy rates with the un empl oyment rates and the 95-
Table 17-1 : Achieving-related P regn an cy Rates

C reighto n M odel FertiliryCare™ System
By Cen ter, 5-Study Com posite and Ordinal M o nth of Use
(per 100 couples)
Marquette
Creighton St. John 's St. Francis St. Joseph Nursing
Ordinal Unive.rsity Merey Med. Ctr. Hospital C!l11ter 5 Study
Month Omaha St. Louis Wichita Houston MiJWaukee Composite
2.1 1.8 5.3 0.7 1.2 2.1

6 10.5 13.6 19.9 7.9 14.0 12.8
12 19.1* 23.7t 28 .0** 14.2 24 .8*** 21.0
18 n/a n/a n/a 17.9tt n/a 25 .6m
n/a = not applicable

2,224.0 couple months of use
2,471 .0couple monthsof use
tt 7,084.5 couple months of use
ttt A total of 17,130.0 couple monthsof use (1 ,876 couples)
percent confidence intervals are graphical ly displayed the method and use effectiveness to avoid pregnancy
in Figures 17-2 and l 7-3 for the unemp loyme nt rates at as well as the use effectiveness to ac hieve pregnancy
the beginning and the midpoint of the study periods. (the ach ieving-related pregnancy rate) was described .7
This was the first time that the latter statistical param-
One ofthe unemp loyment rates appeared to resemble a eter had been defined. The parameter was designed to
statistical outl ier (the unemployment rate for Omaha , assess the capability of the CrMS to be used as a sys-
Nebraska) . In additiona l analysis, the outlier was re- tem of both ac hi eving and avoiding pregnancy as op-
moved and the evaluation was repeated with the four posed to so lel y a natural means of contraception. To
remaining si tes. The trend analyses of the achievi ng- our knowledge, this study is the first attempt th at has
related pregnancy rates and the unemployment rates been made to statistica lly evaluate any system ofnatu-
with th is outli er removed for each ofthe eight time loca- rally regulating birth, usin g life-tabl e system s, for its
tions during the study were evaluated for the corre la- use to ac hieve pregnancy in couples ofnormal fertility.
tion coefficient (r). The p -value of the slope and are
reported in Table 84-3. When the outlier was removed , In this chapter, the " use effective ness to achieve preg-
the correlation coefficients for unemployment rates nancy" is referred to as the " achieving-related preg-
measured in the earlier time period increased signifi- nancy rate" to emphasi ze that it measures ach iev ing-
cantly wi th a l\ of them being greater than 0.9. The p- related pregnancy, described previously in this chapter.
value fo r the slope was statistically significant in nearly Three points should be kept in mind to interpret the
al i comparisons to unemp loyment rates at the begin- meaning of this statistic. First, thi s statistic is calcu-
ning or early part ofthe study periods but not at the end lated for a group ofcouples of apparently normal fertil-
of the study period. The trend anal ysis for four of the ity who entered the programs using the CrMS to avoid
five sites with the outlier exc lud ed for the first three pregnancy and, ata later date, sorne changed their use
fourths ofthe study is shown in Figure 17-4. by selectively having sex ua l intercourse on days offer-
tility and successfu ll y ac hi eve pregnancy. The numera-
tor ofthi s stati stic includes ali achieving-related preg-
lmportant Points to Consider _ _ _ ~ nancies. The denominator includes al \ the couples who
rema in in the study at the point in time that the statisti c
When the statistica l protocol for eva luation ofthe CrMS is measured an d includes many coup les who continue
was füst published in 1984, the li fe-tabl e ana lysis for to use the CrMS to avoid pregnancy. Thus, this rate
Table 17-2: Comparison of Achieving-related Pregnancy Rates (CrMS) with

U nemploym ent Rates for Ali Five Locatio ns
Locat_jons LinearCorrelatlon
Omaha St. Louis Wichita Houston Milwaukee Coefficient (r)
Achieving related 19.1 23.7 28.0 14.2 24.8 n/a

pregnancy rate at
12 months
Unemployment Rates :
At beginning 5.3 6.7 4.1 9.3 6.4 0.7849
At the midpointt 4.1 4.6 4.3 11.0 3.5 0.7961
First 1/2'' 4.3 5.8 4.0 8. 0 5.7 0.7053

First 2/3" 4.4 5.6 4.3 8.5 5.1 0.7600
First 3/4" 4.4 5.6 4.7 8.5 5.0 0.7330
Last 1/3" 4.7 6.6 9.3 6.8 4.8 0.3673

Last 1/4" 4.8 7.0 9. 7 6.4 5.1 0.5120
At the endt 5.6 9.0 9.7 6.4 4.9 0.4728
From: Bu rea u of Labor Statistics for the Respective Metropolitan Statislical Area (MSA) and the years or time periods under
study.
r The actual unemployment rate for the MSA for the months that are at the beginning , midpoint or end of the respective study
period.
- The mean unemployment rate for the MSA under study during the site-specific study period and for the componen! time period
of the study identified _
Chapter 17: Ach ievi ng -Related Pregnancy Rate and lts Natural Adaptability 235
At beginning of study
-C1>
~ 10.0
r = 0.7849
-
o::
e:
C1>
E
7.5
>i 4
o
a. 5.0 •
------------------------------------------------ 1=Wichita
E 2=M ilwaukee
C1>
e: 3=St. Lou is
:::> 2.5
,,''
-------- 4=0maha
,,,'' 5=H ouston
o.o--~~~--~~~ ......~~.......~~~--~~~--~~~~--
35 30 25 20 15 10
Achieving-related Pregnancy Rate
Figure 17-2: Li near correlation of !he site-specific achieving -re lated preg nancy ra te with the site-
specific unemployment rate al the beginning of the site-specific study period (r=O .7849) . The dotted line
indicates !he 95-percent confidence intervals for the linear correlation .
12.5 /
At Midpoint of Study ,'"
-C1>
~
o:: 10.0
r 0.7961 = ,,,''
5
•
-e:
C1>
E 7.5
-......... _____________ ___________ ,,,---------
..,
--
>i
o
a. 5.0
E • 4 1=Wichita
C1>
e:
• 2=Mi lwaukee
:::> 2.5
---------------------------------------- 3=St. Louis
4=0maha
,,,,''' 5=Houston
O.O
35 30 25 20 15 10
Figure 17-3: Linear correlation of the site-specific achieving-rela ted pregnancy rate with the site-
specifi c unemployment at the midpoint of the site-specific study period (r=0.7961) . The dotted line
indicates the 95-percent co nfidence intervals for the linear corre lation .
12.5
First 3/4 of Study
-Q)
ca
e::: 10.0
r = 0.9913 5 ---- -----
--
-eQ): .,,;•"" -- -------

,,,,,""''
.... -
-~-:·~::·:::::~::::...------·---·..---·..-··.
E 7.5
>-
o ----
c.
E
5.0 -- ------------- ------- ----:_-~--~ -------- - 1=Wichita
...... '
Q)
e: --- -- --- 2=Milwau kee
3=St. Louis
:::::> 2.5 -----------
~ --
.... - 5=Houston
o . o-+~~~~-+~~~~-t~~~~~ ..... ~~~~+-~~~~ .....~~~~~~...
35 30 25 20 15 10
Figure 17-4: Lin ea r correlation of th e site-specific achieving-related pregnancy rate with the site-
specific unemployment rate , for the first 3/. of the study period with a single outlier removed (Omaha)
(r=0 .9913). The dotted line indicates the 95-percent confidence intervals for the linear correlation .
Table 17-3 : Statistical Trend An alysis of

Achieving·related Pregnancy Rates* and
Unemploymen t Ratest with O u tlier R e moved (4 sites)
Time periods of Linear correlation

unemployment rates coefficient ( r) p-valuettt
At the beginning•• .9634 .0366

At the midpoint"" .9427 .0573
First 1/2" .9744 .0256
First 2/3" .9986 .0014
First 3/4" .9913 .0087
Last 1/3" .2613 .7387
Last 1/4" .4386 .5614
At the end"" .4272 .5728
See Ta ble 1at the 12th ordinal month far each city.
1 From: Bu rea u of Labor Statistics far the respective Metropolitan Statistical Area
(MSA) and the years or time periods under study.
•• The actual unemployment rate forthe MSA forthe months that are at the beginning ,
midpoint or end of the respective site-specific study period.
11 The mean unemployment rate for the MSA under study during the respective time
period and for the site-specific componen! time period.
111 Answering the question: "Is the slope significantly non-zero."
Chapter 17: Ach ievlng-Related Pregnancy Rate and lts Natural Adaptability 237
retlects the proporti on of coup les who began using the In the current study, a signifi ca nt corre lation in trend
CrMS to avoid pregnancy but later chose to use the ana lys is ex ists between the unemployment rates (whi ch
system to achieve pregnan cy (for whatever reason) and were used to indi cate the overa ll economi c stability of
we re successfu l at doing so. This statistic is demo- the metropolitan area) and the achi ev ing-re lated preg-
graphic in its assessment because it retl ects the dy- nancy rates . As the unemp loyment rates increased, the
namic ofa popu lation ofusers overa defined period of achiev ing-related pregnancy rate decreased (a statisti-
time. In essence, it represents the percentage ofcouples ca ll y significant inverse relationship). This correlation
using the system to avoid pregnancy who then adopt persisted when the unemployment rates at the begin-
the system to achieve pregnancy and are successfu l at ning , the midpoint, the first half, the ftrst two-thirds and
achi evi ng pregnancy over one year 's use. Therefore, the first three-fourths of the tudy were eva luated. At
thi s statistic is not an indicator of the effectiveness of the same tim e, no statistica l correlation existed for the
the system on a cycle per cycle basis to achieve preg- last third , the last fo urth or the end of the study on
nancy. A prev ious study of the CrMS addressed the em pl oyment rates . This strengthen the argu ment that
"method effectiveness to achi eve pregnancy" and found eco nom ic fac tors intluence pregnancy dec isions be-
that, of couples who ac hi eved pregna ncy, 76 percent cause the un empl oyment rate at the beginning of entry
did so by the first cycle ofsexual intercourse during the into the study period is cons idered the most intluential
fe rti le ti me. 11 to a coupl e's overall decision mak ing during the time
span of the study.
Second , the reason a couple chooses to achieve preg-
nancy is not differentiated in the achieving-related preg- Wh en the outli er (Oma ha) was removed and the other
nancy rate. Achieving-related pregnancies are those four sites were eva luated , the correlation in the trend
pregnancies that result from con cious use of the sys- analysis was stronger. However, the main thrust ofthi s
tem by the coup le to achieve pregnancy, regardless of study is the analysis for ali five site (Tabl e 84-2, Figure
their stated motivation fo r doing so. The measurement 84-2 and 84-3) and the stati stica ll y significant corre la-
is objective because it assesses the actual use of the tion of the unemployment rates to their achieving-re-
sy stem. Achiev ing-rel ated pregnancy is a measure that lated pregnancy rates. The analys is of the four sites
retlects accurately the way that th e CrMS is taught and with the outli er removed suggests that fac tors other
used, as has been di sc ussed in detail elsewhere. 5·6 than unemp loyment may have had more influence in
Omaha and highlights the need fo r further study to iden-
Third, sorne couples mi ght have engaged in achiev ing- tify those additional facto rs that may be correlated with
related behavior (use) in previous cyc les (i.e. , had sexua l pregnancy decisions . Furthermore, the finding that
intercourse during known fertile times) but yet did not Omaha is an outli er for this portian ofthe study is dif-
achieve pregnancy. Unfortunate ly, infor mation was not ferent than that observed in the avo iding-pregnancy
ava ilab le from the ori ginal studi es to identi fy what pro- analysis of thi s study when none of the five sites ap-
portion of couples would fa ll into this category, but it peared to be different from the oth ers.1 Thi s suggests
seems likely that thi s number is small and there is no that the instruction and effecti veness of the CrMS to
reason to suspect that it would va ry systematica lly be- avo id pregnancy was simil ar between the five sites, but
tween the sites studi ed. other (yet unidentified) fac tors related to choices to
achi eve pregnancy affect th e Ornaba site.
From a theoretical poi nt ofview, the ach ieving-re lated
pregnancy rate is a demographi c statistic that shou ld Sin ce many other fac tors wo uld intluence a couple 's
retlect the achieving-related dynamics of a population pregnancy decisions, the signifi cant corre lation for thi s
of users. Greater tl ex ibility was anticipated in this par- single economic indicator, whi ch is the onl y indicator
tiCLliar statistic beca use thi s statistic involves the dec i- we have chosen to exa mine thu s fa r, is remarkabl e. A
sion making ofthe marri ed couples in their desires and lim itati on ofthi s study is that we did not have employ-
wil lingness to achieve pregnancy. Thus, certai n exter- ment info rmation specifically for the couples in the study,
na! environmental factors could be expected to intlu- and we ca nn ot show that the overa ll unemp loyment
ence the deci sion making. Those externa! markers were rates fo r each city were indi cative of th e individual un-
not identified at the tim e this stat istica l parameter was empl oyment rates in each of the sam ple popu lation s.
deve loped but, in this study, we have begun the pro- However, it is reasonable to concl ude that the overa ll
cess of producing relevant evidence whi ch suggests economic environment had sorne intluence on coupl es
that externa! environmental intluences affect the couple's that exten ded beyond their personal empl oyment sta-
decision making. tus. Future studi es should test thi s relationship pro-
specti ve ly, exa mine the emp loyment statu s of each
coupl e, and look at other factors spec ific to each coupl e. di ffe rent study sites . The ac hi ev ing-rel ated pregnancy
rate in Houston ( 1983 -1 989) at the l 2th ord inal month
was 14.2 (the low point in the study), while the achi ev-
Additional lnsights -------~ ing-related pregnancy rate in Wi chita ( 1980- 1982) was
28. 0 (the high poi nt in the study). Unli ke the use-effec-
Thi s stud y fo und a pos iti ve co1Te lati on between favo r- ti veness to avo id pregnancy, thi s variation was not a
abl e externa! economi c conditi ons (as indi cated by the fun ction of the time peri od during whi ch each study
proxy measure o f low unempl oyment) and an increas- was conducted.
ing ac hiev ing-related pregnancy rate. At first g lance,
thi s may seem to contradi ct demographi c and economi c Remarkably, the unempl oy ment rate in Houston during
literature, whi ch states that fe rtili ty rates fa ll as a soc i- the first three-fo urths of the stud y peri od, and at every
ety becomes more afflu ent and edu cated. The class ic interval was the highest of a li fi ve sites . At the sa me
in verse rel ati onship of improving economi c conditions time, the unemp loyment rates in Wichita were consis-
with decreas ing fertility is fo und in entire societi e (i.e. tentl y the lowest or near lowest of ali five sites during
countries) that develop economi ca ll y and , as a result, the course of the first three-fourths of that study.
experi ence lower infa nt morta li ty ra tes, hi gher educa-
tional attainment by women, and greater access to fa m- Whi le some ha ve suggested that the avoidance of genital
il y pl anning. Genera ll y, these relationships have been contact whi ch is necessary in the use of a natural mea ns
fo und over decades in countri es that undergo majo r to regul ate fe rtility makes "a considera ble contributi on
changes in these key parameters. 12 •13 to the fa ilure rates of peri odi c abstinence methods," 14
the data in thi s stud y suggest otherwise . In fac t, the
ln contrast, th is study dea ls w ith popul ations w ithin a data support the fac t that there is an orderly bas is u pon
country (the United States) that is alread y we ll deve l- w hi ch peopl e ma ke th e ir dec is ion s reg ard in g the
oped econom ica ll y and where there is little vari ati on in ac hievement of pregnancy parti cularl y w ith the use of a
infant mortality. T he majority of the wom en and men at natural system offamil y planning, which also allows fo r
a li of these site were educated and had access to at the achi evement of pregnancy.
least one method of fa mi ly planning (the CrMS) th ro ugh-
out the stud y. In additi on, these studi es were conducted The stati sti ca l measure known as either demographi c
over a rel atively short period of time. Among educated effecti veness or extended-use effecti ve ness has been
coupl es who are considering hav ing a child , it is rea- u sed to e val uate vari ous contraceptive systems. 15 Stud-
sonable that economic conditi ons wo uld influence the ir ies perfo rmed on the oral contracepti ve, for examp le,
dec ision regarding timing of a pregnancy ; more favo r- show th at its extended-use effecti ve ness (reported as
abl e econom ic cond iti ons res ult in high er numbers of extended-use pregnancy rate) ranges from 8.4 to 24. 3
concepti ons. To our know ledge, thi s is the first stud y percent at the l 2th ord ina l month and studies on the
to exami ne relatio nships between econom ic conditi ons intrauterine device show ranges fro m 4. 8 to 10.1 percent
and decis ions to ac hieve pregnancy under conditi ons (at the I 2th ord ina l month). 16•17 Extended-use pregnancy
where infant mortali ty, fema le education, access to fa m- rates fo r the CrMS have been estimated from 18.5 to
il y pl anning, and long-te rm economi c deve lopment are 22. 5 at the l 2th ordina l month in one stud y (Houston). 5
essentiall y unchanged. The most substanti al component of extended-use preg-
nancy ra tes of the CrMS is the achi ev ing-re lated preg-
In rev iewing the method- and use-effecti ve ness to avo id nancies . Si nce the extended-use pregnancy rate large ly
pregnancy with the CrMS, the 14 years of data co llec- re fl ects the choices of coup les to achi eve pregnancy, it
ti on of that study re vea led a very cl ose, tight congru- can theoreti call y be correlated with economic factors.
ence in th e vario us studi es for the method effecti ve- However, the achiev ing-re lated pregnancy rate is a bet-
ness to avoid pregnancy rang ing from 98.7 to 99.6 per- ter demographic measure to correlate with economic
cent. When the use effecti veness to avo id pregnancy fac tors (as we have done in this study) because it repre-
was eva luated , a ti g ht corre lat io n was show n th at sents pregnancies that result from choices ofthe coup le
ranged from 94 .6 to 97.9 percent. 1 Sorne impro vement in and not onl y the pregnancies that result from weak-
the use effectiveness to avo id pregnancy occurred over nesses in the system or errors in teaching or use.
tim e and was thought to result fro m improved teaching
that occurred du ring th at period oftime. We are awa re of no other studi es to date that have ex-
am ined extended-use pregnancy rates or equi valents of
On the other hand , there was a wide degree of va ri ati on achieving-related pregnancy rates with the externa! eco-
in the achi ev ing-related pregnancy rates between the nomi c or other factors fo r either natura l methods of fa m-
Chapter 17: Achieving-Related Pregnancy Rate and lts Natural Adaptability 239
ily planning or contraceptive method s. We be lieve th at to overa!! pregnancy rates and whether thi s flexibility
this represents an area that is ripe for further inquiry to may be respon sive to the vario us economic parameters
shed light on what influences coupl es' choices to (at least) of the various environmental conditions in
achieve pregnancy, particularl y during the use ofa natu- which individual couples fínd themse lves. Other param-
ral system that offers them a rapid and effective mean s eters besides the econom ic ones are likely. lfth is is the
of doing so. U ser characteristics such as lower educa- case, then the achieving-related pregnancy rate shou ld
tion and lower socioeconomic status ha ve been clearl y theoretically be able to approx im ate the use effective-
associated with less effective use of variou s contracep- ness to avo id pregnancy under conditions of very seri-
tive methods to avo id pregnancy. Thi s is a d ifferent ous reasons to avoid pregnancy. One examp le support-
issue than the choi ce of a couple to use a method to ing this theory is a study from Shanghai , C hina of the
achieve pregnancy. 18 Also, socioeconom ic and demo- Billings Ovu lation Method. In this study, the rate ofuse
graphic characteristi cs have been shown to influence to achieve pregnancy (re ported in different termino l-
wheth er any method offamily plannin g is used at all. 19 ogy but comparable to the ac hi eving-related pregnancy
Thus , this study contri bu tes to a new area of research rate) was around 1 percent. 23 ·24 This extremely low preg-
that seeks to understand the factors that contri bu te to nancy rate is most likely re lated to the one child fa mil y
coup les ' decis ions to engage in proceptive behavior policy, which has been prevalent throughout C hina and
(behav ior to achieve pregnancy) .20 · 22 was prevalent during the course of that study. 25 The
authors would encourage furt her studies of systems of
This study questions whether a greater degree of natu- family planning w here the ac hi evement ofpregnancy is
ral adaptability exists in a natural system with regard an option.
The authors wish to acknowledge the ass istance ofDavid Volkman, Ph .D., Department ofEconomics, Un ivers ity of
Nebraska at Omaha.
1. Hil ge rs TW and Stan fo rd JB : CREIGHTON MODEL 6. Fehrin g RJ , Law rence D, Philpot C: Use Effec ti veness of
NaProEDUCATION Technology for Avo iding Pregnancy: Use th e CREIGHTON MODEL Ovul ati on Method of Natural Farn-
Effec ti veness . J Repro Med. 43:49 5-502, 1998 . il y Pl ann in g. J Obste! Gynecol Neo nata l Nursing. 23 :303-
309, 1994.
2. Hilgers TW, Preb il AM , Daly KD: The Effect iveness of th e
Ovul ati on Method as a Mea ns of Achievi ng and Avo id ing 7. Hil ge rs TW : Th e Stati stica l Eva lu ati on of Na tu ra l Methods
Pregnancy. Presented at th e Edu cati on Ph ase 111 Continu - of Farnil y Planning. lnt Rev Nat Fa111 Plan 8:226-264, 1984.
ing Educa ti on Conference for Natura l Fa111 ily Pl annin g Prac- 8. Tietze C and Lew irt S: Stati sti ca l Eva luati on o f Contracep-
titi oners, Merey Fontene lle Ce nter, 0111 aha, .lul y 198 0. tiv e Meth ods. Am Obstet Gyneco l 17: 121-1 38, 1974.
3. Doud J: Use Effecti ve ness of th e CREIGHTON MODEL of 9. Bu rea u Labo r Sta tisti cs, US Departrn ent of Labor fo r th e
NFP. lnt Rev Nat Farn Pl an 9:5 4- 72 , 1985 cit ies and yea rs cited. www.stats. bl s.gov an d ww w.bls. gov/
4. Howa rd MP: Use Effec ti ve ness of th e Ovul atio n Met hod lauh omc. htm.
(CREIGHTON MODEL) of Natural Fa111ily Pl annin g. Presented 1O. NCSS 2000. Stati sti ca l System fo r Windows. NCSS , Kaysv ill e,
at the Ninth An nual Meetin g of th e A111eri ca n Academy o f Uta h, 1998 .
Natura l Farnily Plannin g, Milw aukee, Jul y 1990.
1 1. Hil ge rs T W, Daly KD, Prebil AM , Hil gers SK: Cu111ulati ve
5 . Howard MP and Stanford JB : Pregnancy Probabilities during Pregnancy Rates in Patient s w ith Apparentl y No rm a l Fer-
use of th e CREIGHTON MODEL FertilicyCare'" System. Arch ti li ty and Fertil ity-Focused lntercourse. J Reprod Med 37( 10):
Fam Med. 8:39 1-402, 1999 86 4-866 , 1992.
12. Sanderson SK, Dubrow J: Fertility Dec line in th e Modern 20. Klennan LV: lntendedn ess of Pregnancy : A Concept in Tran-
Wo rld and th e Original De rn ograp hi c Tran s ition: Test in g s iti on. Mate rn C hild Health J 4 (3): 155- 162 , 2000.
Three Th eo ri es w ith Cross -Na tiona l Data. Population a nd
2 1. Stan fo rd JB , Hob bs R, Jame s P, De Witt MJ, Fisc her RC:
Env ironrn e nl 2 1 (6):5 1 1-5 3 7, 2000.
Defining Dirn e ns io ns of Pregna ncy lntendedness . Mat ern
13. Pan o poul o u G, Tsaklog lo u P: Fertilit y and Econorn ic De- C hild Hea lth J 4(3 ) : 183 -90, 2000.
ve lop rn e nt: Th eo reti ca l Cons id erati ons and Cross-Co untry
22. Miller WB , Pa sta DJ: Be ha viora l lnte ntions: Whi c h Ones
Ev idence. App li ed Eco nornics 3 1: 1337 -13 5 1, 1999.
Predict Fertility Behavior in Marri ed Co uple s? J App l Soc
14. Betts K: Th e Billin gs Method of Fa rn ily Pl annin g: An As- Psyc ho l 25:530-555 , 1995.
sess rn ent. Stud Farn Plan 15:253-266, 1984.
23. Zhang DW and Xu J X: T he Effecti veness of the Ovu lation
15. Tru ssell J, Hatch er RA , Cates WJ , et a l: A Guide for lnter- Method Use d by 688 Co upl es in S ha ng hai. Shang ha i
pre tin g Co ntrac e pti ve Effi cacy S tudi es. Obstet Gy neco l Munic iple Farnil y Plannin g Co mmi ssio n. Pre sen ted at th e
76:558-567 , 1990. Eleve nth Annual Mee tin g of th e Am e ri ca n Aca de rn y of
Na tura l Fami ly Pl a nnin g, Jul y, 199 1. Char leston. West Vir-
16. Tietze C and Lewit S: The !UD and the Pill: Extended Use-
g inia.
Effecti veness. Fa rnil y Plannin g Perspecti ves. 3:53-55, 197 1.
24. Xu J X, Yan JH , Fan DZ, Z han g DW: Billings atura! Farnily
17 . Tietze C and Lewit S: Use-Effectiveness of Oral and lntrau-
Pl annin g in Shan ghai, China. Adva nc Co ntracept 1994. 1O:
ter ine Co ntrace pli o n. Fertil S te ril 22:508 -51 3, 197 1.
195-204, 1994.
18 . Potter LS : How Effect ive are Co mracepti ves? Obstel Gyneco l
25. Heske th T, Z hu WX : The On e C hi ld Farnily Po li cy : The
88 : l 3s-23 s, 1996.
Good, the Bad and the Ug ly. BMJ Jun 7; 3 14 (7095): 1685-
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te rrninants of Co ntra cepti ve Meth od Cho ice in Sri Lank a:
1975 -82. J Biosoc Sci Suppl 11 :4 1-60, 1989.
----~~18
Professional and Academic
lnfrastructure of the CrMS
T he CREIGHTON MODEL FertilityCare™ System

(CrMS) is trul y a unique approach to the natural
regulation of human ferti li ty. It is the first such system
of excellence. Graduates of these programs were of-
fered a professional certiftcation program in order to
make an attestation to the public that a sincere and le-
wh ich strong ly links and networks the ability to ach ieve giti mate effort was being placed into the development
or avo id pregnancy successfu ll y w ith the ability of a and delivery of competent educational services. In ad-
wo man to monitor and maintain her gynecologic and dition to this, a strong network of research was ongo-
reproductive health. This is not only a unique focus of ing so that the CrMS would always be the focus of on-
the CrMS but it is unique in the entire field of fam ily go ing research and development.
planning.
In order to accompl ish a li ofthe above, the American
A stro ng profess io nal and academ ic infrastructure for Academy of FertilityCare Pro fess ionals (AAFCP)
the CrMS was an early-recognized need . Accomplish- was establ ished to provide continuing education , ac-
ing th is was a complex and difficult task because no creditation , certification and service program approva l
such infrastructure had previously been estab li shed for a long with professional and co ll egial support. The Pope
any natural system for the regulation offertility. Thus, Paul VI In stitute for the Study ofHuman Reproduction
ali programs had to be developed de no vo . was established to advance the profe sional educational
and research objectives ofthe CrMS and most recently,
The focus of thi s infrastructure was the development of FertilityCare™ Centers of America and FertilityCare™
a fo rmally written core curriculu m 1 for the professional Centers lnternational were developed to carry on the
ed ucation of the FertilityCare™ Practitioner and In- promotion of these FertilityCare™ programs.
structor. Formal programs of ed ucation for physicians,
nurse practitioners, physician assistants, nurse midwives This chapter outlines sorne ofthe components ofthese
and pharmac ists along with FertilityCare™ Educators organizations and explains the importance ofthese pro-
and Supervisors we re necessary. The accreditation of grams to their ongoing professional development and
these programs was essential so that they met standards support.
241
American Academy of low pos ition. In fac t, within many organizations, mo-
Natural Family PlanninQ ------~ rality had been literall y divorced from profess ional ac-
ti vity. The Board of lncorporators ofthe Academy, how-
In Jul y 1980, at a continuing education confe rence fo r ever, thought that the Academy's mora l integrity should
Natural Famil y Planning Practitioners called "Educa- be a beacon to its profess ional activiti es. Thus, the code
ti on Phase III " held at the Merey Fonten elle Center in of ethics of the Academy represented an im portant
Omaha, ebraska, Dr. Thomas W. Hil gers fo rm all y in - merger of guiding mora l principies and the develop-
troduced th e CrMS and its integrated network of edu- ment of profess ional skill .
cati on and service deli very. 1 As a component of that
presentati on the poss ibili ty of developing the Ameri - The by-/aws ofan organi zati on are its govem ing stru c-
ca n Academy of Natural Fa rnil y Pl ann ing was an- tu re. The by-l aw of th e Academy were deve loped over
noun ced. At th at continuing medi ca! educati on confe r- a two-year peri od during which careful research was
ence, by unanimous consent those in attendance gave conducted into the organi zati onal structure of other al-
acc lamati on to th e deve lopm ent of thi s academy. li ed hea lth profe sional organi zati ons. In thi s way, an
orga ni zation cou ld be developed whi ch would meet the
In February 198 1, th e first ex pl oratory meeting fo r the demands of thi s newl y emerging allied health profes-
deve lopment ofthi s organizati on was held . At th at time, sion. The components of orga ni zati onal structure whi ch
a group of people began to parti cipate in thi s develop- wo uld specifi ca ll y mee t the nee ds of the ne w
ment.3This group represented a wea lth of background CREIGHTON MODEL profess ionalism were identified.
in the fie ld of natu ra l fa mil y plann ing. They ali had a
long-term ex perience in the enti re fi eld and its deve l- In looking at th e organizati onal structure, it wa fe lt that
opment throughout the l 970s. In additi on, they repre- the organizati on had to be membership oriented, mean-
se nted nearl y every maj a r geographic reg ion of th e ing that it would ex ist primaril y to serve its me mber-
United States and, because of their parti cipati on in the ship. In additi on, the orga ni zati on had to be full y demo-
newly developed Educator and Supervisor programs of crati c allowing its membership to have authori ty over
the Creighton Uni versity Natu ra l Family Pl anning Edu- th e orga ni zati on.
cati on and Research Center, th ey had compl ete ex po-
sure to the concept of pro fess ional education and ser- ln attempting to accompli sh these goa ls, the by-laws of
v1ce. the Academy allowed fo r a board of directors to man-
age the organi zati on. The acti ve members el ected the
From February 198 1 to April 1982, thi s group acted as board of director , whi ch was composed of a pres ident,
an ad hoc committee. In April 1982, theAmeri can Acad- pres ident-elect, first vice pres ident, secretary, treasurer,
emy ofNatural Family Planning (AANFP) was officially vice pres ident fo r pl anning and development, vice presi -
incorporated under the state laws of Misso uri. At that dent fo r membership, vice pres ident fo r fiscal deve lop-
time, thi s same group became a boa rd of incorporators ment, and vice pres ident fo r ethi cs and standard s. In
which allowed the AANFP to fun ction as a limited le- additi on, a number of committees and subcomm ittees
ga l enti ty. Severa! orga ni zati onal meetings were then to carry out the work ofth e organi zati on were also de-
held to develop the orga ni zati on's code of ethi cs and ve loped.
by-l aws and the first national meetin g ofthe Ameri can
Academy was held in St. Loui s, Mi souri in June 1982. A number of categori es of membership in th eAcademy
were also deve loped. These in clude acti ve, assoc iate,
At the second annual meeting of the AAN FP in June spec ial, honorary, student and organi zati onal member-
1983 , the code of ethi cs and by-laws were offici all y ship. These rea lly all owed fo r any person interested in
approved and the first pres ident was install ed, making the developm ent of natural fa mil y pl anning to become
way for the next phase ofthe Academy's developm ent. invo lved in the Academy.
Two important deve lopments occurred in the early year The most important profess ional functi ons ofthe Acad-
of the Academy. The Academy's code ofethics was de- emy were to accredit educati onal training programs, and
veloped as a model code; it was not just a model fo r to certify indi vidual practitioners and instructors and
natu ra l fa mily planning but one whi ch represented prin- approve serv ice progra ms. Thi s was acco mpli shed
cipi es of profess ional deve lopment integrated with through the deve lopment of three commissions cover-
moral and ethica l co nsid erati ons. lt was thought th at ing accreditati on, certi fi cati on and servi ce program s.
we li ved in a society where mora l considerati ons and Th e ori ginal board ofin corporators had establi hed th e
professional developm ent had been relegated to a very goa l that educati onal tra inin g program s must meet the
Chapter 18: Professional and A cadem ic lnfrastructure of the CrMS 243
minimum standards ofthe CrMS core curriculum to be has its distinctive definitions of eli gibi lity, criteria fo r
accredited by the Academy. accreditation and operating procedures, but ali ha ve un-
dertaken accreditation activiti es, primarily to provide
quality ass urances concerning ed ucational preparation
The Accrediting Process- - - - - - - - . of members of th e profess ion or occupation.
Accreditation is a system whereby educational institu- The accred iting procedure genera ll y involves five ba-
tions and professional programs are recognized for a sic steps:
leve! of performance, integrity and quality that en titi es
thern to the confidence of the educational community 1. Standards: The accred iting agency, in collabo-
an d the public they serve. In the Un ited States, this rec- ration with educational in stituti ons, estab li shes
ognition is extended primarily through 11011-govemmen- standards. Standards are to be objectively en-
tal, vo luntary, institutional or professional associati ons. forced.
These groups establish criteria fo r accreditation, arrange
2. Self-Study: The instituti on or program seeking
site visits, eva luate those instituti ons and professional
accreditation prepares a se lf-eva luation study
programs which desire accredited status and publicly
that measures its perform ance aga inst th e stan-
designate those which meet their criteria.
dards establish ed by the accrediting agency.
In most other countries the estab li shment and mainte- 3. On-site Eva lu ation: A team se lected by the ac-
nance of educational standards is the responsibility of a cred iting agency visits the institution or program
central govemment bureau. In the Un ited States, how- to determine, first hand, if the app li cant meets
ever, public educational authority is constitutiona ll y the estab li shed standards.
reserved to the states. A system ofvoluntary, non-gov-
4. Publkation: After being satisfied that the ap-
ernrnental accreditation has evo lved to promote both
plicant meets its stand ards, the accred itin g
regiona l and national approaches to determining ed u-
agency li sts the institution or program in an offi-
cationa l quality. Whil e accreditation is basica lly a pri-
cia l publication with other si mil arly accredited
vate, vo luntary process, accrediting decisions are used
institutions or programs.
- as a consideration in many formal acti ons - by gov-
ernment funding agencies, scho larship commissions, 5. Re-evalu ation: The accrediting agency periodi-
foundations, employers, counselors, and potential stu- ca lly re-evaluates the instituti ons or programs
dents. Accrediting bodies, therefore, have come to be that it li sts to ascertain that continuation of the
viewed as quasi-publi c entiti es with certain responsi- accredited status is wa rranted.
bi lities to the many groups which interact with the com-
munity. Although accreditation is genera lly gra nted fo r aspe-
cific period oftime, accred iting bodies reserve the right
In the United States, post-secondary accreditation per- to rev iew member institutions or progra ms at any time.
forrns a number of importa nt functions, including the They also reserve the right to review any substa ntive
encouragement of efforts towards max imum educational change, such as an expansion from undergraduate to
effectiveness. The accredi ting process requires in stitu- grad uate offerings. Upon implementation, such changes
ti ons and programs to ( l) exami ne their own goals, ac- may require prior approva l and/or review. In this way,
tiviti es and achievements, (2) consider the expert criti- accrediting bodies hold their mem ber in stituti ons and
cism and suggestions of an accrediting commission, and programs continually responsibl e to their educational
(3) determine the interna! procedures for action on rec- peers, the constituents they serve and the public.
ommendations from the accred iting body. Since accredi-
tation status is reviewed on a periodi c basis, recogni zed Hi storica lly and currently, accreditati on at the post-sec-
institutions and profess iona l programs are encouraged ondary leve! invo lves the fo ll owing:
to ma intain continuous se lf-st ud y and improve the
l. Fosters excellence in post-secondary ed ucati on
mechan isms.
through the development of uniform national cri-
teria and guidelines for assessing educational ef-
Specialized accreditation of professional schoo ls and
fectiveness;
progra ms is granted by accreditati on commi ss ions set
up by national professional organi zations in such fields 2. Encourages improvement through continuous
as business, dentistry, engineerin g, la w, respiratory self-study and rev iew;
therapy, and occupational therapy. Each ofthese groups
3. Assures the educational community, the genera l American Academy of FertilityCare

public and other agencies or organizations that Professionals ___________~
an institution or program has clearly detined
appropriate object ives, maintains conditions After the establishment of the American Academy of
under wh ich the achievements of those objec- Natural Family Planning, the various presidents and
tives can reasonably be expected, appears to be members ofthe board of directors ofthe Academy over
substantially accomplishing those objectives and the pa t 20+ years have made an incred ibl e leve! of
can be expected to cont inue to do so; comm itment to see to it that this organ ization has con-
tinued to function and to maintain its vitali ty. lt is be-
4. Provides counsel and assistance to establish de-
cause of th is dedicated and com mitted leader hip th at
veloping in stitutes and programs and endeavors
the Academy has been ab le to ex ist over these past 20
to protect those institutions and programs against
years and carry out its mission ofaccreditation, certiti-
encroachments which mightjeopardize their edu-
cation and service program approval along with its mi s-
cational effecti veness.
s ion ofprovid in g very impo1tant co ll egial support and
interaction. It does th e latter through a series of national
Accrediting agencies such as the American Academy meetings , which are held on a yearly basis.
may obtain third party recognition that they are per-
forming their tasks according to acceptable, national In 200 1, theAmerican Academy of atura! Family Plan-
standards. ning officially changed its name to the American Acad-
emy of FertilityCare Profess ionals (AAFCP) and be-
came an organization whi ch represented the goa ls and
Certification -----------~ objectives of the CrMS program. The CrMS is the only
natural system that has exhi bited the degree of interest
Unlike licensure, certification is a vo luntary (and na- that the American Academy requires for its professional
tional) process whereby a non-governmental agency acti vitie .
grants recognition of competence toan individual who
meets certain predetermined quali fications. Certitica- A student entering an FCP training program (or any of
tion currently affects a wide array of health care pro- the other accredited programs) must be assured that that
viders. Certifying agencies customarily impose educa- program is fully accredited by the AA FCP . This ac-
tion, training and competency requirement on app li- cred itation is important beca use in order to qua!ify for
cants and offer certi ficants the right to use specia l pro- certi fication through the Academy one of the criteri a is
fes ional title designation . While certification is not the satisfactory completion of an Academy-accredi ted
usually mandated by government, uncertitied individu- ed ucation program.
als may tind themselves excluded from sorne job op-
portunities where sk ills exceeding those typically dis- Ce1titication also requires a tield serv ice component and
played by entry- leve l professionals are sought by the the documentation to the Commission on Certitication that
employer. Certitication may be ofincreasing importance teaching is being provided in a competent fas hion. Thi s is
as a criterion for the payment of health professionals ali accomplished through a series ofobjectively admini s-
under federal health care financin g programs. tered standards. The student shou ld be assured that ali
judgments with regard to teach ing capability are based
Third party recognition for American Academy ce1ti fy- on objective standards and are objectively administered .
ing activities can also be obtained. The competent health
professional performs accurately, makes judgments, A person who comp letes an Academy-accredi ted ed u-
effectively interacts with other professionals and serves cation program should see itas his or her respon ib ility
to assist patients and their fami lies in cop ing with health to become certified in the appropriate amount of tim e.
problems. Competence must be demonstrated as the pro- The full activity of certitication is explai ned during the
fessional enters practice and it must be maintained course of the educational phases. However, informa-
through one's practicing life. tion on certitication can be obtai ned by writing:
American Academy of
FertilityCare Professionals
6 15 South ew Bailas Road
St. Louis, MO 63141
Emai l: aafcp@ao l.com Web Site: www.aafcp.org
Chapter 18: Professio na l and Academ ic lnfrastru ctu re of the CrMS 245
Pope Paul VI lnstitute for the The Pope Paul Vl Institute for the Study of Human
Study of Human Reproduction ---~ Reproduction serves as a foundation upon which medi-
ca! sc ientists and others can continue to bu ild the pro-
The research progra ms that led to the CrMS officia lly gram ofthe CrMS and NaProTECHNOLOGY. Further-
bega n in 1976 at St. Loui s Uni versity Schoo l of Medi - more, it serves as a resource upon which individuals
cine under the directi on ofDr. Hil gers. Dr. Hil gers was can collaborate in the fu11her development ofthese pro-
an assistant professo r in the depa11ment of obstetrics grams.
and gynecology at St. Loui s Uni vers ity School ofMedi-
cine. Thi s original effort was supported by grants from This coll aboration has been ongoing with such individu-
the Mi ssouri Di vision of Hea lth and the National lnsti- als as Dr. Joseph Stanford, associate professor in the
tutes fo r Child Hea lth and Human Deve lopme nt Department of Family and Preventive Medicine at the
(N ICHO). Th e deve lopers ofthe CrMS began their work University ofUtah School ofMedicine in Salt Lake City,
together at that time. and Dr. Philip Boyle , specialist in medica!
NaProTECHNOLOGY in Galway, Ireland,and the newly
The base of thi s work moved to Creighton Un iversity deve lop ing Jnternational Institute for Cooperative Re-
Schoo l of Medi cine in July 1977. By November 1978, productive Science
the first educati on program for Natura l Fami ly Plan -
ning Practitioners had begun . In th is process, educa-
tional research, organi zati onal research and develop- FertilityCare™ Centers of America
ment and sci entifi c research were ali ongo ing simu lta- FertilityCare™ Centers lnternational ==-1
neously.
In July, 1999, two new organizations were developed
On August 6, 1978, the day that Pope Paul VI died , a for the advancement ofthe CrMS programs. These or-
comm itment was made by Dr. Hilgers and his wife, ganizat ions were FertilityCa re™ Centers of America ,
Susan, to fu ll y respond to the pastora l directive that Pope and FertilityCare™ Centers lnternational.
Paul VI had given in hi s encyc li ca l letter Humanae Vi-
tae to "men of sci ence" and to "p hys icians and hea lth FertilityCare™ Centers of America (FCCA) is a non-
care profess ionals" to become even more invo lved in profit organization that was establ ished for the primary
the furth er development of these programs . Thus, the purpose of promoting the CrMS and the new reproduc-
commitment to bui ld the Pope Pau l VI l nstitute for the tive sc ience of NaProTECHNOLOGY.
Study of Human Reproduction was made.
The purpose was to establish national and international
In September 1985, the offic ial opening of the Pope organ izations to un ite the CrMS services nationw ide and
Paul VI ln stitute occurred. Thi s deve lopment was ex- worldwide under one genera l and identifiable name of
trem ely important fo r th e furt her advancement of the " FertilityCare™." ln this way, the CrMS services could
CrMS. Because of the Pope Paul VI lnstitute, all ofthe be identified by their name and their unique services
research and educati onal program deve lopment efforts cou ld be properly promoted.
were moved into a pos iti on where th ey were given ad-
mini strati ve pri ority. As a resu lt, ongoing progress and The concepts ofthe FCCA were discussed in detail over
development could be made in these areas. a number of years at the annual meetings ofthe Ameri-
ca n Academy of Fertili tyCare Professionals. The fol-
By 1991 , a new wo men 's hea lth science, ca ll ed lowing is a summary ofwhy it was determined that the
NaProTECHNOLOGY (natural procreative techno logy) deve lopment ofthese organizations was necessary:
had been deve loped th ro ugh the research efforts avail-
able at the Pope Paul VI lnst itute. This new women 's The CREIGHTON MODEL FertilityCare™ System is
heal th sci ence was the fruit of the deve lopment of the unique in its field .
Pope Paul VI Insti tute.
• The CrMS has never been a system of on ly avoid-
The ln stitute, at the tim e ofthe publication ofthis text- 111g pregnancy.
book, is now 19 years old . The educationa l programs
• The CrMS teaches couples how to achieve preg-
that the ln stitute now ad mini sters in affi li ation with
nancy as well as avoid pregnancy.
Creighton Uni versity are 26 years old and the research
programs th at underpi n these effo11s are 28 years old. • The CrMS teaches rnen and women an appre-
ciation and understanding oftheir fertility.
246 The Med ica l and Surgica l Pra ctice of NaProTECHNOLOGY
• The CrMS is a system that can be used to moni- Such medica! consultants could be the driving fo rce be-
tor and ma in ta in procreative and gynecolog ic hind a CREIGHTON MODEL FertilityCare™ Center
health. but they must have at least one FCP who will assume
the responsibili ty of ma intaining the sta ndards of the
• The new repro ducti ve sc ience of
FertilityCare™services. The individua l physic ian will
NaProTECHNOLOGY was developed as a re-
be responsible fo r the medica! portion of the program
sult of the research that had been done on the
under the concepts of NaProTECHNOLOGY .
CrMS. NaProTECHNOLOGY cannot be done
without the CrMS .
Those programs that are currentl y in a CrMS ed ucation
• The CrMS is med ica ll y and ed ucati onall y stan- programare not elig ib le for affiliation until th ey have
dardized making the observation of its biologi- satisfactoril y completed their course work. During the
cal markers medica lly signi ficant. course of thei r training, preparation can be made for
such affi li ation in antic ipation ofthe completi on ofthe
• It is a system - not a method - and because of
program.
that is highly versati le.
• The system teaches abo ut selective intercourse Each individual program is give n a considerable amount
and not abstinence. Tt distinguishes between geni - of freedom in choos ing its own name, which must in-
tal and sex ua l contact, and it hel ps couples dis- clude the term " FertilityCare™." For examp le, the pro-
cover what Pope John Il ca lls the "inner soul of gram might be ca ll ed " Fertility Care™ Ce nter,"
hum an sexua lity". Furthermore, the system em- " FertilityCare™Services," " FertilityCare™ Program"
braces Pope Jo hn Pau l TI 's concept expressed in or "Department of FertilityCare™ Services."
his "Theology ofthe Body."
A Fertility Ca r e™ Center ca n e ither "feature
• [n order to spread the message and expand the
NaProTECHNOLOGY" or simply provide CRE IGHTON
services, the phrase " natural fami ly planning"
MODEL FertilityCar e™ services (w ithout the associ-
needed to be retired.
ated medica] co mp one nt ). ln order to " fea ture
• The CrMS is imminentl y marketab le if the ser- NaProTECHNOLOGY," the indi vidual program must
vices are brought under one co mmon identity. have a signed "NaProTECHNOLOGY Collaborative
FertilityCare™is the essence ofthe CrMS. Agreement" for ea ch physician (nurse practitioner, phy-
sician ass istant or nurse midwi fe) who may be partici-
• A considerable amount ofresearch had gone into
pating as a medica! consultant in th e program. These
the support for such a promotional effort amongst
arrangements are reviewed by FCCA and approval is
CrMS teachers and nationally recognized repo-
g1ven.
sitioning experts.
T here are four basic ty pes of affi li ation with FCCA.
By becoming affili ated with the FCCA, the use of the These include:
name " FertilityCare™" is all owed and the development
of a FertilityCare™ Center is promoted . In additi on, I nstitut io na l Affili a tion: This is a FertilityCare™
with the ap propri ate arrangement of a CREIGHTON Center that will be assoc iated with a fo rrn al institu-
MODEL Medica] Consultant to be associated with the tion such as a health care facility, hospita l, a uni ver-
program , it also all ows for the FertilityCare™program sity, etc.
to " feature NaProTECHNOLOGY. " Such a statement
can be used in promotional items. O r ga nizatio na l (Gro up) Affili a ti on : Th is is a
FertilityCare™ Center that is a freesta ndi ng, not-
A li FertilityCare™ Centers require a CREIGHTON for-profit institution on its own merits.
MODE L FCP as a responsible indi vidual within the ad-
ministration ofthe center for the quality control ofthe Diocesan Affiliation : This is a FertilityCare™ Cen-
CrMS program and serv ices. lt is strong ly enco uraged ter that is associated with a Catholi c diocese. ln such
that the FCP be certified through the AAFCP. These a circumstance, whe re it is comrnon to offer severa!
CrMS services must meet the standards that are pre- models of natural fami ly pl anning in struction, the
sented to new teachers ofthe CrMS in AAFCP-accred- designation of " FertilityCare™" can appl y onl y to
ited education programs. For examp le, CREIGHTON the CrMS portion of the program.
MODE L Medica] Consultants who are not practiti oners
cannot, by themselves, set up FertilityCare™Centers.
Chapter 18: Professional and Academic lnfrastructure of the CrMS 247
Ind epen dent Affil iation: This represents a D. The program will respect the inJ1erent God-given
Fertility Care™ Center that is located in a dignity of each woma n, man and chi ld with
physician 's office, for example, or perhaps in some whom it comes into contact, and it will eq ually
other faci lity not mentioned above. lt could also rep- respect the God-given integrity of marriage.
resent a FertilityCare™ Center that is run by an
E. The program will attempt to provide accurate
individual in a non-incorporated fashion.
and up-to-date information regarding the CrMS
and NaProTECHNOLOGY.
A formal affi li ation ag reement is comp leted and signed
and sent to FCCA. A formal certifi cate is issued and F. The program ag rees that it is the right of each
there are annual fees. There are also scho larships avail- married coup le to determine for themselves the
able to help fund some ofthe annual fees ofa program. number of children they wish to ha ve, in consul-
A student (FCPI) who is not assoc iated with an estab- tation with each other, in generosity and in prayer.
li shed FCCA affiliate may establish his or her own
G The program and its leaders and adm ini strators
FertilityCare™ Center once he or she has satisfacto-
sha ll accept responsibility for the exercise oftheir
rily comp leted the ed ucation program and been ap-
professional j udgment.
proved asa n affiliate.
As a component ofthe affiliation agreement with FCCA,

As ofthis publication, there are over 160 FertilityCare™
the name " FertilityCare™" applies to :
Centers throughout the United States and Canada. For
information contact:
A. Services th at are clearly recognized as
CREIGHTON MODEL FertilityCare™ services
FertilityCare™ Centers of America
and that CrMS services will only be provided
690 1 Merey Road, Suite 200
under the name " FertilityCare™. "
Omaha, NE 68106
B. Services wi ll always be provided consistent with (402) 390-9 167 (te l)
the standards establi shed in the training of FCPs (402) 390-985 1 (fax)
and Medica! Consultants in AAFCP accredited www.ferti litycare.org
education programs.
With FertilityCare™ Centers lnternational (FCCI),
C. As a program, ongoing efforts will be made to
progress is being made on the development of severa!
keep up with al! current and newly developing
worldwide regional affi li ates. These include
components ofthe CrMS .
FertilityCare™ Centers of Europe, FertilityCare™
Centers of Latin America and FertilityCare™ System
of Austrailasia . Over the next severa! years, this net-
Basic Philosophical Principies _ _ _~
work of FertilityCare™ Centers should be anticipated
to grow and to expand rather significantly.
As a part ofthe affiliation agreement with FCCA and/or
FCCI, the following philosophical principies are in ef-
fect:
A Final Note ----------~
A. The program will respect the va lu e and dignity
of each human li fe from its moment offertiliza- One of the strength s of the CrMS which is often not
tion ( conception) through the time of natural thought about as muchas it shou ld be is its professional
death. and academ ic infrastructure. lt is the only model ofnatu-
ral birth regulation that now has a complete and thor-
B. The program or its individuals will not prescribe
ough infrastructure in place. There is really no further
or refer for contraceptive age nts, sterilizations,
research and development that needs to go into the ac-
abortion or artifi cial reproductive technologies.
tual development of such an infrastructure. With the
C. The program recognizes that human sexuality is AAFCP, the Pope Paul V I Institute, FCCA, and FCCI,
a function of the who le person and not just a the basic infrastructure is in place. There will , ofcourse,
function of its parts. Tt further recognizes the be fu11her refinement, add ition and expansion of thi s
scripture verse that we are " created in the image structure. However, the intense effort that was neces-
and likeness ofGod" and that such a philosophi- sary in the actual development ofthese organization s is
cal principie ul timate ly dictates the approach to now comp lete.
the human persons that will come under our care.
What is necessary for the future is the growth and de-

velopment of these programs. The real promotion of
these programs!
1. Hilgers TW, Hilgers SK, Daly KD , Prebil AM: The CREIGHTON 3. This group included K. Diane Da ly, RN; Evelyn Eaton, PhD;
MODEL FertilityCare™ System Core Curricu lum 2003-2004. Susan K. Hil gers, BA ; Shirley Hoe fl er, BA; Donald Kramer, MA;
Pope Paul VI lnstitute Press. Omaha, Neb. 2003. Terry Maes, BA; Patric ia McLean, RN; Judy Pittack, MA; Ann
Prebil, RN, BSN; Nancy Sp ielman , BM ; Kathy Rivet , BS ; Joan
2. Hilgers TW, Preb il AM, Da ly KD , and Hil gers SK : The
Wall , BA; and Ann Wa lsh.
CREIGHTON MODEL for the Development of atural Family
Planning Education and Service Programs. Creigh ton Univer- 4. Pope John Paul 11 : The Theology of the Body: Human Love in
sity atura l Family Planning Education and Research Cen ter, the Di vine Pl an. Pau line Books and Media, Boston, MA, 1997.
Omaha, Nebraska, 1980.
Part 11:
~~~ 8"1'1'~ ~t,

NaProTECHNOLOGY
Thomas Hilgers, M.O. "One of the most significant defects in modern reproductive
Chapter 19
medicine is the inability of physicians to consistently evalu-
ate the various hormones of the menstrual cycle ... A whole
variety of new therapeutic approaches can be identified with
the targeted identification of abnormal ovarian function . This
can be helpful in the treatment of a myriad of women 's
health conditions."
249
250
Targeted Hormone Assessment
of the Menstrual Cycle
ne ofthe most significant defects in modem repro- Asan extremely inferior substitute toan assessment of
º ductive medicine is the inability of physicians to

consisten ti y evaluate the various hormone ofthe men-
strual cycle. This difficulty arises from the absence of a
clinically relevant marker for the timing of ovulation
these hormones , a day-21 or day-22 progesterone leve!
is usually drawn (Figure 19-2). Such a practice presumes
that ali menstrual cycles are 28 days in duration. How-
ever, the menstrual cycle is 28 days long in only 5 to 1O
during the course of everyday clinical practice. With percent ofmenstrua l cyc les 1 and this natural irregular-
the advent ofthe CREIGHTON MODEL FertilityCare™ ity ofthe cycle makes the routine timing of a progester-
System (CrMS) and the research associated with it, this one leve! on a particular day of the cycle, for the most
problem has been so lved. The importance ofthe ability part, worthless. Furthermore, as the proge terone and
to target the hormone eva luation ofthe menstrual cycle estradiol levels increase, reach their peak levels and then
cannot be understated. decrease, there are normal levels for each point along
the way. At this point in time, the essential infonnation
The most relevant clinical hormones, estradiol-17~ (E 2 , from an evaluation of these profiles can be obtained
estradiol) and progesterone, are produced in a cyc li c only through a NaProTECHNOLOGY approach .
fashion. The preovulatory production of estradiol in-
creases as ovulation approaches and decreases as ovu- A variety of new therapeutic approaches can be identi-
lation occurs. Following ovulation and with the devel- fied with the targeted identification ofabnormal ovarian
opment of the corpus luteum, progesterone becomes function. This can be helpful in treating a myriad of
the dominant postovul atory hormone. But, estradiol is women 's health conditions. Sorne of these would in-
still ofimportance (Figure 19-1 ). During the postovula- clude conditi ons such as dysfunctional uterine bleed-
tory phase, the progesterone and estradiol levels ining, recurrent ovarian cysts, premenstrual syndrome and
crease reaching their highest point about one week fol- premenstrual dysphoric disorder, recurrent miscarriage,
lowing ovulation and then decreasing again in the week infertility, and even the prevention of pre-term birth .
prior to menstruation . The natural irregularity of the With a proper understanding of an accurately targeted
menstrual cyc le and the variation in the production of follicular and luteal function hom1one profile, one can
these hormones during the course of the cycle have then institute rational therapeutic regimens, which, as
limited the clinical accessibility to evaluating these very this textbook will show in the chapters ahead , can ha ve
important hormones.
251
a ignificant impact on women 's health. and post-ovulatory phases, thus enabling the physician
to properly target the cycle for endocrine evaluation.
When a woman is charting the CrMS, she will identify
the various biomarkers of her menstrual and fe11ility
cycles. These in clude the menstrual flow, the pre-Peak Targeting the Cycle _ _ _ _ _ _ _~
dry days, the beginning ofthe mucus flow through the
Peak Day and the post-Peak phase of the cycle. The To target the preovulatory estradiol profile, one looks
entire length ofthe cycle is well documented anda va- at the previous cyc les charted with the CrMS and iden-
riety of other biological markers of either health or ill- tifies the earliest occu1Tence ofthe Peak Day. The woman
ness can be detined. By identifying a woman 's Peak is then in stru cted to come to th e laboratory or the
Day, which is very close ly associated with the timing of physician 's office to ha vean estradiol level drawn start-
ovulation (ovu lation occu rs on Peak +/-2 days in 95.4% ing on the fifth or sixth day prior to the anticipated Peak
of cycles 2) , the cycle is effectively broken up in to pre- Day (P-5 or P-6). These leve Is are then continued every
IS 16 17 18
L H
I I I I I
Estradiol-17 ~ Progesterone
40.0 ng/dl-t--T-t--t--T-1-.,....""1--T-1-+--llH-~-+--+--+-t--+--+---+-+--+--+----!t--+--+-20 . 0 ng/ml
30.0 ng/dL+-+-¡.;;;;+-+--l-+-+-+--11-+--llH•l-+--+--+-H - - - - - - - - - 1 - 1 5.0 ng/mL
5.0 ng/mL
Fi g ure 19-1: A normal CrMS chart with daily levels of estradiol and progesterone. Th e hormone curve is within normal limits and
it demonstrates the relationships to the mucus cycle, the Peak Da y and the variations in estradiol an d progesterone production
during the course of the menstrual cycle .
22 23 24 25 26 27 28 29 30
M H H M
I I I I I l I
1'
Progesterone
level
Day 22
Figure 19-2: In this woman , a progesterone level was drawn on day 22 of the cycle. The level was not helpful in assessing
ovulatory function because it was drawn at the wrong time of the cycle. The physician thought that she was "anovulatory"
because the progesterone level was still in th e preovulatory phase of her cycle. However, because she was charting her
cycles with the CrMS , it was easy to determine that the level was simply drawn during the preovulatory phase of the cycle.
Chapter 19: Ta rgeted Hormone Assessment of the Menstrual Cycle 253

Targeted Periovulatory and Post-ovulatory Hormone Profiles
Pre-Peak
Menstruation Dry Days Vulvar Mucus Cycle Post-Peak Dry Days
1 1
Peak
Day
~ ~ ~ ~
P-6 P-4 P-2 Peak P+2 P+3 P+S P+7 P+9
Da y
\ /
Targeted Periovulatory Targeted Post-ovulatory
E2 Profile P + E2 Profile
Fig ure 19-3: Th is schematic drawing of the CrMS demonstrates how it is used to target the periovulatory and postovulatory
hormone profiles.
other day (QOD) through P+2 (Table 19-1 ). This, a long the 3-value or the 4-value swn and mean ofthe estradiol
with the targeted postovu latory profile is illustrated in profile. This is illustrated in Table 19-2. The 4-va luesum is
Figure 19-3. calculated by adding four values:the estradiol leve l four
days prior to the peak estradiol leve! (Peak E2-4), the
When the results ofthe estradiol profile return , the phy- value two days prior to the peak estradiol leve! (Peak
sician should look for a peak leve! ofestradiol (Peak Ez). E2-2), the peak estrad iol leve! (Peak E), and the value
For the profi le to be adequately targeted, it is important two days after the peak estradiol level (Peak E2 +2). The
that a Peak E2 leve! be identified by the presence of a mean ofthose four va lues is eas ily calcu lated by divid-
lower estradio l leve l prior to and another lower estradiol ing the sum by four.
leve! after the Peak E2 • In this way, one can be confident
that the estrad iol profile has been captured. lt is neces- A 3-value sum is calculated by adding the Peak E2 -2,
sary to have at least three values with the middle value Peak E2 and the Peak E2 +2 leve ls. The mean ofthe three
being the Peak E2 leve! in order to ha ve a true periovu- values is calculated by dividing the sum by 3.
latory estradiol profile.
In addition, the Peak E2 level itselfcan be ofsome value
This can then be further evaluated by ca lculating either in observing how strong the periovulatory E2 profile is.
This will be considered later when discussing normal
values (Table 19-3).
Table 19-1: Targeting the
P reovulatory E 2 Profile
To target the postovulatory progesterone and estradio l
leve! , the woman identifies her Peak Day (P) charting
the CrMS. Starting on P+3 (see Figure 19-3), the levels
Look al previous cycles charted with CrMS and identify
the earliest occurrence of the Peak Day are drawn every other day for a total of five values (P+3,
P+5, P+7, P+9and P+ l 1- Table 19-4).
Begin E2 levels on P-5 or P-6 and continue QOD until
P+2
To calculate the postovulatory sum for either the proges-
terone or the estradiol profi le during the luteal phase,
one adds each ofthe five values to develop the sum and
Table 19-3: Calculati ng the
by dividing the sum by five, one can calculate the mean
Periovulatory E 2 Sums and Means
(Table 19-5).
An example of a post-Peak progesterone profi le in a

The Peak E2 must be identified by a lower level of E2
woman with an infertility problem is demonstrated in befare and alter the Peak E, level.
Figure 19-4. In this particular example, the proge terone
Far 3 values:
leve ls were drawn on Peak +3, P+S, P+7, P+9 and P+ 1 1 E,-2, Peak E,. E2 +2
ofthe third cyc le charted . Theflrst leve! ofthis profile
Far 4 values :
E2 -4, E2-2 , Peak E,. E2 +2
Table 19-2: Periovulatory E2 Sums and Means- Calculate the mean and the sum of the 3 or 4 values
and compare to the normogram.
An Example
E, -4 8.8 ng/dl
E2 - 2 14.8 ng/dl
Peak E, 26.0 ng/dl
Table 19-4: Targeting the Postovulatory
E2 + 2 12.8 ng/dl
P and E 2 Profil e
4 value sum and mean: Sum Mean
8.8 + 14.8 + 26.0 12.8 62.4 15.6
ldentify the Peak Day (P) charted with the CrMS
3 value sum and mean:
14.8 + 26.0 + 12.8 53.6 17.9 Draw P+E, levels on : P+3, 5, 7, 9, 11
12 13 14 15 16
xi K 1 ••
1
Figu re 19-4: In this chart where six cycles are shown , the Peak Day varies from day 14 of the cycle through day 20 of the cycle.
A targeted progesterone hormone profile was carried out in the third cycle (progesterone levels are in red) . This targeted hormone
profile shows that the luteal phase progesterone in this cycle was clearly suboptimal.
Chapter 19: Targeted Ho rm o ne A ssessment of the Menstrua l Cyc le 255
in most menstrual cycles. Ho wever, in wo men who ha ve

Table 19-5: Postovulatory Progesterone very long and irregul ar cyc les (for exampl e, someone
Sum and Mean-An Example
with polycystic ovarian disease) , targeting is not ve ry
helpful or effecti ve . Thus, as a genera l rule of ma nage-
me nt, the cyc les should be 38 days or less in order to
P+3 9.4 ng/ml accom pli sh this type of targeting. However, the hor-
P+5 14.4 ng/ml
mone profil e that one mi ght obta in in a woma n w ith
P+7 15.7 ng/ml
po lycystic ovarían di sease and long and irregular cycles
is different than in one obtained from wo men with more
P+9 13.6 ng/ml
regular cyc les (see Chapter 43).
p + 11 8.1 ng/ml
5 va lue sum and mean: Sum Mean There is a tendency amo ng medica! practitioners to try
9.4 + 14.4 + 15.7 + 13.6 + 8.1 = 61 .2 12.2 to "shortcut" this type of an evaluati on. However, such
shortcuts w ill ha vea n inh ere nt increased rate of inac-
curacy. Once the physician becomes familiar with as-
sessing the ful! profile of e ith er estrad iol during the
periovulatory phase of the cyc le or progesterone and
estradio l during the postovulatory phase of the cyc le,
on P+ 3 was drawn on day 22 of that pa11icular cyc le. sorne limited approac hes co uld be he lpful for screening
Over the course of the six cycles charted , one can see the cyc le. In infertili ty pati ents who are on treatment
that the Peak Day has occurred from as early as day 14 w ith hormonal sti mul ation of the cycle ( ovul atio n in-
to as late as da y 20. A routine day-22 progesterone leve! duction) to manage their ovarian dysfunction, a P+ 7
would have given inaccurate information w ith regard to progesterone and estradi ol leve l wi ll adequa tely screen
the funct ion of the luteal phase. However, with the
progesterone profile drawn in the third cycle ofthis se-
ries, the profile can be considered to be very suboptima l
Table 19-6: Targeting the Periovulatory
(see Chapter 24) . This interpretation of the progester-
Evaluation of the 17P Estradiol (E 2) Profile
one levels can be confidently made because the entire
projile of luteal function has been o btained a nd it has Creighton M odel System (N=l93)
been properly targeted.
n % Cumu lative
ln a series of 193 cycles in w hich the periovulatory es- Targeted the E, profile accurately 138 71 .5 71 .5
with a Peak level of E,
tradiol levels were targeted as described in this chapter,
Targeted the E, profile accurately 24 12.4 83 .9
an identifiable Peak E2 leve! was present in 13 8 of the with the assistance of the P+3
cycles (71.5%). In another 24 of the cyc les, the P+ 3 es- E, level (and a Peak level of E, )
tradiol leve! was also drawn to assess the lutea l phase Gave a reasonable assessment of 25 13.0 196 9 I
the E, profile-but no Peak level
anda Peak E2 profile could be identifi ed. Thus, in 162 of
the 193 cycles (83 .9%), thi s approach to targeting th e Targeted the E, profi le inaccurately 6 QJJ
estrad iol profile was accurate. In another 25 ofthe cycles,
even tho ugh the Peak E2 leve! was not identifi ed spec ifi-
cally, the estradiol profil e gave a reasonable assessment
of estrogen producti o n during the preovulatory phase
ofthe cycle ( 13 .0%). Thus, thi s system fo r targeting the
Table 19-7: Targeting the Evaluation of the
preovulatory estradiol profil e was acc urate or gave a
Postovulatory Progesterone
reasonable assessment in 96.9 percent ofthe 193 cyc les
and 17P Estradiol (E 2) Profile
of eva luation . ln o nl y 6 of the cycles (3. 1%) , the tar-
geted estradiol profile was inaccurate (Table 19-6). C reighto n Model System (N=620)
n %
In a similar study of luteal phase progesterone and es-
Targeted the postovulatory 609
tradiol profiles invol ving 620 cycles (Table 19-7), the profile accurately
luteal ph ase was accurately targeted in 609 cyc les
Targeted the postovu latory 11 1.8
(98.2%) . In only 11 cycles ( 1.8%), the targeting was in- profile inaccurately
accurate.
This type oftargeting ofthe cycle can be accomp li shed

256 The Medical and Surgical Pra ctice of NaProTE CHNOLOGY
the luteal phase for the purposes of managing med ica- terone levels during the post-Peak phase of the men-
tions. A 3-day sum and mean ofthe profiles ca n be use- strual cyc le are co mpared for wo men of norrnal fertility
ful in patients w here a more lim ited profile might be ad- and w ho have infertility fro m ali causes (Figure 19-5)
equate. In such cases, the levels shou ld be drawn on and fo r women of normal fertility and women who ha ve
P+5, P+7, and P+9. However, these will have a decreased infert ility related to endometriosis (Figures 19-6). Addi-
abi lity to adequately assess th e luteal phase and , when tionally, thi s can be broken down further by comparing
used, one needs to understand those limitations (Table the early portian of the middl e post-Peak phase for
19-8). norma l contro ls to those women who have endom etrio-
sis and to those women w ho ha ve in fertili ty re lated to
pelvic adhesions ora normal pelvis (the difference be-
tween the latter two progesterone levels was not stati s-
Table 19-8: Screening the Post-Peak Phase for tically signi ficant) . The late portian of the mid-post-
Assessing Luteal Function Peak phase can also be further assessed (F igures 19-7
and 19-8). In each ofthese cases, the targeted hormone
levels fro m women with various identified organic causes
Use a 3-day sum and mean (P+S , 7, 9)
of in fert ili ty are signifi cantl y lower than those in a simi-
Use a P+7 level only lar gro up ofwomen w ith notmal fert ili ty. By being able
to target the cycle in this fashion , these types of com-
The limitations must be understood
parisons can be made and, often, they can be made in
very Jarge numbers of patients.
As this textbook unfolds w ith the laboratory su pport

This approach to targeting tbe cycle is within the scope for and the clinical approaches ofNaProTECHNOLOGY,
ofpractice ofthe genera l obstetrician-gyneco logist and the appli cation oftargeted hormone assessment will be
the specificall y-tra ined fa mil y physician , intemi st, or fundamental not onl y to understanding of the patho-
pediatrician. ph ys iologic e nd oc rin e c irc um stances of va rio us
women 's health issues better, but al so to deve lopin g a
Sorne examp les ofhow this can be used are illustrated in rational treatment approach.
Figures 19-5 through 19-8. In these examples, the proges-
Chapter 19: Targeted Hormone Assessment of the Menstrual Cycle 257
Progesterone Levels at Various Stages : Progesterone Levels at Various Stages:

of Post-Peak Phase: of Post-Peak Phase:
Normal Control s and All lnfertility Normal Controls and Endometriosis
- Normal co ntrols (n=23) - Normal controls (n=23)

c:::::J Ali infertility (n=114) c::::::J Endometriosis (n=79)
12.3 12.3
12.0 12.0
:J"
E
10.0 ].'. 10.0
e;
>
B.O
.,e:
~
B.O
e
2
.,"'
Ol
6.0 e
o..
6.0
4.0 4.0
Early Mid Late Early Mid Late

PPP PPP PPP ppp ppp ppp
Stage of post-Peak phase (PPP) Stage of post-Peak phase (PPP)
Figure 19-5: This graph shows the targeted progesterone Figure 19-6: These are the targeted progesterone levels during
levels during the early, middle and late post-Peak phase the early, middle and late post-Peak phase comparing patients
comparing infertility patients with patients of normal fertility. with endometriosis and infertility with patients of normal fe rtil ity.
Each of the infertility levels are significantly decreased from Al each point, the progesterone levels in the endometrios is
the normal. The p-value at the early and mid-post-Peak phase patients were significantly decreased. The p-levels during the
was <.001, and during the late post-Peak phase, <.05. early and mid-post-Peak phase were <. 01 and in the late post-
Peak phase, <.05.
Progesterone Levels Progesterone Levels

14.0 13.4 Late Mid-Post-Peak Phase Early Mid-Post-Peak Phase
'.J' '.J'
E 12.0 E 12.0
Ci Ci
.s .s 10.7
Qj Qj
> 10.0 > 10.0
..S! ..S!
Cll 8.6 Cll
e: e:
o,__ o,__
8 .0 8.0
Cll
¡¡; ~ 7.2
VI
Cll Cll
Cl Cl
o,__ o,__
6.0 6.0
a.. a..
4.0 4.0
Normal Endometriosls Pelvi c adhesions Normal Endometriosis Pelvic adhesions

Controls and normal pelvis Controls and normal pelvis
Figure 19-7: These are the progesterone levels in the early Figure 19-8: These are the progesterone levels during the late
mid-post-Peak phase of the cycle in normal controls, patients mid-post-Peak phase of the cycle in normal controls, patients
with endometriosis and patients with infertility from other causes with endometriosis and patients with other causes of infertility
(pelvic adhesions and a normal pelvis by laparoscopy). The (pelvic adhesions and normal pelvis by laparoscopy) . The
progesterone level in patients with endometriosis was progesterone levels in patients with endometriosis were
significantly decreased from the normal controls (p<.01) and significantly decreased (p< .05) from the normal controls and
the pelvic adhesion and normal pelvis group were significantly !hose who had pelvic adhesions and had other cause s of
lower than the endometriosis group (p<.05). infertility had decreased progesterone levels from the
endometriosis group (p<.025).
1. Vo llman Rf: The Men strual Cyc le. WB Sa unders Co. Phila- 2. Hil gers TW, Abraham GE, Cavanagh D: Natural Farn il y Plan-
de lphia , 1977 . ning l. Th e Pea k Sympto m a nd Estim ated Time of Ovul a-
t ion. Obstet Gynecol 52:575 , 1978.
Sonographic Classification System
he growth and development ofthe ovarian follicle conducted at the Pope Paul VI Institute Reproductive
T has been documented by sequential ultrasound
scanning throughout the course ofthe normal menstrual
Ultrasound Center from September 1985 through May
2001. A sonographi c assessment ofthe ultrasound char-
cycle. 1- 3 The actual rupture of the ovarian follicle has acteristics of ovulation was tabulated on a subgroup of
also been observed sonographically4-7• In addition, sorne 460 consecutive spontaneous cycles in order to estab-
follicles may not contain a cumulus oophorus and may lish a sonographic classification system for ovu lati on
representan ovulation di sorder referred to as the empty disorders. The pre- and post-ovulatory estrad iol-1 713 (E2,
follicle syndrome 8-9 . estradiol) production and postovulatory progesterone
production were assessed and statistica ll y compared to
This chapter presents the work in sonographic observa- a control group made up of cyc les with normal ovula-
tion for the purpose of evaluating and anatomically clas- tion by ultrasound parameters. During the study period,
sifying a ful! range ofhuman ovulation disorders. Such ali cycles leadi ng to pregnancy and al i cycles that did
ovulation di sorders occur in non-medicated, spontane- not result in pregnancy were assessed to give clinical
ous menstrual cycles in women with primary or sec- input to the classification system.
ondary infertility. This eva luation wi ll establish a work-
ing classification ofa broad spectrum ofhuman ovula- Patients involved in this study were being seen for ei-
tion disorders that has app li cation to the clinical and ther primary or secondary infertility. They were ali chart-
the resea rch settings. in g their men strual cycles using the CREIGHTON
MODEL FertilityCare™ System (CrMS) . 1º Therefore,
In subseq uent chapters, the va lidation ofth is classifica- the patients were ab le to track their ferti li ty and men-
tion system is detail through an observation ofwhether strual cycles by observing biological markers such as
or not pregnancy occurred in women with ovulation the vulvar discharge of cervica l mucus to identify the
di sorders and through an assessment of the endocrine Peak Day, which is closely associated with the time of
dysfunction that accompanies them. ovulation 11 • Charting with the CrMS assisted in defin-
ing the time during the cycle when the seria l ultrasound
This study involved the prospective evaluation of 1 914 evaluations and hormonal studies would be performed.
consecutive menstrual and ovu lation cycles and was
259
Transabdomina l a nd transvaginal follicular ultrasound

examinations were performed us ing a Diasonics SPEC-
TRA (M ilpitas, CA) Real-Time System with a 5.0 MHz
abdom ina l probe and 7.5 MHz tran vagina l probe or us-
ing a Medison Voluson 530D digital ultrasound system.
Both the fu l! bladder and empty bladder techniques were
utilized.
The patients were eva luated on the fift h day of the ir

menstrual cyc le for a baseline ovarian ultrasound evalu-
ation . In this way, cystic structures present from the pre-
vio us menstrua l cyc le could be identified and new fol -
licular growth and development could be observed. Each
patient return ed to the center approximately five days
prior to the pred icted Peak Day. 10· 11 • With CrMS fertil-
ity tracking, it is easy to determine the days that a pa- Figure 20-1 : Ultrasound examination of the changes in the
tient shou ld be seen in order to observe the follicular endometrial lining through the course of the menstrual cycle.
Early proliferative (upper left) to late proliferative (upper right)
recruitment stage.
and early secretory (lower left) to late secretory (lower right)
are shown (From : Pope Paul VI lnstitute , Division of
Genera ll y, the patient returned on the tenth day of her Reproductive Ultrasound).
cyc le and was seen daily o nce a dominant fo lli cle is
identified (a dominant fo llicle is defined by an average
1(11 100
measurement eq ua l to or g reater than 1.5 cm) . Daily
observation continu ed until at least 24 hours past foll i-
cul ar rup tu re. The mean fo lli cul ar di a meter (M FD) was
~
g-
75 ¡;
"'
""g_
~
measured in centim eters and was calculated usin g the § 50 3'
fo ll owi ng fo rmul a:
& 50
[
=- ~
'-!:
~ 25 Jl ~
L+W+H = MFD
3
A lso, the patient was usually seen during the mid-lutea l Fil
phase of her cycle for subsequent evaluation ofthe ova- Figure 20-2 : Transition observed from proliferative to secretory
ries. The changes in the endometrial lining were also endometrium during the six days leading up to follicular rupture
(FR ) and the day of follicular rupture (Total N=400): P=
sonographi ca ll y noted as they progress from early pro- proliferative, LP=late proliferative, ES=early secretory and S=
liferative to late proliferative , early secretory, and late secretory (From : Pope Paul VI lnstitute research , 2004).
secretory 12 (F igu res 20-1 and 20-2). Changes in the cer-
vix involving cerv ical dilatation were also observed
(Figures 20-3 through 20-5).
The do minant fo lli cle was followed daily until identifi-

cation of a co mplete o r partial rupture o r an unruptured
fo llicl e. When the fo lli cle ruptures comp lete ly, the
dominant fo lli c le either disappears or decreases dramati -
ca ll y in size. Then , the ea rl y corpus luteum can usually
be identified. In a partial rupture ofthe fo ll ic le, the fol-
li c le col lapses by no more than 7.5 mm. [n unruptured
fo lli c les, the fo ll icle fills in with interna! echoes. This
appearance is documented for two consecutive days.
Also, an observab le increase in the size ofthe unruptured
fo lli c le genera ll y occurs and the endometrium changes
from late proliferative to early secretory type .
Figure 20-3 : The dilatation of the cervix observed in sagittal
view as follicular rupture approaches (From : Pope Paul VI
When the dominant fo ll ic le is identified, the sonographer lnstitute, Division of Reproductive Ultrasound}.
Chapter 20 : Disorders of Human Ovulation : Sonographic Classification System 261
searches for interna! echoe that may represent the cu-

mulus oophorus. These echoes are found adjacent to
the inner wall ofthe fo lli cle (Figure 20-6) . The cumu-
lus is observed as a crescent-shaped , hy perechoic rim
with an interna! hypoechoic area. l t is generally easy to
identi fy and is characteri stic in appearance .
The cumu lu s oophorus must be v isuali zed in both lon-

gitudina l and transverse pl anes to verify its presence
w ithin the fo llicl e. The hi ghest magnification that does
not degrade image reso luti on is used . The size of the
cumu lus oophoru s is measured using electroni c calipers
placed 0 11 the inner lum en wall s. The empty fo lli c le is
Figure 20-4: A transverse view of the cervix as follicular rupture ident ifi ed by the absence ofthe cumulus in both planes
approaches. In this view, the dilatation of the cervix can be (Figures 20- 7 and 20-8) . Thi s protoco l for fo lli cul ar
seen along with severa! cervical crypts extending out from the
evaluation is meticulous and examination generally takes
endocervical canal (From : Pope Paul VI lnstitute, Oivision of
Reproductive Ultrasound) . 15 to 30 minutes.
Figure 20-6: The observa tion of a mature follicle (1.97 cm)

Figure 20-5: The relative incidence of a dilated (open) cervix and its cumul us oophorus (C.O .) in the sagittal plane in 2-0
and undilated (closed) cervix as follicular rupture (FR) (left) and the same cumulus in 3-0 (right). (Med ison Voluson
approaches (complete ruptures on ly) (Tota l N=311) (From : 5300 , 30 -S-VOW, 5-8 MHz, TVP Probe) (From: Pope Paul VI
Pope Paul VI lnstitute research , 2004). lnstitute , Oivision of Reproductive Ultrasound).
Figure 20-7 : A mature follicle on the left with a cumulus oophorus andan empty follicle on th e right (From:
Pope Paul VI lnstitute , Oivision of Reproductive Ultrasound).
Figure 20-8 : An empty follicle on the left (1.95 cm) anda mature follicle on the right in transverse plane (2.15 cm).
The follicle on the right shows a small follicle impinging on the mature follicle at 7 o'clock to demonstrate its
characteristics as distinct from a cum ulus oophorus (From: Pope Paul VI lnstitute , Division of Reproductive
Ultrasound ).
With this approach , we are now able to identify the fo l- 1/. Anatomically abnormal ovulation by ultrasound.
lowing defined ovulatory events: The following anatom ic defects of ovulation can
be identified and are cata logued:
l. An anatomically normal ovulation by u/trasound.
A. A mature fo llicle (wi th a MFD greater than or
A follicle is sonograph ica ll y observed to develop
equal to 1.90 cm) in wh ich the cumu lus oophorus
and reached maturity (defined as a MFD greater than
is either absent or retained (MF: -, Re): these
or equa l to 1.90 cm) and has the positive presence
follicles are observed to completely rupture over
ofa cumulus oophorus (MF: +). This is followed by
24 hours (F igure 20-8 and Figure 20-1 O).
complete rupture of the follicle and the formation
of a corpus luteum over a 24-hour period (F igure B. A luteinized unrupturedfollicle (LUF: +, -): This
20-9). is a follicle that grows and develops but never
ruphires and becomes debris filled. Secretory
changes are positively identified in the en-
dometrial cavity. The cumulus mayor may
not be present (F igure 20- 11 and 20-12).
C. An immaturefo/licle (with a MFD less
than 1.90 cm): This foll icle may be ei -
ther positive or negative for the cumu-
lus oophorus or ma y have a retained
cumulus (lFS: +, - Re). These fo llicles
are observed to comp lete ly rupture
(F igure 20- 13).
D. Partía/ rupture ofthe follicle : This is a

fo lli cular rupture that is observed to be
less than or eq ual to 7.5 mm . These fol-
li c les may be positive or negative for a
cumulus oophorus or may have a re-
tained cumul us (PRS: +, -, Re) (F igure
20-14).
Figure 20-9 : The complete rupture of a mature follicle with a cumulus oophorus E. Delayed rupture of the fol licle (DRS:
in the sagittal (upper left) and transverse plane (upper right) with MFD 1.97 cm
+, -, Re): The fo llicle is observed to
and its corpus luteum (lower left and right) on consecutive days demonstrating
an anatomically normal ovulation by ultrasound (From : Pope Paul VI lnstitute, rupture overa 48-hour period. Within
Division of Reproductive Ultrasound). the first 24 hours , the size ofthe MFD
Chapter 20 : Disorders of Human Ovulati on: Sonographic Classificati on System 263
Figure 20-10 : A retained cumulus oophorus (C .O.) (far right) in a follicu lar rupture over three consecutive days (From : Pope Paul
VI lnstitute, Oivision of Reprodu ctive Ultrasound).
Figure 20-11 : A debris filled unruptured follicle where the Figure 20-12: A twin luteinized unruptured follicle where the
endometrium has been positively identified to have changed endometrium has been positively identified to have changed
to secretory (From : Pope Paul VI lnstitute , Oivision of secretory and both follicles have become debris filled (From :
Reproductive Ultrasound). Pope Paul VI lnstitute , Oivision of Reproductive Ultrasound).
Figure 20-13 : An example of an immature follicle with complete rupture. With serial (daily) ultrasonography the
follicle has been observed to reach an MFO of 1.67 cm (left and middle, tran sverse and sagittal view) and is
com pletely ruptured forming a co rpus luteum measuring 7.9 mm (right) (Medison Voluson 530 0 , 30 -S-VOW, 5-8
MHz, TVP probe) (From : Pope Paul VI lnstitute , Oivision of Reproductive Ultrasound).
is red uced to less than 7 .5 mm .

A comp letion ofthe rupture pat-
tern is observed 24 hours follow-
ing this decrease in size (F igure
20-15 ).
F. Afo/licularism (AF) : Thi follicle
never reaches dominance. In a
regular length menstrual cycle,
this foll icle never reaches an
MFD of greater than 1.4 cm
whereas a dominant follicle be-
gins at 1.5 cm (Figure 20-16).
During the course of the fo lli cul ar ul -

trasound assessment, these patients usu-
ally undergo a targeted hormone evalu-
ation for estradio l and progesterone. Figure 20-14: An example of a partial rupture. The upper follicle (transverse and
sagittal view) with an MFD of 2.00 cm is observed to only partially rupture (5. 7.5
Sorne ofthese patients became pregnant. mm) over 24 hours (bottom , transverse and sagittal views) toan MFD of 1.47 cm
The next two chapters review the find- (From : Pope Paul VI lnstitute , Division of Reproductive Ultrasound}.
ings of these hormone studies and the
observation of cyc les in wh ich preg-
nancy did or did not occur. Thi s review
forn1s the endocrine and clini cal foun -
dation for the validation ofthi s classifi-
cation system.
A tota l of 1,9 14 fo lli cular ultrasound

series were initiated during this 16-year
period. Of this total , 1,8 18 series were
availab le for evaluation and 96 were
never comp leted. Of those available,
1, 172 were spontaneous cycles and 646
were medicated cyc les (C lomid ,
Pergonal, Metrod in, GnRH , etc.). Sub-
groups were carefully studied fo r the
acc urate ultrasonic definition of the
various ovulation-related disorders and
for their correlation to hormonal events.
The first subgroup included a combined

460 consecutive cycles from and sepa-
rate patients. During the course of the
menstrua l cycles, no medications were
being administered (s ponta neous
cyc les). Patients in this study ranged in
age from 22 to 42 years of age with a
mean of30.7 years. The distribution of
ali cycles categorized by ovulation
events in this subgroup are shown in
Table 20- 1. Figure 20-15: This is an example of a delayed rupture pattern . The dominan!
follicle partially ruptured over 24 hours (MFD of 2.08 cm to 1.77 cm) and then
completely ruptured forming a corpus luteum over 48 hours (MF D 0.88 cm) (top
In thi s series, anatomica lly normal ovu- to bottom , transverse and sagittal views) (From : Pope Paul VI lnstitute , Division
lation patterns by ultrasound (M F: +) of Reproductive Ultrasound) .
Chapter 20: Disorders of Human Ovulation: Sonog raphic Classification System 265
were observed in 200 cycles, (43.5%) (Table 20-2). Ana- (n=47); partial rupture of the follic le with a positi ve,
tomically abnormal ovulati on pattems were observed negative or retained cumu lu s (PRS: +, -, Re), 5.2 per-
in the following frequencies : a mature fo llicl e with a cent (n=24); delayed rupture pattern with a positive,
negative or retained cumulus oophorus (MF: -, Re), 23 .5 negative or retained cumulus (DRS: + , -, Re), 3.0 per-
percent (n= 108); luteinized unruptured follicle with a cent (n= 14); and afo llicular cyc les (AF), 0.7 percent
positive or negative cumulus oophorus (LUF : +, -), 13.9 (n=3). The overa ll incidence ofanatomica ll y abnormal
percent ( n=64 ); immature fol li cle with a positive, nega- ovulation patterns by ultra ound was 56.5 percent (n=
tive or retained cumulus (IFS: +, -, Re), 10.2 percent 260).
The cumulus oophorus was present in

59.8 perce nt (n=275) of the va riou s
cyc les. A negative cumulus was ob-
served in 36.3 percent (n= l67) anda
retained cumulus was observed in 3.9
percent ( n= 18). The empty follicles (a
negative cu mulus oophorus) underwent
severa ! forms of fo llicul ar rupture.
These incl uded mature fo lli cles, lu tein -
ized unruptured fo llicles, immature fol-
licles, partial ruptures, del ayed ruptures
and in afo lli cu lar cycles. The empty fol-
licl e was observed more frequently in
unruptured follicles, immature fol li cles,
partiall y ruptured fol li cles and in
afo llicular cyc les. The retained cumu-
lus was more commonly observed in the
Figure 20-16 : An example of an afollicular cycle. These four observations show partially ruptured fol licles, delayed rup-
a follicle reaching 1.37 cm in maximum size (right upper). A beginning corpus ture fo lli cles, and immature follicles .
luteum can be observed as a crescent shape inferior to the cystic structure (lower This working sonograph ic class ification
left) while the progesterone levels began to increase (2.3 ng/ml). Two days later
for the di so rders ofhuman ovul ation is
(lower right) , regression occured and the progesterone level clearly indicated
that a corpus luteum had formed. (From : Pope Paul VI lnstitute , Di vision of outlined in Table 20-3.
Reproductive Ultrasound).
Table 20-1: Distribution of Cycles Categorized by Ovulation Events

Observed by Serial Ovarian Ultrasound Examination - Subfertility Patients (N=460)
Disposition ofCumulus Oopherous
Follicle Description 1 + Re2 Totals
n % n % n % n %
Mature follicle (MF) 200 64 .9 100 32 .5 8 2.6 308 100.0
Luteinized unruptured follicle (LUF) 38 59.4 26 40 .6 n/a nl a 64 100.0
lmmature follicle syndrome (IFS) 21 44 .7 24 51 .1 2 4.2 47 100.0
Partial rupture syndrome (PRS) 7 29.2 10 41 .7 7 29.2 24 100.1
Afollicu larism (AF ) n/a 3 100.0 n\a 3 100.0
Delayed ru pture syndrome (DRS) 9 64 .3 4 28.6 1 7.1 14 100.0
TOTALS 275 59 .8 167 36.3 18 3.9 460 100.0
1. See text far description of the various patterns of follicular growth , development and rupture that were observed .
2. The cumulus could still be seen within the ovary alter the follicle had ruptured .
Table 20-2: The lncidence of Disorders of Human Ovulation

as Observed by Se rial Ultrasound Examination of the O vary 1
by T ype of D efect ( =460)
Percent of Occurrences
Norma Is Abnormals
Entity' n % n %
Automatically normal ovulation by U/S

Mature folli cle + cumulus oophorus (MF: +)2 200 43.5
Automatícally abnormal ovulation by U/S

Mature follicle , negative or retaíned cumulus 108 23.5
oophorus (MF: - , Re)
Luteínízed unruptured follícle syndrome (LUF : +, - ) 64 13.9
lmmature follicle syndrome {IFS: +, - , Re) 47 10.2
Partíal rupture syndrome (PRS: +, - , Re) 24 5.2
Delayed rupture syndrome (DRS: +, - , Re) 14 3.0
Afollicularism {AF ) 3 0.7
Subtotal 200 43 .5 260 56.5

1. See text for description of ultrasound technique.
2. In the parenthesis, the presence (+), absence (-) or retention (Re) of the cumulus oophorus is indicated.
Eissa, et al 13 and Ying, et a l 14 ha ve both repo1ted

Table 20-3 : Working Class ification System
the presence of abnom1al ov ul ation patte rns in in-
for the Disorders of Human Ovulation as
fe rtility pati ents w hen eva luated by ultraso und . In
D etermined by Serial Ultrasound Assessment
the series of Eissa, et al 13 , the overa] ] incidence was
58 percent in a stud y of 136 cycles and , in the se-
ries ofYing, et al , 14 the incidence was 54 percent.
l. Mature follícle (~ 1.90 cm ) (- or Re e .O.)
Thi s is simil ar to the 56.5 percent found in th e MF: - , Re
lnstitute 's much larger seri es. To our knowledge,
11. Luteínízed unruptured follícle (+ or-e .O.)
thi s is the first systemati ca ll y presented obj ecti ve LU F: +, -
classification of norma l ovul ation patterns and dis-
111. lmmature follícle (< 1.90) (+ , - or Re e .O.)
orders of human ovul ati on in patients with repro- IFS: +, - , Re
ducti ve abnormalities that is based on seri al fo lli-
IV. Partial rupture (:;: 0.75 cm rupture) (+ , - , Re e .O.)
cul ar ultrasound eva luati on. This has been a long i- PRS : +, - , Re
tudinal effort over many years and has cu lm inated
V. Delayed rupture (+, - , or Re C.O.)
in a worki ng classificati on for these disorder (see DRS: +, - , Re
Tab le 20-3). Thi s chapter detai ls an anatomic eva lu-
VI. Afollícularísm
ati on of follicu lar growth , development and rup-
AF
ture pattern s th at is useful for diagnostic purposes.
The luteini zed unruptured fo llic le synd ro me has,

by itself, been recognized as an ovu lato ry defect
for a number ofyears 15-n Unruptured fo lli c les are ob- nancies. The sa me assoc iation is also true fo r partia l
vious ly assoc iated with infertil ity: th ey do not re lease ruptures . In afo ll icular cycles, no pregnancies have been
the ovum and are, as a result, anovu latory cyc les (de- observed and del ayed ruptures are associated w ith en-
s pite the fact that most of these occur in women with docrin e abno rma liti es.
regular, norma l-appearing cycles).
Sonogra phi c visualization ofthe cumu lus oophorus was
We have also shown that imm ature fo llicles are ab nor- first reported in 1979 1.3 . Coulam and associates 20 de-
mal. While thi s has been suggested by oth ers 18- 19 , we scribed the empty fo llicle syndrome after observing that
have added observations which show that sma ll fo llicles so rn e follicular as pirates conta in ed no ova. S ubse-
are associated with a hi gh in cidence of ab norma l preg- quently, the endocrine profil e of the fo lli cul ar fluid in a
Chapter 20 : Disorders of Human Ovulation : Sonographic Classification System 267
patient who exhibited the empty follicle syndrome was Thus, serial ovarian fo lli c ul ar ultrasound has a d istinct
in ve tigated 21 . ln these studies, the patients were under- role to play in the diagnosis ofthe underlying di so rders
going ovu lation induction in a11ificial reproduction clin- ofhuman ovu lation, w hich lead to either primary or sec-
ics. Thus, the ovulati on cyc les were being stimulated o ndary infertility. This serial fa llicul ar ultraso und study
hormonally and are not directly parallel to the sponta- aids in assess ing underl ying probl ems of huma n ovul a-
neous cyc les that are the subject ofthis classification. tion and the adeq uacy of certain the rape uti c programs
far patients. Our hope is that this class ifi cati o n system
We ha ve previously described the sonographic appear- will be of assistance so that such studi es can be con-
ance ofthe empty fo llicle syndrome in patients evalu- ducted.
ated by both transabdominal and transvaginal ultrasound
89
· . Sorne authors have q uestioned the ability to define The data in these reports cha ll enge us to approach dif-
the cumulus oophorus 22 suggesting that the structure rep- ferently the eva luation of ovulation in a patient w ith an
resents artifactua l echoes, either side- lobe or slice-thick- infertility problem o r other reproductive a no ma ly.
ness artifact projecting into the anechoic fa lli cle orad- C learly we have, as a profession, been mostly interested
jacent sm a ll fo lli cles w hi c h are misinterpreted as in the question of"ovulation detecti on," in other words,
intrafa llicul ar (Figure 20-8) beca use of slice-thi ckness answering the question " Is this woman ov ulating?" To
a11ifact. After many years ofassessing ovarian fo ll ic les, that extent, we have used such techniques as the time-
we are now convinced that the cumu lu s oophorus can onored basal body temperature curve, endometria l bi-
be assessed and identified. The retention of the cumu- opsies, a sing le serum progesterone leve! ora urinary
lus oophorus has been previously identified 23 · 24 and is LH kit observation.
cons istent with what is reported here.
The data in this study suggest that what we need to be
What is most impressive by this overall evaluation is looking far are the vario us disorders of ovulation and
the high percentage of abnormal ovu latory events in not simply "ovulation detection. "These vario us disor-
menstrua l cyc les of patients with reproductive abnor- ders a re associated w ith both re lative and a bso lute lev-
malities. These disorders of ovu lat ion cannot be deter- els of infe11ility and a va ri ety of ab no rmal pregnancy
mined by a midlutea l phase progesterone leve!, a uri- outcomes (spontaneo us abo rti on , prematurity and ec-
nary test kit assessment far LH hormone, a basal body topic pregnancy). Objectively-identified diagnoses must
temperature curve, or an endometria l biopsy. Even diag- precede treatment programs. More work is needed in
nostic laparoscopy does not a ll ow far the serial eva lua- order to understand how to best correct the underlyi ng
tion ofthe ovary wh ich is essential to understanding the anatomic defects of ovu lation and their associated en-
anatomy ofthe ovu lation process and the diagnosis of its docrinopathy. This effort w ill hopefully help in deter-
disorders. mining effective treatments that will reso lve the infer-
ti li ty and prevent the ab normal pregnancies.
1. Hacke loer BJ , Fleming R, Robinson HP, Adam AH, Coutts, JR: 12. Sakamoto C: Sonographic Criteri a of Basic Changes in Human
Co rrel ation of Ultrasonic and Endocrino logic As essment of Endometrial Tissue. lnt J Gynaeco l Obstet, 1985 ; 23:7-12.
Human Fo lli cul ar Deve lopment. Am J Obstet Gyneco l, 1979;
13. Eissa M K, Sawers RS, Docker M F, Lynch SS, ewton J R: Char-
13 5:122-1 28.
acteristics and lncidence of Dysfu nctiona l Ovul ation Patterns
2. Fleischer AC, Dani ell J, Rodi er J, Lindsay AM, James AF, Jr: Detected by Ultrasound. Fertil Steril 1987; 4 7:603-6 12.
Sonographi c Monitoring of Ovarian Follicular Development. J
14. Ying Y-K, Daly DC, Rando lph JF, Soto-Al bers CE, Maier DB,
Clin Ultrasound, 198 1; 9:275 -280.
Schmidt CL, Riddi ck DH : Ultrasonographic Moni tori ng of Fol-
3. Lenz S: Ultrasoni c Study of Fo lli cu lar Maturation, Ovulation licul ar Growth for Luteal Phase Defects. Fertil Steril, 1987 ;
and Deve lopment of Corpus Luteum During Normal Men trual 48:433-436.
Cyc les. Acta Obstet Gyneco l Scand, 1985; 64: 15-1 9.
15. Marik J, Hulka J: Luteinized nruptured Follicle Syndrome: A
4. Queenan JT, O'Brien GD, Saines LM, Simpson J, Collin P, Subtle Ca use of ln fe rtility. Ferti l teril 1978; 29:270-274.
Ca mpbell S: Ultrasound Scanning of Ovaries to Detec t
16. Kerin JF, Kirby C, Morris D, McEvoy M, Ward B, Cox LW:
Ovulation in Women. Fertil Steril , 1980; 34: 99-105.
lncidence of the Luteini zed Unruptured Fo ll ic le Phenome non
5. itschke-Dabelstein S, Hacke loe r BJ, Stum1 G: Ovu lation and in Cycling Women. Ferti l Steril 1983; 40:620-626.
Co rpus Luteum Form ati on Observed by Ultraso nography. Ul-
17. Katz E: The Luteini zed Unruptured Fo lli cle and other Ovul a-
trasound Med Bic i, 1980; 7:33-39.
tory Dysfu nction . Fertil Steril, 1988; 50:839-850.
6. Konin ckx PR, Renaer M, Brosens IA: Origin of Peritoneal Fluid
18. Lew inthal D, Furma n A, Blankstein J, Corenblum B, Shaler J,
of Women : An Ovarian Exudati on Product. Br J Obste! Gynaeco l,
Lunenfeld B: Subtle Abnormalities in Folli cular Deve lopment
1980; 87 : 177- 183 .
and Horn1onal Profile in Women with Unex plai ned lnfertility.
7. Pi erson RA , Martinuk SD, Chi zen DR, Simpson CW: Ultra- Fertil Steril 1986; 46:833-839.
sonic Visua li zati on of Human Ovu lation. In Evers JHL and
19. Hai nes CJ, Emes AL : The Relationshi p Between Fol licle Di am-
Heineman MJ , Eds. From Ovulation to lmplantation. Elsev ier
eter, Fertilization Rate, and Microsco pic Embryo Quality. Fertil
Science Publishers, ew York, 1990; 73 -79.
Steril 199 1; 55:205-207 .
8. Hilgers TW, Dvorak AD, Tam isiea DF, Ellis RL, Yaksich PJ :
20. Coulam CB, Bustill o M, Schulman JD : Empty Foll ic le Syn-
Sonographic Definiti on of th e Empty Follicle Syndrome, J Ul-
drome. Fenil Steril 1986; 46: 11 53- 11 55.
tra sound Med, 1989; 8:411 -4 16.
2 1. Tsuiki A, Rose BI, Hung TT: Steroid Pro fil es of Follicul ar Flu-
9. Hil gers TW, Kimball CR, Keck SJ , Dvorak AD, Tarni siea DF,
ids from a Patient wi th Empty Follicle Synd rome. Fertil Steril
Yaks ich PJ: Assessment of the Empty Fo lli cle Syndrome by
1988; 49: 104-107.
Transvaginal So nogra ph y. J Ultrasound Med, 1992; 11 :3 13-3 16.
22. Za ndt-Stastny D, Thor en MK, Middl eton WD, Aiman J, Zion
1O. Hilgers TW, Daly KD, Hilgers SK, Prebi l AM: The CREIGHTON
A, McAsey M, Haroski: ln ab ility of Sonography to Detect lm-
MODEL Fertility Care™ System : A Standarized, Case Manage-
minent Ovulation . A J R 1989; 152:91-95.
ment Approach to Teaching. Book 1- Basic Teac hin g Ski lls. 2""
Edition. Pope Paul VI lnstitute Press. Omaha , NE, 2002. 23 . Cra ft 1, Shelton K, Yovich J, Smith D: Ovum Retention in the
Human. Fertil Steril , 1980; 34:537-54 1.
11 . Hil gers TW, Abraham GE , Cavanagh D: Natural Fami ly Pl an-
ning l. The Peak Symptorn and Estimated Time of Ovulation. 24. Stanger JD, Yov ich JL: Fai lure of Human Oocyte Re lease at
Obstet Gyneco l, 1978; 52 :575-582. Ovul ati on. Ferti l Steril , 1984: 4 1: 827-832.
Endocrine Validation of the
he previ ous chapter 1 described an anatomi c c lass i-

T fi cati on system, based on sonographic findin gs, fo r
the diagnos is of va ri ous di sorders of human ovul ati on.
T he CrMS , whi ch specificall y obse rves the externa !
presence or absence of a vul va r mucus di scharge would
illustrate the progress ion of the events of th e cyc le as
The second of thi s seri es of three chapters questions fo ll ows: after menstruati on, there is a peri od of time
w hether or not fun cti onal or endocrine a bn ormaliti es (usuall y severa! days) in w hi ch there is no di scharge of
are assoc iated w ith the various sonographi ca lly estab- mucus (dry days) ; at the concl usion o f these days, a
li shed anatomic di sorders of ovul ation. A number of re- mucus discharge that is characteri tica ll y sticky or tacky
ports have suggested th at a con-e lation exists between in consistency begins and progresses to become clear,
th e norm al and abnormal process of human ovul ati on stretchy or lubri cati ve; th e last day on w hi ch the mucus
and certain endocrine parameters2• 12 . The purpose of thi s is c lear, stretchy and/or lu bri cati ve is considered the
chapter is to present data correlating the circul ating pre- Peak Day; fo llowing the Peak Day there is a dramati c
and post-ovul atory ova rian steroids to the various ana- change bac k to a mucus pattern th at is either sticky or
tomi c di sorders of human ovul ati on th at have been di- tacky aga in or dry; thi s begins the post-Pea k phase of
agnosed by seria l fo lli cul ar ultra ound . the cyc le. T he con-e lati on of the Peak Day to the timing
of ovulatio n has been extensive ly studied. Ovul ati on
Patie nts enro lled in thi s study unde rwent serial fo lli cu- occurs on the Peak Day ± 2 days in 95.4 percent of
lar ultraso und assess ment as desc ribed in the prev ious cyc le . 14 Thus, the observati on ofth e Peak Day is a good
chapte r. 1 During the same cyc le as thei r fo ll icul ar ultra- c lini ca l indicator fo r the timing of ovul ation and the
sound assess ment, they trac ked their fe rtili ty by chart- beginning of the post-Peak ph ase- or lutea l phase- of
in g the ir vul va r mu cus di sc harge pattern s w ith th e the menstrual cyc le. The presence of the mucus cycl e
CREIGHTON MODEL FertilityCare™System (CrMS) . 13 leading up to the Peak Day is a function of the preovu-
In coordinati on with the ir fo lli cul ar ultrasound assess- latory effect of estradi ol on the endocervix as ovulation
ment and fertili ty trackin g, the pati ents also underwent approac hes (see Chapter 15).
a targeted serum eva luation for estra d io l - 1 7 ~ (E 2, es-
tradi o l) and progesterone ( P). The patients underwe nt a systemati c eva luation of se-
rum estradio l and progesterone w hil e they we re under-
269
270 The Medica! and Surgical Practi ce of NaProTECHNOLOGY
going serial fo llicul ar ultraso und assess ment fo r the pres- For progesterone seru m ana lyses, we used the DPC
ence or absence of an anato mica lly identifiab le ovul a- Coat-A-Count so lid phase 125 I radi o immu noassay
ti on di sorder and whil e they were trackin g the ir fe rtility ( RIA) kit. T he Coat- A-Count progesterone procedure
w ith the CrMS . Blood was drawn genera ll y on day 5 of is a so l id ph ase RLA proced ure where in labe led 125 l-
the cycle. Approx imately six days prior to the Peak Day, progesterone competes with progesterone in the patient's
the estradiol leve l was measured every other day through sample fo r antibody sites over a fi xed time. The anti-
Peak + 2. In thi s way, a peak leve! of estradi ol co uld be body sites in the patient's sampl e are imrn obi lized to
identified and three or fo ur values in the estradi o l pro- the wa ll of a po lypro pylene tube. The supernatant is
file could be obta in ed (the peak leve! of estradi o l is a l- then deca nted and thi s te rminates the competition be-
ways the leve! just prior to its fa ll before the ti me of tween the 125 1-labeled an ti gen (progesterone) and the
ovu lation). During the post-Peak phase of the cycle se- patient progesterone . The tu be (bo und fract ion) is then
rum p rogestero ne and estradi ol were measured 3, 5, 7, 9, counted . The sensitivity of th is RIA method is 0.05 ng/
and 11 days after the Peak Day (P+ 3, P+5, P+ 7, P+9, and mL. Within- ru n precision averaged 7 percent and the
P+ 11 ). These data were then co ll ated and eva luated fo r between- run prec ision is 8 percent.
the previously described ovulation di sorders 1: MF: -; LUF:
+, -; IFS: +, -, Re; PRS : +, -, Re; AF; and DRS: +, -, Re. A contro l group was selected by identi fy ing those cycles
in which a mature fo ll icle was observed by ultraso und
(> 1.90 cm mean fo ll icular di ameter). Th e fo ll ic le was
lmmunoassay Method ------~ pos iti ve fo r the cumu lus oophorus and it underwent
complete ruptu re (an anatomi ca lly normal ovu lation by
Analyses for estradi ol and progestero ne were perfo rmed ultraso und). The estradi o l and the progestero ne leve ls
in serum fro m blood that was co ll ected in red to p fo r these cycles (N=57) we re measured in the same way
vacutainer tubes. A li analyses were perfom1ed in du pli- and used as horm onal contro ls.
cate. For estradi o l analyses, the Di ag nostic Prod uct
(DPC) doub le antibody radi oimmun oassay (RI A) kit For each ofthe gro ups, a 3-va lue sum of the periovu -
(Di agnostic Products Corporation, Los A ngeles, CA latory estradiol profil e was calcul ated by adding the Peak
90045) was used . The procedure is a sequenti al RIA E2 -2 days, the Peak E 2 and the Peak E2 +2 days levels
procedure in w hi ch the patient's sampl e is preincubated (F igure 2 1- 1). The 4-va lue sum was obtained by add-
with anti-estradi o l anti serum . 125 1-labe led estradi o l is ing the Peak E 2 -4 day estradi o l leve! to the 3-va lue
added and competes with estradio l in the pati ent sample sum. R espective 3- and 4-va lue means we re calc ulated
fo r antibody sites . After incubating fo r a fi xed ti me, the by di vid ing the 3-value sum by 3 and the 4-val ue sum
bound fract ion separates fro m the free fract ion, and the by 4. Tbe surn and mea n of th e post-Peak progestero ne
antibody- bound fraction is precipitated and counted. The profil e was obtained by adding the P+3, P+5, P+7, P+9
sensiti vity ofthi s method is 0. 14 ng/dl. Withi n-run pre- and P+ 11 leve Is and the mean was ca lcu lated by di vid-
cision is 3.6 percent w hil e betwee n-run prec ision ave r- in g the sum by 5.
aged 1O percent.
Normal Controls . - - -
Periovulatory E2 Profile with
MF:- 11- - - .. Various Ovulation Disorders
LUF _ _.
IFS ... - -+
PRS a - ·- - •
AF X----- iC
DRS ,.. - ·- •
12.8
PEAK E2 PE~~ E2 PEAK E2 PEAK E2

-4 +2
Days ± Peak E2 Value
Figure 21-1 : Periovulatory estrad iol levels in patients with va rious anatomically
identified (th roug h serial follicu lar ultrasound assessment) ovulation disorders.
Ch apter 21: Disorders of Human Ovulati on: Endocrine Validation of the Sonogra phic Classification System 271
Perlovula tory E2 Sums Stati sti ca l compari sons we re made betwee n th e control
Patients with Various
52.0
Ovulation Disorders gro up a nd the gro ups fo r each ovul ati on di sorder. A li
47
(3 Va lues)
44 . 1 statisti ca l co mpari sons used Stude nt /-test w ith th e as-
sistance ofthe NCS S 2000 bi ostati stica l computer pack-
age.15 F irst, a point-by-po int compari son was made be-
29.3
twee n the gro ups.for each of th e po ints o n th e hormone
curve. T hen, the mean of the sum s and th e mean of the
means ofthe 3- and 4-va lue pe riovulatory estradiol pro-
fil es we re also compared fo r each g roup . S im ilarl y, the
mean of the sum s and the mean of the means of the 5-
value post-Peak proges terone profil es were also co m-
ON~S .ci~~5 ~ ~ ~
AF
~
Peri-ovulatory E2 Sum (3 values) pared fo r each of th e indi vidual ov ul ati o n d iso rders to
the contro l gro up .
Figure 21 -2: The periovulatory E2 sums (mean of th e sums)
for patie nt with various anatomi ca lly identifi ed ovul ati on
disorders (using three E2 va lues). The periovul atory estradio l profíl e fo r the control group
an d the vario us ovul ati on di sorders is shown in Figure
2 1-1 . For ali of the test groups except the delayed rup-
ture group (n=8), the estradiol profí le was at one or more
of the points significa ntly lowe r than in the contro l group
Periovulatory E2 Sums
59.3 Patients with Variou s (Student /-test). The mature fo lli cle with a negati ve cu-
54 .8 Ovulation Disorders
54 . 1
512 (4 Va lues) mulus (MF: -) (n= 2 1) had a decreased Peak E2 leve!
44.2
(8=2 1. 5 ng /dL ; p=.0063) . In th e lute ini zed unruptured
fo lli cle gro up ( LUF: +, -) (n= 15), the Peak E 2 -4 (8= 7 .3
ng/dL; p = .043 0) and the Peak E2 leve ls (8=2 l .3 ng/dL ;
29.1
p=.O123) were s ig nifi cantly decreased. Fo r the imm a-
ture fo llicl e gro up (I FS : +, -, Re) (n = 22) , three peri-
ovul ato ry estradio l leve ls we re s ignifí cantly decreased.
These inc luded the fo ll owing va lues: Peak E 2-4 (8= 7. l
ng/d L, p=.0054 ), Peak E2-2 (8= 12.3 ng/dL, p=.0057) ,
DAS MF:- IFS .__l...U.E... ...fB.S_...
NS .0583 NS l..JlliZJ LQQilJ and Peak E 2 (8=22 .9 ng/dL, p = .0370). In the partial rup-
Peri-ovulatory E2 Sum (4 val ues)
ture g ro up (n=8) , three points o n the c urve were a lso
Figure 21-3: The periovulatory E2 sum s (mean of the sums) s ignifí cantly decreased. These inc luded the fo llow ing
for patients with various an atomi ca lly identified ovul atio n
disorders (using fou r E2 va lues).
va lues: Peak E2 -4 (8= 6.6 ng/dL, p = .0389), Peak E 2 -2
(8=8.9 ng/dL, p = .001 ), a nd th e Peak E2 leve! (8= 16.6
ng/dL, p=.0002) . Fina ll y, in th e afolli cul ar group (AF)
(n=4), pe ri ovul ato ry estradi o l was a lso suppressed . A li
of th e leve ls on the pe ri ovul atory estradio l curve we re
Perlovulatory E, Means Perl ovulatory E, Means

17.9
17.3 Patients with Various Ovu lation Oisorders Patien ts with Varlous Ovulatlon Oisorders
(3 Values) (4 Values)
::J' 15.8 :J" 15.8
15.3 o
~ 14.7 14.8
15 di 15
.s .s 13.7 13.6
12.8
e 12.0
"'"'
:¡ 11 .1
9.8
w" 1
~
o 7.3
1ií
:;
>
'i' 5
-~
o.
Nonnat DAS IFS MF:- LUF ,...fBa... AF Normal DAS MF:- IFS LU F ,...fBa... AF
P value NS .0688 [QjjJ [0064]LQQQgJ 1 .0003 1 p value NS .0581 NS ~ LQQ1ª.) l .0046 1
Peri-ovulatory E2 Mean (3 Valu es) Peri-ovulatory E2 Mean (4 Values)
Figure 21-4: The periovulatory E2 means (mean ofthe means) Figure 21-5 : The periovulatory E2 means (the mean of the
in patien ts with va rious anatomically identified ovu/ati on mean s) in patients with va rious anatomica lly identified ovulation
disorders (using three E2 va lues). disorders (using four E2 va lues).
sign ificantly decreased in this group . These included significan t. The sums of 4 values were also lower fo r
the fol lowing va lues: Peak E2-4 (8=3.8 ng/dL, p =.0047), each of the six categories of ovu lation disorders, but
Peak E2-2 (8=9.0 ng/dL, p = .00 12), Peak E2 (8= 15.1 ng/ only the LUF, PRS and AF groups reached statistical
dL, p = .0013), and Peak E 2 +2 (8=5.2 ng/dL, p = .O l 74). significance.
These data are graphicall y displayed for the control
group and eacb ofthe ovulation disorders in Figure 2 1-1 . When the estrad iol means for 3 and 4 values were com-
pared, a similar pattem was observed. lo both compari-
The periovulatory estradiol sums (3 and 4 values) and sons , the estradio l meaos for each ofthe ovu lation dis-
means (3 and 4 va lues) for the various ovulation disor- orders was decreased from the control group . However,
ders compared to the same levels for the contro l group when comparing the 3-value means, only the MF: -,
are shown respectively in Figures 21-2 through 21-5 . LUF, PRS and AF groups were lower with statistical
The sum s and means for the control group (based on significance.
the assessment of e ither 3 or 4 values) are shown with
the sums and means for each ofthe ovulation disorders The post-Peak progesterone profiles for the normal con-
a long with their respective p-values. For the sum s of3 trols and the various ovu lation disorders is shown in
values and 4 va lues, each of the disorders had lower Figure 21-6. For ali ofthe groups, the progesterone pro-
sum s than the contro l group. However, on ly the 3-value file was lower than the contro l group and ata num ber
sums for MF: -, LUF, PRS and AF were statistica lly ofpoints, this had high statistica l sign ifican ce. For the
20 ---~~~~~~~~~~~~~~~~~~~~~~~~~~
Post-Peak Progesterone Profile in Patients

Normal Controls ___... with Various Ovulation Disorders
MF:- lt- - - ..
::::¡- LUF .--
.§ IFS +- - -+ 15.7
.s 15 PRS
AF
• ---·•
• ----- • 13.6
Qi DAS ~ - - · - ·•
>
Q)
_J
Q)
e
e
Q)
10
üí
Q) 8 .1
O>
e
c..
E
2
Q)
(/)
P+3 P+S P+7 P+9 P+11

Days Post-Peak
Figure 21-6 : The post-Peak progesterone profiles in patients with various
anatomically identified ovulation disorders.
1 4~----------------------,
Post-Peak Progesterone Means in Patients
Post-Peak Progesterone Sums in 12.3 with Various Ovulation Disorders
61 .2 ::J' I
Patients with Various Ovulation Oisorders (5 Vatues)
(5 Valu es) ~e 10.7
10.0
51.2 so.o - 1
E 9.3 9.2
45 4 45 4 ::>
U)
7.6 7.6
36.4
33.3
~ ~ ~ ~ J<L~1I
MF:- DAS PRS IFS LUF AF
l<.€&11 J.oos9I J.oos1I 100131 J.001 I J<.0001\ l<.0001J
Post-Peak Progesterone Sums (5 Values) Mean of Post-Ovulatory Progesterone Levels
Various Ovulation Disorders
Figure 21-7 : The post-Peak progesterone sum (mean of the Figure 21-8 : The post-Peak progesterone means (mean of
sums) in patients with various anatomically identified ovulation the means) in patients with various anatomicall y identified
disorders (using five post-Peak p-va lues). ovulati on disorders (using five post-Peak p-values).
Chapter 21 : Dis orders of Human Ovulation : Endocrine Va li dati on of the Sonographic Classification System 273
M F: - gro up (n=71 ), the signiticantly lower points were The growth and development ofthe develop ing fol licl e
at P+7 (8=12.9 ng/mL, p=.0048), P+9 (8=9.7 ng/mL, has been shown to be associated with increasing leve ls
p=<.000 1) and P+ ll (8=5.0 ng/mL,p=. 0001). Forthe of estradiol. 2 ·9 · 16 Conditions such as the luteinized
LUF group (n=54), ali ofthe points were signiticantly unruptured fo llicle syndrome have also been shown to
decreased. These were the fo ll owi ng: P+3 (8=6.6 ng/ be assoc iated with abnormally functioning corpora lutea
mL, p=.0003), P+5 (8=8.7 ng/mL, p=.0001), P+7 (8= as a se sed by measuring lutea l phase production of
9.3 ng/mL, p=<.000 1), P+9 (8=6.9 ng/mL, p=<.0001), progesterone. 17·18 In such cases, the production of proges-
and P+ 11 (8=4.9 ng/mL, p=.0002). For the immature terone has been shown to be decreased. To our know l-
fo lli cle group (n=36), ali progesterone levels were de- edge, this is the first study that has eva luated the pro-
creased sign iticantl y. These were the fo llowing: P+3 (8= duction ofovarian steroids and correlated it with an ob-
7. 1 ng/mL,p=.0031), P+5 (8= 10.6 ng/mL,p =<.0001), jective classitication ofspecific anatomic defects in hu-
P+7 (8= 10.8 ng/mL, p=<.0001 ), P+9 (8= 10.2 ng/mL, man ovulation as observed by serial follicu lar ultrasound.
p=.0009) and P+ 11 (8=5.6 ng/mL, p=.O 122). The par-
tía! rupture group (n=22) was simi larl y decreased with In fact, the current study correlates the function ofthe
the fo ll ow ing va lues being statisticall y signiticant: P+5 developing follicle and its subsequent corp us luteum
(8 = 11 .4 ng/ mL , p=.O 108) , P+7 (8 = 1O.7 ng/ mL , with the previously described anatomic disorders of
p=.0005), P+9 (8=8.9 ng/mL, p=.0004) and P+ 11 (8= ovu lation. The study used an anatomically normal fol-
5.8 ng/mL, p=.0234). The afo lli cu larism group (n= 1O) li cu lar growth , maturation and rupture (mature follicles
had decreased progesterone levels including: P+5 (8= with a cumulus oophorus and comp lete rupture) as a
9.0 ng/mL,p=.0008), P+7 (8=8.3 ng/mL,p=.0002), P 9 ba eline to which these endocrine comparisons were
(8=6.1 ng/mL, p=<.0001), and P+ ll (8=3.8 ng/mL , made. The ana lysis clearly show that each of the ana-
p=.0039). And final ly, the delayed rupture group (n= 12) tomic defects is associated with varying degrees ofen-
had the fo ll owing decreased P va lu es that were statisti- docrine dysfunction. The most dysfunctional periovu-
ca ll y significant: P+7 (12.5 ng/mL,p=. 003), and P+ l I latory estrad iol profiles are observed in those patients
(4.4 ng/mL,p=.0069). who have exhib ited a parti al ru pture or an afo llicular
cycle. Less prominent and yet sti ll highly significant
The post-Peak sums and means of 5 progesterone va l- estradiol suppress ion was observed with (ordered from
ues for the various ovulation disorders compared to the maximum to mínimum degree) the immature follic le,
same leve ls for the control group are shown in Figure the luteinized unruptured fo lli cle and the manire fol -
21-7 and 21-8. The sum and mean for the contro l group licle with a negative cumu lus oophorus (the empty fol-
are shown with the same for each ofthe ovulation dis- li cle). The only one of the six disorders that did not
orders a long with their respective p-va lues. In the case show a signiticant periovulatory estradiol dysfunction
of the post-Peak progesterone sums and means, the lev- was the delayed rupture pattern.
e Is for each ofthe ovulati on disorders was signiticantly
decreased from the control gro up . This was further eva luated using the sums and the means
ofthe periovulatory estradiol profile. This gives an es-
The post-Peak estrad iol sums and means were simi larly tímate of the vo lume of estrad iol produced during this
evaluated. The co ntrol mean estradio l levels (n=54) period of assessment as opposed to a point in time as-
were: P+3 = 8.8 ng/dL, P+5 = 10.8 ng/dL, P+7 = 12.0 sessment.19The fo llicular dysfunction was observed and
ng/dL, P+9 = 12.0 ng/dL, and P+ 11 = 9.8 ng/dL. There found to be the most prominent in the MF: -, LUF, PRS
were on ly a few ofthe study group leve Is that were ob- and AF patterns. With the immature follicle, the sums
served to be sign iti cantl y different. These included: and means were consisten ti y decreased and did approach
MF: -, P+3 = 10.0 ng/dL (p<.05), P+9 = 10.5 ng/dL statistical signiticance suggesting that ifthe samp le size
(p<.05), P+ l l = 7.7 ng/dL (p=<.025); LUF (+, -): P+3 was larger, it eventua ll y may be observed as statisti-
= 12.8 ng/dL (p=<.05) and P+9 = 11.8 ng/dL (p=<.05); ca ll y signiticant. Aga in , the DRS pattern did not show
PRS: P+3 = 10.8 ng/dL (p<.05); and AF: P+ 7 = 9.1 ng/ any signiticant difference when eva luating the sums and
dL (p=<.05) and P+9 = 8.2 ng/dL (p=<.025). means justas it did not when eva luating the point-by-
point protiles.
The only post-Peak estradiol profile sum th at was sig-
nificantly decreased was observed in the AF group, The subsequent function ofthe corpus luteum (as evalu-
8=42.8 ng/dL (w ith the contro l sum = 53.2 ng/dL, ated with serum progesterone levels) was even more
p=<.025). o post-Peak estradio l means were signiti- dramatically decreased than the periovulatory estradiol
cantly different than the contro ls. assessments. In fact, in each ofthe six anatomical ly iden-
ti fied ovu lation disorders , so me degree of disturbance
was identified in the fu ncti on ofthe corpus luteum. The are very significan t beca use ofthe size of the study and
worst of these (i.e., the most suppressed lutea l funct ion it correlati on with obj ective, sonographically defin ed
as assessed by timed progesterone assessment) were the anatomic defects in ovu lation. This assessment prov ides
LU F, IFS, PRS and AF pattems. But, in thi s case, the the cl ini cian and the resea rch investigator with an ob-
MF : - and DRS pattern s also howed a stati stica lly ig- jecti ve means to eva luate, class ify and diagnose the dis-
nificant decrease in lutea l phase progesterone produc- orders of human ovul ati on.
tion. The sums and means of the progesterone pro fi le
confirmed these findings. Somewhat sw-pti singly, the luteal In the first repo1t in thi s seri es, 460 separate spontane-
phase estradiol levels revealed on ly minimal degrees of ous menstrual cyc les were eva luated sonographica lly
dysfunction when compared to that fo und wi th periovu- andan objective system fo r classifying the di sorders of
latory estradio l or lutea l phase progesterone production. ovu lation was presented. The fo ll owing chapter identi-
fies and describes the cycles in whi ch pregnancy did or
The fi ndings in thi s study revea! that there is a defined did not occu r in this grou p. Th rough thi s assessment,
fun ctional disturbance in ali of the six anatomic disor- these di sorders are clini call y documented and validated.
ders of ovulation detected and classified through ul- The second report in th e series presents and describes
trasound assessment. This di sturbance appears to be a the fun ctional (endocrine) abnormaliti es that are asso-
fo lli cul ar dysfun cti on fo ll owed by a lutea l dysfun ction. ciated with these disorders. The anatomi c di sorders of
While it has been thought that abnormal fo lli cul ogenes is ovul ati on are clea rl y shown to be associated wi th sig-
is fo llowed by abnormal luteogenesi ,20 these fi ndi ngs nifica nt fu nctional abnorm aliti es.
1. Hilgers TW: A Sonograph ic Class ification System for Disorders 1O. Bateman BG, Ko lp LA , Nunley WC, Thomas TS, Milis SE: Ferti l
of Human Ovulation. In: Hilgers TW: The Medica l and Surgical Steril 54: 793-798, 1990.
Practice of NaProTECHNOLOGY, Chapter 18, Pope Paul VI ln-
11. Sc heenjes E, te Ve lde ER, Krerner J: lnspection ofthe Ovaries
stitute Press, Oma ha, NE, 2004.
and Steroids in Serum and Peritoneal Fluid at Various Time ln-
2. Hac kel oer BJ , Fleming R, Rob inson HP, Adam AH, Coutts JRT: terva ls after Ovulation in Fertile Women: lmpli cations for the
Corre lati on of Ultrasonic and Endocrino log ic Assessmen t of Luteinized Unru ptured Fo llicle Syndrome. Fertil Steril 54 :38-
Human Fol li cular Deve lopment. Am J Obstet Gynec 135: 122- 41 , 1990.
128, 1979.
12. Kupes ic S, Kurj ak A: Th e A sessment of ormal and Abnormal
3. Polan ML, Totora M, Ca ldwe ll BV, DeCherney Al-1 , l-l ase ltin e Luteal Function by Tra n vagi nal Co lor Doppler Sonography. Am
FP, Kase : Abnormal Ovarian Cycles as Diagnosed by Ultra- J Obstet Gyneco l Reprod Biol 72 :83-87, 1997 .
so und and Serum Estradi ol Levels. Fertil Steril 37 :342-247,
13. Hil gers TW, Daly KD, Hilgers SK, Prebil AM: The CREIGHTON
1982.
MODEL Fertility Care'" System : A Sta ndardi zed Case Manage-
4. Marrs RP, Varqyas JM , Marc h CM: Correla ti on of Ultrasoni c rnem Approach Lo Tcachin g. Boo k 1 - Bas ic Teachin g Ski ll s.
and Endocrin ologic Measurements in Hum an Menopausal Go- Pope Paul VI lnsti tute Press. Omaha, NE, 2nd Ed ition , 2002
nadotropin Therapy. Am J Obste! Gyneco l 145:4 17-42 1, 1983.
14. Hil gers TW, Abraham GE, Cavanagh D: Natura l Farn ily Plan-
5. Petsos P, Chandl er C, Oak M, Ratcliffe WA, Wood R, Ander on nin g 1: The Pea k Symptom and Estimated Tim e of Ovu lation.
DC: The Assessment of Ovulation by a Com binati on of Ultra- Obstet Gynecol 52:575-582, 1978.
so und and Deta iled eri al Hormone Pro fil es in 35 Women with
15. CSS 2000 Statist ical System fo r Windows. 1CSS. Raysv ill e,
Long-standing Unexp lained lnfertility. Cl in Endocrino! (Oxf)
tah, 1998.
22 :739-75 1, 1985.
16. Andreotti RF, Thornpson Gl-1 , Janowitz W, Shapiro AG, Zu mer
6. Len z S: Ultrasonic Study of Follicular Maruration , Ovulation
R: Endovaginal and Transabdomin al Sonography of Ovarian
and Development of Corpus Luteum During onnal Menstrual
Follicles. J Ultrasound Med 8:5 55-560, 1989.
Cyc les. Acta Obstet Gynecol Scand 64 : 15-1 9, 1985.
17. Hamilton CJC M, Wetze ls LCG, Evers JL !-1 , Hoogla nd l-I J,
7. Tsu iki A, Rose BI, Hung TT: Steroid Pro fi les of Fo ll icu lar Flu-
Mu itjens A, de Haa n J: Foll icle Growth Curves and Hormonal
ids from a Pati en t with Empty Follicl e Syndrome. Ferti l Steril
Pattern s in Patients with the Lu teini zed Unruptured Fo ll icle
49: 104- 107, 1988 .
Syndrome. Fertil Steri l 43:54 1-548, 1985.
8. Finn MM , Gos ling JP, TalIon DF, Joyce LA , Meehan FP, Fottrell
18. Hamilton MPR, Fl emin g R, Co utts JRT, Macn aughton MC,
PF : Foll icu lar Growth and Corpus Luteum Function in Women
Wh itfield CR: Luteal Cysts and Unex pl ained ln fe rtili ty: Bio-
with Unexplained lnfertility Monitored by Ultrasonography and
chem ica l and Ultrasonic Evaluation. Fertil Steri l 54:32-37, 1990.
Meas urern en t of Dai ly alivary Progestero ne. Gyneco l
Endocrino! 3:297-308, 1989. 19. l-luang K, Muechler EK, Bonfi glio TA : Follicular Phase Treat-
ment of Luteal Phase Defect with Follicl e-Stimulating l-l onnone
9. Kurjak A, Jurk ov ic D: Ultraso nic Monitorin g of Follicular
in ln fertil e Women. Obstet Gynec 64:32-36, 1984.
Growth and Ovulation in Spontaneous and Stirnul ated Cyc les.
In: Kurjak A, Ed. Ult raso und and ln fertili ry. Boca Raton: CRC 20. DiZerga GS , Hodgen GD: Luteal Ph ase Dysfu nct ion lnfertiliry:
Press 89- 124, 1989. A Seque! to Aberrant Fo lli cul ogenes is. Fertil Steril 35:489-499,
198 1.
Clinical Validation of the
uring the course ofa serial ovarian ultraso und ex- fo r the occurrence of such events.
D ami nat ion to determine the ovu latory status ofan
indi vidua l woman, the cyc les may result in a pregnancy. The pregnancies occurred in spontaneou s ovu latio n
There are also many times in whi ch pregnancy <loes not cycles (unmedi cated) and in stimul ated cycles (medi-
occur. By recording those events and fo ll ow ing through cated). A comparison of these two groups was made. ln
the pregnancies, one can relate both nom1al and abnor- additi on, the occurrence of pregnancies and their out-
ma l reproducti ve outcomes to its origin s at the time of comes could be rel ated to the class ifi cation ofthe ovu -
ovu lation or conception. From the e observati ons, it is lation pattem.
also possib le to determine and substanti ate the ex ist-
ence of ovulation-related di sorders. This chapter rev iews The eva luation of pregnancies and their outcomes was
the 16-year hi story of experience with follicu lar ultra- then subjected to statisti ca l analys is. This included Stu-
sound and the cycles in which pregnancies did or did dent /-test, ch i-sq uare, and Fisher exact test. Data analy-
not occur, and it specití ca ll y relates thi s review to the sis was perfo rmed with the ass istance ofthe CSS 2000
prev iously described class i fication. Statistica l System 4 and GraphPad Prism.5
Pati ents who underwent ova ri an fo lli cul ar ultrasound A total of 1,8 l 8 di agnosti c fo lli cul ar ultrasound series
eva luation at the Pope Paul VI lnstitute for the Study of were used in this sn1dy. No pregnancy was observed
Human Reproduction from November 1985 through 1,748 cyc les (96. 1%). Pregnancy did occur in 70 cyc les
May 200 1 were entered in to thi s study. During the course (3 .8%). Ofthese 70 pregnancies, 35 occu rred in cycles
ofthese exam inations, whi ch have been prev iously de- in which ovul ation-induction protoco ls were being used
scribed, 1.2 .J a group of patients ach ieved pregnancy dur- and 35 pregnancies occurred in spontaneous cycles. No
ing the cycle ofthe ultrasound series . The data on the pregnancies were observed in patients with luteini zed
establi shm ent ofthe pregnancy and its outcome gener- unruptured fo lli cles or afo lli cul ar cyc les (Table 22-1 ).
ated were descriptively related to the prev iously estab-
1ished class ití cation of ovul atory di sorders. Ali preg- Between the two groups of pregnancy cyc les, sponta-
nancies were identitíed because ali indi vidua ls were neous ver us medicated, there was no signi ficant dif-
patients of the Pope Paul VI lnstitute and were fo llowed ference in the patients' age, the grav idity, the pari ty, the
275
276 The Medical and Surgical Practice of NaProT ECHNOLOGY
number of previous spontaneous abortions, the day of

the cyc le on wh ich the fo llicul ar rupture occurred, and Table 22-1: Pregnancies during Cycle
of Ultrasound Assessment of Ovulation
the size ofthe cumu lu s oophorus. There was, however,
(N=l ,818 1)
a statist ically significant increase in the size ofthe ova-
rian fo llicle in those cycles which had been medicated
(had received ovu lation-inducti on medications). The
Pregnanies in spontaneous cycles 35
mean fo llicular diameter in spontaneous cycles was 2. 11
+ 0.25 cm (n=35) and in the medicated cycles it was Pregnancies in medicated cycles 35
2.26 + 0.33 cm (n=35) (p=.O 189; paired /-test). Pregnancies in luteinized unruptured fol licle cycles O
The distribution of ali pregnancies observed in the 1,818

Pregnancies in affollicular cycles o
cyc les of observation is described in Table 22-2 by th eir No pregnancy 1,748
relations hip to the prev iously described classification Total 1,818
system. ln 56 of the 70 pregnanc ies (80 .0%), the fo l-
1. The total number of follicular ultrasound studies com pleted from
licle was mature (> l .90 cm MFD) and, in l I ofthe preg- 1985-2001.
nancies ( 15 .7%) the follicle was imm ature (< 1.90 cm).
There were 3 pregnanci es that occurred in cycles where
the fo llicle onl y partially ruptured (and 2 of these oc-
curred in fo lli c les that we re a lso < 1.90 cm). One preg- ture in those pati ents who achieved a pregnancy that
nancy was observed in a delayed rupture cyc le. ended in ectopi c pregnancy was 1. 80 + .03 cm. When
compared to those pregnanci es that went to full term ,
A tendency toward smaller follicles was observed in the mean fo lli cul ar size was 2.2 1 + 0.27 cm, th e differ-
the spontaneous pregnancy cycles (8 of 35, 22.8 per- ence was statistically significant (p=.O 182; /-test) (spon-
cent we re less than 1.90 cm) as opposed to those cyc les taneous an d medicated cycles combined). In additi on,
in wh ich ovulation-inducti on medications were used (5 the mean fo il icular size for those pregnancies that ended
of 35 , 14 .3%). Larger follicles (>2.50 cm) were ob- in preterrn birth was 1.94 + 0.28 cm as opposed to 2.2 l
served more commonly in the medicated cyc les (5 of + 0.27 cm for full-terrn pregnancies (the difference is
35 , 14.3%) and we re not observed at ali in th e spon ta- statisti ca ll y significant; with p=.0268, /-test).
neous cycles (O of 35) . This finding was statistically
signifi cant using chi-square analysis with chi=5.538 and Pregnancy was observed to occur in sorne cycles where
p=.O186 and usi ng Fisher exact test with p=.0359. a cumulus ooph orus was not identifi ed (n=9) (Table 22-
2). The inc idence of pregnancies occurring in cycles
The pregnancy outcome by size ofthe fo lli clejust prior where a cumulus co uld not be observed was hi gher in
to rupture for 69 of tbe pregnanc ies (in one cycle the spontaneous cyc les (n=6 of3 5, 17. 1%) than it was in
outcome was unkn own) is shown in Tab le 22 -3. Ofspe- the medicated cyc les (n=3 of35 , 8.6%) but this was not
cial interest, 8 out of tbe 13 pregnancies that occurred statistica ll y significant. The ove ra ll pregnancy rate in
with a fo lli cle less than 1.90 cm (61.5%) hada n abno r- those cyc les with a negati ve cumulus oophorus is shown
mal outcome , such as spontaneous abort ion (n=3), pre- in Table 22-4. This rate was 2.6 percent in those cycles
mature birth (n=3) an d ectopi c pregnancy (n=2). The where the cumulus oophorus could not be identified and
incidence of ab normal pregnancy outcomes w ith a fo l- 5.9 perce nt in tho se who had a pos iti ve cu mulu s
licle measuring greater than 1.9 cms, on the other hand, oophorus. The difference is statistically significant with
was onl y 19 .6 percent (p=.003 , chi-squa re ana lys is and ch i- sq uare = 5.824 (p=.O 15 8) and Fisher exact tes t
p=.004 7 by F isher exact test). (p= .0 137).
Abnormal pregnancy outcomes were also found to be This stud y is the first long itudinal one ofwhich we are
sign ificant ly higher in those cycles in which the fo lli c le awa re that has fo llowed the fertility outcomes and the
on ly partially ruptured. ln the complete rupture cyc les pregnancy outcornes a long with a fo llicular ultrasound
(independent ofthe size ofthe fo lli cle) , ab normal preg- stud y. The results document and va lidate the sterile sta-
nancy outco mes occurred in 16 of 65 cyc les (24.6%). tus ofthe lute ini zed unruptured follicle synd ro rne and
l n the partial rupture cycles 3 out of 3 ( 100.0%) were the afo lli cul ar cycle confirming that they are d isorders
abnorma l (chi -sq uare = 8.094 wi th p=.0044; Fisher ex- of hum an ovul ati on assoc iated with the inabil ity to be-
act test, p=.0193). come pregnant. There were no pregnancies observed in
any cycle with ei ther of these two defects (Tab le 22-1 ).
The mean fo lli cular d iameter just prior to fo llicu lar rup-
Chapter 22 : Disorders of Human Ovulati on : Clinical Validation of the Sonographic Classification System 277
The number of patients that were followed with the ful! term . The classification ofsuch a follic ul ar rupture
lutei ni zed unruptured fo lli cle was substantial and the pattern as an ovul ation di sorder is based on our own
data presented could be cons idered defin iti ve. The data empirical observation and that of others. 8 The compl ete
for afo lli cu larism, while sti ll quite small, are consistent rupture of the follic le is genera lly observed to occur
with the theoretica l likelihood of pregnancy occurring overa period of minutes or hours and not days. In the
in such a cyc le bein g very small or zero. previous chapter, the de layed rupture pattern (in whi ch
fo lli cu lar rupture occurs over severa! days) is associ-
The data also docum ent that a sma ll mean follicu lar di- ated with dysfunctional hormone patterns. Thus, this
ameter (MF D) (less than 1.90 cm) is associated with a pattern is considered abnormal. Since this is the least
higher risk of abnorma l pregnancy outcome (6 1.5%) common of the di sorders that we have observed, fur-
(Tab le 22-3). Thus, an immature fo lli cle (one that is ther study of this conditi on cou ld be done.
< 1.90 cm) merits the designation of an ovu lation di sor-
der. Others ha ve observed that a sma ll follic le is associ- Continuing to be perhaps the most controversia! defect
ated with a lower pregnancy rate 6 and is associated with is the so-ca ll ed empty fo lli cle syndrome, whi ch actu-
signficantly decreased embryo quality. 7 Th is is a condi- ally is observed in a vari ety of previously-classified
tion which can be identified pre-conceptionally and then , conditions (e.g, mature fo llicles, immature fo il icles, and
with further study, should also lend itselfto appropri ate
treatment. The treatment goal would be to mature th e
fo lli cle and develop it so that the ovum is better pre-
Table 22-3: Mean FoUicular Diameter
pared at the time of concepti on.
by Outcome of Pregnancy Cycle
with U ltrasound·Assessed Ovulation
The sa me treatment goa l can be app li ed to those pa- Spontaneous and Medicated Cycles (N=69 1)
tients who suffer from a partial rupture ofthe fo llicle (a
rupture of less than 7.5 mm overa 24-hou r period). In <1 .90 cm ?. 1.90 cm Totals
these cases, a high in cidence of abnormal pregnancy Pregnancy Outcome n % n % n %
outcomes was observed (while the numbers in this study Full-term pregnancy 5 38.5 45 80.4 50 72.5
are small , the data are statistica lly signifi cant and thus Abnormal outcome 8 16 1.5" 1 11 19.6 19 27.5
merit the des ignation of a hum an ovu lation disorder). SAB 3 23.1 10 17.8 13 18.8
In the tlu·ee pregnancies in which the follicl e on ly par- Premature 3 23.1 1.8 4 5.8
tially ruptured , we observed two of the three to have Ectopic 2 15.4 o O.O 2 2.9
had fo ll icles less than 1.90 cm, suggesting sorne link- Totals 13 100.1 56 100.0 69 100.0
age between the immaturity of the fo lli cle and its in-
1. In one cycle. the outcome was unknown
abi lity to rupture compl etely. 2 Ch1-square =9 281 , p= .0023
3 Fisher exact test, p=.0047
4 Spontaneous delivery pnor to 37 O weeks gesta11on. In one case the placenta was
circumvallate
One pregnancy was observed in a cycle class ifi ed as a
de layed rupture (Tab le 22-2). That pregnancy went to
Table 22·2: Pregnancies (N=70) in Cycles of U ltraso und Observation (N= l, 818)
by Type of Ovulation Pattern
Mature Follicle lmmature follicle Partía! rupture Delayed rupture Total

Status of - 1.90 cm)
(> {< 1.90 cm) {< 7.5 mm rupture)
- (o ver 48 hours) Totals Group
Cumulus Medlcated s·ponta neous Med icated Spontaneous Medicated Spontaneous Medlcated Spontaneous Medicated Spontaneous
Oophorus n % n % n % n % n % n % n % n % n % n % n %
+C.0 . 1
25 83.3 19 73.1 3 60 .0 2 40 .0 o o.o 3 100.0 o O.O 1 100.0 28 80.0 25 71.4 53 75.7
-C .0 .2 2 6.7 5 19.2 1 20.0 1 20.0 o O.O o O.O o o.o o O.O 3 8.6 6 17.1 9 12.8
e.o. status 3 10.0 2 7.7 1 20.0 2 40 .0 o o.o o O.O o o.o o O.O 4 11.4 4 11.4 8 11 .4
unknown'
Totals 30 100.0 26 100.0 5 100.0 5 100.0 o o.o 3 100.0 o o.o 1 100.0 35 100.0 35 99.9 70 99.9
1. Th e cumulus oophorus was positively identified by ultrasound .

2. The cumulus oophorus wa s not seen by ultrasound.
3. The cumulus oophorus wa s not looked far during the examination.
278 The Medic a l an d Surg ica l Prac ti c e of NaProT ECHNOLOGY
partia l ruptures). The data eval uated in this stud y sug-

gest that while pregnancy may occas iona lly occur in Tab le 22-4: P regn ancy Outcome by
cyc les with an empty follicle- at which point one would Presence o r A bsen ce of Cu mulus O ophorus
presume that the cumulus oophorus was present but the Pregnancies O ccurring during
sonogra phic eva luation was not ab le to identi fy it- thi s Cycle of U ltraso u nd Series (N=l,250 1)
condition is associated with a signifi can tl y lower preg- Status of the Cumulus Pregnant Not pregnant ' Totals
nancy rate (is less fe rtil e) than those cyc les in whi ch a Oophorus (C .O.) n % n % n %
cumulus oophoru s is observed to be present (Tabl e 22- +e.o. 53 5.9 848 94.1 901 100.0
4). While there may be an inbuilt error rate in the ab il- - C.O. 9 12.s>.• I 340 97.4 349 99. 9
ity of ultrasound technology to identify empty fo lli cle
Tota ls 62 5.0 1, 188 95.0 1,250 100.0
syndrorne (a fa lse negati ve), the data upport th e notion
1. Exctudes all cycles wilh retained cumulus oophorus . luteinized unruptured
th at the absence ofthe curnulus oophorus is a true dis- foll1cle, afoll1cularism. or cycles where status of cumulus was unknown.
2 Th1s indues all cycles .n which pregnancy was observed not to occur but exciudes
order of hum an ovulation. cycles w1th a reta1ned cumulus, luteinized unruptured follicle or afollicularism
where absoluta 1nfert11ity has been shown to ex 1st.
3 Ch1-square =5.824 , p= .0158
4. F1sher exact test, p= 0137
Our observatio ns ofthe effect ofthe va ri ous ovulati on
disorders and the clinica ll y relevant association of ovu-
lati on di sorders to re producti ve anoma li es are surnma-
rized in Tabl e 22 -5. The luteini zed unruptured follicle
(LUF : +, -) and afo lli cularism (A F) have been observed
to be assoc iated with abso lute in ferti li ty. The immature Table 22-5: Summary of R eproductive Anomalies
fo lli cle (IF S : +, -, Re), the partial rupture (PRS : +, -, Clinically Associated with the
Re) and the empty fo ll ic le (MF: -) have been observed Disorders of Ovulation
to be associated w ith re lati ve degrees of infert i li ty. The
Ovulatio n Diso rder Reproductive Anomalies
immature fo llicle and the parti al rutpure syndromes have
Luteinized unruptured folli cle Absolute infertility
also been observed to be associated with abnormal preg- (LUF : +, - )
nancy outcomes (s pontaneous abortion , ectop ic preg-
Afollicularism (AF ) Absolute infertility
nancy and pre-term birth). The delayed rupture patte rn
lmmature follicles Relative infertility and
would appear to be anatomicall y dysfu ncti ona l, but thi s
(IFS: +, - , Re) abnormal pregnancies
porti on of the stud y does not va lidate it as an ovu lation
Partial rupture Relative infertility and
disorder because the number of pregnancies observed (PRS: +, - , Re ) abnormal pregnancies
was too small to dra w specifi c conc lusions . The endo-
Em pty follicle syndrome Relative infertility
crine porti on of thi s study (see C hapter 2 1) does sug-
Delayed rupture (DRS: +, - , Re) Needs further study
gest that de layed rupture is ab norrnal.
lt takes much time to co ll ect an adequ ately sized seri es

of patients to relate the ov ul atory event at the tim e of
fo lli cul ar ultraso und studi es to ubsequent pregnancy or a urinary LH kit observati on. lf ultrasound was used
outcome. Th is parti c ul ar proj ect took 16 years to ac- at a ll , it was used to simply observe the growth and
complish . Nonethe less, it does support the idea that the deve lopment ofthe fo ll ic le and its subsequent ruptu re.
described c lass ificati on system 1 for the di sorders of hu-
man ovul ation is credibl e and is a wo rkable class ifica - The data in thi s eva luation suggest that we shou ld be
ti on fo r future eva luation, clini ca l decision making, and looking for disorders ofovulation and not simp ly " ovu-
research. lation detecti on." These various disorders are assoc i-
ated w ith both relati ve and abso lute leve ls of infe rti lity
With regard to how one thinks about norma l eva luation and a va riety of ab normal pregnancies (spontaneous
of ovulation in a patient with an in fe rtility problem or abortion, prematuri ty and ectopic pregnancy). Treatment
other reproductive anoma ly, the data in th ese reports programs mus/ beg in with an objectively identified di-
chall enge us to a new paradigm shift. C lea rly, our pro- agnosis. To that end , thi s book is dedi cated . More work
fess ion has been mostly interested in the question of is c learly needed to find ways to correct the underl y ing
"ovulation detecti on ," or finding the answer to the ques- anatom ic defects of ovul ati on and their associated en-
tio n " Is thi s wo man ovu lating?" To th at ex ten t, we have docrinopath y that w ill reso lve the infertili ty and pre-
used such techniques as th e time-h onored BBT curve, ven t th e a bn orma l pregnanc ies.
endometria l biopsies, a single serum progesterone leve!,
Chapter 22 : Disorders of Human Ovulation : Clinical Validation of the Sonographic Classification System 279
Special Note ----------~
The ultrasound series conducted at the Pope Paul VI

lnstitute are used for diagnostic purposes not therapeu-
tic. Therefore, the pregnanc ies that we re observed dur-
in g the course of these studi es do not reflecta success
rate in the treatment of infertility. T hey were pregnan-
c ies that hap pened to occur at the same time as the di-
agnos tic test.
1. Hilgers TW: A Sonographi c Classifica tion Syste111 for Disorders 5. Motul sky H: Analyzing Data with Graph Pad Prism, 1999, Graph
ofHu111 an Ovulat ion. In : Hil gers TW: Th e Med ica! and Surgica l Pad Software, lnc., San Diego, A.
Practice of NaProTECHNOLOGY. Chapter 18. Pope Pau l VI ln-
6. Bersha C, Broden H, Lundin K, Ha111berger L: Compari sons of
stitute Press, Omaha, NE, 2004.
Fertili zati on, Cleavage and Pregnancy Rates of Oocytes from
2. Hil gers TW, Dvora k AD, Ta111isiea DF, Elli s RL, Yaksich PJ : Large and Small Foll ic le. Hum Reprod 1998 Jul ; 13(7): 191 2-
Sonographic Definition of the Empty Fo lli cle Synd rome. J Ul- 19 15.
trasound Med, 8:4 11 -4 16, 1989.
7. Haines CJ, Emes AL: The Relationship Between Folli cle Diam-
3. Hil gers TW, Ki111ball CR, Kec k SJ, Dvora k AD, Ta111isiea DF, eter, Fertili zation Rate, and Mi croscopi c Embryo Qualiry. Fertil
Yaksich PJ: Assessmenl o f the E111pty Foll ic le Syndro me by Steri l 199 1; 55:205-207.
Transvagina l Sonograph y. J Ultraso und Med, 11 :3 13-3 16, 1992.
8. Pi erson RA , Maninu k SD, Chi zen DR, Si111pson CW: Ultra-
4. CSS 2000 Statistica l System fo r Windows. CSS, Raysv ille, sonic Visuali za tion of Human Ov ul atio n. In Eve rs JHL and
Utah, 1998. Heineman MJ, eds. Fro111 Ovu lati on to lmpl antati on. Elsevier
Science Publ ishers, 1990: 73-79.
Differences Between Laboratories
T he laborato ry assess me nt ofany horm one, electro-

lyte, hematologic index , or any other tests perfom1ed
in a modem laborato ry to assist med ica ! practiti oners
This is fu rther demo nstra ted in the illustrati o n put fo r-
wa rd in Fig ure 23 -2. He re, a n assay fo r progesterone
du ring pregnancy is illu strated w ith both the bio log ic
ha ve inherent va ri abili ty fro m one laboratory to the next, and assay va ri ati on identi fie d. The sum ofthe two types
and fro m o ne procedure to the next w ith in th e sa me of va ri ati o n produce the to tal degree of va ri ati o n.
laboratory. lt is thus inc umbent upo n the phys ic ia n and
third-pa rty payers to unde rstand the di ffe rences that Whe n look ing at the reproducti ve ho rmones in wo men,
may ex ist between la boratories and between the co n- w hethe r those produced du ring the course of the me n-
duct of labo ratory exa minatio ns. Ultimately, inte rpreta-
tion ofth e results oftesting obta ined from a parti cul ar
labo ratory de pends u po n an understandi ng of how th e
laboratory procedure is conducted and how the norma l
values are establi shed.
The perfect test would be o ne in w hi ch th ere is no va ri a-

tion in how the assay itself is perfo rmed o r, fo r th at
matter, w hat th e leve! of the substance to be measured
might be. lf the laborato ry tests could be perfor med ex- A PERFECT TEST AN AVERAGE TEST A BAD TEST
actl y the same each tim e a nd the va lue itse lfwo uld not
Figure 23-1 : An illustration of the normal ranges for proges-
va ry, th en laboratory medi cine wo uld be re lative ly easy. terone in pregnancy. On the left, with all levels being identica l
H owever, both a biologic variation a nd a n assay varia- at the various time-linked points in pregnancy, a perfect test is
tion are inherent in ali phys io log ic para meters th at a re identified in which no vari ati on exists around the mean . On
th e right , a bad test is identified in wh ich th ere is a large
being measured and in the too Is by which they are mea-
degree of vari ation. In the middle, the more common test is
sured. Thi s vari ati o n can be w ide ra ng ing, resulting in a identified where there is a minimum to moderate degree of
test which is not very good, o r it may be moderate in vari ation and it allows for clinica l appli cation and reproducibil-
ran ge of va ri abili ty all owing fo r reasonabl e assess ments ity (From: Chard T: The Hormonal Assessment of Fetal and
Placenta! Function. Cl inics in Obstetrics and Gynecology 1:85-
to be made (Fig ure 23- 1). 1 102 , 1974).
281
Normal range for

laboratory 'A'
Total
QJ
>
Variation
~ §; Normal range for
QJ
~
e: laboratory' B'
o
E "'eo
o E
:e ....
o
:e
28 32 36 40
Weeks of gestation
28 32 36 40
Figure 23-2 : An illustration noting that both the biological and Weeks of gestation
assay variation can be additive to the tota l variation in a par-
ticular assay. This illustration is with progesterone during the Figure 23-3: Th e normal range far two different laboratories,
course of pregnancy. The laboratory must work toward re- Labora tory A and Laboratory B, are shown. A series of re-
ducing assay variation to a minimum (this is accomplished sults from Laboratory B would be grossly inaccurate if judged
through the implementation of quality co ntrol measures). This against the normal range of Laboratory A (From : Chard T: The
illustration also identifies the time-linked variation that may Hormonal Assessment of Fetal and Place nta! Function . Clinics
exist especially in the measurement of reprod uctive hormones in Obstetrics and Gynecology 1:85-102 , 1974).
(From : Chard T: The Hormonal Assessment of Fetal and Pla-
ce nta! Function . Clinics in Obstetrics and Gynecology 1:85-
102, 1974).
strual and fe11 ili ty cyc le or those produced in pregnancy, However, even laboratories th at use the same assay
one additional degree of variati on is identifi ab le. This procedures may also ha ve so rne degree of assay vari-
vari ati on is th e day-to-day or week-to-week vari ati on. ability. Thus, it is in cumbent upon each laboratory to
This is a time-linked variation that makes the assess- estab li sh its norm al ranges.
ment ofthese hormones more complex and di ffic ult. As
noted in Chapter 19, properl y targeting th e menstrual Unfortunately, when it comes to the men strua l and fer-
cycle can help correct the time-linked va ri ation. Or, as tility cyc le and the hormones produced in pregnancy,
noted in Chapter 54, accurate ly identifying the time dur- laboratories com monly do not establish normal leve ls.
in g the course of the pregnancy that the progesterone Thus, the nom1ograms published in thi s textbook can
leve! is drawn (the week of gestation) can help correct onl y appl y to those hormone leve ls performed in the
fo r the time- linked variation in progesterone produc- Nati onal Hormone Laboratory ofthe Pope Paul VI [nsti-
tion that is seen in pregnancy. These two si tuations can tute. lt is important fo r phys ician s not to presume that a
be co ntroll ed by trackin g the biomarkers wit h the laboratory result obtain ed in the ir local laboratory can
CREIGHTON MODEL FertilityCare™System. However, be placed upon the normograms and accurately inter-
there continues to be a bottom-line assay and biol ogic preted. Severa! sa me-patient-date-and-specimen results
variation that needs to be taken into acco unt. from different laboratories compared to the ati onal
Hormone Laboratory of the Pope Paul Vl ln stitute are
ln Figure 23-3 , a normal range for one laboratory (Labo-
ratory A) is compared to the normal range of another
laboratory (Laboratory B) for progesterone in pregnancy.
Table 23-1: Difference Betwee n
The time-linked retrieva l ofthe serum spec im en is as-
Laboratories
sumed to be identi ca l for both laboratories in this ex-
Same Patient, Date and Specimen
ample. The assay variation from one laboratory to the
next puts the results injeopardy ofbeing mi interpreted. National Hormone Outside
In th is example, the results identifi ed are normal if they Laboratory-PPVI Laboratory
were performed in Laboratory B, but th e resu lts would Progesterone 18.5 ng/ml 30.37 ng/ml
be clearly suboptimal if they were performed in Labora- 19.9 ng/ml 22.0 ng/ml
tory A. Estradiol-17 P 10.9 ng/dl 16.6 ng/dl
Chapter 23 : Differences Between Laboratories 283
shown in Table 23- 1. ln sorne cases, the vari ation was

very Jarge, while in other exampl es, the va ri ati on was Table 23-2: Coeffici ent of Variation (%)
minimal. This degree of vari ation makes it espec iall y for Seru m Progesterone Assessm ent-
difficult to rely on other laboratori es when using the The Precision of Assay at Different
normograms published in thi s textbook. R anges of M easurement - 1974 vs. 2004
National Hor!Tlorié
The practicing phsyician may resol ve this in two ways. Laboratory
Progesterone Level 1974' PPVI 20042
The easiest is to use the National Hormone Laboratory ng/ml CV(%) CV(%)
as a national reference laboratory'because these values
have been worked out and identifi ed. A second way is 10.0 8.3 6.3
for the physician to work closely with his or her own 25.0 8.3 5.0
hospital or outpatient laboratory facilities to collabo- 33.0 8.3 5.8
rate wi th the National Hormone Laboratory to draw their 73.2 17.4 9.5
own correlations. As a genera l rul e, at least 100 speci- 121.4 15.3 6.6
mens should be drawn and compared in order to estab- 1. lindberg BS, Nilsson BA , Johansson EDB: Plasma Progesterone Lev-
li sh the variation s that might ex ist between laborato- els in Normal and Abnonmal Pregnancies. Acta Obste! Gynec Scand
53:329-335, 1974.
ries .1 2. Data from Diagnostic Products Corporation and Pope Paul VI lnstitute,
2004.
The assay variation that exists in a particular assay pro-

cedure has significantly improved over the last 30 years.
By looki ng at the coefficient of variation in the assay of assays are much less than they were 30 yea rs ago. This
progesterone and comparing the resu lts from studies is a reflection of improved analytica l technique and does
performed in 1974 against studi es from 2004 (Table 23- help improve the ab il ity to establi sh norma l curves and
2), it is noted that the va riability of the contemporary assess them properly and accurate ly.
1 . Chard T: The Horm onal Assessme nt of Fetal and Pl acenta!

Function. Clini cs in Obstelrics and Gy naeco logy 1:85-102,
1974.
-----,~úu24
Establishing Normal Hormone Levels
P hysicians in modem reproductive medicine use such

inaccurate assessments of norm al function except
far its use of norm al va lues far the assess ment of the
were chosen to undergo dail y fa llicular ultraso und stud-
ies. These patien ts were also undergo ing targeted hor-
mone eva luation as described in Chapter 19. Their cycles
hormones in the menstrua l cyc le or th e hormones in were spo ntan eo us menstrual cyc les, which were
pregnan cy. Most laboratori es report " norma l" va lues sonographi ca ll y identifi ed as containing a mature fa l-
far progesterone and estradiol-1 7~ (E 2, estrad iol) dur- li cle with a pos iti ve cumulus oophorus anda complete
ing the course of the menstrual cycle in th e fas hion rupture ofthe fo lli cle (an anatomically normal ovulation
which is listed in Table 24- 1. This ap proach to the as- by ultraso und - see Chapter 20).
sessment ofnormal leve ls fa r the hormones ofthe men-
strual cycle is complete/y inadequate. Such inadeq uacy The mean leve! and its standard deviation (SD) fa r the
necess itates taking a new look at these assessments. periovulatory targeted horm one profile in this gro up of
patients are li sted in Table 24-2. The 3- and 4-value sum s
As yo u read this chapter, kee p in mind that the normal and means ofthe profile are a lso ide ntifi ed. These data
leve ls far preovulatory estrad io l or postov ul atory
progesterone and estradio l are not a w ide ra nge (as usu-
all y expressed). Rather, these nom1al levels are spec ifi c Table 24-1: M ost Common Laboratory
to a particular time-linked assess ment ofthe ri se and fa ll "Normal" Levels of
of these hormones during the pre- and postovulatory Progesterone and Estradiol-17 ~
phases ofthe cycle. Because ofthi s specificity, one ca n During the Course of the Menstrual Cycle
ac hieve accura te assessme nts, which yie ld great insight
into the underl ying causes of pathophysiologic ab nor- " Normal" Values
Progesterone Estradíol-17~
ma liti es of the men strual and fertility cycles. Those Phase of the Cycle (ng/mL) (ng/dL)
pathophys iologic correlates wi ll be developed late r in
Follicular phase 0.0-1.5 2.5-19.5
this textbook.
Ovu latory phase 0.8-3.0 6.6-41 .1
Luteal phase 1.7-27.0 4.0-26.1
In order to determine w hat nom1a l leve ls are during the
course of the menstrua l cyc le, a gro up of 57 patients
285
286 The Medical and Surg ica l Prac t ice of NaProTECHNOLOGY
th e indi vidua l progestero ne va lues. In any g iven cycle,

Table 24-2: M ean and Standard D eviation of
the maxi mum RPR will always be 1.0. However, in a com-
Periovulatory Estradio l- 17 ~ (E2) Profile 1•2
pos ite set of data such as that expressed in Table 24-4,
E 2 Sums and M eans (3 and 4 Value)
the RPR of 1.0 is not reac hed beca use the hi ghest leve[
Normal Controls 3 (N=57) is not always on P+ 7. Therefare, when the mean of the
RPR far the cornposite group is ca lculated, it will be less
Mean
Day of Profile .(ng/dl) so• than 1.0. The mean and standard deviation (S D) fa r the
composite of the 57 cycles is identifi ed in Table 24-4
E-4 8.8 2.1
and it is graphed in Figure 24-3 . The use of the calcu-
E-2 14.8 3. 1
lated RPR is he lpful in diagnosi ng a late luteal p hase
Peak E2 26.0 5.9
defect (Type llI lutea l phase deficiency). An RPR of .::=:
E2 +2 12.8 6.6
0.50 on P+9 is diagnostic of this type of lutea l phase
E2 Sum (3 value)' 53.6 11 .2 deficiency (see Chapter 35).
E2 Sum (4 value)' 63.2 14.5
E2 Mean (3 value)5 17.9 3. 7 The mean and standard deviation of the post-Peak es-
E2 Mean (4 value)5 15.8 3.6 tradio l leve! along with tbeir 5-value sums and means
are li sted in Table 24-5 and are graphed in Fi gure 24-4.
1. These normal values apply only to the laboratory methods used al the The mean levels are identified with a sa lid line and one
National Hermane Laboratory ofthe Pope Paul VI lnstitute. Because of
variation that exists between laboratories, these values cannot automatically sta ndard deviati on away from the mean is identified in
be presumed to apply to other laboratories where the proper assessment of the dotted line . In thi s fashion,four zones can be iden-
normals has not been undertaken.
2. The E, profile is obtained by drawing E2 levels every otherday from P-5 (or
tified.
P-6) lhrough P+2 (with referenoe to lhe CREIGHTON MODEL FertilityCare™
System ).
3. Obtained from lhe endocrine evaluation of 57 spontaneous cycles which were
In addition to the above, the mean P+ 7 value fa r andros-
sonographically identified as containing a mature follicle with a positive cumu- tenedione, dehydroepiandrosterone sul fa te (DHEAs),
lus oophorus and complete rupture (anatomically normal ovulation by ultra-
sound). prol actin, testosterone, free testosterone, thyroxine (T4),
4. The E, sum is obtained by adding the E, values in the E, profile to include the
level befare the peak level, the peak level and the level after the peak level (3
value sum) or the two levels befare lhe peak leve!, lhe peak leve! and lhe leve!
afterthe peak level (4 value sums). Table 24-3: Mean and Standard Deviation of
5. The E, mean is the averageofthe 3 (3value) or4 (4 value) levels !halare used
to make up the 3- and 4-value sums.
Post-Peak Progesterone Profile 1•2
6. SO = standard deviation and Progesterone Sum and M ean
Normal Controls3 (N=57)
Mea n
Day of Profile (ngl mL ) SD6
are graphed in Fi gure 24-1 . [n the graph, the mean va l- P+3 9.4 4.1
ues are identifi ed by th e sa lid line and one standard P+5 14.4 4.7
dev iation away from the mea n is identified by th e P+7 15.7 5.7
das hed lines. In thi s fas bion , four zones of estradi o l P+9 13.6 5.3
production can be identifi ed . P+11 8.1 5.0
P Sum (5 values)' 61 .2 17.4

In Tabl e 24-3, the mean progesterone leve ls and their P Mean (5 values)' 12.3 3.4
standard deviations fa r the targeted post-Peak proges-
terone profi le are iden tifi ed along with the 5-value su m 1. These normal values apply only to the laboratory melhods used at the National
and mean. These data are graphed complete ly in Figure Hermane Laboratory of the Pope Paul VI lnstitute. Because of variation that
exists between laboratories, lhese val ues cannot automatically be presumed to
24-2. Again, the mean leve! is a sol id line and one stan- apply to other laboratories where the proper assessment of normals has not
been undertaken.
dard deviation away from the mean is identified by the
2. The P profile is obtained by drawing serum P levels on P+3, P+5, P+7, P+9,
hash-mark lines. Once aga in,four zones can be identi- P+11 (with reference to the CREIGHTON MODEL FertilityCare™ System).
fi ed. 3. Obtained from the endocrine evaluation of 57 spontaneous cycles which were
sonographically identified as containing a mature follicle with a positive cumu-
The progesterone levels can a lso be used to identify a sound).
4. The P sum is obtained by adding all five values of the P profile as obtained in
relati ve progesterone ratio (RPR). This rati o is ca lcu- lf2above.
lated by using the hi ghest leve! of progesterone ob- 5. The P mean is the average of these five values.
served during the post-Peak hormone profile (P+ 3, P+5, 6. SO= standard deviation.
P+7, P+9, P+ 11) as the common denominator fa r each of
Ch apter 24: Establ ish in g Normal Hormone Levels 287
Norm al Values , Perio v ulatory Estradiol-17¡3 Profi le

3 and 4 Value Sum and Mean.
National Hormone Lab oratory, Pope Paul VI lnstitute
35.0 130.0
120.0
30.0 110.0
.! 260 100.0
25.0
90.0
"'- ,_
"'-
~ 216 80.0 'T
o
o n1
'5
'5 20.0
~ 179
194
70.0 ~
w
w
648632
,,¡ ..J
~
60.0
a.e 15.0
158
:~
142 536 E
E
50.0
~
•8 7
~ Zone 4 / :' ..' . • 128
122
"' 424
40.0
"'
10.0 Zone 3
ª-~' .· 30.0
5.0
Zone 2
.. 20.0
Zone 1
10.0
O.O +---~-~--~--~--+---l--~-+---+ O.O

E-4 E-2 Peak E2 E+2 E2 Mean E2 Mean E2 Sum E2 Sum
3 Value 4 Valu e 3 Valu e 4 Value
Targeted Periov ulatory Estrad iol -17a Profile
Figure 24-1 : The normal periovulatory estradiol levels and their 3- and
4-value sums and means (N=57). Zones 1 through 4 are separated by
dotted lines one standard deviation away from the mean (Fro m: National
Hormone Laboratory, Pope Paul VI lnstitute for the Study of Human
Reproduction , Omaha , NE , 2004) .
28.0 140.0
Normal Values, Post-Peak Progesterone Profile
26.0 Sums and Mea n (Controls N=57 )
National Hormone Laboratory, Pope Paul VI lnstitute
24 .0 120.0
22.0
·"·.
20 .0 100.0
E
_J
~-
... Zone4 E
e, 18.0 e,
..
e:
e: 16.0 Zone4
15 7
15 7 78 6 80.0 ..
e:
e:
~
14 4
.e
~CD
e
14.0
.. 13 6
. Zone 3
.
;;
CD
o
o.. 12.0 12 3 61 2 n_
60 .0
E Zone3 E
.
2
(/)
10.0
94
~ -------·- ·•. Zone 2 :;¡
~
(/)
89 43 8
8.0 •. 40.0
Zone2
6.0
.. Zone 1
4.0 20.0
Zone 1 •
2.0
o.o O.O
P+3 P+5 P+7 P+9 P+11 P Profile P Profile
Mean Sum
Targeted Post-Peak Progeste ro ne Profile
Figure 24-2: Normal post-Peak progesterone va lues along with the

sums and means (N=57). The zones are separated by a dotted line
representing one standard deviation away from the mean (From :
National Hormone Laboratory, Pope Paul VI lnstitute for the Study of
Human Reprodu ction , Omaha , NE , 2004).
1.0
0.87
o
:;:¡
ni
o:::
Q)
e:
...o
-Q)
1/)
Q)
C>
e
ri.
Q)
>
:;:¡
ni
Qj
o:::
o.o _....___
P+3 P+5 P+7 P+9 P+11
Figure 24-3 : The relative progesterone ratios in a group of control patients (N=57) (From : National Hormone Laboratory, Pope
Paul VI lnstitute for !he Study of Human Reprodu ction , Omaha , NE , 2004).
Table 24-5: M ean and Standard Deviation of

Post-Peak Estradiol-17~ Profile 1•2
Table 24-4: Mean and Standard Deviation of and E 2 Sum. and Mean
Post-Peak Progesterone Profile
Normal Con trols 3 (N=57)
for R elative Progesterone Ratio (RPR) 1
Normal Con trols2 (N=57) Mean
Day of Profile (ng/dL) so•
Day of Profile Mean RPR"' SD' P+3 8.8 3.5
P+3 0.56 0. 24 P+5 10.8 4.4
P+5 0.83 0. 18 P+7 12.0 4.7
P+7 0.87 0.15 P+9 12 .0 4 .7
P+9 0.754 0.20 P+1 1 9.8 5.7
P+11 0.52 0.25 E, Sum (5 va lues)' 53.2 20.2

E2 Mea n (5 values} 5 10.7 4 .0
1. These normal values apply only to the laboratory methods used at the National
Hormone Laboratory of the Pope Paul VI lnstitute. Beca use of variation that
exists between laboratories, these values cannot automatically be presumed to 1. These normal values apply only to the laboratory methods used at the National
apply to other laboratories where the proper assessment of normals has not Hormone Laboratory of the Pope Paul VI lnstitute. Because of variation that
been undertaken. exists between laboratories, these values cannot automatically be presumed to
apply to other laboratories where the proper assessment of norma Is has not
2. Obtained from the endocrine evaluation of 57 spontaneous cycles which were
sonographically identified as containing a mature follicle with a positive cumu- been undertaken.
lus oophorus and complete rupture (anatomically normal ovulation by ultra· 2. The E, profile is obtained by drawing serum E2 levels on P+3, P+5, P+7, P+9,
sound). P+11 (with reference to the CREIGHTON MODEL Fertility Cilre~ System).
3. Calculated by using the highest level of progesterone in the post-Peak hor- 3. Obtained from the endocrine evaluation of 57 spontaneous cycles which were
mone profile (P+3, P+5 , P+7, P+9, P+1 1) as the common denominatorfor sonographically identified as containing a mature follicle with a positive cumu-
each of the individual values to obtain the relative progesterone ratio (RPR ). lus oophorus and complete rupture (anatomically normal ovulation by ultra-
4. An RPR of s 0.50 on P+9 isdiagnostic of a late lutealdefect (Type 111 luteal sound).
phase deficiency). 4. The E, sum is obtained by adding all five values ofthe E2 profile as obtained
in#2above.
5. SD; standard deviation.
5. The E2 mean is the average ofthesefive values.
6. SD ; standard deviation .
Chapter 24: Establishing Normal Hormone Levels 289
26.0 130.0
1
Normal Values, Post-Peak Estradiol-17Jl Profile

24.0 120.0
Sum and Mean (C ontrols, N=57)
22.0 National Hormone Laboratory, Pope Paul VI lnstitute 11 0.0
20.0 100.0
.,,
..J
o.e:
18.0
16.0
.. .• ··· ·· ····· .. .•
Zone 4
90.0
80.0
'§
CI
e:
,_<O.
,_
<O.
Zone 4
14 7 . 73 4 .-;-
o 14.0 70.0 o
'O 12 0 12 o Zone 3 'O
~ ~
~
12.0 60.0
w w
E Zone 4 B 10 7 . 53 2 E
10.0 50.0
~ 8 ~
VJ Zone 2 VJ
..
•.. . ..
8.0 40.0
6.0
Zone 2 -· 67 • 33 o
30 .0
4.0 • Zone 1 20 .0
2.0 Zone 1 10.0
o.o O.O
P+3 P+5 P+7 P+9 P+11 E2 E2
Profile Profile
Mean Sum
Taraeted P ost-oeak Estradiol-1 7 f\ Profil e
Figure 24-4: Normal post-Peak estradiol levels along with th e su m and mean for 57 controls . The zones are separated by the
dotted lines, which are one standard deviation away from the mea n (From : National Hormone Laboratory, Pope Paul VI lnstitute
far the Study of Human Reproduction, Omaha , NE, 2004) .
triiodothyronine (T3) uptake, free thyroxine index (FTI; dio! profile and the postov ul atory progesterone and
calculated), thyroid stimulating hormone (TS H; 3rd gen- estradi ol profile must be taken into acco unt (in much
eration), FSH, and LH are noted in Tabl e 24-6 for this the same way as evaluation and interpretation of proges-
same group ofpatients. The day-5 FSH mean is identi- terone leve ls in pregnancy). Thus, th e standard 95 -per-
fied in Table 24-7. cent confidence interval, whi ch is used for the measure-
ment ofa serum potassium or sodium leve! (forexample),
This group of patients ( =57) was nota perfect group is inadequate for assess ing th e normality ofthe repro-
because each ofthese patients was also infertil e. How- ductive hormones.
ever, by using serial ultrasound to defi ne an anatom i-
call y normal ovu lation by ultrasound para meters, the In the past, when looking at the assessment of proges-
defect in thi s contro l grou p shou ld be considerably terone during the lutea l phase of the menstrual cyc le,
taken into account The hormone leve ls in thi s group of the integrated lutea l phase progesterone was proposed
patients should not be lower than those observed in a to be a conveni ent and reli ab le para meter fo r assessi ng
group where there is suboptimal ovarian hormone func- luteal function. 1 lt was also suggested that an integrated
tion. lfanything, the leve ls in thi s group would be some- progesterone leve! can be determined by tabulating the
what hi gher. Fina JI y, th e author has eva luated other pa- sums ofthe serum progesterone leve ls during the lutea l
tients who have perfectly norm al ferti li ty, as identifi ed phase of the menstrual cyc le. 2 The integrated progest-
by the absence of inferti lity and the presence of ex hib- erone leve! is an estimate of th e total progesterone out-
ited norma l ferti li ty. In patients wi th normal fe rtility, the put during the course of the lutea l phase . The integrated
hormone assessments were nearly ident ica l to these progesterone leve! has been considered the best estí-
curves. Patients of norm al fe rtili ty were not used be- mate for assess ing the funct ion of the corpus luteu m.1.2
ca use their hormone levels were not drawn in the spe- However, the proflle of the production of either estra-
cific targeted fas hi on described in this textbook (a l- diol or progesterone ultimate ly gives the most rel iab le
though very close to it). informati on of hormone production during th e lutea l
phase. For that reason, these graphs are separated into
The time-linked quali ty and nom1al variab ility ofthe hor- various zones (Zone 1 through Zone 4). Ifthe Peak leve]
mone leve ls drawn relative to the periovulatory estra- of estrad iol, for exam pl e, ex hibits a stati stica ll y signifi-
cant decrease on a panicu lar day, severa! situation can

Table 24-6: Mean and Standard Deviation of
be observed where the mean leve! of the stud ied group,
P+7 Endocrine Parameters 1
whi le lower than the mean leve! ofthe contro l grou p, is
Normal Controls2 ( =57) sti ll within the range of one standard deviation away
from the mean .
Endocrine Parameter
P+7 Mean so
This way of evaluating the hormones manufactured
Androstenedione (ng/ml) 1.6 0.5 during the course ofthe menstrual and fert ili ty cycles,
DHEAs (µ g/dL) 155.9 63.1 provides excellent guidance for eva luating of subopti-
Prolactin (ng/ml) 13.7 10.1 mal profiles in various endocrinopathi es of ovari an func-
Testosterone (ng/d l ) 30.5 13.0 tion. lt also pro vides exce ll ent guidance for initiating
Free testosterone (pg/ml) 1.2 0.6 various therapeutic regimens and monitoring those regi-
T, (µ g/dl) 7.6 1.3 men .
T 3 uptake (%) 28.7 1.7
FTI (calculated- mlU/mL) 2.2 0.4 The sa me principi es are appli ed to the assessment of
TSH (third generation-mlU/mL) 2.4 1.9 progesterone in pregnancy. The use of progesterone in
FSH (mlU/m L) 3.9 2.0 pregnancy is di cu sed in detail in Chapters 54 and 55.
LH (mlU/mL) 4.5 4.5
1. These nonTial values apply only to the laboratory methods used at the National Table 24-7: D ay 5 FSH Level 1
HonTione Laboratory of the Pope Paul VI lnstitute. Because of variation that
exists between laboratories, these values cannot automatically be presumed to Mean and Standard Deviation
apply to other laboratories where the proper assessment of nonTials has not
been undertaken. ormal Controls2 ( =57)
2. All levels were drawn on P+ 7 (mid-luteal phase).
Mean
sonographically identified as containing a mature follicle with a posrtive cumu- Endocrine Parameters mlU/mL so•
sound). Day-5 FSH' 8.1 2.1
4. SD = standard deviation.
1. These nonTial values apply only to the laboratory methods used at the ational
HonTione Laboratory of the Pope Paul VI lnstitute. Because of variation lhat
exists between laboratories, these values cannot automatically be presumed to
apply to other laboratories where the proper assessment of nonTials has not
been undertaken.
sonographically identified as containing a mature follicle wrth a positive cumu-
lus oophorus and complete rupture (anatomically nonTial ovulation by ultra-
sound).
3. FSH levels drawn on day 5 of the menstrual cycle.
4. SD = slandard deviation.
1. Wu CH, Minassian SS: Th e lntegrated Luteal Progesterone: 2. Jordan J, Craig K, Clifton DK, Soule MR: Lut eal Phase
An Assessment of Lut ea l Fun ctio n. Fertil Steril 48:937- Defect: The Sensiti vity and Specificity of Diagnostic Meth-
940, 1987. ods in Com mon Clinical Use. Fertil Steril 62:54-62, 1994.
Part 111:
medi.Al
NaProTECHNOLOGY
Thomas Hilgers, M.O. "The CrMS and NaProTECHNOLOGY provide a simple

Chapter26
and reproducible means by which the menstrua/ cycle can
be targeted, thus re-emphasizing the use of hormones that
are natural/y produced in the body "
291
292
Chronic Discharges and the CrMS
F o r wo me n w ho have c hro ni c di sc harges , th e

CREIGHTON MODEL System (CrMS) ca n be used
effecti ve ly. To do so requires th e ass istance of an ad-
considered inferti le. Th ese are imp lemented once the
wo man has been p ro perl y taught and when she COl?fi-
dently identifles her Peak Day.
equately trained FertilityCare™Practitioner (FCP) w ho
und erstands th e concepts used in impl ementin g pre- The pro per use and impl ementati on of ye ll ow stamps
and post-Peak ye ll ow stamps fo r the identi fí cati on of can help the wo man and the couples to understand when
preovul atory and postovul atory infe1ii lity. These ye l- their natu ra ll y occu1Ting ph ases offertility and infe rtil -
low stamps are used in the presence of a continuous ity ex ist. Nevertheless, the wo man who has a continu-
mucus di scharge, whi ch is considered in fe1i ile. ous mucus di scharge poses a parti cul ar chall enge to
the FCP . The continuous di scharge may occasionall y
The use ofpre-Peakye ll ow stam ps in wo men who have lead to a dec rease in overa ll confídence in the use of the
a continuous di sc harge in vo lves identi fy ing a pattem system. Because the system is standardi zed, it is pos-
ofpre- Peak mucus th at is essentiafly the samefrom day sible to interpret the types of di scharge and the pat-
to day (w hat is refe rred to as an essenti al sa meness te rn s of th ose di scharges. Th e types and p attern s of
pattern ,ESP - see Chapter 8). These days are consid- di scharge can then be corre lated w ith phys iol og ic or
ered infe 1i ile because the ovary is qui et and ovul ation pathophys iologic events th at mi ght be occurring. With
has not yet begun . When the mucus pattern changes thi s in fo rm ati on, appropri ate treatment modalities ca n
fro m thi s ESP apoint ofchange ( POC) is identift ed and be in stituted to help norma li ze the cha1ting reco rd and
marks the beg inn ing of the tim e of fe 1tility. The POC to ass ist the couple in deve loping confídence in use of
corre lates w ith the ri sing leve Is of estradi o l-1 7 ~ seen at the system.
th e beg in ning of th e fo lli cul ar phase . 1 Thus, a woman
can be taught how to pros pective ly identify the days of Three bas ic ty pes of patte rns can be correlated to un-
preovulatory infertili ty and the beg inning ofthe fert ile derl ying pathophys io logy. These patterns the continu-
days. ous cerv ica l mucus di scharge, the freq uent appearance
of wet without lubri cation (2 W) observati ons, and th e
Post-Peak yellow stamps are implemented for those days presence ofa green mucus di scharge. Sorne women ha ve
during the p ost-Peak phase of the cyc le that wo uld be a continuous mu cus di sch arge in whi ch there is no ap-
293
294 Th e Medica! and Surgical Practice of NaProTECHNOLOGY
parent pathophys iologic con-e late. A continuous pasty, T he deve lopment of cri te ria is one of the fund amental
c loud y d ischarge (PC) is most 1ikely a norma l vari ant. principies of NaProTECHNOLOGY. lndeed, the CrMS
The presence of a continu ous mucus-type di scharge chart must be carefu lly read looking spec ifi cally fo r the
and the appearance of a non-na! cervix may, however, presence or absence of certain criteria. Ifthe criteria are
re present an undetermined pathoph ys io log ic correlate. present, the potenti al that a parti cular gyneco log ic con-
In thi s case, the di sc harge can be managed with the use diti on ex ists increases.
of ye ll ow stamps. lnvestigati on of thi s discharge pat-
tern w ill be prese nted later in thi s chapter.
Criteria for ldentifying Cervical
lnflammation (Cervical Eversion) --~
ldentification of Cervical lnflammation
(Cervical Ectropion) - - - - - - - - . T he fo ll ow ing are th e criteri a fo r identify ing a cervical
eversion (inflammati on) from the CrMS chart:
Women w ho have an inflammatory condition of the
cervix may ex peri ence a characteri sti c discharge pat- 1. A sticky ( 1/4 inch), tacky ( 1/2-3/4 inch) or gummy
tern . T hi s intl ammatory conditi on is commonl y associ- di scharge present during the earl y pre-Peak phase
ated w ith a cervical eversion or ectropion or w ith a of the cycle (those days prior to the sixth day
cervical erosion. T hese conditions may cause a d is- befare th e Peak Day) .
charge to occur at spec ifi c times du ring th e course of
2. Any sti cky, tacky, stretchy (1 inch or more) or
the menstrua l cycle. T he Pap smear wi ll usua ll y be nor-
gumm y di scharge seen an y time from the fo urth
mal and cul tures will be negati ve. The only ind icati on of
day post-Peak.
infl ammation is the persistence of a disc harge pattern,
whi ch is most likely the result ofthe constant in-i tation 3. A pasty, cloud y di scharge is nota criteria.
of the everted endocervical epi the lium by acid ic vagi-
4. Ye ll ow d isco loration of the mucus is not a crite-
nal tluids (the endocervica l epithelium is used to an
na.
alka line enviro nment).
5. Premenstrual mucus is not a criteri a.
If the physic ian and the FCP know the spec ifi c criteria
that ha ve been deve loped to identify these cervica l ever- If one or both of the fírst two criteri a are present, then
sions, they can identify th e presence of eversion fro m the criteri a fo r a cervica l eversion (infl ammati on) exists.
the chart with a hi gh deg ree of accuracy. In order to During pelv ic examinations fo r cervical assessment, a
unde rstand thi s capabili ty, which is a co nstant com- simple grading system can be used to identi fy the grade
panion of th e CrMS , one must be fami liar w ith the con- ( or the size) of the cerv ica l eversion (Figure 25- l ). One
cept of cri teria that is used in this textbook. Criteria are can also look fo r the presence of nabothi an cysts on
defi ned as specific markers through which, by their the cervix, which will be more frequent (Figure 25-2 and
presence ar absence, a specific judgment can be made. 25 -3). lf the charting criteri a fo r cerv ical infl am mation
ln identi fy ing a cerv ica l eversion, the CrMS chart is a are present, a grade Il or larger inflammatory reaction in
standardi zed system fo r vul var mucus moni to ring that the cervix (cervica l eversion or ectropi on) will be identi-
illustrates the criteri a. fied in over 75 percent of cases. Examples of cycles that
do and do not meet these criteri a and the grade of the
CERVIX GRADING
NORMAL GRADE 1 GRADE 11 GRADE 111 GRADE IV

up to 5 mm 5 mm to 1 cm 1 cm to 2 cm over 2 cm
Fi gure 25-1: A simple grading system of the ectocervix which allows for a standardized assessment of the ce rvica l eversion
and the monitoring of its healing followi ng treatmen t.
Ch apter 25: Chronic Discharges and the CrMS 295
cervix observed are shown in F igure 25 -4. chart. Second, another 103 patients participated in a
study w here an abse nce of cervical eversion was pre-
A three-part study of the cervix has been conducted to dicted from th e CrMS chart. Third , an add itiona l 171
ide nti fy these correlations. First, a total of38 I patients pati ents were eva luated for the condition oftheir cerv ix
participated in a study where the presence of a cervica l at th e time of their postpartum examin ation (at 4- to 6-
eversion (inflammation) was predicted fro m the CrMS weeks postpartum) (Table 25-1 ).
Figure 25-3 : Th e uterus in sagittal view with several naboth-

ian cysts located within the cervix (left, upper right) and a
Figure 25-2: The appearance of nabothian cysts, which form closer view of the same cervix sh owing th e mu ltiple nature of
as the resu lt of a blocked mucus crypt secondary to chronic these nabothian cysts (right) (From : Pope Pau l VI lnstitute
inflammation , on the cervix (From : Pope Paul VI lnstitue re- Reproductive Ultrasound Center).
search , 2004).
15 16 17 18 35
IOCG IOCK t..K IOCK BK te IOK IOK SCG 8CG sce "CG QCG
x3 •a ad -. 1 x i xi 11 1 "ª xa •:il •1 x i 1(1
Figure 25-4: A series of six cycles from differe nt wo men who show the criteria for the presence or absence of cervical
inflammation . Cycle A shows the absence of criteria and the cervix was normal. Cycles B through F show varying signs of both
pre- and post-Peak criteria . In cycles B through E, th e cervix graded 1-IV respective ly. In cycle F, in spite of the criteria being
present, the cervix was normal (From : Pope Paul VI lnstitute research, 2004).
296 The Medical and Surgical Practice of Na ProTECHNOLOGY
Table 25· l : Th ree Studies of the Cervix (N=594)
# of Mean age Mean number

Study Component patients (years) pregnancfos
Cervical information predicted 381 28.5 2.3 1

to be present trom the CrMS chart
11. Cervical information predicted 103 29.1 1.4'
to be absent from the CrMS chart
111. Condition of the cervix recorded al 171 28.3 2.3
postpartum visit (4-6 weeks )
Total patients 594
1. Studentt-test, p<.05
Table 25-2: The Statu s of the Cervix when Ce rvical Eversion is

Predicted to be Present o r Absent
Normal or Grade 11- IV

Cervical eversion Grade 1 Nabothian Cysts Only Total
predicted to be n % n % n Yo
Present 89 23.4 292 1766 1 1 381 100.0

Absent 78 175 7 1 25 24.3 103 100.0
1. Chi-square =98.40, p<.0001
Table 25-3: Status of the Cervix 1 fo llowing C-Sectio n and Vaginal Delivery
with and without R epair of Minor Cervical Lace rations
Normal or Grade U -IV

Grade 1 Nabothian Cx:sts Onlx: Total
DeHvery Status n % n % n /o .
0
C-section 17 100.0 o O.O 17 100.0
Vaginal delivery with:

repair of minor 39 88.6 5 11.4 44 100.0
cervical lacerations
no repair of minor 89 80.9 21 19.12 110 100.0
cervical lacerations
Totals 145 84.8 26 15.2 171 100.0
1. At postpartum visit.
2. When compared to C-section, chi-square =3.888, p=.0486.
Chapter 25: Chronic Discharges and the CrMS 297
Th e res ults of the tirst portion of th is study are shown (F igures 25-5 and 25-6). After the cervix is anesthetized
in Table 25-2. The cervica l intlammation criteria correctly using topi ca l 2% Xylocaine ge l, whi ch is appli ed for a
predi cted the presence of a cervica l ectropi on of grade few minutes to the cervi x, and clea ned with a large cot-
U or larger in 292 of38 I cases fo r a positi ve predi cti ve ton-tipped applicator, the needl e tip of the hyfrecator
value (PPV) of7 6.6 percent (292/38 1). The absence of unit is pl aced 1 mm offthe cervi x and the control button
the criteria correctl y predi cted the absence of a cervica l is turned on. There will be a "spark ga p," whi ch creates
eversion in 78 of 103 cases fo r a negative predicti ve des iccation of the surface epithelium and later results in
va lue (N PV) of75. 7 percent (78/103). The sensitivity of squamous metapl as ia. This converts the cervica l ever-
th e CrMS criteria fo r cervica l ectro pi on was 92. 1 per- sion to a more normal-appea ring cervix. Exampl es ofa
cent (292/31 7) and the specifi city was 53.3 percent (89/ cervix prior to treatment and after treatment are shown
167). Us ing chi-square analys is, the di ffere nce between in Figures 25-7 and 25 -8.
the two criteri a was stati sti ca ll y signifi ca nt (p<.000 1).
1n some cases, cryosurgery may be used, but it is im-
In th e third portion , 17 1 pati ents had their cervix eva lu- porta nt that the cryosurgery unit be set on a superfici al
ated at the time of their postpartum exa mination. These setting so that it does not deepl y penetrate and destroy
were performed foll owing cesarean secti on in 17 pa- the cerv ica l crypts. In the past, sil ver nitrate applica-
ti ents and followin g vaginal deli very in 154 patients. Of tions ha ve also been used on th e cervix. Whil e thi s can
the 154 patients, 44 had the surgica l repair of minor cer- be a very effecti ve treatment (espec iall y if used in com-
vical lacerations and 11 O had no surgica l repair. The bi nation with Aci-Jel), it <loes require multipl e applica-
data on the statu s of the cervix in these cases are shown ti ons and ca n be cumbersome.
in Tabl e 25-3.
Ali ofthe 17 patients who did not ha ve a vaginal deli v-

ery (C-secti on) had a normal or grade 1cervix. Ofthose
who had a vagina l deli very in whi ch min or cervica l lac-
erati ons were not repaired (major cervica l lacerati ons
10 , \ 1
....
I 1 /!G
were repaired), 19. 1 percent had a grade ll through IV IO..., ~ \ ,.. /ID
cervica l eversion (2 1/1 1O). In the group of 44 patients in _,,,

which minor cervica l lacerati ons were repaired usi ng
fi gure-of-eight 3-0 Vicry l sutures at the time of de li very,
5 pati ents (5/44, 11.4%) had cervica l eversions ofgrade
11 through IV The di ffe rence between the cesarean sec-
ti on group and the vag inal deli very group in which mi-
nor cervical lacerations were not repaired is stati stica lly
significant (p=.0486, chi-square analysis). However, the
di fference between the repair group and no repair group
was not stati sti call y signifí cant alth ough the incidence
of grad e 11 through IV cervica l evers ions was lower in
the repair group . In th is analys is, grade 1cerv ica l ever- Figure 25-5: A Birtcher Hyfrecator.
sion is considered to be norma l.
Management Concepts ------~
When th ese pati ents who appea r to have a cervica l in-

tlammati on are refe rred to the phys icia n by the FCP, the
phys ician does a pelvic exa mination and eva luates the
presence or absence of a cervica l eversion. If an ever-
sion is present, it is then treated. The standard treat-
ment currentl y used at th e Pope Paul VI ln stitute is to
hyfrecate the cerv ix at monthl y interva ls until the cervix
hea ls. This is accompli shed us ing a Birtcher Hyrrecator
(a lthough other models are ava il ab le) and a 6- inch ex -
Figure 25-6: A 6-inch needle poi nt extender to a pencil con-
tended needle electrode on a pencil tip contro l handl e trolled hyfrecator designed to be abl e to reach the cervix.
The end po in t of treatment is not necessaril y to revert

the chart complete ly to a " norma l" a ppearance, w here
d ischarge is absent during the earl y pre-Peak and post-
Peak phases of the cyc le. However, with th e treatment
of a cervica l eversio n, a signiti ca nt reducti on in the
amount of abnorrnal rnucus di scharge thereby ma king
the wo rnan 's ab ili ty to detect the points of change dur-
ing both th e pre-Pea k and the imm edi ate post- Peak
phases of th e cyc le eas ier. Thi s fac ilitates th e wo man 's
appl icati on of ye ll ow stamps during the pre-Peak and
post-Peak phases of the cyc le, and it makes the systern
more applicabl e to the couple and helps their confi dence
to increase signi tica ntl y (Figure 25-9).
Side effects ofthe hyfrecating treatment include a wa-

Figure 25-7 : A cervica l evers ion , grade 11 1(Fro m: Pope Paul VI tery di scharge for 7 to 1Odays fo llowing the hyfrecation.
lnstitute research, 2004).
Small arnounts of bleed ing (s potti ng) rnay be assoc i-
ated w ith the treatment fo r a few days. Over the years of
experience, the trea tm ent is avo ided in wo men who are
breast feeding and not ovulating or menstru ati ng. In
thi s case, the cervix seern s to bleed more than usua l and
fo r a longer peri od ofti me- severa l weeks (thus, treat-
ment is avoided). O nce menses and norma l hormone
fun cti on resumes in the breast-feeding wo man, treat-
rnent can be used. T he rout ine treatm ent of the cerv ix at
the six-week postpartum checkup rnay also be consid-
ered. Even though the data are not yet stati stica ll y sig-
ni tica nt, this ap pears to be Iess problemati c with regard
to th e repair ofthe minor cerv ica l lacerati ons that occur
at the tim e of de li very, and the eversions seem to be
somewhat sma ll er. Thus, a one-a pp licati on treatment at
the time of the six-week postpartum checkup with either
a hyfrecator ora sil ver ni trate appli cation is a reaso n-
Figure 25-8 : The ce rvix of Figure 25-7 which has now been
trea ted effectively and the endocervica l epi thelium has un- ab le ongo ing approac h to the manage ment of these situ-
dergon e metaplasti c tran sform ation to a sq uamous epithelium ati o ns.
(Fro m: Pope Pa ul VI lnstitute resea rch , 2004) .
31 32 33 34 35
Befo re
L
L H OAO VL B !OC OAD 4•1 4•1 ~CY 8Y IOCL "6Y MD IOCL 4 •1 IDC PC
a.A.O D ><I x~ xi x.3 x.I xt XI KI hyfrecation
After
º hyfrecation
Figure 25-9: The CrMS chart in a patien t prior to hyfrecation and following hyfrecation for a cervical eversion (From : Pope Paul
VI lnstitute resea rch , 2004).
Chapter 25 : Ch ron ic Discharges and the CrMS 299
About 25 perce nt of the patients who meet th e c riteria When the phys ician has compl eted treatment for the pa-
fo r cervi cal inflammatio n will have a no rmal-appearin g tient, the patient sho uld be referred back to the FCP be-
ectocerv ix. In these c irc um stances o r in ci rc umsta nces ca use the basic patte rn of di scharges, w hi ch is impor-
where the cervi x is treated fo ll owed by no signi fica nt ta nt fo r know ledge offertili ty, w ill have changed. One or
change in the muc us pattern, post-Peak progesterone two fo llow-ups may be necessary to ass ist w ith this tra n-
vaginal-cerv ical suppo rt (PVCS) ca n be used. Progest- sition (Tab le 25-5 and 25-6).
erone vag inal capsul es (3 00 mg) ca n be administered
during the post-Peak phase of the cycle fro m Peak + 3 1n a large number of cases w ith these criteri a, th e cervix
throug h Pea k + 12 every day at bed time (Q D hs). The has been cultured a nd fo und to be negati ve. A va riety
progesterone has a local dry ing effect on the cervix and of d iffe rent antibi oti c approac hes have been used to
often reduces the amo unt of mucus s igni fica ntl y or w ill treat thi s wi tho ut success. T hu s, the most likely ex pl a-
completely dry up th e patte rn. natio n for thi s occurre nce is the re lati onship ofth e cer-
vica l evers ion: the endocervica l g landul ar epithe lium
Th e ave rage numbe r of v is its fo r t rea tm e nt w ith has become visibl e on the ectocerv ix and is traumati zed
hyfrecati on ve rsus treatme nt w ith the use of s il ver ni- by the acidi c vag ina l mili eu. Thi s c reates a chro ni c irri-
trate is shown in Tabl e 25 -4. Hyfrecati o n is a more effi - tation that results in a di scharge fro m those epitheli al
cient fo rm of treatment as indi cated by the fewe r num- ce ll s w hen it wo uld not norm all y be present.
ber of office v is its necessary fo r treatm ent.
An interesting combinati o n offactors and the expected
treatment is shown in Figure 25- 1O. The first cycle shows
Table 25-4: Ave rage N umber of Visits a pro longed mucus cyc le that is cons istent w ith the
for Treatment grade l l cervica l evers ion that was observed o n exami-
natio n and treated . In additi on, a short post-Peak phase
Cervix' grade AgN0 3 Hyfrecation
was identifie d (8 days) . To effecti vely manage thi s, the
1.2 (n=6 ) 1.1 (n=8) patient was given human chorionic gonadi otropin (HCG)
11 2.5 (n=15 ) 1.4 (n=59) 2000 units intra muscul a r (IM) P+ 3, 5, 7, 9 ( cooperati ve
111 3.5 (n=13 ) 2.0 (n=53) progesterone replacement therapy, CPRT). Her post-Peak
IV n/a 2.5 (n=19 ) phase was lengthe ned to 14 days. The earl y muc us did
(not in database)
not clear effecti vely w ith the treatrnent ofthe cervix but,
in coordinati on w ith her FCP, the patient used pre-Peak
ye ll ow sta mps in combin ati o n w ith th e post-Peak HCG
makin g a very useabl e a nd effective fa mil y planning
system.
Table 25-5: Medica! Man age ment P rotocol

for Treating Cervical Inflammation
in Creighton Model Users
Table 25-6: Expectations of Medica!

A. lf eversion is grade 11 or larger: M anage ment Protocol in Treating
1. Hyfrecate superficia lly at month ly intervals Continuous Discharge
until hea led (g rade 1 or less).
2. lf discharge persists and chartin g con fidence
is low or patient has premenstrual tension
syndrome , then .. • Abnorma l discha rge will disappear and norma l
a. Progesterone vaginal capsules 300 mg discharge will be more obvious .
per vag ina QD hs P+3 - P+ 12
• Abnormal discharge will decrease (but not
b. Continue progestero ne therapy far a disappear) and norma l discharge will be more obvious
minimum of 6 months . - lmproves confidence in use of yellow
stamps
B. lf eversion is grade 1 or smaller:
• Physician provides sup port to couple choosing
1. Proceed immediately to steps 2a and 2b CrMS
above if charting confidence is low or palien!
has PMS . • Physician refers patient back to FCP after
treatmen t so charting details can be reviewed
C . Refer palien! back to FCP.
9 10 11 IZ 13 14 15 16 17 18 19 ZO 21
VL M H M L VL
'4><2 OAD OAO
VL M H/ M M
'ª
H H M L L VL ax1 eoc
XI
~ 3 "e
ic2
BC.
wl
IOC
XI
IOC
x2
IOC
i.;2 x2
4.>t 1 ól.AO OAD OAD QAO
OAO CA.O CAD P+S P+1
P+>
1' HCG HCG HCG
Figure 25-1 O: In this figure , the first, untreated cycle shows signs of ce rvical inflammation , a 13-day mucus cycle and an 8-day
post-Peak phase . On examination , a gra de 11 cervix was observed and treated . With the use of post-Peak HCG (see text) and
pre-Peak ye llow stamps , the cycle was very effectively managed (From: Pope Paul VI lnstitute research , 2004).
Frequent 2W Observations ----~

Table 25-7: Observation of "Frequent 2Ws"
The frequent observation of wet without lubrication
lncidence of Positive Cervical Cultures
(2W) referred to as a " frequent 2W" patte rn , has a lso
(N= 18)
been studied . Thi s pattern which occurs during the earl y
pre-Peak phase of the cycle and during the post-Peak Cervical Cultu re n %
ph ase of the cycle fro m Peak +4 onward. When thi s
Positive 15 83.3
pattern occurs, it is associated with a lo w-grade infec-
Negative 3 16 .7
tion of the cervix.
In 18 consec utive pat ients where the cerv ix has been

cultured for ali bacteri a (not simply a ~-strep cul ture), 15
ofthem had positive cultures (83.3 %) (Table 25-7). A ful!
li sting ofthe di ffere nt bacteria that ha ve been identifi ed
in these cases a ppea rs in Table 25-8. In these cases,
anti bi oti c-spec ifíc treatment ca n be helpful. Examples Table 25-8: Organisms Cultured in Patients
oftreatment are sho wn in Figures 25-1 1 and 25 -1 2. With with "Freq uent 2W" Discharge Patterns
appropri ate antibi otic treatment, the 2W discharge dis- (N =l8)
appears .
Organsim n %
Group B ~-Hemolytic strep 5 27 .8

The author has seen one patient who had a continuous
Gardnerella vaginalis 4 22 .2
2W discharge (being managed elsewhere) that was left
uncultured and untreated. The patient, during her preg- Negative 3 16.7
nancy, had a spontaneous rupture of membranes at 32 Gandida albicans 2 11 .1
weeks and s he delivered prematurely. Thus, these dis- Clostridium sp . 2 11 .1
charge patterns are not just of academic interest, but Prevotella sp . 2 11 .1
are clini ca lly very important. Escherichia coli 5.6

Figure 25-11 : A patient who is 36 years old , gravida 2, para 1, and having frequent 2W observations. She is 19.1 weeks
preg nant and culture revealed yeast (Gandida albicans) and Group B {3-strep. Treatment with yeast medication and penicil lin
reverted her observations back to dry (From : Pope Paul VI lnstitute research , 2004).
12 13 14 15 16
IOSL IOSL 105L JOSL IOOL él ~ ~ -.. O 0 0 0 ,a 0 0 0 O 0 0
Frequent 2W's
®Cervical culture = E-coli
Successfully treated wi th Kefiex
Figure 25-12 : This pa tient has freq uent 2W observations during the pre-Peak and post-Peak phases of the first cycle and one-
half of the second cycle. Cervical cultu re revealed E. coli. lt was successfully treated with Keflex and the 2W observations
disappeared (From: Pope Paul VI lnstitute research , 2004).
Green Discharge _________~ lmplantation Mucus ________~
On occasion, the CrMS chart wi ll revea! a persistent There may be time when a chroni c di scharge pattem is
green ish discharge (F igure 25- 13). Cases like this are compl etely normal although it mi ght be interpreted as
rare. However, we have had the opportunity to culture being rel ated to a cervica l inflammation. Such an ex-
fo ur of these pati ents. In three of th em , positive cul- ampl e is present in Figure 25-14. In thi s case, the patient
tures existed (Tab le 25 -9) . An interesting feature ofthi s became pregnant during the course of this cycle, and
particular circum stance is that ali three ofthem had the the standard impl antation bleeding is identified in days
presence of multiple organi ms. Agai n, antibi oti c-spe- 29, 30, and 3 1 of her cycle. However, on day 22 and 23 of
cifi c treatment can be helpfu l in eliminating thi s pattem her cyc le, she had a Peak-type mucus discharge. This
and the subsequent effects that resul t from chron ic in- pattern , whi ch been observed in a numberof patients in
fect ion. earl y pregnancy, i ca lled " implantation mucus." The
freque ncy of this has not been studi ed, but its ex ist-
ence has been clearl y observed. In thi s case, th e mucus
di scharge is a norma l variant and most like ly an en-
dometrial discharge. As a result, no treatment is neces-
sary. Treatment ofthe cervix with any type of mechani-
ca l treatment would be contraindicated during preg-
nancy.
Continuous Peak-type Mucus _ _ _~
The standardi zati on of the mucu s ign, which is the

Figure 25-13: A green mucus observatioíl (From: Hilgers TW, fo undation of the CrMS , has allowed for the adaption
Prebil AM , Daly KD , Hilgers SK: The Picture Dictioílary of the ofthe defi niti on of th e Peak Day in those pati ents who
CREIGHTON MODEL FertilityCare™ System, Pope Paul VI have a continuous Peak-type mucus di scharge. This
lílstitute Press, Omaha, NE, 2001 ). pattem is co mmon ly observed in women who have a
norma l cervix.
Table 25-9: Culture R esults of P atie nts Overa 10-year peri od oftime, research showed that the
with Green Discharge (N =4) last day of clear (K) could be used as a sign of the Peak
Day in women who have regular meo trua! cyc les, a
Results of Culture N % co ntinuous mucus di scharge of Peak-type mucus, and
Postive 1 2 3 75 .0 a normal cervix. In this study, women were identifi ed
Negative 25.0 who had a continu ous discharge of Peak-type mucus
and the description of clear (K), whi ch di sappeared dur-
1. lnduded enterococcus faecalis, Garrinerella vagina/is, Prevotella divin,
Prevotella bivia, Staphylococcus aureus, and Klebsiella pneumoniae ing the post-Peak phase of th e cyc le (excludi ng pre-
2. In all three cases , multiple organisms were present. menstrual mucus). Twenty-six patients were studi ed fo r
a tota l of 4 7 menstrual cycles (Tabl e 25 -9). The age of
this population averaged 31.8 yea rs, but ranged from 22
9 lO U 12 L3 14 IS 16 17 18 23 24 25 26
VVL VL H M L L VL
iiiC OAO OAO OAD ~8
-~
Figure 25-14: A coílceptioíl cycle usiílg the CrM S with Peak Day Oíl day 17. lmplantation mucus was preseílt Oíl days 22 aíld
23 aíld implantatioíl bleediílg Oíl days 29, 30 , and 31 . A positive serum pregílaílcy test Oíl day 34 (Peak +19) was ideíltified . All
of the dates were confirmed by ultrasouíld (From: Pope Paul VI lnstitute research, 2004) .
th ro ug h 40 yea rs of age. The average gravidity was 1.5 tion occurred by K + 3 as indi cated by either a progester-
a nd parity 1. 3 w ith a ra nge fo r both ofO to 6 . one leve! of greater than 2.3 ng/m L or a fo ll icul ar rupture
demo nstra ted by ul traso und. T hu s, the last day of clear
The general protoco l as ked for a p rogestero ne leve! to (K) asan alte rnati ve fo r the Peak Day pro ved to be l 00
be drawn on the third day fo ll ow ing the last day of clear percent re liable in thi s particul a r gro up of pati ents.
( K+ 3). In the actua l study protoco l, 35 of the 47 cycles
had K+ 3 progeste rone levels d raw n. lf the progester- As a resul t of thi s research, a new manage ment proto-
one leve! was greate r than 2.3 ng/mL, the n the wo man co l was adopted fo r the continuous di scharge of Peak-
was postovulatory. That measurement of progesterone ty pe muc us thro ugh the course of the menstrual cyc le
wo uld prov ide th e same in fo rmati o n, based upon bio- in women wi th reg ular cyc les. It is beyond the scope of
chemi ca l para meters as those w hi ch have defin ed th e thi s textbook to go into the deta il s of thi s exact protoco l
stud y of the Peak Day fo r severa ! years. because it is specifi ca lly reserved to the fun ctio n of th e
FCP . Exampl es of th is manage ment pro toco l, however,
Tn thi s study, we also had one cycle in which the proges- are shown in Figures 25-1 5, 25- 16, and 25- 17. But, a cau-
te rone leve! was draw n on K-1 and two cyc les in which ti on is worth noting: there may be a te nde ncy fo r the
the progeste rone leve! was d raw n o n K+4. N ine cyc les FCP a nd the phys ician to begin us ing th e last day of
were also studi ed in nin e di ffere nt patie nts w he re the c lear as a new defini tio n fo r th e Peak Day. Thi s is not
progeste rone leve! was not determined but the wo man what has been developed here. The Peak Day co ntin-
was undergoing an ova ri an ultraso und stud y to deter- ues to have its same defi niti on but, in women w ith a
mine the exact day of ovul ati o n. Table 25 -1 O shows the conti nu ous Pea k-type mucus di scharge ( criteri a), th e
breakdown of the study gro up . " last day of clear" can be identi fie d and substituted fo r
the traditi onal defi niti on of the Peak Day. lt is extremely
The results ofthe stud y grou p for all 4 7 menstrual cycles important not to use thi s new defi ni tion in any other
are summari zed in Table 25- 11 . The two women who had c ircumstance except thi s one!
K +4 progesterone levels d raw n had a mean leve! of27 .O
w ith a range of 26.8 to 27. 1 ng/mL (clearl y postov u- Research continues to look further at thi s issue. lt may,
latory by severa ! days). The mean progestero ne leve! in the fu tu re, be of help. However, at the present time,
for the K+ 3 group (n = 35) was l l .8 ng/m L w ith a range th at resea rc h is just beg inning a nd is not the instruc-
of4 .1 -28.5 ng/mL. The woman whose progesterone leve! ti o n of the CrMS . Women w ho use thi s pro toco l (the
was dra wn on K-1 had a leve! of 2.4 ng/mL (whi c h is last day of clear) also need to be awa re of th e sta nda rd
postovul atory) . Fina ll y, in th e wo men w ho had ul tra- defi niti o n of the Peak Day beca use the last day of c lear
sound studies of ovulatio n, al1ovu lati ons occurred fro m may not be present in every cyc le.
K-2 th ro ug hK+ 1. In all 47 cases ( 100.0 percent) ovul a-
Table 25-11 : K +J Stud y Gro up H o rmon e and

U ltraso und R esults 1 (N=47)
Mean Range
Table 25-10: K + 3 Study Groups
K-1 progesterone level 2.4 n/a
Co nsecutive P atients (N =26) (n=1)
K+3 progesterone level 11 .8 4 .1- 28 .5

(n=35)
Number of patients 26
K +4 progesterone level 27 .0 26.8-27 .1
(n=2)
Number of cycles stud ied 47
U/S series resul ts Fol licular rup ture
Type of study
(n=9) K-2 = 1
K- 1 progesterone level 1 K-1 = 3
K + 3 progesterone level 35 K=2
K +4 progesterone level 2 K+1 =3
Follicular U/S series 9 1. In all 47 cases (100%) ovulation occurred by K+ 3 as indicated by a

progesterone level >2.3 ng/ml ora follícular rupture demonstrated by
U/S.
1 2 3 4 5 6 7 8 9 LO u 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
1 ;,) f ff f f f f f f f ~f tf fff f f f f fff f

H H M/H L
...
L
IOC.
Vl VL
SG
xi !~
"'
.... .,
IOG
xI
~e
..~G
KI
<DG
....
~CK
><1 ...
~K
xI
IOC• IOKL IOt<L toe• SK
I
YL •3 x I AD XI
I
se
• I
4 xa. ~G
• 1
SG IOC. IOC !OC IOC
XI x I <I • I
~G ~G
xI
~G
• 1
IOC IOG roe
xi • 1 xI PE RIC D
1'
a.2.o
pbQ( ES ~RI DNE

lEV L
"'
'" - ,_
1:.
f f... f ~~~ f ~.. f ~ f ~~ f
MIH L 8C 4xa <DG <DG IOC IOG !OC
H H
...
L
IOC
VL VL
"6
• 1
SG
xi
"'
IOG
XI
~e rDG
xI
G>G <>CK G,K IOCK IOKL IOKL IOCK SK
x I X 1 • 1 YL
X3
I
X1 AD • I
I
xI x I
86 IOC IOC IOC. IOC <DG G>G
xO. X1 •1 xI X1 xa xI • I X1 • 1 <I
"'
Fig ure 25-15: A cycle with a continuous Peak-type mucus discha rg e with the last day of clear observed on day 18. A K+3
progesterone level was 22 .2 ng/m l , which is definitively in th e postovulatory range. Thu s, post-Peak ye llow stamps can be
used in a cycle such as this and have been employed in the second line of charting (From: Pope Paul VI lnstitute research , 2004).
1 2 3 4 5 6 7 8 9 IO u 12 13 14 IS 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
~ f f f f f f ~ ~ f t t f f fii~lif f
MM L L VL VL !OC
YL
xa.
"'
x:> xa. ...
IOC IOCK IOCK iOCK IOCK IOCK IOCK IOCK IOCY IOCY IOCY IO PC SCP 'i!CP <>AD <lAJ:l !OC ;JA[) 'i!CY IOCY
Yl YL Lx3 L<3 YL YL Lxa. L•3 GL L•3 Lx :l YL Yx:l Yx;!.
.a.
"ª
xa.
'f' L
XI
xi •a ¡::'-RI JD
t
!S.O
FRO t.JE~ ITE ~01 ~E

"' l E\i tl
... r ~
,_ ~
f f f f f f f f ~ f 4f ...
M M L L VL VL IOC
YL
xa ,,
YL YL Lx3 L<3 YL YL L<O.
X ..
'ª ...
IOC IOC' IOCK \OCK IOCK IOCI< IOCK 1oc•
ex• IOCY IOCY IOCY IOPC 8CP SCP a.AD aAO roe aAD SCY IOCY
GL Lx3 Lx:l YL Yxa Y•ó>.
xO. X ..
YL
• 1
xi
'"
"'
Figure 25-16: The last day of clear is observed on day 15 of the cycle in a woman who otherwise has post-Peak, Peak-type
mucus. Her K+3 progesterone level was 18.0 ng/m l , which is in the postovulatory range. In a situation such as this , post-Peak
yellow stamps ca n be used in the second cycle of charting so long as ali other protocols are followed. lt is shown in this fashion
in the second line of charting (From : Pope Paul VI lnstitu te research, 2004).
1 2 3 4 5 6 7 8 9 IO u 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
~~ ~ f ~ f f t @~ f f ~ f f f f f f f
H H M M L
I
X .. XI
!E
X 1 •I
I
X.. Lx 1 xi
I
...
IOCL ICGI< llOCI< 1oc• IOC• IOCK IOC PC IOCG
x;i. XI
I
IOC IOC IOC G.PC IOG IOCG
xi xi • I •1 x I
I
x i
"G "G ge se se
xi •I x I xi PI RI JO
t
FR
ex: cu ~~ ~~ I~~
Ul
... F( LLI UL ~R
OF
UP' llJR
... - - ,_ - ,----.
n ~ !~ ~ Ir - 1~
f f ~ f ..~ ~ ~ ..~. f
H H M M L IOCL IOCK IOCK IOCK IOCK IOCK IOC
xa XI x I x I
I
I
"' I
Lx l XI
1
PC IOCG
xI
I
IOC !OC IOC
XI x i xi •I
I
XI ..
'-FC IOG !OCG G.CG
xi """
KI
se
xi
se
• I
QC
• I
...
Figure 25-17: In this cycle, daily ultrasound examinations were being performed and foll icular rupture (F R) was identified as
occurring on K-1. Thus, the last day of clear (K), which was on day 11 , would be an excellent indica tor of an alternative Peak
Day. Yellow stamps could be used in the second cycle of charting as depicted here in th is example (From : Pope Paul VI lnstitute
research, 2004) .
Acknowledgements - - - - - - - - - - - - - - - - - - - - - - - - - -
Th e author acknowledges the assistance of Joseph B. Stanfo rd , M.D., MS PH , CNFPM C, associate professor ofthe
Department of Family and Preventi ve Medicine, Uni ve rsity of Utah , Sa lt Lake C ity, Utah in preparation of this
chapter.
1. Ferenczy A: The o rmal Trans fo rmati o n Zone. In : Wri ght 3. Hamm ill HA: Un usua l Ca uses of Vag ini tis. O bstet Gynecol
VC , Lickri sh GM , Ed s. Bas ic and Ad va nced Co lposco py. C lin No rth A me r 16:337-3 4 5, 1989.
Hous to n: Biomed ica l Co mmuni ca ti o ns, 1989, pp . 43-4 8 .
4. l-lilgers TW, Abraham G E, Cavanagh D: atura l Famil y Plan-
2. C vetko vich LL, Hil gers TW, Gentrup BB : Co ntinuo us Mu- nin g 1 - The Peak Sympto m and Estimated Tim e o f O vula-
cus: Correlat io n of Poin t of Change w ith Preov ulatory Ri se ti o n. Obstet Gyneco l 52:575, 1978.
in E s tradi o l-1 7 ~. lnt Rev Na t Fa m Plan 12 :340-352, 1988 .
lsomolecular Hormones versus
Heteromolecular Artimones
for Use in Therapeutics
T he cl assic definiti on of a hormone is a substance

th at is released into the b loodstream at one spec ial
ti ssue site and tra vel s to a di stant set of cell s w here the
excretion of large amounts ofestrogen in the urine dur-
ing pregnancy was reported by Zondek in 1928 . This
fi nding was important to chemi sts who soon iso lated
substance exerts its characte ri sti c effects. 1 Th e term an active substance. A few yea rs later, its chemical struc-
" hormone" was first used by Professor Ernest Henry ture was eluc id ated.-1
Starling. Afte r Bayliss and Starling di scove red th e ac-
ti on of secretin in 1902, th ey recogni zed that the term In 1928, George Com er and Will ard Allen studi ed adult
" interna] secretion" was an inadequate descripti on of ovariectomi zed rabbits after mating to eva luate the ro le
these substances. 2 ln June 1905 , Starling used the term of the corpus luteum . In 1929 , they concluded:
" hormone" in his Crooni an Lecture on the chemica l cor-
" the ev idence is now compl ete that in the ra bbit the
re lation ofthe fun cti on ofth e body. The wo rd hormone
corpus luteum is an organ ofinternal secretion, which
is deri ved from a Greek verb, hormao, meaning to put
has fo r one of its fun cti ons, th e produ ction of a
into quick rnotion, to excite or to aro use. 3 After secretin,
specia l state of th e uterine mucosa (progestati onal
the next hormones identifi ed were thyrox in in 19 14 and
proli ferat ion) .. .the fun cti on of the pro li fera ted en-
insulin in 1922. While ex tracts ofovarian estrogenic hor-
dometrium is to ... protect the free bl as tocysts and to
mone were prepared by severa! in vestigators between
make poss ible the ir impl antation." 2
19 1 l and 191 8, an "ovarian horm one" was first iso lated
by E. A llen and E. Doisy in 1923. 2
Later, they obtain ed crude oily extracts of the corpora
T he results of early investigati ons indicated that the lutea. Thi s ex tract enabl ed them to demonstrate its abil-
ovary secreted at least two substances. 1n 1897 , Beard ity to maintain progestati onal proli fe ration or pregnancy
postul ated that the corpus luteum served a necessa ry in ra bbi ts whi ch had been oophorectomized after mat-
function during pregnancy and , in 1903, Fraenkel showed ing . Comer is credited with the di scovery of the hor-
that destruction of th e corpora lutea in pregnant ra bbits monal acti on ofprogesterone in 1929. 2
caused mi scarriage. By l 926, Loewe and Lange di scov-
ered a fe male sex hormone in the urine of menstruating Will ard A llen, in hi s "Reco ll ecti ons of my Li fe with
women and observed that the concentrati on ofthe hor- Progesterone," reca lled that the name progesterone was
mone vari ed with the ph ase of th e menstrua l cyc le. The " born in a London pub." At the tim e, the favo rite name
~~~~- ~ ~~~~~ 307

for this hormone was " luteo-sterone. " In a move of in- nonnally manufactured in the body. ln fact, med ica! pro-
temational cooperati on, Allen worked with others in the fess ion al meetings that deal with the hormones of the
selection ofthe term, progesterone, which has now been menstrual cycle or reproduction attest to the extensive
universally accepted. 5 misuse oftermi nology in this area.
The development ofthe capacity to produce large quan- In the last half of the 20th century, the focus in repro-
tities of progesterone at low cost is attribu ted to Russell ductive biochemistry and pharmacology has been on
Marker. As a young man , Marker worked as a chemist the use of artificial hormone substitutes rathe r than
for the Ethyl Gaso line Corporation where he was re- the use of the naturally-occurring hormones as they
sponsible for the development ofthe process of octane chemicall y exist. This has been stimul ated by the ab-
rating. In the late l 930s, he became interested in the sence of fundamenta l research in developing systems
problem of mass-producing progesterone cheaply and that wou ld allow for the targeted use of hom1ones in the
decided that searching for a chem ical precursor derived menstrual cycle. S ince both estrogen and progestero ne
from plants was a reasonable approach. Marker's hunch are produced in a cyclic fas hion during the cou rse of
was strengthened by the discovery of a plant steroid, the menstrual cyc le, they cannot be taken on a da ily
diosgenin. Severa! trips were carried out to search for basi s 1ike other hormones. Rather, their use must be
plentiful so urces of thi s plant steroid , and it led to the specifica lly targeted in the menstrual cycle. The absence
jung les of southem Mexico where Marker fou nd that of research in targeted reproductive horm one use has
the roots of a pl ant, cabeza de negra, contained the generated a focus on substitutes that suppress or de-
diosgen in. 6 stroy normal hormonefunction and make it appear sim-
plisticall y that such targeting is unnecessary.
In the early l 960s, Jensen and colleagues suggested
the presence of intracellular receptors for estrogens in The CREIGHTON MODEL FertilityCare™ System
target tissues. This was important hi storically because (CrMS) and NaProTECHNOLOGY provide a simple and
it was the first demonstration of receptors of the ste- reproducib le means by w hich the menstrual cycle can
roid/thyroid super family and because it provided the be targeted, thus re-emphasiz ing the use of hormones
experimenta l approaches used to identify simi lar recep- that are naturally produced in the body. To use such
tors for the other stero id hormones. A second form of hormone preparations, the physician needs to have a
the estrogen receptor has been identified more recently. 4 so und understanding ofbasic steroid biochemistry (and
the importance of such use) a long with the pharmaco-
Over the last century, extraordinary amounts of work logic differences between the various ap plications and
have been done in relation to the ovarian hormones, an understanding of the pharmacokinetics for the use
estrogen and progesterone, and the ir va rious synthetic of such hormones .
substitutes. 1n the first half of the century, most of the
work focused on th e identification and production of
the hormones that are naturally produced in the body. Overview of Steroid Biochemistry ==l
In the second half ofthe century, an overwhelming ma-
jority of the research has gone into the production of Steroids make up a subclass of lipids and are distin-
substitutes fo r progesterone and estrogen . gui shed by a basic skeleta l structure offour fu sed rings
termed perhydrocyclopentanophenanthrene (F igure 26-
Thi s work, in the latter half ofthe 20th century, has been 1). The stero id subcategory of mo lecules is part of a
stimulated by two major factors. T he first is that the large and di verse fami ly of chemical compounds that
pharmace utical industry has focused on developing come under the rubric ofterpenes or isopreno ids. This
compounds that can be patented and protected , thereby disparate gro up includes natural rubber, numerous fra-
deve loping a profit. Second ly, the introduction of the grant o ils, turpentine hydrocarbo ns, caroteno ids, and
oral contraceptive in 1960 led to a strong fundin g base fat-so luble vitam ins. 7
for the pharmaceutical industry to pursue a variety of
different formu lations. In Figure 26-2, steroid carbon atoms are numbered and
the perhydrocyclopentanophenanthrene rin gs are indi-
Unfortunately, this has led to one of the sing le-most cated by letters . This basic structure, with 27 carbon
inexact biochemical, phys iological and pharmaceutical atoms , is found in cholesterol. C holestero l has the dis-
applicati ons in ali ofmedicine. Medica! literature is re- tinction of being the first isopenteno id isolated in pu re
plete with the use ofthe term s " progesterone" and " es- form. The generic form steroid is derived from it. The
trogen" even when the y do not apply to the hormones initi al stage in steroid biosynthesis is the conversion of
Chapter 26 : IMH vs. HMA for Use in Therapeutics 309
26
27
Figure 26-1 : The perhydrocyclopentanophenanthrene ring Figure 26-2: The standard steroid configuration used for
structure (From: O'Malley BW, Strott CA: Steroid Hormones: purposes of nomenclature. The steroid carbon atoms are
Metabolism and Mechanism of Action . In: Yen SSC , Jaffe RB, numbered and ring structures are designated by letters (From :
Barbieri RL: (Eds): Reprodu ctive Endocrinology: Physiology, O'Malley BW, Strott CA: Steroid Hormones: Metabolism and
Pathophysiology and Clini ca l Management. 4th Ed . W.B. Mechanism of Action. In : Yen SSC , Jaffe RB , Barbieri RL:
Saunders Co. , Philadelphia , 1999). (Eds): Reproductive Endocrin ology: Physiology, Pathophysi-
ology and Clinical Management. 4th Ed . W.B. Saunders Co.,
Philadelphia , 1999).
cho lesterol to the c 21 compound , pregnenolone, by los-

ing a 6-carbon fragment (Figure 26-3). This takes place
within mitochondria of cells capable of initiating ste-
roidogenesis. ln addition to the ability ofthe cells in the
adrenal cortex, ovary, testes, and placenta to perform
HO
cholesterol-side-chain cleavage, cells in spec ific areas CHOLESTEAOL
~~a93º
ofthe brain can also perform this function. 7
Stero id synthesis consists of two general pathways, a

pregnenolone (the embryonic precursor from which ali
bio logically active steroid hormone are produced) path-
way and a progesterone (produced from pregnenolone PAEGNENOLONE PAOGESTEAONE
~»~º~
by the action of 3 -~-h ydroxysteroid dehydrogenase)
pathway. Synthesis of the C 18 estrogenic steroids (es-
trone and estradio l - 1 7~) and the C 19 androgenic hor-
mone (testosterone) is shown in Figure 26-3. The kinds
of steroids produced and secreted w ill depend on the
17-HYDAOXY- 17-HYDAOXY-
physio logic (or pathophysio logic) nature of the ste- PAEGNENOLONE PAOGESTEAONE
l~
roidogenic ce l1 and the inactivity of inherent enzyme
l
~~~~
systems .7 o o
The natura l steroids are named after the saturated hy-

drocarbons and when a li rings are saturated , the parent
OEHYDAOEPI- .1 4 -ANDAOSTENE- ESTAONE
name ends in -ane (F igure 26-4). The names for unsatur- ANDAOSTEAONE OIONE
ated or aro matic steroid s are derived from the saturated
T") l l
~JSD-P.--0
OH OH OH
co mpound s by changing the terminal -ane to
-ene, -diene, or -triene, preceded by the number of the
lowest carbon ato m in vo lved. 7
'1 1-ANDROSTENE- TESTOSTEAONE ESTRADIOL

In the metabo li sm ofprogesterone, the liver irreversibl y DIOL
reduces the ring A doubl e bond. Reduction ofthe ring A

double bond is fo ll owed by reducti on of the 3-keto Figure 26-3: The metabolic pathways for the ovarian bio-
gro up . The two reduction steps are commonly combined genesis of estrogen and progesterone (Adapted from :
Loughlin T. Cutler GB : Pro-Opiomelanocortin and Regulation
and referred to as ring A reduction . ln the reduction of
of Adrenal Androgen . In : Lobo BA (Ed). Seminars in Repro-
ring A, the hydrogen at C 5 can be introduced in either ductive Endocrino/ogy, 5: 153-159, 1987).
e
1
e
<
Cholestane Pregnane Androstane
C9 C9 @
Figure 26-4: The structure of the paren! compounds when all of the steroid rings are
saturated (From : O'Malley BW, Strott CA: Steroid Hormones: Metabolism and Mechanism
of Action . In: Yen SSC , Jaffe RB , Barbieri RL: (Eds): Reproductive Endocrinology: Physi-
ology, Pathophysiology and Clinical Management. 4th Ed . W.B . Saunders Co ., Philadel-
phia , 1999).
the alpha or beta position. The reductases of liver re- tomary practice in reproductive endocrinology is to de-
quire nicotinamide adenine dinucleotide phosphate tem1ine the concentrations of biologically active ste-
(NADPH) and are located in either microsomes (5 a- roid hormones in plasma or serum. 7
reductase) or the cell sap (5 ~-reductase) . Beta reduc-
tion at C 5 for progesterone is predominant in humans. Progesterone is secreted by the ovary mainly from the
Reduction ofthe 3-keto group usuall y results in forma - corpus luteum during the second half of the menstrual
tion of a 3 a-hydroxyl group. Progesterone al so under- cycle. Secretion begins just prior to ovu lation from the
goes reduction of the 20-keto group. As indicated in follicle that is destined to release the egg. lfthe ovum is
Figure 26-5, the metabolic pathway goes from progest- fertilized , implantation will take place about seven days
erone to pregnenolone to pregnanediol (an excretory later and, almost at once, the deve loping trophoblasts
by-product). 7 begin secreting human chorionic gonadotropin (HCG)
into the materna l circu lation. HCG is very similar in its
The metabolism of estrogen is shown in Figure 26-6. chemical structure to luteinizing hormone (LH) and one
Estrogen by-products are largely excreted in the urine of its main functions is to stimulate the corpus luteum
as glucuronides and sulfonates of estrone, estradiol , to continue producing progesterone and estrogen.
and estriol along with 2-hydroxyestrone. The compound Thus, it sustains the functional life of the corpus lu-
2-hydroxyestrone can be further metabolized by methy- teum. Measurements ofthe rate ofsecretion ofproges-
lation at C 2 -methoxyestrone. Estrone and 2-hydrox y- terone suggest that a few mi lligrams per day are se-
estrone are the major metabolites in normal subjects.7 creted during the follicular phase ofthe cyc le, but 1Oto
20 mg are secreted during the luteal phase and severa!
Steroids can be transferred from blood to urine without hundred milligrams are secreted during the latter part of
being changed, but in small amounts compared to re- pregnancy. Rates of 1 to 5 mg per day ha ve been mea-
duced and conjugated metabolites. Although steroids sured in men and are comparable to the values in women
and their metabolites can be quantified in urine, the cus- during the fo llicular phase ofthe cycle. 4
CH 3 CH 3 CH 3
1 1 1
c=o c=o
o ~Progesterone
"º_.ctfb H
Pregnenolone
"º.ct95º" H
Pregnanediol
Figu re 26-5 : The pathway for progesterone metabolism from progesterone to pregnanediol (From: O' Malley BW, Strott CA:
Steroid Hormones: Metabolism and Mechanism of Action . In : Yen SSC , Jaffe RB, Barbieri RL: (Eds): Reproductive Endocrinology:
Physiology, Pathophysiology and Clinical Management. 4th Ed . W.B . Saunders Co ., Philadelphia , 1999).
Chapter 26: IMH vs . HMA for Use in Therapeutics 311
H
o
HO ~ Estradiol
~~ o
HO ~ Estro ne
o / ~ ~
"º M ~ º"
HO~ HO
2-Hydroxyestrone Estriol
~ o
CH,O ~M
HO ~
2-Methoxyestrone
Figure 26-6: The pathway for the metabolism of estradiol-17 ~ (From : O' Malley
BW, Strott CA: Steroid Hormones: Metabolism and Mechanism of Action . In : Yen
SSC, Jaffe RB, Barbieri RL: (Eds): Reproductive Endocrinology: Physiology, Patho-
physiology and Clinical Management. 4th Ed . W.B . Saunders Co., Philadelphia,
1999).
The ovaries are al so the princ ipie source of circulating sites where estrone is synthesized from dehydroe pi-
estrogen in premenopausa l women. The maj or secre- androsterone, which is secreted by the adrenal cortex .
tory product is estradiol , which is synthesized by granu- In men, es tro gens are produ ced by th e testes, but
losa cells from androgenic precursors that are provided extragonada l producti on by aromati zati on of circulat-
by the theca cell s. Aromatase acti vity is induced by ing C 19 stero ids (such as androstanedi one and dehy-
gon adotropins, which act via pl as ma memb ra ne recep- droepiand rosterone) appears to account fo r the maj or-
tors to elevate intrace llular concentra tions of cyc l ic ad- ity of circul ating estrogeni c hormones. Thus, the level
enosine monophosphate (AMP). The ovary contains a of estrogens is regulated in part by the availabili ty of
form of 17 ~-h ydroxy steroid dehydroge nase (Type 1) and rogenic precursors. Large quantities of estroge ns
that favo rs the producti on of testosterone and estra- are also synthes ized by the pl acenta, whi ch uses fe tal
diol from androstanedi one and estro ne res pecti ve ly. dehydroe piandrosterone and its 16 a -hydroxy l deri va-
However, the li ver conta ins another form ofthi s enzyme ti ve to produce estrone and estriol, respecti vely. Hu-
(Type 2) that favo rs ox idation of circulati ng estradiol to man urine of pregnancy is thus an abundan! source of
estrone, and both of these steroids are then con verted natu ra l estroge ns. 4 (For those interested in a more in-
to estrio l. Ali three of these estroge ns are then excreted depth rev iew of stero id bi ochemi stry, they are referred
in the urine al ong with the ir g lucuronide and sul fa te to the excell ent rev iews ofLoose-Mitche ll and Stancel4
conjugates . and O ' Malley and Strott7) .
In postmenopausa l women, the principie source of es-

troge n is adipose ti ssue stroma and other non-ovarían
312 The Medical and Su r g ical Pra ct ic e of NaPro T ECHNO L OGY
Progeste rone and Estrogen Receptors di ffe rentl y to vari ous estroge ni c compounds. For ex-
ampl e, whil e both receptors bind es tradi o l-1 7 ~ , the
A sing le progesterone rece ptor (PR) gene is res pon- phytoestroge n Geni stein binds to E R-~ with about a
sib le for producing two isofo1111s of the progestero ne ti ve-fo Id higher aftini ty than to E R-a .4
receptor, PR-A and PR-8 . T he bio log ical acti viti es of
PR-A and PR-B are d istinct and depend on the targeted
gene in question. T he shorter PR-A acts as a tra nscrip- Effects of Progesterone and Estrogen l
tio nal inhi bitor of other stero id rece pto rs. Spec itica lly,
ligan ded PR-A represses the stimul ati on oftarget genes The name progesterone refers to a sing le compound
by estrogen, g lucocorti coids, minera locorti coi d and an- that is identiti able by its mo lecular structure. The term
drogen receptors. ln most cell s, PR-8 med iates the stim u- estrogen, on the oth er hand , refers to a fa mil y of com-
latory activities of progeste rone. PR- A also inhi bits thi s pounds that have a general group of predi ctabl e phys i-
action of PR-8 . T he am ino-termi nus of PR-A is the in- o logica l effects. P roges terone is a natu rally occu rring
hibitory doma in res po ns ible for the transrepressio n c 21 stero id ; testosteron e is a natu ra ll y occ urring cl 9 ste-
caused by PR-A. T hi s inhibi tory domain is present in ro id ; and the estrogens are natura ll y occwTing C 18 ste-
both PR-8 and PR- A, but fo r un know n reasons onl y ro ids.
PR-A has represso r acti vity. 4
T he effects of progesterone on the menstrual and ferti l-
T he estrogen horm ones exert th eir effects by interac- ity cyc le are outlined in Tabl e 26-1. Progesterone inhib-
tion w ith those receptors th at are members ofthe super its the effects of estroge n on the endocerv ical mucus-
fa mil y of nuclear receptors. T here are two di stinct es- produc ing crypts and stimul ates the production of Type
trogen receptors : ER-a and ER-~ (products of separa te G mucus mostly during the postovul atory phase of the
genes). The tirs t one di scovered was E R-a , and it is cycle and during pregnancy. This ty pe of mucus acts as
mostly located in the fe ma le reproductive trac t ( espe- a barrier to sperm penetrati on, what is often referred to
cially the uteru s, vagina, and ovari es), the mamm ary as a c losure of the biol og ica l va lve . In pregnancy, it also
glands, the hypoth alamus, endotheli al ce ll s, and vas- inhibits access of various pathogeni c bacteria into the
cular smooth muscle. ER-~ is expressed in a somewhat- intra uterine cav ity.
d iffe rent tiss ue di stribu tion, fo und mostl y in the pros-
tate and ova ries and fo und in lower abundance in the P rogesterone a lso decreases the frequency of th e hy-
lu ngs, bra in, and vascul ature. Th e recepto rs appear to poth alamic pul se generator and in creases th e ampl itud e
have differe nt bio log ica l fu nctions and may respond of L H pul ses released from the pituitary g land. After
Table 26- 1: Effects of P roges terone o n the Menstrual and Fertility Cycle
Stimulates production of Type G mucus in the cervix during the cycle and in
pregnancy
Decreases frequency of the hypothalamic pulse generator
lncreases the amplitude of LH pulses released from the pituitary
Stimulates the development of secretory changes in the endometrium
Decreased progesterone late in the cycle is main determina n! for onset of

menstruation (with an assist from estrogen)
Induces early decidual changes in the endometrial stroma
Causes cytolog ical alterations toward the condition of pregnancy in vaginal

epithelium
Very importan! in the maintenance of pregnancy
Decreases myometria l contractility
Induces proliferation and maturation of the acini (glands) of the breas!

(especia lly in pregnancy)
Is thermogenic
Adapted from: Loose-Mitchell OS, Stancel GM: Estrogen and Progestins. In: Hardman JE, Limbird LE,
Gilman AG (Eds). Goodman and Gillman's The Pharmacological Basis ofTherapeutics. lntl Ed. (10th)
McGraw-Hill; New York 2001 .
Cha pter 26: IMH vs . HMA for Use in T he rapeutic s 313
ovul ati on, progestero ne producti on decreases myome- nancy in the vag inal epith elium . Progesteron e, whi ch
trial contracti li ty. The progesterone ho1111one is also ther- progresses to very high leve Is during pregnancy, is im-
mogeni c, which acco unts fo r the elevated basa l body portant fo r maintaining pregnancy. 4 Progesterone also
temperature in women during the postovul atory phase decreases myometri al contracti lity and does thi s during
ofth e cycle.8·9 Decrease in progesterone prod ucti on late pregnancy. In the breast, it induces pro li fera ti on and
in the menstrual cyc le is the main determínate for th e maturation of the ac in i (the glands). Whi le thi s does
onset ofm enstruati on (w ith help fro m estrogen). occur to some extent during th e menstrual cyc le, the
effects on the breast are most promi nent in pregnancy.
Progesterone also stimul ates the deve lopment ofsecre-
tory changes in the endometrium , whi ch are essentia l Sorne of the metabo lic and other effects of progester-
for imp lantation ofa bl astocyst. lt can also induce early one are outlined in Table 26-2. Progestero ne does not
dec idual changes in th e endometri al stroma and causes interfere with the benefic ia! effects of estrogen on ei -
cyto logica l alterations toward the condition of preg- ther high-density 1ipoprotein cholesterol (HDL-C) or low-
densi ty lipoprotein cholestero l (L DL-C) profi les. Jt is
Table 26-2: Metabolic and Oth er Effects fo und circul ating in the serum mainly boun d to album in
of Progesterone or cortiso l-binding globulin (CBG or transcortin). It is
metabo li zed in th e li ver primaril y to hydroxylated me-
tabol ites and th eir sulfa te and gl ucuroni de conj ugates.
Does not affect the beneficia! effects of estrogen on These are then elimin ated in the urine. Progestero ne
either HDL-C or LDL-C profiles has a fair ly short half- li fe and undergoes rap id first-
Underg oes rapid first-pass metabolism pass meta bolism. Progesterone also has anxiolyti c and
Is bound to albumi n and cortisol-binding globulin (CBG or antidepressant effects on the centra l nervo us system.4
transcortin ) Progesterone may also protect aga inst fi brocysti c breast
Has short half-l ife di sease, endometrial and breast ca ncer, and osteoporo-
Metabolized in the liver prima rily to hyd roxylated sis. lt promotes fat bumin g fo r energy and can actas a
metabolites and their sulfate and glucuronide conjugates , diuretic.10
which are elim inated in the urine
Has anxiolytic effects in CNS
The genera l effects of estrogens are outlin ed in Ta ble
Adapted from : Loose-Mitchell OS, Stancel GM: Estrogen and Progestins. In:
26-3. The estrogens are impo1tant in the deve lopment
Hardman JE, Limbird LE , Gilman AG (Eds). Goodman and Gillman's The of secondary sex ual characteri stics in fe ma les. Thi s in -
Pharmacological Basis of Therapeutics. lntl Ed. (1Oth) McGraw-Hill; New Yor1<
2001 . cludes the growth and development ofthe vagina, uterus
and fa ll op ian tubes. A long with other hormones, estro-
Tab le 26-3: General Effects of Estrogens

Develop ment of Seco ndary Sexual C haracteristics in Fema les
Growth and development of the vagina , uterus and fallopian tubes
With other hormones, causes enlargement of the breasts through promotion

of ductal growth , stromal development and the accretion of fat
Contributes to molding the body contours, shaping the skeleton and bringing
about the pubertal growth spurt of the long bones
Growth of axillary and pubic hair
Pig mentation of the genital region , nipples and areola (in pregnancy)
Breas! ducts in pregnancy mature
Has positive effects on bone mass
lncreases HDL cholesterol
Decreases LD L cholesterol and lipoprotein A
Adapted from : Loose-Mitchell OS, Stancel GM: Estrogen and Progestins. In: Hardman JE, Limbird LE,
Gilman AG (Eds). Goodman and Gillman's The Pharmacological Basis ofTherapeutics. lntl Ed. (10th )
McGraw-Hill; New Yor1< 2001 .
gen w ill also cause enl argement ofthe breasts thro ug h gen undo ubtedl y has an effect o n the secreto ry ce ll s in
promotion of d ucta l growth, stro mal deve lopme nt and the endo metrium during the postovul atory phase ofth e
the accretio n offat. lt contributes to the moldin g of the cycle, but its exact rol e has not been cl earl y eluci dated .
body conto ur, sha pin g of the ske leto n, and pube rta l Furthe r research in thi s area may be very important in
growth spurt of th e lo ng bo nes ; it a lso has pos itive the future deve lopment of strateg ies for th e treatm e nt
effects on bon e mass. T he growth of ax il la ry and pu bic ofvari ous re productive abn orm alities.
ha ir and the pi gme ntati on of the genital region (as we ll
as the ni pp les and areo la during pregnancy) are a lso Th e gene ral patte rn of ste roid ho rmon e actio n see ms to
estroge n-re lated effects . In pregna ncy, it also indu ces include ali of the fo ll owing2 :
the breast ducts to mature. Estroge n inc reases HD L-C
whi le decreas ing LDL-C and lipo prote in-A.4 l. Upta ke ofstero id by the target cell in bindin g to
specifi c steroid cytoplasmi c receptor.
T he effects of estroge n in the menstrual a nd fe rtili ty
2. T ra nsformati on of the receptor compl ex to an
cyc le a re o utlined in Tabl e 26-4. In the preovul atory
acti ve form.
phase of the cycle, estrogen stimul ates th e g ro wth of a
new pro liferative e ndo metrium fo ll ow ing th e sheddi ng 3. Trans locati o n ofthe transformed steroid-recep-
ofthe endometriu m d uring me nses . lt w ill stim ulate th e to r compl ex to the nu cleus.
endocerv ica l crypts to produce type E mucus, whi c h is
4. Binding of thi s active co mplex to specific "ac-
essential fo r sperm mi grati o n a nd pe netrati o n thro ug h
cepto r" s ites o n the genome (chromatin DNA
the cervix a nd fo r fe rtili ty (referred to as ope ning th e
a nd ac idi c no n-hi ston e pro te in).
bio log ic va lu e). Estrogen w ill also increase rh ythmi c
myo metri al con trac ti ons, whi ch can be ide nti fie d dur- 5. Acti va tion of the tra nscripti onal apparatus ( RNA
ing the preovul ato ry phase of the cyc le w ith the use of po lymerase) resulting in the appearance ofn ew
rea l-tim e ultraso nogra ph y. Th ese contrac ti o ns mayas- RNA species, whi c h inc ludes specific mRNA s.
s ist sperm tra nsport. 4 Estrogen w ill a lso inc rease tu ba!
6. T ra nspo1t of the ho rmon e-induced RN A to th e
muscul ar contractili ty.
cytopl as m resultin g in the synthes is ofn ew pro-
te ins o n cyto pl as mic riboso mes .
Fo ll owing ov ul ation , hi g h estroge n leve Is cause a fee d-
back to the hypothala mic-pituitary ax is to decrease fo l- 7. Finall y, the a ppearance of a speci fic ste ro id-me-
licle-stimulating hormone (FS H) and luteinizing hormone di ated functi o nal respon se characteri sti c ofth at
( LH ) prod ucti on. Thi s is o ne ofthe maj o r postovul ato ry parti cul ar target ti ssue.
effects of estrogen producti o n. Estroge n a lso enabl es
the inducti o n of progestero ne recepto rs a nd induces
the matu ra ti o n of ce ll s in the vagi nal epithe lium . Estro- lsomolecular Hormones (IMH) vs .
Heteromolecular Artimones (HMA) ==l
Table 26-4: Effects of Estroge n on th e With the deve lopm ent of th e oral contraceptive a nd its
Menstrual and Fertility Cycle w idespread marketing in 1960, a cons iderable am o unt
of effo rt has gone in to the research and investi gatio n of
a seri es of bi oc hemi ca ls that ha ve both estrogen-like
and progeste ro ne-like prop erti es, but are neithe r estro-
Induces endometrial proliferation
gen no r progestero ne . The first orall y acti ve estrogen
Stimulates type E cervical mucus production
substitute was the non-ste roidal co mpound diethylstil-
lncreases rhythmic myometrial contractions (which may
bestro l, w hich was synthes ized by E.C . Dodds in 1938. 11
assist sperm transport)
Subsequentl y, it was fo und that an alte ration of th e tes-
lncreases tuba l muscu lar contractility
tosterone mo lecul e y ielded an o rall y acti ve compo und,
Feeds back to hypothalamic pituitary axis to decrease
eth iny 1testosterone (eth isterone ), that had so me proges-
FSH and LH production
tati ona 1-type ac ti vity. 2 ln 1950, it was found that the re-
Enables induction of progesterone receptors
moval of the C 19 carbo n from testosterone resulted in a
Induces maturation of cells in the vaginal epithelium
s ig nifi can t decrease in androgeni c acti vity. 12 Dj erass i
and Rosenkra ntze saw the theoretica l potentia l of these
Adapted from: Loose-Mitchell DS, Stancel GM: Estrogen and Progestins. In:
Hardman JE, Limbird LE . Gilman AG (Ed s). Goodman and Gillman's The new " 19-nor ste roid s" and in 1951 , they synthes ized 19-
Pharmacological Basis ofTherapeutics. lntl Ed. (10th ) McGraw-Hill; New
Yor1<2001 .
no r progeste ron e and ultimatel y no rethindrone, th e 19-
no r vers io n of ethi ste ro ne. Searl e Labo ratories, in 1952,
Chapter 26: IMH vs. HMA for Use in Therapeutics 315
synthesized norethynodrel. Later, norethynodrel was they have been derived from a natural source. These
se lected as a potential oral contraceptive agent for test- hormones are also properly referred to as bio-iden-
ing in a small group of women. lt was later shown that ticct!.
norethynodrel had the ability to suppress ov ul ation but
irregular spotting and bleeding were common, so the Heteromolecular Artimones (HMA):
estrogen mestranol was added to the norethynodrel pill These are chemicals that are distinct and different
to yield a combined medication marketed under the name from the isomolecular hormone to whi ch they are
Eno vid. This pill, Enovid, was the first marketed bi11h often confused. In the case of reproductive hor-
contro l pill. Thereafter, the number ofavailable prepara- mones, they may have estrogen- like and progester-
tions proliferated. 2 one-like activity, but invariably that act ivity is not
the same as the isomolecular horn1ones. Furthermore,
In 1964, ethinyl estradiol was introduced asan alterna- they also have chemical activities in the body that
tive to mestranol as th e estrogeni c component. Severa! are distinctly different from the isomolecular hor-
other progestational agents beca me available. Growing mones. These HMAs are substitutes fo r the "real
ev idence of an association between the estrogen com- thing." Chem ical compounds with biological activi-
ponent potenti ally catastrophic side effects accelerated ties that are progesterone-like have been vario usly
the trend toward " low-dose" combination pi li s contain- referred to in the literature as progestins, progesta-
ing less than 50 µg of ethinyl estradio l. A variety of tional agents , progestagens, progestogens ,
different co mbinati on preparations have sin ce been gestagens or gestogens. Often, however, the term
marketed. These con ta in varying ratios of the estrogen progesterone is used to refer to these hormones and
and progesterone substitutes across a 2 1-day period of that is in accurate. Thus, it is appropriate to refer to
administration in order to minimize the clíni ca! side ef- these substitutes as artimones (artificial hormones)
fects. 2 or more specifi ca ll y HMA progestins and HMA es-
trins.
From a cli nical point ofview, this creates a blurring in
the minds ofphysicians as to what is an estrogen which The molecu lar structures of IMH progesterone, IMH
is produced naturall y in the body and progesterone estrad iol , a variety of HMA progestins and HMA es-
which is also the same as that manufactured in the hu- trins are shown in Figure 26- 7. lt is easy to see how the
man body. The blurring of the distinctions between chemical structures differ.
these two has beco me so signi ficant that, in reading
medica! literature (i ncluding very high pro file treatises), The distinctions between these di fferent chemicals can
the distinction between what is the naturally occurring be demonstrated. 1n Table 26-5, the relative potencies
hormone versus an artificial subst itute, which is not the ofthe IMH progesterone and various HMA progestins
naturally occurring hormon e, has occurred. are shown . These potencies were derived by looking at
the relative doses required to eli cit responses similar to
To <leal with this in NaProTECHNOLOGY, this chapter those seen in premenopausal, secretory endometria. The
introduces new terminology to all ow one to speak fac- HM A progestins are sign ifi cantly more potent than the
tually about the various preparations. The new termi- IMH progesterone. Birth control pi lis contain only HMA
nology includes the terms isomolecu/ar hormone (lM H) progestins, the most common of which is norethindrone
and heteromo/ecular artimone (HMA ). These are de- (Tab le 26-6). The progestational , estrogenic, androgen ic
fined as follows : and endometrial activity ofvarious ora l contraceptive
components is li sted in Table 26-7. In this assessment,
lsomolecular Hormone (lM H): the progestational activity was assessed by the induc-
This is a chemical that is chemically (by nature of its tion of glycogen vac uoles in the human endometrium.
molecular structure), biologically, physiologically While the HMA estrins do not conta in progestational
and pharmacologically identical to the hormone that or androgeni c activity, most of the 19-nortestosterone
is manufactured naturally in the human body. While progestational agents (HMA progestins) have signifi -
these are often referred to as " natural hormones," cant androgen ic activity.
the actual origin ofthe chem ica l is notas important
as the isomolecular nature of it. These chemicals Estradiol metabolism varíes, depending upon the stage
can be synthesi zed from various precursors and of the menstrual cycle becau e of the cyc li c rates of
made to be identi ca l to the human hormone. In fact, production of that hormone. Thus, it is also different
there are virtually no isomolecu lar hormones in use between the pre- and post-menopausal phase of a
at the present time that are natural in the sense that woman 's life. Estradi ol undergoes rapid hepatic bio-
IMH Estradiol-17~ HMA Estrins

H
o
~
OH
~ lÓCi!CH
HO HO(X)
Estrad iol Mestranol Eth inyl estradiol
IMH Progesterone HMA Progestins

'fHJ
. ít~i'"'". ~'"'".
OD95 Proges terone
o~ -
Norethind rone
o~ o~
1
Noreth ynod rel

íÓ'"'"
Norethindrone
ace tate
-
Ethynod iol diacetate Norgestrel
Norgestimate Desogestrel
Figure 26-7 : The structural formula for the HMA estrins and the HMA progestins side by side with IMH estradiol and IMH
progesterone .
Table 26-6: M ost Co mmon HMA Progesti ns in

Combination Birth Co nt rol Pills 1-1995
N %
Table 26-5: Rela tive Potencies of
IMH Progestero ne and Norethindrone 23 62 .2
Ortho- Novum 71717
Various HMA P rogestins 1•2 Ortho-N ov um 1/35
Ortho-Novum 1/50
Levonorgestrel 4 10.8
Triphasil-21
Progsterone
Norgestrel 2 5.4
Dyd rogesterone 10 Lo/Ovral
Medroxyprogesterone acetate (Provera) 50 Norethindrone acetate 2 5.4
Norethindrone 500 Loestrin
L Norgestrel 4,000 Norgestimate 2 5.4

Ortho T ri-Cyclen
1. The relative doses required to elicit responses similar to those seen Ethynodiol diacetate 2 5.4
in premenopausal. secretory endometrium. Dem ular
2. Kina RJB, Whitehead MI : Assessment of the Potency of Oral
Administered Progestins in Women. Fertil Steril 46: 1062, 1986. Desogestrel 2 5.4
Desogen
1. Choice of Contraceptives. The Medical Let1er on Drugs and

Therapeutics. New Rochelle, NY 37:9, 1995
Ch apter 26: IMH vs . HMA for Use in Therapeutics 317
Table 26-7: Bio logic Activity of Oral Contraceptive Components '
Progestational Estrogenlc Androgenic Endometrial

Class Compound Activity 2 Activity' Activfty• Activity 5
19-Nortestosterone progestins
Gonane
Levonorgestrel 2.0 o 15.0 2.0
dl-Norgestrel 1.0 o 7.5 1.0
Estrene
Ethynodiol (ethynodrel ) diacetate 0.53 0.86 1.0 0.5
Norethindrone (norethisterone) acetate 0.44 0.38 2.5 0.067
Norethindrone (norethisterone ) 0.38 0.25 1.6 0.033
Lynestrenol 0.33 2.60 4.8
5-1 O Estrene
Norethynodrel 0.10 2.08 o 0.036
HMA estrins
Ethinyl estradiol o 100.00 o
Mestranol o 67 .00 o
1. From: Dickey RP: Individual oral contraceptiva activity. In: Managing Contraceptiva Pill Patienls. Ed 3. Duran!. OK. Creativa lnfomatics. 1983.
2. lnduclion of glycogen vacuoles in human endometrium. From: Dickey RP, Stone S: Progeslalional Potency of Ora l Contraceptives. Am J
Obstet Gynecol47:106-111 , 1976.
3. Rat vaginal epithelium assay. From: Janes RC, Edgren RA: The Effects of Various Steroids on Vaginal Histology in the Rat. Fertil Steril
24:284-291.
4. Rat ventral prostate assay. From: Tausk M. deViser J: lntemational Encyciopedia of Pharmacology and Therapeutics. Elmsford, NY, Pergamon
Press. Sect 48, Vol 11 , Chap 28, 1972.
5. Delay of menses. From: Greenblatt RB: Progestational Agents in Clinical Practica. Med Sci 37-49, May 1967.
transformation , and its plasma half- li fe is short. On the lyceri des are increased . Breast tendemess and endome-
other hand, ethinyl estradiol is cleared more slow ly than trial stero id receptors are also increased. The 19-nortes-
estradiol dueto decreased hepatic metabolism. The eli mi- tosterone derivatives increase plasma! insu lin while
nation phase half-life of ethiny l estradio l has been re- decrea ing glucose tolerance. They also decrease HDL
ported in various studi es to be 13 to 24 hours. 4 Unlike cho lestero l while increasing LDL cholesterol. Nitrogen
estradiol , its primary root ofbiotransfonnation is via 2- retention is also increased and skin sebum production
hydroxilation and subsequent formation of the corre- is increased (although countered to sorne extent by the
sponding 2- and 3-methyl ethers. Mestranol is the 3- HM A estrin component). CNS effects are also increased
methyl ether of ethinyl estradi ol and , in the body, it and endometrial steroid receptors are decreased by these
undergoes rapid hepatic demethylation to ethinyl es- derivatives.
tradiol which is its active form.
A number of clini cal effects are assoc iated with the
The HMA progestins and HM S estrins are widely used HMAs used in contraceptive medications. These are
in reproducti ve and postmenopausal medicine at this 1isted in Table 26- 1O. They include HMA estrin-related
time. Those more commonly used preparations are iden- effects such as adverse mood changes, the enhance-
tified in Tab le 26-8. They are ali approved by the Food ment of thrombos is, increased blood pressure, venous
and Drug Ad mini stration (FDA). Yet, the distinct ions thromboembolism and hepatocellul ar liver adenomas.
between the isomo lecu lar hormones and heteromolecu- H MA progestin-re lated effects also include ad verse
lar art imones conti nue to be blurred even at the FDA mood changes in addition to weight gain, acne and ner-
leve l. vo usness. The combination of th e two HMAs has re-
su lted in increased myocard ial infarction in smokers over
The metabo li c effects ofthe heteromo lecular artimones, the age of 35 , a delayed time to conception after the
wh ich are common ly used in the contracepti ve medica- di scontinuation of the HMA , and a lower return of the
ti ons, are varied and we ll recogni zed. These are li sted in fert ility rate. Breast cancer diagnosis and invasive cer-
Tab le 26-9. Ethiny l estradiol cau es a decrease in serum vical cancer are al so increased.
album in and so rne ami no acids while resulting in an in-
crease ofthe serum globulins (angiotensinogen and cer-
tai n clotting factors). Sodium excretion, vitamin B com-
plex, and vitamin C are decreased. Cholesterol and trig-
Table 26-8: Commonly Used Preparations in R eproductive and Postmen opausal Medicine 1
Source of active Generic FDA lsomolecular Heteromolecular

Generic Name Brand Name lngredients Available Bio-ldentical Approved Hormone (IMH) Artimone (HMA)
Conjugate estrogens Premarin Pregnant mare's No No Yes No Yes

urine
Estropipate Ogen Synthesized from Yes No Yes No Yes
Mexican yams
Ethinyl estradiol Estinyl Sythesized from No No Yes No Yes
Mexican yams
Estradiol/ Activella Both synthetic No No Yes No Yes
norethindrone acetate
Conjugated estrogens Prempro Pregnant mare's No No Yes No Yes
medroxyprogesterone urine and synthetic
aceta te
Medroxyprogesterone Pro vera Synth eti c Yes No Yes No Yes
aceta te Cycrin, Amen
Norethindrone acetate Aygestin Synthetic No No Yes No Yes
Testosterone Oepo- Synthetic Yes No Yes No Yes
cypionate testosterone
Testosterone Oelatestryl Synthetic Yes No Yes No Yes
enanthate
1. Adapted from : Reed-Kane D: Natural Hermane Replacement Therapy: What it is and what consumers really want. lnt J Cmpd Ph 5: 332-335, 2001 .
Table 26-9: Metabolic Effects of HMAs U sed in Table 26-10: C linical Effects of HMAs U sed in
Contraceptive Medications Contraceptive Medications 1
Effect Clinical Effects
Ethinyl Estradiol Adverse mood changes HMA estrogen

Serum al bum in Decreased over 50 µg
Amino acids Decreased HMA progestin
Globulins lncreased
Angiotensinogen Weightgain HMA progestin
Clotting factors Acne HMA progestin
Cholesterol lncreased Nervousness HMA progestin
Triglycerides lncreased
Sodium excretion Decreased Enhances thrombosis HMA estrogen
Vitamin B complex Decreased lncreased blood pressure HMA estrogen
Ascorbic acid (Vil C) Decreased Venous thromboembolism HMA estrogen
Breas! tenderness lncreased Hepatocellular liver adenoma HMA estrogen
Endometrial steroid receptors lncreased Myocardial infarction in smokers HMAOC '
Delayed time to conception HMAOC
19-Nortestosterone Derivatives Lower return of fertility rate HMAOC
Plasma insulin lncreased Breast cancer diagnosis HMA OC/progestin
Glucose tolerance Decreased lnvasive cervical ca ncer HMAOC
HDL cholesterol Decreased
LDL cholesterol lncreased Adapted from : Míshell DR: Contraception. In: Yen SSC, Jaffe RB, Barbieri
Nitrogen retention lncreased RL (Eds). Reproductive Endocrinology: Physiology, Pathophysiology and
Skin-sebum production lncreased Clinical Management. 4th Ed. WB Saunders Ca., Philadelphia, 1999.
CNS effects lncreased
Endometrial steroid receptors Oecreased 1. OC = oral contraceptive
Adapted from: Mishell DR: Contraception. In: Yen SSC, Jaffe RB, Barb1en
RL (Eds). Reproduct1ve Endocrinology· Physiology, Pathophysiology and
Clinical Management. 4th Ed WB Saunders Ca .. Philadelphia, 1999.
Ch apt er 26: IMH vs . HMA for Use in Therapeutics 319
lsomolecular Hormones _ _ __ __ _, latory increase in the BBT is beca use ofthis thermogenic
action of progesterone.
A va ri ety of isomolecu lar horm ones fo r both progester-
one and estrogen are commercia ll y availab le and are Figure 26-9 il lu strates th e excreti on pattern s (whi ch
ava il able th ro ugh compo unding pharmac ists. These are somew hat retl ect the production pattern s) of total es-
li sted in Tab le 26-11 . These are sometimes referred to as trogens a long with the three major components : estrone
bioidentical hormone preparations, which mean s that (E), estra di o l-1 7 ~ (E 2) , and estrio l (E) . Thi s excretion
they are bi ologicall y and phys iolog ica ll y identi ca l to pattern is a compos ite graph fro m 1Onorma l women. Ali
the hormones natu ra ll y produced in the body. The term three have a pattern of in crease prior to ovul ation, and
" bioidentical hormone" is a good and accurate term fo r sorne increase fo ll ow ing ovulati on although E3 tends to
refen-ing to these preparati ons. Ali of the ingredi ents in pl ateau somewhat more than E1or E2•
the e preparation s are approved by the FDA, alth ough
sorne co mbinations of them have not yet rece ived offí - The production of progesterone and its main excretory
cial FDA approva l. Much ofthi s relates to the avail abi l- by-product, pregnanedi ol, th roughout the co urse ofth e
ity of good research in these areas. Whil e a consider- menstrual cycle is il lustrated in Figure 26- 1O. Progester-
ab le amount ofresearc h has been done, no lobby ex ists one is produced in very small quantities during the preo-
specifí ca lly to promote the iso molecular horm ones at vul atory phase of the cyc le and thi s is mostly fro m the
the FDA level. Thus, the adequate rev iew of these prod- adrenal co ex. Fo llow ing ovul ati on and the stimul ation
ucts has been slow. of the corpus luteum by LH, the progesterone produc-
tion increases to a max imum 6 to 9 days fo ll ow ing ovu-
The thermogeni c action of progesterone is illustra ted lati on. lt then decreases fo r th e next severa ] days prior
with the basal body temperature (BBT) curve (Figure to the onset of menstruation. lts main excretory by-prod-
26-8). During the course ofthe menstrual cycle, the BBT uct, pregnanedio l, can be measured in th e urine and
ex hibi ts a biph as ic temperature pattern with the tem- pro vides an indirect meas u oement of progesterone pro-
perature being lower during the preovulatory phase and ducti on.13
higher during the postovulatory phase. The postovu-
Table 26-11: lsomolecular H ormone Preparations in R eproductive Medicine and

Postmenopausal Wo men 1 J
Source of Active Generic lsomolecular Heteromolecular

Generlc Name Brand Name lngredients Available .Hormona,· (IMH ) Artimone (HMA)
Progesterone Compounded Synthesized from Is generic Yes Yes No

-oral soy or Mexican
-sustained ya ms
relea se
-transderma l
-sublingual
-vaginal
-cream
-injectable
Progestrone Prome trium Synthesized from Yes Yes ¡ves Yes No
Crinone Mexican yams
Triestrogen Compounded Sythesized Is generic Yes No Yes No
-estriol from soy
-estradiol
-estrene
Biestrogen Compounded Synthesized Is generic Yes J Yes No
-estriol from soy
-estradiol
Estradiol Es trace , Synthesized from Yes Yes No No
Climara, soy (or yams)
Estraderm,
FemPatch ,
Estring
/
Testosterone Compounded Synthesized Is generic Yes Yes No
from soy
1. Adapted from: Reed·Kane D: Natural Hormone Replacement Therapy: W hat ~ 1s and what consumers really waqj ) nt J Cmpd Ph 5: 332-335, 2001.
16
B.B. TEMP
12
(F) Progesterone
8 ng/ml
4-
o
-14_12-10 -8 -6 -4 -2 O+ 2 +4 +6 +B +IO+12 +14 +16 8
Days of Cycle 6 - Pregnonediol

4- mg/24hr
Figure 26-8 : An example of the biphasic nature of the basal
body tempe rature curve where the dotted line in the middle is
the LH peak (From : Moghissi KS, Syner FN , Evans TN : ACom- 2
posite Picture of the Menstrual Cycle. Am J Obste! Gynecol
114:405-418 , 1972).
ol----.-~~~~~~--.----,.-r-r--.--~
-14 -10 -6 -2 +2 +6 +10 +14
-12 -8 -4 o +4 +8 +12 +16
Doys of Cycle
Figure 26-10: Th e serum progesterone and urinary preg-
50 nanediol excretion du rin g the menstrual cycle. Day O (dotted
line) represents the day of LH peak and point of reference.
40
Total Vertical bars represen! one standard error of the mean (Fro m:
Estrogens Moghissi KS, Syner FN , Eva ns TN : A Composite Picture of the
30 ,ug/24hr Menstrual Cycle. Am J Obste! Gynecol 114:405-41 8, 1972 ).
20
10 Clinical Effects of lsomolecular Hormones

0'---~~~-.~~~~-+-~~~~~~~----.---..
In 1960, the sa me yea r that the oral contraceptive be-
30 came avail abl e, the Merck l ndex ofChemicals and Drugs
20 li sted th e fo ll ow ing cases fo r use of medica! uses fo r
progestero ne: fu ncti onal uterine bleeding, amenorrhea,
10 premenstrual tension, dys menorrhea, habitual aborti on,
O'--~~-.--.~~~~-+-~~~~....-~~-.~
menopausal synd ro me, and infe rti 1ity. 14 Sin ce that time,
6 with the introd ucti on ofth e HMAs, the usage ofproges-
terone and IMH estrogen has changed significantly.
4
At thi s time, these hormones are mostl y used during
2
the postm enopausa l yea rs, where most of the data ex-
ists. Progesterone has also been used a limi ted extent in
18 - the s upport of pregnancy, th e treatment of ha bitu a l
sponta neo us aborti on and in in fe rtility. With the intro-
14 duction ofNaProTECHNOLOGY, lMR progesterone and
Estrene E 1
,ug/24 hr estrogen now ha ve multiple, new applications fo r post-
10
menopausal and premenopausa l wo men. Many of these
6 appl icati ons w ill be outli ned in other chapters, but the
data re lati ve to IM H progestero ne will be reviewed in
2
this chapter.
01~-r---.----r-r~.--~....--+--.--r~~~....---.--.-~
~4 ~o -6 -2 +2 +6 ~o ~4
-12 -8 -4 0 +4 +8 +12 +16
Progestero ne is a uni que proges tati ona l agen t bein g
Days of Cycle the onl y ava il abl e bi o- identica l and ph ys io logicall y ac-
Figure 26-9 : A composi te curve of the 24-hour urinary ex- ti ve progestational agent. Medroxyprogesterone acetate
cretion of total estrogens, estro ne (E,), estrad iol {E2} and es- (MPA) is the most co mmonl y prescri bed HMA proges-
triol {E3 } throug hout the menstru al cycle in 1O normal wo men.
tin. Whil e the change in the chemi cal structure ap pears
Day O {the dotted line) represents the day of LH peak and
point of reference. Vertical bars indicate one standard error to be small (F igure 26-7), the differe nce in structure pro-
ofthe mean (From: Moghissi KS, Syner FN, Evans TN: ACo m- duces significantl y di ffere nt effects.
posite Picture of the Menstrual Cycle. Am J Obste! Gynecol
114:405-418, 1972).
Chapter 26: IMH vs . HMA for Use in Therapeutics 321
Cardiovascular Disease propria te fo r postmenopausa l women (even those with

cardiovascul ar di sease).
The mostcomrnon cause ofdeath in women in the United
States is card iovascu lar di sease. This in cludes not only Another multi-center, randomi zed, placebo-contro ll ed
co ronary artery disease, but cerebral vascular and petri a! referred to as the Estrogen Replacement and Ath-
riph era l vascu lar di sease as we ll. An estimated 500,000 erosc leros is (E RA ) Tri a!19 used Premarin 0.625 mg/day
women die each year ofthese diseases. Cardi ovascul ar or Premarin plus MPA 2.5 mg/day and compared it with
di sease is less prominent in premenopausal women than a placebo. lt fa il ed to prevent the progress ion of athero-
in men at the same age and it is more prominent in the sclerosis in postmenopausal women who had prev iously
postmenopausal women suggesting that estrogen pl ays documented coronary stenosis. 1n the PEPI Tria! , the
a ro le in the preventi on of cardiovascul ar disease . 15 results indi cated that cyclic IMH progesterone was as
effect ive as cyc lic MPA or continu ous MPA in protect-
Premenopausa l women ex hibit hi gher leve ls of hi gh- ing again st endometrial hyperpl as ia. 17
density lipoprotein cholestero l (HDL-C) and lower lev-
els of low-dens ity lipoprotein chol esterol (LDL-C) than A number of other studies ha ve suggested that adding
those women who are postmenopausa l. Fo llowing meno- M PA to estrogen repl acement may in crease the ri sk of
pause, the LDL-C increases ra pidly and HDL-C de- myocard ial infa rction in humans and primates. Ovariec-
creases graduall y in most women. During thi s same pe- tom ized Rhesus monkeys were treated at the Oregon
ri od of time, the incidence of ca rdi ovascul ar disease Regional Primate Research Center with physiologic lev-
doubles for women. 16 els ofE 2 either alone or in combination with IMH proges-
terone or MPA fo r four weeks. Four weeks after the
The Postmenopausa l Estrogen/Progestin lnterventi on therapy was initiated, the investigators injected the pri-
(PEPI) Tria l17 showed that the HM A progestin s added mates with serotonin/thromboxane, a substance known
to postm enop ausal estroge n repla ce ment program to cause coronary artery vasoconstriction in order to
blunted their effect on the increase in HDL-C. The damp- produce myocardial infarction. In those primates receiv-
ening ofthe HDL-C leve! was related to the addition of ing MPA and estrogen , the inj ecti on provoked unre-
MPA to conjugated equine estrogen (CEE) . Howeve r, lenting constriction ofthe coronary arteri es. The IMH
when IMH progesterone was eva luated in the PEPI Trial, progesterone-treated prim ates, however, ex hibited no
it had less of a blunting effect on the leve! of H DL-C clinica ll y-significant reaction .20 In another study of ova-
when compared to that produced by MPA. ri ectomi zed monkeys, repeated quantitative coronary
artery angiogra phy was used to meas ure the effects on
The American Heart and Estrogen/ Progesterone Re- endothelium-mediated dil ati on ofatherosc lerotic coro-
placement Study (H ERS) was a large multi-center ran- na1y a1teries. After a base line was completed, the monkys
domi zed study of the effects of horm one replacement were studied one month after rece iving ora l dosing of
therapy (HRT) in postmen opausa l women with heart continu ous estrogen, eith er alone or with continuous
disease. In the four-year HERS study, subjects con- low-dose MPA or cyc li c hi gh-dose MPA given 1Odays
sisted of2 ,763 postmenopausa l women with a hi story of the month or high-dose MPA given by itse lffor 10
of coronary hea rt di sease (C H D). It showed that CEE days per month. Changes in the diameter of the left
and MPA produced no decreased risk of coronary ar- circumflex coronary a1tery were measured in response
tery di sease in the subj ects who received HRT. fn stead, to intracoronary infusions of acetylcholine and nitro-
it indi cated a higher risk of events related to coronary glycerin. When these monkeys were treated with estro-
artery disease during the first yea r of treatment. 18 That ge n alone an improved endoth elium-mediated dilation
study also showed that conjugated estrogens (Prem arin) of the arteri es was obse rved. Thi s beneficia! effect was
0.625 mg/day plus MPA 2.5 mg/day provided no sign ifi- dimini shed by th e addition of either cyc li c or continu-
ca nt benefit over pl acebo in preventing secondary car- ous MPA. 21
diovascular events including heart attack and death in
women with a pri or hi story ofC H D. In fact, more sec- More recentl y, 18 postmenopau sa l women were given
ondary cardiovascu lar events occ urred during the first E2 for fo ur weeks and were then randomized to recei ve
year ofthe study in women rece iving HRT than in those for 12 days of concomitant treatment with transvagina l
rece ivin g placebo despite an 11 -percent decrease in proge terone, orall y administered MPA or pl acebo. Af-
LDL-C anda 10-percent higher leve! of HDL-C in women ter a two-week washout peri od during which on ly E2
rece iving HRT. A favorable pattern ofC H D events was was admini stered, patients rece ived the oppos ite regi-
seen fo llow ing severa ! years oftherapy suggestin g that men for 12 more days. The pati ents underwent treadmill
even this type of long-term HRT therapy could be ap- exercise testing after each E2 treatment phase and on
322 The Medical and Surgical Practice of Na ProTE CH NOLOGY
day 1O oftreatment with HMA progestin or IMH proges- lessen myoca rdi al ischemia by reducing myocardial oxy-
terone. The results indicated that progesterone added gen consumption through a decrease in the periphera l
to E2 produced a n increase in exercise time befare any vascu lar res istance or by lowerin g pre-load. A poss ibl e
evidence ofmyocard ia l ische mia. 22 However, the HM A alternative mechani sm is a direct vasodilator effect on
progestin M PA produced no effect on the length of ex- the coronary arte ries. 33
ercise time tolerated by patients already taking E2 alone.
These studies have been con firm ed by oth ers. Similar
In the HERS study, the incidence of ischemic events in res ults we re obtai ned by Volterrani, et al,34with 1 mg of
the group who received both hormones was 50 percent subling ual E 2. Ri ede l, et al ,35 used b lood-tl ow rates of
higher than that of the control group during the first the left common femoral artery in 23 postmenopa usa l
year of therapy. T hese resul ts cont rad icted extens ive wo men asa n o utcome measure ofvascular response to
ev idence that hormone replacement therapy wou ld re- 1 mg ofs ublingua l IMH E 2 • Thi s induced a vasod il ata-
duce the mortality and morbidity from cardiovascular tion of the fe mora l arteries co mpared to base lin e and
disease. In media presentations ofthis, estrogen is sug- placebo. Cacc iatore, et al36 stud ied Iong-tern1 effects of
gested as the cause ofthe increased rate ofheart attack . ora l and tra nsde tm al ho rn1one replacement th erapy on
However, the evidence suggested that MPA inhibited carotid and uterine vasc ular impedance. The patients
the beneficia! effects of estrogen and produced the nega- received e ither 2 mg/day of oral IM H E2 or 50 µ g/day
ti ve effects . Stud ies such as the HERS and ERA tria! transdermal 1M H E2. Both routes of administration were
should be repeated w ith the use of IMH progesterone. vi1tu all y identi cal in their ability to reduce carotid and
uteri ne artery resistance to blood tlow.
In additi on to the a bove, IMH progesterone exerts a
number of other card iovascul ar effects not produced
by the HMA progesti ns. For exampl e, IMH progester- Lipid Metabolism
one has a natruretic and, thus, diuretic effect due to its
mineral corticoid activity. 23 ·24 IMH progesterone in a lMH E2 has been shown to have many positive effects
dosage of200 mg is sai d to be equivalent to about 25 to on lipid metaboli sm. Gi ven ora ll y or transdermally, it re-
50 mg ofspiron o lacto ne .25 IMH progesterone a lso has duces LDL-C and VLDL-C. lt also reduces lipoprotein A
antihypertensive activity. 26·27 leve Is to obta in these positive effects us ing transdermal
progesterone, the dosage needs to be at least 1 mg/
Progestin s such as MPA ha ve also been shown to elimi- day. 37,38
nate the c ho lestero l-improving benefit of estrogen re-
placement,27to increase trig lyceride leve! 28 and to cause
wate r retention ,28 a nd most likely increase the risk of Vasomotor Symptoms
heart attack by negating the beneficia! vasodi lato r ef-
fects of estrogen.2º· 21. 29·30 Progesterone seems to be the Parsey, et al., 39 studied 193 postmenopausal women, ran-
progestational age nt of choice far providing the maxi- do mi zed to rece ive either ora l CEE 0.3 mg/day o r
mum degree of protection that estrogen -repl acement tra nsdermal E2 0.025 mg/day for 12 weeks. The pati ents
therapy can provide fa r cardiovascu lar disease in post- were assessed aft er three 28 -day me nstrual cycles . The
menopausal wome n. Estrad iol has a positive cardi ovas- stud y showed that low-dose tran sdermal IMH E 2 was
cular effect o n postmenopausal women. The pos iti ve as effective as ora lly admini stered CEE in treating vaso-
effects ca n be reached by us ing 2 mg/day ofE 2 orally, l motor symptoms in postmenopausa l women. A signifi-
mg / da y of E 2 su blin g u a ll y or 50 µg / d ay of E 2 cant reduction in vaso motor symptoms with ora lly ad-
transdermally. Patients wi ll benefit from E2 even ifthey ministered estriol (E 3) ata dose of 2 mg/day has a lso
already have cardi ovascul ar disease or ha ve hada hys- been repo rted .40
terectomy. 31 -36 ·
IMH progestero ne has also been shown to ha ve a posi-
Randomized , double-blind studi es have shown that re- tive effect on vasomotor symptom s. Leonetti , et al., 41
placement therapy w ith IMH E2, which results in physi- studi ed 102 hea lthy wo me n in a randomized , do uble-
o logic serum leve ls, does not affect cardiac structu re or blind , pl acebo-co ntroll ed tria! ofthe control of vasomo-
function in normal postmenopausal women. 32 ln add i- tor symptom s in the meno pa use. They rece ived either
tion , wome n g ive n IMH, E2, or placebo were tested w ith 20 mg/day of tran sdermal progesterone cream ora pla-
treadm ill exerc ise tests. The time to 1 mm ST segment cebo. A review of th e subjects' wee kl y diary of symp-
depression and total exerc ise time was increased by 1M H toms chroni cled an improvement in o r resolution ofva-
E2. T he in vestigators hypothesi zed that IMH E2 cou ld somotor symptoms in 83 percent of those treated w ith
Chapter 26 : IMH vs . HMA for Use in Therapeutics 323
transdermal progesterone cream and in 19 percent of pausa! breast cancer was 5.4 times greater in the sub-
those who had received placebo. jects who had an endogenous progesterone defíciency,
when compared to subj ects who had apparentl y normal
The effect ofprogesterone on the quality oflife in post- progesterone leve ls.45
menopausal women was compared with MPA in a cross-
sectiona l survey.42 There were 176 patients receiving The protective effect of progesterone was compared to
HRT with progesterone from one to six months at the that ofTamoxifen in estrogen-induced breast cancer in
time ofthe study, before which they had received HRT small rats. lt was shown that the induction rate, multi-
with MPA. The patients were interviewed by telephone plicity and size of estrogen-induced mammary tumors
using the Greene Climacteric Scale and the Women 's were reduced by the simultaneous ad mini stration ofei -
Health Questionnaire. Women using the IMH progest- ther progesterone or Tamoxifen. This study also dem-
erone-containing regimen reported a signifícant im- onstrated that the inhibitory effect of progesterone or
provement in vasomotor symptoms, somatic complaints Tamoxifen in estrogen-induced carci nogenesis is attri b-
and anx iety and depressive symptoms when compared utable to interference with the binding of estrogen to
with women using the MPA-containing regimen. the estrogen receptors on the target ce ll s. 46
Effects on the Breasts Effects on the Brain
The anti-prol iferative effect of IMH progesterone dif- Progesterone can be synthes ized by Schwann cells and
fers from that ofHMA progestin in that IMH progester- enhance myelin formation in the peripheral nerves. 47
one affects are not limited to the endometrium. The pro- Progesterone also seems to promote myelin repair in
tective action ofprogesterone on breast tissue was dem- the brain. When progesterone was given to animals with
onstrated by Chang, et al. 43 ln this study, 40 menopausal transplanted oli godendrocytes, significantly more axons
women were evaluated for the effects oftopica lly ap- were re-myelinated after three to five weeks. Research
plied E2 and/or progesterone on human breast milk-duct such as this cou ld lead to the deve lopment ofimproved
epithel ial cells. There were four study groups: those treatments for patients with multipl e sc lerosis.
who received a placebo cream, an E2 cream ( 1.5 mg/
day), progesterone cream (25 mg/day), and both E2 and Progesterone may also reduce cerebral swellin g and
progesterone daily. After 1O to 13 days of treatment, a consequent ischemia-induced cell damage that follows
milk-duct tissue biopsy was obta ined during previously brain inj ury. 48 lt has even been suggested that IMH
schedu led breast surgery. The effects of these hor- progesterone may ha ve im portant implications for the
mones on the ce llular proliferation rates were as fol- maintenance of neuronal function during menopause
lows: E2 increased cellular proliferation rates by 230 per- and aging and for the protection aga in st neurodegen-
cent, but progesterone decreased that rate by more than erative diseases such as Alzheimer's disease. 49
400 percent. When the combination of E2 and progest-
erone was applied, th e rate ofm ilk-duct cell ul ar prolif- IM H progesterone and E2 may be benefic ia! to infants
eration remained normal. These data suggest clearly that that have been born prematurely. Premature infants are
unopposed estrogen stimu lates the hyperproliferation deprived ofthe full benefits of intrauterine E2 and proges-
of breast ep ith eli al ce ll s and the progesterone protects terone. A group of 15 preterm infants were given proges-
aga inst that hyperpro li ferat ion. terone and E2 replacement at intrauterine leve ls. When
they were exam ined, they exhibited a normal psycho-
Foidart, et al. ,44repeated this study in 40 postmenopausal motor pattern . However, preterm infants who were not
women. The data from this study strongly supported treated with progesterone and E2 replacement (the con-
the Chang 's observations. lt was concluded that proges- trol group), exhibited delayed psychomotor develop-
terone may produce a beneficia! effect on E2-induced ment. 50 While this research is new, it shows the poten-
epithe li al cell proliferation. tial that exists for investigation in these areas.
A study of 1,083 women who had been evaluated and 1n women , seizure freque ncy varíes with the serum E2 to
treated for infertility were fo ll owed from 13 to 33 years. progesterone ratio. The fluctuation of the ratio during
These women were categorized according to the cause the menstrual cycle is a major factor in catamenial epi-
oftheir infertility in one ofthe following groups: endog- lepsy. In cases of catameni al ep il epsy, IM H progester-
enous progesterone defíciency or non-hormonal causes. one may constitute a ratio nal and effecti ve adj unct to
Results ofth is study revealed that the risk ofpremeno- therapy. 51 Add iti ona ll y, a decline in complex pa11ial se i-
324 The Med ica l and Surgical Practice of NaProTECHNOLOGY
zures and secondary generalized motor seizures has been Other Effects
observed with progesterone therapy. 52
lMH estrogens may also ha ve effects on urogenital com-
plaints , skin ag ing and hypertension . IMH E3 , in par-
Effects on Bone ticular, has been shown to reduce the urogenital and
urin ary tract co mpl aints that are seen in 1Oto 15 percent
IMH E2 has been shown to ha ve a pos itive effect on the of postmenopausa l women.58·59 · ln addition, topical IMH
biochemi ca l markers for bone resorption and on bone E2 (O.O1%) and E3 (0.3 %) improves the elasti city and
minera l density in both the ora l and transdermal dosage firmn ess of the skin and decreases wrinkle depth and
fo rms. 53 · 55 IMH estrí o! (E) may also ha ve a pos itive ef- pore sizes . In additi on, th ey also increase skin moi sture
fect on bone min era l density, however, it may not be as and the number of co llagen fibers. 60
effecti ve in reducing bone resorpti on in women with a
hi story of hysterectomy.5657 No matter what dosage fo rm The systo li c and di asto lic bl ood press ure becomes
of estrogen is chose n to prevent bone loss, sorne ad- hi gher in wo men after the menopause suggesting that
j un cti ve therapy with a fo rm of ca lci um suppl ementa- estrogen defi ciency may influence the age-re lated in-
tion seems clea rl y important. crease in blood pressure. The use of eith er transderma l
or ora l l M H E2 has shown a signifi cantly decreased sys-
Ora l CEE and transdermal IMH E2 on the biochemica l tolic and di astoli c blood pressure in th is popu lation of
markers of bone resorption were compared in 60 hea lthy pati ents. 6 1.62
menopausal women. After three month s of therapy, both
groups had significa nt reduction in hydroxypro li ne/crea- Progesterone can be eva luated in the sa liva by using
tinin e rati os. Th ey also had signi fica nt reduction in various immunoassay methods. Numerous stud ies have
pyridin olin e/creatinine ratios. Th e research concluded demonstrated both the techni ca l feas ibi lity of measur-
that both therapi es were equall y effective in reducin g ing sali vary progesterone leve ls (thought to refl ect the
postmenopausa l bone resorpti on.53 non-bound progesterone fracti on-free progesterone)
and corres pond ing sa li vary progesterone profi les with
Ettinger, et al. ,54 studied IMH E 2 in dosages of0.5 mg, 1 accepted clíni ca ] indicators of lutea l functions, such as
mg and 2 mg per day, over an 18- month peri od in 4 1 pl asma horm one leve ls and ultrasonograph ic visualiza-
menopausa l women. Each pati ent also rece ived 1500 tion. But, while th e results of such studies can be used
mg of calcium ca rbonate daily. With the use of bone- to advocate the usefuln ess of the technique, they do
density rneas urements, it was conc luded that IMH E2 not provide suffi cient data to establish the reference
taken ora ll y had a continuous skeletal <lose-response standards necessary fo r analys is of sali vary progester-
effect and that ca lciurn intake pos itively modifi ed the one levels in both clíni ca! practice and research. Sali-
skeletal response. vary monitoring of progesterone rn ay be suited forre-
search and long-terrn clini cal observation, but the char-
Evans, et al. ,55 studi ed topi ca l 1M H E2 . Us ing bone min- acteri sti cs of sa li vary progesteron e data may lim it the
era l density, they concl uded th at th is was an effecti ve usefuln ess of these va lues fo r indi vidual di agnos is.63
treatment in preventing spine bone loss at ali postmeno-
pausal ages and was capable of do in g it in low dosages.
Preventi on of bone loss at the fe mora l neck was less IMH Hormone Formulations _ _ _ _~
certai n. The hi gher dose was not assoc iated with a
greater res ponse in bo ne mass. IMH triple estrogen combined with mi croni zed proges-
terone is now being used on a widespread bas is during
IMH estrí o! (E) and its effects on bone resorption have th e perimenopause and after menopause. The basis for
also been eva luated. Minaguchi , et al. 56 treated 75 women the fo rmul ati on of tripl e estrogen and progesterone was
fo r 50 weeks wi th 2 mg/day of estriol and 0.8 grams/day ini tiall y made from th e urinary excretion patterns in
of ca lci um lactate. They found that after 50 weeks , the healthy, fe rtil e women. The subsequent change in the
woman 's bone minera l density had increased 1.79 per- tripl e estrogen formulati on was made after severa! years
cent compared to pretreatrnent leve ls. Thi s was a statis- of serum estrogen measurements fro m norm al fe rtil e
ti ca lly signifi cant change. In at least one study where women.16 The ori ginal tripl e estrogen fo rmulati on, which
ca lcium did not supplement !M H E3, bone mass was not was based on th e urinary excretion pattern , was placed
mai ntained.57 at 80 percent estrío! (E 3), 1O percent estradi ol (E 2) , and
l Opercent estrone (EJ Afte r the serum leve Is had been
furth er eva lu ated, the fo rmul ati on was changed to 90
Cha pte r 26: IMH vs . HMA fo r Use in Th erapeutics 325
percent E3, 7 percent E2, and 3 percent E1. It is generall y The major estrogenic components of th e CEE are 75 to
fe lt that the comb ination of 1MH triple estrogen at a 80 percent E1, 6 to 15 percent eq uilin (an equine) estro-
dose of 2.5 mg is equivalent to 0.625 mg of CEE gen, and 5 to 19 percen t E2• CEE, whi ch has been con-
(Premarin). 16 sidered to be the go ld standard for estrogen rep lace-
ment therapy over the years, is an estrogen collected
The dosing equiva lent of 1O mg of M PA, which is the from the urine of pregnant mares (hence the na me). Many
most commonly used HMA progestin, is felt to be 200 metabolites and fonns ofequilin are fo und in CEE, ali of
mg of lMH progesterone ifgiven 10 to 15 days during wh ich have potent estrogeni c effects. 73 Equilin and its
the month and 100 mg if given 25 days during the metabolites are poorl y metaboli zed by the cytochrome
month. 16·64 P-450 system and can produce a pronounced hepatic
response. 74 Metabolites ofequilin are also eight times
Estriol (E,) is considered a weak estrogen or metabol ite. more potent as a uterotrop ic agent than equilin itse lf
lt is con verted from estrone, prim aril y in the li ver and a and are foun d circul ating for longer periods oftim e. 75 .76
sma ll amount is conve1ted from E2• Very small amounts One ofthe metabolites of equilin , eq uilenin, is cytotoxic
may be secreted directly from the ovaries. 65 When com- and causes ox idati ve stress and DNA damage in the
pared with IMH E2 , IM H E3 has a 20 to 30 percent lesser breast and uterine ti ss ue n
affinity for the estrogen receptor in th e cell. However,
IMH E 3 is highly effective if th e concentration is kept
equivalent to that oflMH E2 and it can produce si mil ar Delivery Forms, Dosing Amounts and
biologic responses. 16 Dosing Schedules --------~
One of the justi fication s fo r usi ng hi gher concentra- Various forms of lMH estrogen and progesterone are
tion s of IMH E3 in tripl e estrogen formulations is the ava il ab le from compounding ph armac ists. This allows
find ing from mu ltip le studi es 65 that E3 is antineop las- the physician to tail or therapies to fit patients ' needs.
tic.66-68 However, sorne ora l and intramuscul ar versions oflMH
E2 and progesterone are commerciall y ava il able. Intra-
lMH E3 is also beneficia! in the treatment ofvasomotor muscul ar forms of progesterone can also be compounded
symptoms in doses ranging from 2 to 8 mg per day. 69 in hi gher co ncentration s.
Endometria l biops ies have shown th at in those doses,
it did not induce endometrial hyperpl as ia. The patients A microni zed form is used for capsul es of lMH estrogen
demon strated a mild to moderate lowering ofserum FSH or progesterone. Thi s has an ultra-fine consistency. By
and LH leve ls. decreas ing the particle size with mi cronization, aque-
ous dissolution in the gastrointestinal (G l) tract is in-
Estradiol is the main estrogen secreted by the ovaries in creased and absorpti on is enhanced. Thi s in creases bio-
the premenopause. In th e postmenopausa l period, it is ava il abili ty. The mi cronized powder ca n also be com-
derived primarily by a conversion ofE 1in periphera l ti s- pounded with a slow-releasi ng agent, such as methyl-
sues. Estradiol is con verted in the small bowel to estrone ce llul ose. This provi des a pro longed, even delivery of
by the gut-associated cytochrome P-450 enzymes. 70 the hormone and, espec iall y with progesterone, can sig-
nifi cantly reduce side effects.
Estrad iol has been avai lable in com mercial preparations
for a long time. The commercia l product (Estrace), given Lozenges (troches) can also be com pounded. However,
ata dose of 1 mg, is equiva lent to a dose of0.625 mg of patients have less satisfaction with these forms. Vagi -
CEE. There is good oral absorption when it is mi cro n- na l suppos itories have also been produced. Standard
ized. The negative effect at hi gher Ieve ls of with the suppositori es have genera lly been fa irly messy and have
singu lar administrati on ofE 2 is the potenti al stimul ation been un usa ble with pati ents who are also cha1ting their
of carcinoma of the breast and endometrium in sorne cyc les using the CrMS . However, the microni zed forrn
women. lt appears that E2 should be opposed by E3 th at is compound ed into an oral ge latin capsule can
which is an estrogen receptor binder and modu lator. 16·71 also be inserted into the vagi na and used as a vagina l
suppos itory. This method is less messy and does not
The fin al component of the l MH triple estrogen pro- interfere with the woman 's mucus observati ons.
grarn is estrone (E 1). A 0.75 mg dose ofE 1is equi va lent
to to the standard 0.625 mg ofCEE. Unfortunately es- A number ofskin cream s are available with progester-
trone is fe lt to be pro-carcinogeni c in the breasts and one. However, th e amount of progesterone in most of
the endometrium at hi gh doses. 71·72 the over-the-counter creams is extremely smalJ. 1n order
326 The Medi ca! and Surgi cal Practice of NaPro TECHNOLOGY
to obtain a reasonable leve! of progesterone, a com - tiple studi es and extensive experience) is a cyc li c com-
pounded vers io n produced by a compound ing phar- bined dosing regim en . The estrogen is provided along
macist is preferable. with 100 mg of IM H progestero ne each day for 25 days
on a 28 -day calend ar. T hi s regi men has now been stud-
The recommended dosage of lMH tripl e estrogen is ied in over400,000 patients in Europe. The endometrium
between 2.5 and 5.0 mg/day w ith th e proportions of90 is maintained in an atroph ic pattern ; bleedi ng is mi nima l
percent estri o l, 7 percent estradi ol, and 3 percent es- bleeding; and 85 to 95 percent of patients a re reported
trone .16 This can be g iven e ith er daily orina divided to be ame norrheic after the s ixth month of the regi-
dose tw ice dail y. With the use of a s low-release formu - me n.16·64 There is no ab norm al ang ioge nesis. The dro p-
latio n, the "peaks and val leys" are reduced. o ut rate is reported to be 5 to 11 percent. Because of
these experiences, Dri sko 16 has suggested the dosing
The dose of IMH progesterone (m icronized progester- sc hedu le be placed at a 25 -day comb ined regimen of
one) is generall y placed at 50 to 200 mg/day given ei- IM H tripl e estrogen and progesterone based on a 28 -
ther o n a dai ly do seor a twice daily dose. 16 fM H proges- day ca lendar. The cun·ent recom mendati on for lMH triple
terone has been used in E urope fo r over 20 yea rs. estrogen begins at the 2.5 mg/day dose based on 90
percent estri o l, 7 percent estradi o l, and 3 percent es-
Drisko has provided an excellent description ofthe dos- tro ne formu lation divided in a twice-daily dose. The IMH
ing schedul e fo r these hormones. 16 This appa rently has progesterone is g iven ata ra nge of 100 to 200 mg/day
been studied extensi ve ly in Europe for almost 20 years. amd is taken with foo d. It ca n be given as a twice daily
From 1980 through 1990, th e dosage schedul e was cy- or sing le dose.
cl ic and seq uential : that is, the IMH estro gen and proges-
terone were given for on ly part ofthe month. The IMH A large mu lti-centered tria! is needed in the Un ited States
estrogen was give n for 2 1 to 25 days and the progester- to assess the LM H estro gen a nd progesterone form u Ja-
one was g ive n for 6 to l O days of the month at leve ls tion and thei r ability to protect aga inst osteo porosis, to
100 to 300 mg/day. Thi s dosing has been effecti ve in mai ntain the endometrium wi thout hyperpl asia, and to
preventing endometrial hyperpl as ia. However, it induced protect aga in st card iovascul ar di sease . l MH estro gen
regul ar bl eeding in 80 pe rcent of treated cycles and and progesterone are we l1 tolerated at the aforeme n-
proved to be di sadva ntageo us with poor patient com- tioned doses by most women . T he literature is com pe l-
pli ance. lin g to support these fo rmulati o ns and hypothesized
a biliti es, but furt her wo rk is needed .
From 1990 through 1995 , E uropean investigators con-
tinued the cyc l ic seq ue ntial administration of estro gen
with mi croni zed progesterone . They extended the dura- Absorption Patterns of Progesterone =l
ti o n of the progesterone dosing to 12 to 14 days and
used 200 mg/day of microni zed progesterone ora lly. This Over the years, there has been a cons iderab le amo unt
regime n has been chronicled in prospective, random- ofwo rk do ne o n eva luatin g the va ri o us abso rpti o n pat-
ized stud ies,64 and th e results indi cate that a lth o ug h the terns for the use of IMH progesterone by different modes
endometrium and heart were properl y protected and the of del ivery.
in cidence a nd duration of bl eeding was less when IMH
proges terone was used , the indu ced regu lar bleedi ng In 197 1, N illius and Joha nsson 78 studi ed the pl asma lev-
continued to be unacce ptab le. e ls of progestero ne afte r vaginal, rectal and intram us-
cular admini strati on ofpro gesterone. The results oftheir
In an atternpt to eliminate the bleeding, in vesti gators wo rk are summ arized in Figure 26- 1 1. With ali fo 1m of
eva luated the continu o us combined delivery method. progesterone, abso rption was fairly rapid. However, the
Estrogen was admini stered w ith 100 mg ofIMH proges- hi ghest leve ls we re observed w ith l 00 mg of progeste r-
te rone dail y to suppress bleeding . However, 35 to 70 one provided by intramu scular inj ecti on . The vagi nal
percent of patients continued to experience sorn e epi- and rectal app lication s a lso absorbed well.
sodes of irregular bl eeding o n thi s schedul e after a few
months. H ysteroscopi c eva luatio n determined that ab- Vagin al suppos itories became the mode of de livery fo r
norma l angiogenes is occurred in sp ite of an atro phic or progesterone in th e l 980s. The effects of th e supposi-
sub-atroph ic endometrium .64 The dropout rates were tory base on progesterone deli very were studied. 79 Three
hi g h beca use of th e bl eedin g. different suppository bases th at were studi ed inc luded
g lyce rinated ge la tin , cocoa butte r, and po lyethy le ne
The c urrent regimen used in Europe (resulting from mul- g lyco l. The mean peak leve l of progesterone achie ved
Chapter 26 : IMH vs. HMA for Use in Therapeutics 327
and the area under the curve was hi ghest after supp le- Fu11her study on parti cle si ze determined that, when
mentation from the po lyethylene glyco l-based suppos i- ora l progestero ne was admini stered with small er par-
tori es. The durati on of elevati on above base line was ticle sizes, the absorpti on was better; when the particl e
simil ar, however, for ali three suppos itori es (Fi gure 26- size was larger, the absorpti on was signifi cantly de-
12). creased83 (Figure 26-14 ).
The bioavai labi li ty ofora l mi croni zed progesterone was Change in th e ve hi cle upon whi ch the ora l progester-
presented in 1980 (Figure 26-13). Before this time, proges- one is admini stered ca n signifi ca ntly increase the se-
terone was not norm all y admini stered by the oral ro ute rum leve Is of progesterone. 87 ·88 Oth er stud ies ha ve also
beca use of reportedly poor bi oava il ab ility and a rapid shown the effectiveness ofora l microni zed IMH proges-
clearance rate . The peak con centrations after 200 mg of terone.84-86
ora l mi croni zed progesteron e were equ iva lent to mid-
lutea l phase progesterone concentrati ons in norm al men-
strual cyc les. Ali subj ects exhibited signifi ca nt eleva-
tion of IM H pro gestero ne o ver baseline leve Is th at per-
4 ¡··\ Glycerinated Gelatin
Suppositories
sisted for at least 6 hours after the single ora l dose; it 3 &
/º\ --·-·
returned to initial levels by 24 hours.80 0 ral progester- 2 .,-:>=<¡\_.::;--·~ ~
one had also been admi nistered to pregnant women who 1 ' k , ,o, ¡&~ ---- o
..A;;,et~:-~-~ -....:;:!===-"!--===--"!~·~
· -......._
immediately pri or to electi ve cesarean secti on. Progest- -r· '•" ~·12 =~
erone levels were demonstrated to show a marked in- o 1 2 3 4 6 8 24
HOU RS
crease in the plasma and in the whole myometrium for at
least 150 mi nutes after adm ini stration.81 6
Cocoa Butter
Suppositories
It was also shown that if the ora l progesterone was
adm inistered on a tw ice-daily bas is, the circ ulating con-
centrations of IMH progesterone and th e biologicall y
active metabo lite 20 cx-dihydroprogesteron e we re in-
creased. The du ration of these increases was suffi cient
to evoke progestational responses in responsive end
organs.82
w
z 13
o Polyethylene Glycol
a::
.¡. Prl~ esteron e admin istration w 12 Suppositories
168 ....
(/)
70
50
. I \
\
1
S.A. 9 32
100 mg PROGESTERONE intramusc
W
l.!>
o
a::
JI
10
e
~ 30
\,
25mg
10 mg
a.
e '' - - --· 100mg
- - 100 mg
rec tally
vag inall y
.. 20 \ ,
é..
-:;; 10 ''
•o
"'
''·
"\
~ ~ "\
o
.
E "\
o
ii'. '' "\
...:·•.. -·····
0.5
o2 4 6 8 12 24 36 48 hours
Figure 26-11: Plasma levels of progesterone after intramus-

cular administratio n of 1O, 25 and 100 mg of IMH progester-
one in oil and after vag inal and rectal administration of 100 mg Figure 26-12 : The serum progesterone leve! in the fo ll icular
of IMH progesterone in suppository form to the same subject phase over 24 hours after vaginal inserti on of a 25 mg IMH
on day 7 of the fo llicular phase of five different menstrua l proge ste ro ne suppository made with three different bases :
cycles (From: Nillius SJ , Johansson EDB: Plasma Level s of glyceri nated gelatin , cocoa bu tter, and polyethylene glycol
Progesterone after Vag inal, Rectal or Intramuscular Adminis- (From : Price JH, lsmail H, Gorwi ll RH , Sarda : Effect of the
tration of Progesterone. Am J Obste! Gynecol 110:470-477, Suppository Base on Progesterone Delive ry from the Vagina .
1971 ). Fertil Steril 39:490-493, 1983).
The absorpti on patterns of intravagina l progesterone PROGESTERONE AOMINISTRATION
placed in a non-liquifying base cream has shown differ- 14¡

ent absorption dynam ics than the use of IMH progest- 13
erone g ive n by ora l adm ini stration of ge latin capsules 89 12
(Figure 26-15). Absorption of intravagina l progesterone 11
in postmenopausal women who were receiving estro-
E 10
gen and w ho were not receiving estrogen was com- '"'e: 9
pared wit h sub lingua l administration of progesterone
~ 8
in women who were not receiving estrogen replacement. o
a: 7
w
T he intravaginal appli cation in those women who were 1-
Vl 6
on estro gen repl ace me nt therap y9° had the best absorp- ~
oa: 5
tion (F igure 26-1 6). Progesterone absorption has even '1.
been studied by way of nasal spray admin istration .9 1 4
Adm ini stration in this fash ion was effective in reaching 3

therapeu ti c levels and appea red to be accep table to 2
patients.
o 0.5 1 t5 20 25 3 4 5 6
Absorption of progesterone is enhanced when taken
HOURS
w ith food. Absorption of IMH progesterone was en-
hanced by a factor oftwo-fo ld in the presence offood. Figure 26-13 : The progesterone concentration s over 24 hours
Overall bioava ilabi lity ofthe ora l progesterone was ap- after receiving oral micronized progesterone 200 mg at time
zero (From : Maxson WS, Hargrove JT: Bioavailability of Oral
proximately 1Opercent as compared with intramuscu lar Micronized Progesterone. Fertil Steril 44:622-626 , 1980).
progesterone 92 (F igu re 26- 17).
A variety of studi es on the tran svaginal admin istration

Pla sma
ofprogesterone show that it can induce a nom1al secre- progesterone o--< Micronized progesterone
tory transformation of the endometrium despite low ng/ml particle size 5-1 Oµ
UTROGESTAN Batch n°3
plasma levels suggesting that there is a direct transit 23
• - -e Micronized progesterone
in to the uterus, ora " first uteri ne pass effect." 93 ·94 E ven particle sized 20-40µ
magnetic resonance imagi ng has been used to monitor Standard cryslalized
20 progesterone
the spread ofvag in ally placed products and to eva luate particle size 100>1
coverage oftopica l drugs .95
Figure 26- l 8 illustrates the peak leve Is of serum proges-

15
terone fo llow in g progesterone adm ini stration by a vari-
ety of d iffere nt forms and ro utes. Th is wo rk , done at the
Pope Pau l Vl ln stitute, is fairly cons istent w ith pub-
li shed reports. Serum leve ls w ith the over-the-counter
10
sk in c reams are ve ry low, vaginal progesteron e and tro-
c hes did not reach very hi gh p eak leve Is. Oral progest-
erone in various formats reached mid-level s. Progester-
o ne in peanut oi l (Prometrium) reached the hi ghest lev-
e Is for oral progesterone administration. The hi ghest 5
levels of ali were obtained with 200 mg of intramuscular
progesterone.
One of the more interesting questions is how well does o 2 4 6 8 24h

progesterone given in different formats absorb into the
endometrium. Figure 26-19 shows the progesterone lev- Figure 26-14 : Th e mea n plasma progesterone level obtained
e ls in paired uterine a nd radi a l arterial pl as ma sampl es with three different forms of oral progesterone either micron-
ized (pa rti cle sizes) or standard crystallized progesterone in
obtai ned from 20 postme nopausa l wo men after vaginal th e same tour postmenopausal women at seven-day inter-
admin istra ti o n of 100 mg of mi cronized progesterone. va ls (From: Sitruk-Ware R, Bricaire C, de Lignieres B, et al:
The plasma leve ls in the uterine a1tery a re significantly Oral Micronized Progesterone: Bioavailability Ph armacokinet-
ics, Pharmacologica l and Th erapeutic lmplication s - A Re-
hi g her than in the radi a l artery, suggesting a first-pass
view: Contraception . 36:373-402 , 1987).
Chapter 26: IMH vs. HMA for Use in Therapeutics 329
:'.l 24 24
E
a~ 22 Vaginal cream 22 Oral
w 20 20
z
o
a: 18 18
w
lñw 18 16
C)
oa: 14 14
D.. 12 12
:i
:J 10 10
a:
w
l/l 8
:i
w
l/l 8 6
o
z 4
1
<
z 2 2 l
:5
:E
o 2 4 8 a 10 12 14 18 18 20 22 24 o 2 4 8 8 10 12 14 16 18 20 22 24
HOURS
Figure 26-15 : Serum progesterone concentrations after vaginal application of 300 mg IMH progesterone in a non-liquifying
cream and after oral administration of gelatin capsules containing 300 mg of IMH progesterone in oil (From : Kimzey LM ,
Gumowski G, Merriam GR, et al : Absorption of Micronized Progesterone from a Non-liquifying Vaginal Cream . Fertil Steril 56:995-
996, 1991).
16 16 16
14 A 14 B 14 e
12 12 12
10 ....eg> 10 10
~
e.... 8
"'e: 6
~24
4 4 4
2 2
o 1 2 J 4 5 6 7 24 o 1 2 J 4 5 6 7 24
o ,,,I,
1 1 1 1
o 1 2 J 4 5 6 7
1 1 1 1
HOURS HOURS HOUAS

Figure 26-16: The serum conce ntration of progesterone following intravaginal application of 50 mg of progesterone suspen-
sion in women rece iving estrogen replacement (A), not receivi ng estrogen replaceme nt (B), and after sublingual application in
women not receiving estrogen replacement (C) (From : Villaneuva B, Casper RF, Yen SSC : lntravaginal Administration of
Progesterone: Enhanced Absorption after Estrogen Treatment, Fertil Steril 35: 433-437 , 1980).
_J 100
E
........
OI
e
w
z 10
o
a:
w
l-
en
w
(!J
oa:
a..
~
::::>
a: 0.1
w
(/')
o 4 8 12 16 20 24
TIME (hrs)
Figure 26-17 : Progesterone serum concentrations after ad ministra-
tion of a single 200 mg oral dose of IMH progesterone during fastin g or
non-fasting conditions . A large solid dot equals fasting condi tion , a
large zero equals non-fasting conditions (From : Simon JA, Robinson
DE , Andrews MC, et al: The Absorption of Oral Micronized Progester-
one: The effect of food , dose proportionality, and comparison with
intramuscular progesterone. Fertil Steril 60 :26-33 , 1993).
transit effect into the uterus and endometrium. 96 This Even though serum leve ls afte r intramuscular progest-
was further evaluated and documented with the use of erone were higher than after vagin al appli cation, the
autoradiography and the use of endometrial and uter- endometrial tissue levels of progesterone were higher
ine uptake ofradioactive progesterone. F igure 26-20 il- after vaginal applications ofprogesterone. 91 When com-
lustrates the progressive transit of the radioactive pared to a contro l group, the intramuscular serum leve ls
progesterone through the organ over time afte r vaginal are higher, but the endometria l levels continue to be
application. 97 higher in other stud ies 99 (Figure 26-23). ln our cli nica l
experience, the use of either intravaginal or intramuscu-
Eva luation has shown a distinction between the serum lar progesterone has a stronger endometrial effect than
leve! and endometrial tissue leve! of progesterone after ora l progesterone. Ora l progesterone c lin ica lly appears
vaginal administration ofprogesterone98 (Figure 26-21 ). to ha ve the weakest effect on the endometrium .
120
Peak Levels of Serum Progesterone Following Administration of
Progesterone Through Various Forms and Routes
100
E
......
c:n
e 80
11
e
......
o
11
11
60
c:n
o...
D..
E 40
...
:i
11
111
20
o
0({;~
~(
ó
Va rlou s Forms a nd Routes

Figure 26-18 : The peak levels of serum progesterone following administration of progesterone through various forms and routes.
SR= sustained release. IM =intramuscular (From : Pope Paul VI lnstitute research , 2004).
::J 20 ~-----------------~
_§_
"'
.s.
ª.~
:!!
15
~
5 10
• R11d lo11cdve Teat Substance
• Rad loactiv• Refenmce Substance
E
• •• •
a..
o
-¡ •
>
.
.!!
... .
l .. ·:·
•
E
:¡
~ o '------'-------'-----'-----~
o • w ~ 20
Plasma level ol P in the uterine artery (ng/ml)
Figu re 26-19: The progesterone levels in paired uterine and Figure 26-20 : An illustration of the migration of radioactive
rad ial arterial plasma samples obtained in 20 postmenopausal progesterone after transvag inal application of progesterone
women after vaginal administration of 100 mg of micronized using autorad iography. The schematic views A throug h D
progesterone (From: Cicinelli E, Cignarelli M, Sabatelli S, et al : show the migration of the radioactive substances in longitudi-
Plasma Concentration of Progesterone are Higher in the Uter- nal section after their vaginal application (From : Bulletti C, de
ine Artery than in the Radial Artery after Vaginal Administra- Ziegler D, Flamigni C, et al : Targeted Drug Del ivery in
tion of Micronized Progesterone in an Oil-Base Solution to Gynaecology: The First Uterine Pass Effect. Hum Reprod
Postmenopausal Women . Fertil Steril 69:471-473, 1998). 12:1073-1079, 1997).
Chapter 26 : IMH vs. HMA for Use in Thera peut ics 331
Serum Levels Endometrial Tissue Levels ng P/mg protein

(Day 21 ) (Day 21)
80 15
12
11 .5
70 69.8
10
60 12
e:
"Cii 50
8
o..... _J
40 6
E:
Cl
E 30
p<0.05
--eE
Cl
p<0.05
9
--
Cl
e 20
4
11.9 2
10 1.4 6
o o
IM (n=5)1 - vaginal (n=1 5)t
3
Fig ure 26 -21 : En dometri al and serum levels of progesterone
measured on Day 25 of vag inal administration compa ring the
serum and endometrial tissue leve Is of intramuscular and vagi-
nal progesterone (From : Warren MP, Shantha S : Uses of o
Progesterone in Clin ical Practice. lnt J Fertil 44:96-103, 1999). Control lntravaginal Intramuscular
Figure 26-22 : The endometrial progesterone concentrations

in patients receiving intramuscular and intravag inal progest-
ero ne co mpared with normal controls (Miles RA , Paulson RJ ,
Lobo RA, et al : Pharmacokinetics and Endometrial Tissue Lev-
els of Progeste rone after Administration of Intramuscular and
Vaginal Routes : A Comparative Study. Fertil Steril 62:485-490,
1994).
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1O. Girouard LG, Holm RC: The Role of Natural Progesterone
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19 72.
5 . A llen WM: Recollection s of my Life with Progesterone.
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Chapter 26 : IMH v s. HMA for Use in Therapeutics 333
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Transderm al 17 beta-estra di ol and Oral Conj ugated Eq uine
7 1. Lemon HM , Woti z Hl-I , Parso ns L, el al: Reduced Estriol
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Excre tion in Patien ts with Brea st Ca nc er Pri or to End o-
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and Endometrial Tissue Level s of Progesterone a fter Ad-
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progesterone. Fe rtil Ster il 60 :26-33 , 1993.
pa rative stud y. Fertil Ste ril 62:485 -490, 1994.
Cooperativa Progesterone and Estrogen
Replacement Therapy
hroughout the course of contemporary reproduc- in ways that wi ll cause virtually no harm , wi ll improve
T tive medicine and modern gyneco logy, the use of
either progesterone or estrogen during the menstrual
th e woman 's hea lth, and will enhance fertility without
causing damage to a developing embryo upon achieve-
cyc le as a therapeutic agent for managing women 's ment of a pregnancy.
hea lth prob lems has been a foreign co ncept. The single
most common endocrinopathy in women of ch ildbear- In order to accomp li sh this, however, progesterone and/
ing age is most like ly th e dysfunctional luteal phase. or E2 mu t be used in a cooperative fas hi on. This will
This dysfunction wi ll often present itse lfwit h subopti- ultim ately lead to a new co ncept in medicine that
mal progesterone or with suboptimal estradio l-1 7~ (E 2). NaProTECHNOLOGY calls cooperative progesterone re-
In sorne cases, both ofthem will be suboptim al. placement therapy (CPRT) (Table 27- 1) and cooperative
estrogen replacement therapy (CE RT). The simple con-
lt is thought that if progesterone or E2 is supp lemented cepts fo r this therapeutic program can be outlined in
during the course ofthe menstrual cyc le, it will interfere the fo llowi ng points (Tab le 27-2):
with normal endocrine function. This supposition is cor-
rect if the physician is unable to target th e cyc le prop- l. Progesterone and E2 are produced in a cycl ic
erly with these two hormones. lfprogesterone or E2 are fas hi on: E2 is th e dominant preovulatory hor-
provided to a woman during the preovulatory phase of mone, while both progesterone and E2 are pro-
her cycle, they will both have a tendency (a lthough E2 is duced during the postovulatory phase of the
much stronger) to feed back to the hypotha lamic-pitu- cyc le.
itary axis and suppress the normal pulsatile functioning
2. True repl acement thera py must, therefore, be
of gonadotropin-releasing horn1one (G nRH). This would
provided only during the postovul atory phase
subseq uentl y affect follic le-stimul ati ng hormone (FSH)
of the cycle.
and luteinizing hormone (LH) and ha ve a domino effect
on the production of the ovarian stero ids and ovu la- 3. The preovulatory phase of the cycle is variable
ti on. Contemporary medicine has missed the fact that in length.
both progesterone and E2 can be supplemented as thera-
4. Therefore, one must have a simp le, but reli able
peutic agents during the course of the menstrual cycle
335
means of determining when the patient is in the

postovu latory phase of the cycle. Table 25-2: The Use of the Creighton Model in
Providing Cooperative Progesterone and
5. With the use of the CREIGHTON MODEL Sys- Estrogen Replacement T herapy
tem (CrMS), the Peak Day can be a reliable, re- (CPRT and CERT)
producib le sign for the timing of ovulation and
is the hall mark for the woman to know that she is
enteri.ng the postovulatory phase of the cycle. • Using a given day of the cycle is no!
adequate because of !he variability of !he
preovulatory phase (ovulation occurs on
If one were to start e ither progesterone or E 2 therapy on day 14 in only 13.5% of cycles ).
a given day ofthe cyc le, it wou ld have adverse effects. The Peak Day is the most reliable sign of
The preovulatory phase ofthe cyc le is hi ghl y variab le. the day of ovulation (ovulation occurs :! 2
days of the Peak Day in 95% of cycles ).
Add itionall y, ovulation occurs on day 14 ofthe cyc le in
Therefore, using !he post-Peak phase
on ly 13 .5 percent of cycles. 1 The Peak Day, however, is provides an indicator for CPRT or CERT.
a reliab le sign for estimat ing the day of ovu latio n (wi th
ovul ation occurrin g on Peak Day +/- 2 days in 95.4 per-
cent of cyc les 2 ). Thus, using the post-Peak phase of
the cyc le as an indicator fo r the use of progesterone or
E2 suppl ementatio n provides an ovulation-dependent
means of identify ing the beginning of the true lutea l In order to effect ive ly practice m edica !
phase ofthe menstrual cyc le. Providing either progest- NaProTECHNOLOGY, the physician must be completely
erone or E2 in this way is cooperative with the cyc lic fam ili ar w ith the use of progesterone in a way whi ch is
hormones ofthe menstrua l cyc le and ultim ate ly defines cooperative with the menstrual cycle. The fo llow ing are
CPRT and CERT. ways in which progesterone support can be provided:
1. Oral micronized progesterone capsu les (standard

or sustained release)
Types of Progesterone Support _ __
2. Microni zed progesterone vaginal capsules
Progestero ne support can be prov ided in a variety of
3. Progesterone by intramuscular injection
different ways. The most critica! issue for the use of
progesterone is the timing during the course ofthe men- 4. Human chori onic gonadotropi. n (HCG).
strual cyc le. Progesterone support wi ll not work if it is
not g iven at the right time ofthe menstrual cyc le. Thus,
the cycle must be properly targeted fo r progesterone Oral Micronized Progesterone Capsules
su pport to be of any th erapeutic value.
Progesterone, as a hormone, is genera ll y not abso rbed
fro m the gastro intestinal tract. Thus, ora l preparations
Table 27-1 : The Concept of of progesterone have not been w ide ly ava ilab le, al-
Cooperative Progesterone Replacement Therapy though, a pharmaco logic mixture ofm icroni zed proges-
(CPRT) terone in peanut oil has recently become avai lable. Com-
pounding pharm ac ies are ab le to provide a micronized
fo m1 of progesterone that is absorbed from the gas-
Progesterone is produced in a cyclic trointestinal tract. These can be made up into a stan-
fashion only during !he postovulatory
phase of !he cycle . dard preparation or a sustained-release form.
• Cooperative progesterone replacement
therapy must, therefore , be provided on/y The standard ora l micronized progesterone capsu les will
during !he postovulatory phase of !he
contain between 200 and 300 mg of micronized proges-
cycle.
terone depending upon what the physician orders. The
• The preovulatory phase of the cycle is
variable in length. sustained -re lease fo rm contains a 200-mg maximum
Therefore , one mus! have a simple , but
amo unt of progesterone in the capsule. Between these
reliable means of knowing when !he two forms of progesterone, the sustai ned-release form
patient is in !he postovulatory phase of is tolerated better than the standard oral form. Because
the cycle .
of its quick absorpti on, its first pass through the li ver
and its deve lopment of various metabolic by-products,
Chapter 27 : Cooperative Progesterone and Estrogen Replacement Therapy 337
the side effects frequen tly associated with standard mi- Thus, when using a vaginal appli cati on of progester-
croni zed oral progesterone are li ghtheadedness, dizz i- one, it is recommended that an oral mi cronized proges-
ness and fatigue. However, the oral sustained-release terone capsul e at a dosage of300 mg be pl aced within
fo nn is virtuall y devo id of those side effects, alth ough the vagina at night, every day (QD) fro m Peak + 3 through
the abso lute blood levels are lower. The commercial fol1TI Peak + 12. Thi s will ha ve a moderate stimulus on the
of oral microni zed progesterone in pea nut oil also has a endometrium and the myometrium , so its use in women
hi gh side-effect rati o with the sa me side effects bei ng who ha ve short post-Peak phases or it is useful in preg-
observed. nancy. Genera ll y, these capsul es are easy to use, pro-
duce onl y a mínima! di scharge the fo ll owing day, and
Thus, the author has preferred the use of ora l mi cron- are not messy. They can be used in cooperation with
ized sustained-release progesterone capsul es to be given the CrMS as a fa mil y pl annin g program.
at a starting dose of200 mg by mouth every day at bed
time (QD hs) from Peak +3 through Peak + 12. Progesterone vaginal ca psul es will occas ionally cause
vaginal dryness or vulvar irrita /ion or sometimes a
Thi s targeting of the cyc le is des igned specifica lly to "cakey" di scharge. Thi s can be managed by inserting
cooperate with the lutea l phase . The ov ul ation sequence one or two 400 JU (i nternati onal units) vitamin E cap-
is over in virtuall y 100 percent of pati ents by Peak + 3 sul es in the vag ina along with the progesterone. The
and the average length of the post- Peak phase of th e vitam in E is packaged in a glycerin capsul e, whi ch eas-
cyc le is l2 days. While phys icians often make up their il y di sso lves at body temperature releasing the vitamin
own ro utine, beginning progesterone earl ier (for example E oíl to the mucus membra nes. Vita min E has a superb
on Peak + 1) or continuing progesterone th ro ugh to the soothing effect on mucus membranes and will resolve
time of menstruati on shoul d be cauti ously avo ided. either dry ness or irritati on.
Progesterone must be given in a targeted fas hi on to be
therapeutic. If it is given pri or to ovul ation, it wi ll be less These capsules should be in serted at night so th at they
effecti ve . Jf it is continued beyond th e norma l length of will melt at body temperature whil e the woman sleeps
the post-Peak phase, then it will create its own hor- and will create the least amount of di sturbance fo r her.
monal abnormality because endogenous progesterone
is no longe r bein g produ ced and onl y exoge nous
progesterone is avail able. Thus, fo r th e most effecti ve- Progesterone lnjections
ness, this program o f progestero ne admini stra ti on
should be used. Progesterone is also avail able in an intramuscular (IM)
depot inj ecti on fo rm . The progesterone is contained in
lt should also be pointed out that oral progesterone is a sesame-seed-oil mediu m. Thi s all ows it to have a more
not a stron g agent for lengthening the post-Peak phase. long-acting effect. Th e commercial products are ava il-
Thus, contracepti ve use of oral progesterone is best abl e in a dosage of 50 mg/cc of sesame seed oil. A com-
suited for those women whose post-Peak phases are pounding ph armacy with the appro priate equipment can
reasonabl y norma l in length. Ifo ne is treating a woman also compound progesterone in oíl at a higher concen-
with a short post-Pea k phase (a short lutea l phase) , ora l tration of 100 mg/cc. The sesame seed oil fonn of proges-
progesterone is not sati sfactory beca use it does not terone is generally less irri tating th an the peanut oíl
consistentl y lengthen the post-Pea k ph ase. fol1TI.
The usual dosage of progesterone when used by inj ec-

Micronized Progesterone Vaginal Capsules tion in CPRT is 100 mg lM on Peak + 3, 5, 7, 9 and 11.
However, alternate dosages can also be used. For ex-
In the original work with the CrMS, the only fo rm of ampl e, prov iding a 50 mg dosage on Peak + 3 and 1 1
progesterone availabl e was progesterone made up in along with 100 mg on Peak +5, 7, and 9 will give a boost
vag inal suppositori es with either cocoa butter or proof progesterone that mimics a phys iological dosage form
pylene glycol bases. These suppositories were messy of progesterone.
and were confusing to the women who were observ ing
vaginal di scharges in the CrMS . A standard oral mi - When progesterone inj ecti ons are used, it is extremely
cronized progesterone capsule was substituted fo r the impottant to draw up the progestero ne in to the syringe
vaginal suppositories and thi s became an effective thera- with a different needle th an the needl e th at is used to
peutic strategy. inj ect it. In additi on, it is extremely important to inj ect
the progesterone over a slow peri od of tim e, usuall y
120 to 180 seconds. lf progesterone is given quick ly, it to lerated. It is eas il y admini stered and a very p redict-
can be very irritating. However, if it is given slow ly and able medication. Few side effects are associated with
with proper admini strati on, then it can be very we ll tol- its use. It can also be used by the subcutaneous (SQ)
erated. The hips should be alternated as inj ecti on sites ro ute.
and, after the progesterone is inj ected, it should be mas-
saged into the muscl e. The usual dose is 2000 units on Peak +3, 5, 7, and 9. A
goal in the adm ini stration ofHCG is to bring the proges-
If local irritati on and itchi ng occurs fro m th e progester- terone and E2 levels we ll within the normal range and to
one inj ection, applying vitamin E oil over the surface of keep the length of the post-Peak phase nonnal. If the
the inj ection site and the surrounding skin will prov ide progesterone and E2 level s are too hi gh or the post-
reli ef. On occas ion, inj ectable progesterone can cause a Peak pha e is too long, the dosage can be reduced to
signifi cant amount of irri tati on, espec iall y if given too 1000 units on Peak +3, 5, 7, and 9, or to 2000 units on
quickl y. This is not common if the progesterone is given Peak +3, 5, and 7.
properly. However, if thi s does occur, it may ha ve to be
di scontinued and an alternate route of admini strati on Our practi ce has been to teach spouses to give the in-
may have to be selected. jections of either progesterone or HCG. With proper train-
ing by our nursing staff, the spouses do we ll. This makes
The use of intramuscul ar progesterone during the post- rece iving the medi cations very tolerabl e and very cost
Peak phase of the cyc le should be limited to those situ- effecti ve.
ati ons where th ere is no good alternati ve. lt does ha ve
a strong endometri al effect and will usuall y induce a
menstrual period in those women who are chroni ca ll y Cooperative Estrogen Replacement
amenorrheic or oli gomenorrheic. Thus, it is usefu l fo r Therapy (CERT) - - -- - - - - - - .
women who have oli gomenorrhea secondary to po ly-
cystic ovarían di sease; in th is situati on, it can be used Since E2 is also produced during the post-Peak phase of
100 mg IM on day 18, 2 1 and 24. While thi s is not CPRT, the cyc le, the phys ician may want to admini ster E2 to
thi s protocol is a legitimate use of progesterone be- the pati ent in a cooperati ve fas hion. Any estrogen given
cause it is being used to counteract the otherwise un - pri or to ovul ati on will have the effect of inhibiting ovu-
opposed estrogen effect that is common in secon dary la/ion. This is contrary to th e bas ic principi es of good
oli gomenorrhea. Three inj ecti ons of progesterone in a therapeuti cs .
given cyc le, if properly admini stered, are very we ll to l-
erated. lf the lutea l ph ase E2 leve! is suboptimal, cooperati ve
estrogen replacement therapy (CERT) can also be used.
In doing thi s, an oral microni zed E2 fo nn is available and
Human Chorionic Gonadotropin (HCG)l is active (Estrace) . The usual dosage is 0.5 or 1 rng by
mouth at every day at bedtime (PO QD hs) from Peak +3
Human chori onic gonadotropin (HCG) can also be used through Peak + 12. On occasion, the dosage may be in-
in a cooperati ve way during the course of the menstrual creased to 2 mg fro m Peak + 3 through Peak + 12.
cycle. HCG is an " LH substitute": it has LH-li ke acti vity
(being biochemically very simil ar to LH) and can be used An altern ative route fo r CERT is the use of tri estrogen.
phys iologicall y as a substitute for the LH horm one, Triestrogen is a compounded fo rm of natural human
whi ch is not ava il able at thi s tim e. identica l estrogen whi ch contains 80 percent estri ol, l O
percent estradiol and 1O percent estrone. lf using thi s
When HCG is given during the postovu latory ph ase of for the purposes of CERT, the dosage is 2.5 mg by
the cycle (the post-Peak phase of the cyc le), it will stimu- mouth every day at bedtime (PO QD hs), Peak +3 through
late the corpus luteum to produce more progesterone Peak + 12 or 5 mg in the same timing. These dosages are
and estrogen. This can be monitored by drawing Pea k we ll tolerated with no apparent side effects. One can
+ 7 progesterone and E2 leve Is prior to treatment and meas ure the increased leve l ofE 2 by monitoring the E 2
then fo ll ow in g treatment. One ca n document the in- leve! on Peak +7. This allows fo r the appropriate adjust-
creased producti on of progesterone and E2 in thi s fas h- ment of the dosage fo r that parti cular pati ent. When
ion. The blood draw on Peak +7 shou ld be perfo rmed monitoring the E 2 level in thi s case, the estrogen prepa-
prior to that day 's inj ection of HCG. rat ion is not di scontinu ed pri or to the measurement of
the E2 level.
HCG is given by intramuscul ar injecti on and it is well
Chapter 27: Cooperative Progesterone and Estrogen Replacement Therapy 339
CPRT and Regulatio n of the Menstru al The use of progesterone support during the post- Peak
Cycle _ _ _ __ _ _ _ _ _ _~ phase ofthe cyc le also hada n effect on the subseq uent
men strual cyc le. lt shortened the fo llicul ar pre-Peak
A benefit to the use of CP RT is its effect on the men- phase and , thus, shortened the entire menstrual cycle.
strua l cycle: it has a strong tendency to regulate the This phenomenon has been observed in a large number
cyc le. This is demonstrated in Figure 27-1. of patients to date. T herefore, a form of C PRT (w ith
progesterone vag ina l capsules, progesterone oral cap-
In this examp le, progesterone is started during the post- su les, HCG injections or even progesterone inj ections)
Peak phase ofthe third cycle. Before progesterone was may ass ist in the regulation ofthe menstrua l cycle and
started, the mucus cycle ra nged from 12 to 15 days in the normal ization of the time offerti lity in those patients
duration. The Peak Days occurred on days 19, 20, and who have prolonged mucus cyc les, delayed Peak Days
22 respectively. However, fo ll owing progesterone ad- and longer menstrua l cyc les. This w ill also benefit
min istration , the mucus cycles shortened to 7 and 9 days women who have a tendency toward double peaks.
in duration and the Peak Day occurred on da ys 14 and
17 ofthe cyc le.
6 7 9 lO u 12 13 14 15 16 17 18 19 20 21
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11
MH HH/MM
USE THESE SIGNS : P • PEAK • 1.2.3 • FERTILE DAYS FOLLOWING PEAK • t • INTERCOURSE BSE = BREAST SELF-EXAM
Figure 27-1 : In this case, progesterone was given in th e th ird cycle. lt is vaginal progesterone given Peak +3 through P+12 . The
next two cycles are shorter with a shorter pre-Peak phase and a shorter mucus cycle (From : Pope Paul VI lnstitute research ,
2004).
1. Hil gers TW, Prebi l AM, Hil gers SK, Daly KD : The Occu r- 2. Hilgers TW, Abraham GE, Cava nagh D: Natura l Fam il y Plan-
rence of Ovu lati on al the Mid-Cyc le. lnt Rev Nat Fam Pl an ning 1 - The Peak Symptom and Estim ated Time of Ovula-
4:227, 1980. tion. Obstet Gyneco l 52:5 75, 1978 .
Effects of Stress
tress has an enormous impact on the ovulation and which stress delays ovu lat ion and the "second" Peak
S menstrua l cycles. The stress may be physical or emo-
tional. lt may be acute or chronic.
generally occurs after the stress is relieved. Ovulation
occurs with the "second" Peak. lt is a situation that can
happen to any woman; it may be a protective mecha-
Examp les of physical stress inc lude such things as sick- nism at work.
ness, strenuous activity and trove/.
There are a number of other effects of stress. Some women
Examp les of emotion al stress cou ld be change ofjob, may experience a prolonged Peak-type mucus buildup
bereavement, major decisions, holidays, relatives vis- whi le others may have a de lay in the Peak Day and
iting, weddings and exams. ovulation. In others, the charting pattern may turn to-
tal ly dry or into limited mucus cyc les. Examp les ofthe
Many other stressors can occur in an individual 's life. various effects of stress are observed in Figures 28-1
Those types of stress that are rapid in their onset and through 28-4.
fairly short-lived would be termed acute stresso rs.
Those stressful events that are s/ow in onsel and pro- 1n Figure 28-1 , a woman who has undergone a minor
/onged cou ld be defined as chronic stresso rs. surgical procedure on day 1 l ofher third cycle of chart-
ing has a Peak Day occurring on day 20 ofthe cycle or
Most of the above examples are acute stressors. How- nine days after the surgery. The cycle itse lf is the long-
ever, a change ofjob that puts one into a stressful situ- est (measuring 33 days in duration) she has had in sev-
ation can become a chronic stressor. Most chronic stres- era! cyc les. It is thought that the surgical procedure and
sors are re lated to stressful relationships in the work- the stress leading to it were sufficient to de lay ovul a-
place, in a premarriage or marriage environment, with tion, and this delay in ovulation shows up in her chart-
relatives or friends , and so forth. ing. By inquiring about some basic events in her life
one can piece together the different a pects ofthis par-
Stress can cause a variety of aberrations in the charting ticular charting example.
system. The classic example a charting aberration due
to stress is the "double" Peak. This is a situation m In Figure 28-2, the young woman has a normal length
341
mucus cycle with a normally-occurring Peak Day. How- the overall cycle length and the length of the mucus
ever, during the third cycle ofthis chart, her grandfather cyc le are sign ifi cantly prolonged over what her normal
died ( on day 15). Because this was the Easter holiday, length would be. The stressful event occurred at a time
the funeral was delayed until day 22 ofthe cyc le as can when she wou ld normally ovu late, and so it held the
be seen in the charting examp le . Her Peak Day did not actual ovulation event in abeyance while ovarian fu nc-
occur until day 27. This was fo ll owed by a normal 15- tion continued to produce a Peak-type continuous mu-
day post-Peak phase, but the cycle length itse lf was cus discharge. Again, when a cycle like this is observed,
prolonged at 42 days in duration. The mucus cycle lead- the stressfu l events can usually be pieced together to
ing up to the Peak Day was 20 days in duration. Both explain the charti ng situation . Anoth er interesting fea -
Delayed Peak Day (Ovulation)

Because of Stress (M inor Surgery)
Figure 28-1 : A delay in the Peak Day dueto stress of minor surgery (see text) (From : Pope Paul VI lnstitute research, 2004).
12 13 1 15 16 17 35
I I
Prolonged Mucus Cycle

(Death in family)
Figure 28-2: Prolonged mucus cycle (third cycle) due to death in family (see text). By the last cycle, stress had been relieved
and cycles reverted to normal (From: Pope Paul VI lnstitute research , 2004).
Chapter 28 : Effects of Stress 343
ture of Figure 28-2 is that it took abo ut two cyc les for she did this, she re ve rted back to hav ing normal mucus
her ovulation cycles to recuperate from the stressfu l cyc les. A few cyc les later, she became pregnant and ,
event. from that pregnancy, had a baby boy.
In Figure 28-3, a patient is shown who has a reasonable Figure 28-4 is the chart of a yo ung woman who was
length and character mucus cycle during the first three under stress whil e she was pl annin g her wedding. In
cycles of charting but in her fourt h, fifth and sixth cycles the first two cycles, a lot of activity was taking place.
of charting she has reverted to a compl etely dry pat- Her car broke down severa! times and she was unable to
tern. The patient began a 45-minute jazzercise program get it repaired. She was sent to the phys ician to get her
with sit-ups and leg lifts at the beginning of her fourth cervix checked fo r a cervical eversion. However, it was
cycle of charting. At the same time, she also went on a pred icted by looking at her chart that the cervix wo uld
weight reduction di et and lost 1Opounds (from 122 lbs. appear to be normal since this had the classic appear-
to 1 12 lbs.). These events wou ld be considered stressfu l, ance of a chronic stress cycle. In her first cycle of chart-
and the initi ation ofthem in coordi nation with the onset ing (a 37-day cycle), she has a mucus buildup that ends
ofthe dry cycles is sufficient to draw the parallel. This with a Peak Day on day 12 and then a second mucus
situation has been observed on a number of occasions. buildup beginning on da y 18 and concluding on day 26.
This is one of the classic appeara nces of a stress-in-
Another feature ofthe patient in Figure 28 -3 is that this duced "double" Peak situat ion.
wo man was told at the age of 20 that she could not
become pregnant because of extensive pelvic inflam- In her second cycle of charti ng (a 40-day cycle), she
matory di sease and ad hesions. She was told that she has a prolonged mucus buildup that concludes on day
needed a hys terectomy. However, she underwent sur- 32 of her cyc le. She has a ve ry short post- Pea k phase
g ica l reconstruction ofher pelvis through the Pope Pau l numbering onl y eight days in duration. This suggests
VI lnstitute and the charting that is observed in Figure that the entire cycle wa hormona lly ab norma l. Neither
28 -3 is the charting following her surgery. Because of of these two cyc les meets the cri teria fo r a cerv ica l in-
the dry cycle pattern , she con verted her cycles to in fer- flammation (see Chapter 25).
tile cycles. Thus, it was suggested to her that she dis-
continue the strenuous activity and the dieting. When On exami nation , her cervix was indeed normal in ap-
9 10 u l2 13 14 20 21 22 23 24 25 26 27 28 29 JO 31 32 33 34 35
Heavy exercise and

weight loss program
began fourth cycle
I r
I I I
Stress-induced
1---1-4--1---l~-I--~ t--11--+--+--+---1~+--I
Dry Cycles
Figure 28-3: Stress-induced dry cycles (starting with fourth cycle) because of new diet (see text) (From: Pope Paul VI lnstitute
research , 2004).
pearance. She was then advised that the stressfu l events NaProTECHNOLOGY, we shou ld be abl e to establish
in which she was involved was the cause ofthese pro- those relationsh ips and to provide better forms oftreat-
longed mucus cycles. ment.
In her third cycle of charting, when mu ch of the stress The reasons why stress causes these effects is not en-
was re li eved , her cycles reverted back to normal. In this tirely known at the present time. We do know that stress
cycle, she hada seven-day mucus buildup to the Peak has multiple endocrine and physio log ical effects. The
Day, and her Peak Day occurred on day 17 ofher cyc le. exact relationship to the reproductive system is not well
Her post-Peak phase was 13 days in duration and the understood. One of the theories is the possibility that
overall cycle length was 30 days. ~- endorph in s play a role in block ing the normal pulsa-
tile production of FSH and LH from the pituitary. This
With the self-knowledge that comes with chartin g the blockage, w hile not complete, is sufficient to cause ovu-
CREIGHTON MODEL FertilityCare™ System (CrMS), latory dysfunction . Such ovul atory dysfunction is what
women may be able to take a look at their li festyle and may produce delayed ovu lation and long cyc les.
see what changes mayor may not be necessary to help
reduce stress in their lives so they do not experience We do live in a very stressfu l society and , fo r women,
these effects of stress. monitoring stress with the CrMS can be a sensitive too!
for seeing the end results . With greater util ization, one
One ofthe questions for the future will be to ask what can expect that wo men will become more aware ofthese
long-term effects stress has on a woman ' s overa ll events.
health. As we follow patients with the CrMS and with
6 7 9 10 11 12 13 19 20 21 22 23 24 25 26 27 28 29
M M VL VL VL 10 a.AD ;AD <,,C ;.,\O MO V.O a.AD

B aw 0 • 1 x:>
~Ag ....
A Stress-induced
OAD ~D
Delays of Ovulation
(Aand B) Wedding Preparations
M M IOK IOK IOK IOK 100<. <.CK IOK 4K! 1(-. MO

•! •! AD AD 11.a ica "''
GIPC IOC ~C MD ()tr.0

xi xa Ka
Stress relleved Wedding Over
M M M M O 4¡itf <oK loc.K IOK 10~ 10 IOK C.K 0"'0 0A0 OAO OAO GA.0 OAD OAO 4 x9t 8C 4'1(;;, C.K 0.-.0 OAO
.. ~ ll! .a -.?> ,.,¡ "'' 1( 1
M M L
Figure 28-4: Stress-induced cycles leading up to wedding (see text) (From : Pope Paul VI lnstitute research , 2004).
~--~. . .e~tu,29
Premenstrual Syndrome:
Evaluation and Treatment
he condition now referred to as premenstrual syn- over the years. This should prompt interest and con-
T drome (PMS) has a long and varied history among
medica! investigators. This history dates back to the
cern about finding the underlying causes and treating
them effectively, so that those women who suffe r from
time of H ippocrates, 1 and the first reference in a sc ien- premenstrual syndrome are also given ful! access to
tific journal was by Frank in l 93 l .2 ln 1964, Dr. Katherina opportunities. Furthermore, PMS is a conditi on that has
Dalton brought attention to this co nditi on with her first destroyed relationships, led to divorce and child abuse,
book on PMS, which promoted the theory that this con- and has created numerous aberrant stereotypes about
dition was caused by either a progesterone deficiency the behavior ofwomen.
oran imbalance in the estrogen-progesterone ratio. 3 La ter,
she also extensive ly promoted the use of progesterone Sorne symptoms (both physical and emotional) prior to
therapy for its treatment. 4 At this time, PMS continues the onset of the menstrual period are comm on.5 These
to be a very complex and difficult condition to treat. may occur 50 to 75 percent ofwomen. Moderate to se-
vere premenstrual symptoms that disrupt a woman 's
While its medica! and pathophysiologic components li festyle may occur in 20 to 30 percent ofwomen, and
have been difficult to crysta lli ze, PMS has been locked severe, debilitating symptoms are seen in 2 to 1O per-
in with various politi cal and lega l perspectives. For ex- cent (Table 29-1 ).
amp le, murder convictions and felony charges have
been reduced to manslaughter and misdemeanors re- Premenstrual syndrome is related to premenstrual dys-
specti vely because of the argument that the accused phoric disorder (PMDD). The diagnosis of these two
woman suffered from PMS. Feminists have vo iced con- conditions is different since one is defined by the 1Oth
cern about this trend indicating that the use of PMS as Revision ofthe lnternational Classification ofDiseases
a defense in criminal or civi l matters cou ld result in a (ICD- 1O) whi le the other is identified by criteria from the
negative impact on women's push toward equa li zation 4th Edi tion ofthe Diagnostic and Statistical Manual of
with men. 1 Femin ists plead that generalizations about Mutual Disorders (DSM-I V) (Tables 29-2 and 29-3). The
women should not be made when assessing the lega l or diagnosis of PMS requires onl y one symptom to be
political as pects ofthis condition. Another point of view present for its diagnosis , while PMDD diagnosis re-
suggests that this condition has held back many women quires at least five symptoms to be present at least one
345
Table 29-1 : Inciden ce of P re menstrual Table 29-2: Diagnosis of PMS'

Synd ro me (PMS) in General Population 1
% of women
1Oth Revis ion of the
lnternational Classifi cation of Di sea ses (ICD-1 O)
No premenstrual symptoms 3-10
Mild premenstrual symptoms 50-75 Only one of the following symptoms is required for a
Moderate to severe premenstrual 20-30 diagnosis of PMS:
symptoms that disrupt lifestyle Mild physiological discomfort • Aches and pains
Severe, debilitating symptoms 2-10 Bloating• • Poor concentra tion
Weight ga in• • Sleep disturbances•
Breast tenderness • Change in appetite
1. Mezrow G, Shoupe D : The Prem enstrual Syndrome, In: Mishell's
Swelling of hands and feet
Textbook al lnfertility, Contraception, and Reproductive Endocrinology.
Lobo R, Mishell DR, Paulson RJ , Shoupe D, Eds. Blad<well Science ,
Malden, MA 1997, pp. 403-414. 1. APGO Educational Series on Women's Health lssues. Premenstrual
Syndrome and Premenstrual Dysphoric Disorder: Scope, Diagnosis
and Treatment. APGO , Washington, DC. October 1998.
Also included in Pope Paul VI lnstitute criteria.
week prior to the beginning of menses. In both cases ,

the conditions te nd to decrease afte r menstruati on has
occurred. T hey ha ve characteri stic appearances during
the premenstrual phase of the menstrua l cyc le. The d i- Table 29-3: Diag nos is of PMDD 1
agnos is of PMS is preferred by obstetri cian-gyneco lo- (DSM-IV Criteria)
g ists and primary care phys icians while psychi atrists
and othe r menta l hea lth prov iders tend to prefer the
d iagnos is of PMDD . A summary ofthe di stincti ons be-
At leas! five of the symptoms listed are present one week
twee n PMS and PMDD is shown in Table 29-4. So rne before menses and remit a few days afler onset of
have argued that PMDD poses a risk fo r majar depres- menses :
sive disorder (MDD) and that it may be a prodrome of • Depression* • Conce ntra tio n difficulties
• Anxiety • Lack of energy*
or a causa l ri sk fac tor fo r MDD .5 • Affective li abil ity • Food cravings•
• lrritability • lnsomnia•
• Decreased interest in activities • Feel overwhelmed
The occurre nce of premenstrual symptoms has severa! • Breast tenderness • Headache'
pattem s. These are genera ll y illustrated in F igure 29- 1. • Bloating* • Joint or muscle ache
Premenstrual symptoms are sometimes more prom inent
1. A PGO Educational Series on Wo men's Health lssues. Premenstrual
duri ng the preov ul atory and periovul atory phase of Syndrome and Premenstrual Dysphoric Disorder: Scope. Diagnosis and
Treatment. APGO , Washington, OC, October 1998.
the menstrua l cyc le, and thi s i sometimes referred to as
Also included in P ope P a ul VI lnstitute criteria.
" reverse PMS.''6 Whi le the degree ofpremenstrual symp-
tom severity va ri es w ithin the popul ati on, it tends to be
relatively constant within the individual woman. ln ad-
diti on, it can be influenced by age, race/ethni city and
health status. A symptom severity score fo r emoti ona l
sy mptom s and p hys ica l sympto ms as reported by
Stemfe ld, et al. ,7 is shown in Figures 29-2 and 29-3. In a
recent monograph on these two cond iti ons, the Asso- MensH Ovulallon Me ns es
c iati on of P rofesso rs of Gyneco logy and Obstetri cs B

(A PGO) and the AP GO Medica! Educati on Foundation
reported the most common symptoms of PMS as li sted
?
in Tabl e 29-5. They a lso ind icated that the use ofvag i- e
nal progesterone suppos itories could no longer be ad-
vocated. They reported that ora l progesterone had been
)
fo und to be no more effective than the place bo in the o
treatment of PMS. 8
a I~ ?
Figure 29-1 : Four different tempora l patterns in the occur-
rence of premenstrual syndrome (From : A Practica! Guide to
Premenstrual Dysphoric Disorder: The Expert Con sensus
Guidelines . Th e McGraw-Hill Companies, 200 1).
Chapter 29 : Premenstrual Sy ndrome: Evaluation and Treatment 347
Table 29-4: Su mmary of Differences between PMS and P MDD
PMS PMDD
Diagnostic criteria 1Oth Revision of the lnternational Diagnostic and Statistical Manual of
Classifi cation of Diseases (ICD-10) Mental Disorders, 4th Ed. (DSM-IV)
Providers using these criteria Obstetrician/gynecologists, primary Psychiatrists, other mental health
ca re physicians ca re provide rs
Number of symptoms requi red One symptom 5 of 11 symptoms
Functional impairment Not required 1nterference with social or role-

functioning required
Prospective charting of symptoms Not req uired Prospective daily cha rting of
symptoms req uired for two cycles
- --
" - - ---
~
30
25
20
"
. -~~~~~~~~~~~~~~--
_________, "
.7 .e ·5"' ·3 ·2 ., o , 2 J'
Oeyo!Cycl•
· 1' - 13 - 12 - 11 -10 -9 -8 -7 -6 -5 -' -3 ·2 ·I O 1 2 3 .t 5 B 1 8 9 10 11 12 13 1.c
D•yolCyele
Fig ure 29-2 : The m ean dai ly emotional symptoms score by Figure 29-3 : Mean daily physical sy mptoms sco re by symp-
sym ptom severi ty group . PM DD =
pre m enstru al d yspho ric tom seve rity group. PM DD = pre menstru al dysphoric disorder
d isord er (Fro m : Ste rn fe ld B, Swindle R, C haw la A, Long S , (From : Sternfeld B , Swi nd le R, C haw la A, Long S , Kennedy S :
Ke nned y S : Seve rity of Pre menstrual Symptoms in a Health Severity of Premenstrua l Sy mptoms in a Health Maintenance
Ma in tena n c e Orga n izatio n P op u la ti on . Obste! G y ne co l O rganization Popu lation. O bste! Gynecol 99: 1014-1024, 2002).
99 :10 14-1 024 , 2002) .
Table 29-5: Common Sym ptoms of PMS 1
• Anger (i rri tabil ity)* Food craving s•

• Anxiety GI complaints
• Bloating or weight gain* • Headaches•
• Breas! tenderness• • lmpulsivity
Depression• Mood swings
• Decreased co ncentration • Muscle and joint pai n
Decreased self-esteem • lnsomn ia*
Decreased interest in activities Tension
• Fatigue•
1. APGO Edu cational Series on Women 's Health lssues. Premenstrual

Syndrome and Premenstrual Dysphoric Disorder: Scope, Diagnosis and
Treatment. APGO , Washington , DC. October 1998.
Also included in Pope Paul VI lnstitute criteria .

348 The Medi ca! and Surgical Practi ce of NaProTECHNOLOGY
Exercise and Nutrition : Fuchs 12 and C hakmakjian 13 in association w ith

Non-Pharmacologic Approaches Abraham 14 reported that a specially designed mu lti vita-
to Treatment _ _ _ _ _ _ _ _ _ _~ min-preparation nutritional supplement could have an
impact in reducing the symptoms ofthe various forn1s
A variety of non-pharmacologic approaches to treat- ofpremenstrual syndrome as defined by Abraham . Such
ment have been recommended. These include dietary supplementation could result in an increased produc-
modification such as decreasing caffeine, chocolate, salt, tion of progesterone during the luteal phase. 12
and alcohol intake andan increasing in complex carbo-
hydrates. Calcium supplementation, vitamin B6, aerobic It has also been postulated that a magnesium , zinc or
exercise, cognitive behavioral modification, relaxation calcium deficiency may play a role in the development
training an d group therapy ha ve also been recom- of premenstrual symptoms . 15 -17 Supplementing with
mended. 8 magnesium might assist in treating the condition. 16 Fur-
thermore, the functional hypocalcemia, which has been
Prior, et al. , reported that conditioning exercise decreased observed, may represent the clinical manifestation of
premenstrual symptoms o ver a six-month period. 9 With an underlying abnormality in calcium homeostasis. The
the gradual initiation of a running exercise program over calcium imbalance could emanate from inadequate cal-
a six-month period, a decrease in overa!! premenstrual cium absorption, resulting either from low dietary ca l-
symptoms (specifically related to breast tenderness and cium intake or insufficient vitamin D. In fact, PMS may
fluid retention) were found. The decrease in these serve asan important clinical marker of low ca lcium sta-
moliminal symptoms were thought to retlect physiologic tus in premenopausal women that, in turn , might enable
changes in neurotransmitter levels, perhaps represent- the development of strategies for osteoporosis preven-
ing hypothalamic adaptation to conditioning exercise. tion. 17
Abraham developed a system for categorizing PMS into Vitamin B6 and vitamin E along with the agnus castus
four distinct subgroups.10 These can be summarized as fruit extract have al l been shown to assist in the treat-
follows: ment of premenstrual syndrome. 18-20 1mprovement in PMS
symptoms and estrogen metabolism have also been re-
l. PMS-A (Anxiety): Believed to be related to high lev- ported usi ng a form ulated "medica! food" that comb ines
e Is of estrogen and deficien cy of progesterone . protein, fiber, carbohydrates, fat, anda variety ofmicro-
Women experience irritability, anxiety, and emotional nutrients .21
lability.
2. PMS-C (Carbohycirate craving): Unclear etiology, but Pharmacologic Therapy _ _ _ _ _ _~

may be dueto enhanced intracellular binding ofin-
sulin. Women experience increased appetite, sugar A variety ofpharmacologic treatment approaches ha ve
and carbohydrate cravings, headache, and heart pal- been used in women who ha ve PMS and PMDD. These
pitations. would include such things as danazol , oral contracep-
tives,23·23 GnR.H analogs,24 clomipramine, mefenamic
3. PMS-D (Depression) : Most likely dueto low levels acid 25 and bromocriptine,26 anxiolytics (alprazolam), and
of estrogen lea di ng to excessi ve breakdown of neu- selective serotonin-reuptake inhibitors (SSRis). Even
rotransm itters . Low estrogen may be due to en- laser ablation ofthe endometri um has been recommended
hanced adrenal androgen or progesterone secretion. for treating this condition .27 It should be pointed out
Women experience depression . that oral contraceptives have been considered inad-
equate for managing women with PMS. 28
4. PMS-H (Hyperhydration): Due to increased water
retention , secondary to elevated levels of aldoster- Most of the emphasis in pharmacologic therapy over
one. Elevated leve Is of aldosterone in the premen- the last 1O years has been on the use of alprazolam
strual period may be the result of excess estrogen, (Xanax) or one of many SSRls. A number of studies
excessive salt intake, stress, or magnesium defi- ha ve shown that alprazolam can be helpful in relieving
ciency. Women report weight gai n, breast tender- sorne ofthe symptoms of PMS. 29 -31 In one famous study
ness and fullnes s, swelling of the hands and feet published in the Journal ofthe American Medica! Asso-
and abdominal bloating. 11 ciation, alprazolam was compared to placebo and oral
progesterone in the treatment of severe PMS. 31ln this
study, alprazolam was found to be significantly better
Chapter 29: Premenstrual Syndrome : Evaluation and Treatme nt 349
than placebo or progesterone for total premen strual to the timing of ovulati on were obta ined. This method-
symptoms. However, this particular study hada sign iti - ological fl aw in the tirst group of studi es is serious and
cant methodological flaw. All medi cat ions were admin- renders the studi es inaccurate. In th e second group,
istered from day 18 of the cycle until the tirst day of timing or targeting ofthe progesterone eva luation elimi-
menses with a tapering of the medicati on on th e tirst nates that flaw and signiticantly improves the reliability
two menstrual days . Using progesterone in this fashion of those in vestigations.
is not targeted to the exact lutea l ph ase and is not being
given cooperati ve ly with the menstrua l cycle (see be- In at least one study, the ovarian fo lli cle was fo ll owed
low). by ultrasound in those patients who had PMS and in a
controlled population. 44The group with PMS exhibited
In 1987, a correlation was fo und between decreased se- a signiticantly decreased size of the ovarian follicle prior
rotonin leve ls and depression seores in women who to the time of rupture (p<.0001 ). This is important be-
had PMS .32 This has led to the use ofa variety ofSS RI ca use it has been shown that lutea l ph ase progesterone
as the "tirst line oftreatment"8 for PM S. The initial stud- leve ls are often assoc iated with the integrity and func-
ies were with fluoxetin e. 333 4 ln a review ofnearly 20 pla- tion ofthe deve loping follicle. Thus, it is more credible
cebo-controlled tria Is, Dimm ock, et al. ,35 suggested that to look at the decrease in progesterone production dur-
the SSRls were an effective tirst-line therapy for severe ing the lutea l phase of patients with PMS when the
PMS. fo lli cle diameter has been measured and fo und to be
decreased in this same popul ation of patients.
This led to the marketing of Prozac (fl uoxetine hydro-
chloride) under a new name ofSarafem speciticall y for In sp ite ofth is, APGO has suggested that the consen -
reaching those women who had PM S. While thi s ap- sus with regard to the role of ovarian steroi ds is that
proach is now the standard "tirst line of therapy,"8 the "normal ovarianfunction, rather than hormone imbal-
product in formation on Sarafem itse lfpoints out that, at ance, is the cyclic trigger for PMS and PM DD" (empha-
the sta ndard dose of 20 mg, onl y 6.0 percent have sis applied). 8In making thi s com ment, th ey focused on
marked improvement and 37.O percent ha ve moderate a paper by Schmidt, et al. 47ln thi s experiment, women
improvement, for a tota l improvement rate of onl y 43.0 were given leuprolide acetate (Lupron) with and with-
percent. While thi s was indeed greater than the pl acebo out the add iti on of E2 or progesterone. Thi s conclusion
group (4.0 percent ofthe placebo group showed marked on the role of ovarian stero ids was reached after th ey
improvement), it cannot be considered a hi ghly eftica- observed that the patients who were given leupro lide
cious treatment. acetate plus E2 or progesterone showed a signiticant
recurrence of symptoms. Thi s study design observes a
While alprazolam has been promoted as a routine treat- group ofwomen whose menstrual phys iology was sig-
ment for PMS, it should be kept in mind that it is one of ni ti canti y altered by a potent exogenous suppressant
the most common prescription drugs responsibl e for of hormonal function. When adding either E2 or proges-
admission to drug-dependency units. 36 terone to thi s signiticantl y altered state, the researchers
observed that the patients became wor e and concluded
that "the occurrence of symptoms represents an abnor-
Role of Ovarian Steroids -----~ mal response to normal horm onal changes." This study
des ign is so flawed that such a conclusion is clearl y not
The ro le of progesterone and its various by-products merited.
a long with estradiol- l 7P(E 2) have been studied for over
30 years now in women who have PMS. The studies
ca n be di vided into those that had no signiticant de- Progesterone Treatment -----~
crease in progestero ne and those that had elevated
progesterone in th e patient popu lati on. 31-41Another In October 200 1, the Briti sh Medica! Journal published
group of studies showed decreased progesterone lev- a systematic review ofthe efticacy ofprogesterone and
els during the luteal phase of those women who ha ve progestogens in the management of premenstrual syn-
PMS. 4246 Two methodological ditferences exists between drome.48 This study concluded that the ev idence fro m
the two groups of studi es. 1n the tirst gro up, the proges- their meta-ana lyses did not support the use of proges-
terone leve ls, for th e most part, were drawn according terone or progestogens for managi ng PMS. However,
to the day of the menstrual cycle without particular ref- this systematic review did not address the issue of th e
erence to the timing of ovulation. In the second group, timing ofprogesterone therapy during the cou rse ofthe
progesterone levels that were speciti ca lly timed relative menstrual cyc le. Timed progesterone therapy is an ex-
treme/y importan! issue in the evaluation and treatment The sign ificance ofthis is outlined in Figures 29-5 and
ofthis condition. In fact, in the original publications by 29-6. These two figures exp lain the difference between
Dalton ,3.4 she recommended that treatment begin based non-targeted progesterone therapy versus targeted
upon the day of the menstrual cycle and be continued progesterone therapy ( cooperative progesterone re-
through the beginning ofthe next menstrual period. This placement therapy). In the first instance, progesterone
was a methodological tlaw in her approach to the treat- is started on a given day ofthe menstrual cycle (Figure
ment ofthis condition. 29-5) -on day 16 in this example (typical ofmost stud-
ies). The progesterone is then continued until the be-
There have been six double-blind placebo-controlled ginning of menses or, in sorne cases, one or two days
trials ofprogesterone therapy in women with PMS. 49 - 54 after menses . When ovulation occurs on day 14 ofthe
In five ofthese studies, no improvement could be iden- cycle, the beginning of the progesterone therapy will
tified with the use of progesterone support in the treat- be fai rl y coord inated w ith the beginning of the natu-
ment ofPMS 49 •5º· 52 • 54 while, in one ofthe studies, signifi- rally occurring rise in progesterone. However, by con-
cant improvement was identified 51(Table29-6). lt is note- tinuing the progesterone until the start of menses,
worthy that the study which produced results show ing menses is an artificial ly delayed beca use of the exog-
significant improvement with progesterone used prop- enous ly administered progesterone. When ovulation oc-
erly timed progesterone administration within the men- curs /afer in the cycle, the progesterone will be given
strual cycle. In that stud y by Dennerstein, et al. ,51 the in advance of ovulation and, thus, will have an impact
administration of oral progesterone during the postovu-
latory phase ofthe cycle was started approximately three
120
days following ovulation, confirmed by determinations
ofurinary 24-hour pregnanediol and total estrogen con-
centrations. In the other five studies, the progesterone
110 ---· all subjccts
6 - 6 progcstcronc followcd
by placebo
100 ~--,, O- - - O placebo followcd
was admini stered by the day ofthe menstrual cycle in a
~
by pro¡cstcronc
fash ion similar to Dalton's original work. The improve- \ ''
90 \ ''
ment in the seores on the menstrual distress question- o \ 'a._
naire (MDQ) observed in Dennerstein 's study is shown
o
::!'. eo \ --- --- --a. ,,,,,,_ -- _...,
o \ ''
' /
in Figure 29-4. ~ 70 \ /' ''
\ ~/' '' '
0---------0
In these studies, the methodological flaw, which have ro ~----
been consistent throughout the history of PMS stud-
ies , involves the timing of either the assessment of Luh!<ll Fírst Second Third Frurth
OS"Sessmeri treatment treotmert treotmm notment
progesterone production or the administration of month month month month
progesterone itself. ln actual fact, the percentage of Premenstruol ossessments
cycles in which ovulation occurs prior to and including Figure 29-4: Comparison of total seores in the menstrual
the l 4th day ofthe menstrual cyc le is on ly 34.7 percent. distress questionnaire (MDQ) for all subjects grouped ac-
Ovulation occurs fo ll owing the 14th day in 65 .3 percent cording to arder of treatment (progesterone followed by pla-
cebo , placebo followed by progesterone) (From : Dennerstein
of cycles (Tab le 29-7) . Even at day 20 ofthe cycle, 7.6 L, Spencer-Gardner C, Gotts G, Brown JB , Smith MA, Bur-
percent of cycles still await ovulation. rows GD: Progesterone and the Premenstrual Syndrome: A
Double-Blind Cross-Over Tria l. BMJ 290 :1617-1621 , 1985).
Table 29-6: Double-blind Trails of Progesterone Therapy and

the Precision of Targeting the Luteal Phase
Author Year Targeti ng Lilteal Phase Effectiveness
Sampson" 1979 Calendar No improvement

Van der Meer, et al. 50 1983 Calendar No improvement
Dennenstein, et al. 51 1985 Urinary hormonal assessment Significantly better
Anderschi, et al. 52 1986 Calendar No improvement
Maddocks 52
1986 Day 16 No improvement
Freeman 54
1990 Day 16 No improvement
Chapter 29: Premenstrual Syndrome : Evaluation and Treatment 351
Non-Targeted Progesterone Therapy

20 Ovulation
Q)
e: Day 14
...
o-
Q)
-E
~e, 10
~E
o-
...
c.. Menses
o..._.:::;::::::;::::;:::;:::::;::::;;:::;:::;::::;;:::;:::;:::~......
o 5 10 15 20 25 35 40
20 Ovulation
Q)
e:
Day 16
... -
o-
'* .E
Q) C'I
C'IE
10
o-
...
c.. Menses
o..J....;;:::;:::;:::;:::;:::::;::::;:::;:::;:::::;:::;:::::::;::::;::::;::::;:::::11
o 5 10 15 20 25 35 40
20 Ovulation •1
Q)
e: Day 18 1
••
o-
... - •
'* .E
Q) C'I
C'IE
10 pp :
1
o-
...
c..
Menses
ol-:i;:::;:::;:::;:::;:::::;::::;:::;:::;:::::;:::;:::;:::;::::;::::;::::-.
o 5 10 15 20 25 30 35 40
20 Ovulation
Q)
e: Day 20
....,----....... '
o-
... - ,, ''
'*.E
Q) C'I
C'IE
10 pp ,,,
, ''
' . ADM
o-
...
c.. Menses
o.&-:===;::=:;:::;:::::;=:;=;::==::;:::::;=;::::;:=;::::;::*-1111111111. .
o 5 10 15 20 25 30 35 40
Day of Cycle
PP= Preovulatory Progesterone

EXP= Exogenous Progesterone
ADM= Artificially Delayed Menses
Figure 29-5: A schematic outline of the use of exogenous progesterone in a non-targeted fashion given the circumstances of
ovulation occurring on days 14, 16, 18 and 20 of the cycle with the progesterone starting automatically on day 16 of the cycle
and concluding at the start of menses (From: Pope Paul VI lnstitute research , 2004) .
Targeted Progesterone Therapy
20
Q)
e:
o-
... -
s111 -É10 Ovulation
Cl Day 14
8, E
o-
...
c.. Menses
o+...;:::;:::~=;=;=;::::;=;=:;::::;::::;~::¡_,
o 5 10 15 20 25 30 35 40
20
Q)
e:
... -
o- Ovulation
s111 .§10
Cl Day 16
8, E
o-
...
c.. Menses
5 10 15 20 25 30 35 40
20
Q)
e:
... -
o-
Ovulation
s111 -É10
Cl Day 18
8, E
o-
...
c.. Menses
5 10 15 35 40
20
Q)
e:
o
... --
s111 .§10 Ovulation
Cl Day 20
8, E
o-
...c.. Menses
o~;:::;:==:;::::::;:==:;:::::::;;:::;:==:;::::::;:==:;:::::::;;:::;:::;::::~::::.i....~
o 5 10 15 20 25 30 35 40
Day of Cycle
EXP= Exogenous Progesterone
Figure 29-6 : A schematic illustration of the use of targeted progesterone therapy with ovulation occurring on days 14, 16, 18
and 20. Progesterone is given from Peak +3 through Peak +12 or HCG is provided on Peak +3, 5, 7, and 9 and both are finished
prior to the onset of menses (From : Pope Paul VI lnstitute research , 2004).
Chapter 29: Premenstrual Syn drome : Evaluati on and Treatm ent 353
ion with the post-Peak phase ofher cycle.

Table 29-7: Occurrence of Ovulation
R elative to Day 16 of th e Menstrual Cycle
With regard to th e use of pro gestero ne as a therapeutic
agent, it sho uld be noted th at it <loes have sedative and
% Ovulation occuríng % Ovulation
pr'iór to and íncl udihg,.. Day occuring after ... hypnotic effects after its oral administration. 55 This may
be mediated through its man y metabo lites.
34.7 14 65.3
63.5 16 36.5
78.7 18 21.3
Othe r Associated Findings _ _ _ _~
92.4 20 7.6
1. Hilgers TW, Prebil AM , Hilgers SK, Daly KD : The Occurrence of Ovu- In 1981 , Dalton reported that the binding capacity of
lation at the Midcycle. lnt Rev Nat Fam Plan . 4:227, 1980.
sex-hormone-binding globulin (S HBG) was significantly
lower in those patients who had premenstrual syndrome.
She suggested that leve ls of S HBG-binding capacity
could be usefu l in the diagnos is and even be he lpful in
on.follicular growth and development. This would be exp laining the etiology of PMS 56 La ter, she showed that
expected to lower artificially the natural production SH BG binding capac iti es increased w hen the p atients
o.fprogesterone by causing the development o.fa dys- were treated with three different doses of progesterone
functio nal corpus luteum (as the result o.f an inte1fe r- and, as the dosage increased , so did the SHBG-binding
ence in the developing.follicle). In addition, the proges- capacity. 57
terone environment created .from the continuation o.f
progesterone until the start o.fmenses would artificially Plasma, g lucose and insulin levels during the men strual
delay menses through its exogenous impact. In e.ffect, a cyc les of norm al women and wo men w ith PM S were
non-targeted approach to progesterone therapy cre- studi ed by Spellacy, et al. 58 Although sorne have sug-
ates its own endocrinopathy as a result o.f the exog- gested that carbo hydrate metabo li sm during the luteal
enously administered progesterone. phase ofpatients w ith PMS may be somewhat altered,
they fou nd no statisti ca ll y s ignifi cant changes in the
Thi s can be corrected , as shown in Figure 29-6, when plasma glucose or insulin levels between the two gro ups.
progesterone is g ive n in a cooperative fashion during
the course of the men strual cyc le. In thi s way, progest- Serum leve ls of free testosterone we re s ignifi cant ly
e rone is always g ive n following th e occurrence ofovu- higher in subj ects with PMS. Thi s observation is noted
lati on and discontinued a lmost always prior to the on- during the fo llicul ar phase, arou nd the time of ovul a-
set of menses. E ither oral o r vag inal proges teron e is tion , and during the lutea l phase ofthe menstrual cycle.59
administered o n days Pea k + 3 through Peak + 12 as de- DH EA leve ls were al so s ignificantly hi gher in the PMS
termined by th e us e of th e CREIGHTO N MODEL gro up aro und the time of ovulation and 17-hydroxy-
FertilityCare™ System . Targeted therapy can also be progesterone levels were hi gher during the lutea l phase
provided by giving intramuscul ar progesterone on Peak ofthe cycle.
+ 3, 5, 7, 9 and 11 o r HCG inj ecti ons on Peak +3, 5, 7 and
9. With any of th ese approaches to therapy, suppl e- The pulsatile pattern ofLH secretion has also been evalu-
mentation of progesterone or support ofthe lutea l phase ated. T he changes in pu lsatil e LH secreti on across the
wi ll be cooperative with the normal production o.f cyc le were not different in the PM S pat ie nts compared
progesterone during the course of the postovulatory to norma l wome n, but the mean FSH leve ! during m id-
phase of the cyc le. lutea l phase was hig her in the PM S gro up .6º This was
also fou nd by Lewis, et al. ,61 however, in poo led data
This so lves the greatest c ha ll enge in the treatment of a the length oftime between LH and progesterone pulses
variety of women 's hea lth condition s (d isc ussed in systematica ll y increased across the luteal phase, but in
Chapter 27). Progesterone replacement therapy repre- the PMS group, s ignifi cantl y co incident pul sing oc-
sents the s ing le, most important methodo logica l diffi - c urred ata n unex pected zero time lag o n th e symptom-
c ulty in the studi es done to date o n PM S and a va ri ety onset samp ling day.
of other wo me n 's health issues. Targeting of the lutea l
phase has been , from the beg inning ofth is era of repro- Adrenoco rticotropic hormone (ACTH) leve ls were ob-
ductive medicine, in error. Thi s can be corrected whe n a served to be s ignifica ntl y lowe r in patients with PMS
woman charts her me nstrual cycle, ide ntifi es her Peak during the luteal phase .62 Corti so l leve ls were no t ob-
Day and begins the progesterone in a cooperative fas h- served to change during the course of the cyc le in the
PMS group a lthough PMS subj ects tended to have in- use ofna ltrexone (25 rng tw ice a da y). The acceptab ility
creased corti sol leve ls in th e lutea l ph ase, whi ch was of this drug was consid ered good , but side effects in-
the reverse ofthe directi on found in the control group. cluded nausea, decreased appetite, and dizziness. It was
lnteresting ly, ~- e ndorphin was fo und to be decreased suggested that thi s may represent an effective treat-
in the PMS subjects as well. Beta-endorphin is norrnally rnent fo r thi s syndrorne (Figure 29-9).
co-secreted w ith ACTH and orig in ales from the sa me
precursor. It has been observed c linicall y that intrave-
nous ACTH will reduce depression and anx iety, sug-
gesting that the lower ACTH levels observed in PMS
subjects may re late to the lac k of mood-elevating ac-
tions ofACTH .
o Control
The progesterone metabo lite all opregnano lone has also
15 0 • PMS
M edian
been studi ed extensi vely in women w ith PMS. G irdl er, E
...._ 125
et al.,63 showed that women with very severe PMS had Ol *
lowe r allopregnanol one leve ls than women with less c. 100 o
severe PMS. In both cases, the levels of all opregnan- e
o lone were higher than in the control groups. Rapkin, et .e 75 o
c.
.... ..i..
...'
00
a l,64 showed that subj ects with PMS mani fes ted lower o o
"O o ~
.,..
levels of allopregnanolone during the lutea l ph ase when 50
e -""'- _J_ !
.
00
Q)
compared w ith the co ntro ls . A ll opreg nano lone has 1 JI, 00
Ql. 25
anxiolytic properti es. Dirninished concentrati ons ofallo- o
pregnanol one in women with PMS could lead to an in- T.

o
abili ty to enhance gamm a aminobutyric acid (G ABA)- 7 25
mediated inhibiti on during states of altered centra l ner- Menstrual cycle , day
vous system exc itabili ty, such as ovul ati on or phys i-
ologic or psycho log ica l stress . The lower metabo lite Figure 29-7 : The ~ -endorphin levels for control subjects and
PMS patients on days 7 and 25 of the menstrual cycl e. The
leve ls could contribute to th e genes is of va ri ous mood
PMS group is significantly different from the control group on
symptoms of the di sorder such as anx iety, te nsion and day 25 (p= .000 1) (From : Chuong CJ , Coulam CB , Kao PC ,
depress io n. 64 Bergstralha EJ , Go VLW: Neuropeptide Levels in Premen-
stru al Syndrome. Fertil Steril 44:760-764, 1985).
Chuong and Coulam , et al.,65 studied premenstrual ~
endorphin levels in women with PM S and fo und them
significantl y lower in the luteal phase (Figure 29-7). This
finding was corroborated by Fachinetti and Marti gnoni ,
et al. 66 The PMS pati ents showed a decrease in ~-en dor 15
phin the week preceding menses and du ring the first
days of the menstrual fl ow. The ~- e nd orphin levels re-
12
gained normal va lues during the next fo lli cul ar ph ase E
(Figure 29-8). 'o

.: 9
z
These findin gs ofd ecreased ~ -end o rphin led to a clini- ~
r
I
Q. -o-
cal tria! ofthe drug naltrexone (Trexan, ReVia). A double- g 6
e
blind placebo-controlled crossover study was used to z
eva luate the effi cacy of thi s oral opiate receptor an- "'
1
"'
tago ni st.67 lt was thought that the acute withdrawa l of * * *
opiate inhibition ofbi ogenic immune systems could lead
0
to rebound hyperactivity of neurona l path ways beca use - 11 -B -s -z
ofs lowly acquired receptor supersensi ti vity. Thi s could DAYS ACCORD I NG TO ME NSES
then resul t in irritabili ty, anx iety, tension and aggres-
Figure 29-8: Plasma ~ -en d orphin changes (mean:!: SE) in the
sion, which are common symptoms of PMS. Us ing the perimenstrual period in PMS patients (salid line) and controls
menstrual distress questi onna ire asan obj ective too!, a (dashed line). *p< .05 between groups (From: Facchinetti F,
signifi cant decrease in symptorn express ion during the Martignoni E, Petraglia F, Sanees MG, Nappi G, GenazzaniAR:
Premenstrual Fall of ~-endorphin in Patients with Premen-
luteal phase ofth e menstrual cycle was fo und w ith the
stru al Syndrome. Fertil Steril 47 :570-573, 1987) .
Chapter 29 : Premenstrual Syndrome : Evaluation and Treatment 355
~ - Naltrexone
o
~ 200 - Placebo
a
o
:E
IO 150
N
>.
ns
o 100
oen
+I
50
Naltrexone- Placebo Placebo - Na ltrexone Placebo - Naltrexone

(Combined)
Treatment
Figure 29-9: The effect of naltrexo ne on the day 25 menstru al distress
questionnaire (M DQ) score as compa red to placebo (From : Chuong CJ ,
Coulam CB, Bergstralh EJ , et al. Clinical Trial of Naltrexone in Premenstru al
Syndrome. Obste! Gynecol 72:332-336, 1988).
Pope Paul VI lnstitute Evaluation and ing suicida!, fee ling 'wired,' fee ling anxious, having panic
Treatment Protocol -------~ attacks , fee lin g co nfu sed , fee ling para noid , be in g
anorexic or bulimic, being obsessive-compul sive, hav-
The background provided in the first part ofth is chap- ing an increased frequency of seizures, and hav ing an
ter lays the foundat ion for the successful approach for increased freq uency of sinus in fectio ns.
the treatment ofwomen with PMS at the Pope Paul VJ
ln stitute. Data in thi s evaluation wi ll be presented on a [n Table 29-9, the incidence ofthe 1Ocore symptoms for
group of 14 7 patients carne to us because of PMS and these 147 patients is listed. The most common symp-
on the first 88 of those pati ents that we have treated . toms, occurring in over 75.0 percent of cases, included
Data wi ll be presented on endocrine profiles for both irritability, bloating, cry ing easi ly, fatigue, depression,
progesterone, E2, and ~ - endorp hin on su bgroups of carbohydrate crav ing, breast tenderness and weight
these popul ations. ga in . Headache and insomni a were frequent but less
common than the others.
In the patient population who v isited the lnstitute be-
cause of PMS complaints, the mean age was 33. 1 with a T he average length oftime that these symptom s began
mean grav idity of2.0. Menarche averaged 12.8 years, prior to the onset of menses was 9.4 days. In over 50
the length of menses averaged 5.6 days, the length of percent of patients, the symptoms started 1O days or
tail-end brown bleedi ng which were observed on their more prior to the onset of menses and, in over 90 per-
CREIGHTON MODEL charts was 2.6 days, and the length cent, 7 days or greater (Table 29-1 O). This symptom com-
of the prev ious use o fora l contraceptives averaged 3 7 .2 plex and timing is very consistent with the more seri ous
months.
The diagnosis of PMS at the Pope Paul VI In stitute Table 29-8: Diagnosis of Premenstrual
includes the fo ll owing li st: irritability, breast tender- Syndrome (PMS) - Pope Paul VI lnstitute
ness, bloating, weight gain, carbohydrate craving,
crying easily, depression, headaches, fatigue, and in-
somnia. The important aspect of diagnosis is that these Any of the following symptoms occurring four or more
symptom s must begin at leas! four days prior to the days prior to the onset of menses and fading after
onset ofmenses. lfthey occur with in three days ofthe menses starts:
onset of menses, they are considered to be normal pre- • lrritability • Crying easily
• Breas! tenderness • Depression
menstrual molimina5 (Table 29-8). ln addition to these 1O • Bloating • Headaches
core symptoms (most of which are also a part of the • Weight gain • Fatigue
• CHO craving • lnsomnia
ICD-1 Oand the DSM-N symptom complex), other symp- • Other
toms were also documented in this group of patients.
These included being vio lent, being se lf-abus ive, fee l-
356 The Medica! and Su rgica l Practice of NaPr o TECHNOLOGY
condition of premenstrua l dys ph ori c di sorder (PM DD)

Table 29-9: lncidence of Symptoms Associated
with Premenstrua l Syndrome (PMS) (N=l47 ) In eva luating pati ents at the Pope Paul Vl In sti tute, the
1O core symptoms are e li cited at the time of entra nce
Symptoms % Symptoms %
into the program . Additi onal symptoms are also col -
• lrri tability 92.6 • CHO craving 83.7 lected if the wo men ha ve ex peri enced them. T he pa-
• Bloating 91.7 • Breast tenderness 82 .7 tients are th en referred to the FertilityCare™Center to
• Crying easily (tea riness) 90.2 • Weight gain 75.6
beg in chartin g the CrMS so tha t they can obta in a prop-
• Fatigue 89.1 • Headache 64.4
• Depression 88 .0 • lnsomnia 49.2
erly targeted post-Peak hormone pro fil e. A fter two cycles
have been charted, they return fo r a co mplete physical
examination and fo r the ordering ofthe appropriate blood
tests to further eva luate the ir condition . O nce the b lood
levels are drawn and interpreted, an appropri ate treat-
ment regimen is instituted (Tabl e 29-11 ).
Table 29-10: Premenstrual Synd ro me (PMS) -
N umber of D ays Prior to M enses th at Thi s program, fro m point of entry un ti 1the cycle of treat-
Sympto ms Start ( =11 5 1)
ment, req uires three cycles with treatment coming in the
Number of days sympt oms start premenstrually
fo urth cycle. Ph ys ic ians are often frustrated by th e
4-6 7.9 10-13 14 or more Average length of tim e from the patient's po int of entry to treat-
ment. However, w hen th e process of eva luation and
8.7% 37.4% 29.6% 24.3% 19.4 :!: 3.2 1
eventua l treatment is described to patients (who have
1. Of a total n= 14 7, there were 115 where th is information was available. usually suffe red from these symptoms fo r many years
and have seen multipl e phys ic ians w ithout adequate
assis tance) at th e po int of entry, they are more than
w illing to parti cipate in the ir own care so that a d iagno-
Table 29-11: Recommended Evaluation of sis can be establ ished and proper treatrnent can be imple-
Patients with PMS - mented (th e success of treatm ent is ve ry good). Part of
Pope P au l Vl lnstitute the approach of NaProTECHNOLOGY is to educate pa-
tients pro perly so that they understand what is happen-
ing within their bodies and can become co-parti cipants in
• PMS-specific patient history
their own eva luation and eventual treatment. This allows
• Cha rt CREIGHTON MODEL System for two months
fo r a longer continuity of use and treatrnent program.
• Return for physical examination
After the ph ysica l examination , pati ents are set up to
• Order complete PMS hormone profi le
• Peak +3 , 5, 7, 9, 11 - P+E2 ha ve a progesterone and E 2 leve! drawn on Peak + 3, 5, 7,
• Peak +5, 7, 9 - ~-endorphin 9 and 11. Thi s g ives a full profi le of progesterone and E2
• Peak +7 - TSH, thyroid profile , Total T,. rT,.
T3 :rT 3 ratio productio n alo ng with its sum and mean. In additio n, a
• Return for explanation of test results and implementation Pea k +5, 7 and 9 ~ -e nd orp hin leve! is drawn, a Peak +7
of therapy TSH, th yro id profil e, total T 3 , reverse T 3 , and T 3 :rT 3 ra-
tio are perfo rm ed . T hi s hormona l p rofil e provides a tar-
geted view ofthe progesterone and E2 production a long
Table 29- 12: Post-Peak Progesterone (ng/ mL) Profile'

Controls vs. PMS
Group P+3 P+5 P+7 P+9 P+11 Sum Mean
Controls (n=22) 9.4 13.3 14.5 12.1 6.8 57.4 11 .5

PM S(n=77) 10.6 12.7 11 .5 8.4 4.9 46.6 9.3
p-va lue 2 NS' NS []_TI [QQ] [@ [@

1. From: Pope Paul VI lnstitute research , 2004.
2. Student !-test
3. NS= not significant
Chapter 29 : Premenstrual Syndrome : Evaluation and Treatment 357
VL
DAD
H
2
M
3 4
L
OAO DAD
5
VL
•
6
CAD
7
13
OAD
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DAD
B
9
""º
-~
10
CAO CAD
11 12
4xl
13
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x;¡
~
14
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15
f~f
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xi
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xi
16 17
,_
18
OAD CAD OAO

19 zo
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21
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22 23 24
OAO OAO OAO OAO OAD OAD

25 26 27 28 29 30 31 32 33 34 35
11.0 11.r. ~. 3 8.7 ~. 8

PRIJGE.o TER JNE
S</n' .40 4
7á mL
n
ml
Mea r· s 1 n9 rnL
ES1 iRAC OL 11 élL

~. I 4 .0 a, ,q 3 .7 a4 sum p ¡q,J r i~f!
••.! n ÍfdL
'" """"
e>- i'NC P RF H!N f'9 mL
8.'1 3,q s.~
...
L M M L M L L VL 4XO •x• aAD 4•3 ~·3 4•a •K
f º''f t., f f f
/OC 4•1 OAD <AD 4d ... 4AD . .. 4 •a 4x• 4AO
aw
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4X I 4•1 ••• ••• x•
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;.4.5 111.q 5.5 f.4
PF OGE 5TE ~ONI
sum 50.; ng ;;t mL
Mear .. 10. 1 "9 'mL
ES 'RAt OL 17¡ dl
dnL9
is.a 148 4.3 a.o SUm· 34.3 ng
,_, •A ng c!L
'" 13- ENC ORP H!N P9' nl
IREM NDER: )RD ºR ~ EW li/.RT. >TA f1PS ANI ¡,q
f.~ 1.1
r~AK A~ POI ~TM ºNT FOI FC LO W·UD
"'
Fig ure 29-1 0: The targeted assessment of progesterone, E2 and ~-endorphin in two separate patients with PMS . The evalua-
tion is prospectively accomplished by using the post-Peak phase of the cycle as defined by the CrMS (From: Pope Pau l VI
lnstitute research , 2004).
w ith the P-endorphin production during the lutea l phase is presented in Tab les 29-1 2 and 29-13 and Figures 29-
ofthe menstrual cyc le in a way that is reproducible from 11 and 29- 12. The progesterone levels were sign ificantl y
cyc le to cycle and woman to woman. In addition , it gives decreased beginning on Peak + 7 (p=.03) and on Peak +9
us an exce ll ent review of underl ying thyroid funct ion. (p=.00 l) and Peak + 1 1 (p= .03). The sum and mean ofthe
These data are interpreted re lative to the targeting of 5-value profile was also sign ifi cantly depressed (p=.02).
the cyc le w ith the CrMS (Figure 29-1 O). The E 2 profi le was significantly decreased on ly on Peak
+9 (p=.02) and Peak + 11 (p= .04). While the sum and
The data that we ha ve obtained on the post-Peak proges- means were decreased in compari son to the contro ls,
terone and E2 proftles in patients with PMS were com- the differe nce was not stati stical ly s ignificant. These
pared to a contro l group of patients who spec ifi ca lly findings, especiaUy for progesterone, are consistent w ith
did not have PMS a nd had either exhib ited previously previous studies in whic h a reasonable attempt has been
normal fert il ity or hada normal ovulation pattem wi th a made to ti me or target the lutea l phase.
positive cumulu s oophorus anda complete rupture di-
ag nosed by ultrasound. The data for these two profil es The data regarding P-endorphin production were pre-
Table 29-13: Post-Peak Estradiol-17P (ng/ dL) Profile 1

Controls vs. PMS Patients
Group P+3 P+S P+7 P+9 P+11 Sum Mean
Controls (n=22) 9.1 10.6 11 .8 11.3 9.8 52 .6 10.5

PMS(n=74) 10.5 10.7 10.7 9.0 6.6 46 .0 9.2
p-va lue' NS' NS NS ~ [@ NS NS
1. From: Pope Paul VI lnstilute research, 2004.

2 Student t-test
3. NS= not significant
Table 29-14: Post-Peak ~-Endorphin (pg/mL) Profile 1

Controls vs. PMS Patients
Grou p P+S P+7 P+9 Sum Meah
Controls (n=22) 12.7 14.7 17.3 44 .6 14.9

PMS(n=57) 13.2 13.3 13.8 39.8 13.2
p-value' NS' NS CQI] [@ [QIJ

2. Student t-test
3. NS= not significa nt
Post-Peak Progesterone Profi les - Control group

- PMS
Controls (N=22) vs. PMS Patients (N=77)
16- ~ ~
14.5
14- 6 57.4 11.5 12
13.3
~ K'
_," , ... , 12.1 2
3
,,
12- 12.7-'-)1.5 10
"~ -
_,
11 ~
~ 10.6 a ' ''' ~ o
~E 1
"';¡¡
o- ''' 4 8 """
ce_¿;
Q. -
eJ) " 9.4 r~
'
e ~
c..
E
a- \ 84º -~
' 6.8 3 6 ¡;-
~ s-
'' ' <
t/l
'' ~
4-
'•
4.9
4
2
2-
p-value NS NS ~ ~ [QiJ
P+3 P+5 P+7 P+9 P+11 Sum M ean
Figure 29-11 : Post-Peak progesterone levels in normal controls (n=22) versus PMS (n=77). The levels
on Peak +7 , P+9, and P+11 along with the sums and means for the entire profile are significantly
different from the normal controls (From : Pope Paul VI lnstitute research , 2004).
Post-Peak Estradiol-17 ~ Profiles - Control group

- PMS
Control (N=22) vs . PMS Patients (N=74)
6 12
s NS
11 .8 10.5
5 1 o
=
!:::
''
9.8 K'
2
o ' ' 11 3
9.1 8
:.a ...J 9.Q', ""-" m
~
~~ 8 '' o. ¡;¡
ro.
UJ " '' 6
¡;·
E '• '
~ 6 6.6 .....
t/l
"'
4
4
p-va lue NS NS NS [JD ~

P+3 P+5 P+7 P+9 P+11
Figure 29-12: Post-Peak E2 levels , normal co ntrols (n=22) versus patients with PMS (n =74). The levels
on Peak +9 and Peak +11 are significantly lower !han the control group (From : Pope Paul VI lnstitute
research , 2004).
Chapter 29: Premenstrual Syndrom e: Evaluation and Treatment 359
sented in Tabl e 29- 14 and Figure 29-1 3. Beta endorphins who have decreased ~- e nd o rphin leve ls has been de-
genera lly increase in the normal patient pri or to the on- ve loped that uses targeted lutea l phase support as its
set of menses . However, that increase in ~ -endorp hin is com erstone of treatment and naltrexone, an opi ate re-
blunted in patients who have PMS. This is detectab le ceptor antagoni st, asa n additi onal supportive treatment.
by a significant decrease in ~-en dorp hins w hen com- The dosages for the vari ous lutea l ph ase suppo1t pro-
pared to the contro l population on Peak +9 (p=.02). T he grams are identifi ed in Tabl e 29-1 5 and fo r naltrexo ne
sum and the mean of ~-endo rphin s for 3 val ues is a lso are identified in Table 29- 16.
shown to be decreased sign ificantly during the luteal
phase (p=.04). The primary lutea l phase support program currently in
use is human chorionic gonadotropin (HCG) g iven in
Based upon thi s data, a treatment program for patients a dosage of2000 units Peak + 3, 5, 7 and 9 (Figure 29-1 4) .
Post-Peak ~ -Endorphin Profiles - Control group

Controls (N=22) vs. PMS Patients (N=57) CJ PMS
18 17.3 60
16
14.9
~
-¡¡
16
> 50 14
j ..J 14
e
·-e
~
""m
~
1
.e ,
12 ~ Q
~11:12 40
<g.
"tl
e 1 o 3 5·
"'
=
1 1o r~
30 ~
8 Vi"
8
6 20 6
4 4
10
2 2
P+5 P+7 P+9 Sum Mean

p-va lue NS 1 0.02 I ~ ~
Figure 29-13: Beta endorph in levels comparing the control group without PMS (n=22 ) to patients with PMS
(n=57) on Peak +5, 7, and 9. The Peak +9 level is sig nifica ntly lower !han the co ntrol group and the sum and
mean for these profiles are signifi ca ntly lower (From: Pope Paul VI lnstitute research, 2004).
Table 29-15: Type of Lu teal Phase

Suppo rt used in Conjunction with the
Creighton M odel System
Table 29- 16: Naltrexon e (T rexan , R eVia)
P atients with PMS, Po pe P aul VI lnstitute
• An oral long-acting relative of Narcan (na loxone)

• Human chorionic gonadotropin (HCG) • An opiate receptor antagonist
• Stim ulates corpus luteu m to increase its
production of progesterone and estrogen Labeled uses include heroin addiction and alcoholism
• Intramuscu lar injections (sometimes SQ) • Dosage
• 2000 un its , P+3, 5, 7 , 9 • 0 .25 mg capsu les PO QID x 1O days
OR • Then 0.5 mg QI D x 10 days
• Progesterone oral capsu les • Then 1 mg PO QID x 10 days
• Micronized progesterone • Then 2 mg PO Q ID x 10 days
• 200 mg SR PO Q D hs P+3 -+ P+ 12 • When gets to last do se , stay there , but
• 2000 units, P+3 , 5, 7, 9 eventual ly increase up to 25-50 mg/day (up to
200 mg/day)
OR
Progesterone vagi nal capsules Side effects : dizziness , fatigue , nausea , headache
• Micronized progesterone
• 300 mg caps ules
• QD hs P+3 -+ P+12
antagoni st and it is labe led fo r use in those patients

Table 29-16: Naltrexo ne (Trexa n, ReVia) who ha ve hero in addicti on or w ho are a lcoho lic. How-
ever, it is an extremely good drug fo r pati ents who ha ve
PMS and decreased ~- endo rphin leve ls. In our use of
An oral long-acting rela tive of Narcan (naloxone) naltrexo ne, we have fo und that the starting dosage of
An opiate receptor antagonist 50 mg per day or 25 mg twice a day produces significa nt
• Labeled uses include heroin addiction and alcoholism side effects in a pati ent who is ~-e ndo rphin depleted. In
• Dosage fac t, th at initi al dosage is not we ll tolerated. However,
• 0.25 mg capsules PO QID x 10 days
• Then 0.5 mg QID x 10 days
thi s ca n be so lved by providing an extremely low dos-
• Then 1 mg PO QID x 10 days age of na ltrexone . The standard dosage that we ha ve
• Then 2 mg PO QID x 10 days
used begins with 0.25 mg by mouth fo ur times a day (PO
• When gets to last dose, stay there , but
eventually increase up to 25-50 mg/day (up to QID) fo r 1Odays and then increases to 0. 5 mg QID x 1O
200 mg/day) days, then 1 mg Q ID x 1Odays and then 2 mg QID x 1O
• Side effects : dizziness, fa tigue , nausea , headache days. For many years, we did not go higher than 2 mg
QID . However, recent data (see be low) suggests that
the dosage should go higher if one is to obtain a good
effect. Thus, once 2 mg QlD is reached, the dosage
shoul d be increased even furth er to 4 mg Q ID, then 8
mg Q!D, then 32 mg every day at bedtime (QD hs) and
T hi s stimulates the corpus lute um to increase its pro- then 50 mg QD hs. These are ali cycled on a 10-day
duction of both progestero ne and estrogen. lt is usu- program and, w ith thi s approac h, the overw he lming
ally g iven asan intramuscular inj ection, but it can also maj ori ty of pati ents can take na ltrexone without d iffi-
be given subcutaneously. Progesterone can a lso be used cul ty.
asa n oral micronized, sustained-release 200 mg capsule
g iven by mouth every day at bedtime (PO Q D hs), Peak O n occas ion, we see peopl e even at 0.25 mg Q!D who
+ 3 through P+ 12. Thi s can a lso be titrated to two times have diffi cul ty or problems with this dose. In those cases,
a day (BID) dosage Peak + 3 through P+ 12 if necessary, th e dosage has to be started eve n lowe r. We wo uld
and progesterone ca n be used in add ition to HCG if that suggest that it start at 0.25 mg by mouth every day (PO
is thought to be clini ca lly necessary. Progesterone vagi- QD) fo r 5 days, then 0.2 5 mg two times a day (BID), and
nal capsul es can a lso be used; in that case, a 300 mg so fo rth , to slowly increase the dosage. lt will take longer
mi croni zed ora l capsul e is used vaginall y every day at to get a pati ent on the naltrexone using this ap proach;
bedtime (QD hs) fro m Peak + 3 through P+ 12 (F igure 29- however, the results can be dramati c and it is worth the
15). effort.
altrexone (Trexa n, ReVia) is an ora l, long-acting re la- Once the pati ents are pl aced on therapy, they are fo l-
tive of naloxone (Narca n). T hi s is an opi ate receptor lowed on a monthl y basis to detem1ine the effective-
Tabl e 29-17: R espo nse to Targeted H o rmone Suppo rt in the Treatment

of Premenstrual Synd ro me (PMS) (N =SS)
Progesterone HCG Other

lmprovement Support'" Support'·4 Suppori3 Totals
Response n % n % n % n %
Marl<.ed 11 26 .8 19 51.4 3 30.0 33 37 .5

Modera te 21 51 .2 13 35 .1 4 40 .0 38 43 .2
[]§]] []IT) []Q]] [ªº2J

Minimal 6 14.6 4 10.8 2 20 .0 12 13.6
No ne 3 7.3 1 2.7 1 10.0 5 5.7
Totals 41 99.9 37 100.0 10 100.0 88 100.0
1. lncludes 800 mg progesterone vaginal capsule (n =1 3), 600 mg capsule (n=1 0), 400 mg capsule (n=7), 300 mg capsule
n=1 ), oral progesterone (200 or 300 mg ) (n=6) and IM progesterone (n=4).
2. HCG, 2000 units IM P+3, 5, 7, 9.
3. lncludes naltrexone only (n=5), estradiol- 17~ 1 mg P+3- P+12 (n=1) and HCG and oral progesterone (n=4 ).
4. When comparing the effectiveness of progesterone support vs. HCG support, P=.0012 (chi-square).
Chapter 29: Premenstrual Syndrome : Evaluation and Treatment 361
IS 16 17 18 19 30 31 32 33 34 35
H H M L L VL B
CAD OAO CAD OAO
H H M
M H 8
OAO """ CAD +. I
.. ...
• C e.e. IOS L CAD
• I
11.0 11. • ,,3 8.7 a.S'

8 1.. 1 4.0 a.q 3 .'1 a..4 1q.1 3 .i
13- ndo -phi 8.'1 3.q

••• a1.a '7.1
~~
..
~v
ff ff
106L IOKL ~e
1
OAO
x I x I x I
"""
11.1
Figure 29-14: A typical patient with her CrMS chart during the initial phases of evaluation and treatment. Th e results of the
hormone profile are shown in the third cycle with both progesterone and E2 conside red to be decreased . Th e ~-e ndorphin s
were also very low. Treatm ent with HCG luteal phase support, 2000 IU IM on P+3, 5, 7, 9 is shown in the fourth cycle and the
correspondi ng P+7 progesterone and E2 levels have increased (From : Pope Paul VI lnstitute research , 2004).
Figure 29-15 : In this example, the palien! is being treated with progesterone vaginal capsu les 300 mg per vagina QD hs P+3
through P+12 . In the fourth cycle, the patient decided to discontinue her progesterone . The post-Peak phase shortened and her
symptoms recurred . She resumed treatment again in her fifth cycle (From : Pope Paul VI lnstitute research , 2004).
Comparison of Response to Treatment of Premenstrual Syndrome (PMS)

Targeted Hormone Therapy vs. 20 mg Fluoxetine hydrochloride
Marked and Moderate

lmprovement
86 .5
Marked lmprovement Moderate lmprovement
e:
Q)
~ 5
Q)
a...
HCG ProgesteroneFluoxetine Place bo HCG Prog esterone Fluoxetine Place bo HCG ProgesteroneFluoxetine Placebo
Support Support 20 m g Support Support 20 mg Support Support 20 mg
Figure 29-16 : The compa rison of response to treatm ent of PMS with targeted HCG and progesterone hormone therapy versus
20 mg offluoxetin e hydrochloride versus pla cebo (From : Pope Paul VI lnstitute research, 2004 , and published data on fluoxetine
hydrochloride).
Table 29-18: Prem e nstrual Synd rome (PMS)

Comparison o r R es ponse to Treatment -
Targeted H ormone T h erapy vs. Fluoxetine H ydrochloride
Fluoxetine· Progesterone HCG

lmprovement 20 mg Support' Support9 Placebo'
Response ·/o
0
% % º/~
Marked 6 26.8 51.4 4

Moderate 37 51 .2 35.1 11
Total 43 78.0 5 86.56 15
1. Data basad on 95 patients reportad in product literature of Sarafem (fluoxetine hydrochloride).

2 Based on 41 patients treatad with targetad progesterone support (with and without naltrexone), Pope Paul
VI lnstitute.
3. Basad on 37 patients treatad with targetad HCG support (with and without naltrexone).
4. Data based on 94 patients treated with placebo and citad in product literature of Sarafem (fluoxetine
hydrochloride ).
5. p<.0001 , when comparad to ftuoxetine 20 mg.
6. p<.0001, when comparad to ftuoxetine 20 mg.
Chapter 29: Premenstrual Syndrome: Evaluation and Treatment 363
ness oftreatment. When using post-Peak HCG, at least the fluoxetine group ). This is graphed in Figure 29-16.
one Peak +7 progesterone and E2 level must be drawn in
order to document the occurrence of the increase in In the initial eva luation ofpatients with PMS at the Pope
lutea l phase progesterone and E2 production . The Peak Paul Vl lns titute, naltrexone was adm ini stered in a total
+7 leve! should be drawn prior to the admi ni stration of dosage up to 2 mg by mouth fo ur times a day (PO QID).
the HCG inj ection on that day. When the patients are This is now refe rred to as " low-dose naltrexone." An
seen in fo llow-up, the improvement in symptom response evaluation ofprogesterone and/or HCG support for tar-
is identified usually w ith direct quotes from the patient geted luteal phase support was compared to whether
as to how they are feeling at present compared to be- the patient did or did not take low-dose naltrexone. This
fare the treatment. Thi s is then categorized into a marked, evaluation is showed in Table 29-1 9. We fou nd that the
moderate, or mínima! improvement category or into a no addition of naltrexone at that dosage did not improve
improvement category. Generally, patients stay on thi s the outcome. There was no statistica lly significant dif-
treatment long term for at least one yea r and , after that ference between the two groups. However, sorne pa-
time, consideration can be given to discontinuing the tients on na ltrexone improved signi ficant ly, so the pro-
treatment. However, the treatment common ly needs to tocol was restructu red.
be re-instituted long term . The author has had patients
on post-Peak HCG foras long as 1O years without any In 21 subsequent patients who had had targeted lutea l
difficulties or problem . The husbands are often given phase support, the naltrexone dosage was increased to
instruction on how to administer the injections. Single between 25 and 125 mg per day (now referred to as
women are instructed to use subcutaneous injections, " hi gh-dose naltrexone"). This is more consistent with a
wh ich can be se lf-admin istered. previously published double-blind , placebo-controlled
crossover trial of naltrexone in which the dosage was at
For those who received HCG support, 86.5 percent had lea t 25 mg twice a day. 67 Sin ce converting to that hi gh
either marked or moderate improvement (Table 29-17). dosage, we ha ve observed even more marked improve-
In 78.0 percent of those who received only progester- ment in the sym ptom comp lex of these patients. Most
one support, moderate or marked improvement was ob- patients are on 50 mg per day, but we have had patients
served. However, the frequency of marked improvement up to 200 mg per day w ith out any side effects once they
w ith progesterone was lower than HCG support, and are established on the dosage . In fact, with the usage of
the frequency ofmoderate improvement with progest- the " high-dose naltrexone" program, 90.4 percent had
erone was higher than HCG support. When comparing marked improvement.
progesterone support to HCG support, HCG support
was statistically significantly better (p=.00 12, chi-square We have also assessed the ~-endorphin levels befare
analys is).
The improve ment in PMS symp-

toms w ith targeted hormone sup- Table 29-19: R ole of Low·dose and High-dose Naltrexone on
port was then compared to the pub- Treatment R esponse to Targeted Hormone Support -
1ished data on flu oxetine hydro- Treatment of Premenstrual Syndrome (PMS)
ch loride 20 mg. This comparison is
Without With Low-dose With High-dose
found in Table 29- 18. On ly 43 per- lmprovement Naltrexone1 Naltrexone'.l Naltrexone' ·' ·'
cent of patie nts taking fluoxetine Response n % n % n %
had moderate or marked improve-
Marked 17 34.0 16 42.1 19 90.4
ment, most ofwhich wasjust mod-
Modera te 26 52 .0 12 31 .6 1 4.8
erate. This is sign ifi cantly lower
Minimal 5 10.0 7 18.4 o O.O
than the improvement observed in
None 2 4.0 3 7.9 1 4.8
targeted hormone support for PMS
Totals 50 100.0 38 100.0 21 100.0
in the Pope Paul V I ln stitute proto-
1. lncludes 31 patients with progesterone support, 15 patients with HCG support, 3 patients with HCG and
col. Progesterone support allowed progesterone support and 1 patient on targetad E, support.
for a 78.0 percent moderate to 2. lncludes 1Opatients !reatad with progesterone support, 22 patients with HCG support, 5 patients on
Naltrexone only and 1 patienton HCG and oral progesterone. Naltrexone maximum dose 2 mg PO QID.
marked improvement and HCG sup- 3. p= .6888 (chi-square), when comparad to no naltrexone.
port 86.5 percent. In the placebo 4. lncludes 1Opatients on HCG support, 7 patients on progesterone support and 41 patients on naltrexone
only. Dose was usually between 50 mg and 100 mg PO QD hs but rangad from 25 to 125 mg.
group for the fluoxetine study, 4
5. p<.0001 , (chi-square)when comparad to no naltrexone.
percent showed marked improve- 6. p=.0003 , (chi-square)when comparad to low-Oose naltrexone.
ment (as compared to 6 percent in
the institution of the "h igh-dose naltrexone" therapy

and after the patient was in this therapy (n= 15) (Table Table 29-20: Effect of High·dose Naltrexone
29-20). The leve! on P+ 7 increased from 15.9 pg/mL to on P+7 Seru m ¡3-E ndorp hin Level (N= l S)
22.1 pg/mL when on "high-dose" naltrexone (p= .025).
~- Endorph i n Level
Status of Naltrexone (pg/mL)
On a limited amount of data , we dec ided to compare the
Before naltrexone 15.9
periovulatory E2 sums and means ofthe contro l popu la-
On naltrexone 22 .1'
tion to the PMS population . We did find that, in the
PMS patients, the E2 profile for the sums and the means 1. p=.025, equal variance 1-test.
were both statistically lower. While this is consistent
with the previous finding of decreased follicu lar si ze
( observed by ultrasound in patients w ith PMS)44 (Fi g-
ure 29-17), the small numbers make this oflimited value
at the present time . This should stimulate the potential
for research in this area.
Table 29-21 : CrMS Charting Data
One of the common findings in the patient population in Women with PMS
treated far PMS at the Pope Paul Vl lnstitute is previous
treatment for different types of psychiatric disorders. Variati.o n in Length
The most common is bipolar condition , followed by Mean Mucus of Post-Peak Pha se
Cond it i on Cycle Score Hormone Days
depression , and then followed by perhaps an obses-
sive compulsive disorder. In these patients, it is well Without PMS 1O.O 10.0%
worth the effort to try to elicit the type of symptoms With PMS 8.3 1 62 .5% 2
that are occurring and whether or not a cyclic relation- 1. p=.11 9, equal-va riance t-test (n=17)
ship to the premenstrual phase of the cycle ex ists. ln 2. p=.0009 , chi-square analysis (n=1 6)
many of these cases, after chai1i ng their cycles , prop-

erly targeting the endocrine evaluation as described and
eventual ly treating them , these patients have felt better
and have been able to discontinue their psychotropic
medications.
1 00...-~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
3 Value Sums and Means

Periovulatory E2 Levels
Control (N=2) - PMS (N=6) -
p-values 1,.--.-0 4-55-,1 1 .0055 1
_J
65.0
E
Oi
e
C!1
I'-
..-
1 50
:§
"'O
....
C1l
Uí
w
o
Sums Means
Figure 29-17 : The 3 value sums and means of periovulatory E2 levels in a control group (n=2) and PMS group (n=6). The PMS
E2 levels are significantly lower than the control group but the sample size is very small. This should stimulate further research
(From : Pope Paul VI lnstitute research , 2004).
Chapter 29: Premenstrua l Syndrome: Evaluation and Treatment 365
rience significant premenstrual symptoms. This is simi-

Table 29-22: lncidence of Premenstrual lar to a previously repo11ed incidence of 74.6 percent
Symptoms - Patients with PMS, change ofmood in patients who have infe11ility. 68 This
lnfertility and Spontaneous Abortion raises the possibility that the underlying endocrinopa-
thy and other relative changes that occur in women
Spontaneous
PMS lnfertility Abortion
who have infe11ility problems, sponta neous abortion s,
Symptoms (n=147) (n=252) (n=300) and PMS , may be, in sorne ways, linked to a common
lrritabi lity 92 .6 90.5 73.3
etiology.
Bloating 91 .7 85.3 81 .6
Crying easily 90.2 80.2 63.6
Fatigue 89.1 67.3 55 .2 Final Note -----------~
Depression 88.0 74.1 62.8
CHO cravings 83.7 75.1 64.6
Eva luatin g and successfu ll y treating someone who has
Breas! tenderness 82 .7 85.7 74.4
75.6 69.4
PMS is highly gratify in g. This condition can have an
Weightgain 60.3
Headache 64.4 50 .8 42 .0 ad verse impact on fa mily life, the relationship of spouses,
lnsomnia 49.2 29.0 9.9 and the relationship of the mother to her chi ldren. ln-
deed, for many years, it has been thought that little
could be accomp li shed in treating these patients. More
recentl y, various anti-depressants, especiall y the SSRls,
ha ve been recommended as the main line oftreatment in
Chart analysis (CrMS) on patients with and without PMS thi s area. However, by teaching women how to chart
how that the mucus cycle seores are lower for the PMS their cycles and to observe the changes in their body
gro up (8.3 vs. 1O.O) (Tab le 29-21 ), but it is not statisti- that are assoc iated with fe11ility, by targeting the lutea l
cally significant. On the other hand , the variation in the phase for appropriate progesterone and E, production
length of the post-Peak phase is significantly greater a long with ~-endorphins and thyroid functi-on, and then
for the PMS group (62.5 percent fo ur days or greater by implementing a treatment strategy as outlined in this
variation vs. 1O.O percent for the group without PMS, chapter, incredib le success in the treatment ofthis con-
p=.0009). This biomarker is consistent with the decrease dition can be ach ieved. This, in turn , ca n have an enor-
in progesterone leve ls previously cited. mous impact on the women , their fami li es, and their
spouses.
One other significant observation is the relationship of
premenstrual symptoms in patients who have infertility In presenting this new data, it is recogni zed that others
ora hi story of spontaneous abortion. This is outlined ha ve called for more research in this area using various
in Tab le 29-21. While the symptoms in infertility are not objective psychometric measuring too ls69 as we ll as
as prominent as in women who suffer from PMS specifi- continued cross-discip line work in the fie lds of psy-
ca lly, the profile is very simil ar. In women who have had ch iatry, endocrino logy, neurology, sleep disorders, gy-
previous spontaneous abo11ions, the profile of symp- necology, psychiatry and soc iology. 70 lndeed, conti n-
toms is lower than those women who have PMS and ued resea rch of this kind is needed and now shoul d
infertility, but the profile is sti ll very similar. Overall, about take into consideration the accurate targeting of the
75 percent ofpatients with infertility problems will expe- men strual cyc le.
1. M ezrow G, Sh o upe D: Th e Pre me ns tru a l Sy nd ro 111 e , In : 1 8. Kenda ll KE, Schnurr PP: Th e Effects of Vitamin 8 6 Su ppl e-
Lobo RA , Mi she ll DR , Paul son RJ , Shoupe D, Eds. Mi che ll 's 111e ntat ion o n Pre m e nstru a l S y mpto m s. Ob ste t G y ne co l
Tex tb ook of lnfe rtility, Contra ce pti o n a nd Re produ c ti ve 70: 145- 149 , 1987.
Endocr ino logy. 4 1h Ed , Blackwell Science, Oxfa rd , 1997.
19. Lon do n RS, Sundaram GS , Murph y L, Go ld stein PJ : Th e
2. Fra nk RT: Th e Ho r111 o na l Bas is of Pre111 enstru a l Te ns io n . E ffec t o f A lph a -Toco ph ero l o n Prem e nstru a l Sy mpto m a-
A rch N euro l Psych 26 : 1053 , 193 1. to logy: A Double-Blind tud y. J A111er Co ll N ut 2: 115- 122,
1983.
3. Da lto n K: Th e Pre111 enstru al Syndro111e . He ine 111 ann , Lon-
d o n 1964. 20. Sche ll enberg R: T rea tment fa r th e Premenstrua l Syn d ro111 e
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ontr o ll ed Tri a l of Proge tero ne and Pl ace bo . Brit J Neu ropeptide Levels in Prernenstru al Syndro rne. Fertil Steril
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R, Maidman J: Mood Di sorders, Psych iatri c Sym ptoms and 34:3 13 -3 18 , 1998 .
Postpartum Depression:
T he earliest documentatio n o fp ostpa1t um mental ill -

ness was provided by Hippocrates in 400 8 .C. 1 ln
spite of its e valuatio n over th e mill enni a, postpartum
psycho motor ag itati o n o r reta rdatio n, fa ti g ue or loss of
energy nearl y every day a nd for most of the day, fee l-
ings of wo rthl essness or excess ive g uilt, dimini shed
depress io n has remained an eni gma. Pregnancy, mi scar- abili ty to think o r concentrate, or rec urre nt tho ughts of
riage or pregnan cy loss, infe rtili ty, and th e postpartum death or sui cide. 5 S uch symptoms as appetite and s leep
pe riod chall enge a wo ma n's me ntal hea lth . Virtua lly no change and fa ti gue and dimini shed ene rgy are common
li fe event ri va ls the ne uroe ndocrin e a nd psych osoc ia l and may overl a p the symptoms of pregnancy itself. 6
c ha nges assoc iated w ith pregna ncy a nd c hi ldbi rth .2 T hi s, along w ith a wo man's reti cence to di sc lose such
Because of de press ive epi sodes, up to 32 pe rcent of symptoms, can make detectio n and treatment of depres-
wome n may alter th eir future childbea rin g pla n by re- sion di ffic ul t.
sorting to e ither ado pti on, sterili zati o n, or abortio n.3
Postpartum depression (PPD) is identifi ed in the DSM-
At sorne point in their li ves , 20 percent of wo men w ill lV as a majar depressive disorder with postpartum
suffe r from depress io n.4 Many seek treatment fro m pri- onset. Jt is a majo r depressive epi sode that usually be-
mary care prov iders, but up to 50 percent may go unrec- gins w ithin the first fo ur wee ks fo llowi ng delivery. PPD
ogni zed a nd mo re go untreated. Recogniti o n and treat- can be extreme ly va ri a bl e in both severity and dura-
me nt of depress ive disorde rs in pregna ncy a nd during ti on.7Symptoms include the fo ll owing: dysphoric mood,
the postpartum pe ri od is criti ca ! fo r the hea lthy o ut- loss of inte rest in usually pl easura ble acti viti es, psy-
comes of both the moth er and th e infa nt. cho motor agi tati on or reta li ati on, fa ti g ue, cha nges in
appetite o r s leep, recurrent th o ug hts of death/sui cide,
The Diagnostic and Statistical Manual of Mental Dis- fee li ngs ofworthl essness or g uilt (espec ia ll y fa ilure at
orders, 4th Edition (DSM -IV) criteria fo r maj or depres- motherhood), and excess ive a nx iety over the child 's
sion in clude the presence of fi ve or more ofthe fo llow- health (Tabl e 30- 1). 3
ing sympto ms fo r a peri od of two wee ks or more: de-
pressed mood almost dail y fo r most of the day, dimi n- Depress io n rating sca les fo r thi s patient popul atio n have
ished inte rest or pleas ure in usual acti viti es, sig nifi cant been deve loped to a id physicians in eva luating the post-
we ight loss o r we ight ga in , in somnia o r hypersomni a, pa rtum pe ri od. T hese in clude the Edinburgh Postn ata l
369
370 The Med ica! and Surgica l Practic e of NaProTECHNOLOGY
Table 30-1: Symptoms of Table 30-2: l ncidence of Postpartum

Postpartum Depression 1 P sychological Seq uelae 1
Postpartum mood disorder 40%

Dysphoric mood
Loss of interest in usually pleasurable activities Risk of psychiatric hospitalization in 7x
first three months postpartum
Psychomotor agitation or retaliation
Fatigue Risk of psychosis in postpartum period 22x
vs . pre-pregnancy state
• Changes in appetite or sleep
Recurrent thoug hts of death/suicide Relative risk (RR) of childbirth for 16.1
the development of psychosis
Feeli ngs of wo rthlessness or gui lt, especia lly fai lure
at motherhood
Puerperal psychosis2 0.1-0.2%
Excessive anxiety of chi ld 's health
1. Leopold KA, Zoschnick LB: Postpartum Depression. The Female
Patient. 22:4049, 1997.
Leopold KA, Zoschnick LB: Postpartum Depression. The Female Patient.
22:4049,1997. 2 This is 12-14.5 times the prenatal incidence of psychosis.
Depress ion Rating Scale8 and the Postpartum Depres- The incidence of PPD ranges from 12 to 6 percent or up
sion Checklist. 9 However, use ofthese sea les is uneve n to 25 percent in women with a history of depression.
at the present time . Adolescent pregnancies carry the highest risk fo r PPD
(26 to 32%) (Table 30-3). 16· 26 Ri sk factors that ha ve been
Postpartum psyc hosis (PPP) is a more severe postpar- identifi ed for PPD include lower occupational status,
tum syndrome. lts onset is usua lly w ithin the fírst three prenatal depress ion leve!, persona l psychiatric history,
weeks following de livery and often within thejust a few a hi story ofpremenstrual syndrome (PMS) or previous
da ys. 10 Most epi sodes are re lated to a psychoti c cond i- postpa1tum depress ion, a hi story of mood disorder (b i-
ti on ofbipolar disorder or major depress ion . 11 The symp- po lar or major depression), and a genetic vulnerab il-
to ms of PPP may include delusions, ha ll ucinations, rapid i ty. 2, 17.27-2 9
mood sw ings ranging from depress io n and irritability to
euphoria, s leep di sturba nces , a nd obsess ive rumina-
tions about the baby. The ri sk ofsuicide in PPP is hi gh Etiology _ _ _ __ _ _ _ _ _ _~
(5%) , and up to 4 percent ofwomen with PPP may at-
tempt infanticide . 12 Chang in g reproductive hormo nes, perhaps by affect-
ing the synchrony or coherence between components
PPP is a psychiatric emergency that often warrants hos- ofthe circadian system, may alter the amp litude or phase
pitalization. The prognostic implications for PPP are dif- (timing) re lationships, thereby contributing to the de-
ferent from PPD . early two-thirds ofthese patients w il l ve lopment ofmood disorders in pre-d isposed individu-
suffer subsequent non-puerpera l psychoti c episodes. 13•
15
Table 30-3: lncidence of

Postpartum mood di sorders are common, w ith nearl y 40 Postpartum Depression 1
percent (or more) ofwomen experienc ing them . The risk
of psyc hiatric hospita lization within the first three
months postpartum is seven times more common than Risk of postpa rtum depression ' 12-16%
at other periods in a woman 's 1ife. The risk of psychos is Risk in women with a history of depression 25%
in the postparturn pe ri od is 22 times hi gher than in the
Risk in adolescent pregnancies 2 26-32%
pre-pregnancy state and the relati ve risk deve lo ping
psychos is following c hildbirth is 16: 1. The incidence of 1. Marcus S . Fl ynn HA, Barry KL , Tandon R, Gredber JF: Depression in
Pregnancy and Postpartum: A Review of Critica! lssues. Postgrad
puerperal psychosis is 0.1 to 0.2 pe rcent, which is 12 to Obstet Gynec. 20:1-7, 2000.
14 .5 times the prenata l incidence of psychosi 3 (Ta ble 2. Leopold KA, Zoschnick LB: Postpartum Depression. The Female
30-2). Patient. 22:4049, 1997.
Chapter 30: Postpartum Depressio n: Evaluation and Treatment 371
Comparison of Progesterone Levels

Mean of All Levels at Six-week lntervals
Study group
150.0 Postpartum Depression -
_J Current Pregnancy (N=21)
E
Oi
e - Normal controls
Q)
e c:::J Postpartum depression - current pregnancy
~ 100.0
tí
Q)
Ol
o
il:
E
2 50.0
Q)
(f)
O.O
2- 6 weeks 8- 12 weeks 14 - 18weeks 20 - 24weeks 26 - 30weeks 32-38 weeks
p-value l.0090 4 1 NS' NS NS NS
1. Not statistically sign ifican! Mean Progesterone - Six-week lntervals
2. /-test (equal va riance)
3. t-test (u nequa l variance )
4. Mann-Whitney U test
Figure 30-1 : Comparison of serum progesterone levels at six weekly intervals in patients who developed postpartum depression
(N=21 ) and normal controls (From: Pope Paul VI lnstitute research , 2004).
als. 30 Direct evidence suppo1ts the involvement of the play a role in PPD.3 While evidence the etiologic role of
reproductive hormones estrogen and progesterone in the reproductive hormones is mínima!, changes in cer-
the development of PPD in a sub-group ofwomen. Fur- tain hormonal axes may contribute to depressive mood
thermore, it suggests that women with a hi story of PPD changes in sorne women fo ll owing childbirth. 33
are differentially sensitive to mood-destab ilizing effects
of gonada l stero ids. 3 1 Studies have shown that mater- In an eva lu ation of serurn progesterone leve ls at the
nal mood in the days imm ed iately following delivery is Pope Paul VT ln stitute, women with PPD had higher lev-
related to the withdrawal ofnatural ly occurring proges- els of progesterone during their pregnancies than the
terone. 32 normal controls (F igure 30-1 ) although thi s was statisti-
ca lly signifícant only during the first 12 weeks ofpreg-
The rap id withdrawal ofprogesterone fo ll owing deliv- nancy. lfthe progesterone leve ls are higher during preg-
ery results in the production ofthe metabolite OH-5a- nancy, the larger decrease in progesterone and its me-
dihydroprogesterone. This has a potent, barbiturate- tabol ites at the time following delivery could be a con-
like ligand ofgamma-aminobutyric acid (GABA) recep- tributing fac tor in PPD .
tors . Pregnenolone is also a metabolite of progester-
one, which is rapid ly withdrawn at the time of delivery. Recent data have shown that serum all opregnano lone
These metabo li tes may create sorne ofthe destabiliza- levels are sign ificant ly decreased in women with PPD.
tion previously mentioned, particularly in those patients The adren al synthesis of allopregnanolone may be
who rnight be susceptible to such destabili zation . The blunted and , in turn , would affect maternal mood and
rapid withdrawa l of estrogen following delivery rnay also behavior. The similarity ofthis decrease to that observed
play a role. In addition, the deregulation of the neu- in PMS, which supports the concept that an impaired
rotransmitter serotonin and other biogenic am ines (such GABA anxiolytic response may lead to symptoms. 34
as norepinephrine, ep inephrine and dopamine) may also
Alterations in the hypotha lamic-p ituitmy-adrena l (HPA) During breast feed in g, the use of the se lective seroto-
axis, wh ich wou ld be attributable to chi ldbearing, show nin re-uptake inhibitors (SSRi s) has not been cl early
a remarkab le simil arity to those in women who become estab lished . Wisner, et al., 35·39 pub li shed a thorough and
depressed. 35 Also, postpartum women are at increased critica! review ofthe literature regarding the use of anti-
risk for hypotha lamic-pituitary-thyroidal (HPT) axis dys- depressants during breast fee ding. They noted th at
function, which may also increase affective-d isorder vu l- am itriptyli ne, nortriptyline, desipramine, clomipramine,
nerabi 1ity.33 -36 doxepin , and sertralin e were not fo und in " quantifiab le
amounts in nurslings, and no adverse effects were re-
ported ."
Traditional TherapY -------~
While wai ting for drug respo nse, sorne support and
Sorne have recommended psychotherapy as the first ed ucati on can be impo1tant; during this time, psycho-
line oftreatment for PPD.37 While cognitive behavioral therapy is often used. Various types of psychotherapy
or individual psychotherapy has been effective with may be empl oyed, inc luding cogniti ve therapy, inter-
and without medication, such therapy is often unavail- personal therapy, support of psychothera py, and con-
able, too expensive, or inaccessible beca use of childcare joint therapy.28 Psychotherapy may have a particular ro le
difficulties. As a result, many women opt for sorne type for those women who choose not to take antidepres-
of antidepressant therapy.38 sants or who ex peri ence mi lder depress ion . Such issues
as maternal gui lt (whi ch may translate to a di fficu lty in
Antidepressant therapy can be prescribed during the caring for the in fa nt), poor se lf-estee m, fa mily conflict,
postpartum period except when breast feed in g. Re- and stress can be add ressed. Many be lieve th at the
sponse to any ava il ab le antidepressant requires at least comb inati on of pharmacotherapy and psychotherapy
four to six weeks, assu ming the patient is taking an ap- is th e best overa !! approach to the treatment of PPD .
propriate dose. The likelihood ofsuccess in the patient Drawbacks to this approach include its slow ness (rarely
who completes the first three weeks of treatment (the produc ing an immed iate effect) and its inab ili ty to pro-
initi al drop-out rate from si de effects is approx imate ly duce a long-term turnaround in the symptom com pl ex.
l 5 percent) can reach as hi gh as 60 to 70 percent. 28 lt is As a result, many women become very frustrated with
usually recom mended that, following full remission of this approach to therapy. A review of the dose ranges
symptoms, medication shou ld be continued for an ad- and si de effect profiles ofvarious anti depressants com-
ditional 16 to 20 weeks. At that time, a maintenance dos- monly used to treat PPD is fo und in Table 30-4.
age may be established.
Tabl e 30-4: Dose Ranges and Sid e Effect Pro files o f A ntide pressants
Commonly Used t o Treat Postpartum D epress i o n
Side E'.ffects•
Therapeutic Anticholinergic** Orthostatic Welght gain FDARisk
Drug Range (mg/d) Effects Hypoten sion Arrhythmia (>6kg) Category
Tricyclics
Amitriptylin e (Elavil) 75-300 4+ 4+ 3+ 4+ D
Desipramine (Norpramin ) 75-300 1+ 2+ 2+ 1+ e
lmipramine (Tofranil ) 75-300 3+ 4+ 3+ 3+ D
Nortriptylin e 40-200 1+ 2+ 2+ 1+ D
SSRls
Fluoxetine (Prozac) 10-40 o o o o e
Paroxetine (Paxil ) 20-50 o o o o e
Sertraline (Zoloft) 50-150 o o o o e
O = absent or rare; 4+ = relatively com mon
• • Dry mou th . bl urre d vision, urinary hesitancy, constipation , dro ws iness .
1. Leopold KA , Zoschnick LB: Postpartum Depression. The Female Patient. 22:40-49, 1997.
2. Sussman JL: Postpartum Depressive Disorders. J. Fam Pract 43 (Suppl): 517-524, 1996.
Chapter 30: Postpartum Depression: Evaluation and Treatment 373
The re ha ve been a numbe r of oth er approaches to th e terone therapy fo r wo men w ith PPD .
treatment of PPD . Wo men w ho are pos itive for th yro id
antibodi es (ide nti fi ed by erum leve Is offree th yrox ine,
free triiodothyronine and th yro id stimul ating hormo ne) Phase 1 Progesterone Support Study=¡
in early gestation are most prone to PPD . However, thi s
is no t corrected by the da il y admini stratio n of th yrox ine In th e first ph ase of thi s stud y, patie nts we re enrolled
(TJ .4º fro m th e pati ent popu lati o n of the Pope Paul VI lnsti-
tute alo ng w ith pati e nts who contac ted us fro m the
Most recentl y, estrogen s upport has been used in the FertilityCare™ Centers th ro ughout the Uni ted States
treatment of PPD. 4 1 lt has been hypothes ized that the a nd were trea ted by lo ng di stance. T he re were 20 pa-
rapid rate of change in estrogen fo ll ow ing deli ve ry cre- tie nts enro ll ed in th e first ph ase of the stud y fo r a tota l
ates a n "estrogen w ithd rawa l state." Furthermo re, thi s of23 separate events of PPD .
is pe rce ived as a criti ca! fac tor in dr ivi ng ac ute pu er-
pe ral affecti ve psychos is a nd ea rl y-o nset pue rpera l T hese patie nts co ntac ted th e Pope Pa ul V I ln stitute
major depression . The use of estra di o l-1 7 ~ (E 2) as a beca use of th eir depress ive symptoms. These symp-
s ublin g u a l a ppli ca ti o n , o ra l a dmini st ra ti o n o r toms we re th en eva luated and docume nted to the ex-
tra nsde rmal admini stra tion, has been shown to have a te nt poss ible a nd proges terone thera py wa initi ated .
pos iti ve e ffect on PPD .4 1-4 3 However, its usage by breast- No part ic ul ar protoco l for treatment w ith progestero ne
fee ding wo me n has been questi oned. 42 was util ized. Rather, an ad hoc ad mini trat ion of proges-
tero ne was utilized to see what mi ght prove to be the
Bower and A ltschul e44 repo rted in 1956 that a "stri king most efficacious means of treating th i conditio n. These
be ne fit" could be achi eved thro ug h the use of proges- patients we re then fo ll owed on a dail y to a weekl y bas is
terone in wo men with PPD . In the ir trea tment progra m, un ti l their PPD eithe r reso lved itse lf o r needed furth er
they gave 100 mg of progesterone 1M every day fo r psychi atri c trea tme nt.
abo ut 1O days. lt was the n g ive n ora ll y in doses of 150
mg per da y. Fol lowing thi s, in 198 0, Da lto n45 advocated The pati e nts ra nged in age fro m 27 to 4 1 years w ith a
the use of progesterone fo r th e treatme nt of PPD . Mo re mean of32 .4. They had a mean g rav idity of 4 .5 (w ith a
recentl y, N onacs and Cohen comme nted upon proges- ra nge of 1 thro ug h 1O) and pari ty of3 .3 (w ith a ra nge of
te rone therapy fo r PPD 46 : 1 thro ugh 6) and previo us mi scarri ages of 1.4 (with a
" Severa! autho rs ha ve suggested that trea tment wi th ra nge ofO to 4). In 18 patients in which suc h info rmati on
progeste rone may be help fu l in the manage ment of was ava ilab le, 14 of th em had a prev io us hi story of PM S
postpartum maj o r depress io n. To date, no syste m- (77.8% ) and 12 of th e 18 had a prev io us hi story of PPD
ati ca lly-deri ved data suppo rt the use of progester- (66.7%). Sorne of these occurred also fo ll owing mi scar-
o ne in the treatm ent of puerpera l mood di stu rbance. riage. The mo t common symptoms elicited in thi s group
Fu1the rmo re, sorne ha ve demo nstra ted that proges- of patie nt we re depress io n, anx iety/pa ni c, uncontrol-
teron e may exacerbate sympto ms of de press io n in la bl e c ry in g, fa tig ue, in somni a, poor appetite, a sha ky
wo men with mood di so rder ." fee ling, a nd sui c ida! ideati o ns. In additi o n, othe r symp-
to ms that were conveyed to us inc luded helpl essness,
In 1988 , Dr. Katharin a Da lton vis ited the Pope Paul V I fee ling w ired , hav ing stra nge tho ught , hot flas hes,
lnstitute because ofth e autho r 's inte rest in PMS. Dur- nig ht sweats, a ra pid heartbeat, and na usea .
ing the course of that visit, she com me nted o n her lo ng
ex perie nce with the use of proges tero ne in the treat- T hese pati e nts we re the n treated w ith progesterone
ment of PPD. In additi o n, she seemed to think PPD was using di ffere nt programs oftreatment. Thi s was an open-
a very common problem. In our own clini ca l experi ence, ended stud y progra m beca use exact dosages we re not
thi s condition is rare- the inc idence of PPD at the Po pe known at thi s tim e, a nd the roots ofadmini stra ti o n that
Paul V l In stitute was o nl y 2. 1 percent. At the tim e, we wo uld be best were also not known. A few pati ents we re
summi zed that beca use proge terone suppo1t during a lso treated during pregnan cy w ith proges terone a long
pregnancy in our hi g h-ri sk pregna ncy po pu latio n was with being trea ted during the postpa rtum pe ri od . Intra-
commo n, it may ha ve had a n impac t on the overa ll inc i- muscul ar, ora l and/or vag in al progestero ne (bio-identi-
dence of PPD in o ur pati ent popul ation. ca l progestero ne) were ali used at va ri ous doses. Fro m
thi s, the bas ic effect ofp rogesterone could be observed
These di scuss io ns prompted a n inte rest in the use of and a program fo r improved management could be elic-
progeste rone suppo rt fo r the treatme nt of PPD . Studi es ited. In 20 ofthe 23 epi sodes (86.9%), either an exce llent
we re the n underta ke n to understand the ro le of proges- (73 .7% ) or very good ( 13.0% ) ou tcome was obtained
a nd three episodes had poor o utco mes ( 13 .0% ). 1n ea ch 22 to 43 years). Full-tem1 pregnancies averaged 2.77 (with
of the three cases in w hi ch the o utcome was poor, th e a ra nge of 1 to 9) and spo nta neo us abo rtions we re ob-
patients had prev io us severe epi sodes of PPP and/o r served in 46. 7 pe rcent of the pati e nts.
the use of progeste rone began severa! wee ks afte r the
beginning ofsympto ms. In cases where treatment was A hi to ry of PM S was identified in 63.3 percent of thi s
initiated early and aggress iveiy, !he sy mploms were po pul ati o n a nd a previo us hi sto ry o f PPD in 56.7 pe r-
a!Leviated with exceL/enl or very good results in al/ cent. In both case , thi s was somewhat lower th an in
cases (2 0 out o.f 20) . th e first ph ase of th e stud y. In thi s po pul a ti on , the
proges te rone dosage fo r the 30 pati e nts is identi fie d in
In stud y ing these cases, the re we re a numbe r of treat- Tabl e 30-5 . In fiv e pati ents, a s ing le intramuscu lar dose
ment fac to rs that could be identified. First ofa ll , th e use of 200 mg of progeste rone was th e onl y treatment
of progesterone fo r the trea tme nt of PPD and anx iety needed. In the oth er 25 patie nts, thi s was fo ll owed by
was often d rama ti c w hen used early in the sym ptom an add iti ona l fi ve doses of 100 mg g ive n every othe r
compl ex. Patie nts wo uld te ll us such things as , "Thi s is day. Thi s series was repeated in three additi o na l pa-
a miracle," " I a m fee ling g reat," " I feel considerabl y bet- ti ents and fo llowed with oral progesterone SR (sustained
te r," " I ca nnot be li eve how good 1fee l w ithin two ho urs release) 200 mg by mouth two time a day (PO BID) for
of the progesterone injecti o n," a nd "The differe nce is a va ri able Ie ngth of time. In two of these pati ents, a
betwee n day and ni g ht. " mo re lo ng term (a bo ut two mo nth s) tit rati on w ith eithe r
intra mu scul a r or o ral progeste rone was used (Tab le 30-
Secondl y, th ere was often a s ig nifi cant hi story o fprev i- 5). Progeste rone receptors are absent in the postpartum
o us PMS and e pi sodes of PPD that occurred in th is breast, so progesterone ca n be used during breast fe ed-
popul ati on leading us to think that if th ose could be ing w ith o ut a ny inte rrupti o n of milk suppl y.
identi fie d in ad va nce of pregnancy and treated appro-
priate ly, the a nti cipated diffic ul ties of PPD might be sig- The results of the progesterone therapy in the second
nifi cantl y reduced. ph ase of thi s stud y are sho wn in Ta ble 30-6. The im-
provement response was consid ered to be marked in 26
T he res ul ts wi th progesterone treatme nt were most d ra- of the 30 pati ents (86. 7%). Three of the 30 pati e nts
mat ic w ith the use of intra muscul ar progesterone. The ( 10.0%) had a moderate improve me nt w hil e on ly one
phys ic ian needed to be wi lling to ti trate the dose aga inst had no improve ment at a li (3.3 %).
the occ urre nce of a pati e nt's sympto ms. On man y occa-
s io ns, we had pati e nts te ll us that the symptoms di sa p- An a nalys is of th e symptom compl ex both before and
peared w ithin minutes o r ho urs fo ll ow ing th e inj ectio n afte r treatment was conducted for a li 30 patients (Table
of progesterone. In sorne cases, ora l o r vagina l proges- 30-7). The most commo n symptoms we re depress ion ,
tero ne also had a ro le to pl ay, but in those cases, it was fat ig ue, cry ing, anx iety, helpl essness, stra nge tho ughts,
mostl y as a suppl e me nt to the intra muscul ar progester- poor appetite, and ni ght sweats. Treatrnent with proges-
o ne. As a result of thi s first ph ase progeste ron e sup- te rone provided a stati sti ca ll y s ignifi cant impro ve ment
po rt eva luatio n, a PPD clinica l wo rksheet was devel- in de pressio n, fati g ue, cry ing, anx iety, he lpl essness,
o ped (F ig ure 30-1 ) and a prospective progra m fo r eva lu- stra nge th oughts, poor appetite, ni ght sweats, and a
atio n a nd treatm ent was impl e me nted to beg in a Phase shaky fee ling ( Fi g ures 30-2 a nd 30-3). ln a li othe r cat-
11 proges te rone suppo rt eva luati o n program .
Table 30-5 : Progesterone D osage Patie nts

Phase 11 Progesterone Support Study=J with Postpartum D epression
Phase U Study ( =30)
In the second phase ofthi s study, 30 patie nts w ith PPD
Dose n %
we re enrolled in a simila r fas hi o n as in the first ph ase
200 mg IM on ly 5 16.7
stud y. However, in each ofth ese cases, the c linica l data
200 mg IM then 25 83.4
on the wo rksheet fo r PPD ( Fi g ure 30-1 ) were pros pec- 100 mg QOD x 5 additional
tive ly acc umul ated by the nurses w ho were interacting doses
w ith these pati e nts. A li st ofsymptoms was obta ined in Repeat series ................ 3
a n o bj ecti ve fas hi o n pri o r to and afte r treatme nt. In ad- Titration with ora l dosing . .4
Titration with long-term
diti on, the exact treatment dosage and dates could be IM or oral dosing ............ 2
ide ntified. In thi s gro up of pat ie nts, the average age
was s imil ar to the first phase, 32 . 1 yea rs (w ith a ra nge of
Chapter 30 : Postpartum Depression : Evaluation and Treatment 375
fied in Table 30-8. In thi s group of53 episodes of PPD in

Table 30-6: Results of Progestero ne Therapy 50 patients, marked improvement was identified in 43 of
Second Phase of Study (N=30) the 53 episodes (8 1.1%) and moderate improvement was
o bserved in another 6 epi sodes ( 1 1.3 % ). This resulted
lmprovement Response n %
in a marked or moderate improve ment in 92.4 percent of
Marked 26 86.7 the e pi sodes treated. Treatment resulted in no improve-
Moderate 3 10.0 ment in o nl y 4 ofthe 53 epi sode (7.5% ). This gro up
96 .7
decreased in the seco nd phase of the cycle to on ly 3.3
No improvement 3.3
percent.
While this is an o pen-ended stud y w ithout a control

population , previous studi es cond ucted w ith placebo
contro l groups have fo und that 65 to 74 percent of pa-
egories, an improvement was identified , but the num- tients remain depressed over a fo ur-mo nth period of
bers were too sma ll to ide ntify stati sti ca l s ignifi cance. time when g ive n placebo .46 C learly, there is room for
However, it shou ld be noted that, in the two pati ents mo re stud y to be done in thi s a rea and studi es to be
who had suicida! thoughts, the symptom di sappeared designed in such a fas hion as to take into a consider-
afte r progesterone therapy. ation , a randomized , do ubl e-blind approac h. However,
w hen results are thi s dra matic, they cannot be ig nored.
In this same group of patients, the mean number of symp-
to ms both before and after progestero ne therapy was In the current literatu re, progesterone therapy, is fo r the
also eva luated. The average number of sym ptoms pri or most part, not mentioned . The first line of therapy is
to therapy was 7 .57 and fo ll ow ing therapy w ith proges- often cons ide red to be psychotherapy fo ll owed by a n-
terone treatment it decreased to 2. 1 (p< .001 c hi-sq uare tidepressa nt agents. Everyo ne ag rees, however, th at the
analysi s) (Figure 30-4). prompt recognition and efficac ious treatment of pue r-
pera l mood di sorders are essenti al in order to avo id ad-
Beca use the treatment in both the Phase 1 and Phase l 1 verse outcomes for both mother a nd infa nt. 46
populations ofthis stud y were very s imil ar, cum ul ative
resu lts of both phases were comb in ed and are identi- Because the resu lts presented in th is chapte r on the
Table 30-7: lncidence of Sympto ms B efore and After Progesterone Therapy

P ostpartum D epressio n Phase U Study (N=30)
BeforeRx AfterRx Statlstically

Symptom n % n % p-val ue' Slgnlficant?
Depression 26 86 .7 7 23.3 <.0001 Yes

Fatigue 23 76.7 8 26.7 .0001 Yes
Cryi ng 22 73 .3 7 23.3 .0001 Yes
Anxiety 20 66 .7 5 16.7 <.0001 Yes
Helplessness 19 63 .3 2 6.7 <.0001 Yes
Strange thoughts 14 46 .7 5 16.7 .0125 Ye s
Poor appetite 13 43.3 3 10.0 .0035 Ye s
Night sweats 12 40 .0 4 13.3 .0195 Yes
ln som nia 11 36.7 5 16.7 .0798 No
Shaky 10 33.3 3 10.0 .0283 Yes
Panic attacks 9 30.0 4 13.3 .1172 No
Feelwired 7 23.3 2 6.7 .0706 No
Hot flashes 7 23.3 4 13.3 .3169 No
Nausea 7 23.3 4 13.3 .3169 No
Rapid heartbeat 4 13.3 3.3 .1611 No
Suicida! thoughts 2 6.7 o O.O .1503 No
1. Chi-square a nalysis
376 Th e Medica! and Surgical Practice of NaProTECHNOLOGY
POST PARTUM DEPRESSION

CLINICAL WORKSHEET
Patient's Name: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Tele.#: _ _ _ _ _ _ _ _ __
City/State: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Date: _ _ _ _ _ _ _ _ __
Date of Baby's Birth: _ _ _ _ _ _ _ _ _ _ _ Previous History PMS: Y N
Previous History Post Partum Depression: Y N
# of Pregnancies _ _ : Full Term __ , Miscarriages __ , Preterm Birth _ _, lnduced Abortion __ .
BEFO RE AFTER TREATMENT

SYMPTOM TREATMENT EXACT TREATMENT
LIST Y/N Y/N Y/N Y/N DOSAGES ANO DATES
DATE
Depression
Anxiety
Panic Attacks
Fatigue
lnsomnia
Poor Appetite
Helplessness
Feel Wired
Shaky
Crying
Hot Flashes
Night Sweats
Rapid Heartbeat
Nausea
Strange Thoughts
Suicida!
Other
Date Symp. Began
ppdwo rk .pmS Prepared by

Pope Paul VI lnstitute for the Study of Human Reproduction
Figure 30-2: Postpartum Depression Clinical Worksheet of the Pope Paul VI lnstitute.
Chapter 30: Postpartum Depression: Evaluation and Treatment 377
Symptoms Before and After Progesterone Therapy

Patients with Postpartum Depression (N=30)
86 .7
- Before progesterone
C=:J After progesterone
e
Ql
u 50
Q;
a.
o
Symptoms: Depression Fatigue Crying Anxiety Helplessness Strange Poor Night sweats
thoughts appetite
Chi-square analysis 1<.0001 I
Figure 30-3: Symptoms before and after progesterone therapy in patients with PPD (N=30) (From : Pope Paul VI lnstitute
re sea rch , 2004).
Symptoms Before and After Progesterone Therapy

Patients with Postpartum Depression (N=30)
- Before progesterone
c=J After progesterone
e
Ql
u
Q;
a.
Symptoms: lnsomnia Shaky Panic Feel wired Hot flashes Nausea Rapid Su icida !
attacks heartbeat thoughts
Chi-square analysis NS NS NS NS NS NS NS
Figure 30-4: Addition al symptoms before and after progesterone therapy in patients with PPD (N=30) (From : Pope Paul VI lnstitute
research , 2004).
Mean Number of Symptoms Progesterone for Depression _ _ _~

Before and After Progesterone Therapy
Postpartum Depression (N=30)
7 .57 One case history that was treated at the Pope Pau l V I
lnstitute because of our interest in P MS and PPD is
E! worth reporting. This 50-yea r-old woman had hada to-
.9
0- tal abdomin a l hysterecto my and bil atera l sa lpin go-
t
(/)
o
oophorectomy fo ur yea rs earli er. She had also suffered
.1l from both PMS and PPD in the past. Her husband ca lled
E
z" us to see whether we had treated depression w ith
progesterone. Thi postmenopausa l woman was about
2.1
to be released from psychiatric hospitali zation and was
on multiple psychotropic medi cations but still not fee l-
in g we ll . We informed him that we had never treated
Before Progesterone After Progesterone such a conditi on with progesterone before but we wo uld
be willing to try, see ing no harm in adding progestero ne
Fi gure 30-5 : The mean number of symptoms befa re and
to her regimen.
after progesterone therapy in patients with postpartum
depression (N=30). (From : Pope Paul VI lnstitute research ,
2004 .) A fter receiving progesterone, she bega n to fee l better.
However, when the progesterone was discontinued , she
would get immediately wo rse aga in . Only intramuscu lar
use of intram uscul ar progesterone are so dramatic, it (IM) progesterone worked. While multiple attempts were
demands greater study. A new format has been devel- made to discontinue her supplementa l 1M progester-
oped upon whi ch data can be co ll ected prospecti vely one wi th out succe s, s he has bee n 18 co nsecutive
and in a sta ndardized fas hi on with the use of a more months on l M progesterone, is fee lin g ve ry good, and
spec ifí c protoco l (Tab le 30-9). is off her antidepressants. To date, she has to lerated
the inj ection s of progesterone ve ry we ll and i moti-
Dalton a lso used progesterone, but her program used vated to continue th em beca use of how we ll she fee ls.
progesterone vaginal suppositories . She reported a si g- Ali ofher fam ily members and clinical observation , ha ve
nifícant difference in the recurrence rate in those who documented her improve ment.
were treated with PPD wi th progesterone versu tho e
who were left untreated (Tab le 30- 1O). While IM progesterone i not be ing advoca ted here for
the primary treatment of depression (unrelated to chi ld-
birth), this case report uch sign ifícant improvement
th at furt her research in this area needs to be done.
Tabl e 30-8: Cumulative R esults of Both First and Second Phase of Study
Postpartum O epress ion - Pope Paul V1 lnstitute (N=SJ )
First Phase Second Phase Totals

lmprovement response n % n % n %
Marked 17 73.9 26 86.7 43 81 .1

Moderate 3 13.0 3 10.0 6 11 .3
~ ~ ~
No improvement 3 13.0 3. 3 4 7.5
Totals 23 99.9 30 100.0 53 99 .9
Chapter 30 : Postpartum Depression : Evaluation and Treatment 379
Table 30-9: Treatment Protocol Postpartum

Depression -Pope Paul V1 lnstitute
When symptoms start, give 200 mg progesterone in

sesame oil IM and have palien! call in 24 hours.
lf marked improvement, no need to treat further, but

do follow.
lf symptoms are improved , but have recurred or are

still somewhat present:
c. 100 mg progesterone IM QOD x 5 days.
c. lf markedly improved, no need to treat further,

but have patient call if symptoms return .
c. lf symptoms recur or are persistent, then
repeat progesterone 100 mg IM QOD x 5
doses.
c. lf continues to improve but symptoms persist ,
repeat the above series and add 200 mg SR
progesterone PO BID x 1O days for 2 months.
In about 1 in 20 cases, IM progesterone may be

necessary for up to two months.
Table 30-10: R ecurrence of Postpartum Depression Treated with Progesterone 1•2
Pro esterone
I.w.!fil1 Recurrence Untreated fül!<!J[í!ltl!<!l
Severity N N % N N % p-Value
Mild 35 2 5.7 112 63 56.2 <.001

Moderate 18 3 16.7 64 50 78 .1 <.001
Severe 41 4 9.8 45 38 84.4 <.001
Total 94 9
~ 221 151 ! ss.3 1 <.001
1 . 100 mg progesterone IM QD, first 7 days after delivery, followed by progesterone suppositories 400 mg BID x 2 months or until
mensesstart
2 . Dallan K: Progesterone Prophylax1s Used Successfully in Postnatal Depress1on. The Practitioner. 229: 507-508, 1985.
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sures. J Clin Psyc hiatry 63 [Suppl 7] :31-44, 2002. ti on, 1994 .
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[Suppl 15] :26-32, 1997. Period . J Clin Psyc hiatry 59:9-33, 1998.
3. Leopo ld KA , Zoschnick LB: Postpartum Depression. The 7. Wolkind S, Zajicek E, Ghodsian J: Continuities in Maternal
Fem a le Pat ient 22:40-49, 1997. Depress ion. lnt J Fam Psychol 1:167-181 , 1988 .
4 . Marcu s S, Flynn HA, Barry KL, Tandon R, Greden JF: De- 8 . Cox JL. Holden JM , Sagovsky R: Detection oí Postnatal
pression in Pregnancy and Postpartum : A Review oí Criti- Depressio n. Br J Psyc hiatry 150: 782-786, 1987.
ca! lss ues. Postgrad Obstet Gynecol 20: 1-6, 2000.
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434, 1997.
1O. Brocki ngto n IF, Cernik KF, Schofie ld E ~- et al: Puerperal
Psychosis: Phenomena and Diagnosis. Arch Gen P ychia- 29. Josefsson A, Angels ioo L, Berg G, et al: Obstetric, Somatic,
try 38:829-833 , 198 1. and Dem ographi c Ri sk Factors fo r Pos tpartum Depress ive
Sy mptoms. Obste! Gynecol 99:223-228, 2002.
1 1. McGorry P, Co nn e ll S: The Noso logy and Prog nosis of
Puerperal Psychosis: A Review. Compr Psychiatry 31 :519- 30. Parry BL, ewton RP: Chrono-Bio logical Basis of Female-
534, 1990. Speci fic Mood Disorders. curopsychop h armacology.
25:S 102-S 108 , 200 l.
12 . Kn op ps G: Postpartum Mood Disorders: A Sta rtlin g Con-
tra st to the Joy o f Birth. Postgrad Med 93: 103-116, 1993. 3 1. Bloch M, Schmidt PJ , Danaceau M, et al: Effects o f Gonadol
Steroids in Wome n with a H isto ry of Postpanum Dcpre s-
13. Schoepf J, Ru st B: Followup and Family Study of Postpar-
sion. Am J Psyc hi atry 157:924-930, 2000.
tum Ps ychosis , 1: Overview. Eur Arch Psyc hi atry Clin
Neurosci 244: 10 1-111, 1994. 32. Harris B, Lovett S, ewco mbe RG, et al: Maternity Blues
and Majar Endoc rin e Changes: ardiff Puerpera l Mood and
14 . BenVenuite P, Cabras PL, Cervi P, et al: Puerperal Psycho-
Hormone Stu dy 11 BMJ. 308:949-953, 1994.
s is: A Clinical Case Study wi th Followup. J Affcct Disord
26:25-30, 1992. 33. Hend rick V, Altshuler LL, Suri R: Hormonal Changes in the
Postpartum a nd lmplicati ons fo r Post part um De pressio n .
15. Videbech P, Gouliaev G : First Admission with Puerperal
Psychosomatics 39:93 -1 O1, 1998.
Psychosis: 7- 14 Years of Followup. Acta Psyc hi atr Sca nd
9 1:1 67 -1 73, 1995. 34. Nappi RE, Petragl ia F, Luisi S, et al: Serum Allopregnanolone
Levels in Women wi th Postpartum '"B lues'". Obstet Gynecol
16 . Georgiopoulo AM, Bryan TL, Yawn BP. et al: Popu lat ion-
97:77-80, 200 1.
Based Screeni ng for Postpartum Dcpression. Obstct Gynecol
93:653 -657. 1999. 3 5. Wisner KL, Stowe ZN: Psychobio logy of Postpartum Mood
Disorders. Semin Reprod Endocrino! 15:77-89, 1997.
1 7. Stowe Z , emeroff CB: Women at Risk for Postpartum-
Onset Majar Depression. Am J Obstet Gynecol 173 (2):639- 36. Magiakou M-A , Mastorakos G, Rabin D, et a l: Hypo th a-
645 , 1995. lamic Corticotropin- Rc leas in g Ho rm one Suppression Dur-
ing th e Postpa rtum Period: lmpli ca ti o ns for the lncrease
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and Psyc hiatri c M anifes tat io ns a t thi s Time . J C lin
Ri sk Factors and Predictive Signs of Postpa rtum Depres-
End oc rino ! Metab 8 1: 1912-191 7, 1996 .
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3 7. Susman J L: Postpartum Depressive Disorders. J Fam Pract
19. Posner NA, Unterm an RR, Williams K . et a l: Screening
43 [6 Suppl]: S 17- 24. 1996.
for Postpartum Depression. An Anti-Partum Questionnaire.
J Reprod Med 42 (4) :207-215, 1997. 38. Buist A: Treating Mental lllne ss in Lactating Women.
Medscape Wo me n' s Hea lth eJo urnal. 6 (2) , 200 1.
20. St uart S, Co user G, Schilder K, et al: Postpartum Anxiety
a nd Dep ress ion: Onset a nd Co mo rbidity in a Co mmunit y 3 9. Practice Guideline for Maj ar Deprcss ive Di sorder in Adu lts.
Samp le. J Nerv Ment Di s 186:420-424, 1998 . Am J Psych iatry 150 (Suppl): 1, 1993.
2 1. Watson J P, El li ot t SA , Rugg AJ , Brough DI: Psychiatric 40. Harris B, Oretti R, Lazarus J: Randomized Tria! of Thyrox-
Disordcr in Pregnancy in the First Postnatal Year. Br J ine to Preve nt Postnatal Depression in Thyroid-Antibody-
Psychiatry 144:4 53-463 , 1984. Positive Women. Br J Psychiatry 180:327 -330. 2002.
22. Rouil lon F, Thalassinos M, Mil lcr HD, Lem pericre T: Folatcs 4 1. S ich e l DA , Co hen LS, Ro be rtson LM , et al: Prop hy la ctic
and Postpartum Depression. J Affect Dis 25:235-242, 1992. Estrogen in Rec urren! Postpartum Affective Di sorder. Biol
Psychiatry 38:8 14- 8 18, 1995.
23. Ho lcomb WL , Stone LS, Lustman PJ , Gavard JA, Mostello
DJ: Screening fo r Depression in Pregnancy: Characteristics 42. Gregorie AJP. Kumar R, Everitt B, et al: Transdennal Oestro-
of the Beck Depression ln ve ntory. Obstet Gynecol 88: 102 1- gcn fo r Treatment of evc re Post nata l Depress io n. Lancet
10 25, 1996. 347:930 -933, 1996.
24. Josefsson A, Bcrg G, Nord in C, Sydsjo G: Prevalencc of 43. A hokas A, Kaukoranta J, Wahlbec k K, Aito M: Estrogen
Depressivc Symp toms in Late Pregnancy and Postpartum. Deficiency in Severe Post partum De press ion : Successful
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Pre limin ary Stud y. J C lin Psychi atry 62:332-336 , 200 1.
25. Fergerson SS, Jamieson DJ, Lind ay M: Diagnosing Post-
partum Depression: Ca n We Do Better? Am J Obstet 44. Bower WH, Altschule MD: Use of Proges terone in th e
Gy neco l 186:899 -902, 2002. Treatment of Pos t-Partum Psychos is. N Eng J Med 254: 15 7-
160 , 1956.
26. Ebe rhard-Gran M , Es kild A, Tambs K, et al: Review of
Validation Studies of th c Ed inburgh Postnatal Depression 45. Dalton K: Depression After Childbirth. Oxford Universi ty
Sea le. Ac ta Psyc hi at r Scand 104:243-249, 2001. Press. Oxford , 1980.
2 7. Bernazznai O, Sauc ier JF, David H, Borgeat F: Psychosocia l 46. onacs R, Cohen LS: Postpartu m Mood Di sorders: Diag-
Predictors of Depressive Symptoma to logy Leve! in Post- nosis and Treatment Guidelines. J C lin Psychiatry. 59 [ uppl
partum Women. J Affec t Disord 46:39-49 , 1997. 2]:34 -4 0, 1998.
Ovarian Cysts:
ignificant numbers ofsurgical procedures continue th at are fun ctional or physiologic in their pathophysiol-
S to be performed on reproducti ve age women for ova-
rian cysts. 1-4 ln sorne cases, thi s is du e to adnexal tor-
ogy. Thus, persistentfo llicular cysts or persistent luteal
cysts (luteinized unruptured follicles) are most common ly
sion ;5however, many times that is not the case. ln addi - identified.
tion, oral contracepti ves ha ve been promoted as a form
of treatment, but studies ha ve shown oral contracep- There are other ca uses of ovarian cysts than simp ly
tives ha ve littl e orno effect on the re oluti on of ovarian tho e that are of the functional variety. For example,
cysts. 6 ova ri an teratomas (derm oid cysts) can be seen along
with mu cinous and serous cystadenomas. A variety of
Whi le advances have been made in th e diagnosis of ovarian mali gnant neopl as m wil l also present them-
important ovarian cysts with the use of ultrasound ,7 the se lves asan ova rian cyst on pelvic examination or by
methodology for studying the ovari an cysts has had a ultraso und . Thus, ca reful fo ll ow-up and ongo ing as-
defect. lnadequate evaluation of ova ri an cysts contin- sessment is important.
ues to inhibir understanding of th e etiology. Most stud-
ies using ultrasound parameters are studying th e ova- The majority of ovarian cysts een in the reproducti ve
rian cysts when they are ca using probl ems rather than age group, however, are benign functional cysts. While
tracking them from their ori gi n. With the ex perience ac- many women with ovari an cysts are treated with oral
cumu lated at the Pope Paul VI ln stitute in seria l ultra- contraceptives to suppress the fun ction of the ovarian
sound eva luation of ovulation, progress has been made cyst, many still reso rt to surgica l treatment. However,
in the development of a better understanding of the most ofthese cystic abnormalities probabl y result from
etiology of functional ovarian cysts (see Chapters 20 an underlying hormonal dysfuncti on. By understand-
through 22). ing the basic principi e in vo lved in the eti ology ofthese
fun cti onal cysts and impo11ant approaches to treatment,
The CREIGHTON MODEL FenilityCare™ System often one can reduce the need for surgica l intervention. Al-
enables the identificati on of various types of ovarian most uni versa lly, women with functional cysts will not
cysts. The ovarian cysts that are iden tifí ed are those requ1re surgery.
381
Persistent Follicular Cysts - - - - - - - . giv in g her difficulty and problem s. She was given an
injection of200 mg of IM progesterone and, on day 5 of
With a persistent follicular ovarian cyst, the CrMS will her next menstrual period, she had another ultrasound.
revea! a prolonged Peak-type mucus discharge and a In this examination, the area w here the cysti c structure
delayed Peak Day (Figure 31-1 ). Persistent follicular was previously located shows that the cyst has di sap-
cysts can often be associated with chronic pelvic pain , peared (Figure 31-3) (Table 31-1 ).
which is usually unilateral but may also be bilateral. The
chronic pelvic pain is usually not so significant as to
requ1re surgery.
Follicu lar cysts ha ve, as one oftheir hallmarks, the domi-

nant and prolonged production of estrogen that is un-
opposed by progesterone. This is the reason for the
prolonged Peak-type mucus discharge and the delayed
Peak Day as evidenced in the CrMS chart. By disrupt-
ing the estrogen dominance, a subsequent menstrual
period will occur three to five days following the proges-
terone injection. Once menses occurs, the follicu lar cyst
usually disappears. Use of progesterone is associated
with a marked reduction in pain caused by the ovarian
Figure 31-2: This ultrasound , done on the day of the physi-
cyst. The cyst usually disappears shortly following the cian examination in Figure 31-1 , reveals a cystic structure in
progesterone injection. the right ovary (left) in the presence of an endometrium , which
appears sonographically as proliferative (right) (From: Pope
Paul VI lnstitute Reproductive Ultrasound Center).
The case presented in Figure 31-1 was an 18-year-old
girl who had had two surgica l procedures for recurrent
ovarian cysts. She had been placed on oral contracep-
tives for two years and was brought to the In stitute
because she no longer wanted to be on oral contracep-
tives for this treatment. The chart in Figure 31 -1 shows
her first 39 days of charting. At the time ofthe first visit,
she was already having pelvic pain and, on pelvic ex-
amination, she seemed to have an ovarian cyst. She
was sent for a pelvic ultraso und examination and the
cystic structure shown in Figure 31-2 was identifíed. An
evaluation of her endometrium by ultrasound revealed Figu re 31-3 : The same palien! as in Figure 31-2 , however,
this is on day 5 of her next menstrual period after having
that it was in the proliferative phase. Thus, by ultra- received 200 mg of progesterone IM . The area where the
sound defínition , she had a fol li cu lar cyst, wh ich was cystic structure was present in her right ovary is now gone
(left) (From : Pope Paul VI lnstitute Reproductive Ultrasound
Center) .
1 2 3 4 5 6 7 8 9 IO u 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
,_
VL VL L
1
1
M H H L L VL
~ ~-~
....
OAO OAO
.. ...~
OAO 4xa IOOL <oc L
~
,,,..,
~~~ ~~
..
<oc 8C.
xi ... ... xi
f ~ f f ~,, ~ ~... ~ ~ f ..~ ~
8C. 10;,;. 8Ck se
xi ...
se. ¡¡,c. ¡¡,c.
xa
se se
AO
c.,c 8<1< IOC.
AD xi
se
xi
<o"I< ie
x 1
...
xi
B B B B B B
¡¡,PC <oPC ¡¡,pe C.PC C.PC <oPC
~se ~ ~ ~ Persistent Follicular Cyst

IOC <oc g~
(Ovarian)
x 1 x 1 AO
"' t ...
1
Physician
- - examination
Figure 31-1: This CrMS chart from an 18-year-old woman shows a prolonged mucus cycle with variable return of Peak-type
mucus (VR PM ). On the day of the physician examination , she has pain. Ultrasound examination confirmed the presence of a
persisten! follicular cyst (From : Pope Paul VI lnstitute research , 2004).
Chapter 31: Ovarían Cysts : Evaluation and Treatment 383
ofthe Peak Day (whi ch is quite rare), interpretating thi s

Table 31-1: Treatment of chart as one that reflects a persistent lutea l cyst is accu-
Functional Ovarian Cysts rate in the majority of cases. A pe lvic ultrasound exami -
nat ion on Peak + 16 or 17 or a pelvic examination at that
time ca n provide fu 1ther documentation .
Progesterone by injection :
• Disrupts estrogen dominance in follicular In Figure 3 1-4, the patient underwent ultrasound exami-
cysts nations to study her ovu lation sequence. The ultraso und
• Assists in dissolution of luteal cysts examination on Peak + 17 is shown in Figure 3 1-5. In this
• Both are gene by day 5 of next cycle case, the cyst is en larged, and it has debri s within its
• Significan! pain reduction when progester- fluid. lt was documented asan unruptured fo llicle be-
one is adminstered cause ofthe serial ultrasound exami nations. At the same
• Must follow up patient on day 5 of next time, the endometrium is clearly secretory (a hyperechoic
cycle to make sure cyst is gene (pelvic
exam or ultrasound .
center oval is present in Figure 31-5).
The etiology of the unruptured fo lli cle is not entirely

known , but it is related to a dysfunctiona l hormona l
pattern. For example, both the fo lli cu lar phase estradiol-
Persistent Luteal Cysts _ _ _ _ _ _~ 1 7 ~ leve! and the postovulatory progesterone levels
are suboptimal in this patient population (see Chapter
A persistent luteal cyst is also referred to as a luteini zed 21 ).
unruptured fo lli cle (LUF syndrome). In this situation,
the fo ll icle grows and deve lops to the time ofovu lation, The natura l course of events with an unruptured fo lli cle
but ovu lation does not occur. Thus, the follicle remains is for that cyst to resol ve once menstruation begins.
unruptured and a cyst forms and increases in size dur- Thu s, these cysts are almost universal/y gane by th e
ing the remaining porti an ofthe cycle. Yarying degrees
ofintemal debri s will form within the fo lli cle sugge ting
sorne amount of hemorrhage within that cyst. These are
also observed as hemorrhagic lutea l cysts.
Because this cystic st ru cture becomes luteinized ,

progesterone is produ ced by the cyst and a Peak Day is
observed. However, the amount ofprogesterone being
produced is genera lly suboptima l, and this apparent ly
has a ro le to play in its recurrent nature.
Figure 31-5: This ultrasound examination (performed on Peak
+17) is from the same patient as in Figure 31 -4 . A large cystic
lfthe patient is charting her cyc les using the CrMS, the structure is seen in her left ovary and is consisten\ w ith
post-Peak phase ofthe cycle may be prolonged to 16 or findings of her serial ultrasound examination during the course
more days in durati on. Thi s prolonged post-Peak phase of that cycle. The cystic structure now has debris within it
is suspi cio us for the presence of an unruptured follicle (mild hemorrhage) (left) and the endometrium is secretory
(the hyperechoic halo in the center of the uterus on the right)
(persistent lutea l cyst) (Figure 3 1-4). In the absence of (From : Pope Paul VI lnstitute Reproductive Ultrasound Cen-
pregnancy and in th e absence of th e mi sidentification ter).
6 7 9 10 lJ 12 13 14 15 16 17 18 33 34 35
Prolonged
post-Peak
H H M M M L B IOVL 0-.0 CA.O IOSL JOSL
)( 1 J(,f
AO OAD tóCi< 411 1 411C 1
)( /
phase
...
X1
I I lAP I % 17 days
Persistent Luteal Cyst

(Luteinized Unruptured Follicle - LUF)
Figure 31-4: In this cycle, a 17-day post-Peak phase was observed and a persisten! luteal cyst was documented by serial
ultrasound examination (luteinized unruptured follic\e , LUF) (From : Pope Paul VI lnstitute research , 2004).
fifth day after the beg inning ofthe ne xt period. A fol- unruptured follicle (ora persistent luteal cyst), a nor-
low-up pelvic examination or ultrasou nd examination ma/-/ength post-Peak phase does no/ indicate that the
on day 5 ofthe next cycle is indicated to doc ument it woman has actually ovu lated or that an LUF has not
disappearance . occurred. Most LUFs occ ur in cycles where the post-
Peak phase is normal in length. However, those cystic
A with follicu lar cysts , physicians commonly treat structures that become medical ly problematic w ill most
unruptured follicles with oral contraceptives. However, often revea] themselves with a prolonged post-Peak
oral contraceptives uppresses the hypothalami c-pitu - phase.
itary axis and may be detrimental to the already dys-
functional hormone pattern. This is unnecessary if one An example ofthis is shown in Figure 31-6. In this pa-
understands these functional cysts a nd further under- tient, three full cycles and the beginning of th e fourt h
stands the CrMS . cyc le are charted . ln the third cyc le, the patient had a
erial follicu lar ultrasound assessment. A fo llicl e was
In the cases where a woman experiences pain in asso- identified , and it continued to grow and never ruptured.
ciation with these cysts, intramuscular progesterone can By Peak + 3, it was debris-filled (F igure 3 1-7) . On day 5
be valuab le. The progesterone is given in a dosage of of her next menstrual cyc le, she had a diagnostic lap-
either 100 mg or 200 mg and must be given by intramu - aroscopy and an ovarian cyst, which that started as a
cu lar injection . Oral progesterone and vaginal progest- LUF, was observed (Figure 3 1-8).
erone are not helpful for the ac ute case. HCG is also
contraindicated in this case because it stimulates the
unruptured follicle and makes the pain worse . As with Ovarian Cyst Assessment _____~
the persistent follicular cysts, pain associated with lutea l
cyst is significantly dimini shed once the progesterone In 45 patients who were evaluated for what appeared to
is initiated. Pain reliefcan be expected w ithin an hour. be an ovarian cyst on ultrasound exami nation (Table
3 1-2), ali were treated with progesterone lM. Ln 38 of
While a prolonged post-Peak phase is indicative of an these, the cystic structure disappeared by day 5 of th e
6 7 20 21 22 23
L 8 B 8 0AO ()AD 'PC. • I ~•l. Me O"ID i.IAO '-41>0 (.C. • I <.(M> i.1.-.0 K>Yi,.¿_ '{A¡}
OAO Ol'D 0""0 :b/• I Z. W• I •I
I :r
O~D
L. 14 H L t1 e, 8 8 OACI l. ~ lf•Z.. (.oft::. IOY&o fo(. IOIC f,,f'C. fof'C.. 0 -' 0 OAO DAD O.-..t) O A¡) OAD OAD CAD 0.-.0 o-.tl
º"º b B CUID Ol'O •I ,.¡ •\ •I •\ .a. O ,.3
Ultrasound of Ríght
Ovarían Cyst 1.1'1' ;i .(>t' ). fo\
LO'f
'"""'-"'e,,,.,~
A. >Q. ~.~ l.Ol "?. .10
~c.,...v-i
5.1
"'·'°"' LUF
1•.t 10.7 . .. Progesterone (ng/ml)
Sum = 45.7, mean = 9.4
Laparoscopíc ldentification
- t - - + - - 10- of Ovarían Cyst (Right)
Figure 31 -6: In this example, a woman with normal post-Peak phases had serial ultrasound examinations in the third cycle. Th e
right ovarian follicle continued to grow and became debris filled by Peak +3. A diagnosis of an unruptured follicle was made . In
this same cycle , her progesterone profile is shown . The profile is suboptimal with a sum of 5 levels of 45 .2 ng/ml and a mean
of 9.1 ng/ml. Laparoscopic examination on day 5 of her next cycle revealed the presen ce of that ovarian cyst (see Figures 31-
7 and 31-8) (From : Pope Paul VI lnstitute research , 2004).
Chapter 31: Ovarian Cysts : Evaluation and Treatment 385
Figure 31-7: In this examinati on, th e sag ittal and tran sverse Figure 31-8: Thi s is a laparoscopic photograph of the same
planes of th e right ovarian cyst which now has a mean diam- patient in Figures 31-6 and 31-7 from the laparoscopic exami-
eter of 4.69 cm is sh own (on day 18, patients in the th ird nation on day 5 of her next cycle. Th e right ovarian cyst is
cycle of Figure 31-6). lt is significa ntly debris filled and con- seen in this photograph .
sisten! with a hemorrhagic co rpus luteum , which is th e result
of an unruptured follicle (From: Pope Paul VI lnstitute Repro-
ducti ve Ultrasound Center).
Any surgica l procedure on th e ovary carri es the poten-

Table 31-2: ldentification of O va rian Cysts tial for adhes ion fo rmati on (especiall y if done within the
by Symptoms, CrMS and U ltraso und
context of standard gyneco logic surgica l param eters).
(N= 45)
In th ese women, many of whom are youn g in age and
pri or to considerin g child bearing, it is crucial that their
fertili ty be preserved and not injured. Thus, surgica l
Cysts treated wi th progesterone 38
and disappeared NaProTECHNOLOGY techniques should always be used
in th ese pati ents.
Cysts treated wi th progesterone 7
and did not disappear
lf cysts do not di sappear by day 5 of the menstru al
Serous cystadenoma =3
Large peritubal cysts =2 cycle with the above approaches to treatment, then these
Mucinous cystadenoma =1 cysts need to be ca refull y monitored. Understanding
Muci nous tumor of borderline =1 th ese principi es ass i ts in th e early recogniti on of sus-
malignancy
picious ovari an cysts th at may ha ve a mali gnant poten-
tial.
Recurrent Ovarian Cysts ---------,

next menstrual peri od. In 7 patients, the cystic structure
remain ed. Fo ll ow- up on these 7 pati ents showed that 3 Th e dysfu nct ional horm one patterns that have been
has serous cystadenomas, 2 had very large (greater th an presented here and in Chapter 2 1 tend to be repetiti ve.
5 cm) peritubal cysts, 1 had a mucinous cystadenoma, Functi onal cysts tend to be recurrent. Beca use they are
and 1 had a mucinous tum or of borderl ine ma li gnancy. recurrent, a fo rm of treatment des igned to help sup-
Thus, the use of progesterone as a treatm ent for fu nc- press ovarian fun ction (oral contraceptives) has been
ti onal ovari an cysts has proved to be helpfu l in reso lv- promoted. However, if the woman is taught how to chart
ing the cysti c structure with out surgery and in identi fy- her cyc les us ing the CrMS , has a hormone eva luati on
ing those cases in whi ch fu rther in vestigation is neces- during the post-Peak phase of her cyc le, and receives
sary. So rne pati ents do still need surgica l interve nti on. subseq uent post- Pea k progestero ne therapy on a long-
However, CrMS cha1t ing and th e use oflM progester- term bas is, these rec urrent ovari an cysts can be con-
one clarifí es those cases that require furt her in vesti ga- troll ed. Experience suggests that improved ova ri an func-
tion. Experi ence suggests that thi s is a better treatment ti on resu lts.
than th e use of suppress ive ora l contracepti ve therapy.
In treating pati ents with rec urrent ovarian cysts, the
use ofIM progesterone may be necessary for the initial times a day (BID) from Peak + 3 through P+ 12 is usually
or acute situation where pain is invo lved. However, on satisfactory. The use ofvaginal progesterone is usually
a long-term basis, the use of oral , sustained-re lease not necessary but is also an a lternative that can be help-
progesterone in adose of200 mg every day (QD) or two ful.
1. Hurwitz A, Yage l S, Zio n 1, Zakut D, Palti Z, Adoni A : The O varían Cysts. J Repro Med 44: 399-404 , 199 9 .
Man agement o f Pers isten! Cl ear Pe lvic Cysts Di agnosed by
5. Kruger E, He ller DS: Adnexal Torsio n: A C lini ca l Pathologic
U ltra so nogra ph y. Ob stet G yneco l 72:32 0- 322 , 1988.
Review of3 1 Cases . 44: 7 1- 75 , 1999 .
2. Hasson , HM : Laparosco pi c Management of O va rí an Cysts.
6 . Tas k in O , Yo un g DC, Mangal R, Aruh 1: Preve nti o n and
J Repro Med 35:863-86 7, 1990 .
Trea tm e nt of O va rí a n Cysts w ith Ora l Co nt race pti ve s : A
3. Za netta G, Li ssoni A, Torri V, Da la Va lle C, Tri o D, Rangoni Pros pec ti ve Rand o mi zed Stud y. J G yneco l Surg 12: 21-24 ,
G, Man gioni C : Role of Puncture and Aspirati on in Expect- 1996 .
ant Managem ent o f Simpl e O va rí an Cysts: A Ra ndo mi zed
7 . Ja in KA : So nog raphi c Spectrum o f Hem o rrh ag ic Ova rian
Stud y. BMJ . 31 3: 1110-111 3, 1996 .
Cys ts . .1 Ultraso und Med 2 1:87 9-88 6, 2002 .
4. Fl y nn N K, N iloff JM: Outp ati e nt Mini-La pa ro to my fo r
Unusual Bleeding:
he CREIGHTON MODEL System, with its obj ec- one producti on fo llows the occurrence of an event (the
T ti ve and standardi zed obse rvational syste m, has
opened up a whole new way ofl ooking at various bleed-
development of a corpus luteum). This is a very charac-
teri stic bl eeding episode. Norm al menstru al peri ods or
ing abn ormalities that occ ur within the course of th e bleed ing ep isodes that fo ll ow the previous producti on
menstru al cyc le. In the CrMS , the presence ofbleeding of progesterone are crescendo/decrescendo or decre-
that is dif.ferentfro m a normal menstrual period is called scendo in their patterns.
un usual bleeding. This term resonates with women be-
CrescendolDecrescendo
cause they ha ve confídence in know ing their own men-
L-H-M-L-VL
strual peri ods (which is referred to as usual bl eeding).
Because the CrMS is obj ecti ve and standard ized, it re- Decrescendo
vea ls th ese bleeding episodes are revea led in an ex - H-H-M-M-L
tremely accurate way and in a way that is very help fu l
fo r further eva luation. The above bl eeding pattern s are often assoc iated with
other mil d symptoms of menstruation such as premen-
strual breast tenderness, mild low backache, and mild
Normal Menstruation -------~ menstrua l cra mps.
To understand unusual bl eedin g, one mu st recognize

that a norn1al menstruation is one whi ch fo llows a "ovu- Characteristics of Un usual Bleeding =l
latory event. " An ovulatory event is either ovu lati on
itse lf or an event that mimi cs ovulation. For example, an Bleeding that would be considered un usual is often light,
unruptured fo llicl e is an anovul atory situation, but it very li ght or brown (bl ack) in co lor. Usuall y, it is not
mimi cs ovul ation from a phys iolog ica l point ofview. In crescendo/decrescendo or dec rescendo in its charac-
thi s case, an increase of progesterone and other signs teristics. lt tends to be simil ar fro m day to day. lt is not
fo llow the event and suggest that ovu lati on occurred necessarily assoc iated with the menstrual peri od al-
even though it did not. No rm al menstruation is a bleed- though , on rare occas ions, it may have characteri sti cs
ing episode associated with ali events where progester- of a norma l menstrua l fl ow. Most un usual bl eeding epi-
387
388 The Medical and Surg ica l Practice of NaProTECHNOLOGY
sodes have hormonal causes (dysfunctional uterine CREIGHTON MODEL Definitions. _ _~

bleeding) but sorne may be organic .
ln ad diti o n to the above, there are oth er definitions of
The hormonal causes may include " ovulatory" bleed- bleeding that occur during the course ofthe menstrual
ing. O vulatory bleedin g is a term given to a type of cycle, which are referred to as CREIGHTON MODEL defi-
bleeding whic h is observed around the time of ovul a- niti ons:
tion and is presumed to be associated with the various
estrogen changes that occur at that time. Postmenstrual brown bleeding:
Two or more days ofbrown (black) bl eeding appear-
There are two basic types of ovulatory bleeding: ing at the tai l-end ofthe menstrual tlow. Ge nerally,
th e length ofthe menses in suc h cases is s ix days or
A. Estrogen-breakthrough bleeding:
lo nger, but thi s is not essential to the defi nition.
This is un usua l bleeding observed lead ing up to
Often thi s is referred to as tail-end brown bleeding
the tim e ofthe Peak Day.
(TEB).
B. Estrogen-withdrawal bleeding:
This is unusua l bleeding which is observed im- Premenstrual bleeding:
med iately fo ll owi ng the Peak Day in the count of Three or more days of li ght o r very li ght or brown
three. bleedi ng occurring prior to the beginning ofthe first
modera te day of men strual bleeding (PMB).
Anothe r form of un us ua l bleeding that has a ho1111ona l
cause is that seen in wo men who are oligo-ov ul ato ry or Excessively heavy menses :
anovulatory. The most common situati o n is in women At least one 24 to 48 ho ur p eri od where the wo man
w ho have po lycystic ovarían disease (PCO D). lt is ob- must change pads, tampons or both more freq uentl y
served as periods of L, VL, or B bleeding unassoc iated than every two hours.
with me nses. lt is a ve ry characteristic type ofb leed ing
pattem , w hich can be identified very qui ckly w hen look- In the development of these definiti ons, resea rch at the
ing at the CrMS cha11. Pope Paul V[ lnstitute has shown that the average d ura-
tion of tai l-end brown bl eeding in those cycles whi ch are
consi de red to be abnormal, was 2.2 days (Tab le 32-1 ). ln
Medical Definitions _ ____ _ _ _ ~ those women who sai d they had " heavy me nstrual pe-
ri ods," the ave rage length of time in w hich they had to
To understand the various types of bleedi ng that occ ur c hange pads, tampons o r both was every 77 m inutes
during the course ofthe menstrual cycle, the fo ll owing (Tabl e 32-2). It ra nged from every one-half hour to ev-
standard medi ca! definitions are used: ery fo ur hours in 23 pati ents stu di ed . However, ofthose
Menorrhagia:
Heavier than normal b leeding. Table 32-1 : Length of Period and Number of Days
of Postmenstrual Brown Bleeding in
Metrorrhagia: Hormone Study Gro up (N =ll )
Bleeding between menstrual periods. Total Length Number of Postmenstrual
of Period Brown Days
Menometrorrhagia: 9 4
Heavier than normal menstrual periods and bleed- 8 4
7 2
ing between menstrua l periods.
6 2
6 2
Dysfunctional ute rine bleeding (DUB): 6 2
6 2
Uterine bleeding associated with no identifiable or- 6 1
ga ni c condition ; usually thought to be honnonal in 6 1
5 2
nature. 5 2
Average 6.4 days 2.2 days

In arder to be certa in about dysfunctional uterine bleed-
Range 5- 9 days 1-4 days
ing, the woma n must see her physician and ha ve at least a
pelvic examination that is negative. An ultrasound ex- 1. In control group, the range in the length of the menses was 5 to 7
days in duration with a means of 5.4 days.
am in ation is useful in further eva luating this condi tion .
Chapter 32: Unusual Bleeding : Evaluation and Treatment 389
23 patients, 20 of them changed every two hours or

Table 32-2: Frequency of Changing Pads, Tampons less. These defi nitions were deve loped based om thi s
or Both from History at Time of lnterview type of data.
in Women with "Heavy" Menses (N =23) 1
In addition to the above, very li ght periods have also
Frequency n %
been described . A menstrual scoring system has been
Every 1/2 hour 7 30.4 developed at the Pope Paul VI lnstitute in whi ch a nor-
Every hour 7 30.4 mal menstrual flow wou ld score ~ 6.0 (Tab le 32-3). [n
Every 1 1/2 hours 3 13.0 Table 32-4, l I cycles with very 1ight periods were scored,
Every 2 hours 3 13.0
with the average score being 3 .Oand the average length
in days 3.7. Women who have a decreased intensity of
Every 4 hours 3 13.0
menstruati on tend to have limited mucus cyc les also
Totals 23 2 99 .8 (Tab le 32-5 ). These events may be physiologica ll y con-
1. This historical information was obtained in the patients in which nected.
these question were specifically asked (N=23).
2. Mean= 77.0 minutes.
A typical pattern of unusual bl eedi ng (dysfunctional
uteri ne bl eed ing) is shown in Figure 32-1. In thi s case, a
woman with po lycystic ova ri an di sease and long, ir-
regul ar cycles has multipl e epi sodes of irregular bleed-
ing. These bleeding epi sodes are characteri sti ca ll y dif-
Table 32-4: Menstrual Scoring System ferent from her menstrual peri ods. Her true men strual
periods begin on day 1 of lines 1, 4 and 6. They are
typical decrescendo bl eedin g epi sodes. In addition , the
(H) Heavy 12 points
true menstruations, which are observed on li ne 4 and
lin e 6 of Figure 32-1 , also follow the occurrence of a
(M) Moderate 8 points
Peak Day, which occurred 14 and 13 days earlier respec-
(L) Light 4 points
tive ly. The unusua l bleed ing epi sodes are li ght bleed-
(VL) Very Light 2 points
in g or brown bleeding episodes, wh ich tend to be th e
(B) Brown 1 points
same from day to day. These types of epi sodes are usu-
Assign appropriate score to each day of the first six days of all y assoc iated with the unopposed stimul ation of the
menstruation . To obtain menstrual score, divide the sum of
these seores (for the first six days) by 6. endometrium by low-intensity estrogen, whi ch is being
manu factured by the ovary durin g the course of these
long preovulatory phases.
The causes of premenstrual bl eed in g are thought to

Table 32-3: Menstrual Scoring Syste m
result from the premature breakdown of endometrial cap-
Length Creighton Model Menstrual
ill aries secondary toan inadequate support by the cor-
Oays Description Score 1 pus luteum during th e lu teal ph ase of th e menstrual
VL 0.33
cyc le. In ad diti on, the postmen strual brown bleeding
2 M, VL 1.7 (tail-end brown bleeding, TEB) may be due to an irreg u-
2 M, M 2.7 lar sloughing ofthe endometrium with the retention of
4 M, L, VL, VL 2.7 small frag ments of endometri al tissue and associated
4 M, M, L, L 4.0
4 M, M, VL, VL 3.3
4 M, M, L, L 4.0
5 M, L, L, VL , VL 3.3
Table 32-5: Menstrual Score
5 M, L, L, VL, VL 3.3 Patients with Endometriosis
5 L, M, M, L, VL 4.3 Regular Mucus Cycle vs. Limited Mucus Cycle
5 M, M, O, VL, VL 3.3
Study Group N MS' (x)
Average
3.7 3.0 Regular mucus cycle 2
18 6.4
Range
Limited mucus cycle 2 24 5.1'
1-5 days 0.33-4 .3
1. Menstrual score
1. Menstrual scoring system developed at Pope Paul VI lnstitute.
2. As determined by 3C'S Mucus Cycle Scoring System
The mean menstrual score in normal menses should be ?: 6.0.
3. p<.01
9 10 11 12 13 14 IS 16 17 18 2~ 25 26 27 28 29 30 31 32 33 34 35
H H M 10\X SKL
ot;l 1C r
~e
1C 1
se
xi
~e
:io;;i.
r.c
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101<
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se
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xd,, xiíl K 1
f t.,
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a x?i IOC. OAO 6Cal
X3
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ax3 4AO IOG
•I
4'C
11:a.
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11,I ,.;¡, 1t;i.
8KL
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101<. IOK IOKV C,,,C OAO OAO OAO
•I .el >t;l
H H H <.-C. <oc SY toe <OC c.,c 8C IOK ac AD (oC 8C \OK IOK /OK IOK IOK ~o 4AO se se <oc IOK IOK IOK lOK f&,C IOK..
"'' 1t<:l "' ica xa ;i;I • ;l. •• .:il 11.a x3 11,I -.1 •I • I xa .:a xi 1(1 •I •~ 11..3 xi xi 1ta
B
IOK se
•1 KI
L L <.C ~y 4AO C..C S~ IOK

~D 4-AD IC;\ xi >1.I >CI Xól.
Figure 32-1 : This series of cycles, from the same woman , is an example of a charting pattern observed in a patient who has
polycystic ovarian disease. The cycles are very long and irregular. The first cycle is 80 days in duration . The second cycle is
50 days in duration and the third cycle is not yet complete . The bleeding patterns beginning on day 1 of lines 1, 4 and 6 are all
classic usual menstrual periods. However, the bleeding from days 4 through 10 of line 2, day 23 of line 4 and days 25 through
29 of line 6, are all classic patterns of dysfunctional uterine bleeding (From : Pope Paul VI lnstitute research , 2004).
necrosis and intlammation . This, too, may be assoc i-

ated with decreased progesterone production in the pre- Table 32-6: Summa ry of P+7 Progesterone Levels
vious post-Peak phase ofthe cycle. An analysis ofthe by Fertilicy Status and Type of
Peak +7 progesterone leve ls in a grou p ofpatients who Perim.en.strual Bleedin.g D ysfun.ctio n (PBD)
had premenstrual bleeding, postmenstrual brown bleed-
Mean P+7
ing, very light periods and the absence ofsuch, in com- Fertility Status and PBD n Progesterone
parison to women w ith no perimenstrual bleeding dys-
lnfertile
function (PBD) , is shown in Table 32-6. The progester-
No premenstrual bleeding 13 8.3·
one levels on Peak + 7 in those women who had very (infertile)
light periods and premenstrual bleeding, was signifi- Very light periods 9 8.4.
cantly lower than in the women with no perimen trua! (infertile)
bleeding. Those women w ith TEB had also decreased Premenstrual bleeding ' 13 9.o·
progesterone leve ls, but the decreased levels did not (infertile}
reach statistica l significance. Nonethe less, it is thought Postmenstrual brown 10 9.8

(infertile)
that progesterone levels may play a ro le in this condi-
No postmenstrual brown 11 12.6
tion.
Fertile
An example ofthis is shown in Figure 32-2. In this chart, No PBD 20 12 .3
the woman had three days of TEB at the end of her 1. Defined as three ar more days of light, very light ar brown bleeding
prior to the beginning of a period (CrMS ).
menstruation and her menstrual periods are somewhat
All statistically significan! at p<.05 .
longer than usual (e ight days in duration). At the time
of diagnostic laparoscopy, an endometrial biopsy was
obtained. In that biopsy, fragments of necrotic tissue
were observed w ith secondary chronic inflammatory
12 13 14 15 16 17 18
Figure 32-2: TEB (or black bleeding) in a woman with infertility and endometriosis. At D&C , the endometrium revealed retained
fragments of necrotic endometrial tissue (see Figures 32-3 and 32-4) (From: Pope Paul VI lnstitute research, 2004).
reaction associated with it (Figures 32-3 and 32-4). In shown in Table 32-7. The menstrual discharge itself is
this case, it is thought that the TEB was secondary to a made up of both blood and endometrial íluids as the
chron ic irritation ofthe endometrium that has occurred majar contributors . The hemoglobin (Hb) ofa menstrual
secondaril y toan irregu lar s loughing ofthe endometrial discharge ranges from 4.0 to 5.0 (Table 32-8). Minar con-
lining. This irregu lar s lo ughing is thought to result from tributions to the menstrual discharge may also come
the previous dysfunction of the corpus luteum. There from cervical fluid , vaginal secretions, and perhaps even
are potentially other causes for this, and these will be fluid from the fa ll opian tube (Tab le 32-9).
discussed later in this chapter.
The system for observing bleeding in the CrMS uses a Organic Causes _________~
recording of H = heavy; M = moderate; L = light; YL =
very lig ht; B = brown or black bleeding. This approach A number of organic causes for various abnormal b leed-
to the reporting of menstruation coincides with data ing pattems occur during the course of the menstrual
that was generated on a subjective rating ofthe volume cycle . We ha ve developed a classification of un usual
of menstrual discharge by Fraser, et al. 1 Their data are bleeding based upon the CrMS . This is shown in Table
Figures 32-3 and 32-4: An endometrial biopsy showing a necrotic degenerating fragment in the slightly left of cente r portion
of the histopathology in Figure 32-3 (low power of the microscope). In Figure 32-4 (medium power of the microscope), an
inflammatory rea ction is easily seen. In the center of this necrotic fragment, there are small amounts of hemorrhage.
32-1 O. The bl eedin g ca n be broken down into two cat-

Table 32-7: Su bjective Rating of Volume of egori es: perimenstrua / bleeding and intermenstrua/
M enstrual Discharge in 28 Wo m en bleeding. The premenstru al and postmenstrual brown
Avera e Measured Loss
bleeding and excess ive ly heavy bleeding that has been
Subjective rating Tota l fluid Blood loss prev iou sly menti oned fa ll s into th e category of the
of daily blood loss loss (mL) (mL)
perimenstrual bl eedin g pattern . With intermenstrual
A . Heavy (n=6) 42 .7 13 20 .5 13 bleed ing, the bl eeding epi sodes can occur in th e fo l-
B. Moderate (n=21) 25 .3' 12.0 2 low ing fas hi on: bleedin g ea rly in the mucus bu il dup,
e. Light (n=26) 9.5 2.6 bleeding closer to the Peak Day, pro longed premenstrua l
bleeding, prolonged postrnenstrual brown bl eeding, and
1. With A compared to C. p<.001 .
2. With B compared to C , p<.001 . a vari abl e return of un usual bl eedin g in long (a novu la-
3. A is not statistically different from B.
tory or oligo-ovul atory) cyc les.
From: Fraser IS, McCarron G, Markham R , Resta T: Blood and Total
Fluid Content of Menstrual Discharge. Obstet Gynecol 65: 194-198.
1985.
A rev iew of the hi stolog ic di agnoses in a group of 148
consecuti ve CREIGHTON MODEL users who exhibited
va ri ous un usual bl eeding epi sodes and had a dil atati on
and curettage (D&C) (a nd often a hysterosco py) is
hown in Tabl e 32-11 . In thi s situati on, no spec ific or-
ga ni c path ology was observed in 63 of the patients
(42 .6%). However, ev idence of orga ni c path ology wa
identifi ed in 85 of the pati ents (57.4%). The most co m-
Table 32-8: Menstrual H em oglo bin mon findin g was an endometri al polyp (n=3 I ). How-
Co ncentratio ns Collected directly from Ute ri ever, hom1 onal imbalance (mostly di sordered proli fera -
in T hree W o men ti ve endometrium) (n= 18), endometrial hyperplasia with-
out atypia (n= 14), and chronic endometriti s (n= 1O) were
Hb. of Menstrual also seen frequentl y. Other changes th at were also ob-
Oischarge (gms %) Comment
served but were not as co mmon included cystic hyper-
4 .0 Approximately 35% of plas ia (n=4), endometri al hyperplas ia with atypi a (n=2),
4 .2 venous concentra tions on
5.0 days 1 and 2. adenocarcinoma (n= 1), and ca rcinosa rcoma (n= 1).
From: Ebert R . Nold B: Gerinnungsphysilogische studien aur
menstrualblut. Schweiz Med Nochenscher 36:999, 1956. Based on th ese 148 co nsec utive D&C procedures,
th e ca uses of unu sual bl eeding with perim ens tru al
bl eedin g epi sodes of th e CrMS are ca tego ri zed ac-
co rdin g to th e class ifi ca ti on fo und in Tabl e 32 -1 2.
Ca uses of unu sual bleedin g in use rs of th e C r MS in
whi ch th e bleedi ng wa co nsidered to be interm en-
stru al based on 148 co nsec uti ve D&Cs are shown in
Table 32-9: Co ntributo rs to the Table 32-10: Classificatio ns of Un usual Bleeding

M enstrual Discharge using th e Creighto n M odel System
Majar contri butors Perimenstrual bleed ing

• Blood • Premenstrual bleed ing
• Endometria l glandular secretions • Postmenstrual (brown) bleedi ng
• Endometrial tissue exudate • Excessively heavy menstrual bleeding
Minar contributors lntermenstrual bleeding

• Cervical fluid • Bleed ing ea rly in mucus build up
• Vaginal secretions • Bleedi ng closer to Peak Day
• Fallopian tube fiuid • Prolonged premenstrual bleeding
• Prolonged postmenstrual (brown) bleeding
From: Fraser IS, McCarron G, Markham R , Resta T: • Variable return of unusual bleeding in very long
Blood and Tota l Fluid Content of Menstrual Discha rge . (anovu latory or oligo-ovulatory) cycles
ObstetGynecol65:194-198, 1985.
Chapter 32 : Unusual Bleeding : Evaluation and Treatment 393
Tabl e 32-1 3. Th ese cl ass ifi cat ions are not mutuall y ex - Figures 32-5 and 32-6. In the first exa mpl e, the pati ent
clusive, but they do all ow th e phys ician , when look ing hada large cerv ica l eversion (ectro pi on) with a nom1 al
at the CrMS chart, to begin to ga in an apprec iation for Pap smear. However, the cervix was friable and bled eas-
the potential poss ibili ties that might ex ist within a given ily. After the cervix was properly hyfrecated, th e cervix
situati on. returned to normal and th e bleeding was brought under
contro l.
A review of the vari ous organi c ca uses and their ap-
pearance in CrMS cha rting is now presented. In Figure 32-6, the pati ent had a cervix with a grade 11
cervica l eversion on the posterior lip. A loop electrosur-
gica l excision procedure (LEE P) was performed because
Chronic Cervicitis ___________, of the abn ormal bl eeding. Th e hi stopathology showed
acute immature quamous metapl asia with marked reac-
Two exampl es of a chronic cervicit is caus ing abnorma l tive-appearing epithe li al atypi a in a background of se-
bl eeding and the subsequent treatments are shown in vere acute and chro ni c endocervicitis and borderlin e
mil d dyspl as ia. With th e LEE P procedure, she had an
exce ll ent outcome and her charting returned to normal.
Table 32-11: R esults of 148 Consecutive D &Cs 1
Performed on C reighton Model Users with
Bleeding Abno rmalities Endometritis _ _ _________~
Histologic Diagnosis N %
Examples where endometriti s caused un usual bleeding
No orga nic pathology 63 42.6 are shown in Figure 32-7 and Figure 32-8. In the first
Evidence of organic pathology 85 57.4
case, the bleeding was heavy and not typi ca l of a stan-
• Endometrial polyps (n=31) dard unusual bl eeding pattern . When the cervix and
• Horm one imbalance (n=18)
• Endometrial hyperplasia
endometrium were eva luated, Escherichia co/i was cu l-
without atypia (n=14) tured and the patient was treated with cephalosporin s
• Chronic endometritis (n=10)
(Kefl ex) and intra muscul ar progesterone. The outcome
• Cystic hyperplasia (n=4)
• Polypoid changes (n=4) was exce llent.
• Endometrial hyperplasia with
atypia (n=2)
• Adenoca rcinoma (n=1)
• Carcinosarcoma (n=1)
Table 32- 13: Causes of U nusual Bleeding -
lntermenstrual Bleeding
1. Usuallywith hysteroscopy
Creighton Model System 1
Bleeding early in mucus bui ldup or bleeding closer to

Peak Day
• Estrogen breakthrough
Table 32-12: Causes of Perimenstru al Bleeding • Endometria l polyps
• Adenoma tous polyps
Creigh ton Model System 1 • Adenomatous hyperplasia (adenoca rcinoma)
Prolonged premenstrual bleeding

Premenstrual bleeding • Endometritis
• lnadeq uate hormone support of endometrium • Submucous fibroids
• Premature breakdown of capillaries • Endometrial polyps
Postmenstrual (brown) bleeding Postmenstrual brown (prolonged)
• lnadeq uate horm one support of endometrium by • Adenoma tous hyperplasia

previous corpus luteum • Cystic hyperplasia
• Irregular fragments of necrotic tissue • Adenomyosis
Heavy menses {cha nge pad Q2h) Anovulatory bleeding (DU B)
• Submucous fibro ids • Estrogen breakth rough

• Cystic hyperplasia • Endometrial polyps
• Adenomyosis • Adenomatous hyperplasia
• Adenocarcinoma
1. Based on 148 consedutive D&Cs and hysteroscopies.
1. Based on 148 consecutive D&Cs and hysleroscopies.
12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
B
IOK
X1
8K
,. .;¡
G:oClk
,.¡¡
IOOL 4 .e;I
11 1
4,.¡ MO V4D -..,o 4 irl
..
aw 4x•
...
aw
Figure 32-5 A and 8 : In cycle A, bleeding in this menstrual cycle is occurring in 17 of the 26 days of the cycle . This was
observed in a woman who had a grade 4 cervical eversion with very friable tissue th at bled easily. After having her cervix
treated with hyfrecation and the cervix was healed , her cycle returned to the one shown as cycle B (From : Pope Paul VI
31 32 33 34 35
Figures 32-6 A and 8: In cycle A, the patient exhibits prolonged premenstrual brown bleeding . Her cervix on examination
appeared to be fairly normal , but she had an abnormal Pap smear. After a LEEP procedure and after her cervix had healed , her
cycle reverted back to a normal pattern as shown in cycle B (From : Pope Paul VI lnstitute research , 2004) .
Figure 32-7 : In these two consecutive cycles , the patient showed intermenstrual bleeding associated with her mucus cycle in
the first cycle of this chart and in the second cycle, a nearly continuous 23-day pattern of bleeding. When she was evaluated ,
the endometrium was cultured and E. coli was found . This was eventually treated with cephalospo rins and she was also given
intramuscular progesterone on day 23, 26 , and 29. This resulted in a normal pattern (From : Pope Paul VI lnstitute research ,
2004).
Chapter 32 : Unus ual Bleed ing : Eval uat ion and Treat ment 395
In Figure 32-8, the patient presented with pro longed Premenstrual Bleeding _ _ _ _ _ __
post-Peak bleeding. A D&C was performed and chron ic
endometriti s was identifi ed . Cu lture at that time from A good exampl e of premenstrual bleeding and its asso-
the end ometrium revea led Enterococcus faecalis. The ciated treatment are shown in Figure 32-9. In thi s case,
patient improved dram atica lly fo ll owi ng th e D&C and suboptimal progesterone and estradi o l - 1 7 ~ leve ls were
treatment with Ampicillin (500 mg by mouth four times a ident ified during the post-Pea k ph ase of the cyc le and
day [PO QlD] fo r 1Odays). the patient was treated with post-Peak HCG, 2000 JU,
Peak +3, 5, 7, and 9. This eliminated her premenstrual
Our practice has not incl uded routine endometria l cul- bleeding and corrected th e underlying diffícu lties and
tures. However, a proj ect is currentl y be ing conducted problems.
to accompli shed thi s, spec ifíca lly exam ining endome-
tria l tissue sa mples. However, a set ofrandom endome-
trial cul tures was obtai ned from patients with unu sual Endometrial Polyps _ __ _ _ __ _
bleeding and that data are shown in Table 32- 14. This
does not indicate the overa ll frequency of occurrence Figure 32-1 O shows a patient who had intermenstrual
of the different pathogens or how they are assoc iated bleeding which occurred immediately after the Peak day
wi th specifí c types of abnormal bleeding. But, it does and then agai n in the middl e of the mucus cycle with the
give a perception ofthe types oforgani sms- with En- bleedin g continuing despite post-Peak progesterone
terococcus faecalis and Gardnerella vagina/is be ing th erapy and hada D&C and a hysteroscopy. At the time
the most common- that can be identifíed. ofthe surgica l procedure, an endometrial polyp (a mass
of endometrial tissue appended to the lining of the uterus
by a pedicle) was identifi ed. In the cyc le follow ing the
Table 32-14: Random Endometrial C ultures surgery, the bleeding di sappeared. The overwhelming
Obtained from Patients with majority of endometria l polyps are beni gn and often
Un usual Bleeding (N=20) asympto matic. However, a small number ca n show ma-
lignant tran sformation . Thus, it is important to recog-
ni ze them and treat them appropri ately. Endometri al bi-
Enterococcus faecalis (n=6) op y is not adequate for the treatment of endometria l
Gardnerella vaginalis (n=5 ) polyps; the polyp itself must be removed.
Negative (n=4)
Staphylococcus aureus (n=2)
13-Hemolytic strep (n=2)
Excessively Heavy Menses _ _ _ __
a-Hemolytic strep (n=2)
Prevotella (Bacteroides ) biviua (n=2)
Bacteroides fragilis (n=1 ) Very heavy menstrual peri ods have many different
Enterobacter aerogens (n=1) ca uses. These can include uterin e fibroids , adenomyo-
is, myometrial hyperp lasia (hypertrophy ofthe uterus),
or even coagul ation disorders such as thrombocytope-
9 IO 11 12 13 14 15 16 32 33 34 35
8
!OK IOKL SK SK IOKL IO!<.L tOKL IOK ;,AD aAO .i1AD .;AD ;AD aAD a.AD V. O a.AD ;!AD
.otl 1(1 11.l .AO ic.3 AD ,.a, •I
Figure 32-8 A and B : In cycle A, !he cycle shows prolonged premenstru al spotting . The pali en! had a D&C and a positive
endometrial culture for Enterococcus faecalis. After being treated with Ampici llin , her cycle became normal and is shown in
cycle B (From : Pope Paul VI Jnstitute research , 2004).
10 u 12 13 14 29 JO J 32 33 34 35
13
13
lól.
14
I~
15
Figure 32-9 : This palien! had premenstrual spotting associated with decreased progesterone levels. Following that, she was
treated with post-Peak HCG, 2000 units IM on Peak +3, 5, 7 and 9. This is shown in !he last three cycles of this figure . This corrected
her bleeding abnormality (From : Pope Paul VI lnstitute research , 2004).
Figure 32-10: In this palien!, the first five cycles revealed intermenstrual bleeding in a 48-year-old woman . She underwent a D&C
in the fifth cycle and this corrected the bleeding as shown in the sixth cycle. On pathology examination, she had an endometrial
polyp (From : Pope Paul VI lnstitute research , 2004).
Chapter 32 : Unusual Bleeding : Evaluation and Treatment 397
nía, system ic lupu s, or von Wi ll ebrand disease. ectomy was needed .
There are three ma in types ofuteri ne fibroids. These are Treatment of uterine fibro ids depends entire ly on symp-
submucous, intramura l and subserous. The most com- toms. Most women need no treatment at ali ift hey are
pl ex fro m a bl eeding poi nt ofv iew are the submu cous not symptomatic. Most often, fibro ids do not interfe re
fibro ids. A small subm ucous fibro id can cause extremely with fert il ity although submucous fibro ids mi ght lead
heavy menstrual fl ow. to misca rriage. Fibro ids ha ve a very low ma li gnant po-
tential. Submucous fibro ids are clearly the most prob-
The exact incidence ofbenign fibro id tumors within the lematic because ofthei r heavy bleed ing characteri stics.
ge nera l popul ation is not exact ly known. However,
Nova k, in 1948, estimated that 20 percent of ali women Treatment programs include everything fro m hysterec-
over 30 had fibroid tumors. Sorne have estimated that as tomy to myomectomy. With regard to the latter proce-
hi gh as 40 percent of women over the age of 35 ha ve dure, many pati ents pre fe r a myomectomy overa hys-
fibro id tumors. Submucous fibroids are thought to com- terectomy. These women do not wish to ha ve their uterus
pose about 5 to 1O percent of ali fibro id tum ors. With removed and want an alternati ve fo rm of treatment.
the advent of ultrasound , we are now a ble to see fibro id When exp lai ning the myomectomy proced ure to them,
tumors better and it may change our views on thi s in it is important to po int out that they may conti nue to
time. have sorne increased bleed ing even with a myomec-
tomy and may sti ll req ui re a hysterectomy. Most ofthe
Figure 32- 11 shows th e CrMS chart of a patient with tim e, a myo mectomy will cause a reduction in the vo l-
very large submucous fibro ids. Thi s particu lar patient ume of men trua ! blood loss.
was an intensive-care nurse and, on the day descri bed
as VH (very heavy), he actua lly measured the amou nt Sorne prostaglandin inh ibitors have also been used to
of blood discharged. In one cyc le, it totaled nearly 500 red uce the amount of blood loss. These woul d include
ce. She had a decrease in her hemoglob in wi th each of drugs such as mefenami c ac id (MFA) (Ponstel) and
her menstrual peri ods and even myomectomy did not meclofenamate sodium (Meclomen). Studies conducted
help. Submucous fibro ids were ident ifi ed and a hyste r- on the use of these medications in women with exces-
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
~~~~~~~ ~~~~~~~ ~~~ ~

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Figure 32-11: In thi s patient, she had very heavy menstrual periods. The days labeled "VH" (very heavy) measured nearl y 500
ce of blood flow. She also has prolonged tail-end brown bleeding . Diagnosis in this case revea led multiple submucous fi broids
(From: Pope Paul VI lnstitute research, 2004).
Table 32-1 5: Meas ured Menstrual Blood Loss

with Vario us Gynecologic Disorders
and a Complaint of M en orrhagia
Mean Blood Mean Blood

Loss Befare Loss with
Condition and Treatment Treatment Treatment
Le iomyomata '
Treated with MFA' 102.3 88.4
Treated wilh myomectomy 304 .2 52.4
The Effects of Adenomyosis'

Mefenamic Acid Treated with MFA 85.8 36.4
on Menorrhagia
Endometriosis 1
Treated with MFA 81 .5 53.1
Pelvic inflammatory disease '

Treated with MFA 44 .1 22 .3
Menorrhagia'
(General )
Treated with Meclomen 140 70
Figure 32-12 : The effects of medication (mefenamic acid- 1. From: Fraser IS , McCarron G, Markham R, Resta T, Watts A: Measured
Menstrual Blooc Loss in Women with Menorrhagia Associated with Pelvic
Ponstel) in a palien! with severe menorrhagia . In the first four
Disease or Coag ulation Disorder. Obstet Gynecol 68: 630-633.1986.
cycles without Ponstel , the periods were very heavy. With the
2. MFA- Mefenamic acid (Ponstel)
addition of medication in th e last two cycles, her periods
3. From : Va rgas JM, Campeau JO. Mishell DR: Treatment of Menorrhagia
decreased their intensity significantly (From : Pope Paul VI with Meclofenamate Sodium. Obste! Gynecol 157: 944-950. 1987.
lnstitute research , 2004) .
sively heavy menses are shown in Tab le 32- 15. In a li w ithin weeks and is ofno actua l va lue in predi ctin g
categories ofve ry heavy bl eeding, mefenamic ac id de- endometrial risk.
creased the amo unt of menstrua l tl ow. Thi s has also
been observed with mec lofenamate sodium . Thi s 1s B. Simple or cystic hyperplasia:
shown in Figure 32-12. This diagnosis indicates that greater than 1O per-
cent of the g land s are en larged. A parallel increase
a lso occurs in th e amount of stroma, so th ere is no
Endometrial Hyperplasia _ _ _ _ _~ change in the g land-to-stroma rati o (i.e. , back-to-
back crowding is absent). Therefore, even when the
Endometri al hype rplasi a is a cond iti on in whi ch the en- size of the g lands differs markedl y, th e g lands are
dometrium ex hibits excessive ce llul ar pro li feration. evenl y distributed wi thin the stroma.
Patholog ic interpretati ons of pre-invas ive hi sto logic
changes or precursors to adenocarcin oma of the uterus, C. Complex or adenomatous hyperplasia:
can be inconsisten t. Four fea tures are genera ll y eva lu- Thi s di ag nos is indi cates that greater th an 50 per-
ated: stromal in vas ion , mitotic ac ti vity, nuc lear atyp ia, cent of the large g lands exhibit back-to-back crowd-
an d stratification . Ofthese four, stroma l in vasion is the ing, resu lting in an increase of the gland-to-stroma
most reliable indicator of invasive carc inoma. 2 ratio.
De Lignieres has recently presented a categorization of D. Atypical hyperplasia :

the various degrees of hyperpl as ia . These inc lude the lt is referred to as atypical when ce llul ar aty pia is
fo llowing: 2 present. Ce llul ar atypia occ urs when the nuclei of
e pithe li a l ce ll s are ro unded rather than ovo id and
A. Focal hyperplasia: they tend to be hyperchromati c and show a loss of
Al though it is no longer considered a true hyperpla- po lari ty near th e surface .
sia, this indi cates en largement of less than 1O per-
cent of the g lands in the samp le exam ined. Thi s non- De Li gni eres points out that, ofthese categories, atypi-
signifi cant findin g genera ll y abates spontaneously ca l compl ex hyperp lasia is the most li ke ly to progress to
carcinoma. Th is finding , wh ich should be considered endometrium can be visualized. 3 This can then be ac-
prema li gnant in ali cases, wi ll progress to carc inoma companied with D&C fo r endometrial sampl ing.
within fo ur years in at least 30 percent of cases. Further-
more, in 15 to 25 percent of complex hyperp lasia diag- ln Figures 32- 13, 32-14 and 32- 15, examp les of CrMS
noses, a we ll-di fferentiated ca rcinoma will already be charts in women who have been diagnosed with en-
present in the uterus. lt is less likely, but still possible, dometria l hyperplasia are shown. Different pattems are
that the other types of hyperp lasia wi ll progress to car- observed includi ng bl eeding within the mucus cycle
cinoma: within a 10-year-period , atypical simple hyper- and prolonged premenstrua l bl eeding.
plasia wi ll progress in 8 percent of cases, comp lex hy-
perplasia will progress in 3 to 25 percent of cases, and
si mple hyperplas ia wi ll progress in 1 percent of cases. 2 Dysfunctional Uterine Bleeding
Secondary to Polycystic Ovaries _ _~
Suspected endometri al hyperp las ia must be thoroughly
investigated. An ultrasound measurement of endome- Figures 32-16 and 32- 17 show dysfunctiona l uterine
trial thi ckness that exceeds 8 mm ora morphologic ir- bleeding pattern s seen in women who have pol ycystic
regul arity in which one area is thicker than another indi- ovarian di sease. In both cases, end ometrial biopsies
cates the need for further eva luation by biopsy or hys- were negative.
teroscopy. In fact, such eva luation is essentia l to a de-
finiti ve di agnosis. 3·4 In Figure 32-16, the treatment approach was to provide
intramuscular, isomolecular progesterone 100 mg on
Endometri al bi opsies can be performed on an outpa- days 18, 2 1 and 24. Repeating thi s from cyc le to cycle
tient basis. However, that procedure is both physically all ows for regulari zation ofthe cyc le to occur and also
painful and psychologica ll y stressfu l. In add ition, diag- provide the protection of progesterone to unopposed
nostic certainty is limited by the fact that it is a "blind" estrogen.
procedure and ca nnot sampl e ali of th e endometrium.
Hysteroscopy is the optima! method of assessing en- 1n Figure 32-1 7, a different approach was taken . In th is
dometrial hyperplasia because the entire surface ofthe case, clom iphene citrate (C lomid) has been used to help
19 20 21 22 23 24 25 26
Figure 32-13: This patient revealed intermenstrual bleeding early in the mucus cycle and again in th e middle of the mucus cycle.
At the time of surgery (a D&C ), pathology revealed endometri al hype rpl asia without atypia . In the remaining three cycles, the
bleeding corrected itself (From : Pope Paul VI lnstitute research, 2004) .
17 18 19 20 21 22
D&C =Adenomat.ous
Hyperplas1a
Figure 32-14: In this case, the palien! again had intermenstrual bleeding associated with the early phase of the mucus cycle.
Al the time of D&C , she had endometrial hyperplasia withou t atypia (From: Pope Paul VI lnstitute research , 2004).
12 13 14 15 16
HCG
Adenomatous Hyperplasia
treated with Progesterone Support (HCG)
Figure 32-15: In this example, the patient exhibited tail-end brown bleeding and prolonged premenstrual bleeding . In these
cycles, she bled nearly three out of every four weeks. At the time of diagnostic laparoscopy (4th cycle, day 15), she also had
an endometrial biopsy. The endometrial biopsy revealed endometrial hyperplasia . She was subsequently treated with HCG
luteal phase support and repeat endometrial biopsies six months later revealed normal endometrium (From : Pope Paul VI lnstitute
research , 2004 ).
~~~
°"'º °"'º ~ -~--~~~~--------~-------
°"º CAD Ql\O 0.-.0 OAO
Figure 32-16: In this patient with polycysti c ovarian disease , a classic dysfunctional uterine bleeding pattern is shown
in the first two lines of charting . The type of bleeding seen is a continuous pattern of bleeding which is !he same from day
to day. On days 23 , 26 and 29 of the second line of charting , she was given isomolecular progesterone 100 mg IM. She
was then managed on a cycle-by-cycle basis with isomolecular progesterone 100 mg IM, on days 18, 21 and 24 . This
resulted in regular menstrual cycles andan elimination of the dysfunctional uterine bleeding (From : Pope Paul VI lnstitute
research , 2004) .
Regulation of Bleeding
with Clomiphene Citrate (C)
Figure 32-17 : In this example, a woman with polycystic ovarian disease and long , irregular cycles with prolonged
dysfunctional uterine bleeding (shown in the first three lines of charting) was managed with clomiphene citrate (Clomid)
on days 5 through 9 of her cycle to help regulate her cycles . After clom iphene was given and when follicular growth and
development and corpus luteum formation were established , !he dysfunctional uterine bleeding disappeared (From : Pope
Paul VI lnstitute research , 2004) .
402 The Medica ! and Surgi cal Practice of NaProTECHNOLOGY
stimul ate ovu lation. Thi s allows for the development of years of observati on, she was eva luated hormonal ly
a follicle and a subsequent corpus luteum and, thus, and fo und to ha ve suboptimal progesterone produc-
progesteron e. Although, thi s is a reasonable approac h, ti on. Supplementation w ith both progesterone and HCG
it wo uld not be considered on a long-term basis. On a provided her w ith no benefit to her bleeding pattern.
short-term bas is, however, it is a reasonab le approach Eventuall y, the bleeding became heav ier and the men-
to take. strual periods became painful. Thi s, then , necessi tated
a hysterectomy. At the time ofhysterectomy, it was found
that she had adenomyos is. Now, in looking at simil ar
Thyroid -----------~ charts, we have observed severa! patients with this type
of bleeding pattern associated with adenomyosis.
On occas io n, treatment of th yro id dysfu nct io n o r
suppl ementation with thyroid can be effective in reduc-
ing or eliminating unusual bleeding in the CrMS . In Fig- Truncated Menstrual Cycles ----~
ure 32-1 8, the patient has been supp lemented w ith sus-
tained release triiodothyronin e (T) . With this suppl e- Sometim es, a patient w ill say that she is having amen-
mentation, because her T 3 :rT 3 (reverse T) was low, the strua l period every two weeks. Thi s is rare ly an emer-
bleedin g improved significantl y (F igure 32-18). One gency. Having the patient chart her cycles is hel pful fo r
should always consider thyroid dysfunction as a pos- proper evaluation . In Fi gure 32-20, a woman who had
sibl e underlying prob lem in abnormal bleeding prob- been charting her cyc les for sorne time began having
lems (see Chapter 36). very short cycles, 16 days in duration . We did a hor-
mona l eva luat io n on he r a nd fo und , interestingl y
enough, that her post-Peak progesterone levels were in
Adenomyosis _________ _~ tb e preovulatory range, and yet, the bleed ing pattern
was characteri stica lly simil ar to a true menstrual flow.
The patient shown in Figure 32- 19 was fo llowed for sev- This is one ofthe few situati ons that we have observed
era! years with very long menstrual periods. These peri- in whi ch the bleeding is similar to a true menstruation.
ods were up to 13 days in duration and assoc iated with We have ca ll ed th is a " truncated" menstrual cycle.
pro longed postm enstru a l brown bleed ing. Over th e
1 2 4 6 7 8 10 11 19 20
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3 5 9 12 13 14 15 16 17 18 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
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1
H M
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r
~ ~s
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1
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VL
-
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L M H M L
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s
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...
.•¡
'
EW 1-i~ ~T. ~TA
, 'NT Fm FO LO ·U p r
ANC
-
M H M M L VL
DAD DAD
... V
Figure 32-18: Th e menstrual period s of thi s woman befare and after the implementation of T3 (sustained-release) therapy are
shown . Her periods we re ve ry heavy in th e first three cycles , but on SRT 3 , her menses decreased in intensity significantly
Chapter 32 : Unusual Bleeding: Evaluation and Treatment 403
9 10 u 12 13 14
H L M L L L L L ~ ~ ~ ~ ~
IOBK /OBK IOBt<. 1o&t<. 106K !OSI< 8
(o C,,6 t,S 108GL SBC
AD AD AD AO AD AD AD AD AD x3 X1
M M L VL VL
106K 418 C.0
A 1 x,?i AD
M H M L
I08K
AD
M H fvl L L
""ª c..e
AO AD
I
Figure 32-19 : In this example, the patient's menstrual periods extended for 10 to 13 days . Thi s ongoing pattern existed for many
years and was resistan! to treatment with luteal phase progesterone support. Eventua ll y, it necessitated hysterectomy and , at
the time of hysterectomy, she was diagnosed as having adenomyosis (From : Pope Paul VI lnstitute research , 2004).
1 2 3 4 5 6 7 8 9 IO IJ 12 13 14 IS 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
.. .. f f f f u1
~ ~se ~se '
L
r
M
r
M
I
H M
..
VL
•L
~e
I
'"
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I
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XI
I
se
xI
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Ge.
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~se ~,,,,, IOK
I
oc oc
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r
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1 • Truncated 16-day menstrual cycles
L M M H H H M L L • PPP - 5 days
"' • Hormone testing reveals anovulatory pattern
'"
Figure 32-20: In this example of 16-day menstrual periods , the patient had both estradiol and progesterone levels drawn . Her
Peak +3 and Peak +5 progesterone levels in th e first cycle were in the preovulatory range . These cycles, which can occur
spon taneously, are referred to as "truncated" cycles . They can be treated by giving a follow-up of three cycles of intramuscu lar
progesterone (see text) (From : Pope Paul VI lnstitute research, 2004).
404 The Med ic al and Surgical Practice of NaProTECHNOLOGY
In these cases, th e patients wi ll res pond favorab ly to She subseq uently went to a reproducti ve immunologist
three cyc les of intra muscul ar isomo lecu lar progester- w ho thougb t that her miscarriages were due to an au-
one . Generally speaking, the produ ction of progester- toimmune phenomenon. S he was placed on E nb rel 25
one should beg in pri or to the onset of her next anti ci- mg SQ, every 84 hours. After being placed on the En brel ,
pated menstrual flow. Thus, in a situation such as Fig- her premenstru al spotting and tail-end brown bleeding
ure 32-20 , the progesterone should begin on day 12 or di sappeared. This suggests that perhaps, at least in this
14 in the first cyc le of administration. The progesterone case, premen strua l spottin g may have bad an underl y-
is then give n on days 12, 15, and 18 in the first cycle. In ing immunolog ica l orig in or cause. The author has al-
the second cycle, it is g ive n on days 15 , 18, and 2 1 and most no experi ence in the use of Enbrel ( except in thi s
in the tbird cyc le on days 18, 2 1, and 24. After three one case) but wanted to present it in this chapter.
cyc les of intramuscul ar progesterone used in this fash-
ion, the progeste ro ne feeds back to the hypotha lamus
and restructures the hypothalamic pituitary ovarian axis,
thus stimul ating the return of a normal menstrual cyc le.
A good deal of gyneco logic practice in vo lves women
w ho ha ve abnormal bleed ing episodes for a vari ety of
Possible lmmunological Causes _ _~ reasons. Standard practi ce is to place them on ora l con-
tracepti ves, which regulates thei r bl eeding but neither
ln Figures 32-2 1 and 32-22, a 37-yea r-o ld wo man w ho pays attenti on to the underl yi ng causes nor treats them
had ex perienced fo ur pregnancies , two ofwhi ch ended adequate ly. Sorne of these wo men end up with hyster-
in miscarriage, was seen fo r eva luatio n. Her charti ng ectomi es because of bleeding ep isodes that otherwise
revea led both premenstrual brown bleeding and tail- go undi agnosed.
end brown bleeding. In reviewing her horrnone studi es ,
we fo und th at her periovulatory estradiol profil e was When a wo man begins charting her cycles wi th the
higher than ex pected and that her post-Peak progester- CrMS, an objective patte rn of bleeding can be devel-
one and estradiol profi le was very good. During the oped and an eventual diagnos is can be made with the
course of her fo lli cular ultrasound stud y, her fo lli cle use ofs imple honnone studies ora diagnostic D&C and
appeared somewhat larger than norma l. In this case, hysteroscopy. In additi on, endom etri al cultures can be
premenstrual spotting was occurrin g in the presence of helpful. Then , appropriate management can be instituted
normal progesterone levels. Thus, this was different than and, most of the time without additional surgery, the
our general wo rk ing hypoth eses. problem can be so lved.
Chapter 32: Unusual Bleeding : Evaluati on and Treatment 405
34 35
4AD OAO °"'º OA O CAD DAD OAD OAD
...
I
r
Figure 32-21 : In this patient who had both intermenstrual bleeding and premenstrual bleeding and a history of miscarriages , her
preovulatory estradiol levels were above normal and her postovulatory progesterone and estradiol levels we re also normal.
This suggested that her premenstrual spotting was not hormonal in origin (From: Pope Paul VI lnstitute research , 2004) .
12 13 14 15 16 17 18 19 20 21
PMB and TEB with

above normal P and E2 Profile l--l---l--+--+~-+---1--+--4--i--+--+--+-+--+--t---ir---1--t--1
37y/o G4 P2 SAB2
,,
~e
Premenstrual spotting and

TEB have disappeared
Figure 32-22 : This is the same patient as in Figure 32-21 . The premenstrual spotting is shown in the first cycle of charting . She
was treated by a reproductive immunologist with Enbrel 25 mg SQ every 84 hours. On treatment with Enbrel , her premenstrual
spotting and tail-end brown bleeding disappeared (From : Pope Paul VI lnstitute research , 2004) .
lO ll 12 13 1-' 15 16 29 30 31 32 33 34 35
IOC. IOK. 10CK IOCK K>CK tOK

>el •I 1t ól xi "ª .. 1
Figure 32-23 : In this fina l chart, th is woman with a longstand ing infertility problem was treated with luteal phase support
wi thout benefit (fi rst 3 cycles). Then , she was treated empirically with metronidazole 500 mg by mouth two times a day (PO BID )
for 1O days and the bleeding stopped (From: Pope Paul VI lnstitute research , 2004 ).
1. Fraser 1S, McCarron G, Markham R, Resta T, Watts A: Measured 3. Spencer CP, Cooper AJ, Whitehead M I: Manage ment of Abnorma l
Menstrual Blood Loss in Women with Menorrh agia Associ ated with Bleeding in Women Receiving Hormone Replacement Therapy. Br
Pe lvic Disease or Coag ulation Disorder. Obste! Gynecol 68:630- Med J 3 15: 37-42, 1999.
633, 1986.
4. Gambrell RO JR: Strategies to Reduce the lnc idence of Endometrial
2. de Lignieres B: Endometria l Hyperpl asia: Ri sks, Recogni tion and Cancer in Postmenstrual Women, Am J Obstet Gynecol 177: 1196-
the Search for a Safe Horrnone Replacement Regimen. J Repro Med 1207, 1997.
44: 191 -1 96, 1999.
Osteoporosis and the
Role of the CrMS
steoporosis is a ske letal disease characterized by 50 years ofage wi ll experience one ofthese fractures.
O low bone mass and a deterioration in the bone mi-
cro-architecture lead in g to enhanced bone fragility and
There are 1.5 mi Ili on osteoporosis-related fractures an-
nually in the Un ited States, and these include:
an increased ri sk of fracture 1 (F igure 33-1 ). lt is esti-
300,000 hip fractures
mated that 10 milli on indi viduals have the disease, and
nearly 34 mi Ili on (or 55 percent ofthose 50 years of age 700,000 vertebra l fractures
and older) ha ve a low bone mass, which puts them atan 250,000 wrist fractures
increased ri sk of deve loping osteoporosis and re lated 300,000 fractures at other si tes
fractures. Ofthe l Omi Ilion Americans estimated to have
osteoporos is, 80 percent are women and 20 percent For women , the risk of hip fracture is eq ual to her com-
men. 2 bined risk of breast, uterin e, and ovarian cancer. 2 The
rate ofhip fractures in women is two to three times higher
An osteoporosis-related fracture in one 's lifetime is very than it is in men; however, the one year mortal ity rate
common. One in two women and one in four men over following a hip fracture is nearly twice as high for men
Healthy bone Osteoporotic bone

Figure 33-1: A graphic showing osteoporotic bone compared to healthy bone.
407
as it is for women. The overall mortality rate is quite women who have used oral contraceptives (OC) com-
high. On average, 24 percent of hip-fracture patients pared with those who have never used OCs. 10
aged 50 and over will die w ithin the yea r fo llowing the
fracture. 2
Diagnosis of Osteoporosis _____~
The National lnstitute of Health Consensus Statement
on osteoporosis prevention , diagnosis and therapy The preferred method for diagnosing decreased BMD
(2000) estimates that 10 to 15 billion dollars are spent is dual-energy x-ray absorptiometry (DXA) . DXA em-
an nual ly on the treatment of osteoporotic fracture (Fig- ploys two x-ray beams of different energy leve Is that
ure 33-2). allows for measurement correction based on the vary-
ing beam-path length and on the tissue composition
encountered when measuring BMD at different skeletal
30 . . . . . . - - - - - - - - - - - - - - - - - .
sites. 3 The BMD measurements obtained by DXA at
peripheral sites are most predictive for fractu re risk in
25 women who are o lder than 65 .
,,-...
.,~
._, 20 A T- core is developed and is based on the expected
<l.>
CJ
distribution of BMD for "young, norn1al " adu lts of the
e same sex. The difference is expressed as a standard de-
<l.>
-; 15
viation (S O) above (+) or below (-) the mean. T-scores,
,_><l.> which decline with age, are convenient cut-points for
Q..
10 treatment decisions. The use of DXA is illustrated for
the spine in Figure 33-3 and for the hip in Figure 33-4.
5 ____ Women
Using DXA technology and T-scores, one may make a
_ _ _ Men diagnosis of normal bone densi ty, os teopenia , os-
teoporosi , and severe osteoporosis (Tab le 33-1 ).
55 60 65 70 75 80 85 90
Figure 33-2 : The increase in severe vertebral fracture in
both men and women with advancing age (From: Lunar News,
p 4, Summer 2000).
Table 33-1: Diagnostic Criteria
for Osteoporosis'
BMD' T-s.c ore bel ow

Identifiable risk factors for osteoporosis incl ude certain Diagnosis healthy young mean 3 T-score
non-modifiab le factors. These are advanced age, Cau-
Normal Less than 1 O to -1 .0
casian race, fema le sex, the hi story offractu re in a first-
Osteopenia Between 1 and 2.5 -1.0 to -2 .5
degree relative, anda personal history offracture asan
Osteoporosis 2.5 or more < -2 .5
adult. Other risks factors that are potentially modifiable
Severe osteoporosis 2.5 or more with fragility
include current cigarette smoking; a low body weight fractures
(less than 127 pounds) ; estrogen deficiency inc luding
early menopause (less than age 45), bilateral ovariec-
tomy, or prolonged premenopausal amenorrhea (greater
than one year) ; heavy alcohol intake; inadequate physi -
cal activity; and low calci um intake. 3
Widespread use of hormonal contracepti ve agents cre- Treatrnent ____________--.

a tes concern regarding increased risk of osteoporosis.
While sorne have suggested that there is no relation- Over the years, treatment has focused upon estrogen
ship or that the study designs have not been adequate supp lementation particularly for postmenopausal
to show this concern ,45 other studies clearly show a women. 11 Certain pharmacologic agents have been used
decrease in bone mineral density (BMD) associated with to prevent and to treat osteoporos is . These include
the use ofDepo-Provera .6 · 9 In addition, national popu- alendronate (Fosamax) , calcitonin-salm on nasa l spray
lation-based data from Canada have shown lower BMD (M iaca lc in), and raloxifene (Evista). 12 These various
values for the trochanter and spine in premenopausal medications are effecti ve in treating osteoporosis, but
Chapter 33 : Osteoporosis and the Ro le of the CrMS 409
AP Spine Bone Density

Reference: L2-L4
BMD (g/cm') YA T-Score

T12 1.44 2
1.32
1.20 o
L1
1.08 -1
-2
0.84 -3
L2
0.72 -4
0.60 -5
20 30 40 50 60 70 80 90 100
Age (years)
L3
1 2 3
BMD Young-Adult Age-Matched
L4 Region (glcm ' ) T-Score Z-Score
L1 0.954 -1 .5 -1.6
L2 0.979 -1.8 -2.0
L3 0.948 -2.1 -2.3
L4 0.942 -2.1 -2.3
L2-L4 0.956 -2.0 -2.2
Figure 33-3: A DXA sean of spine, T1 2 th ro ugh L4 . The BMD and T-seo re are shown (From: Pope Paul VI lnstitute Ad ult Bone
Density Center).
DualF emur Bone Density
1 2,7 3
Reference: Total BMD Young-Adult Age-Matched
Region {g/cm ' ) T-Sco ra Z-Scora
BMD (g/cm') YA T-Score Neck
1.24 2
Left 0.852 -1.1 -1 .2
1.12 Right 0.852 -1.1 -1.2
1.00 o Mean 0.852 -1.1 -1.2
0.88 -1 Difference 0.000 O.O O.O
0.76 -2
Total
Left 0.880 -1.0 -1.1
0.64 -3
Right 0.870 -1.1 -1.2
0.52 -4 Mean 0.875 -1 .0 -1 .1
0.40 -5 Difference 0.009 0.1 0.1
20 30 40 50 60 70 80 90 100
Age (years)
Figure 33 -4: A DXA sean of the hip and the BMD and T-seores (From : Pope Pau l VI lnstitute Adu lt Bone Density Center).
they do have side effects that create sorne fear with scans on them and began to co mpare the di ffe rent hor-
regard to their use. monal components to th eir bone densities.
The most signi fi ca nt hormone findin g was a decreased

Hormonal Correlations ______ ~ post-Peak E2 sum along with decreased androstenedi-
one and DH EA leve ls (Tabl e 33-2). Pati ents with de-
Pri or 13 has suggested th at progesterone may be a bone- creased post-Peak E2 sums had significantl y lower bone
tro phic hormone. In a rev iew on thi s topi c, she showed densities in the spine and the fe mora l neck. Lower lev-
that progesterone was acti ve in bone metabo li sm . She els of Peak +7 androstenedi one were assoc iated with
presented a hypothetica l relationship between ph ases signi fica ntl y lower spine BMD, and lower leve ls of
of the bone remodelin g cyc le in suscepti ble popul a- DHEAs were a sociated with stati sti ca lly lower BM Ds
ti ons and the normal menstrual cyc le. This is shown in in the fe mora l neck and the total hip (Table 33-2). When
Figure 33-5. She postul ates that the phases ofthe bone post-Peak progesterone, FS H, LH, total testosterone,
remodeling cycle may para!lel tempora l changes and the free testosterone and periovulatory 3-va lue E2 sums were
gonadal stero id s. lncreas ing estrogen producti on be- eva lu ated, no stati stica ll y signifi cant changes in BMD
fo re ovul ation may reverse the resorpti on occurring in a were identifi ed. When thi s proj ect was begun, the work-
"sensiti ve" bone multice llul ar unit. Gonadal steroid lev- ing hypoth e is was that the post-Peak progesterone
els are also low at the time of th e menstrua l fl ow. The levels would be decreased. However, in thi s group of
bone rernodeling uni t is then ready to begi n a format ion patients, the post-Peak progesterone levels were nor-
phase when progesterone levels peaked during th e mid- mal as were the peri ovulatory E2 leve ls. The luteal phase
lutea l phase. From thi s perspecti ve, she suggests that E2 leve Is though were signi fi cantl y lower. This is pre-
the normal ovulatory cycle looks like a natu ra l bone- sented in the case of one indi vidual in Fi gure 33-6. Thi
activating, coherence cyc le. 13 Lee 14 has suggested that situation is consistent with what has been ca ll ed a Type
the use of progesterone as a treatment approach may IV lutea l phase defect (see Chapter 35). This spec ific
be benefi cia! in improving bone density and perh ap target organ defect is identified with a horm onal dys-
co uld be used in long-term treatment. fun ction that is uniquely E2 in ori gin .
Thi s led us to eva lu ate the re lat ion shi p of th e

Pope Paul VI lnstitute Research _ _~ CREIGHTON MODEL System to bone minera l density.
In Tabl e 3 1-3, the bone minera l density is correlated
These observations led us to begin an interesting bone- with the woman's mucus cycle score. In those women
density evaluati on ofpatients from a hormonal perspec- who had mucus cyc le seores less th an or equal to 5.3,
tive. These pati ents und erwent sta nd ard post-Peak the bone mineral density fo r the hip was signi fica nt ly
progesterone and estradi o l-1 7 ~ (E 2) hormone profi les lower and the BMD fo r the spine was very e lose (p=.055).
because of their in fe rtili ty. They also had oth er hor-
mones measured during the lutea l phase of the men-
strual cycle. As a part of thi s program, we obtained DXA Table 33-2: R elationship of Post-Peak (CrMS)
Ta rgeted Horm on e Yalues and
B one Mineral D ensity (BMD):
R eproductive Age Wo men
PROG
Hormone L, - L, Femu r Neck Total Hip
Parameter BMD BMD BMD
Post-Peak E2 Sum
~ 33.0 ng/dl 1.169 ' 0.971 2
, "'.. 33.0 ng/dl 1.260 1.037
,/
P+7 Androstenedione
~ 1.1 1.194 3
> 1.1 1.256
-12 -10 -8 -6 -4 -2 o 2 4 6 8 10 12 14
P+7 DHEAS
(Menses) Ovulation ~ 92 . 8 0.973' 0. 990 5
> 92.8 1.054 1.057
Resorption Reversa! Formation 1. p=.015
2. p=.025
Figure 33-5 : A fi gure showing th e hypoth eti ca l co ncept of 3. p=.031
bone remodeling as it relates to the menstrual cycle (From: 4. p=.002
Prior JC : Progesterone as a Bone-Trophic Hormone. Reviews. 5. p=.012
11 386-398, 1990).
Chapter 33 : Osteoporosis and the Role of the CrMS 411
9 10 11 12 13 14 30 31 32 33 34 35
AAP RAP
Hip • 1 1
Figure 33-6: A patient whose L2 to L4 T-score is a -2 .0 and hip is -1 .1 using DXA. Her CrMS chart shows a mucus cycle score
of 6.3 anda menstrual sco re of 5.7. Her horm onal profile shows norm al periovulatory E2 levels and postovulatory progesterone
levels. However, her luteal phase E2 levels are significa ntly red uced . This is typica l of a Type IV lutea l phase defect (From: Pope
Paul VI lnstitute research, 2004).
The menstru al score was a lso ca lcul ated. Wh en th e

Table 33·3: R elationship of the C rMS menstrua l score was less than or equa l to 5. 1, th e BMD
Mucus Cycle Score (M CS) and fo r the fe mora l neck and total hip we re stati stically lower
Bone Mineral D ensity (BMD): than the BMD when the menstrual score was greater
Reproductive Age Wo men than or eq ua l to 6 .0 .
Mucus Cycle L2 - L 4 Femur Neck Total Hlp

Seo re BMD BMD BMD
Each of these bi omarke rs- th e mucus cyc le score and
the menstrual score- are hormone dependent. Gener-
.'.': 5.3 (n=17) 1.171 ' 0. 9702 0.986 3
a ll y, it is thought that th e decreased mu cus cyc le score
~ 8.6 (n= 23) 1.227 1.052 1.051 is assoc iated with decreased peri ov ul atory E2 leve ls;
1. p=.015 so, thi s score, by itse lf, does not ex pl ain thi s associa-
2. p=.025
3. p=.031 ti on. No neth eless, decreased mucus cycle seores have
target organ effects that are assoc iated with the de-
creased bone mineral density observed .
Table 33-4: Relationship of the C rMS Menstrual

lmplications for Treatment _____~
Score and Bone Mineral D ensity (BMD):
R eproductive Age Women
Beca use the ti ndings presented in thi s chapter are pre-
Menstrual Femur Neck Total Hip liminary and pilot in their ori entati on, more research
Seo re BMD BMD c learl y needs to be done in thi s area. lfit can be identi-
.'.': 5 1 (n=1 6) 0.971 ' 0.986 2 fi ed that wo men in the premenopausa l yea rs ca n be
~ 6.0 (n=28 ) 1.034 1.042
screened fo r hi gh ri sk of subsequent decreased bone
minera l density and fo r the earl y deve lopm ent of os-
1. p=.041
2. p=.048 teoporos is, then the poss ibili ty ex ists fo r impl ementing
early therapy during the premenopausa l yea rs when
412 Th e Medi cal and Surgical Practice of NaProTECHNOLOGY
women are still in the reproductive age group. lt has

been shown that a low bone mass prior to menopause is Table 33-5: Pilot Stu dy of Triestrogen and Progest-
associated with early postmenopausa l fractures; 13 thus, eron e and lts Effects on
long-term analysis of hormone function in the repro- Bone Mineral Density (BMD)
ductive-aged woman needs adequate eva luation bein Postmenopausal Women
cause ofthe potential for implementing treatment strat-
L,.- . L4 .,. Femoral .Neck
egies during the reproductive years to reduce the im- BMD BMD .
pact of osteoporosis in the postmenopausal wo man sig-
Befare treatment 0.837 1 0.632 2
nificantly.
Alte r treatment 0.939 0.708
With these findin gs, the CrMS becomes an important 1. p; .047 (equal variance t-test)
2. p; .040 (equal variance t-test)
too! for the further evaluation of women w ith thi s di ffi -
culty or prob lem. Because the lutea l phase can be selec-
tive ly targeted with th e CrMS for hormone evaluation ,
it is poss ible that screen ing programs cou ld be estab- significant irnprovernent in the bone density in the spine
lished to identify the women at risk . Supplementation and the femoral neck was observed in this study (Table
with cooperative estrogen rep lacement therapy in thi s 33-5). Treatrnent strategies that wou ld use isomolecular
pati ent group needs to be studied . hormone replacernent therapy (during both the prerneno-
pausal and reproductive years as we ll as postmeno-
A sma ll popu lation of postmenopausa l patients was pausal yea rs) shou ld be carefu ll y evaluated.
g iven a combination oftriestrogen and progesterone . A
1. Co nse n s us De ve lo pm e nt Co nfe renc e: Proph y la xis and 8. Bahamodes L, Perrotti , M, Castro S, et al: Four Arm Bon e
Treatment of Osteo po rosis. Osteoporosis lnt. 1 14 -1 17, De n s it y in Use rs of Depo -P rovera as a Contracept ive
199 1. Method. Fert il Ste ril 7 1: 849-852 , 1999 .
2. Si ri s E: The Mana geme nt of Bone Di sease : What's on the 9. Berenson AB, Radecki C M, Grady JJ , et al: A Prospect ive,
Hori zo n? Presentatio ns in Focu s . A Satel lite Sy mp os ium Co ntrolled Study of the Effec ts of Horm ona l Contracep-
held in Conjun cti on with the 24"' Annual Meet in g of A meri- tion on Bone Mineral Den s ity. Obstet Gy necol 98 :576-
can Soc iety for Bone and Minera l Research (ASB MR). San 582, 200 l.
Anto ni o, TX , Septe m be r 20, 2002.
1O. Prior, JC, Kirkland SA, Joseph L, et al: Oral Contracepti ve
3. Nachti ga ll LE: Di agnos is of Osteoporos is. Th e Fema le Pa- Use and Bo ne Minera l Den s ity in Premenopa usa l Women:
tient. Su pple me nt: 7- 1 1, O ctober 1999. Cross-Secti onal Populati o n-Based Data from the Canadian
M ulti -Cen tre Os teoporosis Stud y. CMA J 165: 1023- 1029,
4. Sulak PJ , Kaunitz AM: Hormonal Con tracepti on and Bone
200 1.
Mineral Densit y. Dialogue s in Contracep tion. USC Schoo l
o f Medicine. Fall 1999. 1 1. Fel so n DT, Z ha ng Y, Han nan MT, et al: Th e Effec t of
Postmenopausa l Estrogen Therapy on Bone Density in Eld -
5. Perrotti M, Bah amo ndes L, Petta C, et al: Forearm Bone
er ly Women. N Eng l J Med 329: 1141-1146, 199 3 .
Dens ity in Lon g-Term Users of Oral Comb ined Contracep-
tives and Depot Medroxyprogestero ne Acetate . Ferti l Ste ril 12. Mar ic ic MJ : Preventio n and T reat ment of O ste poros is.
76:469-4 73, 200 1. T he Female Patient. Suppl. 12- 18, 1999.
6. Cundy T, Corni sh J, Roberts H, et al: Sp in al Bone Density in 13. Pri or JC: Progesteron e as a Bone-T rophic Hormone. Endo-
Women Using De pot Medroxyprogesterone Co ntracepti o n. crine Re views . 11 :386-398, 1990.
Obste! Gyneco l 92 :569-5 73, 1998 .
14. Lee J: Progesterone an d Osteoporosi s : The Mis si ng Link?
7. Scholes D, Lacro ix AZ, Ott SM , et al: Bone Mi nera l Density Med Hypoth es is 35 : 3 16-3 18, 199 1.
in Wom e n Using Depot Med roxy pro ges tero ne Acetate fo r
C o ntracep ti o n . Obs tet Gy neco l 93:233-238, 1999.
~--~· ~~34
Cancer:
NaProTECHNOLOGY and the Potential for
Early Detection and Treatment
T hree maj or cancers affect wo men: endometri a l,

breast, and ovari an cancer. NaProTECHNOLOGY
has the potential to help in each of these. Teaching a
ovarian di sease (PCOD). The chroni c anovulation w ith
its unopposed estrogen effect appears to be the major
unde rlying fac tor fo r endornetri al cancer.
woman to be observant can lead to ea rl y cancer detec-
tion. Endo metri al cancer has a host of other ri sk fac tors. Obe-
sity, dia betes me llitus, hypertension, nulliparity, earl y
NaProTECHNOLOGY has the most immedi ate impact menarche and late menopause, estrogen replacement
on endometrial cancer. However, NaProTECHNOLOGY therapy, the use oftamox ife n (the most widely prescribed
al so has the potenti al to he lp in the earl y di ag nos is of hormone treatment for women with breast cancer), a
certain types of breast cancer and in the identifi cati on ge netic predi spos ition, prev ious cancer hi story (espe-
of those women who are at hi gh ri sk. B y identi fy ing cia ll y of the breast and ovary), and smoking are ri sk
hi gh-ri sk indi vidual s, on can subsequently treat them fac tors fo r endometri al cancer.
effecti vely and prevent the cancer from occurring. More
research is required to accompli sh thi s, but data pre- Earl y detecti on is the best preventi on for developing
sented in thi s chapter w ill revea! that potential. In ova- in vasive e nd o me tri a l ca rc in o ma. As th e di sease
ri an cancer, the connecti ons are subtl e if they exist at progresses, the chances ofsurv iva l decrease markedl y.
a li. N onethe less, presenting case data may spur fu rther Average five-year surviva l rates fo r endometrial cancer
research. are 90 percent fo r Stage 1, 60 percent fo r Stage ll, 40
percent fo r Stage llf, and 5 percent fo r Stage IV Treat-
ing precancerous adenomatous hyperpl as ia with hor-
Endometrial Cancer _ __ _ _ _ _~ mones (progesterone), a hysterectomy, or a D&C can
prevent abn om1al precancerous cell s from developing
The most common endometri al cancer is adenoca rci- into cancer.
noma of the endometrium . Thi s is predominantly a dis-
ease o f pos tm e n o pa usa l wo rn e n bu t ca n occ ur Ab normal vaginal bleeding is one of the rnaj or symp-
premenopausa ll y. Roughl y 25 percent ofyoung wo men toms. The American Ca ncer Society recommends that
w ith endometri al ca rcinoma wi ll a lso have po lycystic a li women at hi gh ri sk fo r endometri al cancer (for ex-
413
ample women with a history of infertil ity or obesity) Case Number 1

undergo an endometr ial bi opsy at the ti me of meno-
pause. Thi s case is a 30-yea r-o ld, grav ida O, para O w ith a hi s-
tory of long and irregular cyc les. She had seen mu ltipl e
Beca use the CREIGHTON MODEL System (CrMS) doctors in the past. Because she was not yet married,
teaches wome n how to observe vagi nal d ischarges- they sa id that she did not need to wo rry about her dys-
which include b leeding observation, it is easy to de- fu nctional uterine bleeding (D UB ) until she was married
tect bleed ing w hen it firs t begins and w hen the symp- and needed to be concerned about her fe rtili ty. After
to m is in its ve ry earl iest stages. One can determine her wedding, no pregnancy occurred in th e first two
w hich patients mi ght be at high ri sk fo r the deve lop- years; then, she sought medi ca! assistance. In F igure
ment of endometr ia l ca ncer, so long-term proges terone 34-I , her firs t three months of charting are shown. This
support can be p rov ided fo r pro phylax is. Thi s is per- shows an abse nce of any menstru al periods but the
haps the most immed iate area ofhelp for women in tem1s presence of dysfu nctiona l bleeding. T hi s is a class ic
of early cancer detecti on and prevention. pattern assoc iated with PCOD.
T he CrMS is ab le to ide nti fy those wome n w ho have Furth er eva lu ati o n s howe d th a t s he had aty p ica l
long and irreg ular cycl es, irregu lar breakthrough bleed- adenomatous hyperp las ia and, at the ti me of hysterec-
ing, and other ty pes of abn ormal bl eeding (unusua l to my, s he had a well -di ffe renti ated adenocarcinoma of
bleeding). W hen that is observed, appropri ate testing the endometri um. She is now seven yea rs post-surg ica l
can be done and long-term proges terone pro phy lax is treatme nt w ith no signs ofrecurrence.
can be implemented . In the Pope Paul V I Institu te pro-
gram, the standard pro phy lax is used fo r wo men w ith
polycystic ovari an di sease and long and irregul ar cycles Case Number 2
is 100 mg of isomolec ular progesterone IM on days 18,
2 1 and 24 of the cycl e. This patient is a 36-year-old, gravida O, para Owith PCOD,
infe rtili ty, and DUB . She was moderately obese and be-
Three case presentati ons will demonstrate the relatio n- gan to deve lop un usua l bleeding as observed in Figure
shi p ofthe CrMS in ea rl y cancer detection. 34-2. Di agnostic testing revea led that she had a well-
di ffe rentiated adenocarcinoma ofthe endometrium with-
out myo metr ial invas ion. Jt was a FIGO Stage l A, Grade
12 13 14 s 6 17 18 19 :w 1 22 23 2 25 26 27 28 29 3-0 31 32
38 y/o G-0, P-0: PCOD, long history DUB

Well-differentiated adenocarcinoma of
the endometrium
LAVH, 850 -1997
Figure 34-1 : A 38-year-old, gravida O, pa ra O wi th a long history of dysfun cti ona l uterin e bleeding seco ndary to polycystic
ovarian disease. CrMS charting revealed the bleeding observed in this figure. She had a well-differentiated adenocarcinoma
of the endometri um when evaluated (From : Pope Paul VI lnstitute research, 2004).
Ch apter 34: Cance r an d NaProTECHNOLOGY 415
1 ca rcinoma. She underwent a tota l abdominal hyster- tero ne. As a result, adenomatous hyperplas ia ca n de-
ectomy and bi lateral salpingo-oophorectomy. Five years ve lop. Thi s gro up of pati ents could prove to be a hi gher
later, she is doi ng very we ll w ith no signs ofrecurre nce. ri sk popul ation even though they do not have class ic
po lycystic ovaries . More research will help to deve lop
these concepts and to broaden our category of ri sk fac-
Case Number 3 tors. Thi s wo uld be extreme ly he lpful because then ap-
pro priate preventati ve treatm ent can be imp lemented.
The fi nal pati ent is a 56-year-o ld, gravida 2, para 2 with
a long hi story of DUB but no ev idence of PCO D. Her
chart is shown in Fi gure 34-3. Thi s chart was observed Breast Cancer __________ _,
during the pre menopausal days of her charting. Two
yea rs after menopause, she bega n hav ing bleeding and , Breast cancer is the second most co mmon type of can-
because s he had been an observa nt CrMS user, s he cer in wo men and the second leading cause of cancer-
brought thi s to the atte nti on of her phys ician. On diag- re lated death . O ne in e ight wo men in the United States
nostic testing, it was shown that she had a Stage l car- wil l deve lop breast cancer du ring her li fetime. The diag-
cinosarcoma of the uteru s. S he underwe nt a tota l ab- nos is of Stage I breast cancer increased 11 3 percent
dominal hysterectomy and bil ateral sa lpingo-oophorec- betwee n 1983 and 1997 (F igure 34-4). The number of
tomy. Seven yea rs late r, she is doing very we ll with no new cases in 2002 was 205,000, and the wo men dy ing
signs of recurren ce. from breast cancer during th at year numbered 40,000 .
Breast ca ncer is second onl y to lung cancer as a cause
Other patterns in the CrMS will eventua lly be identifi ed of cancer death . 1
as ri sk fac tors for pati ents the deve lopment of endome-
tr ia l ca rcin o ma . Fo r exa mpl e, wo me n w ho have The most co mmon fo rm of breast cancer is adenoca rci-
adenom atous hyperpl as ia also ha ve delayed Peak Days noma and the earliest fo rm of thi s d isease is ducta l car-
and long mucus cycl es. However, their overa ll cyc les cinoma in situ ( DCI S). lnvas ive ductal carcinoma (IDC)
are 35 to 36 days in durati on w hich is not considered deve lops from DC lS spreading through the duct wall s
particularl y long. These pati ents appear to ha ve a re la- and invading the breast ti ssue.
ti ve overex posure to estrogen or underexpose to proges-
AP
36 y o G-0 P-0: PCOD/infertility/DUB

OAD OAO 00.0 0AD O<\O OA.O OAO MD OAO
developed well-differentiated
adenocarcinoma of endometrium without
myometrial invasion (1999)
TAH, 850: FIGO stafe 1A Grade 1
Figure 34-2 : Thi s 36-year-old, gravida O, para Owith polycystic ova rían disease and dysfunctional bleeding hada well-differentiated
adenoca rcinoma of the endometrium without myometrial invasion. The bleeding was her first sign of its presence (From : Pope Paul
VI lnstitute research, 2004 ).
Cycle #1 : Cycle #2 : Cycle #3 :

MCS 4.0 = MCS = 4.0 MCS = 4.0 ._-+--+---+--+-1--+--1
ppp = 13 ppp = 20
2
SC L aAD
oc 1
aw -.w aw
AO •a "'a.
OAO QA.D °"° OAO OAO o.o.o OAO OA.D OAD CAD OAD VL VL VL VL VL
OAD OA.D OAO OAO CIA D
3
L L M M M M H H M L L VL VL CAD OA.D ~ OAO IODL IOWL IOWL OAD OAO OAO
OAO O'o.D 0&..0 oa.D CA.O OAD OAD OAO OAD C>\D ()ti.O OA.0 ~ AD x1 x1
56 y o G-2 P-2 with long history DUB
No evidence of PCOD
Had postmenstrual bleeding 2 years
after last period
Stage 1 carcinosarcoma of the uterus ,
TAH , BSO (1997)
Figure 34-3: This 56-year-old , gravida 2, para 2 with postmenopausal bleeding had a Stage 1 ca rcinosarcoma of !he uterus. Her
premenopausal charts are shown in these three cycles with the abnormal bleeding present. Beca use she was monitori ng her
mucus and vag inal discharges she was able to identify th e symptoms of her ca nce r ea rly (From: Pope Pau l VI lnstitute research,
2004 ).
Another form of breast cancer origin ates in the glandu-

Diagnosis lar ti ssue of the breast and is referred to as invas ive
60 lobul ar carcinoma. Thi s acco unts fo r 1O to 15 percent of
invas ive breast cancers. There are also numerous other
55 types of less-common breast cancers. These incl ude
infl ammato ry breast cancer (th e breast ti ssue is wa rm ,
50 appears red, and it tends to spread qui ckl y) ; med ull ary
ca rcinoma (orig inates in centra l breast ti ssue); muci-
o
o 45 nous carcino ma (invas ive; usually occurs in postmeno-
o
oo pausa l women); Paget di sease of the nippl e (ori ginates
....
.... 40
in the milk ducts and spreads to the skin of the nippl es
CI) or areola); phyll odes tumor (a tumor w ith a leaf-like ap-
c.
pearance that extends into the ducts and rarely metas-
....ca
CI)
35
tas izes) ; and tubul ar carc inoma (a small tumor that is
o:: often undetected by palpation). Sarcomas (cancer of
30
the connecti ve ti ssue) and lymph omas (can cer of the
lymph tissue) ra re ly develop in the breast.
25
20 ...,._ _ _ _ _ _ _ _ _ _ _ _ ___
The most common risk fac tor fo r breast cancer, of course,
is being fe male. A lthough men can also develop breast
1983 85 87 89 91 93 95 97
cancer, the incidence is very low. It is l 00 times more
Year common in women. ln addition, age (over the age of50),
Figure 34-4: Th is graph shows the increasing rate of Stage first pregnancy after the age of3 0, long-tenn horm one
1 breas! ca nce r. The diagnosis of Stage 1 breas! ca ncer has replacement therapy (H RT more than 5 years), menstrua-
increased 11 3 perce nt between 1983 and 1997 (Data from: tion befo re the age of l 2, menopause after the age of 50,
Surveillance , Epidemiology and End Results-SEER-Program
and nullipari ty are also important ri sk fac tors.
of the Nati onal Cancer lnstitute).
Chapter 34: Cance r and NaProTECHNOLOGY 417
Other ri sk fa ctors include such th ings as family hi story that breast self-examinati on is not very helpful , it is sti ll
of the di sease (a mother or sister with premenopausa l a recommended exercise. Mamm ography, too, is often
breast cancer), hi story of a breast biopsy or radi ation of crit icized and yet it is one of the few techniques that
the breast, moderate use of alcohol (two to fi ve drinks all ow the earl y detection of breast cancer. The defín i-
da ily), obes ity, personal hi story of the di sease (women tive di agnos is is made by breast biopsy, but the lesion
with a hi story of breast cancera re three to fo ur times mu st be identifíed fírst in order to biopsy it. The key to
more likely to have a recurrence), race (s li ghtly more long-term surviva l with breast cancer is its earl y detec-
common in Ca ucas ians), and sedentary lifesty le. Also, tion and treatment. The ability to accurate ly identi fy
benign proliferati ve breast di sease and mutati ons ofthe those individual women who are at ri sk fo r developing
BRCA-1 and BRCA-2 genes (breast cancer gene) are breast ca ncer and to treat th em before they ever get the
also thought to be risk fac tors. di sease wo uld be the optima! situ ati on.
Often not menti oned in di scu sions of breast cancer Progesterone defí ciency may be a prerequi site to the
are th e known assoc iations with the u e of ora l contra- development of breast cancer. l n comparin g two groups
cepti ves2and with induced aborti on (a dec ision to abort of infe rtil e women, one whose infe rtili ty was associated
and delay pregnancy). These can res ul t also in an in- with progesterone defí ciency and the other whose in-
creased ri sk of breast cancer. 3 · 4 fe11ili ty was related to non-horm onal causes, women
with progesterone defi ciency had a 5.4 times increased
The Treloar data set on menstruation and reproduct ive incidence of premenopausa l breast cancer6 (Table 34-1).
hi story, whi ch began in 1934 and has over 50 years of
recorded menstrual events, has been eva luated for varia- This fi nding led us to eva luate the CrMS charting and
ti ons in menstrua l cyc le pattern s and the risk of breast hormone prod ucti on of women who subsequently de-
cancer. This study showed th at women who had cycles ve loped breast cancer. Thi s study project took approxi-
of extreme length at ages 25 to 29 years had a nea rl y mate ly 15 years. Duri ng thi s peri od oftim e, we coll ected
twofold increased incidence of breast cancer. Whi le these 28 pati ents who were charting their cycles and who even-
data genera lly does not agree with other studi es, it is tuall y deve loped breast cancer. Thus, we coll ected ob-
one of the fe w prospecti ve ly acc umul ated data sets jective parameters oft he menstrual and fe rtil ity cycles
(whereas most previous studies of menstrual fun ction during the pre-breast cancer phase and compared it to
and breast ca ncer ri sk used retros pecti ve reports of women who did not deve lop breast cancer.
menstrual bleeding that are more un re li able). 5
In thi s group of 28 pati ents, 27 (96.4%) had regular
The di agnos is of breast cancer is made in a vari ety of cyc les. Onl y one (3.6%) had irregular cycles and that
different ways. Breast self-examination, phys ician breast pat ient did have PCOD. In additi on, 18 pati ents had
examination , mammography, breast ultrasound , and bi- so rne charting informati on, 1O patients had post-Peak
op y are used. Wh il e vari ous stud ies have suggested progesterone profíl es, and 7 patients had post-Peak
estradi o l - 1 7 ~ profil es prior to their development ofbreast
cancer.
Table 34-1: Incide n.ce of Prem eno pausal
Breast Cancer in P roges terone-D eficient From thi in formation, we were able to evaluate the length
lnfertile Women vs. lnfe rtile Wo m en of of the post-Peak phase, th e mu cus cyc le score, and a
N o n-ho rmo nal Causes comparison of post-Pea k progesterone and estradi ol
profil es.
Number of Cases per
Causes of lnfertility 100,000 Person Years
In Figure 34-5 , the post-Peak estradi ol and progester-
Progesterone defi ciency' 141.6 one profi les in th e breast cancer pati ents were com-
(PO )
pa red to a normal-contro lled popul ati on. The post-Peak
Non-hormonal causes' 27.1 estrad iol profil es were within th e normal range; how-
(NH )
ever, th e Peak +5, 7, and 9 progestero ne leve ls were
PO : NH ra tio significantly lower (p=.005 to .000 1) fro m the control
1. Classified on the basis of endometrial biopsies. tests of cervical group. ln fac t, the Peak + 11 progesterone leve! was also
mucus. BBT, luteal phase defects, Stein-Leventhal, etc.
2. Uterine, cervical, peritoneal or tubal factors.
decreased, but numbers were in suffi cient to detem1ine
stati sti ca l signi fica nce.
From: Cowan LD, Gordis G, Tonascia JA, Janes GS: Breas! Cancer
lncidence in Women with a History of Progesterone Deficiency. Am J
Epidem 114:200-217, 1981 .
The CrMS fert ili ty chart from a patient who developed
418 The Med ical and Surgical Pra ct ice of NaProTECHNOLOGY
Post-Peak Estradiol - 17 ~ Post-Peak Progesterone
Control 1 Control 1
Breast cancer O Breas! cancer O
20.0
15.7
10.
o.o
P+3 P+5 P+7 P+9 P+11 P+3 P+5 P+7 P+9 P+11
NS NS NS NS NS NS p=.005 p =.0001 p =.0001 NS
Figu re 34-5 : On the left , post-Peak E2 levels and on the rig ht post-Peak progesterone levels in breas! cancer
patients and norma l contro ls. The E2 levels were within th e norm al range; however, the progesterone levels
were significantl y lower in the brea s! cancer population (From : Pope Paul VI lnstitute research, 2004).
breast cancer evera l yea rs later is ill ustrated in Fig ure usua ll y a s ign of sig niti cantl y suboptim a l p rogestero ne
34-6. He r proges te rone profil e is iden ti tied and is sub- production) was statistically significa nt (p<.000 1) (Table
o ptimal. She also ex hibits preme nstrua l spotting, w hi ch 34-2).
is a bi omarker of the decreased progesterone produc-
tio n, anda m ucus cyc le score of6.7 (interm edi ate lim- A n exa mple of thi s is show n in Fig ures 34-7 and 34-8.
ited) . Furthermo re, she ha two days oftai l-e nd brown Overa nine-year period oftime, cycles fro m this woman,
b leed ing (TE B), w hi ch suggests dec reased progester- w ho eventua lly deve lo ped a DCIS of the breast, showed
o ne production. a va ri abil ity in the length of the po t-Peak phase rang-
ing fro m 6 to 16 days in du ratio n (a 10-day va ri ability) .
Wh en looking at CrMS, a majo r iden ti tiab le ma rk er is
the variati o n in the le ngth of th e post-Peak phase of the W hen the m uc us cyc le seores were evaluated, the mu-
cyc le. In 16 patients w ith breast ca ncer, 13 patie nts had cus cyc le score in th e breast cancer patie nts was lower
a post- Peak phase with a variabili ty offour or mo re days th an the control gro up (7 .5 versus 10 .05). T he di ffe r-
in du ra tio n (8 1.2% ) compared to a contro l gro up ofonl y ence was stati stica lly signiti cant (p= .03 1) (Fig ure 34-9) .
2 pati ents ( 10.0% ) w ho had thi s type ofvariab ili ty. Thi s This fi g ure also shows the d iffe re nce in the Peak + 7
variation in the length ofthe post-Peak phase (w hich is progestero ne leve! between breast cancer patie nts a nd
the contro l gro up. T hi s was a hi ghl y s igniti cant de-
crease (p= .000 1) and suggests th e poss ible helpfu lness
Table 34-2: The Variability in the Length of th e in screening progestero ne levels fo r thi s particul ar po pu-
Post-Peak Phase in No rmal Fertility Controls and lation.
W omen with Breast Cancer
T he mucus cyc le score of a n indi vidua l patient over a
Variabílity in
Length of Post-Peak Controls Breast Cancer nine-year period of time is shown in Figure34- I O. Whi le
Phase (Days) n % n % the re is so me va ri abil ity in the mucus cycle score from
0-1 9 45.0 o O.O yea r to yea r, the muc us cycle score has a downward
2 5 25.0 o o.o tre nd prior to the onset of breast cancer.
3 4 20.0 3 18.8
Ifa n increased va ri ability in th e le ngth of the post-Peak
4 2 10.0 13 ~ pha e (s uggests subo ptima l progesterone productio n
Tota ls 20 100.0 16 100 .0 d uri ng th e luteal phase of th e me nstrua l cyc le) a nd the
presence of other biomarkers (such as premenstrual pot-
1. Chi-square = 18.57, p<.0001 .
ting, limi ted muc us, or T EB) co uld be associated w ith
Chapter 34: Cancer and NaProTECHNOLOGY 419
f- j j 23
1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 1s 19 201 21 22 24 1 25 26 27 28 29 30 31 32 33 34 35
- MHHMM
xi
fffff f
L YLBBdAD IOSL IOSL IOOL :lAD >AD CAD :lAD dAD >AD :lAD >AD Y L YL B
xi X/
B OAD B
OAD °'D
I0~!4«a
f4AD f4AD <!AD a.AD CAD
.., xa AP
'" ao o nq/, o/
... 15.0 nqA 11I
... 10.0
nQI " '
,,.
:-'
... s.o no.1 1
~EM INmr.?: ~RD ~R r EW KHI RT, ~TA l!IPS AN!

l~AK ~Al POI ~TM ~NT FOI FC LO V·U ~
f'
'" "'
Figure 34-6 : This CrMS chart shows a patient with premenstrual spotting, limited mucus cycle (MCS = 6.7) and TES as a
pa ttern that she had wel l in advance of the development of her breast cancer. She also has significantly decreased progesterone
levels during the luteal phase as noted (From : Pope Paul VI lnstitute research , 2004).
women who deve lop breast cancer, then one could ha ve toms. As a result, it is often di agnosed in its later stages.
the opportunity to intervene and eventuall y to prevent The five-year su rvival rate fo r women with advanced
it. If these women are taught to chart th eir cycles and stage disease is onl y 25 to 30 percent and 70 to 75 per-
observe these markers, a Peak + 7 progesterone leve l cent will present in thi s fashion .7
can screen their lutea l phase. lf a woman has subopti-
mal progesterone production, then post-Peak progest- While ovarian cancer is often considered a "sil ent dis-
erone support can stab i1ize that ph ase of the cycle and ease," there are symptom s assoc iated with it. These
cou ld possib ly prevent breast cancer. More research is symptoms include abdom inal distension, pelvic/abdomi-
necessary in this area. Nonetheless, this preliminary data nal pain, and abnormal uterine bleeding. Bladder pres-
strongly suggest that such research should be done. sure or urinary frequency, excess ive vaginal di scharge,
and dyspareunia can also be symptoms of Stage 1 or TI
ovarian cancer. 8· 9
Ovarian Cancer ---------~
The ora l contraceptive has been advanced as an ap-
Approximate ly 30,000 new cases of ovarian cancer are proach to red uce the incidence of ova ri an cancer. 10• 13
di agnosed and 15,000 women die from thi s disease in a atio nal media outlets have reported, based upon these
given yea r. A pproximatel y 2 percent of al 1women born recommendati ons, that "the ri sk of ovarian cancer is
in the Uni ted States are at risk for deve loping ovarian directly related to a woman 's lifetime number of ovu la-
cancer during the course oftheir lifetime. [t usually ap- tions, or menstrual cycles ... " 14 This suggests that ovu-
pears in women who are over 60 years of age, but it may lati on is patho logic and abnormal , and it prov ides the
occur in you nger women with or without a family hi s- rati onale for the ongo in g use of contracepti ves.
tory ofthe disease. Ovarian cancer is responsible for 5
percent of ali cancer deaths among women. Using ultrasound to determ ine ovulation abnorma lities
may provide sorne insight in to the cause of ovarian can-
Early diagnosis of ovarian cancer is compl ex and diffi- cer, but little emphas is has been placed upon th is. One
cu lt. This is an interna! disease often has very few symp- cannot presume that norma l ovu lati on is assoc iated with
Figure 34-7 and 34-8: This series of cycles overa period of nine years shows the high deg ree of variation of the length of the
post-Peak phase in th is wo man who developed DCIS (From : Pope Paul VI lnstitute research , 2004).
12 13 14 15 16 17 18 l9 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
Figure 34-7
12 1 14 15 26 27 28 29 30 31 32 33 35
pp & q
Figure 34-8
Chapter 34: Ca ncer a nd NaProTECHNOLOGY 421
P+ 7 Progesterone Level Mucus Cycle Score Variability in Length

15.7 of Post-Peak Phase
15.0
...,,,
5.9
.s:::
10.05 Cl.
]
en
.s
10.0
8.1
eo
10
..
~5
. u
~.,
e
e ..
en
u>.
7.5
- o
Cl.
..
~
fil
en
()
,,,::;¡
o
.s:::
c.e
e
o.. u ~
::;¡
E
::;¡ 5.0 :E 5 ·=
;¡¡ ~
en
..
:¡;
·¡: 2.0
>
o.o..- -
Control Breast Control Breast Control Breast
ca ncer cancer ca nce r
P+7 p =.031 p<.0001
p=.0001
Figure 34-9 : The progesterone levels, mucus cycle seores, and variability of post-Peak phase in breast cance r
patients versus norm al controls. In each case , patients with breas! ca ncer had si gn ificantly abnorm al levels. The
progesteron e and mucus cycle seores we re decreased while the va riability in the length of the post-Peak phase
was increased (Fro m: Pope Paul VI lnstitute resea rch , 2004).
Breast Cancer
10.0
...o
Q)
7.3 7.3
(.)
en
e:
·¡¡¡
-
c..
~
o
·¡::
Q)
5.0
>
Q)
en
o.o
1984 1985 1986 1987 1988 1989 1990 1991 1992 1992
Year
Figure 34-10 : Thi s graph shows representative samples of the mucus cycle score of a patient
over a ni ne-yea r peri od of time prior to the diag nosis of her breast cance r. The mucus cycle
seores have general ly decreased during this period of ti me, suggesting abnormal ovarian function
(From: Pope Paul VI lnstitute research , 2004).
422 The Medi cal and Surgi cal Pra ct ice of NaProTECHNOLOGY
the development of breast cancer. lf this were true, Case Number 2

women who have un ilatera l oophorectomies wou ld have
a sign ificantly increased risk of ovarian cancer beca use This patient is a 30-year-old , gravida O, para Owho de-
ali ovulations would occur within the remaining ovary, veloped a mucinous tumor of borderline malignancy.
thus doubling its risk. However, data do not support During the cycle in which she hadan ultrasound series,
this. Focusing on the structura l abnormalities of ovu la- her fo llicle was very large just prior to rupture (3. 14 cm).
tion might yield sorne insights. Her hormone profile before and after ovulation appeared
to be within normal limits. Her mucus cycle score was
Two case presentations from the work done at the Pope 8.0 and her post-Peak phase was 17 days (prolonged).
Paul VI ln stitute can supplement this effort. The hor- The interesting finding in this case was the large follicle
monal correlations to ovarian cancerare certa inl y not prior to its rupture. The average-sized fo llicle prior to
we ll developed. Thus, further study and evaluation of rupture (mean follicular diameter, MFD) is 2.2 cm. When
this is necessary. the MFD is greater than 2.5 cm, the fo llicle is cons idered
large. The exact natu re ofthese fo llicles is not we ll un-
derstood but, in this case, a large follicle was a precur-
Case Number 1 sor to the development of this borderline malignancy.
This, too, begs the need for further research investiga-
The first case is a 30-year-old, gra vida 1, para 1 who was tion (Figure 34- 12).
seen with a hi story ofinferti lity. During an ectopic preg-
nancy, the ovary was removed and a Sta ge l IB papi llary
serous cyst adenocarc in oma of the ovary was identi- Final Note -----------~
fied. In reviewing her CrMS charts and hormone pat-
terns, she exh ibited a late luteal defect and premenstrual NaProTECHNOLOGY may aid in the early detection of
bleeding. Her post-Peak phase was within the normal female cancers and perhaps in the identification of those
range and her mucus cyc le was also normal at 1O.7 (Fig- who mi ght be at high ri sk. Women with long, irregular
ure 34- 11). Thi s documented ovarian dysfunction ex- cycles and DU B (due to unopposed estrogen effect)
isted severa ! years prior to the onset of the ovarían are at higher risk for developing endometri al cancer.
cancer. A 1inkage between the observations and the can- When charting their cycles, women in thi s population
cer cannot be positive ly dete1111ined but is worthy of can be easily identifi ed and subsequentl y treated. In
further evaluation . addition , those women who reach menopause with th is
- f
L
1 2
M
3
M
4
L
5 6 7
VL IOKB SKS
OAO OA.D xL3
...
xól
8
~
9
~~~~~
10
'"'º ""'º
u
..
12
• + •3
I
13 14 15
f.. .f.
IOKL IOl(L IOKL IOKL ec
·-
16 17 18 19 20
4fAD :.q,4.0 4AD 4AO '4A.D 4AD

B B 6
21 22 23 24
aAD ~o ~o QC/K
i
25
•a
26
~
27
~
~
28 29 30 31 32 33 34 35
p R o... GE5 T E R o N E llO.(\ ~5 ~4
30 y o G-1 P-1 with

Stage 11 B papillary serous cystadenocarcinoma of ovary
History of infertility
... Late luteal defect (see above, age 23)
Premenstrual bleeding
MCS 10.7 =
... =
PPP 11 days
...
Figu re 34-11: This patient, who was diagnosed with Stage 118 papillary serous cyst adenocarcinoma of the ovary, had a
hormone evaluation several years prior to the development of her cancer. She had a late luteal defect and premenstrual spotting
Cha pter 34: Cancer and Na ProTECHNOLOGY 423
previous cyc le hi story would be considered as at higher not appear to be different than that of women who do
risk. not ha ve breast cancer. 15· 16 However, the birthweight of
bab ies born to women with breast cancer may be sig-
Whi le furt her eva luati on is needed, the data presented nificantly lower than those of control babi es, 15 and the
in this chapter about breast cancer is very exciti ng. lf spontaneous abortion rate appears to be hi gher. 16 There
the variab le length post- Peak phase along with other was no increased ri sk of con genital anomali es.
signs (such as limi ted mucus cyc les, premenstrual spot-
ting, and TEB) where precursors to the deve lopment The CrMS and NaProTECHNOLOGY have on ly minimal
breast cancers, then teaching women to chart their men- research to offer regarding ovarian cancer. Further re-
strual cyc les using the CrMS wou ld be advantageous. sea rch of the endocrine and structural abnormal ities of
Furthermore, screening the luteal phase with a Peak + 7 ov ul at ion as possible precurso rs to ova ri an cancer
progesterone leve! could be helpful. should be done. Suggesting that normal ovul ation pat-
terns and menstrual cycles are di seased and by them-
The survi val ofpregnant women with breast cancer does se lves a precursor to this condition is inappropriate.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
-~ ~.. ..~ ~.. '"""..f ~ f.. .,.,,f ~~~ I~~~ 1111111'~

M L
6
VL
0).5
a.e :>AD aAO """
"º
I
~e
"'
I
BC
''f" ioc/K
I
aAD 8C
I
K 1 JC 1
I
IC /
I
'"
ov.
VOL MCS: 8.0
PPP : 17days
aa..s
~
3.14 CR
ce CMS TEB :+
"' i±)co
E. 15.q ;¡{).¡, ¡.¡.3 i-a,.s

18.1 31.0 /3.8
ª·"
... p a..3 7. 7 1"7.8 /8.3 ~.O U/S: large follicle (3.14 cm)
E2 profile: normal
FSH 3.3
LH 5.4 P profile : normal
FSH/LH : reversed
01 EAS ¡¡51.(
AN[ IOST NE a.s Androgens : elevated
'"
E1 su '°1 ' qo,
Ea ME IAN • 18.(
p su M •
p MI IAN 'º·
= 14.C
Right ovary: mucinous tumor of
borderl ine malignancy, March 1991 .
"'
1EM NDE~: >RD "R r EW 11tRT, ~TA ~PS ANI
l ~AK o A~ POI iTM ºNT -01 FO LO W·Ub
...
Figure 34-12: This patient with a mucinous tumor of borderline malignancy in the right ovary hada large follicle (3.14 cm) at the
time of rupture when studied by serial ultrasound . Her E2 and progesterone profiles were within normal limits but her FSH/LH
levels we re reversed and her androgens were elevated . This would not be co nsidered a normal ovulation pattern and further
research along thi s line is clearly indicated (Fro m: Pope Paul VI lnstitute research , 2004).
T he author w ishes to tha11k the fo ll ow ing FertilityCare™ Practitioners who ass isted w ith the breast cancer
portion ofthi s stud y: Nancy Botkin, Charleston, WV; Linda Cady, RN , Ornaha, NE; Kath y Cherovsky, Ornaha, NE;
Rosernary C lernents, Lincoln, NE; Mary Egan, Sioux City, lA ; Marcia Gretencord, Lafayette, IN ; Diane Hale, Tarnpa,
FL; Susan Hi lgers, Omaha, NE; Juli anna Jerv is, Reno, NV; Si ster Maril yn Mangan, Toronto ; G. Randall McCas lin ,
Austin , T X ; Ann N erbun, Eastover, SC; Laura Tea!, Austin , TX ; and Jea ni ce Vindu ska, Ornah a, NE.
1. Breast Ca ncer: C li nica l Practice Gui de lin es in O nco logy. J 9. Pi ver MS: Ro uti ne Ovari an Cancer Screeni ng for a Su bset of
Natl Co m p CA net. 1:48- 188, 2003. At- Risk Women. The Fe ma le Pat ie nt. 22: 7 1-87, 1997.
2. Co llaborati ve G ro up o n Hormona l Facto rs in Breast Cancer. 1O. Sanderso n M, Willi ams MA , Weiss N S, et a l: O ra l Co ntra-
Breast Cancer and Ho rm o nal Contracepti ves: Co ll aborati ve cepti ves and Epithe li a l Ovarian Ca ncer: Does Dose Matter?
Rea na lys is of Individ ua l Data o n 53,297 Wo men with Breast J Reprod Med 45 :72 0- 726, 2000 .
Cance r and 100,239 Wo me n w ith o ut Breas! Ca nce r fro m
11. arod SA, Ri sch H, Mos le hi R, et a l: Ora l Co ntra cepti ves
54 Ep ide m io log ica l Stud ies . Lancet 34 7: 17 13- 1727, 1996 . and the Risk of He reditary Ovari an Ca nce r. N Eng l J Med
3. Newco mb PA, Sto rer BE, Lo ngnecker M P, et a l: Pregnancy 339: 424-4 28 1998.
Termin ati on in Re lati on to Ris k o f Breast Ca ncer. J A MA
12 . G ross T P, Sc hl es se lma n JJ : T he Est im ated Effec t o f Ora l
275 :283 -287 , 1996 .
Co ntra cepti ve Use o n the C umu la tive Ris k o f Epi the lia l
4. Th o rp J M, Hartm ann KE, Sh ad ig ian : Lon g-Te rm Phys ica l O va ri an Cancer. O bstet G yneca l 83 :41 9-424, 1994.
and Psyc ho log ica l Health Consequences of lnduced Abor-
13. Hankinson S E, Co lditz GA, Hunter DJ , et a l: A Quantitati ve
ti on : Review of the Evidence . Obstet Gyneco l Surv 58:67 -
Assess ment o f Oral Co ntracepti ve Use and Ri sk o f O vari an
79, 2002 . Ca ncer. Obste t G yneca l 80:708-7 14, 1992 .
5. Wh e lan EA, Sa nd le r DP, Roo t J L, e t a l: Menstru a l Cyc le
14. Assoc iated Press. O vari an Cancer Ri sk Tied to O vulati ons.
Pattern s and Risk o f Breas! Cancer. Am J Epidem 140: 108-
O maha World Hera ld, Wednesday, Jul y 2, 1997 .
109, 1994.
15 . Zeml icki s D, Li shn er M, Degendor fer P, et al: Matern al and
6. Cow an LD , Go rd is L, To nasc ia J A, e t a l: Breas t Ca nc er
Fe ta l Outc o me After Brea st Can c e r in Preg na ncy. Am J
ln c id enc e in Wo men w ith a Histo ry of Progestero ne De fi-
Ob stet G yneco l 166 :78 1- 787, 1992.
c ienc y. Am J Ep idem 114: 209-21 7, 198 1.
16. Velentgas P, Dal ing m., Ma lone K E, et al: Pregnancy A fter
7. Memarzad eh S, Berek JS: Ad vances in th e Management o f
Breast Ca rc in oma: Outcomes and lnfluence Morta lity. Can-
Epith e lial O vari an Cancer. J Repro Med 46:62 1-630, 200 1.
cer. 85 :2424-2432 , 1999.
8. Beck HH , Go ldberg RP, Sand PK: Pat ienl Symptoms in Earl y
Stage O va rian Cancer. 7:79-82 , 200 1.
Follicular and Luteal Phase Deficiencias:
Advancing Concepts and New Terminology
n 1923 , 1928 and 1930, Ogino, in Japan, pu blished hi s gone unnoticed in her ori ginal paper was her descrip-
I first observations on the re lationshi p of ovul at ion to
the menstrual cycle. He fo und that ovul ation was asso-
tion of the jollicu/ar phase def ect (FPD), whi ch was
cons idered uncommon.
ciated with the onset of the next menstrua l period and
that it occurred between 12 and 16 days pri or to the In 1950, Noyes, et al. ,6 publi shed the class ic paper on
onset. 1 Working independently of Ogin o, Knaus pu b- the hi sto log ic dating of the endometri al bi opsy. This is
lished the results of hi s physio logica l law on the ti me of summarized in the class ic chart shown in Figure 35- 1.
ovul ation in women in 1929. 2 Based on the uterine con- From that poi nt forwa rd, major emphas is was pl aced on
tracti ons stimulated by the inj ection of a pituitary ex- eva luating and di agnos ing luteal phase deficiency from
tract and inhibited by the acti vity of the corpus luteum an out-of-ph ase endometri al bi opsy.
(fun cti onal li fe of 14 days), he asserted that ovu lati on
ta kes pl ace on the l 4th to the l 6th day of the fo ur-week An out-of-phas e endometrial biopsy was defin ed ac-
menstrual cyc le. These were the first scientific observa- cord ing to the dating schemata (estab li shed by oyes,
tions that allowed fo r an emphasis to be placed on the et al. 6) on an endometri al bi opsy that was obtain ed two
occurrence of ovul ati on in the menstrual cyc le and the to three days pri or to the anticipated menstrual peri od.
length of the luteal phase. lf the biopsy was two days or three days out of phase,
it was considered to be di agnosti c of a lutea l phase
In 1937, Rock and Bartlett 3 described the histo logy of deficiency.1· 12 One ofthe di ffic ulties in obtaini ng these
the proli fe rati ve and secretory phases ofthe menstrua l biopsies was the lack of precision in timing such a bi -
cycle through an eva luation of endo metri al ti ss ue and opsy two to three days pri or to the onset of th e next
confirmed the observations of Ogino and Kn aus. By menstrual peri od. The basa l body temperature curve
1942, Brewer was able to correlate the histologic changes and/or previo us hi story of menstrual cyc le length were
in the corpus luteum with the changes occurring in the used to identify this time. Studies were done that showed
endometrium . In 1949, Jones 5 defi ned the luteal phase the inaccuracy of thi s approach (Figure 35-2) 13 and how
defect (LPD). She based thi s defi nition upon a tempera- thi s co uld be improved onl y with the additi on of more
ture criteri a, urinary pregnanedi ol studi es, and the hi s- expensive technology (F igure 35-3) 14 · 15 .
tolog ic appearance of the endometriu m. What often has
425
. :
GLAHD MITOSES
Gla11d lt'lllH" """.,. ,..Ollte,. rtorl. T~J
e«w M lftt Me•.- ,.,.ir
l'MPl1tr11M1 Mefl
_ , . . . . . . .fl llH "Df'" ..... Ptwl .. M ·
.,.., "fhot """
\
l'SEUDOST~AT IFIC ATIOH Of NUCL!I
TIM 11 cf'Htf«l9'ttttc of rM ,,ohf9n1 th11
c:=•.""'tt ':' ~::· ,:.~~=·:,.~·~:.:''°"
... ..... he.. ""'°""''' """'"' - '"'°"°"
/~ BASA L VACUOLATI ON
\ °' ...
n 1t .. IM H •httl -~· OVIÑftet
"i.tiofll ... f'lf lflfhl~fflllllTI
I "follow!ftt
"""' ...,1i
' '"" ''"º...,
1Hlttofl '6 .. •e "'°""
\
SECRETION
TN t cvno 'º"'''""''
fM ...ft4 111-; ec lM
• 11.... H~l tlOfl M
MC" tl9'1 fwlh ef1
- · '""'º' 111 thtl
HC•ll lOfl • o t°"'91 loÑ'f l t.......
lfl tpttH d ''-
ST ~OMA L EDEMA
Tltlt '1K!Or •etlet wlt" ~ 1119hoMl11t1~
pel'fk vfilt • IJ 1"9 rltt N lllf ,.ol~ l111 hot1
-1'11c l'l - J be º'"'º''
oflt un l T"4 t fllft0
• "'Clil ou:-....i .. 1 IOC l tl lOfl 11 - · «N't-
t l t lll.
l'SEUDODECI DUAL REACTIOH

nn 111.-d1n1 1,,.,.,_, ,... .,," '°"'
etl d PfOfl UI. . 1,111fol )... t ~ t lOO' t - · -
,,,,._.,
tr uollofl o Mi ptd te,.1 co.,..ct ..,. ., h
STAOMAL MITOSES
"'º'' '"'''"f 1114 1WO ·
,\:- e~·~·::.-: :::,:: ~·~~...
TheH "'' o ltwndenl
=:!'
J
,,,--r-- -
of pr1Mc1duo l IOf""'I'°"
V r",::-.,t:'::~t::· •.:~r:ro.;;!'9.:''-"
LEUCOCYTIC INFILTRATION
f htO\lfl"leu' ' " ' ,,, .. ""• • ., • ••• • ,.
vi ~ Oftltl of ttow
M( . . . S
(MU
,,_,Llr-
(1111.tTIOJll
"'jl>"<>LI"
° ·
,! lt&TOI
UIT'l
'110\. lf-
[IUITllOtl
. _.....
Fig ure 35-1 : Dating of the endometrium according to Noyes (From : Noyes RW,
Hertig AT, Rock J : Dating the Endometrial biopsy. Fertil Steril 1:3-25 , 1950).
Frequency Distribution of ~
100
Actual Date of Biops ies ~
e._
30 <.9
z 75
~
o
20 u.
o 50
>-
u
<{
10 o::: 25
Menses ::::i
u
u
o <{
o BBT ONSETOF
ULTRA LH
~5 3/4 2 SOUND SURGE SHIFT MENSES
Days to Menses
Figure 35-2 : Frequency distribution of the date of th e biopsy Fi gure 35-3: Percent of endometria l biopsy interpretations
based on the subsequent onset of menses. Although all biop- that correlated within two days using four different methods
sies we re planned for two to three days before the onset of of ovulati on predi ction . The onset of menses: p< .05 com -
menses , there is consid erab le va riation in the actu al day of pared with ultrasound (From : Shoupe D, Mishell DR, Lacarra
the biopsy because of variation in the cycle (From: Cumming M, et al : Correlation of Endometrial Matu ration wi th Four Meth-
OC , Hon ore LH , Scott JZ, et al : The Late Luteal Phase in ods of Estimating Day of Ovulation . Obste! Gynecol 73:88-92 ,
lnfertile Women : Comparison of Simultaneous Endometrial Bi- 1989).
opsy and Progesterone Levels. Fertil Steril 43:715-719, 1985).
Chapter 35 : Follicul ar and Luteal Phase Defi cien cies 427
It has been well established that defects in end ometri al su ring findin g. lts absence raised th e suspicion of lutea l
histology occur in 20 to 40 percent ofwomen with infer- phase deficiency. 40 With the use of color tl ow pulsed
ti lity and occur frequently in wo men who have repeti- Doppl er ultrasound, it was shown that the resistance
tive spontaneous aborti on.16-18 However, the accuracy index ofintraovarian blood tlow over the course ofthe
of an endometrial biopsy was questioned. 19-22 menstrual cyc le was signifi cantly hi gher in those pa-
tients who had lutea l phase deficiency as deterrnined
In fact, tbe degree of intra-observer variation suggested by endometrial bi opsy.41
th at th e traditional dating criteria were not precise
enough to quantify corpu s luteum function in the sec- More recentl y, integrins, as markers ofuterine recepti v-
ond half ofthe luteal phase. The amount of within-sub- ity have been studi ed in th e endometrium. 42-43Integrins
ject and between-cycle vari ation impli ed that the result are a class of cell adhesion proteins that project from
of endometrial dating in one cyc le could not be used the surface ofa ll ce lls (except red bl ood cells). When-
reliabl y to predict that ofanother cycle.20 ever one ce ll needs to interact with another, it uses the
integri ns as the "Velero" to accompli sh thi s. The ab-
Along with th ese deve lopments, th e endocrine study sence of these proteins at the " implantation window"
ofthe menstrual cycle and the development of alterna- has been documented and appears to be an important
ti ve parameters for di agnos ing lutea l phase defic iency facto r in both in fe1tility and mi scarriage.
rece ived added e mph as is. 23 -27 This led to ofte n-
usedparameters for the eva lu ation of lutea l fu ncti on. Ad vanees were made in the assessment of lutea l phase
For example, a mid-lutea l progesterone leve! of2'_ 3 ng/ progesterone production and analysis with the intro-
mL of progesterone was shown to be assoc iated with a duction of the integrated luteal progesterone value
secretory endometrium and, thus, presumpti ve ev idence (F igure 35-4).44 In its co mpl ex form it provided an estí-
of ovulation. 28·29 Subsequently, other en docri ne param- mate of the total amount of progesterone produced by
eters were advanced to defi ne adequate corpus luteum the co rpus luteum over the course of the length ofth e
function . Abraham, et al. , used the sum of three proges- lutea l phase. An estímate of thi s was advanced by add-
terone leve Is total !ing 2: 15 ng/mL when drawn from M-
4 to M-11 (M = menses) to be indicators of adequate 18
luteal function .30Jordan , et al. , used a mid- luteal phase

progesterone leve! of less than 1O ng/mL or a sum of 16
three serum progesterone leve ls of less than 30 ng/mL
as the recomm ended test fo r determination of lutea l 14
phase defect. Thi s was the first lin e ofeval uation whil e
the endometrial biopsy was the seco nd line. 31However, ...J
~ 12
it was advised that single horrnone va lues should be e:
interpreted cautiously32 and that a single midluteal phase

serurn progesterone leve ! was not predi cti ve of a sub-
"
~ 10
$
sequent in-phase or out-of-phase endometri al biopsy.33 "e"'"'
The basal body temperature (BBT) whi ch had been used o..
"E
extensively, as we ll , by thi s time was shown not to be ."'
helpful in the diagnosis of lutea l phase defect, alth ough ¡¡: 6
ifthe temperature phase were less than 11 days in dura-

ti on, it was hi ghl y assoc iated with luteal phase defi -
ciency.34 To complicate things more, lutea l phase defi-
ciency diagnosed with th e use of endometria l biopsy
2
was also fo und to occur in the presence of compl ete ly
normal follicular and periovul atory phases 35 -37 and in
normal, fertile women. 38 o 6 10 12 14 DAY
Luteal Pha se t
D
Ultrasound has been used as we ll to eva luate th e lutea l Figure 35-4: The progesterone curve during the postovulatory
ph ase. lt was found that follicular growth and develop- phase of th e cycle is similar to a sine curve. The sine curve
and prog esteron e cu rve are superimposed in this diagram
ment revea led a spectrum of both normal and abnormal
allowi ng for a determination of the "area under the curve"
ovarían cycle events in women with lutea l ph ase de- which is one way of calcu lating the integrated progesterone
fect39 and the presence of a homogeneous hyperechoic level. For full ca lculations see reference 44 (From : Wu CH ,
endometrium on lutea l day +7 was fo und to be a reas- Minassian SS: Th e lntegrated Luteal Progesterone : An As-
sessment of Luteal Function. Fertil Steril 48 :937-940, 1987).
428 The Med ica ! and Surgical Pract ic e of NaProTECHNOLOGY
ing the daily serum progesterone levels starting with

700 •
the day after the LH surge and ending with the day prior
lfi' 200 to the beginning of the next menstrual period. ln thi s
~ 600 o
way, an integrated progesterone leve! could be deter-
"O
o mined which was a lso an estimate ofthe total progest-
:::!
o 500 8 erone output over the luteal phase.31 When thi s was
E 150
e o o
used, it was found that patients with luteal phase defi -
(].) 1 ::::i
co ciency (based on endometrial biopsies) had significantly
e
o 400 3 decreased integrated progesterone level s (Figure 35-
Qj • r
Uí ~ o.. 5)45 and when this was tested against the endometrial
(].) • 100 ~
ei 300 !:E.,
biopsy, infertile women with an out-of-phase endome-
trial biopsy showed a significant decrease in the inte-
o..
"O
(].) grated progesterone concentration (Figure 35-6). 46.4 7 The
~ 200 use ofthe sum ofthree progesterone levels less than 30
Ol
(].) 50 ng/mL obtained between cycle days +5 to +9 (in the
e:
100 p<.0 1
luteal phase) is a reasonable estímate ofthis integrated
progesterone va lue.31
One of the current flaw s in th e evaluation of the luteal

Normal LPD
phase is lack ofan objective means upon which arious
Figure 35-5: The integrated progesterone levels calculated abnom1alities in the luteal phase can be c lassified. A
over the duration of the luteal phase are shown for 28 normal
few attempts ofthis have been undertaken , but each of
(left) and 10 luteal phase deficiency (right) women . The inte-
grated progesterone levels for the LPD patients is lower (From : them have been strikingly different and based upon dif-
Soules MR , Mcl achlan RI , Ek M, et al : Luteal Phase Defi- ferent approaches48 •50 (Figure 35-7). Furthermore, a lack
ciency: Characterization of Reproductive Hormones over the of attention to the fol licu lar phase has made most of
Menstrual Cycle. J Clin Endocrino! Metab 69 :804-812, 1989).
these di scussions significantly incomp lete. 51•52
Limitations of Current Approaches==-J
It seems clear that there are a number of limitations in

24 NORMALS the current approach to the understand ing offollicu lar
::¡- ...... Not biopsied (n=8)
and lutea l phase dysfu nction. The first limitation ap-
E ..... Biopsied (n =6 )
Ci LPD
pears in the nomenclature . The endometrial biopsy,
.s Q)
18 Biopsy, out-of-phase
e (n=10)
o.... P.
-
o
Q)
rn
Q)
Cl
12
....
o.
-4 o 4 8 12 16
Day Relative to LH Surge
Figu re 35-6: The luteal phase mean progesterone levels are Figure 35-7 : Three types of abnormality in progesterone
illustrated for three groups of women: normal women (n=8); secretion are cha racterized . Type A shows low plasma P
normal women (n=6) with in-phase endometrial biopsy; and levels all through the early, mid and late luteal phases. Type B
infertile women (n= 1O) without in-phase endometrial biop- shows low plasma P levels in only the early luteal phase and
sies. The integrated progesterone concentration for the latter type C shows low plasma P levels in the mid and late luteal
group was significantly decreased (From : McNeely MJ , Soules phases (From : Kusuhara K: Clinical lmportance of Endome-
MR: The Diagnosis of Luteal Phase Deficiency: A Criti ca ! Re- trial Histology and Progesterone Level Assessment in Luteal-
view. Fertil Steril 50:1-15 , 1988). Phase Defect. Horm Res 37 (Suppl 1):53-58 , 1992).
Chapter 35: Follicular and Luteal Phase Deficiencies 429
w hich is out-of-phase in a number of patients w ho ha ve With the advent of the CREIGHTON MODEL System
both in fert ility or habitual mi scarri age, is ultimately a (CrMS), it is now possib le to target the cycle in its evalu-
test of endom etri al function and not lutea l function. ation with a degree ofprecis ion whi c h a ll ows for o ngo-
Whi le it may, perhap s even in large pa1t , be related to a ing, reproduc ibl e resu lts. Thi s opens up th e ab ili ty to
dysfunction ofthe corpus luteum , it ultimate ly is a dys- eva luate both the fo lli c ul ar, as we ll as the lutea l phase
function of its own and needs inquiry with regard to its of the menstrual cyc le (F igure 35-8). One ofthe difficul-
etio logy. Thus, it is better ide ntifi ed as secretory phase tie in eva luating endometrial function has been the
dysfu nction and is best identified and studied by en- timing of the endometri al bi opsy. With the CrMS and
dometrial biopsy, study ofthe biochemistry of the secre- knowledge ofthe length ofthe post- Peak phase ofthe
tory ph ase, the express ion of integrins, a nd so fort h. cycle, it is possible to target the immediate premenstrual
phase of th e cycle w ith an increased degree of accu -
When looking at ovarian function , the tem1 luteal phase racy. Fu1thermo re, with its ab ili ty to identify both the
dysfunction is an appropri ate term , but it must be a l- active foll icular and luteal phases ofthe menstrual cycle,
ways viewed in terms offollicular phase funct ion. Thus, targeti ng the cycle for e ndoc rine eval uation also be-
it sho uld not be viewed in an iso lated fas hion. Fu1ther- comes easy a nd reprod ucible.
more, it is well recognized that the post-o vulation phase
of the menstrual cycle can be marked ly decreased in
le ngth in sorne patients and si nce this is a reflection of Length of the Luteal Phase _ _ _ _~
ovarí an function , w hi ch has as one of its targets the
endo metrium , it, too, must be taken into cons ideratio n. A number of studi es have eva luated the le ngth of the
Furthermore, the length of the preovulatory phase of lutea l ph ase. 54 -56 In th e author 's eva luatio n, based upon
the menstrual cyc le sho uld be cons idered w he n think- indirect endocrine parameters identi fy ing the beginning
ing further abo ut the fun cti o n of th e ovari an follicle. of the lutea l phase a nd e nding w ith th e beginning of
With the advent of ul trasound tec hnology to stud y and men struation , the average length of the luteal phase
eva luate the anatomy offo lli cul a r growth a nd de ve lop- was 13 days with a range of9 to 17 days. Thi s repre-
me nt, that, too, must be placed into the eva luation of sented 95 .9 pe rcent ofa ll cyc les present in the study of
both fo lli c ular and lutea l ph ase function. 24 subj ects over 73 menstrual cyc les (Table 35-1 ). The

Targeted Periovulatory and Postovulatory Hormone Profiles
Pre-Peak
Menstruation Dry Days Vulvar Mucus Cycle Post-Peak Dry Days
1 1
\/ \
Peak
Day
~ ~ ~ ~
P-6 P-4 P-2 Peak P+2 P+3 P+5 P+7 P+9
Day
\~-----.--~!
Targeted Periovulatory Targeted Post-ovulatory
E2 Profile P + E2 Profile
Figure 35-8: A diagram illustrating the targeted periovulatory estradio l -1 7 ~ (E2 ) and postovulatory progesterone profiles
obtained with the use of the CrMS (From : Pope Paul VI lnstitute research , 2004) .
ex isting ova ri an fo llicl e and th e subseq ue nt fun ction of

Table 35-1: Statistical Para meter of th e
the corpus lute um is hig hl y signifi ca nt when viewed
Luteal Phase (N=24 subjects, 73 cycles)
from the point ofview ofE 2•
Lutea.1 Phase Length in days
In Figures 35-1 1 and 35-12 , the 5-value sum and mean of
Average length 13 ± 4 days
(95 .9% of cycles ) (9-17 days ) a ta rgeted post-Peak progesterone profile is compared
to the Peak leve! of periovul atory E 2 . Aga in , it is ob-
Range of variability 0-2 days = 83 .3%
0-3 days = 91 .6% served that as the Peak leve! of preovulatory E2 in-
0-4 days = 99 .9% creases, the po tovulatory progesterone also increases .
The re lat ionship is stati sti ca ll y significant. Thi s sug-
1. From: Hilgers TW, Abraham G, Prebil AM : The Length of The
Luteal Phase. lnt Rev Nat Fam Plan 13:99, 1989. gests that th e function of the co rpus lu teum is rel ated at
least to sorne exte nt, o n the function ofthe ovari an fol-
li cle. Whil e these associati o ns a re not new, hav ing a
bas ic statistical concept of thi s is important in fu rthe r
cycle length s of each of those subjects is shown in eva luating both lutea l and foll icular function.
Table 35-2. The subject with a luteal phase, w hi ch ranged
from 9 to 11 , da ys went o n to ha ve six children w itho ut
difficulty. The subj ect w ith th e hort lutea l phase of 6
and 7 days in duration was chart ing the CrMS and nor-
Sum of Targeted Post-Peak Estradiol-17P (E,)
mally had lo nger post-Peak phases (in the ra nge of 1O to
5 Values Compared to Peak Periovulatory Estradiol-17P Levels
11 days in durati o n). Howeve r, during the course ofthis 100
stud y over three cyc les, she was under enormo us o ut- 90
s ide stress. This strong ly su pported the notion that her R"::J" 80 .................................
':- E
6- to 7-day lutea l phases were inadequatel y sho rt. :2 (» 70
"O Q.
~ ~ 60
The variability in length o f th e lutea l ph ase has not _,, _ e;;~
tTI 50
ro >
been adequately eva luated. The a uthor has observed 8'. ~ 40
that most wome n have stable lutea l phases . Thi s is sug- ..!. "'
~ E 30
a. :J
gested in the data in Table 35-2. However, sorne women fü Cf) 20
Q)
have unstabl e lutea l pha e (a judged by the va ri abil- ::;;
10
r=0 .9496
p= .0037
ity in the le ngth ofthe post-Peak phase). In Fig ures 35-
9 and 35-1 O, a correlation between the sum and the mean 10 20 30 40
Peak Level of Estradiol-17p (E,)
of targeted po t-Peak estradiol-1 7 ~ (E) (five va lues-
an estimate of th e integrated postovul atory E2 leve!) is Figure 35-9 : The correlati o n coeffi cien t (r) =0.9496 (From :
compared to the Pea k leve! ofthe pe ri ovul atory E2 pro- Pope Pa ul VI lnstitute research , 2004) .
file. The corre lation between the function of the pre-
Table 35-2: Length of Luteal Phase by Subject Studied

and by D ecreasing Length (N=24 subjects, 73 cycles)
Lengths of Len.g ths of Lengths of

Subject Luteal Phase Subject Luteal Phase Subject Luteal Phase
A 17, 16, 17 14, 15, 16 •p 11 , 13, 13

B 16, 13, 15 -J 15, 14,12 Q 13, 13, 11
e 15, 16 •K 14, 15, 15 -R 12, 12, 13
-O 16, 16, 15, 15 -L 14, 13, 14 , 14 s 13, 12 , 11
-E 15, 11 , 15 -M 14, 14, 14, 13 'T 12, 12
-F 15, 15, 13 -N 12, 14 -U 11 , 11 , 12
G 15, 15, 11 ·o 12, 12, 12, 13 -V 12, 12, 12
H 15, 15, 14 ·w 9, 11 , 10
X 7, 7, 6
Had delivered fu ll term infant prior to study cycles.

Conceived without difficulty alter study cycles.
1. From: Hilgers TW, Abraham G, PrebilAM: The Length ofThe Luteal Phase. lnt Rev Nat Fam Plan 13:99, 1989.
Ch apter 35: Follicular a nd Luteal Phase Deficiencies 431
Mean of Targeted Post-Peak Estradiol-17P (E,)

5-values Compa red to Peak Periov ulatory Estradiol-17P Levels
Evaluation of Luteal Function ------.
"'
e: 20
"'
Q)
::;; /
A study of328 patients with in fe 1ii lity was carried out
..... -···········. using a targeted peri ovu latory E 2 and post-Peak proges-
..--· terone and E2 assessment (see Chapter 19). Thi s gro up
••
_.--- ---··········--
.------ __ ... -----··
1 .-····
was eva luated from the point ofv iew of three types of
~ ---··
.. -- -------~
.. -···
__ ...·
·...--·· .---·· progestero ne defi ciency. These three types include
_____...-·· (Table 35-3):
...----------··
_
Type 1: The post-Peak phase is short (:S 8 days in

__ ...-··············· r=0 .9653
p =.0018
du ration) estim ating a short lutea l ph ase. The last
o +----------~~~~~~~~~_, progesterone leve! prior to the onset of menstrua-
o 10 20 30 40
Peak Level of Estrad iol-17P (E,) tion is :S 2.0 ng/mL
Figure 35-1 O: The mean of targeted post-Peak estra di o l - 17 ~

Type ll : The post-Peak phase is nonnal in length but
(E2}-five values-compared to the Peak periovulatory E2 level.
The correlation coefficient r-0.9653. (From: Pope Paul VI ln- the progesterone pro fil e (Peak + 3, 5, 7, 9, and 11) is
stitute research, 2004). clearl y suboptimal as measured both by the charac-
teristics of the profil e and its sum and mean.
5-Value Sum of Targ eted Progesteron e Profile
Compared to Peak Periovulatory Estra diol-17P (E 2 ) Levels Type III: The post-Peak phase is normal in length
100 ~------------------~
but the progesterone profil e (Peak +3, 5, 7, 9, and 1 1)

"'
E 90
::¡
(/)
80
shows an abrupt drop (2: 50 percent on P+9 and
Q)
e:
e:; .----··..-·· P+ l l).
*
10
C1.l !:
O'> 60
8' ..e: Anoth er eva luation was conducted and two additional
a: tñ 50 .... ······ .... ············. ·········
-"'
ra ~
Q)
40
types of lutea l phase defi ciency were described : Type
<l. >
ilo ~ 30 ..----··· IV and Type V. These will be described later in this chap-
... --··
<l.
e: 20 .. -------···
_ ter because the data are being presented as they evo lved.
.. --·
"'
Q)
::;; 10 •. -----·· r=0 .8424
p= .0353
o +-.-~..-.-..-.-~~,..,..,-.-.-.-...,....~~~.,..,..,...,..,...,.,.,..,...,-,...,....-1
o 10 15 20 25 30 35 40
Peak Level of Estrad iol-17P (E2)
Figure 35-11: The 5-va lue sum of ta rgeted progesterone

profi le compared to the Peak periovulatory E2 levels. The cor-
relation coefficient r-0.8424 (From: Pope Paul VI lnstitute re-
search, 2004).
Table 35-3: D efinitio n of Luteal P hase
D eficiency by T ype
Mean 5-value Targeted Progesterone Profi le DEFINITION
Compared to Peak Periovulatory Estradiol -17p (E,) Levels
15 -r-------------------~
.--·· Type 1
..-·· Short post-Pea k The post-Pea k phase is short
"'e: .---··
.------~ (luteal) phase (.:;: 8 days in duration)
"'
Q)
::;; estimating a short luteal phase .
'.:j" --- --------··· -------------------------------------·
e-§,
Q)
2,,,_ e:
10
-------·
The last progesterone level is
.:;: 2.0 ng/ml
w~
~~
..-··································· Type 11
~::¡
<l. ro Suboptimal The post-Peak phase is normal
-"' > progesterone profile in length but the progesterone
IB~
<l. profil e (P+3, 5, 7, 9, 11 ) is clearly
..!. . / /./ . /
subopti mal.
"'o
<l.
r= 0.8148 Type 111
p= .0483 Late luteal defect The post-Peak phase is normal
O +r..-.-..-.-~~~~rr""'-.-.,..,..,,..,..,-,-,-,-,..,......,......,....~~~-.-1
in length but the progesteron e
o 10 20 30 40
profil e (P+3 , 5, 7, 9, 11)
Peak Level of Estradiol-17P (E2)
shows an abrupt drop (.:;: 50%) on
Figure 35-12: The mean 5-value targeted progesterone pro- P+9 and P+1 1.
file compa red to Peak periovulatory estradiol-17P (E 2) levels.
The correlation coefficient r-= 0.8148. (From: Pope Paul VI
432 Th e Medical and Surgical Practi ce of NaProTECHNO LOGY
Typel Oefici encies in Luteal Phase Progesteron e

Short Post-Peak Phase (Type 1) (N=20)
- Normal Controls
In the Type l lutea l phase deficiency whi ch is defi ned 15 15.7
- Type l Oefect
mostly on the length of the lutea l phase (as estimated ~

14 .4
by the length of the post-Peak phase) and th e produ c- i

0
13.6
ti on of proges terone by th e corpus luteum, the post- ~

~ 10
Peak progesterone and E 2 p rofiles and periovulatory E 2
profiles are shown in F igures 35- l 3a through 35- l 3c. In
j 9.4
8.1
this set of profil es, a marked ly decreased prod uction of ~

Q.
E 4.9
proges terone begins on Peak +5 of the cyc le and con- ~
"'
tinuing a li the way th ro ugh Peak +9 and Peak + 1 1 1
(p<.000 1). The E 2 profi le tends to para llel thi s, a lthough
not as dra matica ll y. In fac t, the leve ls on Peak + 3 and p-value .081 9 l<.00011 l<.0001 1
P•3 P•S P•7 P•9 P+ 11
Peak+5 are significa ntly hi gher than the contro l gro up Days Post-Peak
(which are made up of a group of women who have Figure 35-13a

comp letely nonnal ovul ations by ul trasound parameters:
a mature fo ll ic le whi ch compl etely ruptures and has a
pos itive cumulus ooph orus) . By Peak +7, the E2 leve ls Deficiencies in Luteal Phase Estrad iol -17 ~
Short Post-Peak Phase (Type 1) (N=20)
begi n to decrease and continue on a dow nward trend
- Normal Controls
fo r the remainder of the cycle. The peri ovulatory E2 lev- 15 - Type 1Defect
e Is in th is same group of women were strikingly de-

i
12.5
12.0
creased (F igure 35- l 3c) suggesting ab norma l fo lli cul ar 12.0 12.0
fu nction as at least one pre-ex isting qua!ity of a Type I ~

0
9.8
~ 10
luteal phase defi ciency. =
....
8.8 9.0
:§
.,,
~
w
Typell E
2
4.4
$
.,e
ro
A hallmark of the Type II lutea l phase defic iency is a ::;
p-value l.0035 I l .0276 I 1 oos I 1< .0001 1 1.0119 I

normal length lutea l phase (as estim ated by a normal
P•3 P•5 P•7 P•9 P+11
length post-Peak phase) w ith a marked ly suboptimal Days Post-Peak
lutea l phase progesterone profil e. The endocrin e pa-
Figure 35-13b
ra meters of thi s luteal ph ase type are presented in F ig-
ures 35-l 4a thro ugh 35- l 4c. The lutea l phase progester-
one profi le in thi s group of patients is shown to be
Periovulatory Estradl ol-17~ Levels
markedly suboptim al (p<.000 1). T he postovulatory E2 Normal Controls vs. Type 1 Luteal Phase Oeficiency (N=20)
leve ls, however, are not remarkabl y diffe rent fro m the
- Normal Controls
30
contro l group although the Peak + 3 and +5 leve Is aga in - Type 1Oefect
26.0
are higher than the contro ls and th e leve ls at Peak +9
25
and Peak + 11 are decreased. The periovulatory E 2 pro- :;
fil e fo r this group, however, is once aga in sign ifica ntl y ~ 20

decreased suggesting that abnorma l fo lli cular fun cti on =
:::
"i;
genera ll y precedes a Type 11 lutea l phase dysfun cti on. 15 15
~
UJ
(/)
.,~ 10
Type/11 6.8
p-value NS NS
The third ty pe of luteal ph ase defic iency revea Is a stri k- EP-4 EP-2 EP EP+2
in g decrease in proges teron e prod ucti on by the corpus :!: Days from Estradiol Peak (EP)
luteum in the second half of the lutea l ph ase . T hi s is Figure 35-13c

best demonstrated by ca lcul ating a relative proges ter-
one rati o (RPR) and is demonstra ted in Table 35-4. T he Fig u res 35-13a through 35-13c : The post-Peak progester-
RPR is ca lculated by using the highest post-Peak proges- o ne , e stra d iol - 17 ~ profi le (13a a nd 13b) and the periovu latory
estradio l profi le (35-13c) in patients w ith a Type 1 luteal phase
terone leve! of the p rofil e as the denominator and di vid-
defi cien cy (From : Pope Paul V I ln stitute research , 2004).
Deficiencies in Luteal Phase Progesterone ing into each of the Peak + 3, 5, 7, 9 and 11 va lues. For a
Suboptimal Progesterone (Type 11) (N=115)
Type III lutea l ph ase defect to be defi ned, there must be
a decrease in progesterone of greater th an 50 percent
:J 15
E on Peak +9 and 11 . ln example A ofTable 35-4, a normal
f progesterone profi le is shown and the RPR on Peak +9
"'
~ 10
~
9.4
is 0.63. Thi s does not meet the defi nition of a Type llJ
e 8.5
luteal phase defect. Ln example 8 , the RPR on Peak +9 is
8.3 8.1
~ 0.36, thus defi ning a late luteal defect.
"
~
6.7 6.5
Q_
E
2 5 3.8
In Tab le 35-5 , a gro up of 40 patients with a late luteal
"e
(f)
defect is shown in comparison to the hormone control s.
""'
::¡ The average RPR on Peak +9 fo r the Type IlI lutea l phase
p-value defect was 0.35 . The di ffe rence between the RPR on
P•3 P•5 P+11
P•7
Days Post-Peak
P•9
Peak +9 and Peak + 1 1 of the normal hormonal contro ls
and the Type lII luteal phase defect is statistically highly
Figure 35-14a significa nt (p<.000 l ). In addi tion, interestingly enough,
the Peak +3 RPR is statistica ll y higher in thi s group .
Th is is shown graphi ca ll y with the bar graph in Figure
Deficiencies in Luteal Phase Estradiol-17P
Suboptimal Progesterone (Type 11) (N=11 5) 35-15.
- NC>mlal Conlrols
- Type 11 Oefec!
The post-Pea k progesterone and E2 profiles and the
peri ovulatory E2 profil e fo r a Type IIl lutea l phase de-
fect are shown in Fi gure 35- l 6a through 35- l 6c. The late
decrease in progesterone is clearly seen in Figure 35-
l 6a. Thi s is para ll eled by a late decrease in E 2 as we ll.
Agai n, the E2 leve Is are hi gher on Peak + 3 and Peak +5
than they are in the normal controls. They are also higher
on Peak +?.
p-value NS NS
Wh en looking at the periovulatory E2 profil e, however,
P•3 P+S P+7 P•9 P+11 on a point-by-point bas is, there is no statisti ca lly sig-
Days Post-Peak
ni fica nt diffe rence. This suggests that the decrease in
Figure 35 -14b progesterone in a Type 111 luteal ph ase defect (whi ch is
seen in women with infe rti lity and mi sca rriage, along
Periovulatory Estradiol-17P Levels

Normal Controls vs . Type 11 Luteal Phase Defi cie ncy (N=115) Relative Progeste rone Rati o (RPR) by
Contro l Group • and Late Luteal Defect O (Ty pe 111)
- Normal Controls
30 - Type 11 Defecl
• RPR Norma l
26.0
D RPR Late Luteal Delect
:J25 -
~
R-20
o.
0.75
:Q
"¡;;~ 15 0.56
w 0.52
E
~ 10
10.1
6.8
p-va!ue NS
o - .....__ .___ '--- - ..__ - l....- -
EP-4 EP-2 EP EP•2 ,....w_, P+5 P+7 P+9 P+ 11

± Days from Estradiol Peak (EP) P·values ~ 0.059 NS 1<.OOO t l 1 <.oooq
Days Post·peak
Figure 35-14c
Figures 35-14a through 35-14c: The post Peak progester- Figure 35-15 : Th e relative progesterone ratio (RPR ) by con-
one an d est radio l - 17 ~ profiles and the periovul atory estra- tro l group and patients with a late luteal defect (Type 111 ) (From :
d i ol - 17 ~ profil e (3 5- 14c) in patients with a Type 11 luteal ph ase Pope Paul VI lnstitute research, 2004).
deficiency (From : Pope Paul VI lnstitute research, 2004).
434 The Medica ! and Surgical Practice of NaProTECHNOLOGY
Table 35-4: Calculation Example of R elative

Progesterone R atio (RPR)
Ex:ample A Example B
Normal Post-Peak Late Luteal Defect
Progesterone Curve
Phase of Prog . Level Calculated Prog . Level Calculated
Cycle ng/mL RPR' ng/mL RPR'
P+3 8.3 0.48 8.2 0.57

P+5 14.9 0.86 12.9 0.90
2 3
P+7 17.3 1.00 14.3 1.00
P+9 10.9 0.63 5.1 [Q:ill
p + 11 6.2 0.36 3.3 [Iill
1. Calculated by using the highest post-Peak progesterone level as the denominator and
dividing intoeach of the P+3, 5, 7, 9 and 11 values.
2. In Example A, 17.3 ng/ml, being the highest post-Peak level, serves as the denominator.
3. In Example B, 14.3 ng/ml, being the highest post-Peak level, serves as the denominator.
Deficiencies in Luteal Phase Progesterone Deficiencies in Luteal Phase Estradiol-17P

Late Luteal Defect (Type 111) (N=41) Late Luteal Defect (Type 111) (N=41)
15.7 - Normal Controls - Nomlal Controls

15.7
- Type 111 Defect - Type IU Defect
:; _, 14.8
E 15 :E 15 14.4
o, Cl
.e,
.s
"'>
o; "'
~ 11.9 12.0 12.0
_," _," 10.8
"'-
"e,º ~ 10
8.8
9.9 9.8
:Q
*"e
Cl
c..
9.4
6.2
'O
~
¡;;
w
E 5.7
E
2 2 5
5
"e
.."" .
(/)
(/)
e
::;:
2.9
"
::;:
p-value l .0011 I NS NS 1<0001 1 l<.00011 p-value l .0004 I 1.0019 I l .0243 I 1.0103 I 1<00011
P+3 P+5 P+7 P+9 P+11 P+ 3 P+5 P+7 P+9 P+11

Days Post-Peak Oays Post-Peak
Figure 35-16a Figure 35-16b

Normal Controls vs. Type 111 Luteal Phase Defect (Type 111) (N=41)
- Normal Controls
30 - TypelllDefect
26.0
:::::¡ 25
¡
<e.20
....
o
'O
~ 15
w 12.8
E
~ 10 9.4
(/)
8.8
p-vatue NS NS NS NS
EP-4 EP-2 EP EP+2

± Days from Estradiol Peak (EP)
Figure 35-16c
Figures 35-16a through 35-16c : Th e deficiencies in progesterone and estradiol-17~ in a la te luteal defect (Type 111 luteal phase
defi c iency) and its correspo ndin g pe ri ovulato ry E 2 levels (Fig ure 35-1 6c) ( From : Pope P a ul VI lnstitute research , 2004).
Chapter 35 : Follicular and Luteal Phase Deficiencies 435
Table 35-5: Relative Progesterone Ratios (RPR)

by Control Group and Late Luteal Defect (Type lll)
Late Luteal Oefecf

Oay Hormonal Control s TJ1Qe 111
Post-Peak Mean so n Mean so n p-values'
P+ 3 0.56 0.24 57 0.69 0.21 40 1 00521
P+ 5 0.83 0.18 57 0.89 0.14 40 .059
P+7 0.87 0.15 57 0.87 0.22 40 .707
P+9 0.75 0.20 56 lo 351 0.12 40 1<.0001 1
P+11 0.52 0.25 55 lo16 I 0.10 37 1<.0001 1
1. Compa ring the RPR of normal oontrols vs. those with Type 111luteal phase defect (Student t-test).
with premenstrua l syndrome and bleeding abnorma li- lntegrated Progesterone Assessment
ties) is not secondary to abno rmal fol licular function ,
but rather an iso lated event related to the last half ofthe By summing the five va lues of progesterone or E 2, an
funct ion of the corpus luteum. estímate of the in tegrated progesterone production
during the course ofthe lutea l phase can be determined.
Furthermore, that can be compared to those cycles th at
Summary are con sidered nonnal. This is shown for both progest-
erone and E2 for both the sum and the mean of those
A summary ofthese 328 patients is shown in Table 35-6. five va lues in F igures 35-l 8a and 35-l 8b. The progest-
A bnormal luteal function was identifi ed using this ap- erone sum and mean for ali three types of luteal phase
proach in 53.7 percent of the cycles. A Type 1 luteal deficiency are sign ifi can tl y decreased. However, on ly
phase deficiency was observed in 6. 1 percent, Type 11 the sum ofthe E2 is sign ifi cantly decreased.
in 35. l percent, and Type IlI in 12.5 percent. A summary
of the three types of lutea l phase deficiency compared The data for the preovulatory E2 sums and means, are
to the nom1al controls is shown in Figure 35- l 7a through classified by the three types of luteal phase deficiency
35-l 7c. and are shown for both a 3-va lue and 4-value sum and
mean in Figures 35 - l9a and in Figure 35 -1 9b. The E2
levels during the preovu latory phase of the cyc le are
significantly decreased in Type 1 and Type IT luteal phase
deficiencies when looked at from the point ofview of an
Table 35-6: lncidence of Luteal Phase estimare ofthe integrated periovulatory E2 levels . Thi s
Deficiency by Assessment of Post-Peak is shown for both the sum s and the means for three and
Progesterone Profile in P atients with Infertility
fou r va lues . These types of lutea l phase deficiencies
(N = 328)
ex ist across the board w hen it comes to other causes of
Type of deficlem:y n % infertility that wou ld be cons idered anatomic or organic
in nature .
Type 1
Short post-Peak phase 20 6.1
Type 11 In Ta ble 35-7, the inc idence ofType 1, JI and Ill luteal
Suboptimal progesterone profile 115 35.1 phase deficiencies are shown relative to patients w ho
Type 111 ha ve a laparoscopically-known diagnosis of endometrio-
Late luteal defect 41 12.5
sis, pelvic ad hes ions, proxima l tuba! occlus ion or distal
Total additional cycles evaluated 152 46.3
tuba! occlusion . The overall incidence ofabnormal luteal
Totals 328 100.0 phases in thi s group w hen broken down in this fashion
was 57.2 percent. The hi ghest degree of abnom1ali ty
was in those patients w ith di stal tuba! occ lusion (but it
did represent on ly a small gro up, N=9). However, the
degree to which these abno rma liti es occurred was very
Deficiencies in Luteal Phase Progesterone Deficiencies in Luteal Phase Estradiol-17P

By Type of Defect (Types 1, 11 , and 111) By Type of Defect (Types 1, 11, and 111)
..-e Normal Controls

e--e Type 1Defect
Type lt Defect
....-e Type 111 Defecl
15.7
8.8
9.4
8.1
Type 1 .0055 .0276 .005 <C:.000 1 .0019

Type 1 0819 <.0001 <.0001 < 0001
p-values Type 11 .0114 NS NS .0208 .0177
p-valuesf-T~ype~"+---+--'-"--+--~-+--'-'--'--+--"=-~
<0001 <.0001 <0001 <.OOC)1
Type 111 .0035 0019 .0243 <0103 <.0001
Typell1 <,0001 NS NS <.0001
P+3 P+S P+7 P+9 P+1 1
P+3 P+S P+7 P+9 P+11
Days Post-Peak
Days Post-Peak

Normal Controls vs . Types 1, 11, and 111 Luteal Phase Deficiency
.......-. Normal Controls

30 e-e Type t Defect
Type H Defect
26.0 ......... Type 111 Oefect
-
..J
25
:E
~
;;;:: 20
l'-
0
~ 15
1ñ 12.8
UJ
E
2 10
8.8
c1l
EP-4 EP-2 EP EP+2

:!: Days from Estrad iol Peak (EP)
Figure 35-17c
Figures 35-17a through 17c: A summary graph of the deficiencies in luteal phase progesterone and estradiol- 17P in Types 1,
11and 11 1luteal phase defi ciency (Figure 35-17a and 17b) and the periovulatory E2 profiles far the same th ree cond itions (Figure
35-17c) (From : Pope Paul VI lnstitute research , 2004).
Sum and Mean of Postovulatory Progesterone (P) Profile Sum and Mean of Postovulatory Estradiol-17P (E 2) Profile
(5-Values) in Patients with Various Types of Luteal Phase Deficiency (5 values) in Patients with Various Types of Luteal Phase Deficiency
Sum Mean
53.2 ~2 ~2
61.2 Sum 12.3 Mean
E:ª
10.7 .!.!!:9
-g,
~o
1
~ 10-
;.Q.:4 -9'
CD
~
5()..
~
-9'
CD
10-
E
e ~
V o ~9 o
1ñ '5 '5
V !!'
C> !!'
e
a. ?.E ~
1ñ
w 1ñ
UJ
o o ,,_ o
E 5
§ ~
(/)
§
(/) (/)
e e e
m m m
V V
::; V
::; ::;
:~=~ ~ T~ll T~lll

Normal Type 1 Type 11 Type 111
;:=~~~~ ;::~ ~ ~
Sum of Postovulatory E2 Prolile
p-value NS NS
Mean Postovulalory ~ Profile
NS
Sum of Postovulatory Progesterone (P) Mean PoslovulalOl'Y Progeslerone (P)
Profile (5 values) and luteal Phase Type Profile (5 values) and Luteal Phase Type (5 values) and Lutea1 Phase Type (5 values) and Luteal Phase Type
Figure 35-1 Ba Figure 35-1 Bb
Figure 35-18a and 35-18b: The sum and mean of the postovulatory progesterone profile {five va lues) in patients with Type 1,
11and111 luteal phase deficiency. (Fi gure 35-18a) and the same sum and mean far postovu latory estradiol-17P levels (Figure 35-
18b} (From : Pope Paul VI lnstitute research , 2004).
Chapter 35 : Follicular and L u t ea l P hase Deficie ncies 437
Table 35-7: lncidence of Luteal Phase Deficiency

by Disease Entity and Regular Cycles
Type of . Endometriosis Pelvlc adheslons PTO' OTO' Totals

l ut eal pha se n % n % n % n % n %
Normal 121 44 .0 8 42 .1 6 35 .3 2 22 .2 137 42 .8
Abnormal 154 56 .0 11 57 .9 11 64 .7 7 77.8 183 l 57.2 f
Type 1 31 11 .3 5.3 5.9 2 22 .2 25 10.9
Type 11 99 36 .0 9 47.4 10 58 .8 4 44.4 122 38 .1
Type 111 24 8.7 5.3 o O.O 11 .1 26 8.1
Totals 275 100.0 19 100. 1 17 100.0 9 99 .9 320 99.9
1. PTO = Proximal tubal occlusion.

2. OTO = Distal tubal occlusion.
Preovulatory Estradiol -17P Levels by 3- and 4-Value Sums

Normal Controls vs . Type 1, 11, 111 Lutea_I D_e fects high in ali ofthe other groups as well.
70 3 Value Sum 4 Value Sum
Yarious ultrasound and endocrine parameters are shown
60 for these types ofluteal phase deficiencies in Tab le 35-
:g, 53.6 8. A comparison ofthe size ofthe deve loping follicle at
a. 48.8
CfJ
::;;;
50
the time of rupture, the maximum size of the cumulus
:::>
CfJ
40
oophorus, the day 5 FSH leve! and Peak + 7 (m id- luteal
"',.:. phase) prolactin, FSH and LH levels were ali compared
..J
o 30 to the grou p who had normal ovulations by ultrasound.
o
<{
a: There were no statistically significant differences ex-
>-
CfJ
20
w cept in the Type Il luteal phase deficiency which had a
10 significantly decreased ovarian follicle size (2.3 vs. 2.1
cm, p=.0014) anda decrease in the mid-luteal phase LH
p ~[§] .1992
leve! in those patients with a type !ll luteal phase defi-
TY PE TYPE TYPE
1 11 11 1 ciency (4.6 vs. 2.8mIU/mL,p=.O15).
Figure 35 -19a
Preovulatory Estradiol-17p Levels

by 3- and 4-Value Means
Normal Controls vs. Type 1, 11, 111 Luteal Defects
20
3 Value Mean 4 Vatue Mean
In this current age ofmanaged care and cost effective-
17.9
ness, phys icians are always interested in knowing what
is the least amount necessary to make a diagnosi s. In
~a.
<J)
15
Tables 35-9 and 35- lO, the results ofthe sums and means
z
ili::;;; of a limited progesterone profile performed on Peak +5,
lll 7 and 9 are shown for the different types of luteal phase
~ 10
...J
o deficiency. The normal mean for these three levels was
6 44.1 and for the Type I, 11 , and lIJ luteal phase defi-
<
a:
>-
~ 5
ciency, each ofthem hada significantly decreased sum
and mean for those three values suggesting that a lim-
ited profile might be useful in making this diagnos is.
This is graph ically presented in Figures 35-20a and 35-
20b. lt should be pointed out, however, that it may be
F i gure 35- 19b difficult, in fact practica! experience suggests thi s, to
Figure 35-19a and 35-19b : The three and four value sums differentiate a Type llI luteal phase deficiency from a
and mea n s for th e pe riovu latory estradiol-17~ levels in nor- Type II with on ly a limited profile.
ma l co ntro ls , Type /, 11 and 111 luteal phase deficiencies ( From :
Pope P a u l VI lnstitute research , 2004).
438 The Medical and Surg ic al Practice o f Na Pr oTE CHNOLOG Y
Table 35-8: U ltraso und and E ndocrine Parameters ofType l, ll, and lll Luteal Phase D eficiencies 1
P+7
Foll icle size Maximum CO Da}' 5 FSH Prolactin FSH LH
n cm n mm n mlU/m L n nglm l n m lu/m l n mlU/m L
Control 57 2.3 54 4.3 29 8.1 55 13.7 55 3.9 55 4.6
Type 1 15 2.3 6 4.4 8 9.1 17 17 .2 18 3.8 17 3.7
Type 11 82 [g 64 4.6 48 8.4 111 12.4 111 4.2 109 4.6
Type 111 37 2.2 20 4.1 17 9. 1 38 12.3 37 3.6 35 ~

1. From: Pope Paul VI lnstitute research, 2004 .
2. p=.0014 , t-test
3. p=.015, t-test
From: Pope Paul VI lnstitute research, 2004.
Sum of Limited Progesterone Profile (3 Values)

By Type of Luteal Phase Deficiency
50
Table 35-9: Mean of Sums, Limited

Progesterone Profile P +5, 7, 9 by T ype of
36.4
Luteal Phase D eficiency
Mean of Sums Limited P Pr ofile

23.3
·Mean
Type of luteal phase of Sums so
n p·value' 17.2
Hormonal con trols 44.1 12.77 56

Type 1
Short post-Peak phase 17.2 5.04 14 1 <.0005 I
Type 11 p~= ,::-0~1 ~ ~

Suboptimal progesterone 23 .3 5.87 115 1 <.0005 I Su m Of Umited Progesterone Profile (3 Va lues)
By Type Of Luteal Phase Deficiency
Type 111
Late luteal defect 36.4 8.76 41 1 <.0025 I Figure 35-20a
1. Student t-test, when oompared to 3-value sums of hormonal correlates.
Mean of Lim ited Progesterone Profil e (3 Values)

15 14 .7
12. 1
~
.s 10
Table 35-10: M ean of Limited Progesterone Profile "ee
P+5 , 7, 9 by T ype of Luteal Phase D eficiency "
1ñ
7.8
~
o.. 5.7
Mean of Limited P Profile e
Mean 3l
::;
Type of luteal phase of Sums so n p -value'
Hormonal controls 14.7 4.25 56
Type 1
Short post-Peak phase 5.7 1.68 14 l<.0001 I ,..lml,
l..!.J!QQ!J ~
,Il<lli..!!.,
~
,Im..!!\
Mean Of Limlted Progesterone Proflle (3 Values)

Type 11 By Type Of Luteal Phase Deficiency
Suboptimal progesterone 7.8 1.96 115 l<.0001 I
Type 11 1
Fi gu re 35-20b
Late luteal defect 12.1 2.92 41 l<.0001 I Figu re 35-20a and 35-20b : The sum and mean of a limited
1. Student t-test, when comparad to 3-value sums of hormonal correlatas. progesterone profile (three values- Peak +5 , 7 and 9) by
Type 1, 11 and 111 luteal phase deficiency (From: Pope Paul VI
Peak +7 progesterone and E2 leve Is are often used in Type IV Luteal Phase Deficiency _ _~
screening the luteal phase. Thi s would not be co nsid-
ered adequate for making a di agnos is of either a Type 1, A number ofyears ago, Ku suhara 49 described a type of
11 or 111 luteal phase defici ency. However, in using it to lutea l phase defici ency in whi ch the plasma progester-
screen the luteal phase, it appears to be adequate. Th e one leve ls were low only in the earl y portion of the
mean of the Peak + 7 progesterone and E2 leve Is fo r a lutea l phase. When th is was first described, it was nota
Type 1, 11 and 111 luteal phase defi ciency are graphica lly pattern th at had been observed at th e Pope Paul VI
presented in Figure 35-21 a and 35-2 1b. The Pea k +7 l nstitute. More recently, however, that pattern has been
progesteron e levels are signifi ca ntl y decreased fo r observed, although it is not common. lt is shown, for a
the Type 1and II luteal pha e defi ciencies. They are not case presentati on, in Fi gure 35-22a th ro ugh 35-22c. In
decreased for the E2 leve! in the Type 11 lutea l phase th is parti cul ar case exampl e, the post-Peak progester-
defi ciency (which is consistent with the profil es that one pro fil e begins slow ly and reaches its Peak leve! on
ha ve previousl y been shown). A Peak +7 bl ood draw as Peak +9 and then decreases. The post-Peak E2 profil e in
a screen for a Type II 1lutea l phase defi ciency, however, thi s sa me pati ent is remarkabl y dec reased (Figure 35-
will not make that diagnosis. 22 b) and the periovulatory E2 profil e (Fi gure 35-22c) is
also signifi ca ntl y suboptim al. Further evaluation ofthis
type of defi ciency has not yet been carried out and its
actual incidence is unknown . lt is reported here because
Comparison Mean P+7 Progesterone (P) Levels it has been observed and should be studi ed furth er.
15.7
14.5
Type V Luteal Phase Deficiency _ _~
~
.s When we first rev iewed th e basic corre lates ofthe folli-
"ee 10
"
;;; 8 .3
cul ar and lutea l phase, it was identifi ed that there was a
1J, very cl ose stati stical correlati on between the Peak leve!
e
a.
.
e
~ 5
4.9
of peri ovul atory E2 and the sum and mean ofth e post-
ovul atory E2 leve!. However, as clinica l ex perience was
deve loped, it was found that there was a group of pa-
tients who appeared to have an iso lated postovul atory
~ E2 deficit. Thi s group was identi fied in th eir bas ic hor-
~
Mean P+7 Progesterone Levels And Type Of Luteal Phase Defect
mone eva luati on pri or to being treated and they were
Figure 35-2 1a also identifi ed at the time of treatment when they did
not respond to norm al luteal phase timul ati on. For ex-
ampl e, as the cycle is stimulated with clomiphene, the
Comparison of Mean P+7 Estradiol -17~ (E,) Levels
By Type of Luteal Phase Deficiency postovul atory (Peak +7) E2 levels did not correspond-
15 14.8 in gly res pond even th ough progesterone did . Further-
more, if HCG was used to support the post-Peak phase,
12.0 12.4 th at also tended not to stimul ate the luteal phase E,
profil e. -
9.0
Beca use of thi s, another eva luati on was undertaken.
Thi s tim e, the eva luati on was begun by lookin g at what
appea red to be suppressed postov ul atory E2 leve ls.
Tak ing that group of pati ents, th e progesteron e leve Is
fo r that lutea l phase and the prev ious fo llicular phase E,
leve ls were eva luated. When thi s was undertaken, ~
new phase of lutea l phase defi ciency was identified.
::S":! e@ r:; 11 ~
Mean P+7 Estradiol-176 (E2 ) Levels And Type of Luteal Phase Defect
We have ca ll ed thi s a Type V lutea l phase de fici ency
and it is marked by a predominant decrease in luteal
Figure 35-21 b
pha e E2 producti on in the fa ce of what is otherwise a
Figure 35-21a and 35-21b : The comparison of !he mea n norm al E2 profil e in the preovul atory phase of the cycle.
Peak+ 7 progesterone and e stradiol - 17 ~ leve! comparin g nor- These pattern s are shown in Figures 35-23 , 35-24 and
mal controls to Type 1, 11and111 luteal phase deficiencies (From: 35-25.
Pope Paul VI lnstitute research, 2004).
In Figure 35-23 , the E2 profile is markedly suppressed contro l group, they are not nearly as suppressed as
during the luteal phase ofthe menstrual cycle and shows what one wou ld find in a standard Type II luteal phase
up statistically lower than the control group ori n a group deficiency.
of other patients who were a lso studied in this fashi on.
Finally, in Figure 35-25 , the periovulatory E 2 leve ls are
In Figure 35-24, the progesterone leve ls are shown fo r shown for each ofthese three groups. The Type V luteal
thi s group are shown and whi le they are lower than the phase E2 deficiency has actually a sli ghtly hi gher (when
Normal Values, Post-Peak Progesterone Profile Normal Values, Post-Peak Estradiol -171} Profile
Sum and Mean (Controls, N=57) Sum and Mean (Control, N=57)
National Hormone Laboratory, Pope Paul VI lnstitute 100 National Honnone Laboratory, Pope Paul VI lnstitute 80
25 24 76.18
~-
1 ...... P•!ient 90 70
~ •-. Low 86.0
~ 20
.
# . . . ..... ••
• ··· Low
-• High
~ """ ~
•.. -------.
20 80 60
e
e 1s 70 .,
~ 16 ···-······• ------ ..... ~ 50
53.4
~ 6 1.2
o
;:; 12
_... 12 12
12.24 60
I ,º 8.1
50
~
w
8
6.7 5
.8
1068 40
31 6
E
~
"'
5 .. " 75 7 12 40
36.4
35 6
E
2
~ 4
4 ~
4
632 . 30 1 30.4
20
30
06
Profile 10 Pro file
20 P+3 P+5 P+7 P+9 P+11
P+3 P+S P+7 P+9 P+11 Pro file Sum Pro fil e Sum
Targeted Post-Peak Progesterone Proflle Mean Targeted Post-Peak Estradlol-17 ~ Proflle Mean
Normal Values, Periovulatory Estradiol-171} Profile

3- and 4-Va lue Sum and Mean
National Hormone Laboratory, Pope Paul VI lnstitute so
350 .,..-~~~~~~~~~~~~~~~~~~~
::¡- 300
~ -'
...... Pauent 70
69.2
:a, • ·.. l ow
• ·.. High
60
.,S 2SO
=
~ 53.6
~ 200 50
';; 17.87
~ 150 40
38.0
w
E 100 30
8.77
~ 20
263
10 Proflle
E-4 E-2 Peak E) E•2 Mean Sum
Targeted Periovulatory Estradiol·17P Profl le 3-Value
Figure 35-22c
Figure 35-22a through 35-22c: A case presentation of a patient with a Type IV luteal phase progesterone profile (Fig ure 35-
22a) . The post-Peak estradiol profile is also clearly suboptimal and the periovulatory E, profile is distinctly suppressed (From :
Pope Paul VI ln stitute research, 2004).
Post-Peak Estradiol-17P Levels Post-Peak Sums and Means

Type V Limited Phase Deficiency LPD-V
Control {n=57) vs . LPD -V (n=36) vs. Other (n=36) Control (n=57} vs. LPD-V (n= 36) vs . Other (n=36)
20 20
-+- Control • Con1rol
LPD·V D LPD·V
-9- 0 lher • rnher
14.3 15
1p =.03 1 1••.0121
..J ..J
~ ~ ~
60.7 12.5
"'- 11.4 "'-

.... o.
.... §:
10 9.8 50 10
o 9.5 o ::<
'O 8.8 'O
e 7.8 7.8
;¡;
e ""
~
~
;¡; 6.7
w 6.8
w
r
5.7
Olhe< LJiQ2Jl t@l~~[QQQ!J

LPO-V [QQ§J .004 ~ NS NS
P+3 P+S P+7 P+9 P+l 1

Sums Means
Days Post-Peak
1. Mann-Whllney U
Figure 35-23: A Type V luteal phase deficiency specifically rel ated to an isolated
suboptimal luteal phase E 2 profile (From : Pope Paul VI lnstitute research , 2004).
Chapter 35: Foll icu lar and Luteal Pha se Defic iencies 441
Post-Peak Progestero ne Levels Su ms and Means of Post-Peak

Ty pe V Luteal Phase Deficiency Progesterone Levels --LPD-V
Control (n=57) vs . LPO -V (n=36) vs. Other (n=36) Control (n=57) vs. LPD-V (n=36) vs. Other (n=36)
20 20
-+- Control • Control
LPD·V D LPD-V
_._ Other • 01her
15.7
15
-g ...J
.8"
E 61.2 12.2
g. g.
IR
" e"
e
~ 10 50 10 ~
!e ~C>
8.1
e ~
o._ o._ 3
r
Other ~ NS NS (]'ill NS
LPD-V NS NS ~ ~ NS
o
P+3 P+5 P+7 P+9 P+11
Sums Means
Days Post-Peak
Figure 35-24: The progesterone profile in patients with a Type V luteal phase
deficiency (From : Pope Paul VI lnstitute research , 2004).
Periovul atory Est rad i ol - 1 7 ~ Levels 3-Value Sum s and Mean s

Control (n=21) vs. Type V LPO (n=36) Control (n=2 1) vs. Type V LPO (n=36)
35 100
-+- Control • Conlrol
30.9 LPD- V D LPD-V 90
30 ---- Olher • 01her
28.9
80
...J
"2
"'e
"'-
~
o
'5
~
1ñ
UJ
25
20
15
15.2
14 .9 .
14.8
ff NS
54 .6
70
60
50
40
fJ)
"'2
3
m
!?.
¡¡¡
o.
Q.
:::j
E
2
12.8 "'"
en" 10 10.4 30 '&r
7.7
20
10
~
LPD-V NS NS
Other NS 8 ~
o
e2 2 Peak E
2
E2 +2
3 Value Sum 3 Value Mean
Relationship To Peak E2 Level
Figu re 35-25: The periovulatory E2 profile in a group of patients (N=36) with a

Type V luteal phase deficiency (From : Pope Paul VI lnstitute research , 2004).
considered point by point) E2 pro file, but the three-value

sum and mean fo r the periovulatory leve ls are not sta-
Table 35-11: The lncidence of the Vario us Levels of
ti stica lly di ffere nt from the controls. Thi s Type Y lutea l
Follicular Function in a Group of Patients with
phase deficiency is an important new selective defi-
lnfertility and R egular Cycles (N=104)
ciency whic h needs to be cons idered when looking at
the overa ll gro up of patients w ho might ha ve clini cal E2 Sum 1
signs or symptoms related to a luteal phase deficiency. Classificatfori (3) Type n %
Highly elevated ?. 64.9 AAA 7 6.7

Elevated 59.3-64.8 AA 13 12.5
Follicular Phase Function -----~ Mid-range 48.0-59.2 A 25 24.0
Decreased 42.0-47.9 B 23 22.1
In considering the follicu lar phase as a whole, there Very decreased .'.': 41 .9 e 36 34.6
appear to be differing leve ls offo ll icular function that
Totals 104 99.9
can be identifi ed when eva luating the hormone profil es
1. The 3-va lue periovulatory E, sum, ng/dl.
of this gro up of pati ents. In eva luating this, we ha ve From: Pope Paul VI lnstitute resea rch, 2004.
looked at fo llicular phase function and c lassified it as
100.0
Follicular Phase Deficiencies: Luteal Function With Progesterone Luteal Function With
Levels of Follicular Function By Leve! of Follicular Function Estradiol-17P By Leve! of
~ 90.0 (5 Value Sums) Follicular Function
:;
:; (5 Value Sums)
~ 80.0 ~ 80.0 :g, 80.0 .003
76.8
::> <.0001 .s .s
en 71.3
en 70.0 § 70.0 E 70.0 .017
Q)
::> <.0001 en ::>
en
65.0
e;; 61.9 Q) NS
59.5
> 60.0 6 60 .0 58.3 NS
56.2
~ 60.0
:;; e;;
"'~ so.o
53.0
~0001
;;;
g, so.o .043
>
"'so.o 48.5
NS
47.9
1ii 44.9 48.0 .025
:; !::>
a..
43.0 """'
Q)
.037
40.5
[;, 40 .0 <.0001 ";- 40.0
36.1 "'40.0
-~ Q)
::>
;;;
a.. o
""- 30.0 ~ 30.0 !_ 30.0
.... ....
o 20.0 - """':¡¡ 20.0 <5 20.0
~;;; ~o 10.0
'O
!ll
w 10.0 a..
(¡) 10.0
w
o.o 'T 'T 'T 'T 'T 'T 'T 'T

AAAAAA B C AAAAAAB C AAAAAA B C
n=7 n=13 n=25 n=23 n=36
Levels of Follicular Function
Figure 35-26 : The periovulatory E2 3-value sums and the postovu latory progesterone
and E2 5-value sums in patients with Type AAA, AA, A, Type B, and Type C follicular
phase function . The Type AAA, AA, B, and C are statistically compared to the Type A
sums. The Type A sums are consisten! with the normal endocrine function of a follicle
which ultrasound identifies as a mature follicle with a positive cumulus oophorus that
completely ruptures .
Leve/ AAA, AA, A, B, and C for simplicity purposes (Fig- luteal function first and then going backwards toward
ure 35-26). The incidence ofthese fi ve leve ls offol li cu- follicu lar function. This adds to the weight ofevidence
la r function and their definition are found in Table 35- supporting the need to evaluate both phases of the
1 1. Furthermore, a summary of the characteristics of cycle and where indicated, treat the di fferent phases
these five levels offollicular function are found in Table appropriately.
35-12. The post-ovulatory E 2 profiles generall y parallel
the five level s of fo lli cu lar function. However, the
progesterone profiles are low on ly in the Type B and C Pregnancy Progesterone Levels in Luteal
follicu lar function pattern . When looking at fo llicular Phase Dysfunction -------~
function prospectively re lative to lutea l function , one
sees its own di stinct pattern as opposed to looking at We ha ve also eva luated the progesterone production
during the course of pregnancy in those patients who
start w ith a Type !, 11 and l!I lutea l phase dysfunction .
Table 35-12: Summary of the Characteristics of These results are shown in Figures 35-27, 35-28 and 35-
Various Levels of Follicular Function 29 . With a pre-exi sting and documented Type I luteal
and Types ofLuteal Phase D eficiency phase deficiency, the progesterone production during
Level of PeríovuJatory
the pregnancy fol lowing that is signifi cantl y decreased
Follícular E 2 Sum 1 Post-Peak 5-value Sums throughout the en tire co urse of pregnancy. With a Type
Functíon (3) Prog. E, 11 luteal phase deficiency, the leve ls are decreased dur-
AAA tt normal tt ing the m iddle trimester on ly and in a Type III luteal
AA t normal t phase deficiency, the levels are not significantly de-
A mid-range normal mid-range creased at al i. These findings may be important in man-
B ¡ ¡ mid-range
aging subsequent pregnancies in patients with these
e ¡ ¡ ¡
types of luteal phase deficiencies and is better described
Type of Luteal in the chapter on recurrent spontaneous abortio n.
Phase Deficiency
1 ¡¡ H H
11 ¡ H mid-range
111 mid-range ¡(late) mid-range CREIGHTON MODEL and
IV apparently H ¡ (ea rly) apparently H NaProTECHNOLOGY Correlates --~
V mid-range mid-range to t H
1. Ba sed on a single case. More evaluation is necessary.

In deterrnining the length ofthe luteal phase, there are a
From: Pope Paul VI lnstitute research, 2004. few very spec ific ways in which thi s can be accom-
Progesterone Levels in Pregnancy

plished . One is to measure th e LH surge and measure
148.4
150.0
Previous History of Type 1 LPD (n=15) from that point forward to the onset of the next men-
vs. Norm al Controls (n=109)
strual period . Another is to measure serum progester-
:J • Normal controls
E CJType l LPD
11 3 1
one levels and identify the point of change in the proges-
e;, 103.4
.s 100.0 87.3
terone curve as the corpus luteum forms and count un-
"ee: til the beginning ofthe next men strual period anda third
73.8
u;" is to do daily ultrasound exam inations to observe for
"e
Cl
Q. so.o the growth and deve lopment ofthe follicle and its sub-
sequent rupture and then co unt until the beginning of
the next menstrual flow. In each of these cases, it re-
o.o
quires either daily blood samp ling or daily ultrasound
2-6weeks 6-12weeks 14-18weeks 2().24weeks 26-JOweeks 32-38weeks
exam inations, both ofwhi ch are too cumbersome whil e
p-value NS
at the same time being unnecessary.
Mea n Pro gesterone - 6-week intervals
Figure 35-27 : The mean progesterone levels during preg-

nancy at six week ly intervals in patients with a pre-existing A study was completed on the clinical estimates of the
Type 1 luteal phase deficiency (N=15) (From: Pope Paul VI luteal phase using the post-Peak phase as the indicator
lnstitute research , 2004). and five different basal body temperature phases. The
data on thi s is shown in Figure 35-30. The very best
corre lati on to a clinical esti mate ofthe luteal phase was
1SO.O 148.4 1464
Previous History of Type 11 LPD (n=94)
vs. Normal Controls (n=109) CUNICAL ESTIMATES OF THE LUTEAL PHASE
:J - Normal con trols 20
E
....
CJ Type l LPO 11 POST·PEAK PH>.SE o POST-OIP PHASE •
c. •
..•.
103.4 104.7
.s 100.0
"oe:
~
u;
""'e
73.8 12
'º
..•.~· • ••
••
• •
Q. so.o
•• R =O 82 R = 067
20
o.o 1e
PAEMENSTRUAI.
PHASE • PQST.flAST RISE •
:$º.i:r
2-6weeks 8- 12weeks 14- 18weeks 20-24weeks 2S.30weeks 32-38weeks
p-value / .0127 ! NS .06 NS NS 10 (MEAN-NTERCEPT)~:

1.1· PHASE I
Mea n Prog esteron e • 6-w eek intervals 1•
.•.. .
: •
...• •0
. .•
12 •• • · · •
Figure 35-28 : The progesterone profile during pregnancy at 10 •
six weekly intervals in patients with a pre-existing Type 11

luteal phase deficiency (N=94) (From : Pope Paul VI lnstitute
• . R:: O 71 R • O 66
research , 2004) .
....
20
POST-NADIR . ... POST-COVEAUNE ••
•
1SO.O
Previ o us History of Type 111 LPD (n=34)
1484145 7
,,
14
PHASE
.:1 rij!f·:i• · PHASE
. •tüf!
• •
• .1, ••
. .. .•
vs. Normal Controls (n=109)
'º •
.
:J • Normal controls
E CJType 1 LPO
e;,
.:.. 100.0
103.4103.3 • •
"ee: R =O 87 R =062
!!!
"' 2 4 6 1 10 12 14 16 18 20 2 4 11 1 10 12 M lfí ti 20
e"
Cl
LENGni OF PHASE (OAYS) LENGni OF PHASE (DAYS)
Q. so.o
Figure 35-30 : The cl inical estimates of the luteal phase com-
paring on the vertical axis the length of the luteal phase as
determined by indirect hormonal parameters and on th e hori-
o.o zontal axis as determined by various cl inical estimators in-
2-6weeks 6-12weeks 14-18week.s 20-24weeks 26-JOweeks 32-38weeks
p-value NS NS NS NS NS
cluding the post-Peak phase in various basal body tempera-
ture systems , including the post-dip phase , premenstrual
Mea n Prog esterone - 6-week intervals
phase (mea n-interce pt) post-first rise phase, post-nadir
Figure 35-29 : The progesterone profile during pregnancy at phase, post-cover line phase. R = co rrelation coefficient (From:
six weekly intervals in patients with a pre-existing Type 111 Hilgers TW: Reproductive Anatomy and Physiolog y for the
luteal phase deficiency (N=34) (From : Pope Paul VI lnstitute FertilityCare™ Professional . Pope Paul VI lnstitute Press ,
research , 2004). Omaha , NE 2002).
the measurement of the post-Peak phase of the men- Mucus cycle seores ha ve also been looked at compar-
strual cycle. The correlation coefficient was 0.82. ing a group of patients who were considered normal
fertil ity controls with those patients who had Type l, II
ln addition , the periovulatory E2 sums and means have and fII luteal phase deficiencies (Figure 35-32). In each
been corre lated with the mucus cycle score as deter- case, the mucus cycle score was signifi cantly decreased
m ined from the CrMS chart. The regression lines are in those patients w ith these three types of luteal phase
shown in Figures 35-3 1aand35-3 1b. lt is clearly shown deficiency. These mucus cyc le seores are also shown
that as the periovulatory three-va lue sum and mean infor patients who have pe lvic adhesions, infertility, en-
creases (improved fo llicu lar function) , the mucus cycle dometriosis and polycystic ovarían disease. In each of
score also in creases. Or, lookin g at it from a d ifferent these groups, except the patients w ith pelvic adhesive
perspective, a decreased mucus cycle score is closely di sease, the mucus cycle seores were statistically lower
associated with decreased fo llicular function. than the nom1al contro ls.
MEAN PERIOVULATORY E2 SUM (3 VALUES)

BY MEAN MUCUS CYCLE SCORE (MCS)
3 VALUE PERIOVULATORY E2 MEAN
VS. MEAN MUCUS CYCLE SCORE (MCS)
w
~ 10 ~ 10
o(.) u 9
!/)
r/l
B w 8
l1J ...J
...J
(.) 7
(.)~
> !/) 6 >
(.)
t>u 6
!/)
r/l :E :J 5
:J - u
(.) 4 :J 4
:J :¡;
:¡; 3
z
r =0.9239 <
w
2
:¡;
O -r---t~-t---1~-+-~t---+-~+--+~+---t~~~ o
o 10 20 30 40 50 60 70 80 90 100 o 5 10 15 20 25
3 VALUE SUM OF PERl-OVULATORY 3 VALUE PERIOVULATORY E, MEAN
ESTRADIOL-17 BETA PROFILE
Figure 35-31a Figure 35-31 b
Figure 35-31a and 35-31b : The mean periovulatory estradiol-17~ sum of three va lues (Figure 35-3 1a) and mean of three
values (Figure 35-31b) compa red to the mucus cycle score in the cycle of evaluation . The co rrelation coefficient for the first
graph is 0.9239 and for th e second is 0.9144 (From : Pope Pau l VI lnstitute research , 2004).
Mucus Cycle Score:

Normal Fertility Controls vs.
10 Various Organic Causes of
9.3
lnfertility and Luteal Phase Type
8.5
8 7.6
6.9 6.8 6.7 6.6
6
4.8
Normal Pelvic Type 111 All Type 11 Endometr1osis Type 1 PCOD

Fertllity Adhesion Luteal lnfertllity Luteal n=206 Luteal n=15
Controls Phase Aeg . Phase Phase
n=62 Defect Cycles Defect Defect
n-27 n=299 n=57 n=9
Po.1670 ~ IP<.00021 1 P<.0021 IP<.00011 ~ ~
Figure 35-32: The mucus cycle score in a group of normal fertility controls co m-
pared to patients with Type \, 11 and 111 luteal phase deficiency in va rious other
associated organic findings in patients with infertility (From : Pope Pau\ VI lnstitute
research , 2004).
Chapter 35: Fo llicular and Luteal Phase Deficien cies 445
This data supports the notion that the CREIGHTON optima! luteal function (Figure 35-34).
MODEL chart, which is easy to obtain and allows for
ongoing evaluation from cycle to cycle overa prolonged When evaluating LH pulse intervals, Sou les, et al. found
period oftime, as well as, all owing for between-woman more freque nt LH pulses that were oflower amplitude in
analysis, provides a very sensitive biological marker for women with luteal phase deficiency (determined by en-
the ongoing eva luati on of follicular and luteal phase dometrial biopsy) compared to normal women (Figure
function. 35-35).58 They also found that the integrated LH-immuno
and LH-bio leve ls over the mid-cycle LH surge were
significantly decreased in the luteal phase defect group
Etiology _ _ _ _ _ __ _ __ ~ (Figure 35-36) . The mean LH-bio levels across days 6 -
1 l ofthe luteal phase were also significantly decreased
Follicular and luteal phase deficiency (as opposed to in the luteal phase deficiency group (F igure 35-37). In
secretory phase dysfunction) is clearly a heterogenous separate sh1dies, a decrease in LH pulse frequency in
gro up ofphysiological alterations offollicular growth , the fol licular phase was observed. 57 •59
development, function and subsequent luteal function.
One explanation as to the cause of this heterogenous Using ultrasou nd , Check 60 and Yang 39 showed a de-
gro up would be imposs ibl e to postulate and would be, creased diameterofthe dominant fo llicle in patients with
almost certainly, in error. There has, however, been good luteal phase deficiency. In our studies, we fo und a sig-
work done, which at least points to the potential possi- nificant decrease in follicle size for the Type 11 lutea l
bilities ofabnom1alities that might exist. phase deficiency only.
Clearly, alterations in folliculogenes is lead to abnor- Some have found elevated prolactin levels associated
malities in luteogenes is. This is particularly true in the with luteal phase deficiency, but in our studies ali pro-
luteal phase Type 1 and 11 defects. Jn Type lll and V lactin levels were within the normal range except for the
defects, follicular function appears to be normal. In Type Type B and C levels offo lli cul ar function. At the same
IV, not enough work has been done, although in the time, however, they were also found to be increased in
case presentation, follicular phase deficiency was clearly Level AA and AAA fo llicul ar function suggesting that
in evidence. its physiologic role may be inconsequential. We did
find , however, that in the Type Ill luteal phase defi-
With different leve ls of foll icular phase function , the ciency, the LH leve! on Peak +7 was significantly de-
ones that could be considered abnormal would be folli- creased from the normal controls.
cul ar function Types B and C, which are both clearl y
suboptimal. This, in turn , fo ll ows with suboptimal luteal A functional differentiation in steroidogenesis has been
function.
300 N.S. • Normal
Strott, et al ., 53 observed a lower follicu lar phase FSH/LH 1
D LPD
ratio among women who sporadically had sho11 luteal
phases (s imilar to Type 1). Others have found decreased
-
:J'
Cl
~ 200
FSH leve ls in individuals who had luteal phase dys- :e
en
function defined by abnorma l out-of-phase endometrial u.
Q)
biopsies.23 •56 ·57 In our minimal eva luation ofFSH levels, >
we did not find decreased FSH levels when eva luated ~ 100
!ti
on day 5 ofthe cyc le. Soules, et al.,45 found no differ- o
ence in either immunoreactive or bioactive FSH levels i:D
n=6
during th e follicular phase (Figure 35-33). lt is possible
that the differences in these studies retlect evaluation Follicular Phase
of different types of luteal phase and follicular phase (days -6 to -1)
deficiency. lt is also quite possible that this analysis of Figure 35-33: The mean level of FSH-bio over days -6 to -1
screening the levels ofFSH are not adeq uate for identi- are indicated for the normal and luteal phase deficient women .
fy ing the defect that may ex ist. There was no signi fi can! difference between the groups .
The size of each group and 1 SE are indicated (From :
Schweiger U, Laessle RG, Tuschl RJ , et al: Decreased Folli-
Soules, et al.,46 also identified decreased inhibin levels cular Phase Gonadotropin Secretion is Associated with lm-
in the early follicular phase and the late luteal phase of paired Estradiol and Progesterone Secretion During the Folli-
the cycle in patients who had both shorten ed and sub- cular and Luteal Phases in Normally-Menstruating Women . J
Clin Endocrino! Metab 68 :888-892, 1989).
20
so A
....-. Normal
._. LPO 15
""'
10
~
.s.
60
NOR MAL
Early Follicular Phase
50
*
5
40 *
o ~
-2!:: 30
::r:
...J
400
20
350
300 10
250
200
i""' o 2 4 6
Hours
8 10 12
150
100
60
50 LPD
Early Follicular Phase
o 50
40
20
10
o 2 4 6 8 10 12
Hours
-10 -5 o +5 +10 +15
Day Relativa to LH Surge Figure 35-35: The LH secretory pattern in a normal woman
(top) and a woman with luteal phase deficiency (bottom) in
the early follicular phase . The LH pulses are more frequent
Figure 35-34: The daily mean levels of serum progesterone , with a lower amplitude in the woman with luteal phase defi-
estradiol-17~ and inhibin over the menstrual cycle are indi- ciency as compared to the normal woman . The stars indicate
cated for the normal (blue) and luteal phase deficient (red) the pulses (From: Soules MR , Clifton DK, Colin NL, et al: Luteal
groups . There was a significan! decrease compared with Phase Deficiency: Abnormal Gonadotropin and Progesterone
normal values in the luteal phase integrated levels of these Secretion Patterns. J Clin Endocrino! Metab 69:813-820, 1989).
three hormones in the luteal phase deficient group . There
was also a significan! decrease in follicular phase (days -12
to -5) mean serum inhibin levels in the luteal phase deficient
group compared with normal values (From : Schweiger U,
Laessle RG, Tuschl RJ , et al : Decreased Follicular Phase Go-
nadotropin Secretion is Associated with lmpaired Estradiol
and Progesterone Secretion During the Follicular and Luteal
Phases in Normally-Menstruating Women . J Clin Endocrino!
Metab 68:888-892 , 1989).
Cha pter 35: Follicul ar and Luteal Phase Defic iencies 447
identi fied for two types of luteal ce li s isolated from the Receptors to both estrogen and progesterone in the
mature human corpora lutea .61 These appear to be de- endometrium ha ve been found to be decreased in women
rived from the granulosa and theca cells. The granulosa with lutea l phase deficiency (of secretory ori g in). 62 · 6~
lutein cells appear to be responsibl e for the basa l secre-
tion of progesterone throughout the tutea! phase. The Rel ati ve to the Type IV luteal phase defic iency, it has
theca lutein cel ls are primarily responsibl e for the late been noted that early luteal phase serum progesterone
luteal secretion of progesterone. lt is poss ible that an leve ls are hi gher in successfu l pregnancy cycles. 65 ·66
exc lusive defect in the small theca lutein cells may ex- With regard to a Type V lutea l phase deficiency (E 2-
plain the occurrence ofa shortened luteal phase or per- specific), E2 is necessary to prime the endometrium for
haps even the late defect in the Type 111 tutea! phase progesterone to be effecti ve. At the same tim e, deple-
deficiency. Both types of cells released estrone (E 1) and tion of E2 in the corpus luteum has been found , on the
E2 , but the large ce ll s were more active. one hand , not to adversely affect th e morphological
developmentcapacity ofthe endometrium, while on the
other hand , be associated with early pregnancy wast-
•
D
Normal
LPD
3000
age, presumably due to inadeq uate endometrial sup-
800
pc;_Q1 p<.05 port.67.68
,.,
Ui"
..,"' ,.,
Ui"
:r 600 ..,"' 2000
e, :r Treatment and Luteal Support ---~
=i.
;::; e,
o
e: 400 8
o
"
E :;; In identifying the various forms of lutea l phase defi-
E :i: 1000
±
.J 200
.J ciency and fo llicular phase dysfuncti on and making a
differential diagnosis, one can deve lop a rational plan
n=10 for treatment. With a Type 1 luteal phase deficiency, for
lntegrated LH Surge (days -1 to +1) exa mpl e, the mai n treatment necessary is to support the
lutea l phase. This can best be accom plished by provid-
Figure 35-36 : The integrated LH-immuno and LH-bio levels
over the mid-cycle surge. (days -1 , O a nd 1) are indicated for ing HCG inj ecti ons 2000 íU on Peak +3, 5, 7 and 9. lfthe
the normal and luteal phase deficient groups. Both LH-immuno fo lli cul ar phase is abnormal (Type B or C), then sorne
and bio levels were significantly decreased in the luteal phase type of stim ulation of th e follicle is necessary, either
deficient group. The size of each group and 1 SE are indi-
cated. (Fro m: Soules MR , Clifton DK, Colin NL, et al : Luteal
with clomiphene or FSH/ LH . Clom iphene has been
Phase Deficiency: Abno rmal Gonadotropin and Progesterone shown to adeq uately stimul ate the fo llicl e. 69 -72 With the
Secretion Patterns. J Clin Endocrino! Metab 69:813-820 , 1989). stimulation of fo lli culogenes is, there is almost always
improved luteogenesis although it will not be universal
p< .05 (Tab le 35- 13).
300 1 • Normal
0 LPD
-::J'
C>
2' 2 00
Fo lli cul ogenes is can also be stimulated by using a short
:e
__J Table 35-13: The Effect of Clo miphene and HCG
Q)
> on P+7 Progesterone and E2 Levels
;
(J
100 Medication P+7
o«! .¡. P (ng/ml) E2 Sum '
iii
Before clomiphene 12.2 7.9
n=9 (n=10)
After clom iphene 21 .1 15.6
Luteal Phase (n=10)
p-value .030 1 .002 2
(days +6 to +1 1)
Figure 35-37 : The mean LH-bio level s across days 6-11 of Before HCG 8.8 8.7
(n=28)
the luteal phase are indicated for the normal and the luteal
After HCG 21 .9 12.0
phase deficient groups . There was a signifi ca n! decrease in
(n=25)
the LH-bio levels in the luteal phase deficient women com-
p-value <.0001 2 .008 2
pared with normal values . The size of each group and 1 SE
are indicated (From : Soules MR , Clifton DK, Colin NL , et al: From: Pope Pauvl VI lnstitute research, 2004
Luteal Phase Deficiency: Abnormal Gonadotropin and Proges- 1. Aspin-Welch unequal variance
terone Secretion Patterns . J Clin Endocrino/ Metab 69:813- 2. Wilcoxon Rank-Sumtest
820 , 1989)
448 The Medica! an d Surgi cal Pra ctice of NaPro TECHNOLOGY
course ofFSH/LH. 73 -78 Again, improved fo lliculogenes is - 2 o 2 4 5 l!I 10 12 14 15
should resul t in improved luteogenesis, a lthough it w ill 500 • Con t rol hCC
not be uni ve rsal. In both cases w here clomiphene or • Cr o u p IV ¡
_, 400 * *
FSH/LH are prov ided, adequate endocrine monitoring o~
is necessary as described in Chapter 55 . ºe

<....._ 300
~
UI <>.
.., ~
...
200
lt is often suggested that the lutea l ph ase also be sup-
100
ported . Thi s can be acco mpli shed by prov iding proges-
te rone either in the fo rm of progesterone vaginal cap- o
sules, oral progesterone, or in tramuscul ar progeste r- 50 *
one. 79-82 ..,
z 40
o
"' ~
w-
HCG is often used fo r lutea l phase support as we ll. It ui,
,_E
"'Uc...
JO
has been advanced asan important approac h to luteal 20

o~
ph ase support in infe rtili ty treatm ent. 83 Th e reco m- "'

o.. 10
mended dosage at the Pope Paul V I ln stitute is 2000 o
units give n lM on Peak +3, 5, 7 and 9. In Figu re 35-38,
h CC
the effects of HCG on progesterone and E2 are shown. 4 .0
¡
In F igure 35-39, the effects ofH CG on progesterone and
"'z~
the matu ration of the endo metri al bi opsy is also demon- J .0 -
º~
w -
strated.84·85 HCG may also exert effects in vivo on en- z E
..,.... ...
....... 2 .0
dometri al hi sto logy and p artake in endometri al tra ns- UI
o~
e
fo rm ati on of the luteal phase.86 lt has been suggested "'oz 1. 0

that HCG is superior to progeste rone in lutea l phase <
1 1 1 1 1 1 1 1 1 1
o.o 1
' 1 1
' 1 1
support.87 ln Table 35-14, the properties ofvarious luteal - 2 o 2 4 6 B 10 12 14 16

phase support agents are summ ari zed . LUTEAL DAY
Figu re 35-38: The serum concentrations of estradiol , proges-

HCG can also be given subcutaneously (SQ). lt wo uld teron e and androstened ione standardized to day of mid-cycle
appear there is no signifi cant di ffere nce in HCG levels urinary LH surge (luteal day O) in a group of normal cycling
w ben provided by subcutaneous injecti on vs. lM inj ec- women who received exogenous HCG 5000 IU intramuscu-
tion.88.89 larly on luteal day +8 ( J, ). Asterisks equal va lues significantly
different (p <. 05) from the control groups. (From : Fritz MA,
Hess DL, Patton PE : lnfluence of Corpus Luteum Ag e on the
F inally, sorne pati ents do not respond to either fo llicul ar Steroidogen ic Response to Exogenous Human Chorionic Go-
or lutea l stimul ation in the means described above w hen nadotropin in Normal Cycling Women . Am J Obste! Gynecol
16 7 :709-7 16, 1992).
they ha ve a Type B or C fo lli cul ar phase defi c iency or a
Type V LPD . In those patients, adding E2 to the regimen
Table 35· 14: P ro pe rties of Luteal Phase

Su ppo rt Agen ts
Need Prolongs
Co rp us Post•Peak lncreases Post-Pea.k
Agent Luteum? Phase Prog. 'Esfradi ol
HCG Yes Strong Yes Yes

IM progesterone No Moderate Yes No
(Strong )
Oral progesterone No Weak Yes No
(Moderate)
Vaginal progesterone No Moderate Yes No
(Weak)
Cl omiphene and FS H/LH are luteog enic

by being follicul o genic .
Chapter 35: Follicular and Luteal Phase Defi ciencies 449
Prog ....-----------------~ Endometri al biopsies initi all y became the "go ld stan-
(ng/m l )
Control cycle dard " until it became mo re a nd more obvio us that they
20 Rx cycle
had in-built deficiencies. Attempts we re made to use
serum progesterone levels, but because ofa lack ofstan-
Endo Bx
dardization , this approach never fulfilled its promise.
023-24
i
10
Now, with the avai lab ili ty ofthe CrMS , a wo man's abil-
ity to identify her Peak Day (wh ich is an ovu latio n-de-
pendent observation), the physician can no w in a re-
HCG (25000 IU) producible and comparati ve fas hi on, eval uate the lutea l
0123 4 5 6 7 8 9
ph ase of the menstrual cyc le w ith serum progesterone
Days and E2 leve ls done in a seri al, profil ed fas hi on. In addi-
Figure 35-39: Progesterone levels in the co ntrol and treat- tion , periovulatory E 2 production can also be eva luated .
ment cycles of a patient. HCG, 2500 IU , was given on the By examining these profiles and eva luating th e sum s
fourth , sixth , eighth, and tenth postovulatory days. There is a and means ofthe profiles (whi ch esti mate the integrated
47 percent increase in the area covered by th e progesterone
progesterone leve!), a n objective assessment of both
curve in the treatment cycle co mpared to the control. The
luteal phase is prolonged two days and th e endometrial bi- lutea l and fo llicu lar function can be made. This still leaves
opsy, which was two days behind has become in-phase . open the lack of correlation to these effects on the en-
The control cycle is the blue line; the treated cycle is the gold do metrial biopsy. H owever, c lini ca l experie nce has
line (From: Jones GS , Aksel S, Wentz AC : Serum Progester-
shown that these are significa nt ab normalities and when
one Values in the Luteal Phase Defects . Obste! Gynecol 44:26-
34, 1974.) corrected, produce both symptomati c improveme nt, as
we ll as procreative improve ment.
during the post-Peak ph ase of the cycle may improve With a further subclass ifi cati on and adva ncement of
pregnancy rates. 9º·91 At the Pope Paul VI lnstitute we our understanding of both lutea l, as well as fo llicul ar
ha ve used 1 o r 2 mg of estradi o l-1 7 ~ (Estrace) by mouth phase deficiency, the latter ofwh ich also was addressed
every day at bedtime ( PO QD hs) from Peak +3 through in th e Jones paper in 1949, the physician can now begin
Peak + 12 to accomplish this. Another approach has been to integrate the whole of ovari a n function , which is es-
to use 2.5 to 5.0 mg of triestrogen (not sustained-re- sential if one is go ing to treat reproductive pro bl ems,
lease) as a vaginal capsule every day at bedtime (Q D and othe r cond iti ons which are specifi ca lly related to
hs) from Peak + 3 through Peak + 12 or 5 mg oftriestrogen abnormalities of reproductive hormones. Others have
(sustained release) PO QD hs P+ 3 through P+ 12. In these confirmed that subtle hormone abnormalities do exist in
cases, serum E 2 levels have been shown to be increased patients with infert ility.92 The schemata presented in this
fo llowing treatment. However, the exact effects on the chapter is relativel y inexpensive a nd very reproducible.
endometrium have not yet been determined and im- The biggest problem w ith it, as experience has shown ,
proved pregnancy rates spec ifi ca ll y have not yet been is that physicians tend to take shortcuts beca use of the
s ubstanti ated . pressures of managed care. A nd yet, these "shortcuts"
often produce aberra nt results, which ultimately lead to
greater expense, a lack of attenti o n to the underl y ing
Conclusion -----------~ problem and an inability to treat it.
Over 50 yea rs ago, Jones described lutea l phase defi- The reader is encouraged to study thi s approach care-
ciency and for the last 50 years, there has been a confu ll y, try to und ersta nd its rationale and then begin to
si derable effort to furth er evaluate this. lt has been con- incorpora te it fo r a w hole variety of underl yi ng abnor-
troversia! in many ways beca use there has been no per- malities a nd condi tions.
fect ly good way to be abl e to eva luate thi s condi tion .
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Gy naek 54:464, 1930 . lmpact of lnterobserver Ya ri ability on Endome tria l Datin g
in the Diagnosis of Luteal Phase Defects. Fertil Steril 60:652 -
2 . Knaus HH: Ein e N ue Methode Zur Bestimmung Des
657 , 1993.
Ovu lati onsdenstermi ns Zbl Gynaek 53:2193, 1929.
23. Sherman BM , Core nm an SG: Meas urement of Serum LH,
3. Rock J, Bartlett MK: Bi opsy Studies of Hum an En-
FS H. estradio l, and progesteron e in Disorders of th e Human
dometrium. JAMA 2022-2028, Jun e 12, 1937.
Menstrual Cyc le: Th e ln adequate Lute a l Pha se. J C lin
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Obste! Gynecol 1048 -1 061, Jun e 17, 1942.
24. Go ldstein D, Zucke nn an H, Harp az S, et a l: Co rrelation
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26. Ol ive DL, Thomford PJ, Torres SE, et al: Twe nty-Fo ur
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12. Balasch J, Yanre ll JA , Cru es M, et a l: The End ometri a l
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Chapter 35: Foll icular and Luteal Phase Deficiencies 451
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An Assess men t of Lutcal Fun cti on. Ferti l Ste ril 48:937-
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4 6. McNee ly MJ, Soules MR : The Di agnos is of Luteal Ph ase
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483, 1986.
4 7. Alex andcr SE, Akse l S, Yeoma n RR, et al: Gonadotropin
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and Ova rian Horm one Dynamic s in Lut ea l Phasc De fec ls.
of th e Out- of- Phase End ometrium in Female lnfertil e Pa-
Am J Obstet Gyneco l 166:652-657, 1992.
tients. Feni l Steri l 63:984-988 , 1995.
48 . Clin e DL : Unsu spected Subc lini ca l Pregnanc ies in Pati ent s
65. Yovich JL , McColm SC, Yovich JM , et a l: Ear ly Lutea l
with Lutcal Phase Defec ts. Am J Obstel Gynecol 134:438-
Sc rum Progesterone Concentrati ons are Hi gher in Pregnancy
444, 1979.
Cyc les. Ferti l Steril 44: 185-1 89, 1985.
49. Kusuh ara K: Clinical lmportan ce of Endometrial Hi stology
66. Lenton EA, Sulaiman R, Sobowa lc O, et al: The Hum an
and Proges tero ne Leve ! Assessmcnt in Luteal-Phase Dc-
Menstrua l Cyc le : Pl asma Co nce ntrati ons of Prol actin , LH ,
fec t. Horm Res 37 (Suppl 1):53-58, 1992.
FSH , Oestradiol and Progestero ne in Conce ivin g and Non-
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Depl etion During the Lutea l Ph ase on Endometri a l Deve l-
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ti lity: A Seque l to Aberrant Foll icul ogenes is. Fertil Steri l
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35:489-499, 198 1.
dio l and Pre gna nc y Outcome in Gonado trop in-Releas ing
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38:28 1-300, 1982. Trcated Gamete lntrafa ll opian Tran sfc r Cycl es. J Reprod
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53. Strott CA, Ca rgil e CM, Ross GT, et al: The Short Lutea l
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of lnfertile Wome n with Low Lut ea l Phase Pro ges terone
54. Lenton EA, Land gren B-M , Sexto n L: No rmal Variati on in
Lcvel s. Obstet Gyneco l 59:275-279, 1982.
th e Length of th e Lut ea l Ph ase o f the Mens tru al Cyc le:
ld e nti ficat ion of th e Short Lut ea l Phase. Br J Obstel 70. Down s KA , G ibson M: Clomiphen e Citrate Therap y for
Gy naeco l 9 1:685, 1984. Lutcal Phase Defecl. Fertil Steri l 39:34-38 , 1983.
55. Hilge rs TW, Abrah am G, Prebil AM: The Length of th e 7 1. Murray DL, Rei ch L, Adashi EY: Oral Clomiphene Citrate
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13:99, 1989. Lutea l Phase Dys functi on: A Co mparative Stud y. Fert il
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56. Cook CL, Rao CV, Yu ssman MA : Plas ma Gonadotrop in and
Sex Stero id Hormone Levels Durin g Earl y, Midfollicular and 72 . Kcc nan JA, Herbe rt CM, Bush JR , et a l: Diagnosis and
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Stcril 40:45 -48, 1983. Patien ts Rece ivin g Clo miphen e Citral e for Ovulat ion ln-
duction. Fertil Steril 5 1:964-967, 1989.
73 . Minass in SS, Wu CC, Gro ll M, et al: Urin ary Fol lic le-Stimu- 8 4 . Fritz MA, He s DL , Patton PE: lnflu enc e o f Co rpu s Lu-
latin g Hormone Treatment fo r Lutea l Phase Defect. J Reprod teum Age on the Stero idogeni c Res ponse to Exogenou s Hu-
Med 33: 11-1 6, 1988 . man Chori oni c Gonadotropin in Norm a l Cycli ng Wo rnen.
Am J Ob stet Gyneco l 167:7 09- 7 16, 199 2.
74 . Balasch J, Jove IC, Marquez M, et al: Early Fo llicu lar Phase
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Luteal Phase Defici ency. Fertil Steril 54: 1004-1007, 1990. the Lutea l Ph ase Defects. Obste! G yneco l 44 :26-3 4, 1974 .
7 5. Grazi RV, Taney FH, Gagl iardi CL, et al: The Luteal Phase 86. Fanchin R, Pel ti er E, Frydman R, et al: Huma n Chorionic
Durin g Gonadotropin Therapy : Effects of Two Hum a n Go nad otrop in : Does it A ffect Human Endometr ia l Mor-
Chorionic Gonadotropin Reg im ens. Fe rtil St eril 55: 1088- phology in vivo? Semin Reprod Med 19:31 -35, 2001.
1092, 199 1.
87 . Buvat J, Marco lin G, G uittard C, et al: Lutea l Support after
76 . Di ze rega GS, Hodgen GD: Follicu lar Ph ase T rea trnent of Luteini z ing Horm o ne-R e leas in g Ho rm one Agonist fo r In
Lutea l Pha se Dysfu nct io n. Fertil Steril 35:42 -432 , 198 1. Vitro Fe rtili za tion: S uperiori ty of Hum an Chorionic Gona-
dotropin Over Oral Progesterone. Fertil Steril 53:494, 1990.
77. Wu C H: A Short Co urse of Menotropin after C lo miph ene
Failure in ln fe rtil e Women wi th Luteal Ph ase Defects. J 88 . Elkind- Hirsch KE, Bello S, Es parcia L, et al: Serum Human
Reprod Med 34 :807-8 10, 1989. Cho ri on ic Go nadotropin Leve ls are Corre lated with Body
Mass lndex rather than Ro ute of Adrnini stra ti on in Wom en
78 . Huang K- E, Muechl er EK, Bonfiglio TA : Fo ll icular Ph ase
Und ergo in g in Vi tro Fertili zation- Embryo Tran s fer us ing
Trea tment of Lutea l Phase De fect with Fo ll icle-Stimu latin g
Human Me nopau sa l Gonadotropin and lntracytopla s mi c
Ho rm one in lnfe rtil e Wo men. Obstet G yneco l 64:32-36 ,
Sperm lnj ecti on. American Soc iety of Reproducti ve Medi-
1984.
cine , 2001.
79 . Hami lto n CJCM, Jarodi KA , Sieck UV: The Va lue of Lutea l
89. Ste llin g JR, Chaprnan ET, Frankfurter D, et a l: Subcutan e-
Support with Progesterone in Go nadotropin- lnduced Cyc les .
ous vs. Intramuscular Admini stration of Huma n Chorionic
Fertil Steri l 60 :786- 79 0, 1993.
Gonadotropin during an In Vitro Fe rtili zati on Cyc le. Fertil
8 0. Fri shm an GN, Kl ock SC, Luc iano AA , et a l: Efficacy of Ste ril 79 :88 1-885 , 2003.
Oral Microni zed Proges terone in th e Treatm e nt of Lutea l
90. G le ich er N , Brown T, Dudkiewicz A, et a l: Estradi o l/Proges-
Phase Defects. J Reprod Med 40:521-524, 1993.
terone Substitution in the Lutea l Ph ase lmproves Pregnancy
8 1. Wentz AC, He rbe rt CM , Max so n WS , et a l: Outco me of Rates in St imul ated Cycles, but on ly in You nger Wome n.
Progesterone Treatrn ent o f Lutea l Ph ase ln adeq uacy. Fertil Ea rl y Pregnancy 4:64-73 , 2000.
Steri l 41 :856-862 , 1984.
9 1. Kiider AS, Cou lam CB: Luteal Estrogen Supplementation in
82. Rosenberg SM, Luci ano AA , Ri dd ick DH : The Lutea l Phase Pregna ncies Assoc iated w ith Low Serum Estradi ol Co nce n-
Defect: The Re lative Frequency o f, and Enco ura g in g Re- trat ions. Ea rl y Pregnan cy 4: 19 1-1 99, 2000.
s po nse to , Trea tment wit h Va g in a l Proges tero ne . Fertil
92. Blacker CM, G in sburg KA , Leach RE , et al: Unex pl a ined
Steril 34: 17-20, 1980.
lnfe rtility: Eva luati on of th e Lutea l Ph ase ; Res ult s of th e
83 . So liman S, Daya S, Co llins J, et al: The Role of Lutea l Phase N ational Center for lnfertility Research at Michigan. Fertil
S upp ort in ln fert il it y Treatment : Th e Me ta-Ana lys is of Ste ril 67:4 3 7-44 2, 1997.
Random ized Tria Is. Fe rtil Steril 6 1: 1068- 1076, 1994.
Thyroid System Dysfunction
evera l decades ago it was common practice for nally described Wilson 's syndrome has been criticized
S women with infertility problems to be provided thy-
roid supplementation. Anecdotal stories suggested that
for his thoughts in this area. lf one reviews internet
sources, one sees commentary from physicians sug-
thyroid support would assist them in achieving preg- gesting that Wi !son 's syndrome is real and treatment
nancy. However, with our greater understanding ofthy- has produced significant res ults. At the same time, Dr.
roid disease and with newer tests for thyroid function , Wilson is listed on a webs ite call ed "QuackWatch. " The
the use ofthyroid support in women with infertility prob- American Thyroid Association (ATA) issued a state-
lems decreased sign ifi cantly. ment in 2001 suggesting that "a thorough review ofthe
biomedical literature has fou nd no scientifi c evidence
Over the last 25 years, the author has studied th yro id supporting the existence of Wil son 's syndrome." 3 The
function in infe1tili ty patients by measuring a standard ATA's criticism was partly based on the suggestion that
thyroid profile and thyroid-stimulating hormone (TSH) Wilson 's syndrome used an incorrect definition of nor-
leve! on Peak + 7. Almost universally, those tests ha ve mal body temperature.
proved to be normal and thyroid support has not been
provided. A body temperature of98 .6 degrees Fahrenheit is con-
sidered normal in Wilson 's syndrome. This is based on
Over the past 1O yea rs, patients have brought a condi- st udies that were done over 100 years ago by
tion that is sometimes referred to as " Wilson 's syn- Wunderlich . The ATA suggested, based on work pub-
drome" to the author 's attention. After a review of the lished in l 992 by Mackowiak'\ that the clinical thermom-
books available on Wilson 's syndrome,1.2 we began a etry concept of 98.6-degree-Fahrenheit body tempera-
research investigation to evaluate this condition fur- ture shou ld be abandoned . The Mackowiak paper, which
ther. was cited by the ATA, suggested that recent analys is
showed that the body temperature now averaged 98.2
Wilson 's syndrome was identified as a condition that degrees Fahrenheit.
occurred in women who had a grouping of symptoms
associated with low body temperature and normal thy- The Mackowiak study had 148 subjects. The average
roid fim ction studies. The family physician who origi- body temperature for this group was 98.2 degrees. How-
453
ever, the majority ofthe subjects were men (in Wilson 's change the name to thyroid system dysfunction (TSD),
syndrome, the majority of the subjects were women) which appea rs to be more genera l anda more appropri-
and the average body temperature for the men in this ate description ofthis cond iti on.
study (n= 122) was 98 . 1 degrees Fahrenheit. The aver-
age temperature for women was 98.4 degrees Fahren-
heit (n=26). This suggests that Wilson 's concept of98 .6
degrees Fahrenheit was not far off in the patient popu-
lation that he was treating (Table 36-1 ). Thyroid system dysfunction (TSD) is a condition in
which the patient may ha ve a large number of symp-
A more recent analysis of body temperature studied a toms associated with abnormal thyroid function . How-
sma ll group of young, healthy women and found that ever, in this condition , the standard thyroid function
their average core body temperature during the follicu- studies are usually normal. Diagnosing the condition
lar phase ofthe menstrual cycle was 98 .5 degrees Fahr- rests on the ability to take a series of body tempera-
enheit and during the luteal phase was 99. 1 degrees tures, wh ich wou ld revea! w hether the body tempera-
Fahrenheit. 5 T he temperature was higher during the ture is low, and to eva luate the presence of symptom s.
luteal phase secondary dueto the increase production
ofprogesterone by the corpus luteum (Figure 36- 1) and This conditi on appears to be related to chron ic stress.
(Table 36-2). In the origina l work , Wilson did notad- Under stressfu l conditions, the adrenal g lands respond
eq uately account for these changes in the body tem- by manufacturing cortisol. Cortiso l can inhibit the con-
perature during the lutea l phase ofthe menstrual cycle. version ofthyroxine (T) to triiodothyronine (T 3). Corti-
so l favors the conversion ofT 4 to reverse T 3 (rT) . Re-
Wilson 's syndrome is controversia!. However, i fthe aca- verse T 3 is chemica ll y simi lar to T 3 but it is complete ly
demic comm uni ty in contemporary medicine <loes not inactive (i t has no phy iologic activity). lfthe stress i
agree with the concept, it tends to ignore or denigrate it. prolonged , a cond ition referred to as "reverse T3 domi-
We chose to look at it serious ly and to begin some nance " occurs and pers ists even after the stress passes
investigation s. One of the first things we did was to and cortiso l levels fa ll . Apparently, rT 3 can also act lik e
cortisol and block the conversio n ofT 4 to T 3 .
Table 36-1: JAMA Re-appraisal of Wunderlich's
The conversion ofT4 to T 3 is ve ry important. lt occurs
98.6ºF Body Temperature'
both in the liver and in the individual cells throughout
the body. While T 4 is produced by the th yro id g land in
Conclusion: 98.6ºF should be abandoned as a concept
response to thyrotrop in-re leasing hormone (TRH) and
relevan! to clinical thermometry
38
Number of subjects 148
Average temperature was 98.2°F >- ~ 37. 5
Average temperature- men (n=122) 98.1°F e::>
o 1-
Average tem perature- women (n=26) 98.4°F ID~ U 36
Ww ~
o:: c.
1. Mackowiak PA, Wasserman SS , Levine MM: AC ritical Appraisal of o~
98.6ºF, The Upper Limit of !he Normal Body Temperatura, and other () ~ 36.5
Legacies of Carl Reinhold August Wunderlich. JAMA 268: 1578-1580:
1992.
w 10
z
o
o::-
w _J
1- E
en
W -CI
5
Table 36-2: Core Body Temperature in
C> .s
Follicular and Luteal Phase' (N=S) o
o::
c. o
Core Body Temperature'
8 12 16 20 24 4 8 12
Phase Centigrade (C) Fahrenheit (F)
TIME OF DAY
Follicular phase 36.93 98.5 Figure 36-1 : Core body temperature and progesterone mea-
Luteal phase 37.28 99.1 sured during luteal and follicular phases . Twenty-four hour
progesterone profiles with core body temperature and proges-
1. From: Shibui K, Uchiyama M, Okawa M, et al: D1urinal Fluctuation of terone measured during follicular and luteal phases (FP and LP
Sleep Propensity and Hormonal Secretion Across !he Menstrual Cycle. far eight subjects in mean SC). The plots represen! the values
Bio/Psychiatry. 48: 1062-1068, 2000.
for FP (red) and the LP (blue) (From : Shibui K, Uchiyama M,
2. Temperatura was measured rectally wilh a rectal temperatura appara- Okawa M, etal : Diurnal Flu ctuation of Sleep Propensity and
tus.
Hormona l Secretion across the Menstrual Cycle . Bio/Psychia-
try. 48 :1062-1068, 2000) .
Chapter 36 : Thyroid System Dysfunction 455
TSH (thyroid stimulating hormone), the thyroid hormone In addition, levels of tota l T4 , free T4 , TSH , total T3 , and
itse lf (T 4 ) is not very active. The conversion ofT4 to T3 reverse T3 are drawn. lfthe body temperature is be low
is important to obtain the effect ofthe thyroid hormone. 98.2 degrees Fahrenheit, the li st of symptoms is pos i-
When thi s relationship changes with the predominan t tive and the T3 :rT3 ratio is less than 1O.O, then the condi-
production of reverse T3 (rT), mu ltiple symptoms reti on TSD is sa id to ex ist. Th is is a working and evolv-
lated to thyroid dysfunction develop. ing deflnilion and 110 1 a perfect one. lt will identify
patients who are candi dates for a tria! of therapy.
This reve rse T3 dominan ce causes hypometabo li sm ,
which is associated with TSD and decreased body tem- In the description of thi s condi tion by Wilson , patients
perature. Hormone activity requires hormones to bind were treated with a sustained release fo rm of triiodothy-
with chem ical receptors in the ce ll in order for th e hor- ronine (S RT 3 ) . lt was sa id that, after 30 to 60 days of
mone to be effective. Both T_ , and rT_, bind to the same maintenance th erapy on the SRT 3 , th e conditi on could
receptors. However, when the amount of rT 3 is more be "cured" and the body temperature would stay up
abundant than the amount of T3, the receptor sites be- appropriate ly on its own once the SRT 3 is tapered (F ig-
co me blocked by th e rT 3 and the various chemical reac- ures 36-4 and 36-5).
ti ons associated with the body slow down. When these
reaction s slow down , the body temperature drops be-
cause these reactions normall y produce a certain amount
ofheat within th e body. Thi s drop in temperature slows
down enzymes in every ce ll ofthe body causing a theo- The treatment of thi s conditi on relies on the administra-
retical condition that Wilson ca ll s a " multiple enzyme tion of a susta ined release fo rm of a trii odothyronine
dysfun ction. " (S RT). lt is extreme/y imporlanl that thi s be in the form
of a susta in ed release preparati on because T 3 is an ex-
/reme/y active hormone and has potentially serious
Diagnosis ------------~ side effects. The sustained release form , however, al -
lows for somewhat hi gher doses to be admin istered wh ile
Diagnosis ofthis condition requires three components.
The tirst condition is a decreased average body tem-
Table 36-3: Top Ten Symptoms ldentified in A-Z
perature, the second is a positive list ofsymptoms, and
Symptoms Questionnaire for TSD (N=84)
the third is a decreased T3 :rT3 ratio .
Symptom Percent Positive
The Pope Paul VI In stitute protoco l for making thi s di- 1 eat chocolate 77.0
agnosis invol ves th e measurem en t of body tempera- Fatigue 75.9
ture (oral) on day 5 through 9 and Peak + 5 through 9 of Mood swings 72.4
1 drink colas 67 .8
the menstrual cyc le. Thi s obtains fo lli cul ar and luteal lrritabil ity 64.4
phase temperatures. In add ition, the temperature is mea- Cold inlolerance 63. 2
PMS 62 .1
sured upon awakening and during the day at 11 :00 a.m. , Fluid retention 60 .9
2:00 p.m., and 5:00 p.m. The last three ofthese tempera- Dry skin 59 .2
Depression 57 .5
tures are averaged to obtain the average temperature of Decreased sex drive 57 .5
the day (F igu re 36-2).
From: Pope Paul VI lnstitute research , 2004.
The patient is al so asked to compl ete th e A-Z symptom

check li st (Figure 36-3). This provides a basic assess-
ment ofsymptoms that patient mi ght have. The ten most
common symptoms identifi ed in the questionnaire are Table 36-4: Symptoms of Hypothyroidism Often
shown in Table 36-3 . Many times, thi s represents a con- Not Observed in TSD (<20% Occurrence)
stellation of symptoms that are present, although sorne
are not normally assoc iated with hypothyro idi sm. Stan-
dard symptoms of hypothyro idi sm that are observed in • Listlessness ( <20%)
less than 20% of patients consi dered to have TSD are • lnappropriate weight gain (<20%)
li sted in Table 36-4. While these sym ptoms are more • Coarse skin (<20%)
• Slowed reflexes (< 10%)
commonly associated with chronic hypothyroidism, they
• Thinning of the lateral one-third of eyebrows (<10%)
were not often observed in th e TSD.
From : Pope Paul VI lnstitute resea rch, 2004.
THYROID SYSTEM DYSFUNCTION

(TSD)
TEMPERATURE ASSESSMENT RECORD
INSTRUCTIONS
1. Use a basal body temperatura (BBT) thermometer. Thls can be purchased at most pharmacles. A digita
thermometer is okay to use so long as it is a basal digital thermometer that reads in 0.1° F.
2. Take your temperatura orally for 5 minutes, by the clock (if a mercury thermometer), and until thermom-
eter "beeps" lf a digital thermometer. Do this upan awakening in the moming (lmmedlately - this Is the
8811 and then at 11am,2 pm and 5 pm.
3. Record ali 4 temperaturas In the boxes below on days 5-9 and P+S - P+9.
4. Average the 3 tempa (not lncluding the BBT) and also record it for each day in the box provided.
5. Also record your pulse rate for each of the 11 am , 2 pm and 5 pm time periods.
6. When completad, send the record to your assessing physician .
TEMPERATURE ANO PULSE RECORDINGS
Day5 Day6 Day7 DayS Day9
Upon Awakenlng PulM PulH PUIH PulM

Rata Rata Rata Rata
11:00 am
2:00 pm
5:00 pm
Average Temp.
P+S P+6 P+7 P+S P+9

Pulse Pulae Pulse Pulae Pulse
Upon Awakenlng Rata Rata Rata Rata Rata
1----~=--i
11:00 am
2:00 pm
5:00 pm
Average Temp.
Preparad by
Pope Paul VI lnstltute for the Study of Human Aeproductlon
Figure 36-2: Thyroid System Dysfunction (TSD) Temperature Assessment Record (From : Pope Paul VI lnstitute research ,
2004 ).
Chapter 36: Thyroid System Dysfunction 457
A·Z SYMPTOM CHECK UST

THYROID SYSTEM DYSFUNCTION (TSD)
INSTRUCTIONS: PlleH pi.ce . , -x• In tM box llonplcle MCh symptom thllt you c:u11'911t1y uperfenc:e. For ali thoae thllt 1
mmt.,, •)(" then me tlw ~ty of th• eymptom• u: 1•mlld; 2-modtlrate; 3-ere.
A. GENERAL WELL BEING l. EARS O Irregular Perfods_ _
O Oecreued Concentratlon__ 0 Ear lnfectlona__ O Severo Menstr1Jal Crampe _ _
O DeaNHd Mlll'llOfY__ O Rlnglng In the Ears_ _
0 Decnued S.x Orive_ _ T. MENTAL STATE
o Depnialon__ J. EYES o Arudety_ _
a Fatlp_ _ O Blurred Vlslon _ _ a 0eprua1on_ _
a Uat1MSn888_ _ O OryEyes_ _ O Low Self-Esteem_ _
o lrrllablltty_ _ O Panlc Attacka _ _
O Ughtheadedneas_ _ K. FERTIUTY
O Low Mollvatlon_ _ a lnfertfllty_ _ U. MOUTH ANO THROAT
O Poor Recall _ _ O Mlscarrfage_ _ O Abnormal Swallowtng Sensatlon:
e. ALLERGIES L FINGERNAILS a AbnormaJ Throal Senaatlona

O Allerglell_ _ O Brtttle Flngamalls_ _ O Bad Breath_ -
a ABlhfTllL_ O Unhealthy Nalls_ _ O ClnlatrSo191_ _
O Hay Fever_ _ 0 FHle Uka 1 Thumb la Preaslng
O Hlves_ _ M. HAIR Agaln&t My ThroaL..__
O Sln1.111 Onllnage_ _ O OryHalr_ _ O Thlck, Swoften Tangue_ _
O Stully Noee_ _ O Halr Losa_ _
O Prematurely Grey/Whlte Halr_ _ v. NICOTINE ANO CAFFEINE
O Thlnnlng ol Lateral One-Thlrd O 1 Eat Chocolate_ _
c. BLOOO PRESSURE
of Eyebrows_ _ O 1Or!nk Coffee _ _
O Low Blood Pressure_ _
O 1Or!nk Colas_ _
N. HANDS ANO FEET O ISmoke_ _
o. BOWELS
o
Carpa! TUMBI Syndrome_ _
O Acld lndlgeatlon_ _
O Constlpadon_ _ O Numbness or Tingllng In Hands W. PREMENSTRUALSYNOROME
O Eaophogeal Acld Renux_ _ orFeet_ _ O Fluid Retentlon _ _
O lrrltabla Bowet Syndrome_ _ O Mood Swtngs_ _
o. HEADACHES O PMS _ _
O Ulcera_ _
O Headaches_ _ 0 Re1111nse PMS_ _
O Mlgralnes_ _
E. CHEST
O Chest Palns_ _ X. SKIN
O Palpltatlons_ _ P. INFECTIONS O Acne_ _
O Ear lnlecttons_ _ O Changu In Sktn Plgmentatlon_
O Frequent Colds _ _ O Coansa Sldn__
F. CHOLESTEROL
O Hlgh Cholesterol _ _ O Frequent Sora Throats_ _ O DrySkln _ _
O Frequent Urfnary lnlectlona_ _ O Easy Brulalng___
O Aushlng_ _
G. COOROINATION
O Clumsy_ _ a. INTOLERANCES O lncreased Skln lnlecttons_ _
O ltc:hln..._ _
o Klutzy_ _ O Cold lntolerance_ _
O Poor Coordlnatlon _ _ O Heat lntolarance_ _ O Sldn "BlotchB&º_ _
O Slow Wound HeaJlng___
R. JOINTS ANO MUSCLES
H. OIET
O Easy Welght Galn_ _ a Arthrttls Aches_ _ Y. SLEEP
O Easy Welght Losa _ _ O Jolnt Aches_ _ O Falllng Asleep UncontroUably
O Excesalvely lired Alter Eattng_ _ O Muscular Aches_ _ Ourlng !he Oay _ _
O Food Cravtngs_ _ O Slowad Rellexes _ _ a lnsomnla _ _
O Food lnlolerances_ _
O Hypoglycemla_ _ s. MENSTRUAL PERICOS z. SWEATING
O lnapproprfate Welght Galn_ _ O Frequent Yoaal lnfoctlons_ _ O Nlght Sweats_ _
O Heavy Menses_ _ O SweaUng Abnormalttles_ _
PLEASE ANSWER THE FOLLOWING ADDmONAL QUESTIONS:
1. Compared to a normal penson what percentage (10-90%) ola normal person do you l e a l ? - - - -
2. Compared to the way you tell belore developlng ali ol these symptoms. all thlngs taken together, would you say you leal
(10-90%) ol what you lett lhen? _ _ __
3. 11 you could llx three ol lhe symptoms Usted above, what would lhey be: A. - - - - - - - - - - - - - - -
-------------------------------------------
FOR OFFICE USE ONLY:
General Seora ,. ___]26 " - - " ' Raw Seora= ___197,._ _ _% Ratio ..
Figure 36-3 : A-Z Symptom Check List: Thyroid System Dysfunction (TSD) (From: Pope Paul VI lnstitute research , 2004) .
458 The Med ica ! and Surgical Practice of NaProTECHNOLOGY
not producing wide flu ctuatio ns in blood levels. The T 3

that is adm ini stered decreases the rT 3 a long w ith the T4
and TSH. lt reduces symptoms and increases body tem-
perature (see below).
In th e initial phases ofthis stud y it was thought that the

patient shou ld be "cycl ed up" and "cyc led down" on
the T 3 • However, the protoco l that we are currently in-
vestigati ng is one which cycles the patients up wa rd to
T, Reverse T, a reasonable dosage (genera ll y between 15 and 45 µ g
SRT 3 every 12 hours) . The dosages are admini stered
Figure 36-4: Formation of triiod othyronine (T 3 ) and reverse
T 3 (rT 3 ) from thyroxine (T 4 ) . ora ll y on an every-1 2-hou rs basis, and the patients en-
couraged to take th e medication as close to the 12-hour
po in t as possibl e. Whil e Wil son strongly adv ises that
type ofadmini stration of th e medication , we have bee n
abl e to id enti fy no adverse effects from taking it at or
arou nd every 12 hours.
Results of Treatmen t _ _ _ _ _ _ _~
~ G) Hypothal mus During the cou rse ofthi s stud y, we we re ab le to fo ll ow

() Pituitary 82 pati ents who were treated with SRT3 . The range in
the dosage is g ive n in Tabl e 36-5. The dosages range
-)
from 22.5 to 82.5 µ g every (Q) 12 hours . The ave rage
TSH dose of 45 .4 µ g every 12 hours. The patients started on
a dosage of7 .5 µ g every 12 hours and every two to four
or five days increased the dose by increments of7.5 µ.g.
In other wo rds, the second dosage wo uld be 15 µ g ev-
ery l 2 hours, the third dosage 22.5 every 12 hours, and
so fort h.
The Pope Paul Vl ln stitute program insists that the pa-

lien! does not increase the dosage without reporting
to and getting permission from the physician. The rea-
Figure 36-05: The endocri ne system : T 4 and T 3 production. son for thi s has to do with the potenti al side effects of
Tr Thus, the treatment of thi s condition requi res ex tra
nursing time as the patients ca ll in to report thei r symp-
toms, si de effects, temperatures, and pul ses.
Table 36-5: Range of SRT3 Dose A TSD treatment/temperature log is used to trac k the
Patients with TSD =82) patient (Figure 36-6). Results ofthis in vesti gation sug-
Dosage (Q12h) n % gest that this is an important component of th is treat-
ment approach at thi s time. SRT3 m ust only be adminis-
22 .5 2 2.4
6.1
tered by the most respon sib le phys ici ans and to the
30 .0 5
37 .5 10 12 .2 most responsible pati ents.
45.0 32 39.0
52.5 27 32.9
60 5 6.1 When we eva luated the average ofthree body tempera-
82 .5 1 1.2 tures during the preovulatory (Table 36-6) phase ofthe
Total 82 99.9 menstrual cyc le, a significant increase in the mean body
temperature was observed pri or to treatment. This was
Average dose = 145.4 µg Q12h 1
statistica ll y signifí cant on ali fíve days of the preovu-
latory temperatures. On the other hand , wh il e an in-
crease in temperature was observed during the post-
Chapter 36 : Thyroid System Dysfuncti o n 459
ovu latory phase, it was to a lesser degree (Tab le 36-7). were present by an actual number of symptoms identi-
In on ly one case (on Peak + 8) was the increase ofthe fied (raw score) or by the percentage of basic catego-
postovulatory body temperature statisticall y sign ificant. ries ofsymptoms that were pos iti ve (the category score)
and with the answer to the qu estion, " What percentage
The patients were also asked to monitor their pul ses. of normal do you fee l?" These data are shown in Table
The preovulatory and postovul atory assess ment of 36- 11 for a group of 18 pati ents both before and during
pulses is presented in Tables 36-8 and 36-9. ln both
cases, a statistica ll y significant increase in the pulse Table 36-6: Average of Three Body
rate occurred while patients were on T3 therapy. In gen- Temperatures Before and During T 3 Therapy
era l, the pulse rate increased by 7 to 1Obeats per minute (Preovulatory)
during the pre-Peak phase of the cyc le and by 8 to 9 MeanTemp MeanTemp
beats per minute durin g the postovulatory phase. Temperature at Before T3 During T, p-value'
Day 5 97.8 98.0 .005

The thyroid function studies also change while on SRT3 (n=70 ) (n=63)
therapy. The average leve Is of various thyro id function Day 6 97.8 98.1 .023
studi es both before and during SRT3 therapy are shown (n=72 ) (n=66)
in Table 36- 1O. There was a sign ifi ca nt change in ali of Day 7 97.8 98.1 .0003
(n=72) (n=67)
these levels. The total T4 , free T4 , TSH , and rT 3 ali de-
Day 8 97.7 98.1 .0006
creased while the total T3 increased. As a result, the (n=69) (n=61 )
T 3 :rT 3 ratio also increased signi ficant ly. Day 9 97 .8 98.0 .041
(n=69) (n=60)
Associated with SRT3 therapy was a significant improve- 1. Mann-Whitney U test for difference in medians
ment in symptoms. Using theA-Z Symptom Check List, From: Pope Paul VI lnstitute research, 2004 .
one cou ld identify the percentage of symptoms that
THYROID SYSTEM DYSFUNCTION (TSD) Ph onc numbers _ _ _ _ __ _ _ _

DATE TREATMENT STARTS :_ _ _ _ __
TREATMENTITEMPERATURELOG
CYCLE#: _ _ __ _
Total T4 Date_ _ _ Result _ _ __
NAME:_ _ _ _ _ _ _ _ _ _ _ _ _ _ __
1. On each day of treatment. record your basal temperature upo n awakeni ng and at 11 am, 2 pm and 5 pm
2. Average the 11 am. 2 pm and 5 pm temperalures. Record 1n box
3. You must take your medicines to the minute (every 12 hours) 5. Begin a new log w1th the beginmng of each new menstrual cycle
4. Using the code numbers below. record any s1de effects you may be expenencmg and place a ·p· m the"Cycle Da( box on your Peak Oay.
Date
Cycle Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Dos e
Temp. upan
ulsc
" '" ""'" """ '" 1"1115<
""
, .... l t'\llJt 1'111 ..
'"" , ... ,....
"'" ""'" "'" "'" Pulse
Awakening
11 :00 am
2:00 pm
5:00 pm
Average
Temp.
Side Effects
Pt. toCall On
~~~-ª,~~o~~~d
Date
Cycle Day 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
Oose
Temp. upan Pulse l'ulS<: Pulse f'ulsc Pulse Pu lse Pulse l~• lsc f>u lsc
Awakening
11:00am
2:00 pm
5:00 pm
Ave rage
Temp.
Side Effects
Pt. to Call On
!?~~.ª1~~0~~~
SI DE EFFECTS CODE : O=No Slde Effects 1=Fluid Retention/Putflness 2:cFlu-like Feelings/Achlness J=Dull Headache 4=Edginess/lrritability S=lncreased Awareness o f Heartbeat
Figure 36-6: Thyroid System Dysfunction Treatment/Temperature Log (From : Pope Paul VI lnstitute research , 2004).
SRT3 treatment. In each case on SRT3 treatment, the percent of patients reported no side effects (Table 36-
symptom complex improved significantly. 12). ln decreasing order, the most common side effects
observed were dull headache (68.3 %); increased aware-
Side effects are associated with SRT3 therapy. On ly 15.8 ness of heartbeat (46.3%); edginess/ irritabili ty (43.9%);
flu-l ike fee ling/ac hiness (36.6%), and fl ui d retention/
puffiness (25.6%). Many ofthese symptoms were onl y
Table 36-7: Average of Three Body tempormy while the individual became accustomed to
Temperatures Before and During T 3 Therapy using the medication . Sorne ofthem ex isted prior to the
(Postovulatory) treatment and were not associated with it at ali ; thus, it
is important to inquire about these symptoms prior to
Mean Temp Mean Temp
the onset oftherapy in order to establ ish a baseline. In
Temperature on day Before T 3 During T 3 p-value'
sorne cases, the medication had to be discontinued be-
P+5 98. 0 98.2 NS' cause of side effects. T he most important side effect
(n=63) (n=63)
that we noticed was the increased awareness of heart
P+6 98.1 98.2 NS
(n=64 ) (n=47 ) beat or an increased hea1t rate. 1f the heait rate gets
P+7 98. 1 98.3 NS above 100 beats per m in ute, we ha ve adv ised that the
(n=61 ) (n=50 ) patients either decrease their dosage or, in some rare
P+8 98.0 98 .3 .037 cases, take propanolol 1Omg by mouth (PO) two times a
(n=64 ) (n=46)
day (BID) or three times a day (T ID). This wi ll control
P+9 98. 0 98.2 NS
(n=60) (n=50)
the symptoms but should only be used when the treat-
ment can benefit the patients .
1. Mann-Whitney U testfor difference in medians
2. NS=not statistically significan!
From: Pope Paul VI lnstitute research, 2004. lt does need to be emphas ized that these side effects
are real , but they are a lso mostly temporary or dose
re lated. Thus, patients ca n be managed through the side
effects as they adju st to the medication or the medica-
tion can be discontinued.
Table 36-8: Mean Pulse Before and During T 3
Therapy (Pre-Peak)
Mean Pulse Mean Pulse

Final Note _ _ _ _ _ _ _ _ _ _ _~
Time of Day Before T 3 Durin g T, p-value'
11 a.m. 76 .2 83.6 .0008

The A-Z Symptom Check List used in this project cou ld
(n=62) (n=68) be modified because sorne of the sym ptoms are rarely
2 p.m. 78 .8 85 .1 .0006 observed. In Figure 36- 7, those symptoms which were
(n=64 ) (n=70 )
observed in less than l O percent of the patients and in
5 p.m. 76 .3 86 .5 <.0001
Figure 36-8 those symptom s whi ch were observed in
(n=63) (n=67 )
less than 20 percent of the patients are excluded from
1. Mann-Whitney U test far difference in medians
Table 36-10: Thyroid H ormone Assessment

Before and During T 3 Therapy for TSD
Mean Value Mean Value

Hormone Before T 3 During T, p-va lue'
Table 36-9: Mean Pulse Before and During T 3
Therapy (P+ 7) TolalT, 7 .51 3. 20 <.0001
(n=81 ) (n=45 )
Mean Pulse Mean Pulse 1.03 0.51 <.0001
FreeT,
Time of Day Before T 3 During T, p-value' (n=74) (n=24 )
11 a .m. 78.9 86.0 .01 TSH 1.92 0.041 <.0001

(n=57 ) (n=48 ) (n=79 ) (n=23 )
2 p .m. 78 .6 87 .0 <.0001 Tolal T 3 95.9 21 3.1 <.0001

(n=58) (n=48) (n=74 ) (n=24 )
5 p.m. 78 .7 87 .9 .0002 Re ve rse T 3 21 3.3 87 .2 <.0001

(n=57 ) (n=52) 34 .6 <. 0001
T 3 :rT 3 ratio (n=22) 5.3
1. Mann-Whitney U test far difference in medians 1. Mann-Whitney U test far difference in medians
From: Pope Paul VI lnstitute research, 2004 . From: Pope Paul VI lnstitute research, 2004.
Chapter 36: Thyroid System Dysfuncti on 461
Table 36-11: R elief of Symptoms with T reatment Table 36-12: Side Effects of SRT 3 Therapy
ofTSD wi th SRT 3 (N=82)
Symptoms % Symptoms Present1 Side Effect n %

Question naire Befo re
Assessment Treatment During T, p-value 1 None 13 15.8
Fluid retention/puffiness 21 25.6
Raw score 2 (n=18) 35.3 21 .1 .001
Flu-like feeling/achiness 30 36.6
Category score3 (n=18) 64.3 46.5 .0007 Dull headache 56 68.3
What % of norma l do 67.5 82.8 .006 Edg iness/irritability 36 43.9
you feel? (n=16) lncreased awareness of hea rtbeat 38 46.3
1. Matched pairs befare and during treatment.

2. Percent of symptoms present in the list of 97 symptoms.
3. Percent of general categories (A-Z) (n=26) that had at least one symp-
tom present.
have not been full y eva luated and are an empiri ca l ob-
servati on at the present time. Thi rdl y, a pos itive effect
the chec k list. The check li st has then been mod ified to on the subseq uent mi scarri age rate is bei ng reported in
a revised A-Z Symptom Check List, which is fo und in thi s textbook and is fo und in Chapter 57 under recurrent
Figure 36-9. spontaneous aborti on.
The author debated whether to present th is aspect of The author hopes that peopl e will seri ously consider
th e resea rch bein g co ndu cted in associat ion with thi s. In particular, the target-orga n effects of reverse T 3
NaProTECHNOLOGY. This approach to the evaluation and the competition between rT 3 and T3 at the tiss ue
and treatment of thyro id dysfun cti on employs a new, leve! mu st be furth er eva luated. Beca use T4 co nverts
counter-cultural strategy. Three as pect of thi s condi - itse lf to both T 3 and rT 3 , the subsequent treatment of
ti on intluenced the auth or's decis ion to pu bli sh it. many ofthese co nditions with T4 may actuall y be con-
tributing to the pro blem rather than so lvi ng it. The pro-
First, signi fica nt improvement was observed in patients fess ion has become accustomed to treating a bi ochemi-
who had been properly eva lu ated and subseq uently ca l test (such as an elevated TSH leve!) often without
treated. This was signifi ca nt and many patients com- co nsidering th e symptoms of th e pati ent. Th ose in-
mented pos iti ve ly about it. Second , impl ementati on of vo lved in the management of thyro id di sease and di s-
thi s approach to the treatment of the thyro id appears to cuss ion of thyro id conditi ons should eva luate thi s con-
be assoc iated with an increased number of pregnancies dition and aim fo r a definiti ve conclusion while being
in the infertility program and an improvement in the treat- open-min ded in its eva luati on and thought.
ment of premenstrual symptoms. However, these data
A-Z SYMPTOM CHECK LIST

THYAOID SYSTEM DYSFUNCTION (TSD)
Name: __________________________ Date: __________
INSTRUCTIONS: PIHH pl8Ce en "X" In the box alongalde eec:h aymptom thllt you c:urrently expertenc:e. For ali thon th•t you
merk en "X" then rete th• ••verlty of the aymptoma H : 1 •mlld; 2•moderate; 3.._vere.
A. GENERAL WELL BEJNG l. EARS O Irregular Periods
O Dec:reased Conc:entratlon_ _ O Severa Menstrual Cramps
O Decreased Memory__ O Rlnglng In lhe Ears__ --
0 Dec:reased Sex Orive__ T. MENTAL STATE
O Depresalon__ J. EYES O Anxlety_ _
O Fatigue__ O Blurred Vlslon__ O Depresslon_ _
O Ustlessness__ O Dry Eyes__ O Low Self-Esteem
D lrritablllty__ O Panlc Attacka_-
D Llghtheadedness__ K. FERTILITY
O Low Mollvatlon_ _ O lnfertllity__ U. MOUTH ANO TliROAT
O Poor Recall__ O Miscarriege_ _
B. ALLERGIES L FINGERNAILS O Abnormal Throat Sensatlons_ _
O Allergles_ _ O Brittle Flngemalls_ _ O Bad Breath_ _
O Unheallhy Neils_ _ O Canker Sores_ _
O Hay Fever_ _ O Feels Uke a Thumb Is Presslng
M. HAIR Agalnst My ThroaL__
O Slnus Dralnage_ _ O DryHalr_ _ • •e : T 1
O Stuffy Nose_ _ O Halr Losa_ _
O Prematurely Grey/Whlte Helr_ _ V. NICOTINE ANO CAFFEINE
C. BLOOO PRESSURE • s., ·a R't O 1Eat Choc:olate_ _
O Low Blood Pressure_ _ O 1Dr1nk Coffee_ _
O 1Drink Colas_ _
O. BOWELS N. HANOS ANO FEET
O Acld lndlgestlon_ _
O Constlpatlon_ _ O Numbness or Tingling In Hends W. PREMENSTRUALSYNOROME
orFeet_ _ O Fluid Retentlon _ _
O Irritable Bowel Syndrome_ _ O Mood Swlngs_ _
O. HEADACHES O PMS_ _
O Headaches_ _
O Mlgralnes_ _
n• mm
E. CHEST
O Ches! Pains_ _ X. SKIN
O Palpltatlons_ _ P. INFECTIONS O Acne _ _
O Changes In Skin Plgmentatlon__
F. CHOLESTEROL O Frequent Colds _ _ O Coarse Skln_ _
O Hlgh Cholesterol_ _ O Frequent Sora Throats_ _ O DrySkln_ _
O Easy Brulsln g _
G. COOROINATION O Flushlng_
O Clumsy_ _ Q. INTOLERANCES
O Klutzy_ _ O Cold lntolerance_ _ O ltchlne.._ _
O Poor Coordinallon_ _ O Heat lntolerence_ _ O Skln "Blotches"_ _
O Slow Wound Healing__
H. OIET R. JOINTS ANO MUSCLES
O Easy Welght Gain_ _ O Arthritls Aches_ _ Y. SLEEP
O Joint Aches_ _ O Falllng Asleep Unc:omrollably
O Excesslvely Tirad Alter Eating_ O Muscular Aches_ _ Durtng lhe Dey_ _
O Food Cravlngs_ _ O lnsomnia_ _
O Food lnlolerances_ _
O Hypoglycemla_ _ S. MENSTRUAL PERICOS Z. SWEATING
O lneppropriate Weight Geln_ _ O Nlght Sweats_ _
O Heavy Menses _ _ O Sweatlng Abnorrnalities_ _
PLEASE ANSWER THE FOLLOWING ADDITIONAL QUESTtONS:
1. Comparad to a normal person what percentage (10-90%) of a normal person do you feel? _ _ __
2. Comparad to the way you felt befare developlng ali of lhese symptoms. all thlngs taken together, would you sey you 1.,e1
(10-90%) of what you felt lhen? _ _ __
3. 11 you could flx three of lhe symptoms listad above, what would they be: A. - - - - - - - - - - - - - - - -
ª· ~~~------------- º·-----------~--
FOR OFACE USE ONLY:
Generel Sc:ore • __]26 .._ _ % Raw Score • _ _ _197=_ _ _% Ratio •
Figure 36-7 : A-Z Symptom Check List: Thyroid System Dysfunction (< 10%) (From: Pope Pa ul VI lnstitute research , 2004).
Chapter 36 : Thyroid System Dysfunction 463

Name: ___________________ _____ _ _ _ Date: __________
INSTRUCTIONS: PINH plac:e en "X" In the box alon99lde each aymptom thet you cummtly experlence. For all thoae thet you
mark an "X" then rete the aevertty of tha aymptoma H : 1 .. mlld; 2•moderate; 3•aevere.
A. GENERAL WELL BEING l. EARS O Irregular Perlods_ _
O Decreased Concentratlon__ S E ' ' $' O Severa Menstrual Cramps _ _
O Decreased Memory__ D Rlnglng In the Ears_ _
O Decreased Sex Orive_ _ T. MENTAL STATE
O Depresaion_ _ J. EYES O Anxlety_ _
O Fatigue_ _ D Depresslon _ _
D DryEyes_ _ D Low Seif-Esteem_ _
o lrritablllty_ _ D Panlc Attacks _ _
O Llghtheadedness_ _ K. FERTILITY
O Low MoUvatlon_ _ D lnfertlitty_ _ u. MOllTH ANO THROAT
D Poor Recali_ _ O Miscarriage_ _ o ºh '€ "a ta r st's
B. ALLERGIES L FINGERNAILS
D Aliergles_ _ O Brittle Flngemalls_ _
D Unhealthy Nails_ _
O Hay Fever_ _
M. HAIR
O Slnus Dralnage_ _ D DryHalr_ _
D Stuffy Nose_ _ D Halr Losa_ _
V. NICOTINE ANO CAFFEINE
C. BLOOD PRESSURE rr 1
6 '11 '?;:: O 1Eat Chocolate _ _
O Low Blood Pressure_ _ D 1Orlnk Coffee_ _
D 1 Drlnk Colas _ _
D. BOWELS N. HANDS ANO FEET D ISmoke_ _
D Acld lndigestion _ _
D Constipatlon_ _ D Numbness or Tlngllng in Hands W. PREMENSTRUALSYNDROME
2 E t 1 ' ' '1 9 11 15 orFeet_ _ O Fluid Retention _ _
D Irritable Bowel Syndrome_ _ D Mood Swings_ _
O. HEADACHES D PMS_ _
O Headaches_ _
E. CHEST D Mlgralnes_ _
X. SKIN
a o 1 1 P. INFECTIONS O Acne _ _
F. CHOLESTEROL
O Frequent Sore Throats_ _ O DrySkln_ _
D Easy Brulsing,__
G. COORDINATION O Flushlng_ _
D Clumay_ _ Q. INTOLERANCES
D Kiutzy_ _ O Cok! lntolerance_ _ O ltchlnesa_ _
D Heat lntolerance_ _
H. DIET R. JOINTS ANO MUSCLES

O Easy Weight Galn_ _ O Arthrltls Aches_ _ Y. SLEEP
O Joint Aches_ _ 861'11'' p'' 11 t 1
O Excesslvely Tirad Alter Eating_ O Muscular Aches _ _

O Food Cravlngs_ _ O lnsomnia_ _
O Food lntolerances_ _
O Hypogl~mla_._ S. MENSTRUAL PERIODS Z. SWEATINQ
O Night Sweats_ _ ..
O Heavy Menses_ _
PLEASE ANSWER THE FOLLOWING ADDITIONAL QUESTIONS:
1. Comparad to a normal person what percentaga (10.90%) of a normal parson do you leal? _ _ __
2. Comparad to the way you fati before developlng ali of thase symptoms, ali thlngs taken together, would you say you tuel
(10.90%) of what you tell then? _ _ __
3. 11 you could flx lhree of the symptoms Usted abova, what would they be: A. - - -- - - - - - - - - - - -
c. _ _ _ __________ _ _
ª·----------- - ---
General Seor• • =-- ""
__126 Raw Seora • --~197= _ _ _% Ratio •
Figure 36-8 : A-Z Symptom Check List: Thyroid System Dysfu nction (<20%) (From : Pope Paul VI lnstitute research, 2004).

INSTRUCTIONS: Please placean " X" in the box alongside each symptom that you currently experience. For ali those that you
mark an "X" then rate the severity of the symptoms as : 1=mild ; 2=moderate; 3=severe.
A. GENERAL WELL BEING G. EARS Q. MENSTRUAL PERICOS

O Decreased Concentration C Ringing in the Ears_ _ O Heavy Menses_ _
O Decreased Memory_ _ - -
0 Decreased Sex Orive H. EYES O Irregular Periods _ _
O Depression__ - - O Dry Eyes _ _ O Severe Menstrual Cramps _ _
0 Fatigue _ _
O lrritability_ _ FERTILfTY R MENTALSTATE
O Lightheadedness _ _ O lnfertility_ _ O Anxiety _ _
O Low Motivation O Miscarriage_ _ O Depression _ _
O Poor Recall_- O Low Self-Esteem
J . FlNGERNAILS O Panic Attack s~
B. ALLERGIES O Brittle Fingernails_ _
O Allergies _ _ O Unhealthy Nails_ _ S. MOUTHANOTHROAT
O Hay Fever_ _ O Bad Breath
O Sinus Drainage_ _ K HAIR O Canker Sores_
O Stuffy Nose_ _ O DryHair_ _
O Hair Loss _ _ T. NICOTINEANOCAFFEINE
C. BLOOD PRESSURE O 1 Eat Chocolate
O Low Blood Pressure_ _ L HANDS ANO FEET O 1 Drink Coffee - -
O Numbness or Tingling in Hands 0 1 Drink Colas - -
D. BOWELS orFeet _ _ 0 1 Smoke_ _ --
O Acid lndigestion_ _
O Constipation _ _ M. HEADACHES U. PREMENSTRUALSYNOROME
O Irritable Bowel Syndrome_ _ O Headaches O Fluid Retention
O Migraines - = - O Mead Swings-=-
E. COORDINATION 0 PMS_ _
O Clumsy _ _ N. INFECTIONS
O Klutzy _ _ O Frequent Sore Throats _ _ V. SKJN
O Peor Coordination _ _ O Acne
O. INTOLERANCES O Dry Skin_
F. DIET O Cold lntolerance O Easy Bruising_ _
O Easy Weight Gain _ _ O Heat lntolerance_ O Flushing_ _
O Excessively Tired After Eat- O ltchiness_ _
ing_ _ P. JOINTS ANO MUSCLES
O Food Cravings _ _ O Arthritis Aches W. SLEEP
O Food lntolerances_ _ O Joint Aches - - O lnsomnia_ _
O Hypoglycemia_ _ 0 Muscular Aches_
X. SWEATING
O Night Sweats _ _
PLEASE ANSWER THE FOLLOWlNG AOOITIONAL QUESTIONS:
1. Compared to a normal person what percentage (10-90%) of a normal person do you fee l? - - - -
2. Compared to the way you felt before developing ali of these symptoms. ali things taken together, would you say you feel
(1 0-90%) of what you felt then? _ _ __
3. lf you could fix three of !he symptoms listed above , what would they be: A. - - - - - - - - - - - - - - - - -
c. ________________
ª·-----------------
General Score /26=___% Raw Score = _ _ _191= _ _ _% Ratio = Revised 7/1/03
Figure 36-9 : Revised A-Z Symptom Check List: Thyroid System Dysfunction (From: Pope Paul VI lnstitute research , 2004) .
Chapter 36: Thyroid System Dysfunction 465
1. Wil so n ED: Doctor 's Manual for Wil so n 's Syndrome. 3'' 4. Mackowiak PA , Wasserman SS Le vin e MM: A C riti ca! Ap-
Ed. M uskeegee Medica! Publishin g, 1997 . prai sal of 98 .6 degree s F, ch e Upper Lim it o f th e Upper
Bod y Te mpe rat ure, a nd Oth er Legac ies of Car! Re inh o ld
2. Wi lso n ED : Wi lso n 's Synd rome: The Miracle of Fee ling
Au g ust Wunderli ch JAMA 268 :15 78 -15 80, 1992
Well. Co rne rsto ne Publi shin g, Orlando , 1996.
5. Shi bui K, Uchi yarna M, Okawa M, eta!: Diurn a! Flu cn1ation
3. Webs ite, American Th yro id Associat ion 200 1.
of S leep Pro pensi ty and Ho rm ona l Secret io n across the
Menstrual Cyc le. Bi o/ Psyc hi atry. 48: 1062-1068 , 2000.
The Role of the Compounding Pharmacist
Dana Reed-Kane, Pharm D.
Compounding: The History_ _ __ ~

M any ofthe protocols used in NaProTECHNOLOGY
invol ve th e use o f co mpo unded medicati o ns;
therefore, the compounding pharmac ist plays a vital role Pharmacy began with Hippocrates and Galen, who were
in the practice of NaProTECHNOLOGY. The triad rela- phys icians in the B. C. era and who obta ined their rem-
ti onship between the pati ent, prov ider, and pharmac ist edies, unguents, lotions, eli x irs, and decoctions from
is the bas is of compounding pharmacy. Compounding vari eti es of pl ants, mineral s and, of course, from ani-
pharmaci sts can create customized medicati ons fo r pa- mals. These were to foreshadow a future almost up to
tients in a variety of dosage fo rm s, deli very systems the present day because many of the still-finest rem-
and strength s to uniquely meet each patient's needs. edi es in use toda y come fro m plants, mineral s, and ani-
Proper communi cati on with the pharmac ist is necessary mals. Most chemi call y manipulated compounds ofto-
for cu tomization of th e therapy. lt is important to di s- day are refin ements and manipul ati ons of compounds
cuss types of bases, re lease ch aracteri sti cs, inacti ve and such as benzene, sugar, steroids, aldehydes, and more.
acti ve ingredients, etc. so that the pharmac ist knows
exactl y how the medicati on is to be compounded . Jt is From its beginnings, pharmacy and the use of drugs
also very importn ant to educate the ph annacist about has been acco mpani ed by a certain mystique. A di sease
the protoco ls and the proper admini strati on of the thera- in the o ld days had certain unknowns a bout it and was
pi es so that the patient is coun se led pro perl y at the often allev iated with drugs, which took on " mystic" pro-
pharmacy. porti ons to the superstiti ous. In the l 9th and earl y 20th
centuries, th ose remed ies fo und their way into bottles
Many people are un famili ar with compounding pharma- and exoti c pac kages and were so ld . ln th e earl y l 900 's,
cies and pharmaci sts. The fol low ing info m1ati on de- the " dru gstore" usual ly contain ed a dark, pleasant,
scribes compounding phannacy and its ro le in the de- mysteri ous-smelling back room . .. the prescription room .
li very of healthcare today. T he prescripti on room was fo r compounding. Thi s was
the pl ace where compounding ofremedi es was done by
the pharmacist. Suppos itori es, capsul es, ointments, lo-
467
tions, elixirs, fluid extracts, and tinctures were manufac- different needs, com pounding pharmacy wi ll always be
tured at the drugstore leve!. This went on until those an essential practice of the profession and of health
notable pioneers uch as Eli Lilly, E.R. Squibb, W.E. ca re.
Upjohn and Merck found out that it was very lucrati ve
to manufacture and package these drug delicac ies fo r
dispensation at the drugsto re leve!. They could make Compounding: The Need _ _ _ _ _~
them prettier, tastier, more stab le, and less expens ive ly
than the drugg ist ever could, so the public thought. Th e basis of the profession of pharmacy has always
Together with market ing, this marked the beginning of been the pati ent-ph ys icia n-pharmac ist relationship.
the end fo r the old "drugstore" and the start of the Through this relationship, patient needs are determin ed
pharmaceutical big-box industry. and decisions are made about treatment regimens that
may include a compounded medication . There are a
number of reasons to compound medications in clud-
Compounding: The Definition _ _ _~ ing, but not limited to:
The preparation, mi xing, assem bling, packaging, and la- Medications that are not commerciaUy available:
beling ofa drug or device as a result ofa practitioner's Manufacturers must be assured that there wi ll
prescription drug based on the practitioner-patient-phar- be a return on their in vestment when entering
mac ist relationship in the course of professional prac- the market place with a drug product. Therefore,
tice. Compounding result in a cu tomized medication physicians prescribe and pharmac ist dispense
prepared by a pharmacist according to a doctor 's speci- only limited chemica l fo rm s, dosage forms ,
fications to meet an individual patient need. Compound- strengths, fla vor , and packaging. Compound-
ing pharmacists genera ll y make medications using raw in g allows the ph ys ician to prescribe a custom-
chemicals, powders, and eq uipment. tailored medication that is not available commer-
cially.
Compounding: The Pharmacist _ _ __ Medications that are not stable:

Pharmacists prepare smal l quantities ofthe pre-
Pharmacy schoo l teach students to compound, an d scription more frequently to ensure stabili ty of
state boards ofpharmacy test, license, and regulate this the product for its intended use.
traditional practice of the profession. Recentl y, the a-
tional Assoc iation of Boa rds of Pharmacy deve loped Modified commerciaUy available medications:
"Good Compounding Practices Appli cabl e to State-Li- Physi cians prescribe a commercially ava ilable
censed Pharm ac ies" and the United States Pharmaco- medication in a different dosage form to meet a
poeia Convention , !ne. drafted " Pharmacy Compound- specific pati ent need and ensure pati ent compli-
ing Practices." ln 1997, legislation was passed as part of ance. For example, if a patient is al lergic to a pre-
the Food and Drug Administration Modernization Act serva ti ve or dye in a manufactured product, the
(F DAMA) that set forth the federal legal parameters for compounding pharmac ist can prepare a dye-free
compounding medications. These documents al! rec- or preservati ve-free dosage form. Sorne patients
ognize the importance of compounding to quality medi- have diffi cu lty swa ll owi ng a capsul e require a
ca! care in the United States, and estab li sh standards lozenge. Many pediatric patients will not take
fo r the entire profession of pharmacy. their medicine when it is bitter but will take thei r
medicine once it is flavored to their liking.
The compounding pharmac ist is a problem-so lver in the
community working with patients and physicians to ga in
posi ti ve therapeutic outcomes. No other hea lth care pro- Compounding: Regulation ______
fessional can prepare new dosage fo rm s to meet patient
needs. Even when modern sc ientifi c technologies ha ve Compounding is a fundamental aspect of the practice
produced new chemi ca l entiti es, the abi lity to comb ine ofpharmacy. Pha1macy practi ces, including compou nd-
one or more chem ica ls into a new preparation or pro- ing, have been hi storica lly regulated by state board of
cess the existing dosage form into one that is better- pharmacy. The U.S. Food and Drug Admin istrati on
su ited for the patient has remained the domain of the (F DA) alternative ly regul ares man ufac turers according
pharmacist. Because every patient is di ffe rent and has to Good Manufacturing Practices.
Chapter 37: Role of the Compounding Pharmacist 469
In the late 80 's early 90 's, the FDA began taking en- the FDA decided to issue immediate guidance concern-
forcement action against compounding pharmacists. In ing when it wo uld exerc ise enforcement action again st
1995, the pharmacy profession introduced legislation pharmacy compounding. The CPG identifies two FDA
on Cap itol Hill clarifying that compounded medications focal points related to pharmacy com pounding. FDA's
were an essential part of the practice of pharmacy and first major concern is estab lishing a di stinction between
that Congress did not intend to outlaw this practice manufacturing and compounding. A second concern is
when passing the Food, Drug, and Cosmetic Act of 1938. the quality of compounded medications. The Interna-
tional Academy ofCompounding Pharmacists (IACP)
In November 1997, President Clinton signed the Food and the pharmacy industry ha ve commented to the FDA
and Drug Administration Modernization Act (FDAMA) on many procedural and substantive problems with the
into law. This legislation included Section 503A, which CPG
forma ll y addressed the practice of compounding phar-
macy and invalidated an FDA claim that ali compounded
medications were new drugs in violation of the FDA Compounding: Locating a Pharmacist in
new drug approval process as defined in the Food , YourArea _ _ _ _ _ _ _ _ _ _ _~
Drug, and Cosmetic Act of 1938.
The International Academy ofCompoundi ng Pharma-
Section 503A specifically exempted compounded drugs cists (IACP) is an internati ona l, non-profit association
from the new drug appl ication process and from comp li- established in 1991 to protect, promote, and adva nce
ance with good manufacturing provisions ofthe Food , the ai1 and science of pharmacy compound ing. IAC P
Drug, and Cosmetic Act. However, section 503A also provides support to more than 1,800 pharmacist, tech-
gave the FDA a new ro le in the regulation ofpharmacy nician , physician, and patient members through pro-
compounding by allowing the FDA to address abuse of grams and services inc luding third-party advocacy,
the compounding label and pharmacies manufacturing government representation , regulatory analysis, public
drugs under the gui se of "compounding." relations support, referra l services, literature searches,
anda fellowship program . Ifyou wo uld like to locate a
A gro up of compounding pharmacies challenged the pharmacist in your area cal! 1-800-927-4227 or visit the
marketi ng and advertising provisions ofSection 503A website at www.iacprx.org.
in District Court (Western States Medica! Center v. Th-
ompson) . They claimed that the marketing and adver-
tising provisions violated First Amendment rights of Compounding: Quality Control ---~
free speech. The pharmacists won their case in District
Court. The court decided to sever the advertising sub- Once you have located a pharmacist it is important to
section from Section 503A ofthe FDAMA legislation. make sure they are well trained, ed ucated, law abiding,
and reputable. In order to do this , you can ask the fol-
·The FDA appea led the case to the Court of Appea ls for low ing questions to determine the pharmacist's degree
the Ninth Circuit, where the pharmacists again won their of expertise, qualifications, and quality control mea-
case. However, the Appeals Court decided that the ad- s ures :
vertising subsection ofthe legislation could not be sev-
ered from Section 503A . Thus, the entire FDAMA Sec- l. How man y hours of co mpounding-re lated continu-
tion 503A was discarded. ing education do your pharmacists receive per year?
lfspecialized, how many hours in that specia lty?
The FDA appealed the case to the U. S. Supreme Co urt.
On April 29, 2002 the Supreme Court ruled that the mar- 2. Are you members ofany ofthe fo ll owing organ iza-
keting and advertising provisions in Section 503A were tions:
unconstitutional violations of the First Amendment.
a. PCCA (Professiona l Co mpounding Centers of
However, the ability to sever the adverti sing provision
America)- represent, train , provide continuing
was not appealed, so the decision ofthe Appeals Court
education, and offer technical support for over
carried on that issue. Section 503A was struck down in
3500 compoundi ng pharmacies wo rldwide.
its entirety.
b. IACP (International Academy of Compound-
In June 2002, the FDA issued a Compliance Policy Guide ing Pharmacists)- represent and provide con-
(CPG) for pharmacy compound ing . In the absence of tinuing education for over 1500 compounding
the regulatory framework provided by Section 503A, pharmacists worldwide .
c. ACA (American College of Apothecaries )- rep- 10. Do you have a system in place for dealing with a
resent, train , and provide continuing educa- recalled product, batch , or chemical?
tion for over 700 pharmacists nationwide .
11. Do you have a system in place to deal with dispens-
3. Who does the actual compounding ofthe products ing/compounding errors and ADR's?
and what is his or her train ing?
12. Do you have a quality assurance or follow -up pro-
a. Pharmacist
gram?
b. Intern
c. Certified technician
13. Do you research and supply written and/or verbal
information about the compounded product to the
4. What is your pharmacist-to-technician ratio?
patient and/or provider?
5. How do you ensure proper compounding of prod-

14. Do you uphold the triad relationship of compound-
ucts?
ing, which invo lves the patient, provider, and phar-
a. Do you ha vean analytical balance with printer? macist as the basis for pharmacy practice?
b. Do your pharmacists check the products be-
fore , during, and after the compounding pro- 15. Do you follow current state and federal regulations
cedure? applicable to the practice of compounding phar-
macy?
6. Do you use the most up-to-date technology to docu-
ment compounding procedures? (e.g. computerized 16. Do you compound products that are outside your
logging system which tracks a chemical 's lot, expi- area of expertise? Do you refer to a colleague when
ration, and quantity as well as checking for math- the request is outside your area of expertise?
ematical accuracy)
17. Is your compounding environment suitable for pro-
7. With regard to sterile products compounding: cessing quality products?
a. Do you have a class 10,000 clean room ?
b. Do you ha ve a class 100 hood? lfthe pharmacist you are interviewing can answer these
questions, you can be assured that you have found a
c. Are your clean room and/or hood regularly in-
qualified pharmacist. You yourselfmay not know ali the
spected ?
answers to ali of these questions, but based on the
d. Do you have an autoclave? answers from the pharmacist, you can figure out if they
e. How are your end-products sterilized? are competent. The relationship between pharmacist and
f Do you have your products checked for po- provider is extreme ly impo rtant when using com -
tency, sterility, and pyrogens? pounded therapies for NaProTECHNOLOGY. It is won-
g. Do your compounding personnel undergo pro- derful to have a working relationship with a compound-
cess validation tests? ing pharnrncist in your area that is available at a mo-
ments notice to serve your patients.
h. Are your compounding personnel specially
trained or certified?
1. Do you follow the ASHP (American Society of
Compounding: Natural Hormones _ _~
Health-System Pharmacists) Guidelines on
Quality Assurance for Pharmacy Prepared Ster-
Although natural , bioidentica l hormones have been
ile Products and/or the USP (United States
available to women for over fifty years in both the United
Pharmacopoeia) Chapter 1206 guidelines for
States and Europe, they ha ve not been prescribed widely
sterile product compounding?
by the majority of doctors primarily because ofthe patent
system in the United States.
8. Do you purchase your chemicals from a reliable
source that inspects for quality using USP F guide- atura! , bioidentical hormones cannot be patented for
lines? the same reasons you can not patent natural air, water,
or vitamins; substances found in nature cannot be pat-
9. How do you determine product stability and expira- ented. Our pharmaceutical industry is driven by profit;
tion dating? therefore, there is little orno financia! incentive for phar-
Chapter 37 : Role of the Compounding Pharmacist 471
maceutical companies to spend the $200 million plus Facts about BHRT
necessary to patent, develop, and test even one ofthese
The Medica! Definition : Natural = Bioidentical
hom1ones, and to then get it approved by the Food and
DrugAdministration (FDA). Many more millions would BHRT is currently a topic of great interest to women
then be necessary to bring an approved hormone to and men. Bioidentical hormones have the exact molecu-
market and to promote it to providers and their patients. lar structure as those made in the human body. In other
A patent grants an exclusive right to sell the patented words, the two are isomolecular and indistingu ishable
product for 17 years from the date of issue. The pharma- from each other. Bioidentical hormones produce the
ceutical industry is not interested in researching and same physio logic responses as those of endogenous
developing therapies that are natural because they are hormones. As mentioned above, th e Food and Drug
not unique or financially inviting. Unpatentable natural Administration (FDA) considers bioidentical hormones
bioidentical hormones can be manufactured by any to be natural regardless of their so urce, andas a result,
pharmaceutical company as well as compounded by they cannot be patented .
pharmacists, as long as standards of purity and consis-
tency of dose are met. Misconceptions About BHRT
The public and most members ofthe medica! commu-
With a lack of manufactured pharmaceutical products nity are confused about the significance of BH RT. lroni-
on the market, comes a lack of education by providers cally, consumers tend to be more concerned about the
and a lack ofresearch in the clini cal setting. The phar- sources of hormones rather than the effects produced
maceutical industry pays for a majority of clinical re- by those hormones. Bioidentical hormones can be ex-
search trials. Without industry support, clinical trials tracted and derived from a variety of different sources,
using natural bioidentical hormones are far and few be- such as plants (soy or yams) or anima Is (pigs or horses).
tween. Providers today, who have littl e time to keep up They can also be produced synthetica ll y. However,
with the world of double-blind , placebo-controlled drug hormones of plant or animal extraction that are
trials reported in the top-of-the line medica! journals, bioidentical to human hormones are still not completely
are comp letely in the dark about the use of natural hor- natural in the purest sense because they undergo
mones. Their use is not taught in any medica! school or a laboratory process and severa! synthetic processing
promoted by any pharmaceutical company, the other steps befare the bioidentical end product is obtai ned .
major source of infom1ation for nearly all "conventional" There is no commercially avai la ble or compounded prod-
healthcare providers. Because the pharmaceutical in- uct that is both comp letely natural and bioidentical.
dustry is not interested in these products, the large de-
finitive stud ies that might demonstrate the efficacy and
safety of natural hormones will likely never be done What Consumers Real/y Want
unless the government steps in and funds a tria!.
The Consumer Definition: Natural = Plant Derived and
Bioidentica l
Compounding: What Consumers Really NHRT involves two important issues: the source ofthe
Want ~~~~~~~~~~~~~~~~~ product and the end product. Which is more important?
The physiologic effect of the end product sho uld be
The term " natural" is used often in our society today. the only concern, but the lay public is most comfor/-
To many consumers, "natura l" implies "safer." That able wilh hormones that are obtained from a plan/
perception expla ins the demand for natural skin care source and lhat are a/so bioidenlical. Few com mer-
products, foods , and pharmaceuticals. Often, however, cially available products fit thi s description; however,
the manufacturing ofnatural products is not well-regu- compounding pharmacists can help consumers acq ui re
lated, and the significance of the word " natural" has these products.
different meanings for consumers and manufacturers.
Natura l hormone replacement therapy (NHRT) is a mis- The following examples are types of commercially avai l-
nomer. The correct term is " bioidentical" hormone re- able products that may be construed as being natural.
placement therapy (BH RT) ." Consumers, pha1maceuti- Phytoestrogens may be advertised as a natural hormone
cal companies, physicians, pharmacists, and other treatment because they are derived from plants, but they
healthcare providers must be aware ofthe definition of are not bioidentical to human hormones. Recently, sev-
natural hormone replacement therapy and that the term era! pharmaceutical companies have developed new
"BHRT" is more accurate than "NHRT. " products that are marketed as being nan1ral because
they are derived from plants such as soy or yam, but
few are truly natural because they are not bioidentical. natural progesterone-which became known as proges-
Sometimes, a bioidentical hormone is combined with tin-whic h was strong eno ugh to break in to a woman 's
another completely synthetic nonbioidentical hormone, menstrual cyc le.
and the result is advertised as a natural product. The
most often prescribed estrogen hormone replacement In the l 960s, we saw the birth of estrogen repl acement
available is advertised as a natural product beca use it is therapy for women at midlife. M illions ofwomen began
derived from the urine of pregnant mares, but it is not us ing the estrogen drug Premarin . lt was promoted in
bioidentica l to human estrogen. However, if pure es- the book Feminine Forever by Dr. Robert Wil son, a
trone were extracted and isolated from pregnant mares ' New Yo rk gynecologist, with the support from Ayerst
urine, we would have the first tru ly natural hormone in Laboratories, makers of Premarin. Premarin was and still
the purest sense because it wo uld be obtained from a is manufactured from horse urine and although it is some-
natural source and would also be bioidentical. lnsulin times tou ted as " natural " because of its anima l origin, it
that is extracted from cows or pigs may be obta ined contains estrogens that are fore ign to a woman 's body.
from a natural source, but it is not bioidentical to human What is natural to horses is not natura l to wo men. At
insulin, and thyroid hormone extracted from a pig is first, women were given Premarin alone, and by the l 970s
also not bioidentical to the equivalent hormone in hu- approximately eight mi Ili on women had been prescribed
mans. Ultimately, the source of the product is not as the drug. Then in 1977 , studies done at Kaiser
critica! an element when natural signifies bioidentical. Permanente hospital in San Fra nc isco showed that
women on Premarin had a rate of endometria l cancer
five times hi gher than that ofnon-users. Many women
Meeting the Needs of the Consumer ==J died from this early use of Premarin.
Few commercia ll y available products contain plant-de- In order to remedy this risk of endometrial cancer, we
rived bioidentical hormones, the best source of which saw the birth ofthe progestin Provera (medroxyproges-
is a compounding pharmacy. Compounding phannacists terone acetate). Given a long with Premarin, it could bal-
can prepare plant-derived bioidentical hormones from a ance the un opposed estrogen and protect the uterus
physician 's prescription in a variety of dosage forms , from endometrial cancer. Provera was developed by
strengths, and comb inati ons that can be customized for using natural progesterone as its base substance and
each patient 's needs to improve the outcome of treat- included a chem ica ll y attached medroxy gro up so that it
ment. As mentioned above, compound ing pharmacists could be patented by the Federa l Drug Admini stration
must comply with the regulations of state boards of (FDA) .
pharmacy, and they have access to the highest grade
(Un ited States Pharmacopoeia [USP]) bulk chemicals Natura l hormones ha ve been ava ilable for years . Maj or
and to state-of-the art equipment with which they can drug manufacturers , suc h as Sc heri ng-Pl o ugh a nd
accurately prepare hormone formulations. Upjoh n have been synthesizi ng progesterone, estro-
gen , and testosterone from w ild yam and soy and se ll-
ing it to other drug compan ies to use in their synthetic
Compounding: The History of Natural preparations for years . lt is from these same companies,
Hormones ____________~ that compounding pharmacists are able to obtain these
same high quality FDA approved ingredients fo r use in
Tt was Russell Marker, a chem ist, who in the early l 940s compou nding. Natura l bioidentical hormones have been
made the breakthrough discovery ofhom1ones. He dis- manufactured , are commercially ava il ab le, and are pre-
covered a way to replicate human hormones by synthe- scribed widely in Europe.
sizing the plant substance diosgenin, found in abun-
dance in the wi ld yam plant. Marker 's discovery could
not be patented and this proved fatefu l for women ev- Compounding: Where We Are Today with
erywhere, beca use it meant that no U.S. drug company Natural Hormones - - - - - - - - - . .
would decide to market natural hormones. Without a
patent, a drug company would be unable to control the There are a few natural bioidentical products commer-
marketp lace, thereby limi ting potential profit. cially ava ilable in the U.S. today; however, sorne ofthem
are not manufactured in the most su itable dosage fo rms,
At the time of hi s discovery, scientific interest was fo- strengths, vehic les, or delivery systems. Most of them
cused on birth control , and Marker 's disco very led to have been manufactured into unique dosage forms , a
the development of a patentable synthetic version of back door approach to obtaining a patent for a natural
Chapter 37: Role of the Compounding Pharmacist 473
product. The FDA wi ll grant a process patent for a prod- Compounding: lnsurance Reimbursement
uct to protect the way in which it was manufactured .
This is why there are so many estradiol patches on the A common misconception is that compounded prescrip-
market and also how Prometrium , Crinone, and man y tions are expensive, cost prohibitive, and not covered
others have made it to the market. by insurance companies. This is absolutely fa lse. The
average cash price of a prescription in a compounding
Compound ing pharmacists can tailor the dose and dos- pharmacy toda y is about $35 -$40. With the rising costs
age form to a particular patient's individual needs. This of insurance co-pays and deductibles, many patients
is especiall y important in NaProTECHNOLOGY. For in- are finding it less expensive to use compounded pre-
stance, if a patient is allergic to peanuts, Prometrium scriptions as well as more advantageous dueto the fact
may not be the best choice for progesterone therapy that they are customized to meet their needs. Often times,
because it is contained in peanut oi l. Also, in the case of severa! medications can be combined into one dosage
Progesterone, the dosage form and delivery system are fonn in order to decrease cost, improve comp liance, and
extremely important with regard to blood levels and clini- maximize dosing efficiency.
cal effect. The oral route may not be the preferred route
in every clinical situation. Compounding pharmacists Sorne insurance companies do cover the cost com-
can compound natural estrogens (estrone, estradiol , pounded prescriptions; however they do not reimburse
estriol) , progesterone , testosterone , dehydroepi- the pharmacy adequately to cover ali ofthe costs asso-
andosterone, pregnenolone as well as thyroid supp le- ciated with the prescription. Often , the reimbursement
ments such as T 3 and T 4 in a variety of dosage forms on ly covers the cost of the ingredients and does not
(m icroni zed capsules, oil filled capsules, vaginal cap- include coverage for the labor and expertise ofthe phar-
sules, slow release capsules, creams, ointments, ge ls, macist. Tt is for this reason that many compounding
s uppositori es, injections, sublingual lozenges) and pharmacies do not accept insurance coverage for com-
strength s to meet your individual patient's needs. pounded prescriptions . Many compounding pharma-
cies offer customized claim fom1s for patients wishi ng
to submit claims for reimbursement. This technique has
Compounding: Picking Up the Pieces been successfu lly used by patients ali over the country
After the WH1 ---------~ with a wide variety of insurance companies. Every in-
surance company deals with the processing of com-
Hormone rep lacement therapy has been under constant pounded prescription claims differently. The reason why
scrutiny since WHI. Unfortunate ly though , ali forms of sorne insurance com panies do not cover the cost of
hormone replacement therapy keep getting lumped into compounded medications is because it takes more time,
one and the fact that Prempro®and Premarin®were the energy and paper wo rk to process the claim. Because
on ly forms studied keeps getting dismi ssed. The re- every prescription is unique, every claim has to be dealt
sults from the WHT study cannot be extrapo lated to a li with on an individual basis. lt is easier for the company
forms of hormon e replacement therapy, especia ll y not to cover the claim in most cases. Please encourage
bioidentical hormone replacement therapy. yo ur patients to contact their insurance company, as
wel l as the pharmacy, ifthey are interested in obtaining
insurance coverage for their prescription. Aga in , leav-
ing in surance reimbursement aside, most compounded
prescri ptions are not cost prohibiti ve .
1. The lnternational Academy of Co mpoundin g Pharmaci sts 3. Gilson GR , Zava DT. A Perspecti ve on HRT for Women:
2. Conrad C. A Woman :S Cuide ro Na tural Hormones. New Pi ck ing Up the Pieces After the Women's Hea lth lni tiat ive
York, New York: Pen guin Putnam ln c.; 2000. Trial-Part 1. /111ernationa/ Journal o/ Pharmaceurical Com-
p ounding 2003 ;7 (4)250-256.
4. G il son GR, Zava DT. A Perspec ti ve 011 HRT for Worne11: rianal Jaurnal a/ Pharmace111ical Campaunding
Picki11 g Up th e Pi eces Afte r th e Wornen 's Heal th l11iti ati ve 2002;5(5):33 2-335 .
Trial-Part 2. fnl ernarional Journal o/ Phar111ace111ical Com- 7. Romero, M. Close-Up 011 Ph armaco logy: Bioide11tical Hor-
paunding 2003;7(5) :330-338. 111011e Rep lace rn e11t Th erapy. Advance fa r Nurse Praclilia-
5. Higgs JG. The O/d Drugslare. Tracy, Ca li fornia: Quanturn ners 2002 ; Nov: 47-5 2.
Leap Publi sher, ln c. ; 1999. 8 . Wri ght JV. Na rural Harmane Replacemen l F a r Wamen
6. Reed-Ka11e DL. Natura l Hormo11e Replaceme11t Th erapy: Over 45. Petalurna, Ca li fo rni a: Smart Publicatio11s; 1997.
What lt Is a11 d What Co 11 su mers Reall y Wa 11t. !nrerna -
Part IV:
Thomas Hilgers, M.O. "NaProTECHNOLOGY allows far the diagnosis of the

Chapter 40
underlying problem and the treatment of the underlying
causes. lt has excellent pregnancy rates and, with appropri-
ate evaluation and treatment, it fosters a natural accep-
tance of the underlying condition beca use the underlying
causes are understood... [T]he diseases that cause infertility
are identified and treated, a foundation is laid far future
success, and more total pregnancies per woman are
achieved than with the ART approaches. "
475
476
Trends and Deficiences in lnfertility
nfe1ti lity is usually defined as the inability ofa coup le of ora l contracepti ves increases the delay-in-concep-
I to ach ieve pregnancy when not using contraceptives,
but engaging in random intercourse, over the co urse of
tion time 5 and also contributin g is the increased inci-
dence of sexually-transmitted diseases.
at least one year. This definition is based upon the origi-
nal 1950 investigations of Tietze, et al. , who reported ln ferti li ty is furt her divided into primary and secondary.
that 90 percent of 1727 couples, followed for one year, Primary inferti!ity is the inabi lity to ac hieve any preg-
became pregnant. 1 Th is lea ves 1O percent of coup les as nancy whil e secondary infertility presu pposes the ex -
a gro up wh ich can be classified, by subtraction, as in- istence of at least one prev ious pregnancy. ln most in-
ferti le. More recently, it has been suggested that an in- fe1ti lity programs, about 40 percent ofthe pati ents com-
fertility evaluation can be perfom1ed and treatment initi- ing for medica! assistance will be in the secondary infer-
ated if a couple has fai led to achi eve a pregnancy after ti 1ity category.
six months oftrying.2
Table 38-1: Women with lmpaired
Accord ing to the 1995 Nati onal Survey ofFamily Growth
Fecundity in the U nited States
(NSFG), the only source of current, nationally represen- National Survey of Family Growth: 1995
tative infertili ty data, it has been estimated that there are 1982-1995 1
6.2 mi Ilion women ofreproductive age in the United States
who ha ve impaired fecundity 3 (Table 38- 1). The inci- Nurnber of Wornen Preva lence arn ong
Year with lrnpa ired Fertility Married Wornen (%)
dence has increased sign ificantly from 10.8 percent of
married women in 1982 to 12.9 percent in 1995. 1982 4.6 rnillion 10.8
1988 4.9 rnillion 2 10.7
Proj ections on the number ofwomen with impaired fe- 1995 6.2 rnillion 2 12.9
cundity o ver the next 20 years suggests that it wi 11 in-
1. From: Chandra A, Stephen EH: lmpaired Fecundity in the Unrted States:
crease slightly and that, by the year 2025 , the number 1982-1995. Family Planning Perspectives. 30: 34-42, 1998.
will range from 5.4 to 7.7 mi Ili on, with the most li kely 2. The percentage of women who ever sought medical help was 44%
increasing from 2.1 million in 1988 to 2.7 million in 1995.
numberjust under 6.5 mill ion.4 Reasons for this increase
are not entirely understood, but it is known that the use
477
centto 19 percent between 1976 and 1998. Whil e not ali

of thi s can be pres umed to be associated with increas-
ing rates of infe rtility, so rne of it clearl y is.8
Over the last 35 years, the eva luation and treatment of

th e infe rtil e patient has undergone signifi cant change.
T his was mostly influenced by the introducti on of in
vitro fertili zati on in 1978 . Since that time, most of the
trend in the treatment of in fe rtility has been in develop-
ing means to artifi ciall y replace th e natural procreati ve
1976 1980 1984 1988 1992 1998
system. Thi s has had an enorm ous and , one could ar-
Year
gue, a signifi ca ntl y de leteri ous effect on the medica!
Figure 38-1 : Childlessness am ong wo men 4 0-44 yea rs of care of thi s group ofwomen and on the practice of medi-
age in selected years from June 1976 through June 1998 cine itself.
(Fro m: Bachu A, O'Connell M: Fertility of American Women:
Population Ch aracteri stics. Curren! Population Reports. US
Dept of Commerce. June 1998 [lssued Sept 2000]). lt is the purpose of thi s chapter to critica lly rev iew these
events that bave occurred over these last severa! de-
cades, putting fo rth sorne startling new questi ons.
Infertility takes a psyc ho logical toll on those who suf-
fe r w ith it. Moderate to hi gh leve Is of gri ef and depres-
sion can be seen in women experi enci ng infertili ty. 6·7 Evaluation of lnfertilitY------~
T his creates added stress w hi ch may negati ve ly impact
the evaluati on and treatment of the infertility probl em. The eva luati on of infe rtili ty has undergone somewhat
of a metamorphos is over the last severa ! decades. An
As infe rtility has increased in the population, so has interest in identifying the underl ying ca uses of the in-
childl essness. In a study conducted by the U.S . Cen- fe rtility problem ha ve dimini shed significantly. As a re-
sus Bureau, the percentage of women aged 40 to 44 sult, few di agnostic tests are being perfo nned and sorne
years of age who are childl ess, increased fro m 1O per- of those that are se lected are less meanin gful.
Table 38-2: Basic Infe rtility Evaluatio n according to

R epresentative Autho rities
Repro Endocr Carr and Ryan, aoston

Practice Pattem Blackwell et al IVF
Evaluation ltem 1997' 19982 19993 2G02 4
History & physical Yes Yes Yes

One or more (98 .0) Yes Yes Yes
BBT }
Mid lutea l phase Two or more (86 .1) Yes Yes Yes
EMBx Yes (LH predictor kit )
HSG Yes (96.0) Yes Yes (SHSG ) Yes

Day 3 FSH Yes (54 .3) Yes (if >35) Yes Yes
SFA Yes (99.9) Yes Yes Yes
Clomiphene challen9e Yes (54 .3) Yes
Laparoscopy Yes (89. 1) Optional
Pelvic ultrasound Yes (54 .5)
Hystero scopy Yes (53 .2)
Post-coital Yes (79.0)
1. From: Glatstei n IZ, Harlow BL, Hornstein MD: Practice Patterns Among Reprod uctive Endocrinolog ists: The lnfer-
tility Evaluation. Fertil Steril 67: 443-4 51 , 1997.
2. From: Bradshaw KD, Chantilis SJ, Carr BR: Diagnostic Evaluation and Treatment Algorithms forthe lnfertile Couple.
In : Carr BR, Blackwell RE (Eds.): Textbook of Reprod uctive Medicine, 2nd Ed. Appleton and Lange. Stamford , CT,
1998.
3. From : Rein M S, Barbieri Rl: The lnfertile Couple. In: Ryan KJ , Berkowitz RS , Barbieri RL , Dunaif A : Kistner's
Gynecology and Women's Health. Mosby, St. Louis, 1999.
4. From: Bayer SR,Alper MM, Penzias AS : The Bastan IVF Handbock of lnfertility. Parthenon Publishing Grou p. Boca
Raton, 2002.
Chapter 38 : Trends and Deficiencies in lnfertility Evaluation and Treatment 479
In Table 38-2, tests recommended for a basic infertility inc lu de such things as rubella and hepatiti s sero logy,
evaluation according to representative authoriti es in HIV testing, Chl amydi a sero logy, eva luation for sperm
reproductive medicine are outlined. While most every- antibod ies and sperm penetrati on. 9· 12
one wou ld recomm end that the patient undergo a hi s-
tory and physical examination, there is not always agree- Unfortu nate ly, tests such as the basal body tempera-
men t with regard to the other tests to be performed. ture, mid-luteal ph ase progesterone, endometrial biopsy
Ovul ation assessment needs to be carried out, but tech- and LH testing kits, are not defi niti ve tests for ovu la-
niques such as basa l body temperatures , mid-luteal tion and defi nitely not adeq uate for identifying defects
ph ase progesteron e leve ls and endometr ial biopsy, of ovul ation. The first three will test fo r the production
which , in sorne ways, can be considered "medi eva l" are of progesterone by the ovary (but not dysfu nctional
often recommended. The LH predictor kits whi ch are progesterone producti on). However, in most ofthe ovu-
also recommended by sorne have sign ificant drawbacks. lation defects, a corpus luteum is fonned (even ifovula-
tion has not occurred) and progesterone is produced
Programs also want to test fo r tuba! patency and the causing presumptive signs of ovul ati on when , in fact,
integrity of the uterine cavity. This is often unde11aken ovul ation has not occurred or is defective. In addition ,
with the use of hysterosa lpin gography. Hypothalamic- one can have a perfectly normal LH surge (w hi ch will
pituitary integrity is tested with a day-3 FS H leve! and , show up in the LH test kits) in cycles where an unruptured
of course, the mal e is tested wi th a seminal fluid analysis. fo llicle is present and ovulati on has not occurred. Un-
fort un ate ly, concepts such as " if a woman is having
In add ition to the above, such tests such as a clomi- regul ar menstrual cyc les that are 23 to 39 days in length,
phene challenge test, pelvic ultrasou nd exami nat ion, then she is ovu lating,"2 whil e erroneous, continue to be
post-coita! test and hysteroscopy are used , but only persistent. 13
sparingly. Laparoscopy is often considered an opt ional
examination and not one whi ch would be used routinely. Hysterosalpingography, while hav ing its own va lue, also
has its limitat ions. In the prese nce of a normal
There are other tests that are often recommended in hysterosalpingogram, laparoscopy may identify other
vary ing degrees by different progra ms. These wou ld pe lvic disease in about half of the pati ents. 14
Table 38-3: Causes of lnfertility according to R epresentative Authorities
Johns Boston
Hopkins Yen IVF National
Cause 19951 1999' 2002' 2003 4
Male factor 6.2 25 30 19.0

Tubal factor 39 .2 22 14.8
Tubal/ peritoneal factor 20
Unexplained 23. 6 17 25 11.2
Ovulatory dysfun c t ion 27 20 5.8
Endometriosis 25 .8 5 7.4
Diminis hed ova rian reserve 5.0
Uterine/cervical factor 2.1 5 1.3
lm munological factor 3.1
Multiple factors , femal e onl y 12 .7
Multiple factors , femal e & male 18.2
Othe r 4 5.2
Total does not equal 100% dueto rounding

1. Wallach EE, Zacur HA (Eds): Reprod uctive Medicine and Surgery. Mosby, St. Louis, 1995.
2. Yen SSC, Jaffe RB, Barbieri RL (Eds): Reproductive Endocrinology: Ph ysiology, Pathophysiology and
Clinical Management. 4th Ed . WB Saunders Co. , Philadelphia, 1999.
3. Bayer SR, Alper MM, Penzias AS: The Boston IVF Handbook of lnfertility. Parthenon Publishing Group,
Boca Raton, 2002.
4. 2001 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports.
Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health
Promotion. Division of Reproductive Health. Atlanta, Georgia , December 2003.
480 The Medica! and Surgical Pra ctice of NaProTECHNOLOGY
Causes of lnfertility _ _ _ _ _ _ __ laparoscopy, 68 had pathology of reproductive signifi-

cance including intrinsic tuba! disease (n=24), peritubal
In assessing the literature and seeing patients who ha ve adhesive disease (n=34) and endometriosis (n=43 ) and
been evaluated elsewhere, it is very difficult to get an sorne in cornbination . Although the hystero-
accurate view of the underlying causes of infertility. salpingograrn was read as normal in ali women , tuba!
Represen ta ti ve authorities each ha ve a di fferent view disease was diagnosed lap aroscop ically. The en -
ofwhat rnight be sign ificant. While it is generally stated dometriosis was stage 1-ll in 22 ofthe patients, but stage
that 30 percent of infertility problerns will be related to a [JI in 13 and stage IV in six patients. 16
rnale factor problern, 30 percent to a fernale factor prob-
lern and 40 percent to a cornbination of the two, docu-
rnentation ofthat is difficult to find. Approaches to Treatment _ _ _ _ _--.
In a recent review ofthe causes ofinfertility identified A staircase approach to the current treatment of infertil-
by various authorities (Table 38-3 ), infertility was ity is shown in Figure 38-2. Many programs have devel-
thought to be dueto the mal e factor in a range of 6.2 to oped ornplex algorithms for the implementation of a treat-
30 percent. There were a rnultitude of causes found in ment program for the infertile patient. 2•9• 11 These a lgo-
wornen, including tuba! factor, tubal/peritoneal factor, rithrns involve almost in variab ly, an artificial approach
ovulatory dysfunction , endornetriosis, dirninished ova- to reproduction . The approaches tend to replace the
rian reserve, uterine/cervical factors , imrnunological fac- normal sexual procreative un ion with a physician sub-
tors , and unexplained reasons. But in sorne cases, ovu- stitute for the procreative act. While in rnost textbooks
latory dysfunction was not identified as a cause and in this is referred to as " assisted reproductive technol-
other cases endornetriosis was not identified . In rnost ogy" (ART), in this textbook it is referred to as "artificial
cases, endornetriosis was seen to be a relatively infre- reproductive technology" because it does not rneet the
quent cause ofinfertility. Catho li c definition of " assisted. "
In the national data set from the various IVF centers Treatment usually begins with sorne type of ovulation
around the United States, multiple facto rs affecting the induction protocol often ernploying "super-ovulation
wornan only were identified in 12. 7 percent of patients strategies." 17 Usually sorne form ofartificial insernina-
and rnultiple factors involving both the man and the tion , either with the husband's sperm ora donor sperm
woman were identified in 18.2 percent. is also implemented.
Endornetriosis was identified as the causative factor in When these do not work effective ly, then in vitro fert ili-
5, 7.1 and 25.8 percent ofthe patients, but endornetrio- zation is usually recommended. On occasion, reconstruc-
sis is extremely difficult to diagnose without tive pelvic surgery, either by laparotomy or, most likely,
laparoscopy. Cervical factor was identified in a very smal 1
percentage of patients. Hull , in 1998, pointed out that
cervical mucus defects and disorders are infrequent
causes ofinfertility (3%) and are practically difficult to
IVF
diagnose with certainty. Furthem1ore, he pointed out
that the most obvious defects result frorn cervical sur-
hMGor
gery, particularly conization ofthe lower cervical cana l. 9 hMG - IUI
This was echoed by the Boston IVF group 2 who went CCor
CC - IUI
on to say that "sorne women notice this change in the
cervical mucus, whereas others do not," irnplying that Short Term
Treatment of
this information is not reliable or helpful. In this regard, Fertlllty Factors
the obvious following question would be: Why do sorne ldentlfy Sorne
lnfertlllty Factors
women not notice this change in the cervical rnucus?
Laparoscopic evaluation in the infertile woman has been

known for rnany years to provide a high yield ofsignifi- Figure 38-2: A staircase approach to current evaluation and
treatment of infertility. lt is recommended that for women older
cant pelvic pathology. 15 More recently, this has again
than 35 years , the first two steps should be rapidly com-
been identified in a group of infertile women thought to pleted. For women younger than 30 years of age , more time
be at low risk for altered pelvic anatomy. Of 100 patients can be spent on these steps . CC = clomiphene citrate ; IUI =
with a negati ve reproducti ve workup, up to the point of intrauterine insemination ; hMG = human menopausal gona-
dotropin ; IVF = in vitro fertilization .
Chapter 38: Trends and Deficienc ies in lnfertility Eva luation an d Treatment 481
by operative laparoscopy, is still used but over the last whose husbands have severe oligospermia. 19-22 But the
l Oyears , has been utilized less and less. In fact, there is proced ure presumes the acceptance of an unidentifi ed
great concern at thi s time as to the overall surgica l skill bi olog ical fa ther. This poses signi ficant and leg itirnate
of the reproducti ve spec ialist in providing these types moral and ethi ca l probl ems fo r th e patients.
of therapies.
In reviewing the studi es on AfH , control subj ects who
Since the artificial reproducti ve technologies represent are of simi lar medica! background, and who ha ve ferti 1-
the major approach to infertili ty treatment at the present ity focused intercourse (FFl ), are never used as con-
time, special attention will be given to these approaches. trol s. As a result, an ai1ificial approach to insemination
is used as a repl acement for natural inseminati on with
littl e or no evidence that it is superior.
Artificial lnsemination
This approach to the care offertility-related problems
One of the main techniques used in the curren! practice has also led to a deni grati on of the integrity of both
ofreproductive medicine to help women become preg- marriage and parenthood. lt has been used to impreg-
nant is artificial inseminati on. This is a technique where nate single women23 ·24 and lesbians. 25 The role of the
the physician usurps the role of the husband or fa ther father in the hea lthy parenting ofc hildren has been dis-
by perform ing an in sem ination proced ure. This proce- carded by many ph ys icians. This is irresponsible and
d ure can be done with either fresh o r frozen purposely puts children in danger.
(cryopreserved) sperm from ei ther the husband or a
donor by placing the sperm within the cervix or by by-
passing the cervix through direct inj ection of th e sperm A rtificial Reproductive Technologies
into the uterine cavity. The procedure is usually com-
bined with the stimulation of ovu lati on with either clo- The artifi cial reproductive tec hnolog ies (A RT) in clude
miphene citrate or FSH. The insemination is usually ali fertility treatments in which both eggs and sperm are
timed with the use of ultrasound observation of ovu la- handl ed. ln genera l, ART procedures invo lve surgicall y
tion or the use ofthe urinary LH test kits. rernoving eggs rrom a woman 's ovaries, combining them
with sperm in the laboratory and returnin g them to the
Success rates for non-rnedicated intrauterin e insemina- woman 's body or donating them to another wornan.
tion (IU J) is not rnuch different than for rand om acts of They do not include treatments in which only sperm are
intercourse (Table 38-4). With ei ther clomiphene citrate handled (for example, intrauterine or artificial insemina-
or FSH stirnu lation cornbined with IUI, the per-cycle tion) or procedures in which a woman takes drugs only
success rates does go up but so too does the multiple to stimul ate egg production without the intention of
pregnancy rate. In rev iewing pregnancy rates, the " per having eggs retrieved.
woman " rates are consistently lower than the li fe table
rates. 18 The types of ART include the fo ll owi ng: 26
lt is well accepted that artificial insemination with donor lVF (in vitro fertilization): Thi s involves extracting
sperm (AID) is more effective than artificial in semina- a woman's eggs, fertil izing the eggs in the labora-
ti on with husband 's sperm (AIH ) when used in women tory and then transferring the resulting embryos into
the woman 's uterus through the cervix. For sorne
lVF procedures, fertilization involves a specia lized
Table 38-4: Success R ates of technique known as intracytopl asmi c sperm injec-
Artificial lnse mination 1
tion (lCS I). In ICS I, a si ngle spern1 is injected di-
Success Rate Multiple Pregnancy rectly in to the woman 's egg.
Treatrnent (per cycle) (% ) Rate (%)
Observation 3-4 GCFf (gamete intrafallopian transfer): This involves

Non-medicated IUI' 4 the use of a laparoscope to guide the transfer of
Clomiphene citrate-IUI 8-10 10 un fert ili zed eggs and sperm (gametes) into the
FSH-I UI 15-18 20-25
woman 's fa llopi an tu bes through small incisions in
her abdomen.
1. From: Bayer SR, Alper MM, Penzias AS: The Bastan IVF Handbook af lnfer-
tility. Parthenan Publishing Group, Boca Ratan, 2002.
2. IUl=intrauterine insemination ZCFf (zygote intrafaIJopian transfer): This involves
ferti 1izing a woman 's eggs in the laboratory and then
using a laparoscope to guide the transfer ofthe fer- aged 14.0 percent (wi th sorne centers hav ing up to a 42
tilized eggs (zygotes) into her fallopian tu bes. percent cance llation rate). The latter information indi -
cates that of 100 cyc les started , on ly 86 could move to
In addition, the ART procedures are often categori zed e ith er the retri eva l or transfer stage. T hus, one out of
accord ing to whether the procedure used a woma n 's seven patients automatica ll y ca nnot move into a mo re
own eggs (non-donar) or eggs from another woman advanced phase of treatment beca use of the cancell a-
(donar) and according to whether the embryos used ti on.
were newly ferti lized (jresh) or previously fe1tilized (fro-
zen and then thawed). The A RT procedure includes There is considerab le variation in the li ve birth rate per
severa! steps and is typically referred to as a cyc/e of cycle started (LBRPCS) w hen look in g at the woman's
lreatment. age upon entry into the program. The success rate is
higher for those wo me n less than 35 yea rs of age and
In 1992, the United States Congress passed the Fertility s ignifí cantly lower for those women 38 years of age or
C lini c Success Rate a nd Cert ifí cation Act of 1992 older. While th e initial li ve bi1th rate per cycle started at
(FCSRCA). This required that a ll clinics performingART age <35 years is 34. 1 percent, it decreases to 4.4 percent
in the United States annua ll y repo1t their success rate for women greater than 42 years of age (Ta ble 38- 7).
data to the Center for Di sease Control (CDC) . The CDC Al so in Table 38-6 is the LBRPCS compared to the size
uses the data to publish an annual report detailing the ofthe clinic. The size ofthe clinic is determ in ed by the
ART success rates for each ofthese cl inics. One ofthe number of ART procedures carried out each year. T here
inherent drawbacks to this reporting requirement is the is a slight improvement in the LBRPCS as the c linic per-
fac t that the C DC contracts w ith a professional soc iety forms more a nd more procedures. When repo rting
(The Society of Assisted R eprodu ctive Technology -
SART), to obta in the data published each year in the
ART success rate 's report. SART is an o rgan ization of Table 38-5: Presentation of Success R ates
ART providers affí 1iated with the American Society for wi th ART-2001 National Summ.ary 1
Reproductive Medicine (ASRM). While cooperation of
Number of
the ART c lin ics is important to conduct such a data Data Presented Tables Percent
analysis, it does produce a potential conjlict of interest
Uve birth per transfer 12 44.4
with regard to the type of data reported. Nonetheless,
Uve births per cycle started 10 37.0
the report provides the onl y nationa l data availab le for
Uve births per retrieval 3 11 .1
the United States o n the ART programs . A rev iew ofthe
Ali three represented 3.7
data provided in the D ecember 2003 report (2001 Na-
Unknown 3.7
tional Summary) is now presented.
Totals 27 99 .9
T he success of ART is presented in a va ri ety of differ-
1. From: 2001 Assisted Reproductive Technology Success Rates: National
ent ways. The three major ways include the number of Summary and Fertility Clinic Reports. Centers of Oisease Control and
Prevention. National Centerfor Chronic Disease Prevention and Health
" live bi 1ths per cyc le started," the " live births per re- Promotion. Divisan of Reproductive Health. Atlanta. Georgia, December
trieval," and the " li ve births per transfer. " The most im- 2003.
portant statistic from an infertility pati ent's point ofview

is the " live births per cycle sta1ted" because this pro-
vides that couple with informati on on success at the
point of entry.
Table 38·6: Live Birth Rates per Cycle Started
and Cancellation R ates: ART
In Table 38-5 , one can see the variability in the reporting
2001 National Summary 1
ofthe 200 1 National Summary. Only 3 7 .O percent of the
data was presented by " live births per cyc le started ." ltem Percent
One ofthe diffículties this poses is in the in ab ility to do Uve birth rate per cycle started 27 .O
comparati ve data anal yses with different approac hes. Singleton live birth rates per cycle started 20.2
Cancellation of cycles started 14.0
In Table 38-6, the li ve birth rate per cycle started and
cance ll ation rates in the National Summary is presented. 1. From: 2001 Assisted Reproductive Technology Success Rates: National
Summary and Fertility Clinic Reports. Centers of Disease Control and
The live birth rate per cycle started was 27.0 percent. Prevention. National CenterforChronic Disease Prevention and Health
The s ingleton live b irth rate per cycle started was 20.2 Promotion. Divisan of Reproductive Health. Atlanta, Georgia. December
2003.
percent and the cancellation rate of cycles started a ver-
th e first cycl e with onl y 2 1.7 pe rcent e nte ring a second

Table 38-7: Live Birth Rates per Cycle Started by
cyc le and o nl y 13.3 percent go ing fo ur o r mo re cycles.
Woman's Age (N o Previo us Pregnancies) and
Size of Clinic: Fresh Non-do no r Eggs o r Embryos
The di ffe rent clini cs around th e United States pro vide a
2001 Natio nal Summary1
number of diffe rent serv ices and these are also identi-
Woman 's Age Percent Size of Clinic* Percent fie d in the Natio na l Summary. A lmost ali of the clinics
<35 34 .1 <60 23.4 prov ide cryopreservation serv ices. Thi s all ows for th e
35-37 26.6 60-11 3 26.3 freez ing of e mbryos and often the fre ez ing of gametes
38-40 18.4 11 4-248 26.4
(both sperm and ova). Donar egg services are provided
41-42 89 >248 27 .5
by 89 percent of the clini cs and single women are served
>42 4.4
by 84 percent. In add iti on, surrogates (now referred to
as "gestational carriers" ) a re prov ided by 69 percent
Size of clin ic is detemiined by the number of ART procedures canied out
eachyear. of cli ni cs a nd donar embryos by 58 percent (Tab le 38-
1. From: 2001 Assisted Reproductive Technology Sucoess Rates: National 1O). T hi s strengthens the noti o n that these clini cs a re
Prevention. National Center far Chronic Oisease Prevention and Health
not interested in program s that suppo rt biol ogical par-
Promotion. Divisan of ReprOOuctive Health. Atlanta, Georgia, December enthood w ith both a mother and a fa the r.
2003.
Most of the A RT services provided are by way of in

vitro fertili zatio n eithe r with o r with out ICSI (98.6%).
LBRPCS , one could get th e impress io n th at if eno ugh

cyc les were tried, the preg nan cy ra te wo uld be ve ry Table 38-8: The Number and Estimated
hi g h. While it is imposs ibl e to say, beca use of the way Percent of Wo men with lmpaired Fecundity
that data is presented , just how man y cycles the aver- who are Helped with ART: U nited States, 2001
age woman actual ly goes throug h, the ave rage number
of cyc les started is almost certainly less than two.
Number of women with impai red fecundity 6,200 ,000
(1995)1
One ofthe majar methodologicaljlaws in the nati ona l
Number of live bi rths (2001) 29 ,344
data set is that pregnancy ra fes are not calculated on
Percent of women helped by ART 1 0.47% 1
a "per woman " basis . The stated reason fo r thi s is that
" success rates cannot be ca lcul ated o n a ' per wo rn an ' 1. From: Chandra A, Stephen EH: lmpaired Fecundity in the United States:
1982-1995. Family Planning Perspectives. 30:34-42, 1998.
basis beca use wornen 's names are not reported to SA RT
2. From: 2001 Assisted Reproductive Technology Sucoess Rates: National
and C DC ." 26 This is an in adequate reason fo r not pe r- Summary and Fertility Clinic Reports. Centers of Disease Control and
Prevention. National Center far Chronic Oisease Prevention and Health
forming that type of cal cul ati on. There a re any number Promotion. Divisan of Reproductive Health. Atlanta, Georgia, Oecember
of ways in which a patient 's co nfidentia lity a nd a no- 2003.
nymity can be maintained a nd protected in such a re-

porting systern . U nfortunate ly, thi s leaves one w ith the
mistaken noti o n that if one unde rgoes an ART treat-
ment cycle, it wil l produce an approximate ly 25 percent Table 38-9: Percentage of Wo m en U ndergoing
success rate pe r cycl e and if one undergoes e no ug h their First and Subseq uent ART Cycles
treatment cyc les, one should almost be guaranteed a 2001 National Summary 1
pregn ancy. Howeve r, the dro p-o ut ra te afte r the first Undergoing Percent
cycle is extremely high. Because of dupli cation w itb some
First cycle 53.4
patients recei vin g multipl e cycles, it is imposs ibl e to
Second cycle 21.7
ca lculate how rnan y wo men have actuall y had access to
Third cycle 11.6
thi s fo rm o ftreatrnent. What is known is that in the yea r
Fou rth cycle 6.2
2001 , 29,344 live birth s res ulting in 40,687 bab ies re-
Four or more 7.1
sulted from the ART programs in the Uni ted States. Thi s
arnounts to a rate of 0.4 7 perce nt of ali wo rn en w ith Total 100.0
irnpaired fe cundity w ho a re ass isted by the A RT pro- 1. Adapted from: 200 1Assisted Reproductive Technol-
g ram s in the United States (Tabl e 38-8). In Ta bl e 38-9, ogy Sucoess Rates: National Summary and Fertility
Clinic Reports. Centers of Disease Control and Pre-
the percentage of women unde rgo in g the ir first a nd vention. National Center far Chronic Disease Pre-
vention and Health Promotion. Divisan of Reproduc-
subsequent ART cycl es fro m the 200 1 Na tio nal Su m- tive Health. Atlanta, Georg ia, December 2003.
mary is presented show ing the sharp dro p-o ut ra te after
The Z IFT and G IFT procedu res are provided, overa ll , in a mo unts toan ove1t wastage of e mbryos to obtain these
less than two percent of cases (Tab le 38- 11 ). Fresh ova live births. lt does no t co unt th e embryos that were
are used in 84.4 percent of cases and frozen in 15.6 per- c reated in th e process, stored in freeze rs, most ofwhom
cent. Do no r ova a re used in 1O.7 percent. are term ina l.
W hen these procedures are unde1take n, mo re tha n o ne As a res ult of thi s, a large numbe r ofsuccesses res ult in
emb ryo is almost always placed (93 .8 %) (Tab le 38-1 2). mul tiple pregnancies (Tables 38-14 and 38- 15). In a gro up
l n fact, the estimated average number ofembryos trans- of 2 1,8 13 li ve bi rths fro m ART cyc les in w hi ch fresh
ferred per ART cycle is 3.6. Th e large numbe r of e m- non-donor cycles were used, 35 .8 pe rcent we re multipl e
bryos is pl aced de liberate ly because it is know n that
t he s uccess ra te fo r even a s ing leton pregnancy in -
c reases so mewhat by placing more than one em bryo . Table 38-12: N umber of Embryos Transferred
H owever, thi s a lso means th at the em bryo wastage in- during ART Cycles using Fresh No n-do na r
creases s igni fíca ntly. In fac t, 6. 72 embry os are placed Eggs or Embryos
for every single live birth (Tabl e 38- 13). T he techno l- 2001 N ational Summ ary'
ogy is built u po n th e princ ipi e of creating life through
Number of embryos
destro ying Life. In orde r to obta in the 40,687 li ve babies (or eggs) transferred
bo rn from ART cycl es ( in cluded in thi s number are the per ART Cycle Percent
multiple births), 232,682 embryos had to be wasted. This 6.2

2 27 .3
3 34.5
Table 38-10: Services P rovided
4 20 .6
by 384 IVF Clinics
5 7.2
2001 Nation al Summary'
6 2.8
Service Provided Percent Providing
7 1.3
C ryopreserva t ion 98
Estimated average number =~
Donoregg 89 of embryos transferred per
ARTcycle
Sing le women 84
Gestational carriers (surrogates) 69 1. From: 2001 Assisted Reproductive Technology Suc-
cess Rates: National Summary and Fertility Clinic
Do nor e mb ryo 58 Reports. Centers of Disease Control and Preven-
tian . Natianal Center far Chronic Disease Preven-
1. From: 2001 Assisted Reproductive Technology Success Rates: Na- tian and Health Pramatian . Divisan af Reproductive
tional Summary and Fertility Clinic Reports. Centers of Disease Control Health. Atlanta, Georgia, December 2003.
and Prevention . National Center far Chronic Disease Prevention and
Health Promotion. Divisan of Reproductive Health . Atlanta, Georgia ,
December 2003.
Tabl e 38-13: Number of Embryos Wasted fo r

Eve ry Live Birth using ART Approaches
Table 38-11: T yp es of ART Procedures using
2001 Natio nal Summary'
Fresh No n-do na r Eggs or Embryos
2001 N ational Summary' Type of Cycle Total Number of
Embryos Transferred
Type of
ART Procedure Percent Status of Eggs Percent Fresh embryos fro m non-dono r eggs 204,396
Frozen embryos from non-donor eggs 37,495
IVF with ICSI 49.4 F resh , non-donor 76 .7
Embryos from donor eggs 31,478
IVF wi thout ICSI 49 .2 Fresh , donor 7.7
To tal embryos transferred 273 ,369
ZIFT 0.8 Frozen , non-donor 12 .6
Number of live babies born from 40 ,687
G IFT 0.4 Frozen , donor 3.0
ART cycles
Combination 0.1
Embryos :live birth ratio

Prevention. National Center far Chronic Oisease Prevention and Health Prevention. National Center far Chronic Oisease Prevention and Health
Promotion. Divisan of Reproductive Health. Atlanta, Georgia, December Promotion. Divisan of Reproductive Health. Atlanta, Georgia, December
2003. 2003.
Chapter 38 : Trends and Deficie ncies in lnf ertil ity Eva lua tion an d Treatment 485
Table 38-14: What Percentage of ART Cycles Table 38-17: Multiple Birth Rates per
Result in a Pregnancy? Live-Birth Delivery by T ype of
2001 National Summary1 ART Procedure, 1996 vs. 2001
2001 National Summary 1
Outcome Percent
1996 2001
No pregnancy 66.5 Type of ART Procedure 'lo 'lo
Sing leton pregnancy 19.1
Fresh--<Jonor 41 .6 41 .7
Multiple pregnancy 12.0
Fresh-non-donor 38.4 35 .8
Pregnancy ended in ea rly miscarriage 1.7
Frozen--<Jonor 26.2 28.4
Ectopic pregnancy O.7
Frozen-non-donor 27.0 26.8
Tota l 100 .0
1. From: 2001 Assisted Reproductive Technology Success Rates:
1. From: 2001 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports. Centers ar Dis-
National Summary and Fertility Clinic Reports. Centers of ease Control and Prevention. National Center far Chronic Dis-
Disease Control and Prevention. National Center far Chronic ease Prevention and Health Promotion. Divisan of Reproductive
Disease Prevention and Health Promotion . Divisan of Repro- Health. Atlanta, Georgia , December 2003.
ductive Health. Atlanta, Georgia, December 2003.
Table 38-15: What Percentage of Pregnancies

Result in Live Birth? pregnancies with 32.0 percent bei 11g twi11s a11d 3.8 per-
2001 National ummary1•2 cent representing triplets or greater (Tab le 38- 16).
Outcome of Pregnancy Percent

In comparing the trend over a fi ve-year period oftime,
Singleton birth 53.1 the Natio nal Surnmary showed (Table 38-17) that there
Multiple birth 29.1 has not bee11 rnuch change in the multiple birth rate
Miscarriage 15.5 duri11g this period oftirne in spite of th e fact that there
lnduced abortion 0.9 has bee11 a significa11t comme11tary 011 tryin g to prevent
Unknown 0.8 thi from occurring. 27 -33 Compared with women with
Stillbirth 0.6 naturally-co11ceived pregna11cies, a 25-fo ld likel ihood
of multipl e births among wornen ex posed to these treat-
Total 100 .0
ments has been id entifi ed. 34 With the prematurity rate
1. National Summary does not include ectopic preg- being increased sig11ifica11tly in multiple pregnancies,
nancy, which represents 2.2 percent ar pregnancy
outcomes. these child ren are also e11da11gered by the process.
2. From: 2001 Assisted Reproductive Technology Suc-
cess Rates: Natlonal Summary and Fertility Clinic
Reports. Centers ar Disease Control and Preven- Severa! strateg ies have bee11 recomm ended for reduc-
tion. National Center far Chronic Oisease Preven-
tion and Health Promotlon. Divisan of Reproductive
ing the number of multiple preg11a11cies i11cludi11g re-
Health. Atlanta, Georgia, December 2003. stri cti11 g the 11umber of embryos tra11sferred to two 35 or
perfo1111ing supemumerary preovulatory follicular reduc-
tion .36 Selective reduction (se lecti ve ly aborting sorne of
the embryos or fe tuses), has become one of the mai11
Table 38-16: Distribution of 21,813 Live Births ro utes for managing these situati ons. 37-39· ln one of the
from. ART Fresh Non-donor Cycles recent papers published 011 rnulti-fetal pregnancy re-
2001 National Summary1
duction , the articl e stated that it would a11alyze the ar-
Outcome of Pregnancy Percent guments in.favor of this approach, but that the "ethi-
Singleton birth 64 .2
ca/ issues .. . will not be addressed. "39 011e can11ot help
but ask why it is not addressed and , futherrnore , why a
Twin birth 32 .0
good peer-reviewed medica! journal wou ld allow the
Triplets or more 3.8
author to escap such fundamentally impo1tant issues.
Tota l 100.0
1. From: 2001 Assisted Reproductive Technology Suc- The increase in 11umbers of multipl e births because of
cess Rates: National Summary and Fertility Clinic
Reports. Centers of Disease Control and Preven-
the ART approach has signifi cantly in creased the rates
tion. National Center far Chronic Disease Preven- of triplet and high order multipl e births in the United
tion and Health Promotion. Divisan of Reproductive
Health. Atlanta, Georgia, December 2003. States. A comparison study between 1980 and 1997 is
show11 in Figure 38-3 . 011 a nati onal sca le, there has
250. 0l ~------------------
been a slow increase in the success rates of the A RT
procedures. Part of this increased success rnay have
2000> +------------------~
173.6
been affected by the day of embryo tra nsfer w hi ch has
~
:¡; been shi fti ng over the last few yea rs. In 2001 , about 76
~ 150.0
percent of emb ryo transfers occurred on day 3. Us ing
~ newer laboratory techn iques, embryo growth in the labo-
§_ 100.oi+ - -- - - - - - - - - -
ratory can be extended beyond day 3, most co mrno nl y
ª
~ to day 5. Among those A RT cyc les that progress to the
embryo transfer stage, the success rate was hi gher for
ern bryos that had been cul tured fo r fi ve days th an for
1980 1997 those cu ltured for only three days . However, w ith cul-
Year
Figure 38-3 : Th e rate of triple! and high-order multiple births

tu re to day 5, there is also an increased ri sk that sorne
in the United States in the yea rs 1980 and 1997. Rates are em bryos may not surv ive until day 5. 26
expressed per 100 ,000 li ve-born infants (From : Ma rtin JA,
Park MM: Trends in Twin and Triple! Births: 1980-1997 . Na- Wi th the ART procedures, there is an increased empha-
tional Vital Statisti cs Reports 47:1-20, 1999).
sis on prenatal di agnos is and selecti ve aborti on. Many
patients are advised that a healthy baby cannot be " guar-
been a 4.7-fo ld in crease in the number of th ese tri plet anteed" and thus, it shou ld be dec ided in adva nce that
and hi gh order rnu ltipl e b irths. lt is we ll recognized that prenatal di agnos is be un dertaken so that if an abnorma l
these rnultiple pregnancies are at in creased risk to de- baby is ide ntifi ed, it can be a borted . Thi s prenatal diag-
li ve r premature ly. Prematurity poses a great ri sk to the nos is is accorn pli shed either w ith genetic arnni ocente-
neonates and pl aces an inordinate dernand on hea lthcare sis or, more and more, w ith ea rl y bl astornere diagnos is.
reso urces. Thi s is one of the reasons w hy it is no ted that in Tabl e
38- 15 , wo men w ho have suffe red from in fe 1tility and
There are also maternal co mpli cations to the super-ovu- w ho desperate ly want the pregnancy they are wo rking
lated ART procedures. T he ovarian hyperstim ul ation towards, actua ll y undergo an induced aborti on.
syndrorn e (OH SS) is an exaggerated res ponse to ovul a-
tion induction thera py. Whil e it is not li mited to the A RT
procedures, and rnay theoreti ca ll y occur with any ovu- Has There Really Been Progress?===l
lati on-inducti on protoco l, it is clearl y more com mon in
those wo rnen w ho undergo super-ovul ation techni ques . An enorrnous arn ount of atte nti on has been paid to th e
Thi s condi tion can occ ur in J to 2 percent of ovul ation new re producti ve techno log ies over the last 26 years.
induction progra rns and A RT proced ures and it can be National te levision program s continue to pl ay a grow-
life threatening . The O HSS is typ ica ll y associated w ith ing inte rest in those parents who conce ive sextu plets
exogenous gonadotro pin stirnulati on and is ra re ly ob- or septupl ets and g ive birth as a result of these tech-
served with the use of other age nts (clomi phene ci trate no logies. Th e publi c is led to think that thi s is rea ll y th e
and gonadotro pin-re leasing hormone). lt tends to be onl y approach ava il abl e to the so lution to their prob-
se lf-limiting and reso lves sponta neously wi thin severa ! lern , one rnust begin to rea li sti ca ll y questi on whether or
days, but it can persist fo r longer pe riods of tirn e, par- not any rea l progress has been made.
ticul arl y in concepti on cycles. The syndro me has a broad
spectrurn of clinical mani fes tati ons ra ng ing fro m a mild In 1950 ,42 Meaker repo1ted a series of 65 pati ents who
illness need ing onl y careful observa tion to severe di s- underwe nt ovarian wedge resecti on fo r polycystic ova-
ease requiring hospi ta lizati on and even intensive care. rian di sease. Of thi s gro up, 77 percent w ith irregular
The Practi ce Committee fo r the American Society fo r bl eeding deve loped normal cycles and 66 percent ofth e
Reproducti ve Medicine has recently publi shed the comin fe rtile wo men became pregnant. In the 1960s, clomi-
pl ete descripti on of the patho phys iology, ri sk facto rs, phene c itrate beca me ava il abl e and po lycystic ovari es
c lini cal fea tures and manage rnent of thi s conditi on.40 could be treated medically. However, the pregnancy rate
decreased to about 30 percent43 and it was ha iled as a
Oocyte retrieva l is genera lly acco mpl ished by tra nsvagi- success. More recentl y, in vitro fe rtili zati on has a lso
na l ul traso und a pproac hes. Thi s technique is also not been pro moted fo r treating po lycystic ovari es with suc-
without potenti al pro bl erns. E ven in a non-com plicated cess rates of about 23 to 25 percent per cycle .44 .4 5 There
ultraso ni ca ll y-g uided tran svagin al oocyte retri eva l, an is no questi on that the pregnancy ra te on a "per woman"
estimated average blood loss of 232 .0 rn L has been bas is has dec l ined over the last five decades of treat-
show n to occur.41 O ve r the last severa! yea rs, there has ment of po lycystic ovari an di sease ( Figure 38-4).
100
of 29 percent in a gro up of 50 pati ents who underwent
50 years of "Progress" In Pregnancy
Rates : Polycystic Ovaries microsurgical salpingostomy 48 while the Nationa l Sum-
80
mary for IVF reported a pregnancy rate per cycle started
66 of27.5 for patients with tuba! facto r infe11ility. Whi le the
60
E
pregnancy rate on a " per woman" basis fo r IVF might
~
Q.
perhaps be sli ghtl y hi gher than 27 .5 , on a national aver-
age, the pregnancy rate per cycle started is fairly close
25.4
23.1 to the actual pregnan cy rates "per woman" (this issue
20
will be discussed in detail in the chapter on effective-
ness) (F igure 38-6).
1950 1970 1996 2001
Wedge Clomiphene 0 IVF « IVF'5
Reseclion°
Outcome of Pregnancies -----~

Figure 38-4 : Fifty years of "progress" in pregnan cy rates in
patients with polycystic ovarian disease . In 1950, the preg-
nancy rate from wedge resection was 66 percent. In 2001 , Many years ago ( 1974), Stewart and Cooke 49 made the
the pregnancy rate per cycle started with IVF was 23 .1. important observation that "Once the infertil e patient
becomes pregnant, it does not follow that her manage-
ment has been successfull y completed. The only con-
In women with endometriosis, it was not uncommon at firm ati on ofsuccess shou ld be the deli very ofa health y
al i, 20 years ago, to get " per woman" pregnancy rates in child and so the management of her pregnancy shou ld
the 50 to 60 percent range (o ver a course of 36 months be as importan! as the management of her infertil ity."
of treatment) 46 whi le the 2001 National Sumrnary for the And yet, the curren! approach to infertility in the Un ited
treatrnent of endometriosis claims a 30.8 percent li ve States and much ofthe Western World views infertility
birth rate per cyc le started. 26 The data from the National as an iso lated circum stance and once the patient be-
Surnrnary is interesting in that it has been specifically comes pregnant, she is referred back to her local phys i-
noted by others that patients with endometriosis-asso- cian (e ither an obstetri cian ora fami ly phys ician). In
ciated infei1i li ty who undergo IVF respond with a preg- actual fact , these pregnancies can be highl y comp li-
nancy rate that is almost one- half that of women with cated.
other indications for IV F. 47 In any regard, on a " per-
woman basis," the pregnancy rates with the standard lt has bee n known for a long time that pregnancies
conservative surgery for endornetrios is management achieved with the use of ovu lation induction protocols
were hi gher 20 years ago th an they currently are with caiTy with them an in creased ri sk of pregnancy-re lated
ART approaches (Figure 38-5). complications. These complicati ons wou ld include such
things as prematurity associated with multiple births,50
In 1978, Gorne l reported an intrauterine pregnancy rate and the hi gh incidence oftoxem ia ofpregnancy. 51 A long
100-·. ----------------------. 100-. - - - - - - - - - - - - - - - - - - - - - - .
80 80·
60- 60-
53.9
40 40
30.8 29 27.5
20 20
198 1 2001 1978 200 1

Conservativa ART Micro Surgery 41 IVF :ze
Surglcal Natlonal Data 11
Management
at 36 months'8
Figure 38-5: "Progress" in the development of pregnancies Figure 38-6 : "Progress" in pregnancies over 20 years in
over 20 years in patients with endometriosis . In 1981 , 53 .9 patients with tubal factor inferti lity. In 1978, microsurgical cor-
percent of patients achieved pregnancy over 36 months ("per rect ion of tubal adhesions resulted in a 29 percent "per
woma n") with conservative surgical management. In 2001 , woman " pregnancy rate . In 200 1, the live birth per cycle started
the pregnancy rate per cycle started with IVF was 30.8. with IVF was 27 .5.
488 The Medical and Surgical Practice of NaProTECHNO LOGY
with toxemia in pregnancy, which is also seen more com- Empty Deficiencies of
mo nly in women who have been treated with donar in- "Modern" Reproductive Technologiesl
sem ination ,52 other prob lems such as ectopic pregnancy,
gestationa l diabetes, operative de liveries, fetal distress, Since the birth of the first IVf baby, there has been
low Apgar seores, and low birth weight babies are ali observed an insatiable desire to expand these techno-
observed more frequently. 53 -55 logical front iers fu11her and further. This has been ob-
served in a variety of different ways. And yet, it contin-
More recently, an increased risk oftoxemia ofpregnancy ues to expand its problematic base. Women undergoing
associated with intrauterine insemination ,56 donar in- IVF show higher levels of anxiety and emotional ten-
semination ,57 and donated gametes 58 have ali been re- sion than do control patients. 79 Large numbers of mul-
ported. ln addition , over and over again , complications tiple pregnancies have been created with ali of their
associated with an increased incidence of preterm la- attendant problems. These babies are born prematurely,
bor, low birth weight and very low birth we ight have they are of both low birth we ight and very low birth
been well documented. 59-66 lt is a rare study that sug- weight and these ch ildren are e ndangered by their birth
gests that, even in singleton babies , there is no in- status. The author observed at a monthly meeting of
creased risk for prematurity or low birth weight. 67 E ven his department, a doub ling ofthe incidence oflow birth
there, however, prematurity has been faund in other weight babies bom during that year. When inquiring as
studies to be more frequent in IVF singleton newboms. 68 to the cause (perhaps somewhat naive ly), one of the
lVf has also been associated with a 2. 1-fald increased members ofthe 08-GYN staffsaid rather cavalierly and
º
risk ofpreeclampsia. 69 · 7 with complete acceptance, "That's just the ART factor. "
In any other a rea of medicine, the fallow ing questions
A more comp licated issue is the eventual outcome of would be asked: " Why? What can be done about it?
infants who survive birth after having been conceived How can we reverse the trend?" And ultimately, " How
by ART. A recent study has shown that children who can we stop endangering these ch il dre n. "
are born after lVF have an increased risk ofdeve loping
neurolog ical prob lems, especial ly cerebral pa lsy. These So there has developed a techno logy which creates life
risks are thought to be largely dueto the high frequency by destroying it. Multiple embryos are placed within
of mu ltiple births, low birth weight and prematurity. 71 the uterus in arder to obtain one. In fact, it is estimated
that 6. 7 embryos for every one that is successful. This
Intracytop lasmic sperm injection (ICSI) has received a is justified on the basis that "natura l human wastage" is
good deal of attention . Severa! studies have shown about equal to that, but that view is changing and it is a
evidence of a higher incidence of numerica l c hromo- justification that no longer shou ld be used (see Chapter
some anomalies in sperm-fertil ized human oocytes after 58).
ICST7 2·73 a nda two-fa ld increase in majar bi11h defects
compared to naturally-conceived infants .74 Once the woman becomes pregnant, she is asked to
undergo genetic amniocentesis or prenatal genetic di-
On the other hand , stud ies have also shown no in- agnosis using a blastomere and once more putting her
creased risk of majar anomalies in the JCSI group 76 or pregnancy at risk, ali far the sake of a "guaranteed"
any difference between children conceived after ICSI healthy baby. Sorne very wanted pregnancies end in
and their naturally-conceived peers in terms ofphysical abortion . The techno logy creates li fe by destroy ing it.
health and deve lopment. 75 ·76 In another study, obstetric lfthe woman ach ieves a mu ltiple pregnancy, she is chal-
outcome ofICSl pregnancies was considered to be sim i- lenged to " se lective ly reduce" the number of fetuses .
lar to that of conventional l VF, although multiple births Th is euphemistic term fa r abo11ing sorne of her fetuses
was still the majar concern .77 Th is study presents sorne is creating life by destroying it. Th is has , in fact, be-
concerns along with its fal low-up. Kovalevsky, et al., come so common place that many reprod uctive endo-
have voiced concern that these studies have not had crinologists in their super-ovu lation programs have been
approp riate controls. They have suggested that ideally virtually unconcemed with the multiple pregnancy rate
one should have controls of "babies born to infertile knowing foil well that the perinatologists will " save
couples achieving pregnancy without the use of ART. " 78 them" with their selective red uction programs. This goes
In actua l fact, this too is an inappropriate control group well far them until they come across a patient who, for
far this pai1icu lar popu lation. The proper control group strong moral reasons, will not create li fe by destroying it.
would be natura ll y conceived patients with no previ-
ous reproductive problem or toxicologic abnormality. This ali comes from a profession w hich has focused a li
of its energies over the last 25 years on the
rnicrornanagement ofhuman ferti lity. With its extraordi- others might give birth. Large sums of money have been
nary emphasis on molecular biology, there are times proposed for purchasing such donated ova suggest ing
when it has been unable to see the forest for the trees. that greed has entered into the profession. Sorne physi -
As was pointed out earlier, the Boston TVF group rec- cians have spoken eloquently aga in st this. 86
ognizes that on the day prior to ovu lation there is a
"thi n, watery mucus which spills out ofthe cervical ca- One picks up the newspaper and reads something nearly
nal and covers the portio of the cervix and upper va- every day, i.e., "Babies from Thawed Ovarian Tissue by
gina." But then, they dismiss it by say ing "sorne women 2009 - Experts,"87 " Pregnancy Created with Egg ucleus
notice this change in the cervical mucus, whereas oth- of!nfertile Woman,"88 "Ethics Expert Supports Sex-Se-
ers do not" 2 (which is al i that is to be said about one of lection in IV F," 89 or how about the "S uccessful Preg-
the most important biomarkers in human fertility) . nancy" in a 63-year-old woman. 90 -9 1. Fortunately, sorne
have cautioned against this as well. 92
This is a profession which has fostered masturbation
for the evaluation of the seminal fluid for the male to Then, among other things, there is procreation after
identify male factor infe11ility. This has been done with- death or menta l incompetence. Most ofthese cases have
out any concern or sensitivity to the aesthetic, ethics or to do with posthumous fat herhood. 93 ln reality, the move
rnorals of the person. This is a profession which has toward this type of parenthood seerns very cons istent
accepted cross-species fertilization with the use ofharn- with the "philosophy of nothingness." Why shouldn 't
ster egg penetration assays without any concern for the child be brought into the world without a father?
the potential ethical or moral problems that it poses. 80 -82 More and more, fa th ers have been relegated to a posi-
One has to wonder why the majority of wornen do not tion that is nearly insignificant and unimportant. The
seek infertility care when their fecundity is irnpaired. " philosophy of nothingness" perpetuates the notion
This is a profession, which has redefined the embryo that the father has no fundamental role in the raising of
and introduced the term "pre-ernbryo : the developing his child or that his ro le is completely insignificant and
ce ll s produced by th e division of the zygote until the can be discarded without co ncern.
forrnation ofthe embryo proper at the appearance ofthe
prirnitive streak about 14 days after fertilization." 83 The
author learned rnany years ago that a definition is nota Missing Links ---------~
substitute for knowledge.
lt would appear that modern reproductive medicine has
There are an estirnated 400,000 frozen embryos stored severa! "missing links" which have kept it from rnaking
in the United State .84 lt is recognized that these excess progress in ways which are more consistent with foun-
ernbryos result from our imperfection in trying to dupli- dational eth ica l and medica! principies. Sorne of these
cate natura l reproductive processes. 85 "missing links" would be the following:
The presence of these embryos provides further moti- l. For most patients seeking evaluation for a repro-
vation for the development of continuing experiments ductive abnorrna lity, an adequate diagnosis oftheir
on human embryos and the further development of em- underlying disease is not made.
bryonic stem cell s. Harvard University recently ven-
tured in to the a rea of embryonic stem cells and are mak- 2. Since an adeq uate medica! diagnosis is not mad e,
ing avai lab le these stem ce ll s to others for research pur- an appropriate therapy fo r that medica] cond iti on
poses. They are using private funds to stimulate this cannot be implemented.
research because the government has restricted fund-
ing for that. Why co uldn 't Harvard University provide 3. The major " missing link" from a biological perspec-
funding for further research in to the stem cells that are tive, is the cornp letely inadequate study of the ef-
lost day in and day out in the delivery rooms of Ameri- fects ofthe endocri ne and immune systems on the
can hospitals. Umbi li cal cord and placenta! stem cells target organs of reproduction. The lack of sound
may very well be the hope for the future in this area of procreative educat ion and an objective analys is of
research, but beca use of the poli tics, not so much the the biomarkers ofhuman fertility have led investiga-
science, there seems to be a "protect at ali costs" men- tors down paths which have missed the presence of
tality for the continued research in areas that are unnec- signs which herald the underlying etiology of re-
essary. productive abnorrna liti es.
Wornen have become involved in donating ova so that 4. Combine this with the apparent lack of apprec iation
for the notion that infertility and other reproducti ve pita) committees, professional affa irs comm ittees, and
abnormalities are mu/ti-factorial in their etiology and other programs of professional involvement wou ld be
effective treatment can be obtained only when it is deeply concemed in working towards its correction. Let
implemented in a multi-factorial way. us ali hope that "modern" reproductive technology has
not been canonized to such an extent that its " progress"
5. There appears to be a lack of concem for the health cannot be re versed and real progress introduced .
care of women who suffer from these anomalies.
There has recently been a significant amount of
progress and a better understanding of this con- Final Note -----------~
ceptas it applies to insulin resistance in women with
polycystic ovarian di ease. However, this move Sorne have issued concerns abo ut the potential health
needs to be much broader based and intensely in- problems arising out ofhuman ART programs. 95 Others
vestigated. ha ve pondered whet her the move for more choices has
actua ll y closed opportuniti es and exhibited no bound-
Sorne would argue that an adequate diagnosis is being aries.96 Has the termino logy of " rights" become mean -
made. However, it is c lear that many view " effecti ve, ingless? Rowland , a forme r research coordinator w ith
affordable treatments that produce pregnancy" as be- the !VF program directed at the time by Dr. Carl Wood at
ing "more important to infertile couples than reaching a Monash Uni versity in Melboume, Austra lia, s uggested
diagnosis. " 94 A hi gh ly technological , extreme ly expen- that the stress on choice may g ive the medica] profes-
sive approach to the treatment of reproductive abnor- sion more, not less, control in reproductive issues. In
malities has been developed and is out ofthe financia! the movement toward choosing the sex of your child ,
reach ofmost people (it is a rich man 's treatment). Fur- using donor ova, utili zing su rrogates , promoting em-
thermore, this approach rare ly improves health while bryo experimentation and embryon ic stem cell research ,
often threatening it. In add iti on, whether we ha ve actu- e liminat ing or dimini sh ing the role of fat hers, and the
ally improved overa!! pregnancy rates with this surge in movement toward cloning, it wo ul d appear th at onl y
technology is highly suspect. those wit h expanded knowledge of the biology of hu-
man reproduction are the ones w ho are in contro l. We
In any other a rea of medicine, i f the success rate was ha ve chosen the path ofviewi ng the child as a commod-
decreasing, and the morbidity and mortality (neonatal ity. lt seems that thi s approach was once prev iously
morbidity and neonatal mortality) were increasing, hos- u ed and it failed.
1. Tietze C, Gunmac her AF, Ru sin S: Time Req ui red fo r Con- 7. Reading AE, Kerin J: Psyc holog ical Aspec ts of Prov idin g
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53. Varma TR , Patel RH: Outcome of Pregnanc y Fol lowing
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119, 1988 . meri ca l Chromosome Abnormalities in Spermatazoa lnjected
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and the Ri sk of Low Birth Weight. Fertil Steril 56:668-67 1,
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Conrrolled Study of Karyotyping far 430 Consecutive Ba-
56. Smith GN , Walker M, Te sier JL, et al: Jn creased Jn cidence
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58. Salha O, Sharma V, Dada T, et al: The Jnfluence of Do natin g
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70:638 -642 , 199 8 .
77. Bo nduelle M, Liebaers 1, Deketelare V. et al : Neonatal Data
60. Zuppa AA , Maraglian o G, Scapillati ME , et al: eo natal
on a Cohort o f 2889 Jnfant s Born after ICSI ( 199 1-1 999)
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61 . Tan S-L, Doy le P, Campbel l S, et al: Obstetric Outcome of
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In Vi1ro Fertilization Pregna ncies Compared with Normally
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1992.
79. Sal vatore P, Garibo ldi S, Offidani A, et al: Psychopathology,
62. Seoud MA-F, Toner JP, Krueth off C, et al: Outcom e of
Personality, and Marital Relationship in Patie nt s Und ergo-
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ing In Vi1ro Fertili zation Procedures. Fertil Steril 75 :111 9-
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11 25 , 2001.
1992.
80. Thadani VM: C lu es from Research into C ross-Species Fer-
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Birth Wei g ht and Small-for-Gestati o na l-A ge in Live Bo rn
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64. Fi sch B, Harel L, Kapl an B, et a l: Neonata l Assess ment of
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say and Hum a n In Vi1ro Fertilization. Fertil Steril 45:665-
65. Tough SC, Greene CA, Svenson LW, et al: Effects of !11 Vi1ro
670, 19 86.
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stetric Outcome of I n Vi1ro Fertili zed Singleton Gestation s
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Steril 67: 1077-1083, 1997 . Embryo . Fertil Steril 74 :2 13-2 15 , 2000.
Chapter 38 : Trend s and Defic iencies in lnfertility Evaluation and Treatment 493
86. Sauer MV: lndec ent Propasa !: $5,000 is not "Reaso nab le 92. Sauer MV: Mothe rhood at Any Age? Egg Don ati o n was not
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1999.
93 . O hl DA, Park J, Cohen C, et a l: Procreat ion after Death o r
8 7. Re ute rs. Bab ies from Thawed Ova ri an Tissue by 2009 - Mental ln compete nc e : Medica! Advance or Technology
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88. Grady D: Pregnancy Created wit h Egg Nuc leus of lnfertile 94. Buster JA, Carson SA: Ta kin g a Res ults-Oriented Approach
Wom e n. thenew yo rktim es.com October 14, 2003. to lnfe rti lit y. Co ntemp 08 / GYN , pp 100-1 26 , October
1998.
89. Neergaard L: Ethics Ex pert Supports Sex Se lecti on in IVF.
Assoc iated Press. September 29, 200 1. 95. Leese HJ , Donn ay 1, Thompson JG: Hum an Assisted Co n-
ceptio n: A Ca uti o nary Ta le. Lessons From Do mesti c An i-
90 . Pau lso n RJ , Thornton MH, Francis MM , et al: S uccessful
mals. Hu m Re prod . 15 : 184- 202, 1998.
Pregnancy in a 63 -Year-O ld Woman. Fertil Steril 67:949-
95 1, 1997. 96. Rowlan d R: Socia l lmpli ca ti o ns of Re prod uct ive Tec hnol -
ogy: lnt Rev Na t Fam Pla n 8: 189-205, 1984.
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Medical Risks of lnfertility
nfertility, next to pregnancy and childbirth, affects such conditi ons as chron ic prostatiti s, hormonal dys-
I more women ofreproductive age th an any other con-
dit ion. Literally milli ons ofwomen are affected by thi s
function, varicoce le (vari cose vei n ofthe testic le), and
so rne causes that are not yet known .
condition every year but are notable to recei ve adequate
medica! care beca use the health in surance industry ex- In women, one ofthe main diffi culties with infertility
cludes coverage fo r "fertility-related serv ices" (to be and the organic diseases and hom1onal dysfunctions that
read : " infert ili ty"). are assoc iated with it is th at these same di seases can
also cause both short- and long-term disability, impair-
ln fe rtility is associated with a group of diseases that ment aj one 's quality aj lije and even potenti all y the
affect not on ly the reproductive status of women but shortening ajone 's lije. 1n other words, ferti 1ity-related
also their very hea lth. An enormous amount of insight prob lems in women have a "two-pronged" effect. They
has been ga in ed into th e ca uses of infertility over the not on ly affect a woman 's fertility but th ey also affect
last 20 to 30 years. Infertility is now known to be asso- her genera l hea lth. Because in fe rtility eva lu ation and
ciated with di seases that have a substantial health im- treatment has been exc luded by the in surance industry
pact on women and, ift hese women are left untreated, for so many years, litera ll y thou sa nds, if not millions,
such di seases lead to a decrease in quali ty of life and of women throughout the United States ha ve been de-
the potentia l that life may be either impaired or short- ni ed access to the type of medi ca! care th at they de-
ened. serve fo r these medica! condition .
lnfe1tility is usuall y assoc iated with sorne degree of ei- Such problems as pelvic pai n; dysmenorrhea; dyspareu-
ther organic disease, ar hormonal or ovulatory dys- ni a; irritable bowel syndrome; vari ous metabolic effects
junction. In women, these in clude such conditions as including increased ri sk for heart attack, and diabetes;
endometriosis, ovulation-related disorders, vari ous hor- the potentia l onset ofvariou s cancers including ovarian
monal dysfu nction s, pel vic ad hesive disease, polycys- cancer, endometrial cancer and breast cancer; osteoporo-
tic ovari an di sease, various forms oftubal occlusion and si ; and the ri sks of subsequent pathologic pregnancies
anovul ati on. Ma le ca uses of infertili ty are associated and low birth weight in fa nts are ali assoc iated with th at
wi th low sperrn counts, and the e are associated with "two-pronged" effect. [t has become irrespons ible for a
495
496 The Medical and Surgical Practi ce of NaProT ECHNOLOGY
soci ety not to recogni ze these medi ca! effects and risks mechanisms underlying this loss may be similar to those
exist w hil e deny ing a ppropri ate thi rd-party re imburse- seen in cancers. It has been observed in assoc iati on w ith
me nt for the ir medica ! care . sma ll bowe l obstructi on,2 the invo lvement of th e ure ter
leading to kidney obstructi on and uremi a (kidney fa il-
ure),3 and other areas of the urinai)' tract. 4•7 The sigmoid
Endometriosis ----------~ co lon has been perforated during pregnancy as a res ult
of endometri os is8, and massive ascites can also be as-
E ndometri os is is notori ous fo r causing such pro bl ems sociated with endometrios is. 9· 10E ndometri os is has been
as severe pelvic pain , menstrual cramps , and pain with observed in the lung, 11 -12 the sc iatic nerve, 13 the di a-
intercourse. B ut it is also assoc iated with irritable bo wel phragm ,14 an d in the rectal/vaginal area 15 a long w ith
syndrome, hormonal dysfunctio ns, and a variety of can- many other areas .
cers .
Endometriosis is treated e ither surg ica lly or medi ca lly, Hormonal Dysfunctions Associated
but the surg ica l approac h is genera lly better fo r th e re- with lnfertility _ _ __ __ _ _ _~
li ef of pa in and fo r fu ture fe rtility pu rposes . However,
surgica l procedures must be done expertly in such a fash- Hormonal dysfu nctions are ve1)' common in wo men w ith
ion so as to prevent adhesions (or scar tissue) fro m fo rmin fe rtili ty probl ems. These probl ems are often associ-
ing as a resul t of the surg ica l procedure itself. E ve n w ith ated with the abnormalities that occur in associati on w ith
these treatments, there is sorn e rate of rec urre nce with infertility re lati ve to the occurrence of ovul ati on. Ab-
the di sease. However, long-lasting re lief can be ant ici- norma l events of ovu lati on are common in women w ith
pated espec ia ll y w ith surg ica l treatment. infert ili ty and because of thi s, the hormona l dysfu nc-
tions assoc iated with ab nom1al ovu lations are also com-
It is well kn own that certain aspects of endometriosis mon.
are simil ar to those of mali gnant di sease. 1Endometrio-
sis may pro life rate and invade other ti ssues due to a In F igure 39-1 , the lutea l phase progesterone leve ls are
loss of control of growth and pro li fera ti on, and the shown for wo men who have in fe rtili ty fro m a li causes.
Post-Peak Progesterone
Post-Peak Progesterone Profile Sums and Means
Control (N-57) vs. All lnfertility
Control (N=57) vs. All lnfertility with Regular Cycles with Regular Cycles
...-~~~~~~~~~~~~~~~~~~~ ......~~~~----~--~~~"'9- 1 00
• Control group
• Study group 90
15
80
11 .9 12.2
.1--------f.,,
70 w
2
..
,,' ....... 61 .2 3
60 -a
9.4 /
/
,/ ''<10.0
',,
50 ;.
.a
<C
8.7 ! ',,, 8.1 a

',, :::J
,, 6.8
40 ..
'S'
ce.
30 E:
20
10
p= ~ 1ooos l l<.0001 11<.0001 1 ~
º. . . . N= 280 288 289
..;.;..~~~~....,~~...,..~~.,....~....,~~...,..
278 250
.....
~ o
P+3 P+S P+7 P+9 P+11 Sum Mean
N=240 N=240
Days Post-Peak
Figure 39-1: Postovulatory (post-Peak) prog esterone profil e in patients with infertility and regular cycl es
(N=240, dotted line) compared to a co ntrol group of women with normal ovulatory function. Ali level s in the
infertility group are significa ntly lower than in the control group (From: Pope Paul VI lnstitute research, 2004 ).
Chapter 39 : Medical Risks of lnfertility 497
In patients with endometriosis, polycystic ovarían dis- Pelvic Adhesive Disease -----~
ease, pelvic adhesive disease, and distal and proximal
tuba! occlus ion , the production of progesterone during Pelvic adhes ions are formed in a variety of different
the postovulatory phase ofthe cycle has been shown to conditions. Endometriosis, for example, is notorious for
be significantly decreased. causing very thi ck and dense pelv ic scar tissue. How-
ever, pelvic infecti ons such as Ch lamydia and gonor-
Progesterone is very important to the support ofpreg- rhea also ca use such problems.
nancy and it a lso modulates or modifies the immune
system. It supports the immune system and , w hen the When a women has pelvic adhesions, it is often associ -
progesterone leve Is are low, the immune system becomes ated with pelvic pain and increases her risk oftubal preg-
less effective. lt is thought that these decreased proges- nancy. Pe lvic adhesions cause infertility or other repro-
terone leve ls are one reason w hy wo men with inferti li ty ductive problems by scarring the fa ll op ian tubes and
ha vean increased ri sk of vario us types of cancers (see causing tuba! blockage.
late r).
[n Figure 39-2, the androgen levels in women with poly- Polycystic Ovarian Disease ----~
cystic ovarían disease are shown. Testosterone and an-
drostenedione, are spec ificall y elevated. In women with In women who have polycysti c ovaries, the cond ition is
polycystic ovaries (PCO D), hirsuti sm , acne, obesity and associated with long and irregular menstrual cycles.
hypertension are ali assoc iated with these elevated an- These ovaries do not respond norma lly and so these
drogen level s. F urthem1ore, sorn e of the cancers that women are chroni cally anovu latory or oligoovulatory.
are associated with long-term, untreated PCOD are as- Mu ch of the ir infert i1ity is due to the fac t that they are
soc iated , at least in part, to the elevated androgen lev- not ovulating regu larl y and, of course, treatment is aimed
els (see below) . at try ing to ass ist them w ith this.
Po lycystic ovarían di sease is often assoc iated with a

variety of different metabo lic abnormalities (see later)
P+7 Androgens in Patients with PCOD

Control Group vs. Study Group - Control
CJ PCOD
2.15 2.09
50 2.0 2.0 200 47.5
179.1
'5 E 1.60
ECD
~
Q)
g'ª' :g,
e: e:
e e CD
e:
t.>
.§.
o
* *
o
o; 25
CD
f-
-¡¡;
B
(/)
CD
f-
CD
1.0
~e:
2
e
1.0
(/)
<
w
:r:
e
o
f-
~
u.
'O
¿
o----------- Total
Testosterona
Free
Testosterona
Androstenedione DHEAs
p = 1 <.0002 I 1<.0001 I 1 <.001 1 .0862
Figure 39-2: Androgen levels in patients with PCOD compared to a control population without PCOD.
Total testosterone, free testosterone and androstenedione levels are all stati stically significantly higher
and DHEAs levels are higher and approach statistica l significance (From: Pope Paul VI lnstitute
research , 2004).
and the increased risk of endometrial cancer is signi fi - Gastrointestinal Problems, Irritable Bowel
cant. These cancers are preventable with adequate eva lu- Syndrome -----------~
ati on and treatment and , more and more, th e me ta bo l ic
abnorma lities are a lso treata bl e as wel l. Endometrios is can frequentl yin vo lve the intestinal tract
(approx imate ly 25% of cases 31). Thi s may invo lve the
sigmo id co lon, th e rectum , the te rmina l ile um, cecum
or appendi x. When such involve ment occurs, it can cre-
Pelvic Pain , Dysmenorrhea and ate sympto ms of irritable bowel syndrome,partial bowel
Dyspareunia ~~~~~~~~~~~----, obstruction, 2 and even mimic primar;; gastrointestinal
cancers on x-ray imag in g. 32 Furthermore, the ovarian
The long-establi shed associati ons between endometrio- steroid hormones (esp ec ia ll y progesterone) have long
sis and pelvic pa in and between endo metri osis in gen- been thought to have important effects on the motor
era l and inferti lity ha ve been confirmed .16 The fre quency activity of the gastro intestina l tract and to determine
of symp toms in assoc iati on w ith wo men w ith en - the express ion ofthat acti vity. Dysfun cti on ofthese hor-
dometrios is are identified in Table 39- 1. In a survey mones has been observed in pati ents w ith idiopathic
conducted by th e Endometriosis Assoc iation, 72% of fun ctional bowel disease33 and , w ith the decreased pro-
patients had symptoms fo r six or more years before they ducti on of progesterone observed in a va riety of in fe r-
eventuall y obta ined adeq uate eva luat ion and treatment. tili ty states , it is easy to understand how thi s could be
F urthermore, 60% ofwomen saw more tha n three phy- made wo rse . In these conditi ons, the ab ility of p rogest-
sicians an d 32% saw five or mo re physicians. This data erone to quiet the bowel is less intense, and fun cti onal
suggests th at wo men with endometrios is cont inue to ex- bowe l disease may be exacerbated . These symptoms
perience signiflcant delays in the diagnosis and treat- ca n be debilitating fo r wo men and lead to a sign ifi cant
ment of thi s co nditi on and they suffer considerable di s- decrease in th eir quali ty of li fe.
ruptio n in the ir li fe . 17
F urthermore, pelvic ad hesive di sease and chron ic pel-

v ic infections, w hil e associ ated with infe rtility, can also Metabolic Effects of PCOD ----~
be an assoc iated fi nding in chro ni c pelvic pa in . 18
lt has been clearl y recog ni zed now that polycys ti c ova-
C hroni c pe lvic pa in is associated wi th endometri osis in rian syndrome is assoc iated with majar metabolic dis-
7 1 to 87% of cases. 19- 23 S uch pe lvic pai n and its associ - turbances w hich are re lated to insulin resistance and
ated dysmenorrhea can be extremely debilitating but also that same insul in res istance pl ays a ro le in the deve lop-
can be treated quite adequately if the wo man is give n ment of the reproducti ve abnorm alities that occur w ith
access to medi ca! care. 24 -29 this di sorder. lnsulin res istance and e levated low den-
si ty lipoprotei n (LDL cho lestero l) leve ls are observed
l nterestingly enough, women with endometriosis and pel- in women with PCOD. Furthermore, brothers ofwomen
vic pain who conce ive are less li kely to experience per- wi th PCOD have insulin res istance and elevated DH EAs
sistent pelvic pain throughout the ir reprod ucti ve li fe. 30 leve ls which suggests that these are geneti ca lly related
conditi ons. 34-35
Polycysti c ovari an disease is a meta bol ic disorder w hj ch

affects mul tipl e organs. Studi es have suggested that
Table 39· l: Frequency of Symptoms wo men who ha ve thi s condition are at ri sk for deve lop-
Associated with Endometriosis 1 ing Type JI diabetes mellitus, hypertension, dyslipidemi a
(increased triglycerides, increased cholesterol), and even
Symptom Frequency
an increased risk of myoca rdi a l in farcti on. 36- 38 In addi-
Dysmenorrhea 68% ti on , wo men w ith pre-ex isting po lycystic ovarian d is-
Bowel changes 52% ease have an increased risk fo r developing di abetes when
Dyspareunia 32%
they are pregnant. 39 T he impa irment of g lucose to ler-
ance in normal women and women with po lycysti c ova-
Back/thigh pain 20%
ria n di sease is identified in Table 39-2. Chron ic fa tigue
1. Halstead L, Pepping P, Dmowski WP: The Woman with syndro me is also observed more fre quentl y in wo men
Endometriosis: lgnored, Oismissed and Devalued. Th e
Second lnternational Symposium on Endometriosis. The w ho ha ve po lycysti c ovari es .40
Endometriosis Association , 1989.
Chapter 39: Medical Risks of lnfertility 499
PCOD, Dysfunctional Bleeding and evated risk for breast cancer, ovarian cancer, 11011-
Hirsutism Hodgkin 's lyrnphorna and rnelanorna in women with en-
dornetriosis. In additi on to this, the study indicated
Additional symptoms associated with PCOD include elevated ri sks for these cancers in the farni li es ofwomen
dysfunctional uterine bleeding. This dysfunctional with endornetriosis.46 Furthermore, the risk of ovarían
bleeding is associated with the prolonged absence of cancer, breast cancer, and non-Hodgkin 's Lymphoma
ovulation and the chronic stimulation of the enha ve been shown to be increased by others 47 in patients
dometrium with estrogen which is unopposed by proges- with endornetriosis.
terone. Because ofthe unopposed estrogen stimulation
ofthe endometrium, the endometrium breaks down and
the woman experi ences chronic bleeding, which is not A. Ovarían Cancer
a true menstrual period . This is truly an endocrine dis-
order, but it does need to be properly evaluated and Because ovarian endornetri osis may play a role in the
treated. 41 pathogenesis of sorne ovarian cancers, it has been re-
cen ti y suggested that ovarian endometriosis should be
Excessive hair growth on the ch in , upper lip, sideburns, recognized as a precancerous condition and strictly fol-
chest, abdomen and upper thighs is also a comrnon con- lowed up. 48 Nu llipari ty and infertility are both associ-
dition associated with PCOD. This is usually thought to ated with an increased risk of develop ing ovari an can-
be associated with the increased androgens (rnale hor- cer with these women nearly three times more likely to
mones) that are associated with this condition (Figure develop ovarian turnors co mpared to women who have
39-2). Such hirsutism can be disfiguring and very prob- been pregnant. 49 Malignant transforrnation of en -
lernatic decreasing the quality of life for these wornen. dornetriosis is a well documented process especially with
Without proper medica! evaluation and treatment this regard to ovarían endometri osis. 50-52
condition cango on unabated. However, it does respond
fairly well to med ica! treatrnent. 42 -45 lt has been suggested that genetic factors contribute both
to the developrnent of endornetrios is and also to ova-
rian cancer and that there rnay be sorne comrnon link-
ages53 to that genetic inheritance. lt has also been sug-
lnfertility and Cancer _ _ _ _ _ _ _~ gested that infertility and endometrios is rnay be inde-
pendent risk factors for ovarían cancer and that both,
It is clear that sorne forms of infertility are associated therefore, should be taken into consideration as risk fac-
with the developrnent of certain types of cancers. ln tors. 54 In any regard, the linkage between infertility,
sorne cases, this connection is well estab li shed whi le in endometriosis and ovarian cancer is strong and has been
other cases it is more specu lati ve. Nonethe less, there we ll documented in the medica! literature. 55-65
are certain types of cancers that are clearly assoc iated
with problerns rel ated to inferti li ty. This is particularly
true for ovarian cancer, endornetrial cancer and breast B. Endometria/ Cancer
cancer.
An increased risk fo r endometrial cancer has been found
With regard to endometri os is, the Endometriosis Asso- among a variety of subgro ups of infertile wornen. It is
ciation recently co nducted a survey that showed an el- suggested that chronic anovulation is prirnarily respon-
sibl e for this linkage. 66 In anovul ation, the endometrium
is exposed to chronic estrogen stimulation unopposed
Table 39-2: lncidence of Glucose Tolerance by progesterone. Progesterone is normally produced
in Normal Women and Women with PCOD ' following ovulation. In the absence of ovu lation , of
course, progesterone is no longer produced. Th us, this
Normal Control Polycystlc
Glucose Women Ovar les presents a situation where there are relatively high es-
trogen and low or absent progesterone and this is clearly
Normal 89.7 61.4
associated with an increased risk of endometria l can-
lmpaired 7.8 31.1 cer.67-68
Diabetes mellitus 1.0 7.5
1. Du naif A and Thomas A: Current Concepts in Polycystic Ovary

The most commonly cited pre-existing linkage with
Syndrome. An nu Rev Med 52: 401-41 9, 2001 . endometrial cancer is poiycystic ovarian disease because
it is often associated with lon g and irregular menstrual
cyc les and p rolonged peri ods of anovu lati on. T hi s situ- in part, a progesterone defic iency di sease w hi ch is ex-
ati on sets itself up for prolonged ex posure of the en- ace rbated in wo men w ho ha ve a pro longed cbronic de-
dometrium with estroge n and a situati on that is proges- fic ie ncy of progestero ne during th e ir rep rodu cti ve
terone defi c ient. 69-71 With proper evaluation and treat- years.82
ment- with th e us e of exogenous progest erone
therapy- the incidence of endometrial cancer can be
significantly reduced. However, wo men mu st ha ve ex- lmmune Deficiency and lnfertilitY --~
posure to medi ca! care in order fo r thi s to be acco m-
p li shed . lt has been though t for a number of yea rs that en-
dometri os is may be assoc iated w ith sorne type of alter-
ation in cell-mediated immunity.83 In fac t, endometrio-
C. Breast Cancer sis fulfi lls ali the classic charac/eristics of an autoim-
mune disease- polyc lonal B cell acti vati on, tissue dam-
Ove r the past 20 yea rs, the overa ll inc idence of brea t age, multi-organ invo lve ment, fe male preponderance,
cancer has increased (see Fi gure 39-3). Furthermore, fa milia! occurrence, and increased concurrence w ith
one ofth e clear ri sk factors fo r the development ofbreast other autoimmune di seases. 84
cancer is de layed onset of the first pregnancyn lt has
been long recogni zed that progesterone deficiency states In women with endometri os is, there is a defect in natu-
have been associated with an inc reased ri sk of breast ra l kill er cell acti v ity, and the natu ra l kill er ce ll activity
cancer parti cul arl y of the premenopausa l type. 7º· 73 • 74 of the peritonea l fluid mononuc lear cell s is decreased
in endometri os is. This corre lates signifi cantl y w ith th e
Furtherm ore, it has been shown that wo men w ho have severi ty of the di sease in both the peripheral bl ood and
elevated androge n leve! and decreased progesterone the peritonea l fluid ofwomen w ith endometriosis. 85 ·86
leve ls also have in creased ris ks of breast cancer.15 -79
Whi le tbe re lati onship of the fac tors rema ins contro- Substanti al evidence indi cares that endometriosis shares
ve rsia! , the risk factor of delayed onset of pregnancy many simi larities with autoimmune diseases. The theory
(whi ch is common in in fe rtil ity pati ents) is incontro- of an altered immune system and endometriosis sug-
ve rtible. Considering a lso th at these are patients who gests that changes in ce ll-medi ated immuni ty and/o r
often have signifi cantl y decreased lutea l pha e proge - humora l immuni ty may contribute to the deve lopment
terone production and in sorne cases e levated and rogen of the di sease. Many inves ti gators now are looki ng at
leve ls ( Fi gure 39-2), thi s is someth ing th at needs to be immun omodul aters and infl ammatory modul ators as
fu rther di scussed and studied .8º poss ible innovati ve treatments for endometri osis.87 -89
Osteoporosis ----------~ Salpingitis lsthmica Nodosa and

Ectopic Pregnancy --------~
In patients w ith hypothalamic amenorrhea, the infe rtil-
ity is dueto the lack of ovul ation. The reason the wo man Sa lpingitis isthmica nodosa (SIN) is a cond iti on w hi ch
does not ovul ate is because the hypotha lamu operates usuall y affects the portion of the fa ll opian tube that
dysfu nctionally and the pituitary does not respond with im med iate ly enters the uterus. The prox imal fa llopi an
the needed cyc lic gonadotropin production. In such con- tube that is invo lved w ith thi s condi tion results in e ither
ditions, w ithout ov ulati on occurring, tbe wo man is ex- complete or partial blockage of that fa llopian tube.
posed to chronic low levels of estrogen and the com- Most commonl y, the b lockage of the fallop ian tube is
p lete absence of progesterone. In such c ircumstances, parti al. Because the bl ockage is only partial , it d isturbs
the wo man is signifi cantl y at increased ri sk fo r os- th e norm al transmi ss ion of the fertili zed ovu m down
teoporosis.81 the fa ll opian tu be and into the uterus. Because of thi s
abnorrnali ty, the bl astocyst or earl y embryo may get
ln additi on, beca use wo men w ith regular menstrua l caught in tbe fa ll opi an tube resulting in an ectopic preg-
cycles who ha ve infertili ty also have decreased proges- nancy. Such a pregnancy i dangero us for the wo man
tero ne production by their ovaries, there is the likeli- because the fa ll opian tu be can rupture unexpectedly and
hood that they may be at in creased risk fo r osteoporo- cause uncontro ll abl e hemorrhage . l t may requ ire emer-
sis in the long term as we ll. In fac t, tbere is ev idence to gency surg ica l interve nti on.90-93
s uggest that progesterone is a bone-building hormone
and that postmenopausa l osteoporos is may be, at least
lnfertility and Subsequent Pregnancy attitudes than other women and also an increased ri sk
Complications ----------~ of di sordered eating patterns. With these types of prob-
lems, psychological interventi on and support may be
Women suffering from infe rtili ty who then achi eve a necessary. 114
pregnancy are also at increased ri sk for subsequent preg-
nancy-re lated complicati ons. For exampl e, it has been
known fo r a long time th at the incidence of spontane- Socioeconomic and Health Costs of
ous aborti on, ectopic pregnancy, intrauterine growth re- lnfertility Care - - - - - - ------.
tardation, and stillbirth are ali increased in a subseq uent
pregnancy followin g infe rtility. 94 • 105 The above ri sks lt has been shown that most women with impaired fer-
occur in women who have pre-ex istin g endometrios is tili ty do not obta in infe rti lity ervices. 11 5 This means that
but also occur in wo men with hyperprolactinemi a. 100 the underlying medica! ri sks of their infe rtili ty problem
are not being eva luated or subsequently treated. It al so
In women who have polycystic ova rí an disease, the in- means that a large number of women are not being evalu-
cidence of gestati onal di abetes and pregnancy-induced ated or subsequently treated. lt also rneans that many
hypertension is increased significantly. 106 • 107 In fact, even wo men are bein g signifi cantl y underserved when it
the pre-ex isting di agnos is of infe rtili ty wil l increase the co mes to their bas ic hea lth needs.
risk of pregnancy-induced hypertension in a subsequent
pregnancy. Standard insura nce pl ans genera lly have language that
excl udes coverage fo r "an expense or charge fo r the
It has also been known that a pre-ex isting hi story of diagno is or treatrnent of fe rtility or infe rtili ty or pro-
infe rtility is a risk factor when it co mes to preterm de- moti on offertili ty including (but not lim ited to): ( 1) fe r-
li very. Babi es born to mothers who have previous in- tili ty tests and procedures; (2) reversa ! of surgica l ster-
fe rtili ty have a signifi cantly increased ri sk of havi ng a ili zation and (3) any attempts to cause pregnancy ...".
low birth weight infant due either to premature deli very Thi s language has led to signifi cant prob lems in th is
orto intrauterine growth restri cti on.108- 11 0 area of medicine fo r phys icians, hospitals and pati ents.
These probl ems include but are not limited to the fo l-
As a result of these medi ca! findin gs, pregnancies that low ing:
occur in women who have pre-ex isting in fe rtili ty are
more commonly high ri sk and demand to be fo ll owed
more carefull y and with more foc used medica! inter-
vention. With pre-ex isting know ledge of the cause of Diagnosis
the underlying infertili ty facto r, a more specific fo rm of 60
interventi on can be made.
55
General Medical Problems -----~ 50

8
o, 45
There are also a number of other genera l medi ca] pro b-
lems that occur more commonl y in women who have 8
~ 40
infertility. For example, women with endometriosis have .....
been shown to have heavier menstrual fl ow and signi fi - 8.
~ 35
cantly hi gher abnotmal menstrual seores than those who o
c.::
do not have the di sease. 111 Thyro id di sease is often as- 30
soc iated with fertil ity probl ems of one type or another.
Vari ous types of subfe rtility is assoc iated with both 25
hyper- and hypothyroidism. 11 2- 113 Thus, these patients
req uire a comp lete eva luati on of thyro id fu nction as a
part ofth eir eva luation fo r infert il ity. '83 85 87 89 91 93 95 97
Year
In women who have hypothalamic amenorrhea, it has Figure 39-3: This shows the increasin g rates of stage 1breas!
been shown that certain psychosocia l stressors may be cance r. Th e diagnosis of stag e 1breas! ca ncer has increased
assoc iated with thi s condition.114 These women often 113% betwee n 1983 and 1997 (data is from the Surveillance ,
Epide mio logy and End Re sults-SEER- Pro gra m of the
report more depressive symptoms and dysfu nctional National Can cer lnstitute72 ) .
1. The language is extremely vague and leads to This clearl y opens up the problem of gender-
an inability on the part of the physician or the specijic discrimination where the exclusionary
patient to reasonably interpret the provision. This causes, which most often affect wo men, have
leads to a very u neven and unfair adm ini stration been targeted .
of the provision.
6. lt has been known , in addition , that nuns, w ho
2. An example of this would be that many " fertil- may have hom1one problems associated with
ity-related" procedures are, in fact, often paid their menstrual cyc les, are at times denied cov-
for by insurance coverage and are not excluded erage because of it being " fertility related" when
by these provis ions . These include such things it is quite obvious that the medica! eva luation
as surgical steri 1ization, various methods of con- and treatment has nothing to do with fertility.
traception , and abortion procedures. lf, in fact,
7. In addition , patients w ho ha ve premenstrual syn-
an insurance program excludes contraceptive
drome, which is also often observed in women
coverage, the plan will often subsidize the use
who have in fertil ity, are often denied coverage
ofbirth control pi li s for the treatment ofvarious
for both the evaluation and treatment of their
women 's health problems even though those pi lis
conditi on because it is tagged as "fertility re-
are technically " fertility related. "
lated" when , in fact, it is not at ali fertility re-
3. Patients complain that the administration ofthis lated in these cases. The same is true far va ri ous
provision is often irrational. For example, insur- hormone-related causes of abnormal bleeding.
ance may cover a particular surgical procedure
8. As a result, this has led to a very contentious
for the treatment of a particular disease, but it
and confrontational relationship between women
wi 11 not pay for the diagnostic laparoscopy which
and their insurance companies w hen it comes to
is necessary for the physician to adequately and
issues related to the reproductive system. lt is
accurately diagnose it and thus prescribe the
not uncommon for these couples to hire attor-
proper surg ical procedure.
neys to represent them in their negotiation s with
4. This exclusion is often dependent upon the re- their insurance com panies, to constantly be on
view of the cla im s person in charge of review- the telephone with their insurance plan trying to
ing the particular claim at the insurance com- straighten out the claim 's process and to often
pany. lt is often open to their interpretation even enter into very contentio us appeals hea rin gs
though they are not medically qualified to as- which are stressful and quite unbecoming the
sess the medica! aspects of the situation , and premium paid to the insurance company far
experience has shown that the actual app li cation health coverage.
ofthe provision is extremely uneven. The c laims
9. Finally, some physicians have been targeted by
review person is usually not medically trained
the insurance industry in reta li ation far sorn e of
and not prepared to deal with a l1 of the varia-
the contentiousnes .
tions of evaluation and treatment that might ex-
ist far the condition. The same is often also true
The current use of "exclusion of coverage" clauses by
for those physicians employed by the insurance
the insurance industry far "fertility-related services" is
industry for review of these c laims. They are
very problematic and needs to be remedied. Further-
often not up-to-date with current capabilities of
more, it is out of date with our modern knowledge of
diagnosis and treatment.
the underlying diseases that actually cause fertility-re-
5. Medica! problems associated with male infertil- lated problems.
ity are often covered without any questions
asked. For example, antibiotics far the treatment It has been arg ued that managed care organizations
ofprostatiti s which will improve fertility ; a sur- should take the lead in providing inferti le couples with
gica l procedure for the repair of a varicocele an organized, humanistic approach that is mindful of
which also may improve male fertility ; testicu- the attending soc ial and health issues .11 6 ln this way, care
lar biopsies which will assist in the diagnosis of far infertility and its attendant health risks can be made
various male diseases that may be associated with more accessible and comprehensive.
infertility and, of course, the use of Viagra for
male impotence which may improve a male's fe r- ln a recent stud y ofthe costs ofan infertility evaluation
tility by correcting impotence are often , without and treatment, infertility costs accou nted for only a sma ll
question , reimbur ed by the insurance industry. fraction of the total health care costs of the p lan. Fur-
Chapte r 39 : Medica! Risks of lnfertility 503
thennore, the additi o n of infe rtil ity specific eva luatio n nose and treat these conditi o ns fro m an in fe tii lity per-
and treatme nt program s co ul d be obta ined for a nomi- spective are also used to di ag nose and treat th ese di s-
nal month ly fee. This was estimated to be an additional eases from a purely wo me n 's hea lth perspecti ve. Di ag-
m ember p er month h ealth care cost of $0.67. 11 1 nostic tools include laparoscopy, ultrasound assessment,
test ing of various hormo nes, testin g fo r blockages in
the fa ll opi an tubes, va ri ous types of bi opsies, and semi-
Summary and Conclusions _ _ _ __ nal fl uid analysis in men. Treatment procedures that treat
th e underly ing di seases inc lude vari ous surg ical proce-
Infe rtility is the inabi/ity ofa woman to achieve a preg- d ures, hormona l thera pi es, progra ms that treat ovula-
nancy o ver a period of one year of unrestricted inter- tory dysfunction , and a ntibioti cs.
course. In rea li ty, it is o nl y a sy mptom o.f underly ing
disease. While many years ago infe rtili ty was tho ug ht Therefore, it seems that legis latu res must understand
to be "a li in yo ur head," wo rk that has been do ne over the rea li ty ofthe underl y ing diseases and medica ] ri sks
the pas t 30 yea rs has shown that th e inab il ity to ach ieve that infertili ty poses. These wo men often suffe r fro m
pregnancy is the result ofa mul ti-factor ial combin ation severe pelvic pain, dysmeno rrhea and dys pareunia. They
of organi c, hormo nal and immuno logica l d iseases. may have gastro intes tina l abno rma li ties a nd irritabl e
bowe l synd ro me. Th ey may have severe hormo na l de-
The c urrent approac h of insura nce plans to exclude cov- fic iencies, whi c h result in fo rmation of cancers suc h as
erage fo r " ferti lity-related services" does not recognize ovaría n cancer and endometri al cancer in wo men w ho
thi s change in the understanding ofthe underl ying prob- have pre-ex isting infe rtility. Futi henn ore, the risk of
lems of in fe rti lity. lt still appears to observe infertil ity breast cancer is defi ni te ly increased in those wo men who
as mo re of a psycho logica l pro bl em tha n a med ica! o ne. have had pro lo nged epi sodes of in fertili ty.
In fa ct, next to pregna ncy a nd child birth, it is th e
m ost common m edica! p rob le m affecting reproduc- Other hea lth risks include the grow in g know ledge th at
tive age wome n. And yet, because of exc luded cover- there a re sim ilari ties between certai n types of in fe rti li ty
age, the insurance industry has specifi ca ll y ta rgeted th is and sorne ofthe auto immune di sorders such as thyro idi-
group of wome n w ith poor medi ca ! care . tis, syste mic lupus, a nd rhe um atoid arth ritis. Furth er-
more, wo me n who have pro lo nged anovul ati o n are at
There are many iss ues th at a re in vo lved in thi s c urrent increased risk fo r osteoporosis w hich can be a de bi li-
probl em. The primary issue, however, shoul d be the tating di sease no t o nl y in yo unge r wo men but most im-
questi on ofwheth er o r not wo men sho uld be g iven the portant ly as those wo men age.
ri g ht to have re productive hea lth ca re speci fi c to th eir
gender. Whi le a U.S. Di stri ct Court in C hicago ru led Perhaps one ofthe most hidden ofa ll ofthe factors rela-
that infe rtili ty fit the defi ni tion ofa di sabil ity and was tive to the infert ili ty medi ca ! c ris is is the issue of w hat
the refo re subject to the an tidi scrim inatio n enforcement happens to these wo me n whe n they become pregnant.
under theA mericans w ith Disability Act, 116 th is approach The ev idence that shows that the pregna ncies are at in-
ultimate ly deni es the fund ame nta l iss ue that thi s is a creased risk o nce the wo man becomes pregnant after a
hea lth care issue encoun tered by women. lt is not on ly pre-existing in fertil ity pro bl em is overwhelming. W ith
a health care issue specifi c to the ir imm ediate hea lth better med ica! kn ow ledge and unde rstanding of the ba-
but also, and pe rhaps most impo rta ntl y, their lo ng-term sic underl ying pro bl e m of the infertili ty that ex ists-
hea lth . whether that be organic or ho rmo nal or immune sti mu-
lated- the physician is in a better pos itio n to adequately
lt is qu ite poss ible that the c urre nt procedu res fo ll owed treat that pregnancy and reduce th e types of pro bl ems
by the insuran ce industry of exc luding infe ti ility cover- associa ted wi th those pregnancies . Tak ing s impl y o ne
age fro m the standa rd hea lth care plans ofwomen dis- exam pl e, the exam pl e of prematurity, w ith medi ca! in-
c riminate against wo men mostly o n a gender basis . In te rve ntion , th e prematuri ty rate can be expected to be
fact, fro m actu al practice, it is clear that thi s exc lusio n decreased if the phys ician has a better understanding of
specifi call y targets wo men because sim ilar co nditions the underlying causes . The cost fo r the deli very of a
w hi ch ha ve a two-pronged effect of affecting one 's fer- pre mature infa nt to that in fa nt as we ll as to the in sur-
tili ty and also one 's hea lth that in vo lve men are no t sub- a nce in d ustry and to soc iety in genera l, is exorbitant.
j ect to similar di scrimination. Any headway that can be made in the red uction of those
premature bi rths and the improvement of the o utco mes
It should also be pointed o ut that ma ny of the very sa me of those infa nts can onl y benefit the hea lth insura nce
tests, procedures and treatments that are used to diag- in dustry and society in genera l not to speak at ali of the
individual baby and the ir fami lies (which ultimately are and infertility is covered by the sta ndard hea lth insur-
the most important). ance plan, the actua l per member cost is extremely low.
Currentl y, it is estimated at being less than $ 1.00 per
Finally, this can ali be done ata rel atively low cost. lt month.
has been shown that ifthe standard exclusion is removed
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variate Ana lysis of 106,345 S ing leton Births frorn the 1994
202-205, 1992.
Statew ide Peri nata l Survey of Bavari a. Eur J Obstet Gynaecol
Rcprod Biol. 80: 183- 189, 1998.
111 . Verce llin e P, De Giorgi O, Aimi G, Panazza S, Ugli elli A, 115. Wi lcox LS , Mosher WD: Use of lnfcrtility Services in th e
Cros ignani PG: Menstrual Characteri stics in Women With and Unit ed Stales. Obstet Gynec. 82: 122- 127, 1993.
With out Endo metriosis. Obstet Gynecol. 90: 264-268, 1997.
11 6. Bron MS, Salmon JW: lnfertility Services and Managed Care.
112. Thomas R, Reid RL: Th yro id Disease in Reproducti ve Dys- Am J Man Care. 4: 7 15-720, 1998.
function: A Review. Obstet Gynecol. 70: 789-798, 1987.
11 7. tova ll DW, Al len BD, Spa rks AET, Syrop CH, Saunders RG,
11 3. Krassas GE: Th yro id Di sease in Female Reprod uction. Fertil Van Voorihs BJ: The Cost ofln fe11ility Eva luation and Therapy:
Steri l. 74: 1063- 1070, 2000. Findings ofa Self-lnsured Uni vers it y Hea lth Care Pl an. Fertil
teri l. 72: 778-784, 1999.
114. Marcus MD, Louch s TL, Berga SL: Psychological Correlates
of Funct ional Hyptothalamic Amenorrhea. Fertil Steril. 76:
3 10-316, 200 l.
---------~~tu-40
NaProTECHNOLOGY in lnfertility:
nfe rti li ty is a symptom of underl ying disease. 1 Th e Ultraso und technology was still mired in sector scan-
I di seases that cause in fe rtili ty have a "two-pronged
effect." They not only hinder the fu ncti oning offertility
ning and rea l-time ultrasonography was not yet avail-
abl e. Selective hysterosa lp ingography had not yet been
but they also cause both short and long-term hea lth developed and the fa llopi an tubes could not be cath-
problems. The persistent un willingness to address in - eterized. The CREIGHTON MODEL FertilityCare™ Sys·
fe rtility problems from thi s point ofv iew or perspective tem (CrMS) began its fírst all ied hea lth educati on pro-
is one ofthe major fl aws in the current approach to th e gra m fo r FertilityCare™ Practitioners (FCP) in 1978.
treatment of infe rti 1ity. Th is means of objecti vely monitoring the biomarkers of
the menstrual and fertili ty cycles was onl y in its begin-
Ferti lity problems also carry with them signifícant emo- ning stages.
tional sequelae.2 This is fa irly we ll recognized by those
who work in this fí eld and psychosocial di stress can lt is leg itimate to ask why there was such a quick and
contribute signifi cantly to the eti ology ofsome fo rms of rapid response to the artific ial reproducti ve techno lo-
infertility. gies. One can, of course, only specul ate as to why thi s
occurred. lt definitely could be stated that it was diffi -
Up until 1978, most of the effort in medicine in eva luat- cult, ifnot impossible at times, to actually determine the
ing and treating women with in fert il ity was placed into underlying causes. Frustrati on with thi s approach made
trying to identi fy and treat the und erlying ca uses. In ART appea ling. We live in a society where there is a
1978, in vitro fe rtilizati on produced a paradigm shi ft . Jt perce ived need fo r a qui ck so lution, the so-called "in-
led to a "s kipping over" of the causes and this conti n- sta nt gratifi cation" society. The patients have an emo-
ues up to the present time to be the fo undational man- ti onal intensity to them whi ch is somewhat unique and
agement approach. ln essence, thi s is a sy mptomatic or thi s is related to the importance of human fe rtili ty. Phy-
"Band-Aid " approach to treatment not one that gets to sicians at times have been emotionall y unabl e to dea l
the root causes. When the artificial reproducti ve tech- with thi s intensity and the virtue of pati ence has some-
nologies began to take hold, now over 25 years ago, times been non-ex istent.
diagnostic laparoscopy was in its in fa ncy. Horrnone as-
sessment, whil e ava ilable, was not readil y accessi ble. There are perhaps other reasons as we ll. Sorne of these
509
are economic. Training in infertility eva luation and treat- When the CREIGHTON MODEL program füst began its
ment over the years has been exceptionally poor (both investigations of the Billings Ovulation Method in pril
medically and surgically). Third-party reimbursement 1976, that chart and set of circumstances was known to
has long held a policy against reimbursing for "fertility us, however, its exp lanation was completely unknown.
testing and treatment" which is a throw-back to the This led us to a series of investigations which began
notion that infertility is "a li in your head." l fthe physi- the research in reprod uctive health that is presented in
cian is not going to be adequately reimbursed for hi s this text book .
time and efforts, there is no incenti ve to become in-
vo lved with these patients. And, of course, ph ys icians In Figure 40-2, a normal cyc le is charted with the corre-
can financia ll y profit enormous ly from the a11ificial re- lating estradiol-1 7 ~ (Ez) and progesterone levels shown.
productive technologies . Both profi les are completely normal. When a completely
dry cyc le was eval uated (Fi gure 40-3), a significantly
suboptimal preovu latory E2 profile and suboptimal luteal
The Missing Link - - - - - - - - - . ph ase progesterone and E2 profile were observed. Thi
hormone combi nation is cons istent with signifi ca ntl y
In the mid-l 970s, the Doctors Billings published a se- abnormal fo lli cu logenesis fo llowed by ab norma l
ries of cyc les in their A tlas of the Ovulation Method 3 luteogenesis.
from a woman who had been unable to ach ieve preg-
nancy (Figure 40-1 ). This series of cycles was from a Another dry cycle eva luation with three days of pre-
woman who had had difficulty achieving pregnancy over men trua! brown bl eeding is shown in Figure 40-4.
a seven-year period of time. She indicated that she had While this hormone profile is notas severely blunted as
noticed clear, stretchy mucus once or twice in the past that in Figure 40-3 , it is still significantl y suppressed
but not in recent years. ln the cycles shown , com plete when compared to Fi gure 40-2 .
dryness was record ed except fo r the day fo ll owing in-
tercourse (a seminal fluid di scharge). Ovarian hormone ln Figure 40-5, a woman with a limited mucus cycle was
levels were measured and provided indirect evi dence studied. In thi s cycle, the preovul ato ry E2 profil e is sup-
that ovu lation was occurring. However, acts of inter- pressed signifi ca ntl y as is the postovulatory profi le. ln
course close to the time of ovu lation did not resu lt in addit ion, the post-Peak phase ofthe cycle was 19 days
concepti on. in duration and with studies that came later, th is was
r2
Figure 40-1 : A series of cycles from an infertility patient published by the doctors Billings in th eir Atlas of the Ovulation Method
in 1976. The cycles are dry except for sorne discharge observed after intercourse. The urinary hormone levels suggest that
ovulation was occurring (From : Billings EL, Billings JJ , Catarinich M: Atlas of the Ovulation Method : the Mucus Pattern s of Fertility
and lnfertility. Advocate Press PTY. LTD. Melbourne, 1976).
Chapter 40 : NaProTECHNOLOGY in lnfertility: Evaluation and Treatment 511
Progesterone
40.0 ng/dl -+---t-+--+-l-+--+---t-+--+--tl-. .i-+--+-+--+--+-._-+--+-1--+--+--tl--+--+-~ 20.0 ng/ml
30.0 ng/dl -+--+-+-+-+--t-+--+--+--t-+--4111-1..,.1--+--+--+--tl-I l--+--+-+--+--1~-+--+- 15.0 ng/m 1
20.0 ng/dl -+--+-+-+-+--t-+--+--+--t- l--+--11-+-....-+--+-1 O.O ng/ml
5.0 ng/ml
Figure 40-2: A normal CrMS chart with daily levels of E2 and progesterone. The hormonal profiles are normal. The mucus cycle
score is 15.7 and post-Peak phase is 1O days (From : Pope Paul VI lnstitute research, 2004 ).
40.0 ng/dl-+-+--+---tl-+--+--+-+--+--+-+--+--+-+--+--+-l-+-+-l-+--+-l-+--+-l--+-20.0 ng/ml
30.0 ng/dl-+-+--+---tl-+--+--+-+--+-+-+--+--+-+--+--+-l-+-+-l-+--+--tl--+--+-l--+- 15.0 ng/ml
20.0 ng/dl-+-+--+--tl-+--+--+-+--+--t•+--+--+-+--+--+-l-+--+-1-._-+--il-.,_-+-l--+-1 O.O ng/ml
Figure 40-3: An infertility palien! with a dry cycle and daily levels of E2 and progesterone. Both the preovulatory and the
postovulatory profiles are very suboptimal revealing very poor folli culogenesis followed by abnormal luteogenesis (From : Pope
Paul VI lnstitute research , 2004).
29 30 31 32 33 34 35
Progesterone
40.0 ng/dl -1-+-+-....-+--+-l-+-+-l--l--+-+--+-_..-l--+-_.,-l--+-_..-l--+-...¡.--11-..+-_..-20.o ng/ml
30.0 ng/dl -1--+--+-t--+--+-t--+--+-1-....,-+-1-.¡...-+-1-.¡...-6-1-.¡......¡._1-.¡...-'---11-.¡......¡._15.0 ng/m l
20.0 ng/dl -+--+--+-+--+-l-+-...l-l. .•-l--1-.¡_...¡.......¡._¡.......¡..""""'_.¡_...¡.......¡._.¡_...¡.._.._........¡.......¡._1 O.O ng/ml
Figure 40-4 : Another dry cycle with decreased hormone parameters. Preme nstrua l spotting is also ob served in this cycle
40.0 ng/dl -l-+-+-....-+--+-l-+-+-1--1--...-,.......,........,.....,,......,...-+-l-4--+--il-4--+-11-4--+-20.0 ng/ml
30.0 ng/dl-t--+--+-..l--+--+-t--+--+-l-..._-+-1-.¡......¡.__¡1-+..-6-l-+-....¡.--11-+....¡.,--11-+......¡.-15.o ng/ml
-l--+--+-+-....¡.~-1--+--+-1-.....~-+--+--+-1-.¡...-1-1--1--+-l--t-...¡.-1-...¡..-+-10 . 0ng/ml
Figure 40-5 : A ve ry limited mucus cycle (mucus cycle score = 3.0) and prolonged pos t-P eak phase (19 days) wi th a
preovulatory and postovulatory hormone profile . The hormone profile is significantly abnormal and the prolonged post-Peak
phase strongly suggestive of the luteinized unruptured follicle (From : Pope Paul VI lnsitute research , 2004).
Chapter 40 : NaProTEC HNOLOGY in lnferti lity: Evalu at ion and Treatment 513
found to be consistent with the ultrasound fi nding of a it became apparent that she had signifi cant premenstrual
lute inized unruptured fo lli cle. spotti ng. When her hormone profi le was drawn the E2
leve Is were blunted but most prominent was the si gnifi-
In Fi gure 40-6, another cyc le is shown with th e hor- cant suppress ion of her luteal phase progesterone pro-
mone profile. In thi s case, there was a significant dro p duction . The premenstrua l spotting was thought to be
(greater than 50%) in the secretion ofp rogesterone over dueto inadequate hormone support fo r the endometrium
a 24-hour peri od between Peak +5 and Peak +6 of thi s and was at least one of the underlying causes of her
cycle. This cycle was one of the first where we were mul tiple mi scarri ages. Premenstrual spotting has been
abl e to identi fy the presence of a late luteal defect (Type observed in about 15 percent of pati ents with regular
ITI luteal phase defect) whi ch is often assoc iated wi th a cycles who are experiencing infe ti il ity (p=.0028, chi-
fairly normal periovulatory E2 profile. sq uare) (Table 40-1 ).
In Figure 40-7, a chart from a woman who had fo ur con- Whil e on occas ion, there is a glimpse of interest shown
secutive mi scarriages is shown. As she began charti ng, in the medi ca! literature with regard to abnormal men-
strual cyc le patterns4 , vulvar di scharge pattern s such
Table 40-1: The CrMS as these illustrated have been virtual/y ignored by the
lncidence of Pre menstrual Spotting reprod uctive medicine communi ty. That lack ofprocre-
Normal Controls vs. All lnfertility 1 ative education and focus on the natura ll y occ urring
fe rtility cycle is ultim ately the missing link in current
Premenstrual Sgotti ng reprod uctive medi cine.
Total Yes NO
Study Group N n % n %
Normal controls 54 o O.O 54 100.0 Philosophy of NaProTechnology --~

All infertility 114 17 1149' 1 97 85.1
As one looks at the evaluation and treatment approaches
1. From: Pope Paul VI lnstitute research, 2004.
2. p=.0028 , chi-square analysis in NaProTECH NOLOGY it becomes striking that there
is a signi fica ntl y different philosophi ca l approach that
15 16 17 18
Progesterone
Limited
Mucus Cycle
40.0 ng/dl_,._+--+-_.-+-+--+--l••+--a.--.-...-...--.......-..--1-...¡..___._¡_+.....¡..___._l--+--+-20.0 ng/ml
_,.._,._....._._..,_...1-1-_....~..._....._.¡_ ..,_..._.....,...._ ........__,_..-_ ._...__,_..-_._..._..-. 15.ong/ml
5.0 ng/ml
Figure 40-6: A CrMS chart in a patient with infertility. The E, and progesterone levels are completely normal up to Peak +6 when
the progesterone level shows a significa n! decrease (at arrow) (Type 111 luteal phase deficiency) (From: Pope Paul VI lnstitute
resea rch, 2004 ).
514 T he Medic al and Surgical Prac t ice of NaPro TECHNO LO GY
12 13 14 IS 16
Progesterone
Limited Mucus
Cycle
40.0 ng/dl - - - - - - - - - - - - - - - - - . . - - - - - - - - - - - - - - - - - -.... 20.0 ng/m l
30.0 ng/dl - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -.....- -... 15.0 ng/m l
20.0 ng/dl -+~-+--+-+--+--+~-+-- -+--11...,1---+--+~-+--+-~ 1O.O ng/m l
5.0 ng/m l
Fi g ure 40-7: A woman wi th premenstrual spotting , a history of four consecutive spontaneous abortions and a preovulatory
and postovulatory hormone profile . The periovu latory estradiol levels are decreased but what is most remarkable is the
significan! decrease in postovulatory progesterone (From: Pope Paul VI lnstitute research , 2004).
is taken to the care ofthese patients. To begin w ith , the Domon Vitae addresses the suffering caused by infer-
child is viewed differentl y. tility in marriage by outlining the context to which ap-
proaches would be appropriate (Table 40-3): " ... mar-
[n NaProTECHN OLOGY, the child is viewed as a gift as riage does not confer upon the spouses the right to
opposed to a rig ht. This is defended in the Vatican in - ha ve a child , but on ly the right to perform those natura l
struction on the Respect for Human Life (Donum Vitae) acts w hi ch are per se ordered to procreation." 5
which is the instruction on the evaluation and treat-
ment of infert ile couples (Table 40-2): "A true and proper Domon Vitae recogni zes w hat every phys ic ian knows
ri ght to a child wo uld be contrary to the chi ld 's dignity whe n it comes to the treatment ofthe inferti le couple. lt
and nature . T he chi ld is notan object which one has a is not possible to become 100 percent effective in their
ri ght nor can he be considered as an object of owner- treatment. ln most cases, one cannot even come close
ship; rather a child is a gift, ' the supreme gift ' ... and is a to 100 percent effectivenes . Thus, Dom1111 Vitae high-
li v ing testimon y ofthe mutual giving of his parents." 5 li ghts other important services to the life ofthe human
person (Table 40-4) 5 : " Physical steri lity, in fact, can be
Table 40-2:
Table 40-3: T he Suffer ing Caused
T he Child: A R igh t o ra G ift? 1
by lnfert ility in Marriage 1
"A true and proper rig ht to a child would be contrary to

the child 's dignity and nature. The child is not an object " ... marriage does not confer upon the spouses the right
to which one has a right nor can he be considered as an to have a child, but only the right to perform those
object of ownership; rather a child is a gift, 'the natural acts which are per se ordered to procreation ."
supreme gift' .. .and is a living testimony of the mutual
giving of his parents."
1. Donum Vitae , Origins, March 19,1987.
1. Donum Vitae, Origins. March 19,1987.

Chapter 40 : NaProTECHNOLOGY in lnfertility: Evaluation and Treatm ent 515
for spouses the occasion for other important services sist with successfu l family building by being
to the li fe ofthe human person, fo r example: adopti on, supporti ve of adoption.
various forms of educational work, ass ista nce to other
families , and assistance to poor or handi capped ch il - The goa l in the deve lopm ent of NaProTECHNOLOGY
dren."5 wa to provide reproductive hea lth servi ces which were
both mora lly and profess ionall y acceptable. The cre-
These principies are foun dationa l to the approac h of ation of the CrMS was a key element in the ability to
NaProTECHNOLOGY. In addition , on ly married couples carry this through. In additi on, the Pope Paul VI lnsti-
are accepted into evaluation and treatment so that if a tute far the Study of Human Reproduction, where basic
child results, they will have the benefit ofboth a mother clini ca l research and continued ed ucation was avai l-
and a fat her. This is not beca use we are farced to accept able were critica! to its eventual expansion.
these principi es but rather because these principies make
sense, they are conn ected to an overa ll hierarchy of Figure 40-8 presents a bas ic version of the staircase
values, they are integrated and consistent and th ey al- approach to the management ofpatients with infert ility
low far an orderly program of deve lopment for the eva lu- using NaProTECHNOLOGY. The underlying causes are
ati on of these most signifícant and diffícult probl ems. aggress ively sought; they are th en aggress ive ly treated
Furthermore, and ultimately what is most importan t, fa r periods of time whi ch are agreeab le to the patient
these principies protect the di gnity of women , the in- and the physician. When pregnancy occ urs, the preg-
tegrity of marriage and a respect for the di gnity and nancy is supported . If pregnancy does not occur overa
integrity ofthe child . They are prin cipies that should be period oftime, then adoption is recommended.
ampli fted rather than reduced.
As soon as ado ption is mentioned as a part of an infer-
ti li ty program, there is a natural tendency to think one
Table 40-4: Other lmportant Services of two things: either the program is giving up on the
to the Life of the Human Person 1 individual couple or the program does not have sufft-
cient confídence in its own approach to think that it will
be effecti ve. ln actual fact, both of these could develop
"Physica l sterility in fact ca n be for spouses the ift he program is not carefu l in how it is approached.
occasion for other importan! services to the life of the
human person, for example:
• Adoption However, in a legitimate NaProTECHNOLOGY program,
Various forms of educational work NaProTEC HNOLOGY is viewed as a rea li stic approach
• Assistance to other families
Assistance to poor or handicapped children ."
to fa mil y build ing when , in fact, through proper evalua-
tion and treatment, the woman has not achieved a preg-
1. Donum Vftae , Origins, March 19,1987. nancy overa period of time which is mutually agreed to
by th e coup le and the phys ician. In that regard , the
author has recogni zed that couples who are in vo lved in
infertility treatrnent ha ve different resources upon which
to draw in their search to so lve their in ferti lity problem.
The Goals of NaProTECHNOLOGY ==l Sorne ha ve very little stam ina to be involved in a treat-
ment program while others have an incredible amount
A NaProTECHNOLOGY approach to the in ferti le couple of stamina to be involved. Thus, it is only when that
has the fo ll owing goa ls (Table 40-5) :
Table 40-5: Goals of Working with Patients

l. lt works tow ard s assessi ng the und erl yi ng
with lnfertility through NaProTechnology
causes of the reprodu ctive abnormality.
2. lt all ows for the treatment of these underlying
ca uses. 1. Assess for the underlying causes
2. Treat the underlying causes
3. lt assists the coup le in achieving pregnancy while
3. Achieve pregna ncy
maintaining the natural acts of procreati on.
4. lf unsuccessful, resea rch for unknown causes .
4 lf the treatment progra m is un success ful , re- 5. lf medically unsuccessful, assist with successfu l
search into the unknown causes is undertaken. family building (adoption).
5. lf medi ca ll y un succe sful , the program will as-

516 The Medica! and Surgical Practice of Na ProTECH NOLOGY
With th e adve nt of the Billings Ovulation Method and

1 Adoption
subsequentl y the CrMS, there has been an emphasis
::-re-at-, C"""y...,
.---:T cle~
on identifying fe rtili ty a well as infe rtility. For the firs t
1 0
~n~~~ ~g~t Ó~~;~ time, a fa mily pl anning system exi sts which allows the
Dysfunclion
coupl e to eith er ac hieve or avo id pregnancy by selec-
Treat Organic ti ve ly having intercourse ata time offertili ty or infertil-
Dlsease
ity. The ac hi evement of pregnancy is demonstrated in
Figure 40-9. With intercourse occurring at the time of
Hormones
Ultrasound
Laparoscopy
fert ility (jertility-focused intercourse: FF!), pregnancy
SHSG
is ac hi eved.
-- ---'1
CrMS
The success of such an approac h in the ac hi evement of

pregnancy was publi shed in 1992 6 (Table 40-6). In thi s
Figure 40-8: A staircase approach outli ning the basic prin-
group of pati ents of completely normal fertility, 76.0 per-
ci pies of a N aProTEC HNOLOGY eval uation protocol for in-
fertility. Eval uation and treatment protocol fa r infertility. cent achi eved a pregnancy in the first cycl e th at they
se lected the time offetiili ty fo r intercourse. By the third
cyc le, 90.0 percent were pregnant and by the sixth cyc le
stam ina runs out and the progra m has not been effec- 98.0 percent were pregnant.
tive that the coupl e can legit imately be recommended
fo r adopti on. lt recognize on ly that the progra m (no These data suggest that the defi niti on of infe rti lity can
matter which one it is anyw here in the world) cannot be be changed fro m the principie of "subtraction" which is
100 percent successful. However, the progra m, thro ugh curre ntl y used to a principie of testing one's actua l fe r-
its s uppo rt of adopti on progra ms, can ass ist these tility wi th fe rtili ty-foc used intercourse. lfa couple has
coupl es in ac hi eving their goal of building a fa mil y. not achi eved pregnancy within three cycles, there is a
strong suspicion that an infe tiility problem exists. If preg-
na ncy has not occurred by th e sixth cycle, then testing
Defi ning lnfertility _ _ _ _ _ _ _ __ ca n begin . [n the infe rtili ty program of the Pope Paul Vl
lnstitute alm ost everyo ne who comes into th e program
T he standard defi ni tio n of inferti li ty us uall y invo lves meets the standard defí ni tion of infertili ty after one year
the absence of pregnancy in a couple who is engaged of ra ndom intercourse. Thi s is because so few peopl e
with random acts of intercourse over a twelve-month are yet, overall , charting their cycles . However, in eva lu-
period of ti me and pregnancy has not occurred. Thi s ati ng those cases of indi vidua ls who have been chart-
approac h to the definiti on ofi nfert ility is one of"sub- ing fo r a peri od of six cyc les w ithout achi ev ing preg-
tracti on." [n other wo rds, it isn' t one that trul y te ts nancy, no case has ever been fo und where some or-
one's fe rtili ty but rath er by the absence of expressed ga ni c and/o r underl ying abnormality was not identifí ed.
fe rtili ty, the person is defin ed as infert ile.
Table 40-6: The Creighto n M odel System

lncidence of Pregnancy R esulting
when T im e of Fertiliry used by Cycle of Use'
(SO Pregnancies Pros pectively Studied*)
Pregnant Cumulative
Number of Cycles Used n '1lo %
One 38 76 .0 76 .0
TV\O 5 10.0 86 .0
Three 2 4.0 90 .0
Four 2 4 .0 94 .0
Five 2 4 .0 98 .0
Six o O.O 98 .0
Se ven 1 2 .0 100.0
Average length of use of the infertile time only prior to pregnancy = 5.72 cycles
Range of previous use of the infertile time only = 1-17 cycles
27 were multiparous, 23 were nulliparous
1. From· Hilgers TW, Daly KD, Prebil AM, Hilgers SK: Cumulative Pregnancy Rates
in Patients with Apparently Normal Fertility and Fertility Focused lntercourse. J
Repro Med 37: 864-866, 1992.
Chapter 40: NaProTECH NOLOGY in lnfertility: Eval uat ion and Treatm ent 517
tokL 1okL /Okt

oAO llf "'º AD °"'º C'AO oAo º"'°
:r I
PREGNANCY
TEST
+
O~D OAO ~P 0'10 oAl> OAO oAO o.40 OAO OAt> Ol+D
Figure 40-9: In this cycle, the couple is using the time of fertility (fertility-focused intercourse) and have successfully achieved
a pregnancy (From : Pope Paul VI lnstitute research , 2004) .
lnfertility Evaluation Protocols - - - - . mented. The patient 's hi sto ry is taken upon entry in the
program; she is instructed to go toan lntroductory Ses-
Inferti lity evaluation protoco ls in NaProTECHNOLOGY s ion for the CrMS and after two cycles of cha1tin g, to
are basic and direct. They are not overly compl ex, al- return for a phys ical exam ination and initi ation oftest-
though a fundamental understanding ofthe pathophysi- ing. The tests that are conducted include a semina l fluid
ology is extremely important, so that the underl ying con- a nal ys is on the husband , a ful! se ri es menstrual cyc le
dition s can be properly understood. In depth reviews hormone profile (Table 40-8), a fo lli cular ultrasound se-
of sorne of these conditions is presented in the chap- ri es a nd a diagnostic laparoscopy, hysteroscopy and
ters that immediate ly fo llow and is not the focus ofthi s se lecti ve hysterosa lpingogram.
chapter.
Once ali of these tests are compl eted (from beginn ing
The approach to investigation begin s with the type of until end usuall y requ ires abo ut four months), then the
menstrual cyc le with which the patient presents: Regu- patient returns for a comprehensive management re-
lar menstrual cycles, long and irregular cycles or amen- view in whi ch the videotape ofher laparoscopy is shown
orrhea. At the first visit that information can be eas ily to her and her husband and ali ofthe tests are rev iewed
obtained andan infertility eva luation can begin. w ith the idea of NaProTECHNOLOGY so lutions in mind.
To assist the taking of an entry hi story, the Female Gen-

Regular Menstrual Cycles era l ln format ion Form (FG IF) in Figure 40-1 Oand the
Gynecological History Form in Figure40-l 1 is very help-
The most common forms of infe rtility a re observed in ful. The husband is a lso requested to fill out th e Male
women who have reg ular length menstrua l cyc les. In General Info1111ation Fonn (MGIF) in figure40- J2. These
these patients the protoco l li sted in Table 40-7 is imple-
Table 40-7: NaProTechnology Table 40-8: Full Series Menstrual Cycle

lnfertility Evaluation Protocol: Hormon e Profile
Regu lar Cycles
Day 5: FSH , ~ -en do r p h i n
P-5 through P+2 (every other day): E2

• Take the patient's history (upan entry)
• Chart CrMS far two cycles • P+ 3, 5, 7, 9, 11 : P+E2
Return far physical exam ination and arder !he
following : • P+5, 7, 9: ~ -en do r phin
, Seminal fiuid analysis P+7: Testosterone FSH Tota l T4
• Full series menstrual cycle hormone profile Free testosterone LH Free T4
, Follicular ultrasound series Androstened ione prol actin TSH
• Diagnostic laparoscopy, hysteroscopy and DHEAs Total T3
selective hysterosalpingogram Reverse T,
• Comprehensive management review T 3 :rT3 ra tio
NaProTECHNOLOGY
Female General lnformation Form

Pope Paul VI lnst1tute • 690 1 Merey Road • Omaha, NE 68106 • Ph# 402-390-6600 • Fax # 402-390-985 1
Date: _ _ _ _ _ _ _ _ __
Name: Age : _ _ DOB: _ _ _ _ _ _ _ __

Last F1rst
Nameofspouse: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Age : _ _ DOB: _ _ _ _ _ _ _ __

Last F1rst
Referring physician: - - - - - - - - - - - - - - - - Primary care physician: _ _ _ _ _ _ _ _ _ _ __
Trying to conceive? No o Yes O 11 SO how long? _ _ _ _ _ _ _ (years and months)
Gynecological History
Please circle the appropriate answer:
Abnormal pap (date of last pap) yes no Mom took DES yes no
Acne yes no Mycoplasma yes no
Breas! discharge yes no Ovarian cysts yes no
Chlamydia yes no Painful intercourse yes no
Douche yes no Pelvic adhesions yes no
Endometriosis yes no Pelvic infection yes no
Excessive fear yes no Physical abuse yes no
Fibroids yes no Poor sense of smell yes no
Gonorrhea yes no Prior IUD use yes no
Herpes yes no Sexual abuse yes no
Hotflashes yes no Vaginal lubricants yes no
Irritable bowel syndrome yes no Vision problems yes no
Lack of bladder control yes no Weight gain > 1O lbs yes no
Mammogram yes no Weight loss > 1O lbs yes no
Social History
Please circ/e the appropriate answer:
Alcohol weekly yes no Marijuana yes no
Caffeine yes no Regular exercise yes no
Cocaine yes no Smoke yes no
!Vdrugs yes no Weight change yes no
Figure 40-1 Oa : A general intake form for women with reprodu ctive abnormalities (From : Pope Paul VI lnstitute).
Chapter 40 : NaProT ECHNOLOGY in lnfertility: Evaluation and Treatment 519
N.1ProTECHNOLOGY Fema le General tntormatlon Form 2
Family History
Has anybody in your family had any of the fol/owing:
Birth defects yes no Mental retardation yes no
Bleeding disorders yes no Muscular dystrophy yes no
Blindness yes no Ovarian cancer yes no
Breast cancer yes no Polycystic kidneys yes no
Chromosome problem yes no Psychiatric disease yes no
Cystic fibrosis yes no Recurren! miscarriage yes no
Deafness yes no Sickle-cell anemia yes no
Diabetes yes no Spina bifida yes no
Down syndrome yes no Stillbirth yes no
Early menopause yes no Tay-Sachs disease yes no
Heart attack ( <50 years) yes no Thyroid disease yes no
Hemophilia yes no Tuberous sclerosis yes no
High blood pressure yes no Other genetic disease yes no
Ancestral Background
There are certain ancestral backgrounds that ha vean increase frequency of sorne genetic disease. Please indicate if
either your mother or father are of any of the following backgrounds:
O African O French Canadian O Latin American
O Asian O lndian O Mediterranean
O Caribbean O Jewish O NativeAmerican
O Non e of the above
Medical History (Review of Systems)

Ha ve you ever had any of the following:
Abdominal pains yes no Heart disease yes no
Anemia yes no HeaVcold intolerance yes no
Antibiotics yes no Hepatitis, liver problems yes no
Anxiety yes no High blood pressure yes no
Appendicitis yes no Kidney problems yes no
Arthritis yes no Mitral valve prolapse yes no
Asthma yes no Neck/back pain yes no
Autoimmune disease yes no Neurological problem yes no
Blood clots yes no Nose/gum bleeds yes no
Blood in stool yes no Palpitations yes no
Blood transfusion yes no Problems with vision yes no
Cancer yes no Psychiatric treatment yes no
Chicken pox yes no Seizures yes no
Diabetes yes no Severe headaches yes no
Dizziness yes no Shortness of breath yes no
Easy bruising yes no Stomach problems yes no
Epilepsy yes no Stress yes no
Excess (ch ron ic) constipation yes no Swollen joints yes no
Excessive thirst yes no Thrombophlebttis yes no
Fainting yes no Thyroid problems yes no
German measles yes no Tuberculosis yes no
Headache yes no Urinary infections yes no
[•?~Y.tret-
Figure 40 -1 Ob
520 The Medical and Surgic al Pra ct ice of NaProTECHNOLOGY
N~ProTECHNOLOGY Fema le General lnformatlon Form 3
Pregnancy History
Times pregnant _ __ _ Term births _ _ __ Premature births _ _ __
Miscarriages _ _ __ lnduced abortion _ _ __ Adopted children _ _ __
Contraceptive Use
Type Dates of use Reason d1scont1nued
1.
2.
3.
4.
5.
Operations and Hospitalizat ions

Date Diagnosis Operat1on Locat1on or hospital Phys1c1an
1.
2.
3.
4.
Medications
P/ease list al! prescriptions and over-the-counter drugs used during the past year:
Med1cat1on Dosage and frequency Dates of use Reason for tak1ng
1.
2.
3.
4.
5.
6.
Allerg ies
To what (drug or substance)? When What type of react1on?
1.
2.
3.
4.
5.
Figure 40-10c
NaProTECHNOLOGY Female General lnfonnation Form 4
History of Tests , Procedures and Treatments

A. Tests
Diagnosis of Ovulation Tests Dates & Results
a. BBTused yes no
b. Endometrial biopsy yes no
c. LH testing (urine) yes no
d. Ultrasound series (for ovulation assessmenl) yes no
Hormone Studies
e. Complete hormone profile yes no
l. Hormone testing , other (describe) yes no
g. Serum progesterone yes no
Male Fertility Testing
h. Post-coita! test (Huhner test) yes no
i. Seminal fluid analysis yes no
j . Sperm antibodies yes no
Miscellaneous
k . Thyroid testing yes no
l. Beta-endorphins yes no
m. Other yes no
B. Procedures Procedures Dates & Results

a. Hysterosalpingogram yes no
b. Selective hysterosalpingogram yes no
c . Hysteroscopy yes no
d. Laparoscopy yes no
e. Transcervical catheterization ot tallopian tu bes yes no
f. Other yes no
C. Treatments
Medica/ Treatments Treatments Dates
a. Birth control pills (lor endometriosis) yes no
b. GNRH analogs (Lupron, Syneral , etc.) yes no
c. Serum progesterone yes no
d. Clomid or serophene yes no
e. HMG (Pergonal-like drugs) yes no
l . Mucus enhancers yes no
g. Progesterone (11 so, what kind?) yes no
h. HCG yes no
i. Glucophage yes no
j . Thyroid Rx yes no
-- ----
Surgical Treatments
k. Cauterization of endometrial implants yes no
l. Laser laparoscopy yes no
m. Laser laparotomy (open abdomen) yes no
n. Myomectomy yes no
o. Ovarian drilling yes no
p. Ovarian wedge resection yes no
q. Tubal Surgery yes no
r. D&C yes no
[•~tu~}-
Figure 40-1 Od
NaProTECHNOLOGY Fema le General lntormatlon Form 5
ART Treatments
s. IVF yes no
t. ICSI yes no
u. GIFT yes no
v. ZIFT yes no
w. Artificial insemination yes no
lntrauterine (IUI) yes no
Husband (AIH) yes no
Donor(AID) yes no
Male
X. Variocele repair yes no
y. Male on medication yes no
z. Other male infertility treatment yes no
CtMS
aa. Fertility-Focused lntercourse yes no
bb.Other yes no
Figure 40-1 Oe
Chapter 40: NaProTECHNOLOGY in lnfertility: Evaluati on and Treatment 523
NaProTECHNOLOGY
Gynecological History
Pope Paul VI lnstitute • 6901 Merey Road • Omaha, NE 68106 • Ph# 402-390-6600 • Fax # 402-390-9851
Last Pap: _ _ _ _ _ _ __ LMP: _ _ _ _ _ __

Date: _ _ _ _ _ __ _ Height: ___ Weight _ _ BP: _ _ _ __
Name: ____________________ Age: __ G_ P_ P_ T_ SAB_ IAB_ LC_
Last First
Menarche: _ _ __ Reg/irreg.: _ _ __ Periods: _ _ _ _ Cramps/pain (circle): mild mod. sev

11 cramps mod./sev. , describe further: Pain score: _ _ _ _ __
Occupation: Marital status: M S W D
Husband's name: Age: __ Occupation: __________
Last First
Length of marriage: # of marriage (1,2,etc.): PT __ spouse _ _
Previous methods of contraception (type, dates of use): - - - - - - - - -- - - - - - - - -- - - - - - -

Length of time no contracpetion : _ _ __ Length of time no IUP: _ _ _ __ _ __
Current Medica! History
Unusual bleeding yes no Premenstrual spotting yes no (v #oldays _ ) Tail-end brown bleedng yes no (v •oldays_)
lntermenstrual bleeding yes no Rectal bleeding yes no Rectal pain yes no Dyspareunia yes no
Past Medica! History
Past Surgical History
Allergy History: ________________ Exercise History: ________________
Medications: Previous: _____________ Curren!: _ __________________
Do you ever notice mucus discharge? yes no 11 yes, when? _ _ __ How much? _ __ _
Premenstrual symptoms: Do you ha ve any of the following prior to your period:

lrritability y n Breast tenderness y n Bloating y n Weight gain n CHO craving y Teariness y n
Depression y n Headaches y n Fatigue y n lnsomnia y n Other y
How man y days prior to your period do these symptoms start? _ _ __
Figure 40-11a : A gynecologic history fo rm used at the Pope Paul VI lnstitute for wo men who have va rious reproductive health
problems (From : Pope Paul VI lnstitu te).
NaProTECHNOLOGY Gynecologlcal Hlstory 2
Optional
Tests
BBT: yes no U/S: yes no
Endo Bx : yes no Dx lap.: yes no
HSG : yes no SFA: yes no
Hormones yes no Other: yes no
Do you lose a lot of hair when you brush it? yes no Do you like cold weather? yes no
Do you ha ve brittle nails? yes no What is you r body temperature? warm cold
Do you have dry skin ? yes no
Other
lmpression
O Adenomyosis (617.0) O Eroision/ectropion of cerv ix (622.0) O Pelvic peritoneal adhesions (614.9)
O Amenorrhea (626.0) O Fatigue , general (780.9) O Persisten! follicular cyst (620.2A)
O Anomaly- cervical mucus (628.4) O Habitual SAB (Hx of) (629.9) O Persisten! luteal cyst (620.2B)
O Cervicitis & endocervicitis (616.0) O Hypersecretion-ovarian andro (256.1) O Polycystic ovaries (256.4)
O Ch ronic endometritis (615.1) O Hypoth-pit-ov. dysfunction (258.8) O Polyp of endometrium (621.0)
O Dysfunctional uterine bleeding (626.8) O Irregular menstrual cyc le (626.4) O Premenstrual dysphoric disorder (625.4)
O Dysmenorrhea (625.3) O Leiomymoma- fibroid uterine (218.9) O Premenstrual tension syndrome (625.4)
O Dyspareunia (625.0) O Menorrhagia (626.2) O Thyroid disorder (V77.0)
O Endocrine receptor disorder (259.9) O Ovarian cyst (620.2) O Other: _ _ _ _ __ __ _
O Endometriosis (617.9) O Pelvic pain- unspecified (625.9)
Plan
CrMS Other: _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __
PE : next visit _ _ _ _ _ _ _ (weeks/months)
Hormones ~------~
OCE
SFA
_ _ Lap/hyst.-possible laser with KTP
with LUNA
with cults.
with D&C
SHSG
HSG
Pelvic U/S
_ _ D&C, hysteroscopy
Physician's signature: _ _ _ _ _ __ _ _ _ _ __ Date: _ _ _ _ _ _ __
-------[~?i~t-
Figure 40-11 b
Ch apter 40: NaProTECHNOLOGY in lnfertility: Evaluation and Treatment 525
NaProTECHNOLOGY
Male General lnformation Form

Pope Paul VI lnstitute • 6901 Merey Road • Omaha. NE 68106 • Ph# 402-390-6600 •Fax# 402-390-9851
Date: _ _ _ _ _ _ _ _ __
Name: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Age: _ _ DOB: - - - - - - - - - -

Last Firsl
Nameofspouse: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _~ Age : _ _ DOB: _ _ _ _ __ _ _ _

Last First
Referring physician: _ _ _ _ _ __ _ _ _ _ _ _ __ Primary care physician: _ _ _ _ _ _ _ _ _ _ __

Number of years married: _ __ Number of prior marriages: _ __
Age(s) of children , if any: _ __ Number of pregnancies with previous spouse : _ __
Past Medical History

Hadmumps yes no Lung problems (asthma, etc.) yes no
Heart problem s yes no Muscle or joint problems yes no
Hormonal problems yes no Neurological problems yes no
(thyroid, diabetes, etc.) Stomach problems yes no
Other medical problems yes no Other surgery yes no
Curren! medications yes no
ALLERGY to medications yes no
Male History
Abnormal sexual development yes no Puberty was late yes no
Bladder or prostate surgery yes no Sex drive problems yes no
Ejaculation problems yes no Sexually transmitted disease yes no
Epid idym itis yes no Undescended testicles yes no
Fever within the last three months yes no Urinary tract infection yes no
Had hernia repair yes no Varicocele diagnosis yes no
lnjury to the testicles yes no Vasectomy yes no
Problem achieving erections yes no Vasectomy reversa! yes no
Puberty was early ( <12 years) yes no Other family member with fertil ity problem yes no
Figure 40-12 : A general intake form used formen in further evaluating their fertility in a NaProTECHNOLOGY driven infertility
prog ram (From: Pope Paul VI lnstitute).
~ProTECHNOLOGY Male General lnformatlon Form 2
Social History
Drink alcohol ( # drinks/week _ ) yes no Regular exposure to heat yes no
Exposure to chemicals yes no (sauna, baths, jacuzzi)
Rad iation exposure (not routine x-rays)yes no Smoker (# packs/day _ ) yes no
Recreational drugs yes no
Family History
Has anybody in your family had any of the following:
Blindness yes no Mental retardation yes no
Birth defects yes no Muscular dystrophy yes no
Chromosome problem yes no Polycystic kidneys yes no
Cystic fibrosis yes no Psychiatric disease yes no
Deafness yes no Sickle-cell anemia yes no
Diabetes yes no Spina bifida yes no
Down syndrome yes no Tay-Sachs disease yes no
Heart attack (<50 years) yes no Thyroid disease yes no
Hemophilia yes no Other genetic disorders yes no
High blood pressure yes no
Ancestral Background
There are certain ancestral backgrounds that ha vean increase frequency of sorne gene tic disease. Please indicate if
either your mother or father are of any of the following backgrounds:
O African O French Canadian O Latin American
O Asian O lndian O Mediterranean
O Caribbean O Jewish O Native American
O None of !he above
Other Possible Concerns

Biopsy of testicles yes no Physical abnormality yes no
Cancer yes no Prostatitis yes no
Colitis yes no Psychiatric treatment yes no
DES exposure in womb yes no Seizures yes no
Diabetes yes no Strenuous exercise yes no
Genital herpes yes no Tight underwear yes no
Genital warts/condyloma yes no Varicocele yes no
High blood pressure yes no Varicocele surgery yes no
Mumps with injury to testicles yes no Urethritis/epididymitis yes no
Penile discharge or pain yes no
Comments
Figure 40-12b
Chapter 40: NaProTECHNOLOGY in lnfertility: Evaluation and Treatment 527
fo rm s assist great ly in obtaining, in an orderly fashion, biomarkers include the type and intensity ofthe mucus
the type of info1mation that will allow for an orderly and cyc le, the length and stabi lity of the post-Peak phase,
yet thorough intake of information. the length of the pre-Peak phase, the overa! 1 length of
the cycle, the presence of premenstrua l spotting or tail-
When the patient returns after two months of tracking end brown bleeding. These can ali be externa! signs of
their fertility cycles using the CrMS, the physician re- underlying pathophysiology.
views it with the idea in mind of paying special atten-
tion to the biomarkers of the CrMS . The basic The appearance of limiled mucus cycles wi ll suggest
biomarkers to be reviewed are li sted in Table 40-9 and abnormal reproductive hormone function and an in-
severa! charti ng examples illustrating sorne of these creased risk of ovulatory defect. A short post-Peak
biomarkers are shown in Figure 40-13. The important phase will indicate the presence ofan inadequately short
luteal phase. A long post-Peak phase may suggest the
presence of a persistent unruptured fol li cle. Premen-
Table 40-9: NaProTechnology Assessment-
strua / spotting and/or tail-end brown bleeding may
Paying Attention to the Biomarkers
indicate the possibi lity of low progesterone levels. These
can also be assoc iated wi th chroni c endometritis.
• The type of mucus cycle
A seminal fluid analysis is obtained as described in the
• The length and stability of the post-Peak phase
chapter on male in fertil ity. However, the only change
• The length of the pre-Peak phase (and its character-
istics) from the protocol outlined in Table 40-7 is ifthe spenn
• The length of Ihe cycle count comes back zero. 1f azoo permia exists, then the
• Presence of premenstrual spotting
count should be repeated a second time and fr uctose
• Presence of tail-end brown bleeding
should be measured in the sem inal fluid to see ifthere is
an obstruction of the vas deferens. lf azoospermi a ex-
ists, then the remaining eva luation can be cance led un-
less there are sorne other medica! reasons why such an
30 31 32 33 34 35
Figure 40-13 : Charting examples from women with regular cycles who may be experiencing infertility. Limited mucus cycles
are seen in cycles A and 8 , a dry cycle in cycle C, a short post-Peak phase in cycle D and a normal mucus in cycle E (From: Pope
Paul VI lnstitute).
528 The Medic al and Su rg ic al Pract ice of NaProTECHNOLOGY
eva luation should continue (for examp le chroni c pelvic to do a true ovarian fo ll ic ul ar ultrasound seri es because
pa in, severe dysmenorrhea, dyspareunia, and seve re of the unpredi ctabili ty of the occurrence of ovu lation .
premenstrual symptoms). Also, because ofthe nature of the cyc le pattem, a differ-
ent set of hormones are better to eva luate in order to
At the second visit, the phys ical examina/ion is co n- esta bli sh the fo undati on. Th e initi al phases ofthe pro-
ducted and afi1ll series menstrua/ cycle hormone protocol are identical to that for women with regul ar cycles,
file is ordered. This profile is outlined in Table 40-8. A however, at the time of the phys ica l examination, an
follicular ultrasound series is also ordered according amenorrh ea profile (Tabl e 40-12) anda bas ic pelvic ul-
to the scheduling protoco l shown in Table 40-1 O. These
studies need to be done by people who are ex perienced
in conducting them. Finally, the di agnostic laparoscopy,
Table 40-11: NaProTechnology
hysteroscopy, and se lective hysterosa lpin gogram is
lnfertility Evaluatio n Protocol:
discussed in greater detail. This procedure is recom-
Long and Irregular Cycles
mended because its yield is so hi gh. In none of the
above tests is the search for a " needle in the haystack"
being conducted. Th e results of these tests will un- • Take the patient's histary (upan entry)
cover the mu/ti-factorial aspects of most infertility prob- • Chart CrMS far twa cycles
• Return far physical exam ination and arder the
lems. Each ofthese will be di scussed in greater detai l fallawing :
later in thi s chapter. • Seminal fluid analysis
• Amenarrhea prafile
, Pelvic ultrasaund
• Twa-haur glucase and insulin talerance test
Long and Irregular Cycles • Diagnastic laparascapy, hysterascapy and
selective hysterasalpi ngag ram
Camprehensive management review
In those women who present with long and irregu lar
cyc les, the infe rti lity eva luati on protoco l outlined in
Table 40-11 is used. In these cases, it is usually di ffic ult
Table 40-12: Amenorrhea Profile

Table 40-10: Follicular Ultrasound Series:
Scheduling P ro tocol
FSH Testasterone Tata lT,

LH Free testasterone FreeT,
Day 5: Baseline pelvic ultrasaund
Pralactin Androstenediane TSH
P-5 thraugh fallicular rupture : Daily ultrasaund
examinatians ~-endarphin DHEAs TatalT,
Reverse T,
• P+7: Pelvic ultrasaund T3 :rT3 ratia
J) 34 35
íl. q Q
·v ·:.:r 'tJ
"'"" to"'-
L AD .AD .x f
e ve
io1<1. li
l/
AD
Figure 40-14 : An example of a woman with a long menstrual cycle, infertility and polycystic ovarian disease . The cycle is 51
days in duration (From : Pope Paul VI lnstitute) .
trasound is ordered. The most common prob lem assoc i- Figure 40-14, it is aLmost patb ognomoni c fo r polycystic
ated with long and irregul ar cyc les is polycystic ova- ovarian di sease. However, there appears to be a small
rian disease and these two tests will genera ll y clarify percentage (about 5%) that may be ofprimary hypotha-
that situation . lami c origin.
lt is good to schedule a two-hour glucose and insulin

to lerance test to see if the patient is hyperin sulinemic. Amenorrhea
After fas ting levels of glucose and insulin have been
drawn , the patient is given a 75-gra m ora l glucose load. Patients who come with a hi story ofprolonged amenor-
Fo ll ow-up glucose and insul in leve ls are drawn at 30, rhea should fo ll ow the protoco l shown in Table 40-13.
60, 90 and 120 minutes. Normal and abnormal curves are
shown in the chapter on PCOD.
Table 40-13: NaProTechnology
lnfertility Evaluatio n Protocol:
In addition to the above, a diagnosti c laparoscopy, hys-
Amenorrhea
teroscopy and se lecti ve hysterosalpingogram are also
recommended. Many women with polycysti c ovaries
(over 50%) wi ll also have endometri os is. Thus, a di ag-
Take the patient's history (upon entry)
nostic laparoscopy will all ow fo r that di agnos is to be • Chart CrMS for four to eight weeks
made and usually it can be treated with laser at the time • Return for physical examination and order the
following :
of the diagnostic procedure. In addi tion, a confirm ati on , Seminal fluid analysis
of the diagnosis can be made by direct observation of , Amenorrh ea profi le
, Pelvic ultrasound
the ovari es and an eva luati on of th e ovary fo r poss ible , Diagnostic laparoscopy, hysteroscopy and
wedge resection sometime in the future can also be un- selective hysterosa lpingog ram (optiona l)
Comprehensive ma nagement review
dertaken.
When one views a cycle pattern such as that seen in
A
B
Figure 40-15: A woma n with infertility associated with amenorrhea . In example cycle patte rn A, !he prominent pattern is one of
dryness with occasional mucus patches . In cycle pa ttern B, !he pattern is one of a variable return of Peak-type mucus (From :
Pope Paul VI lnstitute).
530 T he Medical and Surg ica l Pra c tice of Na Pr o TE CH NOLOGY
This table is identical to th at of patients who ha ve long or ten ofthe cyc le . Jn thi s way, th e endometrium is still
and irregu lar cyc les except that they need to chart onl y thin and access to the interna! os of the fallopian tube is
for fou r to e ight weeks prior to coming back for their relative ly easy.
physical examinati on. The diagnostic laparoscopy is
considered optional in these cases. The most common
cause of amenorrhea is hypothalamic ameno rrhea and Classification of Mucus Cycles _ _ _~
in cases such as that, endom etriosis is ve ry rare. The
ameno rrhea profi le shown in Tab le 40-12 is also used in With the use ofthe Vaginal Discharge Recording Sys-
this group of pati ents. tem (VDRS), it is possible to objectively classify the
mucus cyc le. This class ification system and the mean s
The charting sequences that are observed are shown in by which it is obtained is described in C hapter 14. For
Figure 40-15 . A predominant pattern of dry ness or a rev iew, the class ification categori es are presented m
predominant pattern ofm ucus (a variable retum of peak- Table 40- 14.
type mucus) are the two dominant patterns. The most
important fea tu re, however, is the absence of menstrua- In a group of289 patients who carne into the program
tion and, of course, the absence of ovulation. with in fertili ty, their mucus cycle seores were calculated
and the mucus cycles c lass ifi ed. These are shown in
In sp ite ofth is bei ng a reasonably ominous-ap pearing Tab le 40-15. In 68.2 percent ofthi s group, the mucus
condition, sorne of the very best success rates are ob- cycles we re either limited or dry. This is in contrast to a
tained in the treatment of th is group of patien ts.
Table 40-1 5: lncidence of Mucus Cycle Pattern

Timing of Fertility Tests _ _ _ _ _____, (CrMS) in Patients with lnfertility
(Regular and Irregular Cycles) (N =289)
With the use ofthe CrMS va ri ous fertili ty tests can be
timed much more acc urate ly than previous ly. lt a ll ows lncjdence
Type of Mucus Cycle n º/ó
for a very simpl e but reproducibl e system for the woman
to keep so that it will te ll the physic ian and th e labora- Dry 33 11.4
tory w here she is in her cycle. The most obvio us timing Limited 124 42 .9
of tests is in the targeted hormone evaluation wh ich lntermediate limited 68.2 40 13.8
becomes common place in NaProTECHNOLOGY. How- lntermediate regular 31.8 32 11 .1
ever, such things as a postcoital test w ill not provide Regular 57 19.7
correct information ifit is not timed to occur at the time VRPM 2
3 1.0
when the good Peak-type mucus is present. Diagnostic
laparosco py is best performed during the preovu lato ry Tota ls 289 99.9
phase of the cycle so that an interruption of a preg- 1. From : Pope Paul VI lnstitute resea rch , 2004
2. VP RM = variable retum of Pea k-type mucus
nancy is not a co ncern and a se lective hysterosa lpin-
gography is best performed between day four and eight
Table 40-14: Th e Creighton Model System

Table 40-16: Patien t's Historical Assessm ent of
Types ofMucus Cycle
th e Presence of a Mucus Discharge (N =224)
using Objective Assessment
n' %
Range of
Mucus Cycle Score Not present 31 13.8
l. Regular Present 193 86.2

A. Regular 9.1 - 16.0 o. Not sure of amount 53 23.7
B. lntermediate regular 7.6 - 9.0
1. Not much present 71 31 .7
11. Limited 2. Sorne present 17 7.6
A. lntermediate limited 5.7 - 7.5 3. Fairly good 8 3.6
B. Limited 0.1-5.6 4. See quite a bit 35 15.6
5. See all the time 9 4.0
111. Dry o.o
1. From: Pope Paul VI lnsfüute research, 2004
Chapter 40 : NaProTECHNO LOGY in lnfertilit y : Evaluati o n an d Treatment 531
group of normal fe rtili ty contro ls where the limi ted mu- Percent Lim ited Mucus Cycles
cus cyc les were observed in onl y 2 1.7 percent of pa- Normal Fertility Controls vs . lnferti lity
by Laparoscopic D iagnosis and SAB
tients (Figure 40- 16).
100
% Limited Mucus Cycles
87 .5
90
Pati ents were also in vestigated upon entry in to the pro-
80
gram w ith regard of their own assess ment of the pres- 71 .9
70 64.6 65.8
ence or absence of a mucus di scharge. In 224 patients,
60 55.6
86.2 percent of them sa id they had a mucus di scharge
~ so 50.0
w hile 13.8 percent indicated that it was absent (Tab le ~
a_
40-1 6). Thi s was fo ll owed up w ith a question relati ve to 40
the timing in the cyc le when thi s was observed. Whil e 30

21 .7
the majori ty indicated that the mucus discharge occurred 20
at the time ofth e mid-cycle (73.4%), there was a signifi- 10

cant percentage w ho felt that it occurred at other tim es o
Controls Normal Pelvic Endometrlosis Ali SAB No
of the cycle (Table 40-1 7). F urthermore, the patients who Normal pelvis adheslon infertility infertility laparoscopy
fertility infertility lnfertility group infertility
said they did not ha ve a mu cus di scharge present, were N= 23 N=1 0 N=9 N=79 N=114 N=32 N=16
furth er eva luated in subsequent cyc les. Onl y 17 .8 per- p-value .2148 .0960 1.0003 1 1.0001 1 1 .0007 I l<.0001 1
Flsher's exact test
cent of them actua ll y had dry cyc les whil e another 60
percent had either limited or intem1edi ate limi ted mucus Fig u re 40-16 : The percen tage of li mited mucus cycles in
patients with no rm al fertility versus inferti lity arranged by
cycles. There we re sorn e, however, w ho had regul ar
laparoscopic diagnosis and spontan eou s abortion category
mucus cycles (F igure 40-1 7). (Fro m: Pope Paul VI lnstitute research, 2004).
A compari son ofth e wo man 's descri pti on on entry in to

the program w ith regard to her percepti on of the pres-
Comparison of Patients' History of No Muc us Discharge
ence of a mucus di scharge is correlated w ith the ubse- to Actual CrMS Charting of Mucus Cycle (N=31)
quent cl ass ifi cati on of th e mucus cycle using the CrMS 50
42.2
in Fi gure 40-1 8 fo r 193 separate pati ents. The corre la-
40
tion is actually quite u neven suggesting that a wo man 's
retrospective reca ll of th e para meters of the mu cus di s- ~30
~
a_
ch arge and/or its importance is not ve ry acc urate. ln
other wo rds, in order to obta in good in fo nnati on on the 20 17.8 17.8
13.3
presence or absence of th e mu cus di scharge pattem
8.9
10
and the class ifi cation of the mucus cycle itself, the indi -
vidual must track the ir fe rtili ty cyc les using the CrMS in
Dry Limitad lntermediate lntermedlate Regular
a prospecti ve fashi on. limitad regular
Type of Mucus Cycie ActuaUy Observad (CrMS)
In another group of patients w ho had endometrios is

Figure 40-17: A co mparison of th e patient's history of having
( 152 patients w ho underwe nt conserva tive surg ical ex- observed no previous mucus discharge and the actual CrMS
ci sion of endometri os is), 77.6 percent ofthem either had charting pa ttern of the mucus cycle (N =31) (From: Pope Paul
VI lnstitute research, 2004).
Table 40-17: Patient's Histo rical Assess m ent of

Table 40-18: The Creighton M odel
Where in the Cycle the Mucus Discharge
Types of Mucus Cycles in P atients with
O ccurs' (N=l74)2
Endo m etriosis treated with
Time in the Cy c le n % Con servative Surgery 1 (N= 152)
Mid -cycle 130 73.4 Type of Mucus Cycle n %

All the time 17 9.6
Before the peri od Regular 34 22 .4
13 7.3
Limited* 102 67 .1
Occasionally 7 4 .0
Dry* 16 10.5
Not sure 6 3.4
Alter the period 4 2.2 Totals 152 100.0
1. From: Pope Paul VI lnstitute research, 2004 . 1. From: Pope Paul VI lnstitute research , 2004.
2. lncludes only patients with history of regular menstrual cycles 77.6% limitedordry
Comparison of Patient's History of a Mucus Discharge with

Actual CrMS Charting of Mucus Cycle (N-193)
60
50
40
30
20
10
o
lntermediate Regular
Intermedia te Umited . r.J>'-' º('i
.j.~'
(,\?;
o~"'
Figure 40-18 : A comparison of th e patient's history of a mucus discharge with the

actual CrMS charting of the mucus cycle (N = 193). Th e patient's entry description is
on the lower left and the actual CrMS mucus cycle classification is in the lower right
(From: Pope Paul VI lnstitute research , 2004).
limited (67 .1% ) or dry ( 10. 5% ) cycles . lt is offurther ments w ith regard to pathologic entiti es such as en-
interest to note that in the dry cycle popul ation (n= 16) dometri os is, pe lvic ad hesive disease and pol ycysti c
there was onl y one subsequent pregnancy in that popu- ovarían syndrome are shown in the chapters in those
lati on and that was an ectopi c pregnancy (Table 40-18). respective secti ons.
lt should be pointed out, however, that there is a signifi-

Ovarían Hormone Dysfunction cant endocrinopathy w hich is observed in women who
ha ve infertility and regular cyc les. These endocrinopa-
A summa ry of the findings of the targeted hormone as- thies are important because they are a lso associated
sessment of the menstrual cycle in a large gro up of pa- with severa! ovulation-related di sorders (see bel ow) and
tients w ith infertili ty who a lso have regular cycles is the abnormal mucus pattems observed in many of these
shown in Figure 40- 19 thro ugh 40-2 1. These studi es patients.
show that the Peak in the E 2 leve! during the periovu-
latory time period is significantl y decreased and, most In additi on to the above, women w ith regu lar cyc les
notabl y, the progesterone profil e is decreased as well. and infe rtili ty have a very high incidence of premen-
T hi s shows up not onl y in the indi vi dua l levels of the strual symptoms (Table 40- 19). These symptoms are al-
p ost-Peak hormone profile but a lso in th e five va lue most as frequent as wo men w ho have premen strua l syn-
sum s and means. Indi vidual targeted hormone assess- drome. The hormonal ab normalities which underli e pre-
menstrual syndrome (see chapter on premenstrual syn-
drome) are very simil ar to the hormonal abnormalities
Table 40-19: lncidence of Premenstrual
observed in pati ents w ith regular cycles who also expe-
Symptoms in Ali Patients with
rience in fertili ty. It is highl y likely that there is an under-
Regular Cycles and lnfertility 1•2 (N=252)
lyi ng hormonal linkage between these different condi -
Sym ptom % Symptom %
tions. ln other words, there appears to be a pathophysi-
o logic link between the underl y ing problems that exist
lrritab ility 90.5 Depression 74.1
in premenstrual syndro me and in those that ex ist in in-
Breas! tenderness 85.7 Weightgain 69.4
fertil ity.
Bloating 85.3 Fatigue 67.3
Teariness 80.2 Headache 50.8
CHO craving 75.1 lnsomn ia 29.0
1. Symptoms began at least four days prior to onset of menses.

2. From: Pope Paul VI lnstitute Research, 2004.
3. CHO=carbohydrate cravi ng
Chapter 40: NaProTECHNOLOGY in lnfertility: Evaluation and Treatment 533
35 100
Periovulatory Estradiol-17j3 Levels 3 and 4 Value Periovulatory
Control (N=21) vs. Ali lnfertility with Regular Cycles E2 Sums and Means 90
Control (N=21) vs. All lnfertility with
30 Regular Cycles 60
NS 70 en
~
- Control group
25 63.3 - Stucty group
~
¡e- 60 3
~
~ 20 50 [
~ ~
w
E 40 ~
~
2 15 '>?.
"'" 12.8
12. 1
30 ~
20
10 9.5
8.8
10
p= NS NS Em NS
N= 94 148 168 142
o
E,-4 E,-2 Peak E, E, +2 3\lalue 4 llalue 3\lalue 4 v....
N=1Z3 N=75 N=- 123 N"'75
Relationship to Peak E, Level &.m Mean
Figure 40-19
Posl..Peak Progesteron. Soma and Mean•

Post-Peak Proges terone Profile Control (N=57) YS. AJI k'lfertUity with
Control (N=57) vs. All lnfertility with Regular Cycles R~ ular CycJes
100
- Control group
15.7 - Sludyg'°"' 90
15
14.4 60
13.6
~
.E
12.2
11;-------t,,
1 P:-0004 I 70 en
2
.
"'
.s
. /'
/ '•,
........ 10.0
81.2 3
60..,
é10 / 'l. 8
$
..
"'
94
87 ,
/ ~
'\
~
50 ¡;
•, 8.1
.a
.ª'
~
c. 40
E i 8.8 :;
2 <e.
30 3
CI) 5 !:-
20
,,. ~ l .ooosl 1<.00011 1<00011 ~ 10

N• 280 258 289 278 2SO
o o
P+3 P+5 P+7 P+9 P+11 &.m
N-=240
......
N=2..0
Day Post-Peak
Figure 40-20
100
Post-Peak Estradlol-1711 Proflle Post-Peak Estradiol -1711
Control (N=57) vs. All lnfertility wíth Regular Cycles Sums and Means 90
Control (N=57) vs.
15 All lnfertlllty wlth Regular Cycles
60
_,
'.!;!
12.3
- eono-o1....,
70 en .
- Sludy-
f2.0
="'
e
··---.,_ NS 2
3
60 m .,
:f.., 10
.Q
u f ....,
'• 9.8
54.8
~
50 c.
e 8.8 1 8.9 o
¡¡;
w :::.....
40
..
E
2
CI)
5
30 r
"'"
~
20
P" NS NS NS <03 NS 10
-
N= 21!1 278 289 287 219
o o
P+3 P+5 P+7 P+9 P+11 &.m
Days Post-Peak N=211 H=211
Figure 40-21
Figures 40-19 through 40-21 : These fi gures show th e periovulatory estradiol

profile and the postovulatory progesterone and E2 profile in a gro up of patients who
had regular menstru al cycles (N=20 1) but a/so experience infertil ity (From: Pope Paul
VI lnstitute research, 2004).
534 The Medica! and Surgical Practice of NaProTEC HNOLOGY
Ultrasound Findings defects. T he latter is extremely important if one is to

design treatment strategies that meet the spec ific de-
lt has been suggested that if a woman has normal regu- mand ofthe underlying problem.
lar menstrual cycles that she can be considered to be
ovulatin g norm ally. 7 Noth ing could be further from the
truth. ln addition , current approaches to studying ovu- Laparoscopy Findings
lation in infertility programs are signifi cantl y tlawed.
Standard tests such as basal body temperature curves, There are two main problems whi ch confront the cur-
endometrial biopsies, a mid-luteal phase progesterone rent use oflaparoscopy in the eva luation ofthe infertile
leve! and/or urinary LH detector kit simpl y do not give patient. The first has to do with the current laissezfaire
adequate information about the ovulation process to attitude w ith regard to its utilization. Because there has
be considered reliable. been a de-emphasis on making a diagnosis of the un-
derlyi ng problems, the actual use of diagnostic
In patients who have infertili ty problems, the incidence laparoscopy has lagged.
of ovu lation-re lated defects ranges fro m 56 to 61 per-
cent (F igure 40-22). This can be determined by the care- The second problem that ex ists is the genera l lack of
ful conduct ofseria l fo llicular ultrasound examination ski ll in doing good diagnostic laparoscopy. The skill s
of the ovaries aroun d the timing of ovulation. Data on outl ined in this textbook with the application of " near
this are outlined in detail in Chapters 20 through 22. contact" laparoscopic techniques and a good every day
understanding of the appearance of su ch conditions as
The question often asked in an infertility program is, " Is endometriosis, polycystic ovarían disease and pelvic
this woman ovulati ng?" That is the incorrect question adhes ive disease are essentia l to implementing a good
to be asking. A better question to ask is, "Is ovu lation diagnostic strategy when using laparoscopy.
normal? Or is there a defect in ovu lation?"
Again, it shou ld be emphasized that the implementation
ln acn1al fact, when one stud ies ovulation closely by of the ro utine performance of diagnostic laparoscopy
serial ultrasound and hormonal parameters, one realizes in this group ofpatients is not look ing for a " needle in a
that there are a number of different "ovulatory events " haystack. " In 250 consecutive laparoscopies performed
which mimic ovulation but either are comp lete ly anovu- for infertili ty, the main postoperative diagnosis is shown
latory or representa sign ificant defect in the ovulatory in Table 40-20. ln this group of patients 72.8 percent had
mechanism. An example of an ovu latory defect which is endometriosis. lf yo u were to apply these data to a group
anovu latory is the luteinized unruphired foll icle syn- ofwomen who had regular menstrual cycles and infer-
drome. An example ofan ovu latory defect in which the tility ( excl uding those patients who had polycystic ova-
ovulation process is significantly defective is the imma- rían disease and anovulatory patterns), nearly 80 per-
ture follicle. While ultrasound is commonly used to cent of the patients had endometrios is. This is signifi -
monitor ovu lation inducing medications, it is rarely used cantly different than that reported in major medica! text-
for studying spo ntaneous ovulation patterns and their books rangi ng from 5 to 25 percent of the inferti le pa-
100
Table 40-20: Main Postoperative Diagnosis
Con secutive Laparoscopies for Infertility 1
80
(N=250)
6 1.1 60.3
60 56.5 Main Postoperatíve Diagnosis n %
~
..• 40
Endometriosis 182 72 .8
Pelvic adhesions 21 8.4
PCOD 16 6.4
20 Normal pelvis 15 6.0
Tubal obstruction 10 4.0
Anovulation 6 2.4
PCOD Endometriosis Pelvic Adhesions Peri-adnexal adhesions 4 1.6
n=18 n-331 n=69
Figure 40-22 : In this figure , the incidence of ovulation related Totals 250 100.0
defects of patients with endometriosis , pelvic adhesive dis- 1. From: Pope Paul VI lnstitute research, 2004.
ease and polycystic ovaries is presented (From : Pope Paul VI
Chapter 40 : NaProTECHNOLOGY in lnferti l ity : Evaluation and Treatment 535
tient population . Ultimate ly, diagnostic laparoscopy is organ dysfunction (68.2%), ovulation-related disorders
an under-utilized and an under-skilled procedure and, (56.5%) and luteal phase deficiency (53.7%). Pelvic ad-
as a result, patients are not well served. hes ive di sease (with or w ithout endometriosis) is seen
in 38.9 percent, tuba! defects in 23.9 percent, polycystic
ovaries in 15.6 percent and pure anovu latory infertility
Diagnostic Summary _______~ in 0.9 percent. The totals add up to more than 100 per-
cent beca use most patients experience severa! of these
When one reads in major textbooks of reproductive at the same time.
medicine that there are certain causes for infertility and
the listing of these causes suggests that each pati ent A nonnospermic male was observed in only 45 .5 per-
has a s ingle cause for their infertility it is extreme ly mis- cent ofthe patie nts. Severe oli gospennia was observed
leadi ng. And yet, it is recogni zed that the etiology of in only 8.1 percent and azoospermia in 1.7 percent.
infertility causality is often multifactorial.8·9
A comprehensive diagnostic grid for both women and
A NaProTECHNOLOGY evaluation allows one to elicit men in patients with both primary and secondary infer-
the various underlying causes and put together these tility following comp lete eva luation is shown in Figure
multip le factors so that a comprehensive, multifacto- 40-23. The diagnoses in the woman are broken down by
rial treatrnent approach can be implemented. This, along whether o r not they are the num ber one, two, three, etc.
w ith the CrMS, is w hat allows for NaProTECHNOLOGY diagnosis at the time ofthe laparoscopic review (com-
to be so successful in the treatment for in ferti li ty and prehensive management review). When observed in this
other reproductive anomalies. fashion , the most common number one diagnosis is tar-
get organ dysfunclion fo ll owed by endometriosis, ovu-
In Table 40-21 , a large group of infertility patients evalu-
ated through the NaProTECHNOLOGY protocols out-
lined in this chapter are shown with the actua l incidence Table 40-22: Classification of
ofthe underlying ab normalities shown. This is split into Seminal Fluid Analysis 1
the female and ma le diagnostic categories. Furthennore,
Count Motility Morphology
the classification of the seminal fluid ana lysis into (mlllion) (%) (%)
normospermia, mild, moderate and severe oligosperm ia,
Normospermia >20 >60 >60
is shown in Table 40-22 for reference.
Oligospermia
Mild <20
Jt can be seen that in women , the top four associated <60
causes of infertility are endometriosis (77.4%), target <60
Moderate <60 <60
<20 <60
Table 40-21: Total Female and Male Diagnosis of Severe <20 <60 <60
<20 <60
Patients with Primary and Secondary lnfertility
Azoospermia No sperm present
fo llowing Complete NaProTECHNOLOGY Evalu ation 1
1. From: Pope Paul VI lnstitute research, 2004.
Feryiale Diagnosis % Male Diagnosis %
Endometriosis' 774 Normospermia 45.5

Target organ dysfunction3 68.2 Mild oligospermia 26.7
Ovulation disorders (anatomic)' 56.5 Moderate oligospermia 18.0
Table 40-23: Multiple Pregnancy Rate in
Luteal phase deficiency' 53.7 Severe oligosperm ia 8.1
Pelvic adhesions 2 38.9 Azoospermia 1.7 lnfertility Patients Treated with
Tubal defect' 23.9 NaProTECHNOLOGY 1
PCO D 2 15.6
Anovulation ' 0.9
Number of pregnancies 617
1. From: Pope Paul VI lnstitute Research, 2004.
2. Based upon a complete evaluation of 660 patients with infertility. Number of multiple births 20 2
3. Based on the mucus cycle score of 289 consecutive patients with regular lncidence o f multiple pregnancy 3.2%
menstrual cycles and infertility.
4. Based upan the ultrasound evaluation of ovulation disorders in a subgroup of
1. From: Pope Paul VI lnstitute research, 2004 .
460 patients with regular cycles.
5. Based upan a targeted hormone evaluation of postovulation progesterone 2. There were 17 sets oftwins , three sets of triplets and
production in a subgroup of 328 separate patients. no pregnancies beyond triplets.
536 The Medical and Surg ical Pra ctice of NaProTECHNOLOGY
Target Organ lnsufficiency

Dry cycle , Limited mucus cycle)
ndometriosis
----.,,-..-rruulation Defect
onnone Dysfunction
elvic Adheslons
COD
50
40 ~
30 ~
20
10
Figure 40-23 : This diagnostic grid for both female and male diagnosis in patients with
primary and seconda ry infertility is sh own following complete NaProTECHNOLOGY
eva luation (N=660). The diagnoses are presented accordi ng to their presentation as
th e most importa n! or secondary diagnoses (From : Pope Paul VI lnstitute ).
lation related disorder and hormonal dysfun ction. to address the vari ous organic abn orma lities such as
endometri osis and pelv ic adhes ive di sease. Th ese sur-
lnfe rtility is clearly multi fac tori al in its ori g in. Thi s can gica l approaches, described in deta il in the section on
be di scovered if good di agnostic testing is conducted surg ical NaProTECHNOLOGY, have as their prim ary
and an effort is made to find the underl ying causes. goa l the correcti on of the underl y in g problem while ac-
Without such efforts, these factors will not be di scov- compli shing surgery in a " near adhes ion-free" environ-
ered. ment. A thorough understanding and knowledge of these
approaches are necessa ry in order to provide the who le
spectrum ofNaProTECHNOLOGY care to the in fe rti le
coup le. The reader is referred to those chapters fo r the
deta iIs of those treatment specifi cs.
In a NaProTECHNOLOGY-driven program, treatment is
des igned to address the vari ous underly ing causes that O ne of t he d ist in c t a d va nt ages of t he
are identifi ed . For example, if an underl ying honn ona l NaProTECHNOLOGY approach to the treatm ent of in-
dysfun cti on is identifi ed, then that hormona l dysfu nc- fe rtili ty is its strikingly low mu ltip le pregnancy ratio. At
ti on is corrected. If an ovulation re lated ab norma lity is the Pope Paul V l lnsti tute, thi s rate is 3.2 percent (Table
identifi ed then tha t is corrected. Ifa n orga ni c abnormal- 40-23). In Ireland, thi s rate is abo ut the same (3 .4 per-
ity (such as endometriosis, pe lvic adhes ive disease, tu- cent) . With the nati ona l multipl e pregnancy ra te aver-
ba! obstructi on, or so fo rth) is identifi ed, th en th at too aging 35 .8 percent, this represents an J1.2/old decrease
is corrected. w ith its subsequent benefits to the fa mil y and the neo-
nates.
With the use of the CrMS one can impl ement treatment4
strategies which pro perly target the menstrual cycle.
For exampl e, the ability to use progesterone in the men- Case Presentations _ _ __ _ __ --.
strual and fe rtili ty cycl e requires definiti ve kn ow ledge
that one is in the postovul atory phase. Th e CrMS ro u- In F igure 40-24, a 29-year-old gravida Opara Owho had
tinely provides that in fo rm ation at virtuall y no charge been trying fo r seven years to try to achieve pregnancy
to the pati ent. Thus, these treatment protocol s can be w ithout success began charting the CrMS. T he teacb-
implemented in a long-term fas hi on without a great dea l ing of thi s client was done by long di stance and the
of diffi cul ty. cl ient was never directl y seen. However, she had under-
gone extensive infertility evaluation including basa l body
A variety of surgica l techniques have been deve loped te mperatu re curves, semin al fluid ana lys is, hysterosal-
Figure 40-24 : In this palien! with dry cycles and seven years of infertility, vitamin 8 6 was recommended as a mucus-enhancing
supplement. In the last cycle, limited mucus was observed and pregnancy achieved without any additional assistance except
fertility focused intercourse (From: Pope Paul VI lnstitute research , 2004).
pingography and diagnostic laparoscopy. She also un- program at the time of instruction . 8ecause she was an
derwent ovulation induction with clom iph ene citrate intern, the chart was submitted to her supervisor andas
(Clomid) and artificial insemination ali wi thout success. the supervisor was reviewing the case, she showed it to
the author and asked ifhe had any input. At one glance
She had heard ofthe work ofthe Pope Paul VI lnstitute ofthe chart, it was stated that "I think she has polycys-
and called the FertilityCaren• Center at the lnstitute. tic ovarían disease ." The patient went back to her phy-
She was ass igned one of the FCPs who taught her the sician with this information and said that she was told
charting as seen in Figure 40-24. No pregnancy occurred that she may have polycystic ovaries. The physician
in the first severa! cycles so the teacher impl emented a told her that, "We knew that but we didn 't think treating
" vitamin 8 6 protoco l." This protocol al lows for the pa- it would be successful. "
tient to take vitamin 8 6 as a mucus enhancing agent. In
the very first cyc le in which she took Vitamin 8 6 , she ln this case, charting the CrMS led to a conceptual di-
had a mucus discharge which she had never seen be- agnos is (without laboratory confirmation) which would
fore. The couple had interco urse and ach ieved a preg- have led her to a form oftreatment wh ich wou ld give her
nancy. The chart not only shows the pregnancy cycle a 70 to 80 percent pregnancy rate with appropriate medica!
but also the ultrasou nd showing the intrauterine preg- and surgica l therapy wi th a very low risk of multiple
nancy. pregnancy. However, she was not afforded that dignity
and was, instead, put through a truly horrific pregnancy
In Figure 40-25, a CREIGHTON MODEL chart of a woman loss situation.
who had previously undergone in vitro fertilization is
shown. This chart is her cycle pattern after her IVF. In In Figure 40-26, a patient who fa iled in vitro fertil ization
her case, she ach ieved pregnancy with sextupl ets from on two previous occas ions. She carne to the Pope Paul
the IVF approach . Unfortunately, she lost ali six babies VI lnstitute for further eva luation and instruction. Dur-
at about the 20'h week of pregnancy. After this occurred, ing the course of the eva luation , it was found that she
she entered a FertilityCare™ program and began to had limited mucus cycles, suboptima l progesterone pro-
chart the CrMS. Her teacher was an intern in the FCP duction and endometri os is. The endometriosis was
1 l 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 211 21 22 23 24 25 26 27 28 29 .10 JI 32 33 34 J5
Ell!i~~~~~~fff~f ~~fffff ffff~ff

~~~~~~~~~~~~~,~~~~~~~~~~~~~~~
1
• I .. a. 3" ;;• / M I" I" I" • -,:
I r r. r r
JOCL K>CL IOCL WC

wl "ª
;¡-
>ti
I"
1t&
Figure 40-25: Th is palien!, who previously los! sextuplets from an ART procedure , shows her CrM S chart wh ich is strikingly
consisten! with polycystic ovarian disease (From : Pope Paul VI lnstitute).
VVL
2
VL
OAO OAD
3
H M
4 5
VVL VL
°"'º
6
OAD
7
1•
...
11
8
1 11
9
~ L
Fo lía lor
UN ose und
lO
~~ ~tf t
..
11 12
• I
r
13
IOWL
"
14 15 16 17 18
f-
IOWL /OWL. IOWL OAD OAD Qlt.D MO OA.D
~o
1.11
+
e.o
AD
~ . 03
+
CD
... os
+
e.o CR
"º
19 20 121 22
OAO OAO
J 23
°"°
1 25
OAD 0\0
26 27 2 29 30
MCS
ppp
JI
:
32
s.o
33
10 ( >ys
34 35
Esf od; In ~ 30.0 ~I ., ao.o rafN 1 Pro ¡¡esi ~ ro 11 e

Svc fue ,um = 4~.4
26 3 svc ue """' . e.s
~ .5 ,rgtdl ., '" 15.0
. 141.s
""' ,1
Svc fue ;um
S ve fue ""'º • q _¡,
15.0 lra.€1 ... -

'"
..--- ,.,
10.0 nq/, 1
o
-- - -
.
1.5 lrd!I
>EM l'tDER: ~RO ~R r EW

rMK A¡PQI ~TM 'NT
...
Ht~T. pTA '1PS ANI
-m FO LO W·UD
"
- -
...___
"
>---
"
- ~
s.o nat. hl
... "
Figure 40-26: Limited mucus cycles, endometriosis, ovarian dysfunction and a husband with a very low sperm co unt were
identified in this palien! who failed two previous IVF procedures. In spite of these abnormalities with proper N aProT ECHNOLOGY
treatment, she achieved a pregnancy and had a normal healthy baby (From : Pope Paul VI lnstitute).
Chapter 40: NaProTECHNOLOGY in lnfertility: Evaluati o n and Treatment 539
treated with laser laparoscopy and this 42-year-old

woman was treated prospective ly with clom iphene to Table 40-25: Side-by-side Comparison
NaProTECHNOLOGY vs. ART
induce ovulation and to help correct the underlying
horm onal dysfuncti on. Her hu sband's initial sperm Comparison Subject NaProTECHNOLOGY ART
count was 0.3 mi Ilion with 1Opercent motility. He under-
Diseases are identified Ye s No
went a varicocele repair (prior to coming to the ln sti -
Disease are treated Yes No
tute) and took clomiph ene to improve hi s count. In the
Foundation is laid far future Yes No
eighth cycle of treatment she ach ieved a pregnancy success
which eventuall y resulted in a nice healthy live born More total pregnancies are Ye s No
achieved
baby.
Fertility-focused intercourse Ye s No
Speed to pregnancy is greater* Yes
Cycle-by-cycle pregnancy Yes
What does NaProTECHNOLOGY rate is greater*
Accomplish?_ _ _ __ __ _ _ _~ Built on foundation of No Yes
destroying life
More cost effective Yes No
NaProTECHNOLOGY allows for the diagnosis of the
When successful, but overall much lower "per woman" success.
underlying problem and the treatmen t ofthe underlying
causes. Tt has exce ll en t pregnancy rates (see Chapter
51) and, with appropriate evaluation and treatment, it
foste rs a natura l acceptance of the underly ing condi- important in helping these couples reso lve their long-
tion because the underlyi ng causes are understood. In standin g infertility and th eir search for rational causes.
sorne ways, if the woman does not become pregnant,
she reaches an acceptance leve! ofthe conditi on whi ch In the futu re, a search fo r the vari ous etiologies which
has led her to thi s dilemma. In many ways it is simi lar to we still do not und erstand will continue under the aus-
a death and dying situation where an indi vidual will go pices ofNaProTECHNOLOGY. Only with such an ap-
through various stages of anger and denial. But once proach ca n a cure to infertili ty eventually be fo und.
the ind ividual reaches acceptance, then one can move Potenti ally, NaProTECHNOLOGY can cause a new para-
on with their life (Table40-24). 1º In NaProTECHNOLOGY, di gm shi ft in the thinking of a profess ion.
this happens ali the time. In 25 years onl y a handful of
patients have left the NaProTECHNOLOGY approach In Tab le 40-25 , a s id e - by-side co mp a rison of
and gone to artificial reproducti ve technology. This NaProTECHNOLOGY and the a1tificial reproductive tech-
natura l acceptance ofthe underlying causes is extremely nologies (ART) is shown. In NaProTECHNOLOGY, the
Table 40-24: Phases of lnfertility Treatment and Counseling Tasks -

without ART
Phase Task
1. Acknowledging a fertility problem : Support

seeking help Education , infarmation and resources
11 Undergoing medical evaluation Psychosocial assessment and support
Education
Preparation far treatment
111 . Treating infertility problems Support and education
ldentifying coping mechanisms
Stress management
Emotional and therapeutic counseling
Preparing far outcome
IV. Further treatments : investigating Stress management and coping strategy
and treating additional diagnosis Emotiona l and therapeutic counseling
Providing support
V. Deciding to end treatment and Grief and therapeutic counseling
redefine family: adoption and Pursuing adoption
ch ildlessness Preparing far outcome
Adapted from: Feldman PR: lnfertility: A View to its Medical and Emotional Aspects. In: Counseling the lnfertile
Couple (IX). Proceedings of 23" An nual Postgraduate Course: American Society for Reproductive Medicine.
Washington, DC, Oct. 13-14, 1990.
540 The Med ical and Surgical Practi ce of NaProTECHNOLOGY
d iseases that ca use infertility are identified and treated , tua l number of pregnanci es ac hieved or the pregnancy
a fo undation is laid for future success, and more total rate " per woman" is much lower. In addition the ART
pregnanc ies per woman are achieved than w ith the ART approaches are built on the foundation of destroying
approaches. However, it does take longer and therefore li fe which is not present in the NaProTECHNOLOGY
the speed to pregnancy is greater in ART. The cycle by approac h. NaProTECHNOLOGY is also more cost ef-
cycl e pregnancy rate is also greater. However, because fective (see Chapter 51 ).
so many people di scontinue ART approaches, the ac-
1. Dickey RP, Taylo r S , Rye PH , et al: ln ferti liry is a Symp- 6. Hil gers TW, Da ly KD, Prebil , AM and Hilgers SK: C umu la-
tom Not a Di sease. Fertil Steril 74: 398, 2000. tive Pregnanc y Rates in Patien ts w ith Apparently No rm a l
Fertilit y in Ferti li ty-Focused lnt e rco urse . J Repro Med.
2. Wassersk Sewa ll G, Soules M R: Psychosocial Stress as a Cause
10:864-866, 1992.
of lnferti li ty. Ferti l Steril 59 : 658-689, 1993.
7. Bayer SR, Alper MM , Penz ias AS: The Boston IVF Hand-
3. Billings EL, Bi lli ngs JJ , Catarinich M: At las of the Ovula-
book of lnfertility. Parthenon Publi shin g Group. Boca Raton ,
tion Method: the Mucus Pattern s of Ferti lity and lnferti l-
2002.
ity. Advocate Press PTY. LTD. Melbourne , 1976.
8. Jan sen RPS: Elus ive Ferti lity: Fecundability a nd Ass isted
4. Kol stad HA, Bonde JP, Hjollund H et al: Menstrual Cycle
Conception in Perspective. Fertil Steril 64: 252-254, 1995.
Pattern and Fertility: A Pros pect of Foll ow-up Steady of
Pregnancy of ear ly Embryonal Los s in 295 Couples Wh o 9. Stanks GC, Grimes EW: C linical Management of lnfertility
Were Pl ann in g Their First Pregnancy. Fertil Steril 7 1: 490- due to Mu ltiple Causes. Sem Reprod Endocrin 3: 185 - 192,
496 , 1999. 1985.
5. ln structi o n on th e Respect for Human Life in its O rigin and 1O. Bums LH, Cov ington S H: Lnfertility Counselin g: A Compre-
o n the Dignity of Procreation (Donum Vírae) . Vatica n Con- hensive Handbook for C li nicians. Parthenon Publi shing. ew
gregation for the Doctrine of the Faith . March 10, 1987. Yo rk , 2000.
Hypothalamic-pituitary-ovarian Dysfunction
and lts Target Organ Effects:
lmplications for Treatment
n study ing the menstrual cycle and investigating its review wi ll also look at work that has been done on
I various relationships to underlying reproductive and
gyneco logic pathophysiology, one ca nnot help but think
receptor physiology and the possibility that many of
these conditions (includi ng many causes of inferti lity,
that there is a central origin to many of the observed spontaneous abortion, premenstrual syndrome, abnor-
phenomena. With the introduction ofthe CREIGHTON mal bleeding, recurrent ovarian cysts), might be related
MODEL FertilityCare™ System (CrMS) and its objec- to a receptor deficiency syndrome.
tive and standardi zed observational system for the vari-
ous biological aspects of a woman 's menstrual and fer-
ti 1ity cycles, there are certai n events that continue to Review of Basic Physiology _ _ _ _--.
recur that appear to have an end ocrine basis to them. In
some cases, th is appears to be related to a primary de- Gonadotropes are the anteri or pituitary cel l types which
fect in hormone manufacture or function and in other are responsible fo r the synthesis and secretion of LH
cases, a dysfunction of receptor formation or function. and FS H. They represent se ven to 15 percent of the
And , then again, in some cases, perhap a dysfunction total number of anterior pituitary cells. 2 There are at least
of both. two populations of gonadotropes in the human pitu-
itary gland. Based upon morphologic features , there is
In further eva luating this, it continues to point to, as one that conta in s large, ovoid cells and another with
So u les, et al 1 have pointed out, the result of a dysfunc- small, angu larce lls. ln the human pituitary, gonadotropes
tiona l supra-hypothalamic neuroendocrine modulation are sparsely dispersed throughout the pars distalis
of the gonadotropin-releas ing hormone (GnRH) pulse among acini composed predominantly of other anterior
generator. At the Pope Pau l Vl lnstitute, over the many pituitary cell types. 3
years of stu dy, this has been a subject of great interest
where research has been focused both in evaluating These gonadotropes can produce either LH or FSH, LH
existing research and in our own investigations. This and FSH or FSH alone (Figure 41-1 ). Depending upon
chapter intends to review the basic physiology of the this production effect, these ce ll s are referred to as ei-
hypothalamic-p itu itary-ovarian ax is along with those ther mono-honnonal or bi-honnonal. Gonadotrope secre-
stressors which mi ght cause it to be dysfunctional. This tory granu les may selectively store either FSH or LH. 2.4.s
541
542 The Medi cal and Surgical Practice of NaProTECHNOLOG Y
30 FSH The biosynthesis and sec retion of the gonadotropins

mlU /mL are tightly regulated across the menstrual and fe rtility
20 cycle. The release ofgonadotrop ins can be modified by
a number offactors including hypothalamic facto r (pri -
10
mari ly Gn RH , intra-pituitaiy factors) the peptides, activin
o ...._.,....................................-.....+-...--.-....................-.........-...... and follistatin and go nadol feedback (steroida l and pep-
tide).3
120
100 LH For the reader who wou/d /ike a more in-depth discus-
mlU/mL sion ofthese general tapies that review the basic physi-
eo ology, they are referred to tvvo excel/ent reviews: Loose-
60 Mitche// DS, Stance/ GM: Estrogens and Progestins.
In : Hardman JB, Limbird LE and Gilman AG (Eds).
40 Goodman and Gilman 5· the Pharmacologic Basis of
Therapeutics. I()" Ed. , 2001 and Halvorson LM, Chin
WW Gonadotropic Hormones: Biosy nthesis, Secretion
Receptors and A et ion. In : Yen SSC, Jaffe RB, Barbieri
-14 -10 -6 - 2 +2 +6 +IO +14
-12 -8 -4 o +4 +8 +12 +16 RL (Eds.) : Reproductive Endocrinology: Physiology,
Days of Cycle Pathophys iology and C/inica/ Management. 4'" Ed.
WB Saunders Co ., Phi/adelphia, 1999.
Figure 41-1: Serum LH and FSH levels throughout the men-
strual cycle in 1O normal subjects . Day O= Day of LH and FSH
peaks. Vertical bars represen! one standard error of the mean
(From: Moghissi KS, Syner FN , Evans TN : AComposite Picture Hypothalamus and
of the Menstrual Cycle . Am J Obstet Gynecol 114:405-418, GnRH Pulse Generato r------~
1972).
The hormone LHRH (luteinizing hormone releasing hor-
mone) , now referred to as gonadotropi n-releasing hor-
Under the intluence ofGnRH , LH and FSH may be e- mone or GnRH , is a polypeptide hormone. Schally et a l,
creted together or selective ly, and o ne may be ecreted elucidated the structure ofGnRH in 1971 and its truc-
over and above the other. LH and FSH belong to a fam- ture was confirmed by synthesis in 1972. 6 Later work
ily of g lycoprote in hormon es that a lso includes human showed that GnRH bound itselfto specific receptors in
chorionic gonadotropin (HCG)-an LH homologue. the anterior pituitary gland and stimulated the synthe-
sis and secretion ofboth luteinizing hormone (LH) and
The human pituitary has two pools of LH. Thi s allows follicle-stimulating hormone (FSH).
for a biphas ic release ofLH , which is observed durin g
GnRH infusion. The initial re lease of LH peaks at 30 GnR H neurons originate in the olfactory placode and
minutes and the secondary ri se begins after 90 minutes migrate to the medial basal hypothalamus (MBH). The
continuing up to four hours. Estradiol-17~ (E~) augments majority ofthese cell bodies are located within the arcu-
the second response while progesterone increases both ate nucleus ofthe MBH .7 The GnR.H which is produced
the early and late responses following estrogen treatin these cells is transported down axons, where it is
ment. lt has been ugge ted that the ex istence of a pre- eventually released into the hy pophysial portal sys-
formed LH pool that releases rapidly following GnRH , tem , which bathes the anterior pituitary gland .3
may be the source of LH released during the pul satile
pattern ofplasma LH as well as those w ith disorders of This hormone is norn1a lly released in a pulsatile fashion
the hypothalamus, pituitary or gonads . In addition, the rather than in a continuo us signa !. Knobil and co l-
second pool cou ld represent the more coord inated re- leagues8were the first to demonstrate that this pu lsatile
lease of the gonadotrope-granule population together pattern ofGnRH was required to increase gonadotropin
with stimulation of hormone biosynthesis. 3 expression (Figure 41-2). This observation was confim1ed
in two different ways . First, gonadotropin secretion can
FSH reacts somewhat differentl y. An early response in be restored in those women who are GnRH-deficient
plasma FSH is absent, perhaps reflecting the lack ofan when GnRH is exogenously administered in a pu lsati le
ac utel y releasable FSH pool. Thus, there is only a s ingle fashion. 9 Secondly, the admini tration of continuous
prog ressi ve ri se in FSH occurring during the infusion GnRH suppresses the function of the gonadotrope. 10
ofGnRH. 3 This inhibitory effect ofthe continuous adm in istration
Chapter 41: HPOD and lts Target Organ Effects: lmplications for Treatment 543
Neuronal
Activity
(discharges ¡......,_ _ _ _.__
permin)
LH
(ng/ml)
medial
D 2 3 4
TI ME (hrs)
neuroendocrine
relationships
controlling
LH/FSH
relea se
pituitary
1
1 portal
\ vasculature I
\
' ,' I
''.
. . ....
estrogen estrogen
E progesterone progesterone E
Figure 41-2: The hypothalamic pulse generator located in the arcuate nucleus of
the hypothalamus functions as a neuronal "clock" that fires at regular intervals
(A). This results in the periodic release of gonadotropin-releasing hormone (GnRH)
from GnRH-containing neurons into the hypothalamic-pituitary portal vasculature
(B). GnRH neurones (B) receive inhibitory input from opioid , dopamine and gamma-
aminobutyric acid (GABA) neurons and stimulatory input from noradrenergic neu-
rons (NE , norepinephrine). The pulses of GnRH trigger the intermittent release of
luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from pituitary
gonadotropes (C), resulting in a pulsatile plasma profile (D). FSH and LH regulate
ovarian production of estrogen and progesterone which exert feedback controls
(E) (From: Loose-Mitchell DS , Stancel GM : Estrogens and Progestins . In : Hardman
JG, Limbird LE, GilmanAG (Eds). Goodman and Gillman'sThe Pharmacologic Basis
of Therapeutics. 10"' Ed 2001 ).
of GnRH has been used as a treatment far a variety of closely corre late with the release of GnRH and its
different disorders including precocious puberty, en- pulses. 12· 13 As a result, frequent measure of LH pulses
dometriosis, prostate cancer and breast cancer. 11 can be used asan accurate indicator ofGnRH secretion
patterns.3 However, that also is not clinically very user
The measurement ofGnRH in the clinical setting is not friendly. lt is, however, an excel lent too! from a research
useful. This is in part because it has a very short half- point ofview.
life and also in part because it would require blood sam-
pling every 1Ominutes overa six to eight-hour period of The epi sodic release ofGnRH is sometimes referred to
time. Because of the short half-life, there is a large as "the hypothalamic pulse generator" (or the fertility
dilutional effect which makes the pulses difficult to de- pacemaker). 14 In studying ovariectomized monkeys,
termine. While it cou ld be helpful to measure GnRH lev- Knobil used the technique of measuring multi-unit elec-
els within the hypophyseal portal venous system, this trical activity (MUA). Every alteration in LH pulse fre-
is not possible at the present time for a variety of differ- quency which they observed was mirrored in simulta-
ent technical and ethical reasons. neous changes and MUA volleys (F igure 41-3). In liter-
ally thousands of observations, every MUA electrical
Circulating levels of LH , however, have been shown to vo ll ey observed had been followed by an LH pulse. 15
50
250
40
Total
'.:j"
..§ Estrogens
Ol
.s 150 30 µg/24hr
I
_J
20
50
3000 ¡§ 1o
)>
~
2000 :<' 0 -.............................,.--.........--.....--.--..----......- -
1000
"'!!!.2. 30
2-
20
120 240 360 480
Time (min ) 1O
Figure 41-3 : Characteristic volleys of electrical activity (MUA) o.._.,......,......,......,.-.--.........-__...,...___.,................,.-.--
recorded from the medial basal hypothalamus in relation to LH 6
pulses in the peripheral circulation in an ovariectomized mon-
key (From : Knobil A: The GnRH Pulse Generator. Am J Obste! 4
Gynecol 163:1721-1727, 1990).
2
o-..-................-.--.........---.....--..---..........- ......- -
During the early fol licular phase ofthe menstrual cycle, 18
the LH (GnRH) pulses occur approximately every 100
14
minutes (Figure 41-4) and since serum E2 levels are low,, Estrone E1
10
µg/24hr
this GnRH stimulus releases both FSH and LH. The half-
life ofFSH, whi ch is approx imately 180 to 200 minutes,
6
exceeds the interval between GnRH pulses. Thus, FSH
concentrations exceed those of LH .16 2
0 -.....................-.--............-+......--..--.--...-...........--.-.--
-14 -10 -6 -2 +2 +6 +10 +14
During the mid-follicular phase, the rise in serum E2 now -12 -8 -4o +4 +8 +12 +16
being manufactured by the maturing follicle (Fi gure 4 l - Days of Cycle
5), se lecti ve ly inhibits FSH release and plasma FSH de-
Figure 41-5 : Composite of 24-hour urinary estrone (E,), es-
creases. This increase in E2 most likely increases the
tradiol (E2 ) , estriol (E3 ) , and total estrogen throughout the men-
GnRH pulse frequency to about one pulse per hour strual cycle in 10 normal women . Day O (dashed line) repre-
during the mid-follicul ar phase (Table 41-1 ). 16 sents the day of LH peak and point of reference. Vertical bars
indicate one standard error of the mean (From : Moghissi KS ,
_J
Syner FN , Evans TN : A Composite Picture of the Menstrual
E Cycle. Am J Obste! Gynecol 114:405-418, 1972).
:3 : r FP
E
I
_J
2~ ~
_J
:: ~ LFP
E
:3 Table 41-1: Pulse Frequency of Pulsatile LH
E Secretion during the Normal M enstru al Cycle
I
_J
o 1
_J Pulse Frequency
~ MLP
E Stage of the Cycle (in minutes)
:3 ::
E Early follicular 87- 113
I
_J o ~ .~ Mid-follicular 61- 73
0800 1200 1600 2000 2400 0400 0800 Late follicular 67- 83
Clock Hours Ea rly luteal 100 - 109
Mid-luteal 161 - 265
Figure 41-4: Luteinizing hormone (LH ) pulsatility in the 24-
Late luteal 192 - 339
hour secretory profiles of a woman in the early follicular
phase (EFP), late follicular phase (LF P) and mid-luteal phase From: Crowley WF, Filicori M, Spratt DI , Santoro N: The Physi-
(MLP) of the menstrual cycle (From: Rossmanith WG : Ultradian ology of Gonadotropin-Releasing Hormone (GnRH ) Secretion
and Circadian Patterns in Luteinizing Hormone Secretion Dur- in Men and Women . Recent Progress in Hormone Research .
Academia Press, 41 : 473, 1985.
ing Reproductive Life in Women . Human Reproduction 8:77-
83, 1993).
Chapter 41 : HPOD and lts Target Organ Effects: lmplications for Treatment 545
As the E2 levels rise, it augments the LH respons ive- pothalam ic neural network may act to help regulate GnRH
ness to GnRH and immedi ately before the LH surge, the pul satili ty. 18
LH pulse amplitude increases. The progesterone leve!
also begins to ri se just pri or to the LH surge, whi ch GnRH is required for LH synthes is, whil e at the sam e
augments gonadotro pin release. Thus, the LH surge is time, the slow, irregular patterns ofGnRH secretion which
most likely ca used by the pos iti ve effects of ovarian occ ur during th e mid-lutea l ph ase, may al so reduce the
steroid s in the presence of ra pid pul se GnRH. 17 produ ction of pituitary LH.
After ovul ation , the pulse frequency of LH (G nRH) de- Wi th the reduced LH synthes is and the intermittent re-
creases signifí cantl y. The amplitude of the pul ses in- lease of LH occurring at the same time, the depl etion of
creases at the same time. By the mid-lutea l phase, the pi tuitary stores of LH will occur. The low pl as ma FSH
LH pul se frequ ency fa ll s to less than 50 percent of th e leve ls during th e early luteal phase occur because of
frequency during the early fo lli cular phase and the pulse the elevation of plasma E2 whi ch selectively inhibits FSH
amplitude becomes much more variable: The small pulses release. As a result, pitui tary FSH stores are maintained.
are interspersed among larger pulses of pro longed du- With the demi se of th e corpu s luteum, both serum E2
rati on. The fa ll in GnRH pulse frequency is the result of and progesterone levels fall . The fa ll in progesterone
the increasing producti on of progesterone fro m the cor- all ows the Gn RH pul se frequency to in crease and since
pus luteum (Fi gure 4 l-6). Na loxone, an op iate receptor the LH stores are depl eted, FSH release predominates
antagonist, will in crease LH frequency during the lutea l during the last few days of th e menstrual cyc le. As a
phase suggesting that progesterone may act by increas- result, the increase in pl asma FSH which occurs in the
ing hypothal ami c opioid acti vity.17· earl y portion ofth e menstrual cycl e and is necessary for
th e ini tiati on of the deve lopment of the ovari an follicl e
The vari ati ons in GnRH pulsatil e release are believed to in the next cyc le, actuall y beg ins during the lutea l phase
be achi eved th ro ugh ovarian stero id feedback whi ch of the prev ious cyc le and is caused by an increase in
modul ates th e " intrin sic" pulse pattern . lt can also be the stimulation ofthe pitui tary by GnRH which is primed
furth er modifi ed through the acti on of loca ll y re leased to re lease FSH. 17
fa ctors. For exampl e, opi oids exert inhibitory effects,
whil e norepinephrine is beli eved to stimul ate GnRH re- lt might be postul ated that the absence of a se lecti ve
lease. Dopamine treatm ent can produce both a stimul a- ri se in FS H during the lutea l phase of one menstrual
tory and inhibitory GnRH response depending upon cyc le, mi ght lead toa n abnormali ty in fo lli cular matura-
the phys iolog ic state. Th is suggests th at an intra-h y- tion in the next cyc le. However, if thi s occurs over one
cycle, it is thought to not have much of an effect. How-
ever, if FS H stimul ation is suboptimal over a seri es of
16 severa! cyc les, the fo lli cles may not mature and a dys-
12 fun ction can appear. At the same time, if the corpus
Progesterone 1uteum secretes an in adequate amount of progesterone
8 ng/ml and E2 , the pulse frequency of GnRH would not de-
crease and the re lease of LH and FSH would continue.
4
Thi s could lead to a dysfuncti onal corpus luteum and
oL..,-=;~~~==;::t:;:!:+-~...-..-,.....,,.....,....!,.~ the late lutea l ri se in FSH might not be as marked and
8 thi s could furth er lead to dysfun cti onal ovulati on-re-
lated patterns. 17
6 Pregnanediol
4
mg/24 hr
GnRH Receptor - - - - - -- ----.
2
GnRH binds to a GnRH receptor (G nRH-R) with a very
-14 -10 -6 -2 +2 +6 +10 +14 hi gh affi ni ty. Thi s receptor is located on the cell surface
-12 -B -4 O +4 +8 +12 +16
Days of Cycle of the gonadotro pe. The relati ve number ofG nRH-R 's
observed between hi gh and low-frequency GnRH pulses
Figure 41-6: Serum prog estero ne and urinary pregnanediol
excretion during th e menstrual cycle. Day O (dash ed line)
di ffe rs by a facto r of two to three fo ld. The number of
represents the day of the LH peak. Vertical bars indicate one GnRH-Rs is regulated by varyin g GnRH pulse frequen-
standard error of the mean (From: Moghissi KS, Syner FN , cies and other hormonal fa ctors. Th e concentrati ons of
Evans TN : A Composite Picture of the Menstru al Cycle. Am J GnRH -R in the pituitary gland is highest when the GnRH
Obstet Gynecol 114:405-41 8, 1972).
pulse frequency is 30 minutes, and lowest with a pulse at approximately one-third the potency of inhibin . Bio-
frequency of two hours . chemically, activin and inhibin are related, which pro-
vides a system in which ce ll s may alternate relatively
There have also been identified GnRH-binding sites in easily between the production oftwo factors which have
tissues other than the pituitary gland. Extra-pituitary opposing actions.21 Fo lli stati n is structura ll y unrelated
sites include the ovary, testes (male), brain (hippocam- to either inhibin or activin.
pus), hypothalamus , prostate, brea t and placenta . The
physiologic roles ofthese extrapituitary sites ofGnR.H- There are two types of activin receptors: Type 1 (Act-
R expression are not known .3 R.I) and Type TI (Act-R.I 1). A specific receptor for inhibin
has yet to be identified. But inhibin can bind to the Act-
R.11 receptor and it is thought that inhibin may act
Gonadotropin Biosynthesis and Secretion through a competition with activin for the activin recep-
tor sites. Folli tatin may act through a modulation of
The biosynthesis and secretion of gonadotropins are activin or inhibin action. 22
modulated by two gonadal feedback systems - the go-
nadal steroid and the activin-inhibin-follistatin systems. Of these three peptides, inhibin is believed to be the
The actions of these two sy tems are superimposed on most important for the feedback regulation of gonadot-
the pulsatile stimulatory activity ofGnRH. 3 ropin gene expression (Figure 41- 7). Inhibin increases
significantly during the luteal phase, peaking in the mid-
The steroids, progesterone and estrogen appear to ex- luteal phase and decreasing at about the sa me time a
ert their effects both at the hypothalamus and the ante- circulating progesterone. It is thought to be primarily
rior pituitary gland. Receptors for these two hormones ovarían in origin and F H secretion is cons istent with a
have been identified in the gonadotropes and within role for inhibin in the modulation of pituitary function
the hypothalamus. Receptors for these sex steroids have through a feedback mechanism. 3
also been identified in a number of neuronal ce ll types,
including those that release dopamine and ~-endorphin.
Receptors have not, however, been identified in the 30 400
GnR.H-containing neurons ofthe arcuate nucleus. Loss
of estrogen feedback following ovariectomy is associ- o 300 ...!..
::;- 20
..J
ated with marked increases in circulating levels ofboth 2.
LH and FSH. Replacement with estrogen rever es this ª-
J:
(/")
200 ~
lll
:¡:
effect. The majority ofthe inhibitory effects of estrogen ~ 10 ~
are likely to be mediated through the pituitary gland. 3 100
Estrogen can also have a positive feedback effect on .5 15

gonadotropin secretion at the time ofthe mid-cycle LH
surge. This effect is estimated to require a sustained
o
2000 50
~
.
serum E2 concentration ofmore than 20.0 pg/dL for ap- ~ o
proximately 50 hours. 19 o 40 E
E . .s
.e: 30 ~~
..J
o :! o
Progesterone exhibits an inhibitory effect on GnR.H pulse 1000 -Q'.
frequency but may require estrogen priming to exe1t its º

~
ll'.
1-
20 :i ~ (/")
UJ
(/")
~
most optima! effect. The decrease in GnRH pulse fre- UJ 10
o
o ll'.
quency may also be mediated through increases in the Q.
hypothalamic ~-endorphin system 20 (see later in this ·15 .5 5 15

DAY OF CYCLE (LH SURGE)
chapter).
Figure 41-7 : Concentration of immunoactive inhibin , estra-
diol , progesterone , LH and FSH in peripheral plasma of five
Activin-lnhibin-Follistatin System --~ women , mean +/- SE . The values have been grouped +/- the
onset of the LH surge. Note that in the follicular phase of the
cycle, there is no change in inhibin concentration at a time
Three polypeptide factors have been isolated from fol- when there is a significan! fall in the concentration of FSH .
licular fluid: lnhibin, activin and follistatin. lnhibin de- (From : Baird DT, Fraser HM , Hillier SG, et al : Production and
creases and activin stimulates gonadotropin function. Secretion of Ovarian lnhibin in Women . In: Yen SSC , Vale WW
(Eds). Neuroendocrine Regulation of Reproduction . Serano
Follistatin also suppresses FSH-~ gene expression , but Symposia , Norwell , MA, 1990.)
Chapter 41 : HPOD and lts Target Organ Effects : lmplications for Treatment 547
Acti vin can also be detected in the serum, but it is re la- screens gonadotropin producti on, it i suffic ient to iden-
ti vel y low and remains stab le across the reproducti ve tify a go nadotropin defic iency whi ch one suspects
cycle. Follistatin leve ls are also stab le across th e men- wo ul d be th e result of a hypothalami c pituitary dys-
strual cyc le. 3 fun cti on. Thi s is shown by laparoscopi c diagnosis in
th e in fe rti le pati ent with FSH leve Is drawn on day 5 of
Whil e these three substances were ori ginall y iso lated the cycle in Figure 41 - 1O.
from fo llicular fluid , it appears that they can be expressed
by a wide vari ety of both reproducti ve and non-repro- During the post-Peak phase ofthe cycle, when one looks
ducti ve ti ssues and serve fu nctions which go beyond at FS H and LH producti on on Peak + 7 (7 days after th e
the control of FSH secreti ons.23 The ability of acti vin , Peak Day) in patients with in fe rtility and di ffe rentiated
inhibin and foll istatin to aid in the regulati on of gona- by the type of underlying organi c disease identifi ed at
dotro pin bi osynthesis and secretion has been fir mly the time of laparoscopy, one sees that FS H leve ls tend
establi shed.3 to be increased and reach stati stica l significance with
the pelvic adhes ion and PCOD group (F igure 41-1 1) but
are not different for the other gro ups. The LH levels,
Pope Paul VI lnstitute Efforts _ __ ~ however, tend to increase signi fica ntl y and are statisti-
ca ll y signifi cantly elevated in the endometri os is and
Over the last 28 years of our research with the CrMS , proxi mal tuba! occlusion gro up, as we ll as, the PCOD
scoring ofth e mucus cyc le, eva luati on ofthe cyc le with group (Figure 4 1- 12). Whil e th e latter increase in LH is
various endocrine para meters, the use of seri al ul tra- we ll recogni zed in pati ents with polycysti c ovari es, the
sound examination to eva luate ovul ati on pattern s and elevated leve ls of LH obse rved in women with en-
the use of di agnosti c laparoscopy fo r the identifi cati on dometrios is and prox im al tuba! occ lus ion, may very
ofvari ous organic di sorders, questi ons have arisen re la- we ll be re lated to a type of endocrine dysfu ncti on that
ti ve to the underlying ca uses of sorne of the clini ca l is here in described. Where the producti on of progest-
signs that were being observed. For exampl e, nea rl y 60 erone is suboptimal, th e feedback to the pulse genera-
percent of women with infertility pro bl ems have been tor would res ult in in creasin g pulse frequencies and
observed to have stru ctu ra ll y abnormal ovul ati on-reli ke ly, an increased output of LH .
lated events when studi ed by ultraso und (see Chapters
18 to 20). In addition , when infertili ty patients are stud- Women with li mited mucus cycles (mean MCS 4.78) were
ied hormonally, they have show n the pattern s which compared to a group ofwomen with hi gher mucus cycle
are summari zed in Fi gure 4 l-8A-C. In thi s comparison seo res (mean MCS 8.2, p=.03, equal va ri ance /-test) by
between women with normal ovul ation patterns by ul - conducti ng GnRH chall enge tests on day 5 of the cycle
trasound and a group of infe rtil e women with regul ar in each group. ln response to GnRH , the output ofLH in
menstrual cycles, using targeted horm one assessment, th e lim ited mucus cycles group was in excess of that of
we have been abl e to establi sh that the periovul atory E2 the group with higher MCS (a lthough not stati sticall y
profiles peak ata slightl y lower leve! in the in fe rtili ty signifi cant - Figure 41-13 ). The output of FSH was not
group than in the contro l group (F igure 4 l -8A). Fur- differe nt in the two groups.
thermore, tbe sum and the mean ofthe 3-va lue E2 pro fil e
were also observed to be signi fica ntly decreased in the When the LH:FS H rati os of the two groups were com-
peri ovu latory phase. pared, however, the rati os were signi fica ntly higher at
eac h po int over two hours in the group with limited
When thi s is followed into the lu tea l phase ofthe men- mucus cycles. Thi s would appea r to be consistent with
strual cycle, the post-peak progesterone profil e shows the ro le of suboptimal progesterone producti on by thi s
a remarkabl e decrease in producti on fo r both the ind i- sa me group. lt does not, however, expl ain whi ch comes
vidual va lues, as well as the sum and the mea n of the first or what the exact eti olog ic components are. Jt does
profil e (Fi gure 4 l -88 ). The post-Peak E2 profil es were suggest, however, a central role in the ovarian ho1mone
not stati sticall y significantly di ffere nt (Figure 4 l-8C). dysfu ncti on.
In trying to evaluate thi s further, we looked at FSH lev-

els at day 1 and 3 of the menstrual cycle and compared Role of Beta-Endorphin -----~
the control group to the infe rtili ty popul ation. Thi s is
shown in Fi gure 41-9. In both groups, whil e the FS H Beta-endorphin (endoge nous mOiphine = endorphin)
leve ls were increasing, the infe rtili ty popul ation showed is the best known of the opi o id pepti des whi ch are re-
a significant decrease in FS H. Whil e thi approach on ly lated to the reproducti ve system. In an unu sual twist,
Periovulatory Estrad i ol - 17 ~ Levels 3- and 4-Value Periovulatory

Control (N=21 ) vs . All lnfertility with Regular Cycles E1 Sums and Means 90
Contro l (N=21 ) vs. All lnfertility
3 with Regula r Cycles
80
NS • Controlgroup
- Sludy group 70 g'
63.3
60 ~
!);'
;
¡
;;;
2
50 ª'
w
16.0 ¡/ 40 .b
ª
E
2 15 / 10.8 =>
~
30
////
20
9.5
8.8
NS NS NS
94 148 168 142
o
E2 -4 E,-2 Peak E2 E2+2 3 Value 4 Yalue 3 Value 4 Value
Ns123 N=75 N=123 N ..15
Relationship To Peak ~ Level Sum Mean
Figure 41-Sa
Post-Pea k Progesterone Profile

Control (N=57) vs. All lnfertility w ith Regula r Cycles
100
Post-Peak Progesteron e
Sums and Means
15.7 Control (N=57) vs. All lnfertility 90
15 w ith Regular Cycles
80
• Controlgroup
1p•.0004 1
/
.
11.9
,/ -----~------,,
12.2
' ,10.0
• Study group 70
60 "
"'"'2
3
g
9.4 /
/ "t,
\,
50 !!!
..
4! \\,
..a"'
8.7 8.1
40 =>
---. 6 .8 =>
30 i
20
10
p• ~ 1ooos l !<00011 kooo1I ~
o-L-~N~·=--~~2~
80'--~~
288
~~~2~89
,,_~~2~78,__~~2~
5-0'--~~--'- o
p +3 P+5 P+7 P+9 P+l 1
Sum Mean
Days Post-Peak N-=240 N::240
Figure 41-Sb
100
Post-Peak Estrad i o l- 17 ~ Proflles Post..Peak Estrad i o l - 17 ~
Control (N=57) vs. All lnfertility w ith Regular Cycles Sums and Means 90
Control (N=57) vs. All lnfertility
15 with Regular Cycles
80
12.3
• Control group
'5 70 (/)
g. NS • Study group "'~

=
.... 60 !);'
10 ;c.
o 50 §:
'5 8 .8
~
;;;
w
E
40 .b=>
2
"'
(/)
5
30
20
ª
10
P• NS NS NS GQi] NS
N• 261 278 289 267 219
o
P+3 P+5 P+7 P+9 P+11
Days Post-Peak Sum Mean
N=211 N=21 1
Figure 41-Sc
Figure 41-Sa throug h Figu re 41-Sc : The periovulatory E2 levels in women with infertility and regular cycles along with their
3 and 4-value peri ovu latory E2 sums and means are shown in Figure 41-BA. The post-Peak progesterone profile for that same
group and the post-Peak progesterone sums and means is shown in Figure 41-88. The post-Peak E2 profil es fo r that sa me
group, along wi th the respective sums and means are shown in Figure 41-BC . Th ey are all compa red to a control grou p of
women who have normal ovulation patterns by ultrasound evaluation. (From : Pope Paul VI lnstitute research , 2004).
Chapter 41 : HPOD and lts Target Organ Effects : lmplications for Treatment 549
Mean P+7 LH Leve! in lnfertility Patients

_ _ _ _ _ _ . 13.9 with Different Organic Diseases 10.0
ti .O - - - - - - - - - - _......-! 11 .4
10 7.6
6.7
5.6
6.0 4.2
__...,_ Nonnal Fertili ty Controls

- - - Infertility with Endometriosis
0.007 0.029
OTO Endometriosis Pelvic PTO PCOD
Adhesions
Oa y of 1he Cycle
p = .6758 . 1497 ~
Figure 41-9: FSH levels during the first three days of the Figure 41-12: The mean LH level on Peak +7 (mid-luteal phase)
menstrual cycle in women of normal fertility and infertility. The in a group of infertility patients with different organic dis-
FSH levels for !hose women with infertility are significantly eases (From : Pope Paul VI lnstitute research , 2004).
decreased from the normal (From : Pope Paul VI lnstitute re-
search , 2004) .
60.0 - , - - - - - - - - - - - - - - - - - - - - - - - ,
LH: Controls, mean MCS = 8.22 -
LH: lnlertility, mean MCS = 4.78 - -
50.0
Mean Day 5 FSH Leve! in lnfertility Patients
with Different Organic Diseases 40.0
~ 3o.o
8 .9
8.0 7.9
E
7 .6
7.3 _,
:r:
6.9
20.0
10.0
3.8
p .097 .07 .06 .07 .09 .07
O.O Equal Variance t ·test
FSH: Controls
FSH: Sludy Group - -
30.0
Pelvic OTO All Endometriosis PTO PCOD

Adhesions lnlertiHty _,
p= .4658 .3491 ~ G:QjJ ~ 1<.001 I E 20.0
Figure 41-10 : FSH levels in a group of infertility patients

"E
:r:
VJ
u.
measured on day 5. Patients with various organic diseases
10.0
NS NS NS NS NS NS
Equal Variance t ·test
0.0 + - - -- - - - -- - - - - - - - - - - - - - - 1
LH: FSH Ratio: Controls
LH: FSH Ratio: Study Group -
Mean P+7 FSH Levels in lnfertility Patients 3 .0
with Various Organic Diseases
4 .9
.g 2.0
4.3
(}_
4.0 4.1 :r:
3.9 VJ
u.
:5
1.0
O.O
p C2iJ [®2) [®2) ~ ~ cm
Equat Variance t·test Aspin-Welch, Unequal Varia.nea t-1es1 . Wilcoxon Rank-sum
Baseline 15 30 45 60 120
and
Time From Baseline In Minutes
GnRH
Administration
Control Endometriosis PTO OTO Pelvic PCOD Figure 41-13 : LH , FSH levels and the LH :FSH ratios of two
Ad~ns .0769
p= .4517 .4704 .2560 groups of infertile women . The difference in the two groups
~
was determined by the presence of limited mucus cycles
Figure 41-11 : FSH levels in a group of infertility patients mea- (mean MCS 4.78) and women with higher mucus cycle seores
sured on Peak + 7 (mid-luteal phase). Patients with various (mean MCS 8.22) (p=03). They were each cha llenged with a
organic diseases (From : Pope Paul VI lnstitute research , standard dose of GnRH on day 5 of the cycle (From : Pope
2004). Paul VI lnstitute research , 2004).
opioid receptors were first isolated in the brain by ade of the receptor si te by naloxone should result in a
Goldstein et al 24 in 1971. This was followed by the isola- dissipation of such symptoms. lt is he lpfu l if similar
tion and characterization ofthe first endogenous opio- responses can also be obtained with other opioid an-
ids by Hughes et al 25 in 1975. ~-endorphin was found to tagonists such as naltrexone (Trexan, ReVia).
be composed of the amino acid sequence 61-91 of the
previously discovered protein, ~-lipotropin. 26 ~-lipotro In evaluating radioimmunoassay studies for ~-endor
pin was then considered to be the parent structure. phin, it is important to note whether the antiserum used
Another opioid peptide was characterized in 1975 and has a significant cross-reactivity with ~-lipotropin hor-
called dynorphin .27 mone. This may result in an overestimation of the ~
endorphin measured. ~-endorphin is also a relatively
There are three classes of endogenous opioid peptides labile hormone and it does require extraction. Further-
and these are cal led endorphins, enkephalins and more, ~-endorphins are generally measured in the pe-
dynorphins. These are composed of a group of com- ripheral blood but concentrations in the hypophyseal
pounds derived from three similar, but yet distinct pre- portal system tend to be much higher and, therefore,
cursor proteins. These peptide opioid precursors are plasma concentrations do not equate with the po1tal
pro-opiomelanocortin (POMC), pro-enkephalin A and blood concentrations (F igure 41-14). The plasma con-
pro-enkephalin B. POMC is also the parent molecule for centrations retlect secretion and clearance distribution
adrenocorticotropic hormone (ACTH) and ~-lipotropin. and spi ll over from extra-CNS sources.
The ~-lipotropin mo lecule is cleaved to produce ~-en
dorphin. Pro-enkephalin A is a precursor to the enkepha- ~-endorphin is secreted in parallel with ACTH in re-
1ins and pro-enkephalin B is a parent structure for sponse to stressful stimuli and this peptide is found in
dynorphin. the same anterior pituitary cell s a ACTH. 3 1 ~-endor
phin has been demonstrated to be involved in the regu-
POMC is found in its highest concentration in the pitu- lation ofthe secretion ofa variety ofpituitary hom1ones
itary gland, but it is also found in the brain, syrnpathetic including gonadotrop in s, prolactin, ACTH, growth hor-
nervous system, adrena ls, gastrointestinal tract and pla- mone, vasopressin and oxytoc in .32 ·33 Its involvement in
centa. Pro-enkephalin A has its highest concentration the regulation of the menstrual cycle started with the
in the adrenal medulla but can also be found in th e pos- observation that morphine could block ovulation 34 •35 and
terior pituitary gland , brain, spinal cord and gastrointes- the description that narcotics could produce menstrual
tinal tract. Pro-enkephalin B is found in the brain and dysfunction in IV narcotic addicts. 36
the GI tract. ~-endorphin is found in its highest concen-
trations in the intermediate lobe ofthe pituitary, as well
as the arcuate nucleus and the median eminence ofthe PORTAL PERIPHERAL
6000
hypothalamus .28 ·29
The mechanisrn ofaction ofthese peptides relies upon 5000

their interaction with op ioid-b inding sites . These sites
are found in the central nervous system, as well as in a
variety of peripheral tissues. There are five opioid re- -
~
4000
ceptor subtypes that have been suggested. These in-

-E
clude the mu-(µ), delta-(8), kappa- (K), epsi lon- (E) and
sigma- (a) receptors. Morphine acts preferentially at the
µ-receptors whereas the enkephalins act preferentially
-C>
Q.
a..
w 1
3000
c:i.. 2000
at the 8-receptors. The ~-endorphins act at the E-recep-
tors and dynorphins at the K-receptors . These receptor
si tes are not totally specific anda "cross-over" interac- 1000
tion can be demonstrated with sorne ofthe other recep-
tor sub-types. Na loxone (Narcan) is known to block ali
0....L.--
sub-types ofreceptors, but with different affin iti es. The
Fi gu re 41-14: The beta-endorphin concentration in hypo-
µ- and E-receptor si tes are more naloxone sensitive than
physeal portal blood compa red to levels in peripheral blood .
the 8- and K-receptors.30 These samples were collected from pigtailed monkeys at ran-
dom stages of their menstrual cycle (From: Ferin M, vanVugt
Naloxone is often used asan "opioid probe." lf certain D, Wardlaw S: The Hypothalamic Control of the Menstrual
Cycle and the Role of Endogenous Opioid Peptides. Academic
symptoms are related to ~-endorphin activity, then block- Press 40:441-485, 1984 ).
Chapter 41 : H PO D and lts Target Organ Effects : lmplications for Treatme n t 551
Using a primate model , Ferin, et al37 presented fo ur lines 3. Na loxone (Narcan) in creases gonadotro pin re-
of evidence which supported the concept of ~-endor lease suggesting ton ic inhibition of gonadotro-
phin modul ating gonadotropin secretion during the pin release by ~ -endorphin.
menstrual cycle (Figure 41-15). These four points are: 30
4. Ovarían stero id horm ones regu late ~-endorphin
l. ~-endorphin neurona l ce ll bodies have been secretion by the hypoth alam us and also modu-
found to be concentrated in the arcuate nucleus late gonadotropin release. lt has been show n,
where GnR.H and dopamine are also found. Fur- for example, that fo llowing ovariectomy, the por-
therrnore, ~-e nd o rphin , GnR.H an d dopamine tal blood ~-endorphin concentrations become
have been found together in hypophysea l por- undetectable by RI A. 38 Fu rth ermore, ~-end o r
tal blood at greater conce ntrati ons than fou nd phin is produced in a cyc li c fas hion during the
in the peripheral blood. course of th e menstrual cyc le with the highest
concentrati ons fo und during the luteal phase and
2. Administration of op ioid and agon ists inhibit lower concentrations in the late fo lli cu lar phase.
gonadotropin release. This was establi shed wi th
the intravenous inj ection of morphine or an in- lt has been shown that nal oxone induces an increased
traventricular inj ection of~-e nd orp hin itself. frequency and amp litude of th e pulsatile release of LH
durin g the late fo lli cul ar and mid-lutea l phases of the
menstrual cycle, but not in the early fo lli cul ar phase. 39.4°
In our own studi es with ~-e ndorphin , we have fo und a

Medial basal hypothalamus
polynomial di stributi on of ~-e ndo rphin in the periph-
era l plasma during th e course of the menstrual cyc le.
Thi s type of distribution is shown for a woman of nor-
mal feitility with a 28-day menstrua l cyc le in Figure 41-
16. In a contro l gro up of 11 pati ents, this di stributi on of
peripheral ~- en dorphin concentration was identified in
each .
At the same time, when one looks at patients who have

endometri os is and inferti 1ity and com pares th em to
.• women ofnormal fe rtility, decreased ~-e nd o rphin leve ls
are observed. This is shown in Figures 37- 17 and 37-18
'"o
Q.
for the first four days ofthe menstrual cyc le and aga in
during the mid-luteal phase (Peak + 7). 1n each ofthese
cases, the ~-endorphin leve ls fo r th e pati ents with en-
dometriosis (and in fe rtility) were stati stically signifi -
Beta Endorphin Curve in Pat ient of

Exhibited Normal Fertility - 28-day Cyc le, Age 41
e
.e
o.. 30
o
"O
e
w-
rtl -É 20
- Ol
Figure 41-15: The site of beta-endorphin regulation of LH ~a. DAY 1
rtl
secretion. Four possible mechan isms by which beta-endor-
phin could inhibit gonadotropin secretion are depicted (1) beta- fü
rtl
10
endorphin which is released into the hypophyseal portal ves- a::
seis and is transported to the pituitary, could act directly on
the gonadotropin. The three other possi bilities depicted in-
volve an interaction with GnRH . This interaction may occur at - 10 -5 Ov. +5 10
the cell bodies in the arcuate nucleus (2) at the nerve terminal
Days ± Ovulation
in the median eminence (3) or at the posterior pituitary gland
(4) (From: Ferin M, vanVugt D, Wardlaw S: The Hypothalamic Figure 41-16: The measurement of plasma beta-endorphin
Control of the Menstrual Cycle and !he Role of Endogenous levels in a patient with a 28-day cycle and exh ibited normal
Opio id Peptides. Academic Press 40:441-485, 1984 ). fertility (From: Pope Paul VI lnstitute Resea rch , 2004).
40 ~~~~~~~~~~~~~~~~~~~~~
P·Endorphin Leve ls els were not evaluated , there was a sign ifi cant improve-
ment in symptoms in those w ho took naltrexone com-
pared to those taking placebo. Naltrexone was first re-
~ 30
leased fo r use in those patients who were heroin ad-
"'a.e:
:ea. dicts and because heroin is an op iate, it has a place as
~ an op iate-receptor antagonist in patients where it might
e:
'l'
20
19.s¡-
1
---------
1 17.2 appear that an increase in the opiate-receptor concen-
.
=
E tration (which has never really been studied) might rea-
ci"' 10 sonably be assumed . In this way, the use of a neutral
- Normal Fertility Control s
--a- lnfertility with Endometriosis opiate receptor antagon ist wou ld decrease the deleteri-
0 .094 0.042 ous effect of that opiate-receptor bond.
1,2 3,4
Day of the Cycle
~-endorphin in the plasma and cul-de-sac fluid ofwomen
Figure 41-17 : Plasma beta-endorphin levels during the first
four days of the menstrual period in women with normal fer- w ith regular mucus cycles and limited mucus has a lso
tility versus those with infertility and endometriosis (From : been studied (Table 4 1-2) . The plasma leve ls in the two
Pope Paul VI lnstitute research , 2004) . groups were not signi ficant ly different. However, the
cu l-de-sac fluid levels were significantly lower in each
ofthe two groups but much more so for the women with
P+7 P-Endorphin in regular mucus cycles. These studi es were performed
Normal Fertility Controls vs.
during the periovulatory phases ofthe cycle. The exact
lnfertility with Endometriosis
significance of these findings has not yet been identi-
..J
fied .
E
e, 20
a.
e: One ofthe cons iderations that has not been adeq uately
:E
a. stud ied up to the present time is the question of the
o
'C
w
e: opiate-receptor bond which clearl y ex ists with ~-endor
"°- phins. ln fact, as ind icated earli er, this ne uroe ndocrine
.."'
E
"'
¡¡: 10
10.96
substance was first thought to exist through an identi-
fication of its receptor. When a person becomes ad-
dicted to heroin or opium , it binds to the op iate-recep-
tors and it has signifi cant effects. It cou ld very well be,
although , to our knowledge, stud ies have not yet been
done in this area, that an endogenous op iate addiction
o (an increased absorption of~ -endorp hin s to the op iate-
Normal lnfertility wilh
Fertility Endometri osi s receptors) is one of the foundat ions for the hypotha-
lamic-pituitary-ovarian dysfunction which appears to
Figure 41-18: Pla sma beta-endorphin levels during the luteal
phase (Peak + 7) in women of normal fertility versus those exist.
with infertility dueto endometriosis (p< .01) (From: Pope Paul
VI lnstitute research , 2004).
Table 41-2: P lasma vs. Cul-de-Sac Fluid Levels of
~-Endorphin: By T ype of Mucus Cycle
cantly lower than the ~-endorphin levels for those pa-
tients with normal fertility. Plasma. Cul-de-Sac
pglmL pg/mL p-valu11
The decreased ~-endorphin leve ls we have observed in Regular mucus cycles 40.6 7.3 <.004 1
(n=8)
the mid-lutea l phase ofthe menstrual cycle are sim ilar to
Limited mucus cycles 38.8* 16.7** <.004 2
that in patients w ith premenstrual syndrome. 4 1. 42 In our
(n=19)
own studies, we have fou nd a very high frequency of
Tota l group 38 .0 13.8 <.0001 2
premenstrual syndrome in those patients w ho have en - (N=29)
dometriosis and infertili ty suggesting a simila ri ty in
1. Aspin-Welch unequal variance t-test.
the pathophysiology of these two conditions. 2 Wilcoxon Rank-Sum test.
• Not significantly difieren! from plasma p-endorphin levels in regular
mucus cycles.
Chuong, et al,43 reported a double-bl ind , placebo-con- .. The cul--Oe-sac levels of beta-endorphin were significa ntly higher !han
beta-endorphin levels in the cul-de-sac flu id of regular mucus cycles
tro ll ed, cross-ove r stud y to evaluate the efficacy of (p=.0 17, Aspin-Welch unequal variance 1-test).
naltrexone on PMS symptoms. While ~-endorphin lev-
Chapter 41 : HPOD and lts Target Organ Effects: lmplicat i ons for Treat men t 553
Other Considerations _________, nism. While much of th e focus ofthi s has been related
to Cushing syndrome, a good deal more research is nec-
The secretory activity of the adrena l gland increases essary to take a look at its effects in women who are
during times of stress. The necessary elements of the under stress and the effects on their menstrual and fer-
adrenal component of the stress response include cor- tility cyc les.44
ticotropin-releasing hormone (C RH ) and, probably, other
hypothalamic ACTH secretogogues such as vaso- lt has been suggested that a stress-ind uced co nnec-
press in , the products that result from the processing of tion between the endoge nou s opioid system and the
the POMC molecule includin g ACTH and the endog- hypothalamic-pituitary-adrenal axis rnay exist in hurnans.
enous opiates W-endorphin) and cortisol. The impact In fact, elevated P-endorphin and cortisol levels have
of CRH on reproductive function has been shown to been observed in human subj ects under stress. The
have profound effects. Studies in the Rhesus monkey, role of P-endorphin and its connection to the secretion
for example, show that an intravenous infusio n ofCR.H of gonadotropi ns provide a physiologic basis for ex-
can completely suppress the GnRH pulse generator (Fig- plaining the relationship between psychogenic stress
ure 41- 19). The effect can be blocked with the adminis- and reproductive function . lt could be that a cornrnon
tration of naloxone suggesting that the endogenous pathway of physiologica l and psychological stress is
opiates mediate, in sorne way, the etfect ofCR.H. While mediated by the release ofC R.H into the hypothalarnus.
the clínica! manifestation of a CRH-mediated reproduc- This has been shown to reduce GnRH secretion and
tive dysfunction has usually been thought of as "stress cause the release ofnorepinephrine vía the sympathetic
amenorrhea," it is quite possible that different stages nervous system and the release of ACT H and P-endor-
and perhaps, more subtle stages, might create dysfunc- phin fro m the anterior pituitary. 30
tion within the otherwise regular menstrual cycle.44
While rnost of the foc us has been on hypotha lamic
Cortisol ca n also effect gonadal function directly. For amenorrhea in the discussion on stress-induced effects,
exampl e, women undergo ing ovu lation induction with it has been shown that ovulatory menstrual cycles can
menopau sa l go nadotropin s have an attenuated re- be induced in these women by the daily adrninistration
sponse to a standard dose of hMG ifthey are receiving ofnaltrexone. After the naltrexone is discontinued , the
a small dose of dexamethasone at the same time. 44 lt has women once agai n become amenorrh eic. These data
been suggested the cortiso l ha an effect on the secre- support a pos ible role of P-endorphin in hypothalam ic
tion of gonadotropins by the hypothalamu and pitu- arnenorrhea. But a consideration must also be given to
itary gland. Stress activates the hypothalamic-pituitary- the possibility that P-en dorphins play a maj or role in
adrenal axis probabl y through the combined action of the hypothalarnic-pituitary-ovarian dysfunction that
CRH and perhaps vasopressin . CRH is a powerful modu- exists in many women's hea lth issues.
lator ofthe GnRH pulse generator and perhaps through
the intermediary action of an op iate-dependent mecha- There is also evidence th at dopamine rnodulates en-
dogenous op ioid tone, raising the possibility of a feed -
ovx OVX - AOX
back loop between hypothalamic opioids and catechola-
mines. Dopamine-receptor antagonists increase levels
of P-endorphin in the hypothalarnus, pituitary and pe-
ripheral serurn of rodents. aloxone studies also sug-
gest that dopamine antagonism results in increases in
endogenous opiate tone. Endogenous catecholamines,
primarily dopamine, appear to inhibit pulsatile LH re-
lease.
Clonidine has also been shown to be signi ficantly more

effect ive than placebo in reducing PMS symptom s
HOU R OF lNFUS ION
whi ch depress leve ls of P-endorphin .45 Cloni dine is be-
Figure 41- 19 : The effects of intracerebroventricular lieved to act at the loc us ceru leus by decreasing
co rticotrophic releasing hormone (CR H) infusion in an ova- amounts of norepinephrine at pre-synaptic sites. Nore-
riectomized monkey befare (left) and after (right) adrenalec-
tomy on luteinizing hormone (LH ) and follicle-stimulating hor- pinephrine is thought to be down-regulated by µ-re-
mone (FSH) secretion (From: Ferin M: Stress and the Gonadal ceptor sites at the locu s ceruleus in op iate addition .
Axis in the Female Rhesus Monkey: Interface Between the When narcotics are no longer ava ilab le, the down-regu-
lmmune and Neuroendocrine Systems. Human Reproduction
8:147-150, 1993).
lation is precluded and rebound fl ood ing ofthe sympa-
thetic system w ith nore pine phrine occurs, prec ipitating w ith E 2-specifi c receptors w ill respond. The receptor
w ithdrawal symptoms. 30 tra n ports the hormone to th e target ce ll nucleus which
leads to the producti on of messenger RNA, protei n syn-
thesi s and a response characteristic for the hormone.
Receptor Physiology _ _ _ _ _ _ _~
The FSH receptors are present on the granul osa cell s
The general pattern of steroid hormone ac ti on includes and are induced by FSH itself. Th e LH receptors are
the fo llowing:46 present on the theca cell s and initiall y absent on the
granul osa cell s, but as th e fo llic le gro ws, FSH induces
1. The uptake of the steroid by the target ce ll in th e appearan ce of LH receptors on th e granu losa ce ll s.
binding to specifi c stero id cytoplas mi c receptor. Gran u losa ce ll s also conta in estrogen-spec ifi c rece p-
tors .
2. Transforn1 ati on of the receptor compl ex to an
acti ve fo rm .
Th e principi e acti on of steroid hormones is regul ation
3. Translocati on o fth e transfo rmed stero id-rece p- of intracell ular protein ynthes is by means ofthe recep-
tor compl ex to th e nuc le us. tors. ln targeted ti ss ues, that respond to steroid hor-
mones by growth (e .g. endometrium), nucl ea r binding
4. Binding ofthi s acti ve compl ex to spec ifi c "ac-
and pro lo nged nucl ea r retenti on directly lead to in -
ceptor" site on the genome (chrom atin D A
creased DNA synth es is. 14
and acidi c non-hi stone protein).
5. Acti vation of the tra nscripti onal apparatus ( RN A Estroge n increases target ti ss ue responsive ness to it-
pol ymerase) resulting in the appearance of new se lf and to progesterone by increasing the concentra-
RN A spec ies w hi ch includes spec ifi c mRNAs. ti on of its own receptor and that of the intracellul ar
progesteron e rece ptor. This process is cal led rep lenish-
6. Transport of the hormone-induced RNA to th e
ment. Progesterone anda drug such as clom iphene limit
cytoplasm and res ulting in the synth es is of new
ti ssue response to estrogen by b locking the rep lenish-
prote ins on cytoplasmi c ribosomes, and
ment mechani sm. Bio log ic acti vity is ma intained only
7. Th e appearance of a specific stero id-medi ated w hil e the nucl ear site is occupi ed with the hormone-
fun cti ona l response characteri sti c fo r that par- rece ptor complex. 46
ticul ar target ti ssue.
The maximum concentrati on of estrogen recep tors oc-
Estrogen receptors are members of the super fa mil y of curs during the mid to late part ofth e proliferati ve phase
nuc lear receptors. Estrogen receptors (ER) existas : ER- of the menstrua l cyc le. Th e relationships of serum and
O: and E R-~ . The o: receptor, th e first one di scovered, is ti ssue leve Is of E2 to total estrogen receptor content are
located in highest abundance in the female re produc- shown in Fi gure 4 1-20. The tissue leve ls of E 2 rise rap-
ti ve tract, especi a ll y the uterus, vag ina and ovary, as idly du ri ng the late proli ferative phase ofthe cycle reach-
well as in the mammary gland , hypothalamus, endothe- ing peak leve ls of over 800 pg/gm of ti ssue pri or to
li a l ce ll s and vasc ul ar smooth musc le. Th e ~ receptor ovul ati on and decline rapidl y after ovu lation . Ti ss ue
has its hi ghest ex press ion in the prostate and ovaries levels of E2 remain low durin g the lutea l phase of the
and less express ion in lung, brai n and vasc ul ature. 14 cyc le despite elevated levels ofE2 . Receptor levels of E2
also reach the ir max imal concentration during the mid-
After entering the ce ll by pass ive di ffusion th ro ugh the to late-proli ferati ve phase ofth e cycle concurrently with
plasma memb ra ne, the estroge n hormone binds to an ti ssue leve ls of E 2• An d like the tissue leve ls of E2, the
E R in th e nucleus. In the nu cleus, the ER is present as a concentrati on of E2 receptors is low in secretory and
monomer and u pon binding e troge n, a change in con- dec idual endometri um. 47
fo rmation occurs that res ults in dimeri zation whi ch in-
creases the affini ty and th e rate of receptor binding to With progesterone, the ti ssue concentrations mimic the
DNA. 14 serum concentrati ons and duplicate the ovarian pattern
of progesterone secreti on ( Fi gure 41 -2 l ). The max ima l
There is onl y a s ing le progesterone receptor ( PR) gene, concentration of progesterone receptors is fo und dur-
but it produces two isoform s of the progesterone re- ing the late proli fe rati ve and ea rl y secretory phases of
ceptor, PR-A and PR-B . 14 FSH stimul ates se lected ova- th e cycle . Thu s, it appea rs that progesterone receptors
rian ce ll s to synth es ize and secrete E 2• Free c ircul at ing are induced during periods of estrogen stimulati on and
E 2 rapidl y di ffuses into the ce ll s, but onl y those ce ll s do not corre late w ith serum or ti ss ue leve Is of progest-
Chapter 41 : HPOD and lts Ta rget Organ Effects : lmpl icat ion s fo r Treatment 555
eron e. I n fact, it i s now ui~ d erstood that E 2 induces th e sis and in a gro up of wom en w ho served as contro l
synthes is ofp roges terone recep tors. 4 7 Estradi ol ind uces subj ects . These data are shown in Figure 41-22 . It was
th e sy nth es i s of both rece p to r s. W heneve r t hese noted th at the LH receptors began to decrease in the
mechani sm s are d isturbed, undes irab le res ul ts or dy s- last week pri or to th e onset of menstru ati on and conti n-
functi on m ay occur. ued to be decreased during th e first two w eeks of the
subseq uent cycle i n pati ents w ith endometriosis. l t was
As early as 1984, an LH receptor di sorder was identifi ed suggested that end o m etri osis-assoc i ated i nfertility
in women w ho had endometri os is. LH receptor concen - mi ght be a consequence of a defect in the mechanism
tration s in ovari an fo lli cles and corpora lutea were mea- m ed iating LH acti on in th e ovari es .48
sured in patients with histo logicall y proven endometri o-
l n th e cerv ix , estroge n receptors have been fo und to be
300 either absent or decreased in women w ho have poor
cerv ica l mucus49 (F igure 4 1-23). These pat ients ali had
E 250 regu lar menstrua l cyc les and sorn e of them had en-
24>
dometriosis. Jt was suggested th at an estroge n recep-
"' 200
...J
E
o,
c.150 E 12
o " 11
'5 ~ 10
E 100 ..J 9
tí E 8
4> gi 7
o 50 6
e"
e 5
4
A $ 3
-10 .5 o 10 "e"'"' 2
/l. ót..._~~~!!!!!!!l!!!!!!!!!!!!t!~!........__~.._~~ A
-10 .5 10
1000
4>
:::l
"'
"' 800
:;::
25
.!:!}
~ 600
" 20
o "
'5 400 ~"'
E .E'
tí4> 200
g' 15
o "eo
B Q;
üí 10
-10 .5 o 5 10
""'e
/l.
e:
·¡¡; 10
ec.
9 B
Cl
.§
o 7 e
~
[
....
6 e
Q. 3.0
o 5
c. .É"'
fl 4 ~ 2.5
~ c.
~ 2.0
2 .,,
o
~ 1.5
e sc.
-1 0 -5 o 10 ~ 1.0
E
Day from LH peak "e o.s
$
Figure 41 -20 : The serum (A), ti ssue (B), and receptor (C)
""'e"' -10 .5 10
e
concentrations of E2 during th e menstrual cycle of ovu latory /l.
women . The data were normalized to the time of ovulation. Day from LH peak
The LH surge was used as a marker of ovulation . The shaded Figure 41-21: The serum (A), tissu e (B), and receptor (C)
areas of each line represen! the mea n standard error (From : concentrations of progesterone during th e menstrua l cycle
Edman CD : The Effects of Steroids on the Endometrium . In: (From: Edman CD: The Effects of Steroids on the Endometrium.
Speroff L, (Ed ). Seminars in Reproductive Endocrinology. In: Speroff L, (Ed ). Seminars in Reproductive Endocrinology.
1:179-187, 1983) . 1179- 187, 1983) .
- Control 10 In this case, mueus eycle seores ofa ll the differen t types
- Endometriosis
• of ovu lation-related anatom ica l disorders are deereased .
However, in the delayed rupture syndrome and the par-
8 - tial rupture syndrome with a positive eumulus oophorus,
the data were not statistically sign ificant. In ali other
3 • • cases, the data are striking ly statistieally signi fica nt.
• • This suggests that there is a commonality between the
•
e:
:!o
... 2
•
•
6
-
•
8
o
o
•
1- 1-
estrogen effect on the endocerv ix and the LH effect,
and perhaps an FSH effect on the deve loping fo llic le
and its rupture. The data presented on receptor dys-
---- •
o
Q.
Cll
• 4 ~ function suggest thi s possib le mechanism.
ñí 8
.J:J c9
Cll 1
Ol
•# In Figure 4 1-26, the Peak + 7 FSH levels are shown for a
o
rt
o
E 1
o
group of patients who ha ve different types of mucus
~
o 1
•
• o 2 cycles. As the mucus eyc le beeomes more and more
Ol
.E • • c9 •• o c9
o
o
• limited (with the exception of dry cyc les ofwh ich onl y
E
LL o
• o two patients were studied), the FSH levels on Peak +7
e • increased as the mucus cycle beeame more and more
o o
6-1 0 6-10 11-1 5 11-15 14-19 14-19 20-30 20-30
limited. Thedifference between the Peak +7 FSH leve! in
Day of Cycle Day of Cycle
women w ith limited mucus eycles (5.09) and those with
Figure 41-22 : The LH receptor concentrations in the graa- regular mucus eyeles (3. 19) is statistica ll y sign ifi cant
fian follicles of patients without (. ) and with (o) endometriosis (p=<.05).
during the early (Cycle Day 6-1 O) and late (Cycle Days 11-15)
follicu lar phase of the menstrual cycle and during the early
(Cycle Days 14-19) and late (Cycle Days 20-30) luteal phase Asan additiona l set of observations, we ha ve looked at
of the menstrual cycle. The only comparison that is not statis- the ~-endorphin levels in the serum ofwomen who had
tically different is the day 14-1 9 comparison (From : Ronnberg limited mucus eyc les versus nom1al mucus cycles (Table
L, Kauppila A, Rajaniemi H: Luteinizing Hormone Receptor Dis-
order in Endometriosis. 42 :64-68 , 1984 ).
41-2) . There was no statistica ll y signifícant difference
~ 70
tor deficiency might existas a possible related factor
-'1: •
rn
with regard to poor cervica l mucus. This is consistent
o
with our own observation of patients with endometrio-
60
sis who have limited mucus cycles or dry cycles using O> 2
the CrMS. The incidence oflimited mucus and dry cycles .§ 50
in that population is 77 percent. 111
Q)
In another study of inferti lity patients and endometrial ~ 40

receptors, the ER was fo und to be signi fieant ly lower in o •
out-of-phase endometria. 50 'EQ,) 30
In our own work in looking at mucus cycle seores in
u..
o:: 20
o
.,•
women ofnonna l ferti lity and women who have infertil- w
ity, we have identifíed a sign ifi cant decrease in the mu- o 10
-
111
cus cyele score ofwomen with regular cycles who have o •
in fert il ity and in women with endometriosis. The mucus >. 0 ~~~~0~~~~~f#/####/##á
u Gp 1 Gp 2
cycle seores in women with pelvic adhesive disease are
also deereased, but not statistieally signifícant (F igure
Figure 41-23 : Cytosol estrogen receptor (ER) conce ntra-
41-24).
tions in fentomoles/mg protein in endocervical biopsies. In
group 1 (inferti lity patients with poor cervical mucus) and
When thi s is combined with data from elass ifícation of group 2 (pa tients with normal ferti lity). Less than 3 is nega-
ovu lation-related defects by ultrasound , the data shown tive. lntermediate or borderline 3-20. Positive greater than 20.
The horizontal line indicates the mean of the cytosol ER con-
in Figure 41-25 are obtained. This is a comparison of a centrations . There is a significan! difference between the
group ofpatients and their mueus cycle seore who have two groups (From : Abuzeid MI , Wiebe RH , Aksel S, et al:
normal ferti lity with those patients who have infertility Evidence far a Possible Cytosol Estrogen Receptor Deficiency
and documented disorders of ovulation by ultrasound . in Endocervical Glands of lnfertile Women with Poor Cervical
Mucus. Fertil Steril 47101-107 , 1987).
Chapter 41 : HPOD and lts Target Or gan Effects : lmpl icati ons for Treatment 557
Mucus Cycles
Mean Mucus Cycle Seores in Patients with
Normal Fertility vs. Patients w ith Regular Menstrual P+7 FSH Level
5.0
Cycles and Various Organic Conditions Limited vs. Regular
4.23
B.5 p= .0.161
4.0
G 3.56
"i5 ]
bl 6.9
6.7
"
~ 6 3.0
ü :r:
Cl"J
u..
,..,
V)
2.0
"
Cl
1.0
Pe Me AH lnlert1lity Endometnos1s MCS 7.6-16.0 0.1-7.5

Adhes1ons Regular Cycles N=206 Regular L1mucd
N:41 N=299 N= l04 N=78
p=.1670 1 p< .0002 1 1 p< .000 1 I Mucus Cycle Classification and Score
Figure 41-24: The mean mucus cycle seores in patients with Figure 41-26: The mean level of follicle stimulating hormone
normal fertility versus patients with regular menstrual cycles, (FSH ) on Peak+ 7 (mid-luteal phase) during the same cycle in
infertility and various organic conditions (From : Pope Paul VI which the mucus cycle was scored and classified . Th e dif-
lnstitute research , 2004). ference between the FSH level for regular mucus cycles
(3.56) and limited mucus cycles (4.23) is statistically signifi-
can! (p<. 05) (From: Pope Paul VI lnstitute research , 2004).
Mean Mucus Cycle Score in Patients with

Normal Fertility vs. Patients with Documented
10 9.3 Disorders of Human Ovulation by Ultrasound
7.6 7.4
~ 6.6 6.6
o 6.4 6.2
o 6.2 6.0
Cf)
5.3
u"'>. 4.9
ü 5
<I)
::>
o
::>
::;;
o Normal DAS PRS+ Ali LUF:- Ali Ali MF:- All lFS- PRS-
Fertility N=1 1 N=10 lFS N=16 LUF PRS N=60 CO- N=14 N=6
Control NS NS N=35 N=38 N=18 N=96
N=62
1 p<.004 1 ~ le<.00021 ~ I P<.0001I IP<0001I 1P<.001 1 ~
Ultrasound Disorder of Human Ovulation
Figure 41-25: The mean mucus cycle score in patients with normal fertility versus patients with
documented disorders of human ovulation by serial ultrasound examination (see Chapter 20)
between the plasma ~- e ndorphin leve ls in those two Receptor Deficiency Syndrome?_ _~
populations. However, when one looks at the cu l-de-
sac fluid levels in patients with in fertil ity, there is a sig- An enormous amount of work has been done over the
nificant decrease in the ~-endorphin leve! in patients last 30 years on the clarification ofthe interactions be-
with infertility. When the cul-d e-sac fluid ~ -e ndorphin tween the hypothalamus, pituitary and ovarian ax is. The
leve! is eva luated from the point of view of a regular di scovery ofG nRH and work relati ve to ~-endorphins
mucus cycle ora limited mucus cycle, it was fo und that has increased our understanding significantl y. Clearl y
the limited mucus cyc les had increased leve ls of ~- en there is evi dence for abnorma l function ofthe hypotha-
dorphin in the cul-de-sac fluid and th at it was statisti- lamic-pituitary axis in vo lving a dysfu ncti on of gona-
ca lly significant (p=.O17). dotropin-releasing hormone and its stimulation of FSH
and LH. Data relative to endocrine abnormalities ob-
served in patients with in ferti lity and regular menstrual
cycles along with women with other apparent hormona l
dysfunctions (s uch as premenstrual syndrome) suggest
that this has a cascading effect on the stimul ati on, or Indirect ev idence of thi s is suggested by observati ons
lack th ereof, of th e ova ri an ste roi ds , estroge n and made with the CrMS in which women w ith infe rtil ity and
progeste ro ne . regul ar menstrual cycl es have a strong tendency to-
wards decreased mu cus producti on in spite of other-
lt seems reaso nabl e that th ere wo uld a lso be a receptor w ise, at least at times, norm al peri ovul atory estrogen
defi ciency that could be identified and eventually treated leve ls. Furthermore, th e eva luation ofthe structu ra l in-
and that along w ith the endocrine abnorrnality, increased tegri ty of th e ovul ati on process by ultraso und suggests
hope fa r patients with these condi tions. In fac t, there is th at there is a stro ng correlation between ovu lati on-
evidence of an estrogen rece ptor dysfuncti on in th e related defects and the occurrence of in fe rtili ty or mi s-
endocervix of pati ents w ho ha ve poor mucus and in fe r- carriage. Whil e ali of these considerati ons may not prove
tility, as we ll as, an LH receptor dysfun cti on in the ova- to be universa l, that is to say, the only ultimate probl em
ries of women with endometriosis. Fwthennore, endome- that ex ists in these situati ons, it is very reason abl e to
tri al receptors ha ve also been fo und to be dys fun ctional suspect that s uch a receptor defici ency syndrome ex-
in pati ents with infe rtili ty. lt is quite likely that receptor ists, and that, in fact, mov ing towards treatment ofsuch
dysfun cti on a lso occ urs in the fa ll op ian tu be and the could enh ance th e effecti ve ness of therapeut ic pro-
myometriwn . grams.
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26. Li C H: Lipotropin , A New Active Pepti de from Pituitary
4 1. Chuong CJ, Co ulam CB, Kao PC, et al: Neu rope ptide Levels
Gland s. Nature 20 1:924, 1964 .
in Premenstrual Syndrome. Fert il Steri l 44: 760, 1985.
2 7. Goldstein A, Tachibana S, Low ney LI , et al: Dynorphin ( 1-
42. Facchinetti F, Marti gnoni E, Petragli a F, et al: Premenstru al
13) - An Ex traordin ary Potenl Opioid Pepti de. Proc Na tl
Fall of Pl as ma Beta-end orphin in Patients with Premen-
Acad Sc i USA. 76 :6666, 1979.
stru al Sy ndrome. Ferti l Steril 47:570 , 1987 .
28. Wilkes MM , Watkin s WB , Stewa rt RO, et al: Locali za ti on
43. Chu ong CJ, Co ulam CB, Bcrgstralh EJ, et al: Cl ini ca l Tri a!
and Quantilation o f Beta-e nd orphin in Hum an Brain and
of Naltrexo ne in Prem enstrual Syndrome . Obstet Gyneco l
Pituitary. Ne uroend oc rin ology 30: 113, 1980.
72:332, 1988.
29. Watkin s WB , Yen SSC, Moore RY: Presence of Beta-endor-
44 . Loriaux L, Nieman S: Stress and Reproducti on: The Role of
phin-like lmmunoreacti vity in th e Anterior Pituitary Gland
Coni so l: In: Yen SSC, Vale WW (Eds). euroendocrine Regu-
of Rat and Man and Eviden ce for th e Di fferentrn l Localiza-
lati on of Rep rod ucti on. Serono Sym posia 307-3 1 1, 1990.
ti on with ACTH. Ce ll Tissue Res. 2 15:577, 198 1.
4 5. Giannini AJ, Su lli va n B, Sarachene J, et al: Clonidine in the
3 0. Seifer DB, Co llin s RL: Current Concepts of Beta-endorphin
Treatm enl of Premenst ru al synd rome: A sub-gro up study. J
Phys iology in Female Reproducti ve Dysfun cti on. Fertil Steri l
Clin Psyc hiatry 49:62, 1988.
54:757-771, 1990.
4 6. Gru hn JG, Kazer RR: Horm onal Regulation of the Menstrual
3 1. Guill emin R, Vargo T, Rossier J, et al: Beta-en dorphin and
Cyc le: The Evo lution of Concept s. Pl enum Medica! Book
Ad renocorticotropin are Sec reted Co ncomitan tl y by the
Co mpany, New York , 1989.
Pituitary G land. Science 197: 1367 , 1977.
4 7. Edman C D: The Effects of Ste roid s on th e Endom etrium .
32. Morl ey JE : Th e End oc rin ology of th e Opiates and Opi oid
In : Speroff L (Ed) Seminars in Reproductive Endoerinology.
Peptides. Metaboli sm 30: 195, 198 1.
1:179- 187, 1983.
3 3. Grossman A, Rees LH: The euroe ndoc rinol ogy of Op ioid
48. Ronnberg L, Kauppil a A, Raj aniemi H: Luteinizing Hor-
Peptides. Br Med Bul 39 :83, 1983.
mone Receptor Disorder in Endometriosis. 42:64-68, 1984.
3 4. Barrac lough CA, Sawyer CH: lnhibiti on o f th e Release of
49. Abuze id MI , Wiebe RH , Ak se l S, et al: Evidence for a Pos-
Pi tui tary and Ovu latory Horm one in the Rat by Morphine .
sib le Cytoso l Es trogen Receptor Deficiency in End ocervi -
Endocrinology 57 :329, 1955.
ca l Glands of lnfe rt ile Women wi th Poor Ce rvica l Mucu s.
35. Pang CN , Zimmerman E, Sawye r CH: Morphine lnhibition Fertil teril 4 7: 10 1-1 07 , 1987.
of the Preov ulatory Su rges of Pl asma-Luteinizing Hormone
50. Hi ra ma Y, Ochiai K: Estroge n and Progestero ne Receptors
and Follic le-Stimu latin g Horm one in the Ral. Endocrino l-
of the Out-of-Phase End ometrium in Female lnfertile Pa-
ogy 101:1726 , 1977.
tients. Fe rtil Steril 63 :984-988, 1995 .
Endometriosis and lts Effects on Fertility
terval. 8 Severa! examples of its appeara nce are shown in

E ndometriosis is a di sease marked by the ectop ic
implantation of endometrial ti ssue in locations other
than the intrauteri ne cavity. The first known descripti on
Figures 42-1 through 42-7.
of thi s disease was by a German physician , Daniel Diagnostic laparoscopy req uires a " near-contact" tech-
Shroen , in 1690. 1 lt is thought to affect abo ut 5 million nique and a thorough understanding of the va ri o us
Ame rican women; 2 a lth o ug h, that is almost for certain appearances of endometriosis. Thi is ali detailedin later
an unde restimate. The research regi stry of the En- chapters ofth is textbook. To assist the surgeon in these
dometriosi s Assoc iation , in an ana lysis of 3,020 case techniques, newer laparoscopes with a11iculating shafts
histories, notes the following symptoms associated w ith w ith a video camera in the tip of the scope have bee n
endometriosis: dysmenorrhea, pelvic pain, dyspareunia, developed and are improving visualization. " Blue light"
infertility, heavy or irregu lar bleeding, nausea at the time techniques have also bee n deve loped to ass ist in the
of menses, diarrhea and/or painful bowel movement, visua li zation espec ially of mi croscopi c e ndometrios is. 9
di zziness, headaches w ith men es, fatig ue, low-grade
feve r and low resistance to in fect io n.3
Diagnosis ____________~
C linica l hi story, phys ical exam ination and other no nsur-

gica l attempts to diagnose e ndometriosis are notoriously
in error. 4,; The "gold standard" for di agnosis is a di ag-
nostic laparoscopy with hi sto logica l co nfir matio n.6 · 7
Laparoscopy sho uld be performed in the first halfofthe
menstrua l cyc le (the pre- Peak phase) because laparos-
copy is often combined with la parosco pi c treatrnent,
a nd treatme nt prior to me nstru ati on is associated w ith a Figure 42-1: Peritoneal implants, incl uding hemosiderin de-
posits, on the left and right posterior bladder (From: Pope Paul
hig her recurrence rate with a sho11er recurrence-free in-
VI lnstitute research , 2004).
561
Figure 42-2 : Hemosiderin deposits deep in the posterior cu l-

de-sac consisten! with a diagnosis of endometriosis . The
small black spots (pepper spots) are carbon deposits from
previous laser vaporization (From: Pope Paul VI lnstitute re-
search , 2004).
Figure 42-3: Endometriosis on the left ovarian ligamen!, pos-

terior wall of the uterus, and the left ovary. The ovarian liga-
men! is adhered densely to the posterior broad ligamen! on
the left side and the left posterior portian of the uterus (From :
Pope Paul VI lnstitute research , 2004).
Figure 42-5 through 41-7 : Peritoneal defects are observed

in the left and right posterior broad ligamen! in Figure 42-5 .
Closer observation in Figure 42-6 allows sorne suggestion of
endometriosis deep in the pseudodefect. As !he laparoscope
gets closer in Figure 42-7 , the lesion of endometriosis can
clearly be seen (From : Pope Paul VI Jnstitute research, 2004) .
Figure 42-4: Endometriosis on the anterior rectum (From :

Pope Paul VI lnstitute research , 2004 ).
Chapter 42 : E n domet riosis and lts Effec t s on Fe rtil ity 563
Location of Endometriosis_____~ ma lignancy arising from endometriotic deposits, and

there is substantial hi stologic ev idence that endometrio-
Redwine has published a thorough evaluation of the sis can be associated with endometrioid carcinoma and
anatom ic di stribution of endometriosis in 1,785 patients clear-ce ll carci noma of the ovary. 27 lt has even been
(Tab le 42- 1). This distribution is very similar to what we identified in men.28
have fo und in our involvement with thi s disease. What
is most striking is the involvement of the peritoneum as
the major location and site (over and abo ve the ovary) Pathogenesis _ _ _ _ _ _ _ _ _ _~
and the relative lack of in vo lvement of the fa ll opian
tubes. In addition, the frequency with which the sig- Endometriosis is as close to a malignant disease as one
moid colon, anterior rectum, terminal ileum and cecum can get while still remaining beni gn (Table 42-2). Those
are invo lved is striking but must be specifica lly evalu- aspects of endometrios is whi ch are similar to malignant
ated at the time of laparoscopy. 10 di sease include its ab ility to metastasize both locally
and distantly, the ab ili ty to attach to other ti ssues and
Endometrios is has also been found in a variety of other invade and damage them, andan ability to exhibit cellu-
locations. These would include the lung, 11 - 14 ureter 15- 17 lar pro li feration , cel lul ar invasion and neoangiogenesis.
(evento the extent ofrena l damage 18) , the diaphragm , 19-
2 22
20 the sciatic nerve, 1. the perineum , 23 · 24 the uterine The pathogenesis of th e disease most likely represents
25 26
artery, and the liver. In additi on, it can undergo ma- many different poss ib le pathways. The class ic exp lana-
lignant transform ation; alth ough, thi s is not common. tion is one of retrograde menstruation. However, it can
There are, nonethe less, numerous reported cases of also be spread hematologically and lymphatically, it
has a genetic predisposition, there are omnipotent cells
whi ch may give ri se to it, impaired cellular immunity
Table 42-1 : Anatomic Distribution of
may pl ay a ro le, and it can be surgically transplanted
Endometriosis in 1, 785 Patie nts treated
(Table42-3).
SurgicaUy by R edwine
No. of Patlents with The most commonly expressed theory is that of retro-
lnv o lvement Of sité (% )
gra de menstruation . Th is was fir st de sc ribed by
Site Of Endometriosis n %
Pelvic (n = 1,781) 1
Cul-de-sac 1,202 72.2
Left broad ligamen! 865 52 .0 Table 42-2: Aspects of Endometriosis that are
Left uterosacral ligamen! 744 44 .7 Similar to Malignant Disease
Right broad ligamen! 722 43.4
Right uterosacral ligamen! 689 41.4
Bladder 546 32.8
Left ovary' 303 18.2 • Can be both locally and distantly metastatic
Right ova ry' 290 17.4
Fundus' 265 15.9 • Attaches to other tissues and invades and damages
Left fallopi an tube 154 9.3 them
Right fallopian tube 111 6.7 Exhibits cellular proliferation , cellu lar invasion
Left round ligamen! 59 3.5 and neoangiogenesis
Right abdominal wall 54 3.2
Left abdominal wall 41 2.5
Right round ligamen! 29 1.7
Intes tinal (n = 453) 3

Sigmoid 297 17.8
Rectal nodule 213 12.8
lleum 69 4.1 Table 42-3: What Causes Endometriosis?
Cecum 33 2.0
Appendix' 45 2.7
Severa! Factors are lnvolved
Note: Total of percentages exceeds 100% because most patients had more
than one area of involvement.
1. Four patients had only intestinal endometriosis with no pelvic involve- • Retrograde menstruation
ment
Hematolog ic or lymphatic spread of endometrial cells
2. One hundred ninety-four patients with endometriosis with previous hys-
terectomywith orwithout castration have been excluded. Genetic (hereditary)
3. One hundred fifty-four patients had more than one intestinal area of
endometriosis. • Presence of omnipotent ce lls
4. Sorne patients had previous appendectomy. • lmpaired cellular immunity
From: Redwine DB: Ovarian Endometriosis: A Markerfor More Extensive Surgica l transplantation
Pelvic and Intestinal Disease. Fertil Steril 72:310-315, 1999.
Sampson. 29 The basic theory is that women. during the which the disease can be positively identifí ed . In these
course of their menstrual flow, will ha ve endometrial same cases , pelvic ultrasound examination is of some-
cells which flow backward through the fallopian tu bes, wha t limited val ue un less there are ovarian endometrio-
land at various sites in the pelvic cavity and implant mas . Peritoneal endometrios is, for the most pa1t, cannot
themselves. The troubling part ofthis theory has been be detected by ultrasound.
that nearly ali women ha ve retrograde menstruation to
sorne extent but ali women do not get endometriosis. 30·31 Over the years, there has been a good dea l of discus-
Thus , there must be sorne other aspect to this event s ion as to whether or not ovari an and lutea l phase dys-
which makes the person who gets endometriosis par- function occur in women who ha ve endometri os is. T he
ticularly susceptible to it. This may be an impaired cel- possibility that luteal phase a nd receptor dysfunction
lular immunity. The basic defenses aga in st the forma- occ urs in this gro up of patients has been both sup-
tion of endometriosis would be seem to be the immune
mechanisms. These mechanisms are clearly suppressed
Table 42-4: Severity of Menstrual Cramps in
in women who ha ve endometriosis and thus retrograde
Women with Endometriosis (N =327)
menstruation may become a v iab le option for the de vel-
opment of this disease. Severity of Dysrnenorrhea n %
Severe 132 40.4

There is no question that lymphatic and vascular spread
Moderate 63 19.3
can also occur, and this wou ld explain metastases that
Mild 65 19.9
are distant. In addition , endometriosis has been ob-
Non e 67 20 .5
served in the pelvic lymph nodes of approximately 30
From: Pope Paul VI ln stitute research, 2004.
percent ofwomen with the di sease. 3 1 While lymph node
dissection is not generally part of the surgical proce-
dures involved in the treatment of endometriosis, this
involvement of the pelvic lymph nodes might be one
explanation for why pelvic pain is not erad icated in sorne Table 42-5: Patients with Endometriosis
women who have surgica l treatment of endometriosis. lncidence of Normal Pelvic Exami nation
(N =336)
The ce lomic ep ithe lium , from which the müllerian duct
Pelvic Exarn n 31,2
is derived during fetal development, may undergo meta-
plasia and thus give rise to endometriosis. This multi- Retroverted uterus 62 18.4
Cul-de-sac nodules 45 13.4
potential cellul ar development would expla in why en-
Tender uterus 34 10.1
dometriosis can be observed in prepubertal gi rl s, women Tenderadnexa 16 4 .8
with the congenita l absence ofthe uterus and (rare ly) in Deviated uterus 9 2.7
men. Normal pelvic exarn 189 56.2
1. Also includes: enlarged uterus (n;4. 1.2% ); uteru s irregular in
Endometriosis bas also been observed in the abdomi- shape (n;2, 0.6%); double cervix, utenus (n-1 , 0.3% ) and deferred
examinations, (n-2, 0.6%).
nal wall after cesarean section and in the periumbilicus.
2. Total ad ds to greater than 100 percent becau se in sorne cases
This supports the theory ofits ability to be transplanted. more than one abnormality was observed .
Association with lnfertilitY -----~
In our own population of patients, the most common Table 42-6: T he Creighton Model System:
symptom seen is that of infertility. These women a lso Types of Mucus Cycles in Patients with
ha ve symptoms of dysmenon-hea (Table 42-4) and pel- Endometriosis treated with
vic pain . On physical examination , the majority have a Conservative Surgery (N=l5 2)
normal pelvic exam (Table 42-5 ). While man y see pelvic Type of Mucus Cycle n %
pain , dysmenorrhea, and dyspareunia as the three ma-
Regular 34 22.4
jar symptoms associated with endometriosis (along w ith Limited• 102 67 .1
abnom1al bleeding), in the infertility population , it is Dry• 16 10.5
quite common for the severe dysmenorrhea to be ab- Total 152 100.0
sent and for the patient to have a normal pelvic exam. 77 .6% is limited ar dry
Thus, diagnostic laparoscopy becomes the on ly way in
Chapter 42 : Endometriosis and lts Effects on Fertility 565
ported and rejected .33 -40 In our own stud ies, we have terone and estradio l- 17~ (E 2) profile is shown in Figure
found a very high incidence ofboth limited mucus cycles 42-8, in a patient with endometriosis_ Her mucus cyc le
and dry cyc les in patients with endometriosis who are score is 4. 7, the three-value periovulatory E2 sum was
charting the CREIGHTON MODEL System (CrMS). In 41 .6, and her postovulatory progesterone sum was 57. 7
Tab le 42-6, a series of 152 patients who underwent a and E2 sum 41 .8. The average mucus cyc le score in a
conservative surgery for endometriosis are shown with group of patients with infertility and endometriosis is
the category of their mucus cyc le identified. Of this 6.7 and is shown in comparison to normal fe11ility in
group, 67. 1 percent had limited mucus cycles and 10.5 Table 42-7.
percent had dry cyc le (77.6 percent either limited or
dry). Thi s wou ld compare to about a 20 percent inci- 1n a group of patients who had endometriosis and were
dence of limited mucus cycles (a nd only rarely dry tudied hormonally, the periovulatory E2 peak was some-
cycles) in a normal fertility population. What is addi- what suppressed and the postovulatory progesterone
tiona ll y interesting about this population is that, in the profile was found to be markedly decreased (Figures
16 patients who had dry cycles, only one of them be- 42-9A through 42-9C). The postovulatory E2 pro file was
came pregnant and she had a tuba] pregnancy. An ex- not significantly different from the contro ls. This sug-
amp le ofth is type ofpattem with its associated proges- gests that there is a strong frequency ofType 11 luteal
phase deficiency in patients who have endometriosis.
Table 42-7: Mean Mucus Cycle Score of
Patients with Normal Fertility vers us The incidence ofType 1, 11, and 111 luteal phase defects
Patients with lnfertility and Endometriosis in patients with endometriosis is id entifi ed in Table 42-
8. In this group of 228 patients, a luteal phase defect
MeanMucus was observed in 54 percent ofthe patients studied . The
Group n Cycle Score
most common type of defect was a Type 11 luteal phase
Normal fertility controls 62 9.3 deficiency. The progesterone profile during pregnancy
Endometriosis 206 ~ is decreased , as wel l, and is shown for a group of pa-
1. From: Pope Paul VI lnstitute research. 2004.
tients with endometriosis in Figure 42- 1O.
33 34
r I I r r
1,;a IM a .;is 0 .16
~ ~ CR.
41.8
8.4
Figure 42-8: This Creighton Model chart from a palien! with endometriosis shows a mucus cycle score of 4.7 anda post-Peak
phase of 15 days. The follicle was mature, had a positive cumulus oophorus and ruptured completely. However, the periovu-
latory E2 sum is somewhat decreased as is the postovulatory E2 sum (From : Pope Paul VI lnstitute research , 2004).
30 Periovulatory Estradiol-17P Levels 3 and 4 Value Perlovulatory 100

Control (N=21) vs. Endometrlosls E, Sums and Means
Control (N=21) vs. Endometrlosis 90
25 - Control 60
- Study group
::::¡ NS
70 (/)
:g,
~
633
.:.
=
,._ 20 60 m
~ ~
"'~ 50 ~
~ 15 40 ""
E
12 8 ~
~ 12 0 30 ~
10 96 20
88
10
N•
NS
103
NS
161
Gfil
182
NS
156
E,-4 Er 2 Peak E, E,+2 3 value 4 value 3 value 4 value

Relationshlp to Peak E2 Level ns137 n=84 n• 137 n•264
Sum Meen
Figure 42-9A
Post-Peak Progesterone Profile Sums and Means
Control (N=57) vs. Endometrlos ls Control (N=57) vs . Endometrlosls
~~~~~~~_:_~-'-~~~~~~~~~~~~~..C....~-'-~~~~~~~ 100
- Control
- Study group 90
15
80
i.,e 10
94
i
a.
E
86
81
67
2
c?l 5
20
10
p= ~ l < .001 1 1<00011 1<0001 1 @I]
N= 266 294 296 282 252
P+3 P+5 P+7 P+9 P+11
Figure 42-98
100
Post-Peak Estradlol-17 ~ Proflles Post-Peak E s trad l ol - 17 ~
Control (N=57) vs. Endometrlosls Sum1 and Mean1 90
Control (N:.57) va. Endometrlo1ls
15
80
12.2
::::¡ 70 g>
i NS
60
2
3
=
:::
~
10
10.6
88
9.8
8.9
54.2
50
i
5·
::;:
~ =
....
iíl 40
E ~
2 a:
c?l 30 !::::
5
20
10
p• NS NS NS ~ NS
N• 270 284 295 272 226
o o
P+3 P+5 P+7 P+9 P+11 Sum Mean
Days Post-Peak N=218 N•21 8
Figure 42-9C
Figure 42-9A through 41-9C: T he pe riovulatory E2 p rofile and the postovul atory
progesterone and E2 pro file in a la rge group of patie nts wit h e ndo m etriosis . The peak
level of E2 in the periovulatory phase is sig nifica ntly d ecreased a long with the three
va lue sum and mean . The postovulato ry progeste ron e profile , how ever, is m a rkedly
sup pres sed . The post-Peak e stradiol p ro fil e is basica lly in the normal ra nge (Fro m :
Chapter 42: Endometriosis and lts Effects on Fertil ity 567
150.0 148.4 These patients with endometriosis were also studied

139.8
from the point ofview ofthe ultraso und characteristics
oftheir ovu lation patterns. This is shown in Table 42 -9.
103.4
In 33 1 patients who underwent serial ultrasound exam i-
100.0 97.8
nation for identification of eith er an anatomica lly nor-
::r mal ovulation or a defective ovu lation by ultraso und
E 73.8
e, 87,!1
.:. parameters, it was found that 39.6 percent did have a
~
e
e 50.0
!52.•
'48.8 normal ovulation pattern but 60.3 percent of them had
~ an abnormal ovulation pattern. The most common three
~
o.. ovulation defects observed were, in descending arder:
o.o
a mature fo lli cle with a negative cumulus oophorus, a
.02 NS
1·12WHkS
.01
20·24-kl 21·30WHkl
.O• NS
32·3fWHkl
luteinized unruptured fo ll ic le, andan immature fol licle.
Figure 42-1 0: The progesterone profil e during pregnancy, at

six weekly intervals , in a group of patients with known en-
Finally, plasma ~-endorphin levels ha ve al so been stud-
dometriosis compared to a group of normal constro ls. ied in patients with in ferti lity who ha ve endometriosis.
The results of that eva luation are shown in Figure 42-
11. The mid-luteal phase ~-endorphin leve ls in those
patients with infertili ty were significantly decreased
Table 42-8: lncide nce of T ype 1, Il, and lll (p<O.O 1) from the normal fert ili ty controls. Keep in mind
Luteal Phase Defects in Women with lnfertility what has been previously pointed out in this textbook
and Endom.etriosis (N=228) with regard to patients who ha ve regular cycles, infertil -
ity and endometrios is. This group ofpatients also has a
n %
high incidence ofpremenstrua l symptoms, making the
Normal luteal fun ction 105 46 .0 underlying endocrinopathy sim ilar to that observed in
Type 1 defect 15 6.7 women with premenstrual syndrome.
Type 11 defect 84 36.8
Type 111 defect 24 10.5
Total 228 100.0
Classification System _ _ _ _ _ _ _~
From: Pope Paul VI lnstitute research , 2004.
A number of classification systems ha ve been devel-

oped over the years in a rd er to stage the degree to
which endometriosis is present. However, the most com-
mon one used is that developed by the American Soci-
P+7 ~-Endorphln In Normal Fertlllty Controls vs. ety for Reproductive Medicine. The most recent such
lnfertlllty wlth Endometrlosls
classification system, developed in 1996, is found in
Figure 42-12.•1 This is the classification system used in
thi s textbook .
..J
~ 20
e:
:.E
e- Table 42-9: lncidence of Ovulation-related Defects
º
'O
e:
UJ as Determined by U ltrasound Assessments: Patients
di
with Endometriosis and lnfertili ty (N=331)
"'~ 10.96
~ 10 Type of Ovulation Pattern n % n °/o
Normal ovulation by u/s 131 39.6

mature follicles, CR , +CO
Abnorma l ovulati o n by u/s 200 60.3
Mature follicle (-C.O.) 67 20.2
o Luteinized unruptured follicle 54 16.3
Normal lnfertility with lmmature follicle 34 10.3
Fertllity Endometriosis Partial rupture 23 6.9
Delayed rupture 12 3.6
Fig ure 42-11: P-endorphin levels in normal fertility controls Afollicularism 10 3.0
and patients with infertility and endometriosis drawn on Peak
Totals 331 99.9
+ 7 (midluteal phase). The P-endorphin level in the patients
with endometriosis is significantly decreased (p<0.05) (From : From : Pope Paul VI Division of Reproductiva Ultrasound, 2004 .
American Society for Reproductive Medicine

Revised Classification of Endometriosis
Patient's name - - - - - - - - - - - - - D a t e - - - - - - - - - - -
Stage 1 (minimal) 1-5

Stage 11 (mild) ~15
Stage 111 (moderate) - 16-40 Laparoscopy _ _ Laparotomy ___ Photography _ __
Stage IV (severe) >40 Aecommended treatment
Total--------- Prognosis--------------------
E
::i
Q) Endometriosis <1Cm 1-3 cm >3cm
e
E
·¡: Superficial 1 2 4
(IJ
a.. Deep 2 4 6
A Superficial 1 2 4
~ Deep 4 16 20
o"'> L Superficial 1 2 4
Deep 4 16 20
Posterior Partial Complete

cul-de-sac
obliteration 4 40
Adhesions < 1/3 Enclosure 1/3- 2/3 Enclosure >213 Enclosure

~ A Filmy 1 2 4
o"'
> Dense 4 8 16
L Filmy 1 2 4
Dense 4 8 16
A Filmy 1 2 4
Q)
.D
Dense 4• s· 16
::i
1- L Filmy 1 2 4
Dense 4• e· 16
·11 the fimbriated end of the fallopian tube is completely enclosed, changa the point assignment to 16.
Denote appearance of superficial implant types as red [(A), red, red-pink, flamelike, vesicular blobs,
clear vesicles], white [(W), opacifications. peritoneal defects: yellow-brown]. or black [(B), black,
hemosiderin deposits, blue]. Denote percent of total described as A_%, W_%, and 8_%. Total
should equal 100%.
Figure 42-1 2: The revised Classification System for Endometriosis from the American Society for Reproductive Medicine :
1996. (From : American Society for Reproductive Medicine: Revised American Society for Reproductive Medicine Classification
of Endometriosis: 1996. Fertil Steril 67 :817-821, 1997).
This classification has been tested by a number of in- tors). These can induce or suppress ce ll growth and
vestigators. lt has a number of drawbacks including its proliferation, angiogenesis, and the inflammatory re-
inabi li ty to adequately predict the pelvic pain aspects sponse (Tab le 42- l O).55
ofendometriosis and the future ferti lity components. In
addition to this, an absence of a fun ctiona l component
to thi s classification system makes it espec ially diffi-
cu lt. The lack of a measure of target organ response
and/or visual and objective parameters for fertility- Ultimately, endometrio is is a urgical disease. Although
wh ich can not be determined simply by evaluating the medica! therapy- s uc h medications as danazo l,
endometriosi s itself- needs to be incorporated . leuprolide, ora l contracept ives- may offer temporary
pain relief, no medication can be used effective ly for
endometriosis-associated infertility. In addition, while
Effects on FertilitY- - - - -- - --. pain reliefmay occur with medications, the medications
are often given without a definitive diagnos is and they
There is li ttle question that endometriosis has an ad- ha ve a long 1ist of side effects.
verse effect on fertility by be ing strongly associated
with infertili ty4 2 anda likely association with a hi gher To improve fertili ty, endometri os is must be removed so
risk ofspontaneous aborti on43-46 although this increased that the infl am matory toxins can be removed , thereby
risk has been questi oned. 47 improving fert ili ty. An effective surgica l treatment must
cons istently and reproducibly erad icate the disease. An
The peritoneal fluid in women with endometrios is in- extensive meta-ana lys is has show n convincing ly the
creases in vo lume. 48 This is particularly true at and superiority of su rgica l treatment for th e treatment of
around the time of ovulation. In peritoneal fluid from endometriosis-related inferti 1ity 56 (Tab le 42-1 O).
infertile women who have endometri os is, it has been
fo und th at it is toxic to the growth and deve lopment of
mouse embryos when compared to th e fluid from nor- Final Comment ---------~
mal women and in fert il e women without endometrio-
sis.4950 Furthermore thi s fluid from infertile patients with Endometrios is is a condition which affects a large num-
endometri os is has been fo und to be detrimental to the ber ofwomen and, in parti cul ar, adversely affects their
mouse sperm-ova interaction.5 1•53 lt has also been sug- quality of li fe and their ferti li ty. lt is a disease that should
gested that the in fertility may be due to poor quality be aggress ive ly identified and treated . In women ofre-
embryos deri ved from impaired oocytes obtai ned from productive age, treatment should be aim ed at preserv-
malfunctioning ovaries. 54 ing reprod uctive function if that is the patient 's desire.
By surg ica lly excising the di sease or vaporizing it, one
The peritonea l fluid from women with endometrios is cannot only preserve fert ility but also enhance it. By
ultimately appears to be toxic or hostile to either the treating the underlying endocrine and target organ dys-
embryo or the gamete. lt has mitogen ic, angiogeni c and function , fei1i lity is also improved (Figure 42-13).
chemoattractant activity. lt also contains multiple growth
factors (endocrine factors) and cytokines (immun e fac-
Table 42-11: Does Therapy for Endometriosis
Enhance Co nception?
A Meta·Analysis of Different Approaches 1
Table 42-10: Peritoneal Fluid from Women
with Endometriosis may be Toxic or Hostile to No. of
the Embryo or Gametes 1 Studies The Better
Comparison Reviewed Treatment
None/medical vs. surgery 22 Surgery

• lt has mitogenic, angiogenic, and chemoattractant None/medica l vs . laparoscopy 12 Laparoscopy
activity
None/medical vs. laparotomy 14 Laparotomy
• lt contains multiple growth factors (endocrine factors
No Rx vs . medical Rx 13 No difference
and cytokines (immune factors )
between approaches
• These can induce or suppress cell growth and
Surg ery only vs . 14 No difference
proliferation, angiogenesis and the inflammatory
surgery & medical between approaches
response
1. Guidice LCC, Tazuke SI , Swirsz L: Status of Current Research in 1. Kim AH, Adamson GD: Does Therapy far Minimal Mild Endometriosis Enhance
Endometriosis. J Reprod Med 43: 252-262, 1998. Conception? lnf Reprod Med Clin North Am 8: 623-<i37, 1997.
570 The Med ica! and Surgical Practi ce of NaProTECHNOLOGY
15 16 17 l 19 20 21 22 33 34 35
MCS •3.0
H H M L VL VL OAO "PC WPC .;111 OAD OAO OAD MD IO K OAO O.A.O OA <:~ OAO OAO OAD O.O.O OAO CA.O OAO OAO OAD
•3 • • 111; 1
OAO OAO OAD
u/s MFD 1.5 1 1.% 1. 53 FR

.o.
20 9
11.s 11 .7
109 111
92 10.0 S val es m•33.
Figure 42-13 : This patient is a 35-year-old gravida O, para O, who had a history of severe dysmenorrhea , premenstrual
syn drome and infertility. She had a diagnostic laparoscopy which revea led endometriosis , an immature follicle with complete
rupture and a very suboptimal periovulatory E2 profile and a suppressed postovulatory progesterone and E2 profile. She was
treated successfully for her endometriosis, limited mucus and ovarian dysfunction . She successful ly achieved a pregnancy
and delivered a normal full-term infant.
1. Kn app VJ : How Old is Endometri os is9 Late 17"' - and 18''-

9. Demco L: Nove l Approach es to Dia gnosing and Treatin g
Ce nlu ry Euro pea n Descri pli ons of the Disease. Fcrtil Sleril
End omelri os is. Contempora ry OB/GYN 12-1 8, Apr il 15,
72: 10- 14 , 1999.
2004.
2 . 1-lastings JM , Fazleabas AT: Future Direcli ons in Endomelri o-
1O. Redwin e DB : Ovarí an End ometrio sis: A Marker for More
sis Research. Se111 Reprod Med 2 1:255-262, 2003.
Exlens ive Pelvi c a nd lntes tional Di sea se . Fertil Ste ri l
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Pulm onary Endo rn et ri os is in a Patient with Un ico rnuate
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24 . Dou ghert y LS, Ha ll T: Perinea l End orn etri os is with Anal
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198 8.
2 5. Jani ck i TI , David LJ , Skaf R: Mass ive and Acute Hemoperi-
ton eum Du e to Rupture of th e Uteri ne Artery by Erosion 46 . Olive DL, Franklin RR, Gratki ns LV: The Assoc iation Be-
from an Endorne tri oti c Le s ion. Fertil Steril 78:879-88 1, twce n End ometrio sis and Spontaneous Abortion: A Retro-
2002. spcct of Clini cal Study. J Reprod Med 27 :333-338, 1982.
26 . Crave ll o L, D' Ercole C, Le Treu t Y- P, et al: Hepatic En- 4 7. Mctzger DA, Olive DL, Sto hs GF, et al: Assoc iation of En-
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Gro up Selection. Fertil Steril 45: 18-22 , 1986.
2 7. Th omas EJ , Campbell IG: Evi dence th at Endometriosis Be-
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5 1:426-430, 1985. 49. Marcos R , Gibbon WE : Effect of Peritonea l Flu id on In
Vitro Cleavage of 2-Ce ll Mouse Ernbryos: Poss ibl e Role in
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ln fe rtilit y Assoeiated with Endometriosis. Fertil Steril
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44:678, 1985 .
nea l Cavity. Arn J Obstet Gyneco l 14:422, 1927.
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struat io n in Healt hy Wornen a nd in Pat ie nt s with En-
in g of th e Amer ican Fertility Soc iety. Abstrae! #58, 1985.
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3 1. Bartosik D, Jacobs SL, Kell y LJ: Endorn etrial Tissue in Peri -
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32. Khan-Sabir N, Carr BR : Endometriosis, Part 1: Di agnosis
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33. Cheesrna n KL, Chees man S D, Chattcrton RT, et al: Alter- Fertil Stcri l 58:284-289, 1992.
ati ons in Progesterone Metaboli sm and Lutea l Function in
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ln fertile Women with Endometriosis. Fcrti l Steril 40: 590-
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595, 1983.
Mee tin g o f th e American Fertility Soc iety. Ab strae! #23,
34. Pitt aw ay DE, Max son W, Daniel! J, et a l: Luteal Ph ase 1986.
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7 16 , 1984.
on Endomet ri os is. J Reprod Med 43:252-262, 1998 .
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No rth Am 8:623 -637, 1997.
3 7. Dmowski WP, Radwanska E, Bina r Z, et al: Mild Endometrio-
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789, 1986.
Polycystic Ovarian Disease:
Medical Effects and Effects on Fertility
n 1934, at the Central Association of Obstetricians and rogen and LH leve ls, an in creased LH :FS H ratio,
I and Gyneco logists in New Orleans, Doctors Stein and
Leventha l described a series of seven cases in whi ch
sorne increase in serum estrogens, increases in fasting
or cha llenged insulin levels, and occas ionally increased
amenorrhea was assoc iated wi th bil atera l polycystic prolactin leve ls. Sex hormone binding globulin may be
ovaries. Th ey also reported surgical wedge resection as decreased.
a treatment wh ich "was successfu l in compl etely restor-
ing phys iologic function . Menstruation in every in- The incidence of po lycysti c ovaries (PCO) has been
stance became normal and remained so during the pe- observed to be 14.2 percent in a grou p of otherwise
riod of observation." 1 hea lthy women. These patients were diagnosed by pel-
vic ultrasound and had hi gher serum testosterone lev-
At that tim e, the conditi on was seen to be assoc iated els, low FS H levels and increased LH:FSH ratios. Women
with amenorrhea or oli gomenorrhea, hypertens ion, hir- with PCO had signifi cantly more irregular cycles (44%
suti sm, infe rtility and obes ity, and became known as the vs. 19%) and had increased prob lems wi th conceivi ng
Stein-Leventhal synd rome. For many years, polycystic (25.9% vs. 9.2%) than women with normal ovaries. These
ovarian di sease (PCOD) was thought to be present only women did not have th e fu ll -blown polycystic ovary
in those women who presented with ali ofthe cli nical synd rome (PCOS) . The preva lence of PCOS is thought
aspects of thi s syndrome. We now know that thi s con- to be fo und in about six percent ofwomen.2
dition is more preva lent than previously thought and
may occur in women who are not obese or hyperten- Adams, et al. fou nd that in symptomat ic women , the
sive; although hirsutism, irregular cycle and sorne form incidence was much hi gher. Again using ultrasound, 87
ofreproductive anoma ly ( usuall y infetiili ty) is still quite percent of patients with oligomenorrh ea and 92 percent
common. We also know that it can now occur in women with idiopathic hirsuti sm (hirsuti sm with regular men-
who not on ly have long and irregular cyc les but also in strual cycles) had evidence ofpo lycystic ovaries. 3 This
those women whose cycles are regular. is a condition wh ich, overa ll , is more com mon than once
though t and may actually exist in different stages of
The clinical features of polycystic ovaries are shown in severity.
Tab le 43- 1. This gro up of patients often has elevated
573
Table 43·1: The Spectrum of Clinical Manifestations of the

Polycystic Ovary yndro me
% Patients Associated
System Affected Endocrine Manifestation Possible Late Sequelae
Obesi ty 38 r androgens (testosterone and diabetes mellitus (11%)

androstened ione)
Menslrual disturbance 66 r luteinizing hormone (LH ) ca rdiovascular disease
Hyperand rogenism 48 r LH :FSH ratio hyperinsu linemia
ln fe rtil ity (73% ofanovulatory r serum estrogens high LDL, low HDL
infertility)
Asymp toma tic 20 r fasling insulin endometrial carcinoma

r prolactin hypertension
~ sex hormone binding globulin
FSH=follicle stimulating hormone: LDL=low-density lipoprotein ; HDL=high-density lipoprotein

From: Balen AH, MacDougall J, Jacobs HS: Polycystic Ovaries and their Relevance to Assisted Conce ption . In: Brinsden PR (Ed .), A
Textbook of In Vitro Fertilization and Assisted Reproduction. 2nd Ed. Parthenon Publishing, UK, 1999.
Thi s is a conditi on that not onl y has fe rtility-related pati ent. Whil e 70 percent o f obese PCOD pati ents ex-
pro bl ems but a l o has a signi fíca nt impact on a woman 's hi bit exaggerated in sulin secreti on, it is also present in
hea lth . The inc idence of adult-onset diabetes melli tus, 20 to 40 percent of non-obese pati ents with PCO D.5
fo r example, is estimated to be 11 percent. Cardi ovascu-
lar di sease, hyperinsulinemi a, dys lipidemi a (inc luding
hi gh LDL-C and low HDL-C) leve ls are al so observed Diagnosis ------------~
(Tab le 43 -2). Th ere is also thought to be an increased
ri sk in the long term of endometrial, ovari an and breast Pres umpti ve ev idence of po lycysti c ovari es can be elic-
cancer and hypertension. ited w hen the fo ll owi ng clin ica l manifestati o ns are
present :
The prevalence ofobes ity in PCO D is rather hi gh, ra ng-
ing from 30 to 60 percent,4 and hyperins uli ne mi a is C linica l ev idence of hyperandrogeni sm (e.g. , hirsuti sm,
prese nt in more than 50 percent of PCO D patients. 2 acne, and roge ni c a lopec ia) and/ or hyperand rogenemi a
Hyperinsulin emi a is not, howeve r, limited to the obese ( e .g ., e levated tota l or free testosterone ).
Oli go-ovulation (i.e., cycle durati on greater than 35 days

Table 43-2: Risk Factors associated with in durati on or less than eight cycles per yea r).
Polycys tic O va ries
Table 43-3 : Histological Features of

Dysl ipidemia Polycystic Ovaries
Non-insu lin-dependent diabetes mellilus
Gestational diabetes
Hypertension Whole ovary hypertrophy
Cardiovascular disease • Thickened capsule (> 100µ )
• Thrombosis lncreased number of subcapsular foll icle cysts
Endometrial cancer • Scarcity of copora lutea or albicantia
• Ovaria n ca ncer • Hyperplasia and fibrosis of the ovarian stroma
Breast cancer • Decreased th ickness of lhe granu losa layer
• Atretic pattern of the granulosa layer
Adapted from :
lncreased th ickness of the theca interna
1. Dahlgren E, Janson PO: Long-term health implica tions far
Women with Polycysitic Ovary Syndrome. In: Kovacs GT (Ed. ). Prema ture luteinization of theca cells
Po/ycysticOvary Syndrome. Cambridge University Press, 2000.
2. Ciampelli M, Lanzone A: lnsulin and Po/ycystic Ovary Syndrome: From: Robert Y, Ardaens Y, Dewailly D: lmaging Polycystic Ovaries.
A New Look atan Old Subject Gynecot Endocrinol 12:277-292. In: Kovacs GT (Ed.). Potycystic Ovary Syndrome. Cambridge University
1998. Press. 2000.
Chapter 43 : PCOD: Medical Effects and Effects on Fertility 575
Exc lusion of other related disorders (e.g. , hyperpro-

lactin emia, thyroid dysfunction , androgen-secreting tu-
mors, 21 -hydroxy lase deficiency). 6
With advances in ultrasound technology, it is possible

to visualize these ovaries very we ll. The volume is often
exaggerated and the ovaries tend to be more spherical
than ovoid . The main histologic features of PCO are
presented in Table 43-3. The ultrasonic criteria used for
the diagnosis ofpolycystic ovaries is li sted in Table 43-
4.1
More definitive evidence for the existence ofpolycys-

tic ovari es can be obtained by measuring the ratio be-
tween LH and FSH, an and rogen profile (including tes-
tosterone, free testosterone , androstenedione and
DHEAs), performing a transvagina l ultrasound exami-
nation which looks for the classic appearance of the
cystic arrangement within the ovaries, anda diagnostic
laparoscopy which will revea! the classic pattern ofth is
condition.
At the time of laparoscopy, the ovaries will be seen to

be en larged (Figures 43-1 through 43-3). These ovaries
te nd to be classic in ap pearance. They are en larged,
very smooth on the ir surface , usually quite white and
have small gray areas seen through the cortex. These
are the small cystic follicles present under the ovarian
capsule. U ltrasound exam ination will revea! a classic
"string of pearls" peripherally located in immature fo l-
licles (F igures 43-4 and 43-5). Three dimensional (vo lu-
metric) ultrasound is also very dramatic (Figure 43-6).
Table 43·4: Ultrasonic Criteria Used for the

Diagnosis of Polycystic Ovaries
Figure 43-1 through 43-3 : Laparoscopíc photographs of
polycystic ovaries. In 43-1 , a full view of the uterus, tubes
and ovaries. In Figures 43-2 and 43-3 , a close-up view of
Externa! Morphologic Signs two different appearances of polycystic ovaries (From : Pope
Paul VI lnstitute, 2004).
• lncreased ovarían area or volume
• lncreased roundness index (ovarían width : ovarían
length ratio ) (>0.7)
• Decreased uterine width/ovarian length ratio (U/O)
(<1)
Interna! Morphologic Signs

• Number of small echoless regions <10 mm in size
per ovary (microcysts )
• Peripheral repartition of microcysts
• lncreased echogenícíty of ovarían stroma
• lncreased surface of the ovarían stroma on a
cross-sectíonal cut (by computerízed measure)
From: Robert Y, Ardaens Y, Dewailly D: lmaging Polycystic Ovaries. Figure 43-4: An ultrasound view of a polycystic ovary with
In: Kovacs GT (Ed.). Polycystic Ovary Syndrome. Cambridge University multiple cysts located peripherally. In this unique view, the
Press, 2000. exam was performed after laparoscopy when th e ovary was
immersed in Hyskon .
Figure 43-5 : A standard two dimensional ultrasound view of

a polycystic ovary showing the peripheral "string of pearls"
alignment of the small follicles (From : Pope Paul VI lnstitute
Division of Reprodu ctive Ultrasound , 2004).
Figure 43-6 : A three-dimensional (volumetric) ultrasound pi c-

ture of a polycystic ovary (From: Pope Paul VI lnstitute Divi-
The most striking feature of the ho rmo ne para mete rs sion of Reproductive Ultrasound , 2004).
a re a reversa ! ofth e FSH-to-LH ra ti o. No rmall y FS H is
produced in excess ofLH but in PCOD, LH is produced
in excess ofF SH (an reversed FS H:LH ratio). Androgen ti ve. 11 When groups are defin ed, both sonogra phi ca ll y
leve ls are o fte n inc reased but not a lways and need not and by endocrine para meters, there is defin itely an over-
be a part of the ho rm o ne pa rameters fo r makin g thi s la p.12 However, it is best to combine the two, tra nsvagi-
di agnos is. The cycl es are cl ass ica lly long a nd irregul ar. nal ultraso nograph y a nd hormo nal pa ramete rs, to com-
The co ndition ex ists in four to s ix percent of wo men of plim ent the di ag nosti c methods fo r po lycysti c ovarí a n
re produ c ti ve age a nd in at le a s t 75 pe rce nt of di sease . 13
hype rand rogeni c patie nts.8 On occas io n, however, lo ng
a nd irreg u la r cyc les ca n b e co mpl e te ly
no rmogonado tro pi c and no rm oand rogene mi c. In these Etiology _ _ _ _ _ _ _ _ _ _ _~
cases oflo ng and irregul ar cyc les (approximately 5% ), it
is presumed that the i1Tegular nature ofth e cyc les is due The eti ology of thi s condition is c lea rl y comp lex. In
to a hy po th a la mi c d ys fun c ti on a nd not re la ted to hyperandrogenemi c ado lescent girls w ho are des tined
hyperandrogene mi a. to deve lop PCOD, a nocturnal inc rease in ovaría n ste-
roids may no t be adequate to s uppress the GnRH pu lse
PCOD is a co nditi on in w hic h the maj o rity of wo men generator leading to a pers istently ra pid LH pu lse fre-
recei ve inadequate treatment in spite of the lo ng-te rm que ncy, impaired FSH producti o n and inadequate fo ll i-
ris k fac to rs.9 Studi es of e lectro logists suggest that edu- c u lar deve lo pme nt. 14
cation fo r them about the hirsuti sm associated w ith poly-
cysti c ovaries mig ht be he lpful. In these clients, a s ig- In additi on, there a re at least fo ur e ndocrine ab no rm ali-
ni fica nt percentage are assoc iated w ith po lycys ti c ova- ti es assoc iated w ith po lycys ti c ova ri es :
ries a nd ve ry fe w of them rece ive medi ca! ca re. 10
1. The prevalence of gonadotropin abnormalities is very
In atte mpting to make a diagnos is of polycys tic ova- high in wo me n with PCOD se lected o n pure ly clíni-
ri es, th e ultraso nographer needs to be we ll prepared to ca! gro unds.
look at th ose ultraso und findin gs that are class ic fo r
PCOD . The eas iest to loo k fo r is th e obse rvati o n of 2. The pos iti ve re lationship between LH pulse fre-
periphera lly located " string of pea rl s" that can be eas il y q ue ncy and both pool LH a nd LH- to- FSH ra ti o sup-
made by tra nsvaginal ultrasound . The eva luation ofstro- ports the hypotheses that a ra pid freq uency of GnRH
mal/a rea ra ti o by ultrasound has also been ve ry predi c- secreti o n may play a key eti o log ic ro le in the gona-
Chapter 43: PCOD : Medi ca l Effects and Effects on Fertil ity 577
dotropin defect observed in patients with PCOD. Hormonal Correlates -------~
3. Pool LH and LH pulse ampl itude are inversely re- In comparing LH and FSH levels in patients who have
lated to body mass index and percent body fat in a PCOD with women with normal and regular menstrual
continuous fash ion. cycles, the LH levels tend to be increased and the FSH
levels somewhat decreased. In Figure 43-7 this is clearly
4. The occun-ence of a continuous spectrum of gona- demonstrated.
dotropin abnorn1alities varying with body fats sug-
gest that non-obese and obese patients with PCOD Data from the PopePaul VI lnstitute, which agrees with
do not represent distinct pathophysiologic subsets other published reports, show that total testosterone,
of this disorder. 15 free testosterone, androstenedione and DHEAs levels
tend to be e levated in this condit ion . This
The proximate cause ofthe anovu lation or oligo-ovula-
tion associated with PCOD is an abnormality in the se- "'4 EAN ! SE
100
cretion of gonadotropin to which the elevated circulat- ! N Q~ MA. L CYCLE 11 6 )
ing LH levels and insufficient FSH levels to sustain +P. e o. U6l
80
folliculogenesis are evidence. Chronic exposure to the
endogenous LH excess results in the development of 60
LH
both stroma l and thecal hyperplasia with ensuing ova- mfu/ ml
40
rian hyperandrogenism. The anovulation or oligo-ovu-
lation is mostly associated with the decreased FSH pro-
duction. The more rapid GnRH pulse frequency prob-
ably exp lains why the FSH levels are lower. The exact
mechanism of this is not yet well substantiated. 16
There is also clearly a genetic linkage to the develop- FSH

miu;hil
ment of PCOD. When mothers and sisters were evalu-
ated, the rates of PCOD were significantly higher than
that observed in the general population, suggesting the -1 4 -12 -10 -8 -6 -4 -2 o 2 4 6 8 10 12 14
involvement of a major genetic component to the disor- DAY OF CYCLE
der. 17A clear mode of inheritance or candi date gene has Figure 43-7: Daily conce ntrations of LH and FSH (mean ~
yet to be identifi ed; however, because many of these SE) in 16 patients with polycystic ovaries compa red to the
women tend to cluster in fami lies, a careful family his- mean daily concentrations (mean~ SE) in 16 normal women
during the cou rse of the menstrual cycle . Most prominent is
tory may uncover other affected women within the fam-
the significa ntly elevated LH levels in PCOD (From: Rebar RW:
ily sorne ofwho may not yet ha ve been diagnosed. Be- Gonadotropin Secretion in Polycystic Ovary Disease. In : Chang
cause ofthe long-term medica! side effects ofthis con- RJ (Ed): Seminars in Reproductive Endocrinology. 2:223-230 ,
dition, identifying these individuals is important to their 1984)
long-term health . It is likely that one gene or severa!
genes are linked to the suscept ibility to develop P+7 Androgens in Patients w ith PCOD
Control Group vs . Study Group
PCOD. 18
lt has also been recently identified that there are high '° 2.0 2.0 200 • 7.5
179.1
concentrations of anti-ova ri an antibod ies associated
with polycystic ovaries. This suggests that an immune
~
.s 1 '[
.,,,
.s ~
reaction is associated with this condition . This also ~ ~
suggests the possibility that polycystic ovaries may
~
...."ií '' 11
....
LO LO :l
w
I
o
1
have an autoimmune component to it. 19 ~ ~

... ~
lt sho uld also be noted that women with normal men-

strua l cyc les (that is regular menstrual cycles) can have • eon1ro1
Total
Testosterone
Free
Testos1erone
Androstenedione DHEAs
polycystic ovaries. This is particularly true if they are PCOO p: 1 <.0002 I 1<.0001 I 1 <.001 1 .0862
hyperandrogenic. In this group of women, 74 percent Fig ure 43-8: Total testosterone , free testosterone , andros-
had evidence for PCOD. 2º tenedione and DHEAs on P+ 7 in patients with PCOD vs. nor-
mal fertility controls without PCO (From : Pope Paul VI lnstitute
Research , 2004) .
100
Periovulatory Estrad lol-17 p Leve ls
3- and 4-va lue Periovulatory
Control (N=12) vs . PCOD
E2 Sums and Means 90
Control (N=21) vs . PCOD
25
80
• Control
B - Study 70 gi
63.3 "'- 2
B 60
3
53.6 52.7 !b:
:2 15 ¡¡;
~
50
~
;;; 12.8
w ....
40
E =
~ 1
(/) 8.8 8.7 30 ~
20
10
p. NS NS GQiJ NS
N• 31 43 45 41
o
E ~
2 E2-2 Peak E
2
E +2
2 ...,.
3 V.... 4Value
N=-28
3 Volue
Na39
4V-
N=28
Relationship To Peak ~ Level
Sum .....,,
Figure 43-9 : Periovulatory E2 levels wi th 3- and 4-value sums and means in
patients with PCOD and normal fertility controls (From : Pope Paul VI lnstitute
research, 2004).
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 1 00
Sums and Means
Control (N=57) vs . PCOD 90
15
- Conlroi 80
13.6
- Study
Group
g'
i
70
2
60 ~
"e1o .8
"
1ñ so m
~
<>
a
a. 40 ~
E
2 .g_
"
(/) 30 ª-
20
10
p: 1 <.003 I I< 00011 l<.00011 1<00011 QD
N: 55 5S 63 55 50
o o
P+3 P+5 P+7 P+9 P+11
Days Post-Peak
Figure 43-10 : Post-Peak progesterone levels with 5 value sums and means in
patients with PCOD and normal fertility controls (From : Pope Paul VI lnstitute
research, 2004).
100
Post-Peak Estradiol-17P Profiles Post-Peak Estradiol-17P
Control (N=57) vs. PCOD Sums an d Means
90
Control (N=57) vs. PC OD
15
• Control 80
- Study
.
en
1
~
11 2
NS
62.6
G- 70 2
3
ih'
o
'6
10 ..• 60
50
ii"
º'
Q.
88
i!! ....
;;;
w
E 40 ;'.:
:>
2
"
(/) 30 i
20
10
NS NS NS NS
56 60 S3 48
o
P+3 P+S P+7 P+9 P+11
Sum Mean
Days Post-Peak N=44 N=44
Figure 43-11 : Post-Peak E2 levels with 5-value sums and means in patients wi th
PCOD and normal fertility co ntrols (From : Pope Paul VI lnstitute research , 2004).
Chapter 43: PCOD : Medica! Effects and Effects on Fertility 579
hyperandrogenemi a is what leads to the symptoms as- comes down significantl y. FSH does not change, but
sociated with the condition (Figure 43-8). the LH:FSH ratio is significantly red uced. This endo-
crine change is most likely what is responsibl e for the
lfone looks at th e periovulatory E2 levels (F igure 43-9) rec urrence of regular menstrual cyc les in a very hi gh
and the subsequent postov ul atory progesterone and percentage of patients (over 90%) fo ll ow ing ovarían
E2 leve ls (Figures 43- 1Oand43-1 1), one sees in patients wedge resection. These types of data have also been
with PCO D that the sum and mean ofthe E2 levels in the generated by others. 22•25
periovulatory time peri od are signifi cantly lower than in
a normal ovulation pattern. The postovulatory proges- In 26 pregnant pati ents with prev iously documented
terone levels are also sign ifi cantly decreased although PCOD, serum progesterone levels were fou nd to be sig-
the E2 leve ls are not. lt has also been shown that LH nificantly lower during the course oftheir pregnancies
receptors in the preovulatory fo llicl es of patients with (F igure 43 -1 2). This suggests a degree of placenta! in-
PCOD are decreased. 21 Thus, the hypothalam ic-pituitary suffic iency which fo ll ows the lutea l phase deficiency
dysfu nction that exists in thi s conditi on ex hibits abnor- observed in these pati ents.
mali ties which al so affect the target orga ns.
These target organ effects are also reflected in a high Progesterone Levels In Pregnancy
148.4
Previous History of PCOO
frequency of ovul ati on-related defects. Wh ile most at- 150.0 Normal Controls (N=109) vs . PCOD (N=26)
tention over the years has been placed on the obvious • Control
135.4
1E PCOO
irregu lar nature of ov ul at ion (o li go-ovu lation) fre-
quently seen in this group of pat ients, when the actual 103.4
ovul ation event is studi ed, it too, is freque ntl y abnor- ..J 100.0 960
mal. While it is diffi cu lt to study these events by ultra- ~

73.B
1
sound because of the irregular nature of their occur- 67.3
rence, 18 cycles in patients with PCO D have been studied

52
at the Pope Pau l VI lnstitute. In this population, 11 ofthe 50 0
·' 49.7
ovulations (6 1.1%) were defective (see Table 43-5). 35.3

J0.1
The androgen leve ls can be treated med ica lly but the
gonadotropin leve ls respond on ly to surgery. In Table o.o
2-8 weetcs 8-T2weekl 14- 18weeQ 20-24weelits 26-JOWN«s 32- 38weell.1
43 -6, the resu lts of the various androgens, LH and FSH, ....... NS NS NS
both before and after ovarían wedge resection , are Mean Progesterone ~ week lntervals
shown. There is a stati stica lly signifi cant decrease in Figure 43-12: Progesterone levels in pregnancy in patients
with a previous diagnosis of PCOD . The levels at six weekly
testosterone, free testosterone, androstenedi one and intervals are decreased when compa red to normal controls
DH EAs followin g wedge resection. In additi on, LH (From: Pope Paul VI lnstitute research, 2004).
Table 43-5: lncidence of U ltraso nograp hically Table 43-6: Endocrine C hanges Observed in
ldentified Ovulatio n Disorders in Matched Pairs Before and After O varian
Patien ts with P COD 1 (N= 18) Wedge Resectio n in Patie nts with PCOD
Norma l Ovulation Result

Ovulation 2 Disorder Before Wedge Alter Wedge
Ovulation Status n % n % Hormone N Resection Resection p
Mature follicle (M F): + 3 7 38.9 Te stosterone 31 78.0 43 .3 .0004 1

Free testosterone 30 3.1 1.8 <.00012
MF : - , Re 3 16.7
LU F': - 2 11 .1 Androstenedione 30 2.3 1.7 .0013
IFS 3 : +, - 3 16.7
DHEAs 29 225 .3 159.2 .03'
PR S' : + , - 2 11 .1
DRS': + 5.6 LH 25 9.1 5.9 .017'
FSH 25 4.2 4.8 .667 1
Totals 7 38.9 11 61 .1
LH :FSH ratio 25 2.57 1.8 .036 '
1. PCOD
2. LUF = luteinized unruptured follicle
1. Wilcoxon rank-sum test
3. IFS = immature folicle syndrome
2. Aspin-Welch unequal-variance test
4. PRS = partial nupture syndrome 3. Equal-variance t-test
5. DRS = delayed nupture syndrome From: Pope Paul VI lnstitute resea rch, 2004.
ate the effects of estrogens on endometrial cell prolif-

Table 43-7: lncidence of Endometriosis in eration.34
Patients with PCOD ' (N=SS)
n % lGF-binding protein type 1 (IGFBP-1 ), which is induced

by progesterone in the endo metrium,35 inhibits the re-
With endometriosis 28 50.9
ceptor bind ing of lG F- 1, thus, functioning as a protec-
No endometriosis 27 49.1
tive factor for endometrial cancer. lnsulin, in tum , sup-
1. As determined at the time of laparosoopy. presses the synthesis of endometrial lGFBP- l .36 ln
From: Pope Paul VI lnstitute research. 2004. hyperinsulinemic women , the low endometrial IGFBP-1
synthesis might permit unopposed stimulation of en-
dometrial cell proliferation by IG Fs. 37
lnsulin-like growth factors (IGFs) seem also to be impli-

Endometriosis and PCOD -----~ cated in the pathogenesis of breast cancer,38 another
pathology that is more frequently observed in women
For many years it was the common beliefthat endometrio- with PCOD. Coulam, et al. 39 fo und a threefold increase
sis was not associated with PCOD. This was thought to in postmenopausal breast cancer in women with po ly-
be the case because these women had very long and cystic ovarie . lt has also been observed that breast
irregular cycles and their pelvic tissues were under- cancer risk is increased in hyperandrogenic women. 40.4 1
stimulated by the ovarian steroids. With this as a ratio- Others have reported that PCOD protects against pre-
nale, it was thought that endometriosis, which is a hor- menopausal and early postmenopausal breast cancer,
monally dependent tissue, would not normally be ob- but small sample size and the effects of other treatments
served. ha ve elicited sorne criticism ofthese data .42.43
However, it has now been shown that endometriosis These patients also ha ve an increased risk of dysfunc-
<loes coexist atan increased incidence in patients with tional uterine bleeding (a form of estrogen breakthrough
PCOD who also have infertility. 26 In our own population bleeding) because ofthe unopposed estrogen effect. ln
of patients (Table 43- 7), we ha ve found an incidence of fact, this group of patients much more frequently un-
endometriosis in patients with PCOD of50.9 percent. dergoes hysterectomy because of this type of prob-
lem.44 Ovarian cancer is also increased.45HDL-C is lower
and triglycerides are elevated in this patient popula-
Long-term Medical lmpact _ _ _ ___ tion. Jn addition , homocysteine leve ls are increased in
this patient group which may also increase their card io-
This condition has a number of implications for a vascular ri k. 46 PCOD is also reported more often in
woman 's long-term health and quality oflife. Not only women with chronic fatigue syndrom e. 4 7
is it associated with obesity, abnormal hair growth, skin
problems and abnormal men strual periods but is al so
associated with much more significant longer-term health Hirsutism - - - - - - - - - - - - - - - .
consequences. Women who have PCOD have at least a
seven times increased risk ofheart attack and heart dis- Hirsutism is characterized by the excess growth of an-
ease than other women. 27·28 They are at risk for hyper- drogen-dependent ha ir in women and is largely defined
tension and, by the age of 40, 40 percent of them will by personal and socia l norms. 48 ln women, the presence
develop type ll diabetes. 29 ln addition, there is a long- of termina! (coarse) ha ir in usua 11 y androgen-dependent
term risk of endometrial cancer which develops beca use areas such as the upper lip, chin , chest, areolas, abdo-
ofthe unopposed low-dose estrogen stimulation, which men and anterior thighs denotes a hirsute state. 49
affects the endometrium .
Androgens, produced by the adrenal gland , ovaries and
While it is well established that PCOD constitutes a ri sk va rious forms of peripheral conversion, can stimul ate
factor for endometrial cancer dueto the prolonged un- ha ir follicles and when present in excess concentrations
opposed action of estrogens on the endometrium,30.J 1 contribute to acne vulgaris and hirsutism. When the
hyperinsulinemia has more recentl y been propo ed as androgen levels are really marked , it can result in viri l-
an independent risk factor for endometrial cancer.30.3 2·33 ization with temporal balding, hirsutism , deepening of
It may be that this association is mediated by the insu- the voice, clitoromegaly, increased muscle mass anda
lin-like growth factors (lGFs) that are assumed to medi- male escutcheon. 48
Chapter 43 : PCOD : Medical Effects and Effects on Fertility 581
In approaching the treatrnent of this cond iti on, there will arnp li fy reprod ucti ve abnormaliti es observed in
are severa ! different medica! approaches. Quite often PCOD. The insulin-sensitizing drugs may be helpful in
ora l contracepti ves are used to both regulate the men- the treatrnent ofthe in su lin resistance related to PCO D.62
strual cyc le and suppress the androgens. However, the
use ofthe cornbined oral contraceptives are assoc iated 1nsu lin resistan ce is usuall y thought of as a condition
with increased total cholesterol with a tendency towards in wh ich the peripheral ce ll s requ ire more in su lin to be
increasing levels oftriglycerides. Thus, it is notan idea l able to mai ntain a norrnoglycemic state. In such cases,
approach to treatrnent. 50 One of the more benign ap- the patients are not technically diabetic because their
proaches is to use dexa rnethasone in a dosage of 0.25 glucose levels are normal. However, in response to a
rng by rnouth every day (PO QD) or by rnouth every glucose load, their insulin levels wi ll be elevated. They
other day (PO QOD). This wi ll decrease the adrena l pro- are elevated because ofthe resistance that exists in the
duction of androgen and reduce th e stirnu lation of the peripheral cel ls.
hair follicles; however, it will not elimin ate the hirsutism
and it may aggravate th e hyperi nsulini srn. If one uses To rnake this diagnos is is not necessarily easy. ln pa-
dexarn ethasone on a long-terrn bas is, th en electro lys is tients with docurnented PCO D at the Pope Paul the Vl
wi ll also be necessary. The rnajor side effects to dexam- ln st itute, it was fo und that nea rl y ali patients were
ethasone are weight gai n and bloating. This is a sec- norrnoglycemic and slightly over 50 percent had elevated
ondary corticosteroid effect. Dexarnethasone is a repro- fasting insu lin levels (Tab le 43-8). When the insulin lev-
ducti ve category e drug. e Is were eva luated further by the patient's we ight, a
statistica ll y significant assoc iation was observed be-
Of the other approaches that have been used, spirono- tween obesity and elevated fa ting in su lin levels (Table
lactone (A ldactone) seems to be one of the better ap- 43-9). However, sorne have used the fasting glucose-to-
proaches. 51-54 Spironolactone does affect the androgen insulin ratio to determine insulin resistance. 63
receptors and wi ll , over a pro longed period ofti rne, re-
duce the hirsuti srn on its own. Good results can be ob- A more specific way fo r id enti fy ing these patients is to
tained from it as long as one is pati ent. The side effects use a standardi zed glucose load (75 gra ms of ora l glu-
are rninirnal. lt is a category D drug. cose) and to do a gl ucose tolerance test, rneasuring not
only the glucose leve ls but also the serurn in sulin leve ls
Other medica! approaches ha ve also been used to treat o ver the period of the two-hour glucose tolerance pro-
hirsuti srn . Cirnetidine has been shown to produce a 64 cedure. This has recently been reported by Yildrirn , et
percent decrease in the rate of ha ir growth , but patients al64 and resu lts for the glucose tolerance test are shown
did have to take 300 rng five times per day for three in Figure 43- 13 for control pati ents. Patients with PCOS
rnonth s to accornpl is h this. 55 Also drugs suc h as and the serurn ins ulin responses are fo und in Figure 43-
flutamide (Drogenil , Eufl ex, Eul exin) 56·57 and fi nasteride 14. When looki ng at these two in compari son, the glu-
(Propec ia, Proscan)58-61 ha ve been used; but, fin asteride cose to lerance test is near normal; although, th ere were
is a category X drug. Flutamide is a category D drug. two points at 30 and 90 minutes where the glucose re-
sponse in the PCO D patients were signifi cantly elevated .
However, when looking at the serum insulin levels, the
lnsulin Resistance - - - - - - - - - . . response is rnuch more drarnatic and clear cut. Ali of the
levels after the fasti ng leve Is were statistica lly increased .
The polycystic ovary synd rorne has major rnetabolic as This has becorne our preferred way now for eva luat ing
well as reproductive rnorbiditi es. lt is an irnportant risk patients who have polycystic ovaries and are suspected
fac tor for those wornen who deve lop type 11 di abetes ofbeing in sulin resistant.
mellitus. It is associated with insulin res istance which
Table 43-9: Fasting lnsulin Levels in Patients
Table 43-8: Patients with Documented PCOD with Documented PCOD by Patient's Weight
and Fasting Glucose and lnsulin Levels lnsulln n Patlent's Weight 1
Glucose lnsulin Normal 19 165.62
n % n %
Elevated 11 216 .1
Normal 15 93.8 10 52 .6
1. lnpounds
Elevated 6.2 9 47.4 2. p=.002 (eq uat-variance t-test)
From: Pope Paut VI lnstitute research. 2004. From: Pope Paul VI lnstitute research. 2004.
582 The Medica l and Surgical Practi ce of NaProTECHNOLOGY
There is ev idence to suggest that treating these pa-

tients with metfo nnin (G lucophage) can be beneficia l. 65
Metfo rmin has been shown to directly inhibit and rogen
~PCOS
prod uction in the human theca l ce ll s66 and to have a
~
"" 1
150
~control
direct effect on ovarian stero idogenesis. 67 lt also has an
Cl
.so; effect, ofcourse, on loweri ng in sulin leve ls and reduc-

> 120 j ing aromatase activity. 68 Along w ith thi s, metform in
.,.
~
! therapy has been shown to improve the menstrual pat-
o
o 90 J tem in pati ents with PCOD.69 -7°
"
-¡;,
E ¡
.,2 60 - Metfo nnin is a biguanide agent able to red uce insulin
"'e res istance in IDDM. Ameli orati on ofi nsulin insensi-
.,"'
:::;: 30 ti vity by metformin treatment appears to be dueto an
enhancement ofboth decreased non-ox idati ve glucose
o- --- -- metabolism and translocati on of glucose transporters
o 30 60 90 120
75-9 oral glucose tolerance test (min) fro m the intracellul ar poo l to the plasma membrane. 71
Figure 43-13: Serum glucose levels (mean ± SO ) during a With the recent ava il abili ty of the extended-release fo nn
75-gram oral glucose tolerance test in women with the poly- (G lucophage XR) the signi fica nt G I side effects have
cystic ovary syndrome (PCOS) and controls (* p<.05 ) (From : been greatl y reduced.
Yildrim B, Sabir N, Kaleli B: Relation of intra-abdom inal fat
distribution to metabolic disorders in non-obese patients with
polycystic ovary syndrome. Fertil Steril 79: 1358-1364, 2003). lt has been thought that in creas ing the regul ari ty ofthe
menstru al cyc le with the use ofrn etforrn in will also in-
crease pregnancy rates, espec ially if used in coopera-
ti on with clorniphene citrate. 72 However, the effecti ve-
ness and the role of rnetfo rrnin in the treatment of PCOD-
re lated infert ility is diffi cult to assess from currentl y
150 l ava il ab le research.73 lt does appear to improve ovu la-
~PCOS tion rates, but its effect on pregnancy rates is not strik-
~control
i ng. 74 lt has rece nt ly bee n s how n, th o ugh , th at
rnetforrni n adrnini strati on modulates and may restore
120
:::¡- lutein izing hom1one spontaneous episodic secretion and
§ ovari an fu nction in non-obese pati ents with PCOD .75
3 Regardl ess of its irnpact on future fe rtili ty, it is clear that
~ 90 th ose pati ents who are insulin res istant should be prop-
.91
_!; erl y treated with drugs such as metfo rmin . Thi s is a
3
"'
_!; 1 signi fica n! metaboli c abnonnali ty that has long-term
E
2 60 ~ hea lth problems assoc iated with it and thu s, needs to
C1>
be treated.
"'e
~'"
There are other app roaches that have also been used.
30
N-acetyl-cyste ine (NAC) treatm ent has been shown to
1
improve in sulin sensiti vity in pati ents with PCOD as
J o 30 60 90 120
we ll. NAC is co mmonl y used as a safe mu co lytic drug,
but at hi gher doses it increases th e ce llular levels of
reduced glutathi one (G SH), an antiox idant, wh ich has
75-g oral glucose tolerance test (min)
been shown to influence insulin receptor activity in vivo.
Figure 43-14: Serum insulin levels (mean ISO) during a 75-
gram glucose tolerance test in women with polycystic ovary Thi s may representa new treatm ent or adjuncti ve treat-
syndrome and controls. All comparisons were statistically ment fo r the improvement of circul ating insuli n leve ls
significan! (p<.001 ) (From : Yildrim B, Sabir N, Kaleli B: Rela- and insulin sensiti vity in hyperinsulinemic pati ents with
tion of intra-abdominal fat distribution to metabolic disorders PCO D. In addi tion, in NaProTECHNOLOGY and with
in non-obese patients with polycystic ovary syndrome. Fertil
Steril 79:1358-1 364, 2003). the CREIGHTON MODEL System (CrMS) where limited
mucus cycles may be a pro blem, the use of th is muco-
lytic agent may be ofsome additional ass istance. 76 Other
drugs such as ros iglitazone77 •78 have also been used. D-
Chapter 43: PCOD: Medica l Effects and Effects on Fertility 583
chiro-inositol has also been shown to increase the ac- sponse to the GnRH stimulation test in hype rinsulinemic
tion of insulin , improvi ng ovu latory function and de- patients. This suggests a possible invo lve ment of insu-
creasi ng serum and rogen concen trations, blood pres- lin in the gonadotropin di sturbances ofthe syndrom e.92
sure and plasma triglycerides. 79
The opiate receptor antago ni st, na ltrexone, has been
PCOD, w ith its assoc iated insulin res istance <loes ap- studi ed in patients w ith PCO D .93 Na ltrexo ne, in
pear to be an increased ri sk factor fo r gestational diabe- hyperinsulinemic patients, reduced the insulin response
tes,8º· 81 and the use of metform in therapy during the to a gl ucose load by 30 percent. Liver insulin metabo-
course of pregnancy will reduce the development of li sm was significantly improved with opioid antago nist
gestational diabetes in these patients.82 administration. Na ltrexone may also improve growth
hormone releas ing hormone-induced growth hormone
Women who have recurrent pregnancy loss also ha ve a secretion in patients with PCO D. The growth hormone
signjficantl y increased prevalence ofinsulin resistance,83 response is heterogeneously represented in re lation to
and continuing metformin th ro ughout the course ofthe both obes ity and hyperinsulini sm.94
pregnanc y appears to reduce the inc idence of sponta-
neous abortion. It <loes appear to be safe when given in
pregnancy and does not appear to be tera togenic. 84 CREIGHTON MODEL System in PCODl
Studies have been done on mouse e mbryos and have
shown that it does not have tox ic effects on mouse The hallmark of a patient who is charting her menstrual
embryo development. 85 Thus, for those patients who and fert ility cyc les w ith the CrMS and who has PCOD
are on metfo rmin for insulin resistance and are being will be long and irregular cyc les usually greater than 38
treated for infertility, the metformin shou ld be contin- days in duration. Cycles that are 32 to 38 days in dura-
ued during the course of th e pregnancy. tion are often associated with PCO as well , but more
research is needed to clarify thi s. In Table 43-1 O, vari -
ous parameters are shown. The average cycle length is
21-Hydroxylase Deficiency _ _ _ _~ 44.6 days, the average post-Peak phase is 15 days (but
it can be hi ghl y variabl e) and the mean mucus cyc le
No n-class ic adrenal hyperp las ia (NCA H) is a homozy- score is 4.82. This is sign ificantl y decreased from nor-
go us recessive di sorder diagnosed by elevated 17-hy- mal (p=.00 1).
droxyprogesterone levels ( l 7-0HP). The prevalence of
NCAH is approximately 50 times less than that of PCOD lf an ovarían wedge resection is performed, the effects
affectin g between o ne perce nt and l O percent of of that can also be monitored and s hown dec isive ly
hyperandrogenic women. Howeve r it can be di ffi cult to whe n th e woman is pro sp ect ive ly c hart in g her
distinguish between PCOD and NCAH so lely on clini- biomarkers. Examples of charting assoc iated with poly-
cal gro unds as both may have vary in g degrees of cysti c ovari es are shown in Figures 43- 15 and 43-16.
hyperandrogenism and ovul atory dysfu nction. Thus,
the measurement of a 17-0HP leve! should be incorpo- IfC lom id is used to stimul ate ovulation , then the effects
rated into the evaluati on of a li hyperand rogeni c pa- ofC lomid can be fo llowed and monitored with the use
tients.8 There does appear to be a cross re latio nship of the CrMS . in additio n, post-peak progesterone lev-
between PCOS and NCAH as 40 percent of pati ents e Is can be used to monitor the biochem ica l effective-
with NCAH will also demonstrate ev idence ofpo lycys- ness ofthe C lomid .
tic ovar ies .
Beta-Endorphins --------~
Table 43-10: Creighton Model System Charting
Correlates in Women with Prove n PCOD
lt has been suggested that ~- end orphi n s may play a
role in glyco regu lation .86 ~-endorphi n s have been dem- Cycle Parameter Ran ~e Meall
onstrated in the pancreas 87 and they may sti mulate in-
Cycle length-days (n =16) 29- 133 44.6
sulin and glucago n release . Both acute and chronic in-
Post-Peak phase-<:lays (n=11) 11 -25 15.0
hibition of opioid tone (with naltrexone) have been
Mucus cycle score (n =1 5) 0.0-10.7 4.82 1
shown to reduce th e exaggerated in su lin secretion in
women with PCOD .88 -91 The same treatment was also 1. When compared to patients of nonmal fertility (MCS=9.3) p=.001.
effecti ve in reducing the luteinizing honnone (LH) re-

584 The Medical and Su rgical Pract ice of NaProTECHNOLOGY
15 16 17 18 19 20 21 22 23 24 25 26 27 28
VL VL M M l Vl Vl VL CA.O OAD OAD CAD MO IOK IC)c/K fOC/K Sclk IOCK 10Clk IOKL KllU. IOKL IOKL IOK IOC/t< 8C 4..: 3 9C a• .3 OA D OAO a.AD 4 x3
aA0 aA0 !~ ~~ ~~ aAO AD J(I ,,.,~ JC a.. xa rt.~ KI .:1 AD AD x.3 JCI "ª Jtl
FSH = 4 _q
LH = 7.5
.o LH' SH= 1.53
IO.O
Figure 43-15 : Thi s 33-day cycle was fo llowed hormonally by ultrasound and with the CrMS . T he ultrasound is classic fa r
PCOD , the LH :FSH ratio is reversed (1.53) an d the periovulatory E2 profile is suboptimal (From : Pope Paul VI lnstitute resea rch,
2004 ).
17 18 19 20 21 22 23 2 25 26 27 28 29 3 31 32 33 34
IOSL IOSL IOSL /OSL lost... IOSL IOKL CAD QA.D IOKL IOKL K>SL OAO IOK L ~O ()A.O IOK
AD AD AD AD AO AD x 1 xa "1 AD x 1 A0
PCOD Before
Wedge Resection
H H H M V L 00.0 CAD
OAO
CAD OAD IOSL IOSL O.A.O
xi xi
°""° 0-.0 OAD IOSL IOSL IOSL tOSL ;&A.O
AD AD AD AD
Ql\O
First Cycle After

Wedge Resection
Figure 43-16 : This CrMS chart shows a classic cycle which is afien observed in wo men with PCOD . Th e cycle is 46 days in
duration . In the second cycle , the fi rst one followi ng ovarian wedge resection, the cycle has shortened to 28 days.
Chapter 43: PCOD : Medical Effects and Effects o n Fertility 585
Progesterone Prophylaxis -----~ lnfertility and PCOD ------~
Because women with polycystic ovaries ha ve long and In eva luating patients with long and irregular cycles,
irregular cycles and do not ovulate regu larly, the en- the main aim is substantiating the diagnos is. This is
dometrium is exposed to low thresholds of estrogen accomplished by fo ll ow ing the protoco l outlined in
stimulation without opposition from progesterone which Tables 43-1 1 and 43-12. Th is will allow the documenta-
usuall y comes with the forn1ation ofthe corpus luteum . ti on of the characteri st ic horm one patterns, th e ultra-
Thi s unopposed estrogen stimul ati on is what is thought sou nd findings of th e po lycyst ic ova ry a nd it s
to be associated with the formation of adenomato us laparoscopi c identification. Also at laparoscopy, the
hyperpl as ia and subsequently, adenocarcinoma of the endometriosis, which is often present, can be eva luated
endometrium . As a result, wo men with long and irregu- and usually treated.
lar cycles should be regulated with IMH progesterone
in a regul ar fas hi on so that a regular oppos ition to the Lt is com mon for women with polycystic ovarian dis-
estrogen stimu lation is provided. This wi ll give sorne ease to ha ve problems with inferti lity. There are severa!
degree of protection to the forn1ation of adenomatous reasons why this mi ght occur:
hyperplasia and endometrial cancer.
l. Because ofthe long and irregular cycles, ovu lation
There are two main ways in whi ch this can be accom- is occurring irregularl y and not as frequent ly as
plished. At the Pope Paul Vl Jnstitute, the preferred usual , thus decreasing fertility.
method is to give IMH progesterone in a dosage of l 00
2. When ovulation does occur, it is often abnormal.
mg on day 18, 2 1 and 24 ofthe cyc le (F igure 43-17). ln
Ovulation defects are common in women with PCOD.
this way, at about th e 28th or 30th day of the cyc le,
another menstrual period will occur. This intram uscular 3. Endometrios is is common in women with PCO D.
progesterone will regul ate the menstrual cycle and pro-
4. Women with PCOD ha ve limited mucus cycles sug-
vide protection to the endometrium. lt is given long-
gesting target orga n dysfu ncti on.
term, so long as the menstrual cyc les remain long and
irregular. 5. Endocrine profí les show abnormal function of the
developing fo llic le and subsequent corpu s luteum .
It should be noted that it is not unusual for ovu lation to
occur on a more regular basis once progesterone is given In addition to the above, there are undoubted ly other
in thi s fashion. There appears to be a feedback mecha- factors that may contribute to the infertility. Major among
nism to the hypothal amic-pi tuitary ax is by the IMH th ese wo uld be the insulin resistan ce that is often asso-
progesterone which helps regulate GnRH production. ciated with thi s condition.
So long as the progesterone is provided in thi s fash ion,
sorne regulation of ovulation often occurs. When it is Eva luation of these patients begi ns by see ing them in
noted that the mucus cycles are occurring ea rli er and the office and taking a pertinent hi story. At that time,
the woman is experiencing a Peak Day, then the admin- they shou ld begin tracking their ferti lity cycles using
istration of the progesterone shou ld be changed to be the CrMS (Tab le 43-11 ). After two months of charting,
given cooperatively with the cyc le. In that case, the
progesterone can be given in a dosage of 100 mg on Table 43-11: NaProTeclmology
Peak +4, 7, and 10. Thi s wi ll continue the progesterone lnfertility Evaluation Protocol:
support and regulation of the cycle. long and Irregular Cycles'
An alternate approach to this is to use vaginal IMH

progestero ne in a dosage of300 mg capsu les every day • Take the patient's history (upon entry)
at bedtime from day 18 through 27 ofthe cycle. Usua ll y • Chart CrMS for two months
• Return for physical examination and order the
one or two days after th e last progesterone dose, the following :
menstrual peri od will begin. lf ovu lation begins to oc- • Seminal fluid ana lysis
• Amenorrhea profile
cur on th is dosage, then the dosage shou ld be changed , Pelvic ultrasound
to Peak + 3 through 12. • Diagnostic laparoscopy, hysteroscopy and
selective hystero sa lpingogram
• Comprehensive management review
1. In addition, a two-hourglucose and insulin tolerance test with a 75·

gram glucose load shou ld also be pe rformed.
Figure 43-17 : Th is woman , with long cycles characteristic of PCOD, is managed with IMH progesterone , 100 mg IM on day 18,
21 , and 24 (From : Pope Paul VI lnstitute research , 2004).
9 IO 11 12 13 14 15 16 17 18
M M M OC
KI
8C
x!
IOC
•I
SKL IOCL IKL IOKL IOCL IOSL S
•I •' . a . a. • I AD .1
OC '4AO
•I ...
I ""
they can retum for eva luation of thei r charting and a

complete physical examination . At that time, the fo llow- Table 43-12: Amenorrhea Profile
ing tests shou ld be performed:
• Seminal fluid ana lys is (wh ich can also be per- FSH Testosterone TotalT,
formed prior to thi s time) LH Free testosterone FreeT,
• A n amenorrhea profil e Prolactin Androstenedione TSH
• A pelvic ultrasound exam in atio n P-endorphin DHEAs TotalT 3
Reverse T3
• A diag nostic laparosco py, hys teroscopy a nd T3 :rT, ratio
selecti ve hysterosalpingogram
The amenorrhea profil e (Tab le 43-12) inc ludes a com-

plete evaluation of th ose horm ones that might be in-
vo lved in creating the hypoth alami c dysfunction that nodosa in patients w ho have polycysti c ovaries .
results in long and irreg ular cyc les . This wo uld include
an FSH and LH level , prol actin , ~-endorphin , an andro- When thi s eva luati on is completed , the patient returns
gen profile and complete thyro id profi le. for a com prehensive management review which reviews
the findings ofthe laparosco py and ali of the other tests
With the FSH and LH profil e, one is looking for a rever- including th e CrMS charting. A treatment pl an is then
sa! of the FSH:LH ratio. Us uall y FS H is prod uced in outlin ed .
excess ofLH, but in PCO D, LH is produced in excess of
FSH. Prol actin leve ls are usually normal, but ~-e nd or ln treating these patients , ovulati o n inductio n with clo-
phin leve ls are often quite low. Androgen levels mayor miphene is the first line oftreatment (see Chapter 46) .
may not be elevated and th yroid di sturbances may or Thi s treatment program should continue fo r approx i-
may not be detected. mately s ix cycles. An approximate 30 percent pregnancy
rate can be ex pected. However, the re are many women
On ultrasound examinati o n, one looks for the type of w ith PCOD that are resistant to clomiphene and the onl y
changes described previo us ly in this c hapte r. ln order- treatment that really is effective is ovarían wedge resec-
ing such a pelvic ultrasound examinati on, it is good to tion. In the case of clomiphene resistance, ovarían wedge
discuss with the radiologist o r the ultrasonographer, resection should be the treatment of c hoi ce (see C hap-
the type of eva luation yo u a re requesting and the type ter 66).
of clíni ca! findings you are workin g w ith . By describing
PCOD to the radiologist and the type of ultrasound find- When usi ng ovulation-inducing medicati ons, espec iall y
ings characteristic of thi s condition , the exam ination clomiphene, it almost always requires so rne type of
w ill tum out to be much more productive. mucus-enhancing medi catio n because of the a nti-es-
trogen effect of the clomiphene. The ovulation-induc-
A diagnostic laparoscopy is pe rfo rm ed for severa! reation protoco ls a nd muc us-enhancing agents are out-
sons. First of ali , thi s provides the definiti ve diagnosi s lined in detail in Chapter 4 1 (The Method Treatment of
of polycystic ovaries. In additio n, w ith 50 percent of Ova rí an and Ta rget Organ Dysfuncti o n).
women with PCOD also hav ing e ndo metrios is, this can
usua ll y be identifi ed and treated at th e time of the An example ofa wo man w ho has achieved a pregnancy
laparoscopy. Hys teroscopy and se lect ive hysterosa lp- w ith out medication fo ll ow ing ovaria n wedge resection
ingogra phy is also helpful in further eva luating the en- is shown in F igu re 43- 18. The success of these a p-
dometri al cavity and the patency of th e fa ll op ia n tubes. proaches in the treatment of infertility associated with
We have observed, for exa mpl e, sa lping iti s isthmi ca thi s condition is shown in Chapter 75.
"º I
MCS •1.!
°"°
l
°'° °"° °'° OAO
BT BT eT eT eT
Pregnancy in PCOD
with Wedge Resection and FFI
Figure 43-18 : This chart shows a pregnancy occurring in the second cycle following ova rian wedge resection for PCOD. No
medications were used in the cycle of conception . Cycles prior to the wedge resection were consisten tl y 50-60 days in
duration (From : Pope Paul VI lnstitute , 2004).
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lin Rati o is a Usefu l Measure of lnsulin Sens it ivity in Wornen 80. Lanzone A, Caruso A, Di Si mone N, et a l: Po lycysti c Ovary
w ith Po lycys ti c Ovary Syndrome. J C lin End ocrin o ! Metab. Di sease, A Ri sk Factor for Gestational Di abetes? J Reprod
893 :2694 -2698 , 1998. Med 40:312-316 , 1995.
64. Yild irim B, Sabi r N, Kaleli B: Relation of lntra-Abdomina l 8 1. Antt il a L, Karjala K, Penti ll a T-A , et al: Polycystic Ovar ies
Fat Di stribu tion to Metabo lic Di sorders in Non -obese Pa- in Women w ith Gestatio nal Diabetes. Obstet Gynecol 92: 13-
t ie nt s wit h Po lycyst ic Ovary Syndrome. Fertil Steri l 16, 1998.
79: 1358 -1 364, 2003 .
82. G lueck CJ , Wa ng P, Kobayas hi S, et al: Metfonnin Thera py
65. Nest ler J E: S hou ld Pati ents with Polycystic Ovarian Syn- Throughout Pregnancy Reduces the Developrnent of Gesta-
drorne be Treated with Metforrnin ? An Enthusiastic En- tional Diabetes in Women with Pol ycystic Ovary Syndrorne.
dorse m ent. Hum Reprod 17: 1950-1953, 2002. Ferti l teril 77:520 -525 , 2002.
66. Att ia GR , Raine WE, Carr BR : Metforrnin Direct ly lnhi bit s 83. Cra ig LB , Ke RW, Kutteh WH: lncreased Prevale nce of
A nd roge n Productio n in Hum an Thecal Cells. Fertil Steril ln s ulin Res istance in Wornen w ith a Hi sto ry of Recu rrent
76 :517-524 , 200 1. Pregnancy Los s. Fertil Steril 78: 4 87 -490, 2002.
67. Mansfield R, Ga lela R, Brincar M, et al: Metfonnin ha s 8 4. Glueck C J , Phillip s H , Carneron D , e t al: Contin uin g
Direct Effects on Hu rnan Ovarian Steroidogensis. 79:956- Metformin Throu g hout Pregna ncy in Women wit h Poly-
962 , 2003. cyst ic Ovary Syndrorne Appears to Safe ly Reduce First-Tri-
mester Spontaneous Abort io n : A Pi lot Study. Fertil Ster il
68. Marca A, Mo rgan te G, Pa lurnbo M, et a l: ln sulin-Lowerin g
75:46-52, 200 1.
Treatm ent Reduces Arornatase Activi ty in Response to Fo l-
licl e-Stim ul at in g Horrn one in Women w ith Po lycysti c Ovary 85. Bedaiw y MA , Miller KF, Go ld berg JM , et al: Effect of
Syndro me. Fertil Steri l 78: 1234-1239, 2002. Metformin o n Mouse Ernb ryo Deve loprne nt. Fert il Ste ril
76: 1078- 1079 , 2001.
69. Morin-Papunen LC , Koiv unen RM , Ruokon e n A, et al:
Metforrnin Therapy lmproves the Menstrua l Pattern with 86. Giugliano D, Cer iel lo A, Salva tore T, et a l: a-Endorphin
Minimal Endocrin e and Metabolic Effects in Women with lnfus io n Resto re s Acule ln s ulin Respon ses to Glucose in
Po lycyst ic Ovary Synd rome. Fert il Ster il 69:69 1-696, 1998. Type 2 Diabetes Me llitus. J C lin Endocrin o ! Metab 64:944-
948, 1987.
70. Velzque z E, Aco sta A, Mendoza SG: Men strua l Cyc licity
After Metforrn in Therapy and Polycystic Ovary Syn dro rn e. 87. lpp E, Dobb s R, Unge r RH : Morphin e and a-Endorphin s
Obstet Gyneco l 90:329-395 , 1997. ln fluence the Secretion of the Endoc rin e Pancreas. Nat ure.
276:190- 19 1, 1978.
71. Ciampe lli M, Lan zone A: ln sulin and Polycystic Ovary Syn-
drom e: A New Look at an Old Subject. Gynecol Endocrino!. 88. Fu lg hesu AM , Cia mpell i M, Fortini A, et al: Effect of Opioid
12 :277-292, 1998. Blockade on lnsulin Metabolism in Pol ycystic Ovarian Dis-
ease. Hu m Reprod 10:2253 -2257, 1995.
72. Vandermo len DT, Ratts VS, Evans WS , et al: Metforrnin
lncreases the Ovu lato ry Rate and Pregnancy Rate frorn C lo- 89. G ive ns JR , Kurtz BR, Kitabch i AE , et a l: Red uc ti o n of
rniphene Citrate in Pa ti ents wit h Pol ycys tic Ovary Syn- Hyperinsu li ne rni a and ln sulin Resistance by Opiate Recep-
dro m e Who are Res istan! to Clorniphene Citrate A lone. to r Blockade. J C li n Endoc ri no! Metab. 64:377-382 , 1987.
Fertil Steri l 75:310-3 15, 200 1.
90. Fulghesu AM , Lanzo ne A, C uc in e lli F, et a l: Lo ng-Term
73. Coste ll o MF, Eden J A: A Systernati c Revi ew of the Repro- Na ll rexo ne Treatment Red uces th e Exaggerated lnsul in Se-
ductive Systern Effects of Metformin in Patien ts w ith Poly- cretion in Pati ents w ith Polycysti c Ova ry Disea se. Obstet
cys ti c Ovary Synd ro me. Ferti l Steri l 79: 1- 13, 2003 . Gyneco l. 82:19 1-1 97, 1993.
74. Lord JM , Flight lH K, Norman RJ: Metforrnin in Polycysti c 91. Lan zo ne A. Ful ghesu AM , Forti ni A, et a l: Effect o f Opiate
Ova ry Syndrorne: Systernatic Re view and Meta-Analysis. Receptor Blockade o n the ln sul in Response to Ora l Gl ucose
Br Med J 327: 1-6, 2003. Load in Po lycystic D isease. Hum Reprod. 6: 1043-1049 ,
199 1.
75. Ge nazza ni AD, Battag li a C, Malavasi B, et a l: Metformin
A dmini strati o n Modulates a nd Re to res Lutein iz in g Ho r- 92. Lan zo ne A, Fulghesu AM , C uci ne lli F, et a l: Evidence of a
rn o ne Spontaneous Ep iso di c Sec reti on an d Ovarian Fun c- Distinct Dera ngeme nt of Opioid Tone in Hy perinsulinemic
ti o n in No n-Obese Pati e nt s with Polycystic Ovary Sy n- Patients w ith Polycystic Ovary Syndrom e: Re lationship with
d rorne. Fertil Steril 81: 114-11 9, 2004. lnsulin and Luteinizin g Horm one Secreti on. J C li n Endocrino!
Metab. 80: 3501-3507 , 1995.
76 . Fulghesu AM , C iampelli M, Mucj G, et al: N-acety l-cysteine
Trea tm e nt lrnp roves ln sulin Sensitivity in Wornen w it h 93. Fulghesu AM , Cia mpell i M, Gu ido M, et al: Ro le of Opioid
Po lycystic Ovary Syndrome. Fe rtil Steril 77: 1128-1135 , Tone in the Pathophysiology of Hy perinsulinemia and ln-
2002. sul in Re s istance in Po lycyst ic Ovarian Di sease. Metabo-
lisrn. 47:1-5 , 1998.
77. G hazeeri G, Kutt eh WH , Br yer-A sh M , e t al: Effect of
Rosig litazo ne on Spon taneo us and C lorn iph ene Citrate-ln- 94. Vil la P, Va lle D, Mancini A, et al: Effect of Opi o id Bl ockade
duced Ovu lat ion in Women with Pol ycys tic O vary Syn - on lnsulin and Growth Ho rm one (G H) Secretion in Pat ients
drorne. Fertil Steril 79 :562-566, 2003. w ith Po lycys ti c Ovary Sy ndro m e: The He teroge nei ty oí
lm paired GH Secret ion is Related to Both Obes ity and Hy-
78. Cate ldo NA , Abbas i F, McLau ghlin TL, et al: lmprovernent
perinsu lin ism. Fertil Ste ril 7 1: 11 5-1 2 1, 1999.
in lnsu lin Se ns iti vity Fo ll owed by Ovul atio n and Pregnancy
in a Worna n w ith Po lycystic Ovary Syndrome Treated w ith
Ros ig litazo ne. Fenil Ste ril 76: 1057- 1059 , 200 1.
Pelvic Adhesive Disease
and lts Effects on Health and Fertility
elvic adhesive di sease is assoc iated with a variety Th is chapter will dea l with those conditi ons assoc iated
P of different short and long-term health problems.
These include such things as pelvic infl ammatory dis-
with postinfectious adhes ion format ion and those con-
ditions which produce proximal tuba! occ lusion. lt will
ease (PID), ectopic pregnancy, chronic pelvic pain, in- present data relative to the horm onal integrity of th e
fert ility and spontaneous abortion. The main causes of menstrual cycles of those women who have these con-
pelvic adhes ive di sease include endometrios is, ad he- ditions , descri be th e findings observed in the
sions secondary to previous pelvic or abdominal sur- CREIGHTON MODEL FertilityCare™ charts, describe a
gery, postinfectious adhesions and proximal tuba! oc- means of eva luati on and present the concepts of treat-
clusion secondary to such co nditi ons as salpingitis ment. Ad hesions related to en dometri osis and previous
isthmica nodosa. 1 surgeri es have been covered elsewhere in this textbook
and wi ll not be further addressed in this chapter.
Table 44-1: Ten Leading Nationally Sexually Transmitted Diseases ---~

Notifiable lnfectious Diseases
United States, 2000 In the Un ited States we are in the midst ofan epidemic
of sexuall y transmitted di seases (STD). 2 The 1Oleading
No. of No. of
Disease Cases Disease Cases causes of nationally notifiabl e infectious di seases in
the Un ited States fo r the year 2000 are listed in Table 44-1.
Chlam ydi a 702 ,093 Shigellosis 22 ,922
Go norrhea 358 ,995 Lyme disease 17,730
Ofthese, five are sex ua lly transm itted and Chlamydia
AIDS 40 ,758 Tuberculosis 16,377 and gonorrhea are the majar causes of pelvic adhesive
Salmonellosis 39 ,574 Hepatitis A 13,397 disease seen in associati on with pelvic inflammatory
Syph ilis 31,575 Hepatitis B 8,036 disease (PID). The fo rmation ofthese pelvic adhesions
Human Papilloma Virus (HPV) and Herpes Simplex Virus (HSV) are not
ca uses tuba! obstructi on either at the di stal tube, the
notifiable diseases. Source: Centers for Oisease Control and Prevention. prox imal tube or ad hesions which are within the lumen
Summary of Notifiable Diseases-United States, 2000. MMWR 2002; 49
(53): 1-1 02. of the fa ll op ian tube (intratubal adhes ions). Ri sk fac-
tors for inferti lity caused by tuba! obstruction from sexu-
591
ally transmitted diseases are listed in Table 44-2. In al- Ch/amydia

most ali cases, these are associated with a promi scuous
approach to sexual encounters. The two microbes most The single most common infectious disease in the United
common ly observed in PID are Chlamydia trachomatis States is Chlamydia trachomatis. Most women w ith
and Neisseria gonorrhoeae. thi s cond iti on are asymptomatic; however, up to 40 per-
cen t with an untreated Chlamydia infection may de-
Pelv ic pain is caused by these STDs beca use of chronic ve lop PID. 45 The consequences of such an infection
inflammation; decreased mobili ty of the uterus, tu bes are very significant. Many (about 9%) wi ll ha ve a tuba!
and ovaries ; and obstruction of the distal tu be, prox i- pregnancy, others wi ll suffer from chronic pelvic pain
mal tu be or intratubal portion s of the fallopian tu be. ( 18%) and sti 11 others wi 11 beco me infertile (20% ). 6·7
lnfertility is c lose ly associ ated with the number of epi-
sodes a woman experiences with PID (Table 44-3 ). lnfer- The tests used for screening women for gen itourinary
tility follows a single episode of PID in approximately 12 tract Chlamydia and gonorrhoeae infection is outlined
percent ofwomen , after two ep isodes thi s increases to in Table 44-4 . A new generation of nonculture tests,
25 percent, and after three or more episodes it is greater called nucleic acid amp lifi cation tests (NAATs), amplify
than 50 percent. 3 and detect Chlamydia-specific DNA or RNA sequences.
These tests do not require viabl e organisms because
they detect nucleic acid sequences w hich are specific
for an organi sm and require as littl e as a single copy of
th e target DNA or RNA .
Table 44-2: Risk Factors for lnfertility Chlamydia can be devastating from a fertility point of
Caused by Tuba! Obstruction view and can cause exten sive pelvic adhes ions includ-
ing ovarian and extensive pelvic adhesions (Fi gure 44-
Variable Odds Ratio
1) a long with extensive tuba! and ovarian investment
Alcohol consumption 11.2:1 adhesions (F igure 44-2). These adhesio ns tend to be
History of pelvic surgery 11.0:1 film y in appearance but can extensively invo lve the
Frequent anal sex 4.61 uterus, tu bes, ovari es, posterior cu l-de-sac, anterior rec-
Number of lifetime sexual partners 4.2:1
(four or more )
tosigmoid co lon, omentum, etc. The distal tu be may also
History of abortion be in vo lved and can create co mpl ete occ lusion (Fig-
One 3.3:1
Twoorm ore 4.0:1
llleg al abortion
One ormore 3.4:1 Table 44-4: Tests Used for Screening Women
History of STO 2.1:1 for Genitourinary Tract lnfection
Smoker 1.9:1
Age at first intercourse (<1 5 years) 1.6:1
From: Bahamondes L. Bueno JGR, Hardy E. et al: ldentification

Chlamydia trachomatis
of Main Risk Factors for Tubal lnfertility. Fertil Steril 61 :478-482,
1994. A nucleic acid amplification test (NAAT) performed
on an endocervical swab specimen, if a pelvic
examination is acceptable ; otherwise, an NAAT
performed on urine
An unamplified nucleic acid hybridization test, an
enzyme immunoassay, or direct fiuorescent
antibody test performed on an endocervical swab
specimen
• Culture performed on an endocervical swab
specimen
Table 44-3: The lncidence of lnfertility
Neisseria gonorrhoeae
following PID: By Number of Episodes' Culture performed on an endocervical swab
specimen ; if transport and storage conditions are not
Number of Episodes % lnfertlle cond ucive to maintai ning the viability of N.
gonorrhoeae , an NAAT or nucleic acid hybridization
After one episode 12 test can be performed on an endocervical swab
specimen
After two episodes 25
An NAAT performed on urine
After three or more episodes >50
Source: Centers for Disease Control and Prevention. Screening Tests to
1. From: Sciarra JJ : Sexually Transmitted Diseases: Global
Detect Chlamydia trachomatis and Neisseria gonorrhoeae infections-
lmportance. lnt J GynecObstet 58: 107-119, 1997.
2002. MMWR 2002 ; 51 (RR-15): 10.
Chapter 44: Pelvic Adhesive Disease and lts Effects on Health and Fertility 593
Figure 44-1: Extensive pelvic ad hesions secondary to previ- Figure 44-2: Extensive peritubal and periovarian investment
ous infection with Chlamydia trachomatis . The adhesions adhesions secondary to previous infection with Chlamydia
have covered the entire posterior uterus and cul-de-sac (From : trachomatis (From : Pope Paul VI lnstitute research , 2004).
ures 44-3 and 44-4). The distal tube may also be partially The CDC recommended reg1mens for treatment of
occl uded and associated with phimosis, nearly com- Chlamydia trachomatis are azithromycin 1 gram ora ll y
plete occlusion with only tufts of fimbria showing, or in a sin gle dose, or doxycycline 100 mg orally twice
com pl ete occlu sion and hydrosalpinx formation. daily for seven days . Both treatments tend to be very
effícacious and azithromycin is safe and effective in preg-
lt has also been shown that Chlamydia infection is as- nancy.
soc iated with spontaneous abortion. Electron micros-
copy stud ies have suggested the possibility of direct
oocyte infection by Chlamydia in such circumstances. Gonorrhoeae
Two models have been proposed for the pathogenesis
of Chlamydia-re lated early abortions. These include Neisseria gonorrhoeae is second only to Chlamy dia
direct zygote infection and/or immune response to heat trachomatis amongst communicable infectious diseases
shock proteins expressed by the zygote and triggered in the Un ited States. Uncomplicated N. gonorrhoeae
by previous Chlamydia infections. 8 infection is usually confíned to the mucosa of the cer-
vix , urethrae, rectum and throat. lt, too, is often asymp-
Figures 44-3 and 44-4: A large hydrosalpinx with complete distal tubal obstruction of the left fallopian tube (44-3) and a closer
up view (44-4) (From : Pope Paul VI lnstitute research , 2004).
tomatic among fema les; but, if left untreated, can lead to 5. In this examp le, both tubes are tota lly occl uded by
PID resulting in tubal infertility, ectopic pregnancy, and scarring and fibromusc ular hyperplasia. These changes
chronic pelvic pain . Culture testing continues to be the could be the result of a congenital malformatio n, inflam-
referenced s tandard for N. gonorrhoeae, but mation or previous endometriosis.
noncu ltured tests simi lar to those for Chlamydia have
been developed a nd are out lin ed in Tab le 44 -4 . Salpingitis isthmica nodosa (S rN) is defined as the rni-
Gonorrhoeae has been known to become resistant to croscopic presence of irregular, benign extensions of
penici ll in and tetracycline antibiotics. Resistance has the tuba! epithelium into the myosalpinx associated with
also developed to other antibiotics . reactive myohypertrophy. The tuba! nodules ofSrN are
genera lly described as variab le in size. lts etiology is
Both Chlamydia and gonorrhoeae can produce en - not clear, but sorne ha ve thought it is a form of tuba!
dometritis , sa lpingitis , tubo-ovarian abscess and/or adenomyosis. For others it is a seque! of chronic inter-
pelvic peritonitis. They are sometimes seen in associa- stitia l sa lpingiti s ora congenita l ma lformation .11
tion with other organ isms such as E. coli, enterococ-
cus, Enterobacter faecalis, etc. This then becomes a The best way to diagnose a proximal tu ba! occ lusion is
polymicrobial infection and it is estim ated that it af- by se lective hysterosa lpingography and transcervical
fects 1.5 million women in the United States an nua ll y. 9 catheterization of the fallopian tubes (described else-
where in this textbook). This is superior to standard
hysterosa lpingography because it all ows for an iso la-
Proximal Tubal Occlusion -----~ tion of the prox imal tu bes and for each to be stud ied
independently. In addition, palpating the lumen ofthe
Proximal tuba! occ lusion occurs when the obstruction fa ll op ian tube by transcervical catheteri zation provides
is limited to the cornua l or early isthmic po1iions ofthe a reasonably definitive di agnosis ofproximal tuba! oc-
fa llop ian tu be. In a study of 25 patients who had com- c lusion , even if it is partial ; however, it <loes not g ive
plete obstruction ofthe proximal fal lopian tube as diag- specifics as toan etiology. As Table 44-5 indi cates , the
nosed by both se lect ive hysterosalpin gography and etio logy may be ofmultip le orig ins.
transcervical catheteri zation ofthe fa ll op ian tubes, the
most cornmon cause ofthe proximal tuba! occlusion was Proximal tuba! occlusion dueto these conditions is as-
salpingitis isthmica nodosa (Table 44-5). However, other sociated not on ly w ith infe1iility but a lso ectop ic preg-
causes were a lso observed including endometriosis, nancy. 12 One in five patients with proximal tuba! disease
lumina l stenosis, fibros is, chron ic sa lpingitis, fibromus-
cular hyperplasia, acute salpingitis, and intraluminal fi -
brous po lyp w ith ca lcification. 10 G. Right--Normal G. Right--Obstructed
A n examp le of such obstruct ion is shown in Figure 44-
Table 44·5: Pathologic (Histologic)

Diagnosis in Patients with Complete
Obstruction Proximal Fallopian Tube (N=25)
Histol ogic Diagnosis n' %
Salpingitis isthmica nodosa 10 40.0

Endometriosis 8 32 .5
Luminal stenosis 5 20.0
Fibrosis 4 16.0
Chronic salpingitis 4 16.0
H. Left--Normal H. Left--Obstructed
Fibromuscu lar hyperplasia 3 12.0
Acute salpingitis 4.0 Figure 44-5: Micropathology photographs show a normal
lntraluminal fibrous polyp with 4.0 area of the right fallopi an tube (upper left) and an obstructed
calcification area of the proximal portian of the right fallopian tube (upper
right}. In addition , a normal portion of the left fallopian tube is
• Total rrorethan 25 becauseof the presence of mu~ple diagnoses
in sorne cases shown in the lower left and an obstructed portian of the left
From: Hilgers TW. Yeung P: lntratubal Pressu re Befare and After fallopian tube is shown in the lower right. These changes are
Transcervical Catherization ofthe Fallopian T ube. Fertil Ste ri l secondary to scarring and fibromuscular hyperplasia sec-
72:174-178,1999.
ondary to congenital malformation , inflammation or previous
endometri osis.
will also have sorne endosalpingeal damage ofthe amp-

ullary portian of the fa ll opian tube. 13
Table 44-6: Grading the Ampu llary Mucosa Adnexal Adhesions ________~
Grade Descríption TheAmerican Society for Reproductive Medicine (for-

merly th e American Ferti lity Society) has developed a
Normal mucousa l folds seen
classification system fo r ad nexal adhesions (Figure 44-
11 Major folds are sepa rated, flattened , but
otherwise normal 6).14 This classification system can be of assistance in
111 Focal ad hesion s between the mucosa! folds eva luatin g the extent of the adhesions present and al-
are seen low ing for pre-and postoperative results to be compared.
IV Extensive adhesions between the mucosa!
folds and/or disseminated flat areas are
present
V There is a complete loss of the mucosa!
Findings at Salpingoscopy _ _ _ _~
fold pattern
[n pati en ts with adnexal ad hesions, eva luating the amp-
From: Puttemans PF, Brosens IA, Delattin, et al .. Salpingoscopy versus
Hysterosalpingography in Hydrosalpinges. Hum Reprod 2:535-540, ullary mucosa by sa lpingoscopy can provide meaning-
1987.
fu I results with sorne pro g no s ti c s ig nificance.
Puttemans , et al. ha ve developed a simple grading sys-
tem for the mucosa (Table 44-6). 15 There is a sign ificant
correlation between the terrn pregnancy rate and the
lower (G rade 1 and 11 ) sa lpingosco pic grades. 16•17 The
greater the damage to the amp ullary mucosa, the poorer
the prognosis.
THE AMERICAN FERTILilY SOCIETY CLASSIFICATION OF ADNEXAL ADHESIONS
Paticnt's Name - - - - - - - - - - - - -- - - - Da1c _ _ _ _ Chart • - - - -

A¡¡e _ _ G __ P _ _ Sp Ab _ _ VTP _ _ Ectopic _ _ lnfcr1ilc Yes _ _ No _ _
Othcr Signiflcant History (i.e surgcí)', infcction, et c.) - - - - - - - - - - - - - - - - - -
HSG _ _ _ Sonogr:iphy _ _ _ Pho1ogr:iphy _ _ _ Laparoscopy _ _ _ Laparotomy _ __
ADHESIONS < l l j Endosurt: 113 · 213 Endo!>urc: >2 3 Endosure

R Film}
>-
~
,. Dcn.-.e 16
o L filmr
lkn~· 16
R Filmr
"' lkn)l.(_" 4· s· 16
¡::"' L Fiim}
ÜC:'ll)l.t" 4' s· 16
· lí 1hc fimbnatl'<l c:nd uf thc fallop1 an tubc ""l.'umpk1t:ly t:ndosc:d. dungt: lht.' po1ni assignmt:"nl w 16.
Prognosc.Jc Cla.ssificacion for Adnexal Adhesions Addhional Findlngs: - - - - - - - - - -

LEFr RJ(jtff
A. Mimmal
B. Mild
C. Modcr:llt: 11-20
D. S.,·e re Zl -32
Prognosis for Con ccpdon a SubsC'qUC'nt Vlable lnfantºº
T~atment (Surglcal Proccdurcs): - - Exccllent ( > 75'A, )
--Good 1 so. -s·x. J

_ _ fai r (25'X.- 50'»)
- - l'<>o< (< 25»)
'· Phrsician ·s judgmt:"nt ba.st:d upon adnex:i wtth least amo Wlt
of pathv'ugy
Figure 44-6 : The American Fertility Society Classification of Adnexal Adhesions (From : American
Fertility Society. The American Fertility Society Classifications of Adnexal Adhesions , Distal Tubal
Occlusion , Tubal Occlusion Secondary to Tubal Li gation , Tubal Pregnancies, Müllerian Anomalies and
lntrauterine Adhesions. Fertil Steril 49:944-955, 1988).
lncidence of Ovulation Defects and For prox imal tuba! occlusion, the endocrine profiles are
Hormonal Dysfunction ------~ hown in Fi gures 44-1 O through 44-1 2. The periovu-
latory E2 and the post-Peak E 2 leve ls are not decreased
Patients who have regul ar cyc ies and peivic adhes ive signifi cantl y (F igure 44-1 2). However, once again, the
di sease aiso ha ve a frequ ent occurrence of ovulati on- progesterone levels are sign ificantl y decreased in a clas-
re lated defects. When studi ed by seri al uitrasonogra- ic type Il luteal phase defi ciency pattem in thi s group
ph y, ovul ati on defects were ob erved in 56. 5 percent of of patients. In Fi gures 44- 13 th ro ugh Figure 44-1 5 the
menstrual cycies. The most common ovu lation defect is hormone profil es in pati ents with di tal tuba! occ lu sion
a luteini zed unruptured fo lli cie ( 17.4%). The in cidence are shown. In thi s group, the peri ovulatory E2 leve is
of the remaining defects is shown in Tabl e 44-7. and post-Peak progesterone leve! are signifi cantly de-
creased whil e the post-Peak estradi ol ieveis are normal.
Pati ents with peivic adhesion along with those who
spec ifi ca li y have di stal tuba! or prox im al tuba! occiu- A group of39 pati ent with a prev ious hi story of peivic
sion have been studied hormonally as well. Stud ies done adhes ive di sease have been fo ll owed with progester-
at the Pope Paul VI lnstitute using targeted horm one one leve ls during th e course of their pregnancy. That
eva luation in this group of patients (F igures 44-7 through curve is shown in compari son to the normal contro is in
44-1 5) revea! the various abnom1aliti es. Figure 44-1 6. The levels are somewhat higher in the pel-
vic adhes ion group th an they are in the normal controi s
In Figures 44-7 th rough 44-9, the group of pati ents wi th and in so rne cases are stati sticall y significant. Keep in
peivic adhes ive di ease i hown. There are bas ica lly mind, however, that thi s is a treated group of patients
no signifi cant changes in the pre and postovul atory with pelvic adh es ive di sease, hav ing both th e adhe-
estradiol ieve ls (w ith tbe single excepti on of the Peak +3 sions treated surgicall y and the underlying endocrine
E2 leve!). However, the luteal-ph ase progesterone lev- abnorm ali ty treated prospecti ve ly pri or to th e onset of
e ls are markedl y abn orm al and suboptima l. This is pregnancy. Thi s does suggest, however, that with ad-
shown not on ly in the day-to-day profil e but also in th e equate treatm ent, good progesterone levels during the
fi ve va lu e sum and mean fo r the enti re group. cour e of the e pregnancies ca n be obtain ed.
In those pati ents who had di stal tuba! occ lusion, asome-
w ha t s imil a r patt ern is o bse rve d a lth o ug h th e CREIGHTON MODEL Charting _ ___
peri ovul atory E2 levels are signifi cantly lower. Th e
postovui atory E2 leve ls are nonna l, but the post-Peak The CREIGHTON MODEL charting in th ese patients has
progesterone leve ls are al so significa ntl y decreased. also been evaluated. The mucus cycle score in the overall
gro up of patients with pelvic adh es ions was 8.3 com-
pared to the normal ferti 1ity controls of l 0.1 (Table 44-8)
(p=. 138). However, if one breaks down the pel vie adhe-
Table 44-7: lncidence of U ltrasonographically sion group by whether or not the ovulati on pattern by
ldentified Ovulatio n Diso rders in Patients
with Pelvic Adhesio ns 1 (N =69)
Table 44-8: Mucus Cycle Seores in Patients
Normal Ovulation
Ovulation 2 Disorder
with Pelvic Ad h esions
Ovulation Status n % n % and by Ovulation Defect 1
Mature fol licle (MF): +3 30 43.5
MeanMucus
LUF : +, - 17.4 Group Cycle Score
12
MF: -, +, Re 10 14.5
Normal ferti lity controls 10.1
IFS : +, - 9 13.0
(n=19)
AF 3 4.3
DRS: - , Re 3 4.3 Pelvic adhesions (total group) 8.32
PRS: + 2 2.9 (n=35)
Pelvic adhesions (MF: +) 9.93
Totals 30 43.5 39 56 .5 (n=16)
Pelvic adhesions (ovulation defect) l 7.0' 1
1. From: Pope Paul VI lnstitute Research, 2004 .
(n=19)
2. ldentified by ultrasound parameters. A mature follicle with a +
cumulus oophorus and complete rupture.
3. + = cumulus oophorus present 1. From: Pope Paul VI lnstitute research. 2004.
- ;;; cumulus oophorus absent 2. p=.138 (Wilcoxon Rank-Sum Test)
Re = cumulus oophorus retained 3. p=.45 (equal variance 1-test)
4. p=.023 (equal va riance 1-test)
35 100
Periovulatory Estradlol-17P Levels 3 and 4 Value Periovulatory E2
L,
Control (N=21) vs. Pelvic Sums and Means
Adhesions Control vs. Pelvic Adhesions 90
30
• Controlgroup 80
NS NS
¡//
c:I Stuáygroup
i5 ....~.6 .0 68.8
70 (/)
63.3 64 ·8
"'
<I>
e 25
\\I
2
""- 3
,.:. 60 m
/ 53.6 !!l
21 .1 iil
o 20 50 a.
'6 : Q:
i!1
1ñ 17.8
w 40 ....
E // .,;.
2 15 NS
a>
(/)
14 .8
30 <Q.
g,
"
12.8 22.9 NS
17.9
10 10.11/ 15.8 16.2 20
8.8
10
p= NS NS NS NS
N= 8 11 11 10
5 o
E2-4 E2-2 Peak E2 E2+2 ~ 4V8iü8 3"'Vai'üe"" 4 Value
Relationship To Peak~ Level N• 10 N,.7 N=10 N=7
Sum Mean
Figure 44-7
15.7 Sums and Means 90
Control (N=57) vs. Pelvlc Ad hesions
15
80
• Control group
f€'
~E.
O Study group 70
2
"'e1o
10.4
60;
"' 9.4 •• y--------1 --------r .8
r/
1ñ 50 ~
'·r:;
¡¡;
a.
? 40
a
¡¡¡
E
2 ~
(j) "' 5 30 ª-
20
10
P• NS l<.00011 J<ooo5 1 1<.006 1 NS
N• 19 20 20 18 18
o o
P+3 P+5 P+7 P+9 P+11
Days Post-Peak
Figure 44-8
25'-r-~~~-
P-o-st--P-e_a_k_E_s_t-ra_d_lo-1-
- 1-7_p_P_r_o~fl-le-s~~~~~--.~~P-o-s-t--P-e_a_k_E_s-tr_a_d_lo-1--1-7~
P ~--,. 1 oo
Control (N=57) vs. Pelvlc Adheslons Sums and Means

Control (N•57) vs. Pelvlc Adheslons 90
NS 79.5
I I /LJ.. . !...
- Control group 80
::r 20 O Study group
'{?
:g, 70 2
E. 3
"'- m
,.:. 60 !!l
o
'6 15
162 .._
53.2
50
~
~
w •····... ,;;· "' "º ··.\. . ....
40 -tP
E
2
"'
(/)
30
~
~
9.8
8.8 20
10
p. ~ NS NS NS NS
N• 17 19 20 17 15
5 o
P+3 P+5 P+7 P+9 P+11
Days Post-Peak
Figure 44-9
Figures 44-7 through 44-9 : The periovulatory and post-Peak estradiol levels and post-
Peak progesterone levels in patients with pelvic adhesive disease (From : Pope Paul VI
lnstitute research , 2004) .
30
Periovulatory Estradiol-17P Levels 3 and 4 Value Periovulatory E2
Control (N=21) vs . Proximal Sums and Means
90
Tubal Occlusion (PTO) Control (N=21) vs. PTO
25 80
• Control group
u NS D Study group
70 <¿,>
"'
=
e
.:. 20 NS
63.3
60 ~
53.6
g
o 50 ~
u
!11
¡;¡
w 15 14.8 40 -..¡
.¿,
t.
E
~
2
Q) 12.8
(f) 12.4 30
10.1
10 20
a.a
10
p= NS NS NS NS
10 13 15
N= 11
o
E,-4 E2-2 Peak E2 E2+2
Relationship To Peak E2 Level
Sum Mean
Figure 44-1 O
Post-Peak Progesterone Profile

Control (N=57) vs . Proximal
Tuba! Occlusion
(PTO)
15
14.4
13.6
"E
o,
.s
<1> 10.0
:51
Q;
1ií
9.4
...-~ rº .. -------1----....
e
<1>
a..
E
_ . -r
7 6 .-·· -.,
·r a.1
7.5
2 6.1 r
<1>
Cf) 5
P= l.002 I k ooo1 I l cooo1 I G:QU NS

N= 19 19 20 19 1a
o
P+3 P+S P+7 P+9 P+11
Days Post- Peak
Figure 44-11
Post-Peak Estradlol-17P Proflles

Control (N=57) vs . Proximal Tubal Occluslon (PTO)
15
12.0
-'
"e
="'
.:. .. 10.2
10 10.8 9.a
o 8.9
'5 8.8
!11
1ií
w
E
2
"
(f)
5
P= NS NS NS NS NS
N= 17 17 19 18 17
o
P+3 P+S P+7 P+9 P+11
Days Posl-Peak
Figure 44-12
Figures 44-10 t hrough 44-12: The periovulatory and post-Peak estradiol levels and post-
Peak progesterone levels in patients with proximal tuba l occlusion (From : Pope Paul VI
Periovulatory Estradiol-17 ~ Levels 3 and 4 Value Periovulatory E2

Control (N=21) vs. Distal Sums and Means
Tubal Occlusion (OTO) 26.o Control (N=21) vs . OTO 90
80
- Control group
NS
CJ Study group 70 gi
i
63.3 B4.B
16.7 60
53.6
¡¡¡
~ 15 50 §'.
~
w 35.4 40 .¿,
"
E
.,2 1
~
(f) lp <.003 1 30
NS
17.9
15.8 16.2 20
10
P= ~ ~ ~ ~
5 5 5 5
N=
o
E -4
2
E,-2 Peak E2 E 2+2
Relationship To Peak E Level
2 Sum Mean
Figure 44-13
,--P-o_s_t--P-e_a_k_P_r_o_g_e_s_te_r_o_n_e_P_r_o_fi_le~~~~~~~~~~-.-~~P-o_s_t--P-e_a_k_P_r_
o_g_
es_t_
e-ro_n
_e~---,. 1 00
Control (N=57) vs . Distal Sums and Means
Tubal Occlusion 15_7 Control (N=57) vs. OTO 90
15 (OTO)
80
13.6
Figures 44-13 through 44-15: The periovulatory and post-Peak estradiol levels and post-
Peak progesterone levels in patients with distal tubal occlusion (From: Pope Paul VI lnstitute
research , 2004).
600 The Medica! and Surg ical Pra ctice of NaProTECHNOLOGY

Previous History of Pelvic Adhesions (N=39)
150.0 vs. Normal Controls (N=109)
- Control group
D Study group
...J 100.0
E
e,
.e:
e:
e
.."'
$
"'o
el: 50.0
o.o
2-6 weeks 8-12 weeks 14-18 weeks 20-24 weeks 26-30 weeks 32-38 weeks
p-value ~ NS NS [Qill ~ NS
Mean Progesterone - 6 week intervals
Figure 44-16 : The progesterone levels in pregnancy in patients with a previous history of
pelvic adhesive disease versus normal pregnancy controls.
ultrasound was normal (a mature follicle with a positive history of infertility, possibly pelvic pain and a previ-
cumulus oophorus versus a patient with an ovu lation- ous history of sorne other abnormal event such as an
related defect) , the mucus cycle seores were different. ectopic pregnancy. In such situations, the infert ility
ln the normal ovulation group by ultrasound , the mu- eva lu ation is simil ar to any patient w ho might come in
cus cycle score averaged 9.9 (p=NS). In the pelvic ad- w ith a history of regular menstrual cycles. This eva lua-
hesion group where there was an ex isting ovu lation tion is outlined in Table 44-9. lfthe adhesions are thought
defect identified by ultrasound , the mucus cyc le score to be dueto Chlamydia, it is not common for the infec-
was significantly lower at 7 .O (p= .023). tion to be active but a Ch lamydi a antibod y titer can
often document the previous infection.
An example ofthe CREIGHTON MODEL charting ofa
patient with a distal tuba! occlusion associated with
hydrosalpinx is observed in Figure 44-17. The progest-
erone profile is also shown. What is sign ifi cant about
these patients with extensive pelvic disease, associated Table 44-9: NaProTechnology
with either distal or proximal tuba! occlusion, is that the lnfertiliry Evaluation Protocol:
organic problem ofthe adhes ive disease is not the only R egu lar Cycles and Pelvic Adhesive Disease
problem associated with their underlying infertility.
There appears to be a target organ defect by nature of
the limited mucus cycle observed andan ovarian dys- Take the patient's histary (upan entry)
• Chart CrMS far twa cycles
function as indicated by the significant luteal phase Return far physical examinatian and arder the
dysfunction observed. fallawing :
, Seminal fluid analysis
, Full series menstrual cycle harmane profile
• Fallicular ultrasaund series
Chlamydia antibady litre
lnfertility Evaluation in Pelvic Adhesive , Diagnastic laparoscapy, hysteroscapy and
Disease - - - - - - - - - - - - - - - . selective hysterosalpingagram
• Camprehensive management review
Most women who have pelvic adhesive disease wi ll

have regular menstrual cycles as opposed to long and
irregular cycles or anovu latory (a menorrheic) patterns.
In situations such as this, the patient wi ll present with a
L
1
OAO
M
2
1
3
M L
4 5 6
VL VL
OAD OAD OAO
-7
QAD
...
r
8 9 IO
06.D QA.D ~O 4AO

11 12 13 14
04.0 00.D dAD

f
"
f
_.._
15 16
ft
101<: OAD CAD
I
17 18
..... a
r
19
°'º
20 21
OAO OAO
r
22 23
4•.il ~D
24
ax¡
25 26
AAD 04.0
r
27
°"°
28 29 30
MCS
PPP
JI
=1.7
Menstrual score
32
=12 days
33 34
=4.7
35
R:>l/1 .le 41 % qs "

M..- mer FI<
'
By U 'ro< P r ~ :,o
... 1111.C nqlf Roe esft ron
... IS.O lnqfrt'J I Pro< ;este ro1 ~
... 10.c nq¡c~I Pro1 este ror~
8.6
,__ ,_
8.6
-
...
REM NDE R: 1bRD R r EW IC11t RT. ~TA '1PS ANI
l nAK ~M !POI HM ~NT Fm FC LO W·UD
- ---
- -
6.0
o;.r,
""'' 1r:rcx ~ste ron -
...
Figure 44-17: The CrMS chart , ultrasound seri es and progesterone profil e in a patient with exten sive pelvic ad hesions and
bilateral hydrosalpinges. The MCS = 1.7, post-Peak phase is 12 days and menstrual score = 4.7. Th e progesterone profil e is
decreased.
Treatment of lnfertilitY----------, retrospect ive ana lyses and ra ndomi zed control trials
have not been undertaken. Thus, the recom mendati on,
The bas ic approach to treatin g these pati ents is to first while supportin g the general thrust of the profession to
identi fy the exact nature of their underl ying condi tions. in vo lve themse lves in JVF, is not based upon objecti ve
This eva lu ati on wi ll all ow th e phys ician an opportuni ty scienti fic ana lys is. [n additi on, the meta-analyses whi ch
to identi fy the exact phys ica l nature ofthe pe lvic adhe- were used to support thi s reco mmendati on showed that
sive di sease, the underlyin g endoc rine ab normality whi le hydrosa lpinges did decrease the chance fo r preg-
which mayor may not ex ist, and the underlyi ng ov ula- nancy by approx imate ly one halfw hen compared with
tion-related abnormali ty. A surg ica l procedu re can then patients wi th a tuba! factor but no hydrosa lpinges, none
be prescribed as outlined in th e secti on ofthi s textbook of the meta-analyses addres ed the issue ofwhether or
under surgica l NaProTECHNOLOGY and treatment of not pregnancy rates were improved by perfo rmi ng sa lp-
the underlying horm onal dysfunction can be imple- ingectomy prior to the IVF cyc les. In fact, onl y one pro-
mented with those strateg ies outli ned in the chapter on spectively conducted, nonrandom ized tri a! in pati ents
treating hypothalamic pituitary gonadal dysfu nction. who underwent sa lpingectomy ve rsus those who did
There are a few comments whi ch are important here. not was cited and the pregnancy rates were not signi fi-
cantly di ffe rent. Fu11hermore, permanent dra inage ofthe
An official recommendation ofthe American Society for hyd rosa lpi nx via mi crosurgica l fimbri oplasty and recon-
Reproducti ve Medi cine and the Society of Reproduc- structi on ofthe distal tube was not compared. Thi s ap-
ti ve Surgeons for pati ents with adva nced tuba ! disease proach has been shown to produce equi va lent preg-
who des ire fertili ty is in vitro fe rti li zation (IVF). Thi s nancy rates when compared to IVF 19 and shoul d redu ce
has been deemed to be the treatm en t of choice. 18 The the other sequelae observed in pati ents with hydrosa l-
outcome appears to be worse i fa hydrosalpinx is present pi nges because these same prob lems were not observed
and sa lpingectomy pri or to IVF is often recom mended. in patients with tuba! factor but no hydrosa lpinges.
However, thi s approach is based predomi nantly upon
1. Bahamondes L, Bueno GJR, Hardy E. et al: lden tifi cati on of 1O. Hil ge rs TW and Yeung P: lnt ra tubal Pressu re Befare and
Main Risk Factors for Tuba! lnfertility. Fertil Steril 6 1:478- A fter Transcervica l Cath eteri zati on of the Fallopian Tu bes.
4 82 , 1994. Ferti l Steril 72: 174 -1 78, 1999.
2 . Alexander LL, Cates JR, Herndon N, Ratcliffe JF: Sex uall y 1 1. aracoglu FO, Mungan T, Tanzer F: Salp in giti s lsthmica
Transmitted Di seases in America: How Many Cases and at Nodosa in ln fertility and Ectopic Pregnancy. Gyneco l Obstet
What Cos t? Prepared for the Kaiser Family Found ati on by, ln ves t 34: 202- 205 , 1992.
American Social Health A soc iati on. Dece mber 1998.
12. Homm RJ, Holz G, Garvin AJ: Fertil Steril 48:756-760, 1987.
3. Sciarra JJ : Sex uall y Transmitted Diseases: G loba l lmpor-
13. Gurgan T, Urman B, Yarali H, et al: Sa lpingoscopic Findings
tance. lnt J Gynec Obstet 58 : 107- 11 9. 1997 .
in Women with Occlusive and onocc lu s ive Sa lpingitis
4. Rees E. Treatmen t of Pel vic ln ílammatory Di sease. Am J lsthmica adosa. Fertil Steril 6 1:46 1-463, 1994 .
Obstet Gynecol 138: 1042- 1047, 1980.
14 . America n Fertility Society. The American Fertility Society
5. Stamm WE, Guinan ME, Johnson C, et al: Effec ti vc Treat- C lassifica ti ons of Ad nexa l Adhesions, Di stal Tuba l Occlu-
ment Regimens for Neisseria Gonorrhoeae on Simultaneous sion, Tuba! Occlusion Secondary to Tuba! Li ga ti on, Tuba!
lnfec ti on w ith Ch/amydia Tra chomaris . N Engl J Med Pregnanc ies, Mü ll eria n Anomalies And lntraute rin e Ad he-
3 10:54 5-549, 1984. sions. Fertil Ste ril 49:944-955, 1988.
6. Center for Di sea se Con tro l and Preventi on. Screening Tests 15. Puttemans PJ . Broscns IA, Delattin PH , et al: Salpingoscopy
to Detect Chla mydia Tra chomaris and Ne iss eria vers us Hysterosa lpin gogra phy in Hydro sa lpin ges. Hum
Gonorrhoeae ln fec ti ons - 2002. MMWR 5 1 (No. RR-1 5) Reprod 2:535 -540, 1987.
2002.
16. Marana R, Rizzi M, Muzii L, et al: Correlation Between the
7. Westrom L, Joesoef R, Reynolds G, et al: Pelvic lníl amma- Ame rican Fertility Society Cla si fic ati ons of Adnexa l Ad he-
tory Disease and Fe rtility: A Cohort Study of 1,844 Women sions and Distal Tuba! Occlusion, Salpingoscopy and Repro-
w ith Laparosco picall y-Ve rified Disease and 65 7 Contro l ductive Outcome in Tuba! Surgery. Fertil Steril 64 :924-929,
Women with ormal Laparoscopy Resu lts. Sex Transm Dis 1995.
19: 185- 192, 1992.
17. Marana R, Catalana GF, Muzii L, et al: The Prognostic Role
8. Vi g il P, Tap ia A, Zac hari s S. et a l: First-Trimester Preg- of Sa lp ingoscopy in Lap arosco pic Tuba ! Surge ry. Hum
nancy Loss and Active Ch lamydia Trachomaris lnfe cti on: Reprod 14:2 99 1-2 995, 1999.
Co rrel ati on and Ultra stru ct ur a l Evidence. Andro logia
18. Practi ce Com mitt ee Re port. Sa lp ingectomy for Hydrosal -
34 373-378 , 2002.
pinx Pri or to IVF. Ameri can Society fo r Reproducti ve Medi-
9. Sulak PJ : Sex uall y Tra nsmitted Di seases. Se min ars in Re- ci ne and Society of Reprod ucti ve Surgeons. Jul y 200 1.
productive Medicine (Ca rr BR , Ed.) 2 1:399-4 13, 2003.
19 . Gomel V: Salpingostomy by Microsurgery. Fert il Steril
29:380-387. 1978.
Amenorrhea and Anovulation
A n uncommon cause ofinfertility is anov ul ation as- lege student who is under stress in taking exami nations.
~ociated with amenorrhea (0.9%). However, ifthe However, prolonged absence of menstruation in these
underlying etiology can be identified, it represents one patients can be a cause ofinfertility. lt can al so be a pre-
of the most successful groups of patients who can be condition towards the development of osteoporosis
treated. because of the hypoestrogenic state.
There are a variety of different causes associated with In patients who have hyperprolactinemia, their prolac-
this, but four wi ll be considered here: tin leve! will be highly elevated in the face ofwhat oth-
• polycystic ovary syndrome erwise are normal hormone Ievels. Us uall y this type of
• hypothalami c amenorrhea hyperprolactinemia is caused by a prolactin-secreting
• hyperprolactinemia microadenoma of the pituitary gland. Eva luation in-
• premature onset of the menopause. cludes not on ly prolactin levels, but also MRI evalua-
ti on ofthe cella turcica, which will revea! the presence
In polycystic ovary syndrome, the most common cyclic of the adenoma.
pattern observed is one of long and irregular cycles.
The actua l occurrence of amenorrhea is not common,
but it can, on occasion, occur. Thus, an evaluation for
polycystic ovaries is important in the overall evaluation Table 45-1 :Amenorrhea Pro file
protocol for this condition. Polycystic ovaries are di s-
cussed in detail in Chapter 43 .
FSH Testosterone TotalT,
LH Free testosterone FreeT,
In hypothalamic amenorrhea, the standard amenorrhea
pro file (Table 45- l) will be normal. Hypothalamic amen- Prolactin Androstenedione TSH
orrhea is caused by a dysfunction between the hypo- ~-endorphin DHEAs TotalT 3

Reverse T 3
thalamus and the pituitary gland secondary to chronic T 3 :rT 3 ratio
stress. One of the more common associated causes of
hypothalamic amenorrhea is associated with the col-
603
Treatment ofhyperprolactinemia is either bromocriptine gins to ha ve hot flashes and upan evaluation hormo n-
(Parlodel) , which w ill suppress the production of pro- all y, her FSH and LH levels are highly elevated. On oc-
lactin and help shrink the tumor, ora newer medication cas ion , these hormonal characteristics w ill di sappear
called Dostinex. A lmost always these tumors ca n be on their own and normal function will resume. However,
brought under control with th ese types of medications , most often it is permanent. ln addition , it is res istant to
although on occasion, they can cause fairly extensive the treatment with either gonadotropins or GnRH. These
damage. patients need to be treated w ith hormone replacement
therapy so as to prevent bone loss s ince this occurs so
Another condition to be discus ed in the cond itions of early in their li fe.
amenorrhea is in wo men who have Kallmann syndrome.
This is a condition of ame norrhea and anovulatio n as- The eva luati on protocol far patients with infertil ity re-
sociated with anosmia (the inability to smel l). These lated to ameno rrh ea/anovu latio n i shown in Table 45-
patients have primary amenorrhea , which means they 2. In addition , the CREIGHTON MODEL charting pat-
never develop menstrual periods . They need suppl e- terns that are seen in this population ofpatients is shown
mental estrogen to deve lop secondary sexua l charac- in Figure 45-1 A a nd B. In Figure 45-1 A , the pattern is
teristics when they are teenagers. Pregnancy can be one of predominant dryness in the abse nce of men-
achieved in these patients with the use of pulsatile go- struat ion. In Figure 45 -1 B, a pattern more consi tent
nadotropin-releasing hormone . w ith the variable return of Peak-type mucus is illustrated.
This latter pattern is apparentl y due to a waxing and
A final consideration in the diagnosis of amenorrhea is waning of low leve ls of estrogen which are enough to
the question of the premalure onsel of the menopause. timulate the cervix and produce a muc us discharge.
This actually is one of the more common associated
causes of ame norrhea. The di fficulty with the prema- There are, of course, other conditi ons that mi ght also
ture o nset of the menopause is that it a lmost always be associated w ith chronic anovulation. This m ight in-
comes unexpectedl y. The periods stop , the woman be- clude conditions such as anorex ia nervosa, malnutri-
Patterns of Amenorrhea
and Anovulation
A
8
Q
·;,"r
.,
10 <
r I
."... ... ... .9
("\ ("\
8
~
·~ ~ · ~
<~. ~ t~ ·~
,,,
'º" ,,,
"'" ..
e•
:r
Figure 45-1A and 1 B: Two different CrMS patterns observed with amenorrhea/anovulation. The upper pattern (A) is dry in the
absence of menstruation . The lower pattern (B) shows a variable return of Peak-type mucus in the absence of ovulation and
menstruation (From: Pope Paul VI lnstitute research , 2004).
Chapter 45: Amenorrhea and Anovulation 605
tion, Cushing syndrome, and gonadal dysgenesis. In

Table 45-1: NaProTechnology sorne rare cases, th e anovu latory pattern may have an
lnfertility Evalu ation Protocol: autoimmune etiology.
Arnenorrhea
Those patterns assoc iated with polycystic ovaries, hy-
pothalam ic amenorrhea, hyperpro lacti nemia , and
• Take the patient's history (upan entry) Kallmann synd rome ali lend themselves nicely to
• Chart CrMS far four to eight weeks
• Return far physical examination and arder the NaProTECHNOLOGY-related treatment interventions for
following : infertility (see Chapter46).
, Seminal fluid analysis
, Amenorrhea profile
, Pelvic ultrasound
, Diagnostic laparoscopy, hysteroscopy and
selective hysterosalpingogram (optional )
Comprehensive management review
~ptu,46
Medical Treatment of
Ovarian and Target Organ Dysfunction
ver th e years of treating women with infertility This is an extremely important concept in approaching
º prob lems, a major emphasis has been placed on

techn iques re lated to the induction of ovulation .1•3 Al-
most uniformly, this has resu lted in an emphasis on pa-
tients whose inferti lity is related to either oligo-ovula-
the question ofusing vari ous ovulation-inducing med i-
cations. In fact , the entire reproductive system needs
to be treated effectively in order to sustain pregnancy.
While there is not yet a cu re for OTOD, significant
tion or anovulatory conditions. Two major concems arise progress has been made in approaching these issues
from this approach. The first is the overall lack of em- and this is introduced and described in this chapter.
phas is on women with regular menstrual cycles who
experie nce infert il ity and the second is the narrow ap-
proach to ovul ation induction itself. Keeping Perspective _ _ _ _ _ _~
The overwhelmi ng majority ofwomen who are infertile The CREIGHTON MODEL FertilityCare™ System
have regu lar menstrual cycles. While this group of (CrMS ) becomes the foundational element for keeping
women has not been studied well over the yea rs, it is perspective as one approaches both the eva luation and
now clear that they suffer from a very high incidence of eventual treatment of these patients. As the va ri ous
ovul ation-re lated abnormalities along with a dysfunc- target organ dysfunctions of drv cycles. limited mucus
tion of various target organs. These organs would in- cycles, premenstrual bleeding, tail-end brown bleed-
clude the cervix, endometrium, the ovary, the myometrium ing, continuous mucus discharge, "ji-equent 2 W" pat-
and fa ll opian tube. Thus, to approach patients from the terns, prolonged post-Peak phases, short post-Peak
po int ofv iew of"ovu lat ion induction" only, is too nar- phases, and so forth, are observed and eva luated, they
row and constrictive. A N aProTECHNOLOGY approach provide insight into approaches to treatment. Further-
to the treatment ofthe infertile woman takes a more com- more, the CrMS also becomes a means by which the
prehensive view toward the eventual treatment ofthe e woman can be adequately monitored for the effective-
patients. Thus, ovarian and target organ dysfunction ness of such treatment. lt is important to keep in mind
(OTO D) becomes a major, multi-factorial focus of a the relationships ofthe CrMS fertility cha11 and its as-
NaProTECHNOLOGY approach to treatment. soc iation with the various hormones of ovarian func-
607
1 2 3 4 5 6 7 8 9 l m 1u 1u i 13 1 14 15 16 17 18 19 20 21 22l23 l 24 25 26 21 l 2s 29 30 31 32 33 34 35
11
Vl OA.O
VL VL OAO
- f f... f f f ~f 4.f-
OAO OAO OAD CAD tOCL IOKL IOKL 1OKJ 1OKL IOKL CAD CAD OAD Qo\D OAO OAO 0A0 OAD OAO loAo
L H M L L xa AD AD x ól
...
OAD xi
CAD CAD
°"º
I I I I I I
1 1
-
Estradiol-17 ~ Progesterone
-
1
-40.0 ng/dl
1 1 ... 1 1 1
20.0 ng/ml-
-
-30.0 ng/dl
... lo.
~
15.0 ng/ml -
-
-20.0 ng/dl
... .... - 10.0 ng/m l - -
~
-
- 10.0 ng/dl
IREM INDI ~: l PRO Rf EW HtRT,
l ~AK A~POI HM "NT -01 F~
...
¡\I s ~I
5.0 ng/m l -
-
l ... 1• . - .. . i• ¡, ..
Figure 46-1: Daily serum levels of E2 and progesterone shown in correlation with the CrMS chart, the menstrual cycle and the
fertility cycle (From : Pope Paul VI lnstitute research , 2004).
ti on (Figure 46-1 ). the patient can be treated with the princ ipies of thi s
chapter in mind . One needs to keep in mind, however,
In the cornprehensive eva luati on ofthe wo rnan experi- th at if the latter approac h is taken, then the overa ll suc-
encing infe rtili ty, using a NaProTECHNOLOGY-dri ven cess of the NaProTECHNOLOGY approach w ill not be
approac h, the endocrine fun cti on of her menstrual and as high as it could be. Only with the comprehensive
fe rtili ty cycl e, the ovul ation-related structu ra l changes approach to the infertili ty eva luati on and treatment ca n
and the orga ni c a bnormal iti es present in the pe lvis are the hi ghest effecti ve ness rates be observed .
a li evaluated . As a general rul e, the organi c abn ormali -
ti es such as endometrios is, pelvic adhes ive di sease, and In NaProTECHNOLOGY, a technique known asfertil-
tuba! obstructi on should be treated first. In some cases ity:focused intercourse (FFI ) (Figure 46-2), also appears
where a fa mil y physician may be in volved in eva luating to be uniq ue . The author has attended severa! different
the pati ent, or w here access to surgical correcti on of confe rences on the eva lu ati on and management of in-
underly ing organi c abnom1alities is not ava il a bl e, then fe rtili ty and the concept o ffertili ty-focused interco urse
Figure 46-2: The use of fertility-focused intercourse in achieving pregnancy (From : Pope Paul VI lnstitute research , 2004).
Chapter 46: Medica! Treatment of Ova r ian and Target Organ Dysfunction 609
is not recognized. However, with the CrMS 's unique

ability to identify the time offertility in the menstrual
cycle, the couple has within their own ability the oppor-
tunity to identify fertility and facus interco urse at that
Table 46-1: NaProTechnology: time. FFI identifies the fertility cycle and selects inter-
Fertility-Focused lntercourse course far the days on which the mucus is of the best
W ith the CrMS
quantity and best quality and the tirst two days after-
ward (Table 46-1 ). This is illustrated far a patient with
ldentify the fertility cycl e
polycystic ovarían disease in Figure 46-3 and far two
• Select intercourse for the days in which patients with severe oligospermia in Figure 46-4 and far
the mucus is of the best quantity and
quality and the first two days afterward a patient who achieved pregnancy with FFl following
surgical treatment with reimplantation ofthe fallopian
tubes far salpin gitis isthmica nodosa (Figure 46-5).
The medica! support that can be provided to a woman
27 28 29 30 J1 32 33 3~ 35
9C i PC IOKL OAO 4AD OAO '4-Ka 'PC SKL OAO 10 SK IOKL IOCK IOCKL 4 x a 4AO
L M M .. 1 "r xi 1(1 l'f 1 :oc a wl xi xa xa
'~~
l I
aAD IOKL 4AO IOCKL 4AD 4AD 4 K a. OAO OAO OAD OAO .aAD CAD o.o.o 00.0 se OAO OAO 4AD OAO OAO OAO °"°
IC 1 11 1 •I
(f) PG
I I "" I I I T ST
Figure 46-3 : A pregnancy achieved in association with Peak Day on day 4 of the second line confi rmed by ultrasound timing .
This palien! had polycystic ovaries and achieved pregnancy with fertility-focused intercourse (From : Pope Paul VI lnstitute
research , 2004).
12 13 14 15 16 17 18 19 20 21 22 23 24 35
®
HHM M~~~~~~ ~ ~~~~~~~W~~~ ~ ~
., I
&si! r rrrr r
tO KL OAD fo PC ~ PC OAO 4 x a d.X41 4 1ll DAD 4x ~ ~ OA O QA.0

xa "' l'l <l
I I
®
OAO °"'º . . . ~ OAO °'° (±:) PG
¡ TES asr:
Figure 46-4: In the first cycle, pregnancy was achieved with an effective sperm count of 1.3 million . In the second cycle , the
effective sperm count was 1.55 million . Fertility-focused intercourse was the main treatment (From : Pope Paul VI lnstitute
research , 2004).
-
1 2 3 ~ 5 6 7 8 9 IO 11 12 IJ I~ 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
f f f f f f., f.. f.. f f.. ~ f f f.. f ~ ~ f i ~----

J.~ li.'
f")i! r.'f;
M H M L B IOC IOCl<l IOCKI • GV IOGC IOCL IOCL IOCK IOCL IOCL JOCL ~e iOCL IOCL 4AD IOY L IOCL 4AD 4AD 4AO 4AD 4AO +AD VL V L 4AO 4AD ~ 4AO
""'º ., "ª • I KI
• I AD X1 x I xa AD • I
se AD
•' •' G) PG tESl
I
r r
"' r r r r I I I
"'
Figure 46 -5 : This patie nt achieved preg nancy after tre atment of her e nd ometriosis and salpingi ti s isthmica nodosa (From : Pope
Paul VI lnstitute resea rc h, 2004).
Table 46-2: NaProTechnology:

M edica! Suppo rt of O va rian and Target Order D ysfu nctio n
(lnfertile Wom en with R egu ar Lengt h Cycles)
Follicular Phase Defic iency

• Clomiphene • Menotropins • HCG • GnRH
Lutea l Phase Defi ci ency

• HCG • Progesterone • E, • Clomiphene Menotropins
Ovulation Disorders
• Clomiphene • Menotropins • HCG • GnRH
Mucus Enhancers
• Antibiotics (Amoxicill in, Ampicillin , Ceclor, etc.)
• Vitamin 8 6 • Guaifenesin • Prednisone
Abnormal Bleed ing (PMB, TEB )

• HCG • Antib iotics • Progesterone
Continuous Disch arg e

• Hyfreca tion • Antibiotics
General Support
• Naltrexone • Bromocriptine • Dexamethasone
• Nutrition • Exercise
with regular menstrual cycles w ho is ex pe ri enc ing in - Mucus-enhancing agents in clude antibiotics such as
ferti lity and fo r w hich treatment is be ing prov ided fo r amox icillin, a mp icill in or cefac lor (Cecl o r), vitamin B6
OTOD is o utli ned in Tab le 46-2 . A comprehens ive ap- ( py rid ox ine hydroc hl o rid e ), g uai fene s in (Mu cinex,
proach to managem ent can be defín ed by rev iew ing the Humibid-LA) a nd/o r predni sone. Va rio us abnormal
data provi ded by the eva luatio n of the pati ent fo r fo il i- bleeding patterns can be treated with HCG, an tibiotics
cu lar phase and lutea l phase de fi c ie ncy, ovulatio n-re- o r proges te ron e a nd continuous discharge pallerns ca n
lated di sorders, abno rma l muc us cycl e patte rn s a nd be treated w ith hyfrecation or antibiotics.
abno rm al bleeding, co ntinuo us discharges, a nd overa ll
genera l suppo rt. In additi o n to th e above, general support can be pro-
vided w ith the use of naltrexone, bromocripti ne, dexam-
For.fol/icu/ar phase deflciency, the use of clo miphene, ethasone, adequate nutritio n a nd exercise prog ra ms.
me notropin s ( HMG), hum an chorioni c gonadotropin Each of these items w ill be eva luated in greater deta il in
( HCG) and gonado trop in-releasi ng ho rm one ca n ali be thi s chapter.
used fo r spec ifi c s ituati o ns. lutea/ phase defl ciency
can be treated with th e use of HCG, progesterone, estra- To dete rm ine the approach o ne mi ght take, one must
di o l -1 7 ~ (E ) and/o r clomiph ene a nd the menotro pins. start w ith whethe r o r not the woman has a regular men-
2
Ovulation disorders themse lves can be treated w ith clo- strua/ cycle, a long and irregular menstrua/ cycle, or is
m iphene, menotropins, HCG, or GnRH . not me nstrua ti ng at al1(complete amenorrhea - anovu-
lation).
Chapter 46 : Med ical Treatment of Ovarían and Target Organ Dysfunction 611
Before thi s is undertaken, a rev iew ofthe bas ic pha rma- C lom iphene c itrate is capab le of interacting w ith estro-
co logy of clomiphene citrate, the menopausa l gonadot- gen receptor-bind ing proteins in a manner genera lly aki n
ro pins and go nadotropin-re leasi ng hormone wil l be pre- to that of na ti ve estrogens. 15 C lomiphene citrate is best
sented . characte ri zed by the tend ency to di spl ay prol onged
nuclear rece ptor occupancy. In fact, clomiphene citrate
has been shown to occupy nuclear receptor proteins
Clomiphene Citrate _ _ _ _ _ _ _~ for weeks on end , a phenomenon sharpl y contrasting
w ith th e ra ther bri ef interaction of nati ve estroge ns,
C lomiphene citrate (C lomid ; Serophene) was synthe- which are known to clear the cell within 24 hours. C lomi-
sized in 1956 and was first introdu ced fo r clini ca l tria ls phene citrate has been shown to possess no proges ta-
as earl y as 1960.4 Thi s was fo ll owed in 196 1 by the fírst tio na l, corti cotropi c, and roge ni c or anti and roge ni c ac-
publ ished report of its successfu l use for the induction tiv iti es. While thousand s of bas ic and clini ca l investi-
of ovulation in humans. 5•6• 14 The F DA approved it fo r gations have been contri buted to an unde rstanding of
clin ical use in 1967 . clomiphene, the mechanisms and sites ofacti on remain
large ly unknown. Currentl y, it is th ought that it wi ll ini-
C lomiphene is a triphenylethylene derivative bound with ti ate an ovul atory sequence pri maril y, and perhaps ex-
citri c acid, chl oride and an acetoxy gro up. lt is a non- clu sive ly, to its abili ty to be recogni zed and to interact
stero idal age nt w hi ch consists ofa mi xture oftwo iso- with estrogen rece ptors at the leve ! of the hypo thala-
mers: a cis-i somer (referred to as zuclomi phene) and a m us. lt is thoug ht to di spl ace en dogenous estroge n
trans-i somer (referred to as enclomiphe ne) (Figures 46- from hypotha lamic estroge n receptor sites, thereby al-
6 and 46-7). C is-clomiphene is the active component. [t leviating the p utati ve negative feedbac k effect exerted
is weakl y estroge ni c and has an ti-estrogen ic proper- by endogenous estroge ns.
ti es. It competes w ith endogenous estrogens for hypo-
thalamic estrogen receptors in patients who demonstrate Keri n, et a l. 16 showed th at there was a signi fica nt in-
evidence of fo llicular functi on. The lowest effective dose crease in the pul se frequency of luteini zing hormone
necessary to achieve ovul ati on is des irable to minimize (LH) (from 3.3 +/- 0.7 per eight hours on day 2 to 6.8 +/-
its anti-estroge nic effects. 0.8 per eight hours on day 5) with clomiphene. ln addi -
tion, the pul se frequency offollicle-stimul ating hormone
In cli ni cal use, clomiphene citrate is provided as a race- (FS H) inc reased fro m 3.8 +/- 0.6 to 5 +/- 1.4 per eight
mic mixture of its two stereochemical isomers. The race- hours (Figures 46-8 and 46-9).
mi c mi xture is ge nera ll y made up of 38 perce nt
zuc lomiphene citrate and 62 percent of enc lomiph ene The starti ng dosage of clomiph ene is usuall y thought
citrate. to be 50 mg per day from day 5 thro ugh 9 or 3 thro ugh 7
of the menstrua l cycle. However, the determinati on of
this dosage was fa r less than sc ientific. lt makes fo r a
very interesting reading w hen one goes bac k and re-
views the wo rk that led to the recomm endati on of thi s
dosage. For exa mple, clomiphene was admini stered to
women in doses of25 to 200 mg continuously fo r peri-
ods rangi ng fro m one to six months in durati on. Eventu-
a ll y, by way of subtracti on, th e curre nt dosage sched-
2-[p-(2-chloro-1 ,2-dipheny lvinyl) phenoxy] tri ethylamine dih idrogen citrate ule was reco mmended. 7• 14 · 11-22 lt is not we ll recognized
Structural formula of clomiphene citrate that extreme ly low doses of c lomiphene can be utilized
to obtai n sorne ofthe same effects, especially in wo men
Figure 46-6 : The stru ctural formula of clomiphene citrate.
with regular cyc les.
OCH, -CH,-N!C,H,), C lomiphene is not a perfec t pharmaco log ic age nt by

any means. The fact that we continue to rely on it 40
years after it was introduced is a comm en tary in and of
CI
itse lf on the overa ll statu s of research in thi s area. C lo-
•C.H,O, miphene has the effect ofbeing extremely antiestrogenic.
Thu s, it can res ult in the reduction in cervical mucus
TRANS= Enclom iph ene citrate CIS= Zucl omiphene citrate
produc ti on and in the re lati ve thinning ofthe lining of
Figure 46-7: Th e stereochemica l isomers of clomip hene cit- the endometrium .
rate .
612 T he Med ica ! and Surgical Practice of NaProTECHNOLOGY
25 While birth defects ha ve been observed in patients who

have become pregnant with the use ofclomiphene, the
l0CLOMID 1
incidence ofthese birth defects appears to be no differ-
20 ent than that observed in the population at large. 13-30
..J
-E
::::>
E
15
The incidence of miscarriage following the use of clomi-
phene citrate also conforms to that observed in the popu-
lation at large. 31
10
Human Menopausal Gonadotropins==l
5
The use of gonadotrop ins derived from the pituitary of
human cadavers was fírst reported in 1958 by Gernzell.3 2
o However, it was prohibitively expensive to extract it in
25 this fashion. Donini developed a technique for purifica-
I@ CLOMID 1 tion of gonadotropins from the urine of postmenopausal
women. 33 The fírst human pregnancy resulting from
20 ~ HMG therapy was in J 962. 34
..J
-E 15
::::>
E 10
The menopausal gonadotropins are glycoproteins simi-
lar to pituitary gonadotropins. Urinary follicle-stimulat-
ing hom1one (FSH) has a smaller molecular weight than
pituitary FSH and has fewer sugar residues per mol-
eCLile. The biologic activity of urinary FSH is 780 JU/
5 gram compared with 14,000 IU/gram ofpituitary FSH .
However, the clinical effects ofthe two preparations are
indistinguishable when comparable doses of FSH are
o 1 1
administered. 4
0800 1000 1200 1400 1600
Figure 46-8 : The effect of clomiphene citrate on LH pulsing The gonadotropins extracted from the urine of meno-
(From: Kerin JF, Liu JH , Phillipou G, et al : Evidence for a Hypo- pausal women are frequently referred to as menotropins.
thalamic Site of Action of Clomiphene Citrate in Women . J Clin
Endocrino! Metab 61 :265 , 1985).
They are supplied as lyophilized powder which con -
tains 75 lU ofFSH and 75 fU ofLH per ampule.
A "pure" form of FSH has been obtained by removing

LH FSH the LH from the urinary preparation of H MG by
immunochromatography anda new recombinant FSH
8 8 (r-FSH) is al so now availab le. Pure LH is generally not
**
commercially available at the present time.
.r: 6 6
co These medications are both extremely potent as well as
(¡;
<!) being somewhat unpredictable. As a result, individuals
.!!!.
::J
Cl. 4 4 will respo nd differently to the same dose.
Overstimulation of the ovary is a very real consider-
ation and thus, the patient must be monitored ve1y care-
2
fully.
The gonadotropins work directly on the ovary by bind-

o ing to receptor sites and they produce their effect by
Before After Before Afte r way of a C-AMP-mediated second messenger mecha-
nism. The FSH binds to the granulosa cell to stimulate
Fig ure 46-9: The effect of clomiphene citrate on LH and FSH
pulsatility (From: Adashi EY: Clomiphene Citrate - lnitiated its proliferation and induce the aromatase enzyme. The
Ovulation: The State of the Art. In: Wallach EE , Zacur HA LH component binds during folliculogenesis to thecal
(Eds) . Reproductive Medicine and Surgery. Mosby, St. Louis , cells and la ter to granulosis cells after the FSH has stimu-
1995).
Chapter 46: Medical Treatment of Ovaria n and Target Organ Dysfunction 613
lated th e production of LH receptors on the granu losa curs rare ly in these cyc les. This is not always easy to
ce lis of grow ing follicles. The human menopausal go- accomp li sh and does req uire proper timing.
nadotropins promote follicular growth and maturation.
However, in the vast majority of cases, espec iall y those While FSH is the gonadotropin responsible for initia-
who sta1t off with being completely anovu latory or amen- tion of follicular growth , there is ampl e evidence that
orrheic, ovulation and luteini zation will not occur with- LH is also req uired for norm al fo llicul ogenes is.
out an additional inj ection of human chorioni c gona-
dotropin (HCG) to simul ate the LH su rge. For reasons
not entirely understood, a spontaneous LH surge oc- Gonadotropin-releasing Hormone __~
Gonadotrop in-releas ing hormone (Gn RH ) was first iso-

lated , seq uenced and sy nth es ized by Sc ha lly and
Pulsatila Continuous Pulsatile 200
20
Guill em in in 1971. 35 lt was subseq uentl y di scovered that
the continuous infu sion ofG nRH suppressed pituitary
150 ~
function (F igure 46-1 O) wh ile admini stration ofGnRH
.,"'
:r
by discrete pul ses every 90 minu tes could restore nor-
~
100!:
1
mal gonadotropin release (F igure 46-11 ). 36•37 Knobil went
on to show that the normal, co mpl ete menstrual cycle
50 cou ld be restored in Rhe u monkeys with un varying
pulsatile doses ofGnRH .38 This was the essenti al clue
10 10 15 20 25 30 35
to the appropriate admini strati on of GnRH fo r the in-
Days
duction of ovul ati on in women. The first report of preg-
Figure 46-10: The FSH and LH levels during pulsatile or co n- nancies with pul sed GnRH th era py in ano vul atory
tinuous infusion and arcuate lesioned Rh esus monkeys (From :
women was published in 1980. 39 GnRH is a decapeptide
Belchetz PE , Plant TM , Nakai Y, et al : Hypophyseal Responses
to Continuous and lntermittent Delivery of Hypothalamic-Go- and it is now ava iJabl e in synth eti c form as a powder,
nadotropin-releasing hormone. Science 202:631 , 1978). so lubl e in aq ueo us so lution under the name Factrel
(Ayerst Laboratories, ew York) in 100 mcg vials. Its
primary indication is fo r women who ha ve hypothalamic
1 Pulse/hour 5 Pulse/hour 1 Pulse/hour
amenorrhea. In that case, it is used with a computerized
40
35
pump whi ch gives a preset pulsatil e intravenous <lose
30 of the medication. Jt can also be used subcutaneously
I
::;
25 in se lect circumstances (see below).
~ 20
3 15
10
Low-dose Clomiphene Progession ==l
A While it is still widel y recogni zed that the starting <lose
994
of clom iphene citrate is 50 mg per day fro m day 5 through
1 Pulse/hour 1 Pulse/3 hour 1 Pulse/hour 9 of the cyc le, it is clear that much lower doses of clomi-
50
45
40
...
500
400
phene can be used with success. 40 •42 At the Pope Paul
¡ 35 350 1
~
::; 30 300 ~
e Table 46-3: Low-Dose C lomiphene P rogression:
E 2s 2soi3
lnfertile Wom en with Regu lar M enstrual Cycles
3 20 200 r;
15 150
10 100
50
Slart wilh .. 25 mg clomiphene
20 15 10 5 o 5 10 15 20 25 30 35 .(O PO QD d. 3-5 of cycle
B
then move to ... 50 mg clomiphene
Figure 46-11 : FSH and LH levels during pulsatile infusion of PO QD d. 3-5 of cycle
GnRH with dose intervals of one hour, 12 minutes (A) or 3
hours (8 ). Note the increase in FSH and decrease in LH at 3- Maximum dose 50 mg clomiphene
hour dose interval (From : Wildt L, Hausier A, Marshall G, et al : PO QD d. 3-7 of cycle
Frequency and Amplitude of Gonadotropi n-releasing hormone
stimulation and Gonadotropin Secretion in th e Rh esus Mon-
key. Endocrinology 109:376 , 1981 ).
614 The Medical and Surgical Practice of NaProTECHN OLOGY
Table 46-4: Periovulatory E, Levels

with Clomiphene and Gonad~tropins
Compared to Unstim.ulated Normal Ovulation Controls 1
Mean Levels ng/dL
Study group PE, -2 PE 2 PE, +2 SUM MEAN

Normal ovulation controls 14.8 26.0 12.8' 53.6 17.9
Clomiphene
25 mg d. 3-5 41 .2 68.9 45.9 156.0 52.0
(n =2)
50 mg d. 3-5 17.8 27.3 10.1 55 .2 18.4
(n =4)
50 mg d. 3-7 39.0 65.5 33. 2 137 .7 45.9
(n = 5)
Gonadotropins
75 IU FSH/LH 19.0 40.3 18.9 78.2 26.1
d. 3-7 (n =2)
150 IU FSH 30.8 53.6 20.2 104.6 34.9
d. 3-7 (n =2)
1. From: Pope Paul VI lnstitute resea rch , 2004.
VI Institute, a low-dose clomiph ene progression has length of the post-Peak phase is either too short or too
been used and deve lo ped for treating infertil e women lo ng, then treatment ofluteal ph ase deficiency needs to
w ith regular menstrual cycles (Tabl e 46-3). ln thi s probe impl e mented . lfthere is abnorma l bleeding, that too
g ression, the starting dose is 25 mg of clomiph ene ( 1/2 must be addressed. lf a patient deve lops an ovaria n
tablet) by mouth dail y, from day 3 through 5 ofthe cycle. cyst (which is very rare o n thi s program), prolongation
In the great maj ority of th e cases, this wi ll stimulate of the post-Pea k phase and sorne abnormal bleeding
adequate follicular growth and develo pment. lf this is a long wit h the pre me nstrual or tail-end portion of the
deemed inadequate, then 50 mg per day, day 3 th rough next menstrua l period wi ll be observed.
5, is th e next step up . Finally, ifthe response is still not
adequate, then the standard starting dose of 50 mg per The CrMS is also impo rta nt in monitoring the progest-
day from days 3 through 7 is utili zed. Generally speak- erone and E 2 leve ls fo r patients o n c lomiphene. This
ing, if clomiphene is started earlier than day 5, it w ill can be acco mplished in a re producible fashion by mea-
also result in more rapid follicular growth .43 suring th e progesterone and E 2 levels on Peak + 7. This
monitors luteal fun ction and indirectly follicular fim c-
ln Table 46-4, peri ovul atory E2 leve ls are shown wit h tion . The aim is to achieve a progesterone leve! that is
varying doses of c lomiphene citrate and gonadotro-
pins . These are compared to unstimul ated norm al ovu-
Table 46-5: Monitoring Low-Dose Clomiphene
lation contro ls. While the numbers in each of these in-
Medica! Support Program
di vidual circumstances are small , it is c lear that even
with low doses of clomiphene, signifi ca nt stimul ati on Monítoring Téchnique lmportant Observation
ofE2 from the developing fo llicle can be observed. Thi s
CrMS • Mucus cycle intensity
is true a lso with the go nadotropin s. • Length of post-Peak phase
• Presence of abnormal bleeding
When an indi vidual is receiving a low-dose clomiphene • Other factors
medica! support program, the CrMS becomes an impor-
P + 7 Progesterone • Monitors luteal fun ction and
tant monitoring technique. Not onl y is the intensity of and E, level indirectly follicular function
the mucus cyc le obse rved and recorded, but the length • Progesterone level should be
13-15 ng/ml or greater
of the post-Peak phase a nd the presence of abnormal
• E, level should be 12 ng/dl
bleeding pattem s can also be docum ented . lf th e mu- orgreater
c us inte ns ity is decreased s ig nifi ca ntl y, then mucus-
enha ncing age nts need to be utili zed (see be low). lft he
Cha pter 46: Medical Treatment of Ovarian and Target Organ Dysfunction 61 5
13-15 nglmL or g reater and an E 2 leve! which is 12. O ln each case, there was a significant increase in the
ngldL or greater (Table 46-5) . postovulatory progesterone leve!. This was greatest
with the addition of prednisone and dexamethasone.
Peak +7 progesterone levels with a low-dosage clomi-
phene program, both before and with treatment are docu-
mented in Table 46-6. In this case, even with low doses Low-dose Menotropin Progression===l
of clomiphene, there is observed a significant increase
in the production of luteal phase progesterone. This is Tt has been shown that a low-dose, preovulatory imp le-
apparently because of the stimulation of more normal mentation ofhuman menopausal gonadotropin therapy
folliculogenesis. The use of dexamethasone or pred- can be effective in the treatment ofthose patients with
nisone in add ition to clomiphene has been promoted as regular menstrual cycles and poor cervical mucus.47This
a means ofallowing the clomiphene to work more effec- program utilized one ampule (75 TU) ofHMG from days
tive ly.44-46 5 through 11 ofthe cyc le. lfthere was no response, the
dosage was increased to two ampules . In this case, be-
In Table 46-7, the en tire group of patients studied, who cause these women were having regular cycles to begin
were using either clomiphene alone or clomiphene with with, the use of HCG was not necessary to insure ovu-
Vitamin B 6and/or prednisone-dexamethasone is shown . lation. This HMG protoco l was found to be more effica-
cious than IUl, lVF or GIFT. 47
Table 46-6: P+7 Progesterone Levels
with Low-Dosage Clomiphene The low-dose menotropin progression is shown in Table
Before and With Treatment 46-8 . The program starts with one ampule (75 IU) given
intramuscularly (IM) days 3 to 7 ofthe cycle. lfthere is
: Before After not an adequate response, then two ampules are given
Mean Mean
( 150 ru) from days 3 to 7 ofthe cycle. lt is possible to go
Treatlllellt Program llg/111[ ng/m l
somewhat higher than this but it is extremely important
Clomiphene 50 mg d. 3-5 9.3 23. 3 1 that careful monitoring with ultrasound and E 2 leve ls be
(n=5)
done. Low-dose menotropin therapy needs to be mon i-
Clomiphene 50 mg d. 3-5 with 9.9 16.6 2
Prednisone or dexamethasone tored carefully. The monitoring system is outlined in
(n=7) Table 46-9.
Clomiphene 50 mg d. 3-7 8.9 16.4 3
(n=20)
The CrMS is again used to monitor the intensity ofthe
Clomiphene 50 mg d. 3-7 with 7.9 20 .04
Prednisone or dexamethasone
mucus cycle, the length ofthe post-Peak phase and the
(n=9) presence ofany abnom1a l bleeding . Pre-Peak E 2 levels
are obtained every other day from Peak - 6 through Peak
1. p=.090 (Aspin-Welch)
2. p =.021 (Equal-variance t-test) +2. lt is the aim to ha ve the E 2 Peak leve! at greater than
3. p=.015 (Wilccxon Rank-Sum test)
4. p=.015 (Wilccxon Rank-Sum test) 26.0 ng/dL and less than 90.0 ng/dL. Ultrasound exami-
nations should also be do ne at least on Peak - 2 and
Peak + 3. The first ultrasound evaluates the presence of
follicles and the number stimulated . The Peak + 3 ultra-
sound evaluates the presence of a corpus luteum or a
Table 46-7: P+7 Progesterone Levels luteinized unruptured fo ll icle (LUF) . Finally, Peak +7
Before Clomiphene and with Clomiphene progesterone and E 2 levels are also obta ined with the
Befóre Rx AfterRx.
Mean ... Mean Table 46-8: Low-Dose Menotropin Progression:
Tr~atinelltF>rogram llglmL •. nglml
lnfertile Women with R egular Menstrual Cycles
Clomiphene alone 8.0 16.3 1
(n=34)
Clomiphene with Vitamin B6 9.7 14.82
(n=10) Start with .. One amp (75 IU)
3
day 3-7 of cycle
Clomiphene wi th prednisone 6.6 19.8
or dexamethasone
then move to ... Two amps (150 IU)
(n=24)
day 3-7 of cycle 1
1. p=.0001 (Wilcxon Rank-Sum test)
2. p=.029 (Wilccxon Rank-Sum test) 1. One may go somewhat higherthan th is but very careful monitoring
3. p=.0001 (Wilccxon Rank-Sum test) with ultrasound and E2 levels is manditory.
616 The Medica l and Surg ic a l Pra c t ice of Na ProTECHNOLOGY
same goals in mind as with the low-dose clomiphene the post-Peak phase is too long on that dosage, then it
protocol. can be decreased to Peak + 3, 5 and 7. If the progester-
one and E2 level s are too hi gh, then the overall <lose can
be decreased to 1000 IU .
Use of HCG _ _ _ _ _ _ _ _ _~
For follicular phase support, a " mini-dose" HCG can be
The use ofHCG in support of ovarian function in infer- provided. This dosage is given in the amount of 100-
tile women with regular menstrual cycles is outlined in 200 lU , HCG, SQ, beginning seven days prior to the
Table 46-10. In fact, HCG can be used for three pur- Peak Day and continuing every day through Peak +2.
poses: luteal phase support, follicular phase support HCG is used as an LH substitute. lt has recently been
and/or a follicular rupture triggering dose. shown that with the use of low-dose HCG during the
preovulatory phase ofthe cycle there was an enhanced
In luteal phase support, HCG is generally provided ata production of preovulatory E 2 by the developing fol-
dosage of2,000 IU , IM or SQ on Peak +3, 5, 7 and 9. lf licle. This resulted in a decreased amount ofrFSH <lose
necessary to stimulate the ovarian fo ll icle whi le replac-
ing it with the much less expensive HCG.
Table 46-9: Monitoring Low-Dose Menotropin
with or without Mini-Dose HCG Therapy ln the normal menstrual cycle, continued dominant fol-
Medical Support Program licle growth, in spite of declining FSH levels is likely
Monitorin g Tech nique lm portant Observa tio n
brought about by LH stimulation of granulosa cell s that
have acquired LH receptors . It was dernonstrated that
CrMS • Mucus cycle intensity low-dose HCG is capable of directly stimulating ovarian
• Length of post-Peak phase
follicle development in the presence offixed or increas-
• Presence of abnormal bleeding
• Other factors
ing FSH levels. 48-49 HCG se lectively binds to LH recep-
tors and exerts the same ac tions as LH , however, be-
Pre-Peak E2 levels • E, Peak level
cause its half-life is more prolonged , HCG is approxi-
QOD P-6 through P+12 > 26.0 ng/dl
• E2 Peak level mately six times more potent than LH. This longer half-
< 90 .0 ng/dl life is somewhat ideal in that the longer decay period of
Ultrasound exami nati o n • P-2 ultrasound evaluates
HCG can insure a more stable stimulation ofLH recep-
P-2 through P+ 3 presence of follicles and tors over the 24-hour interva ls between hormon e ad-
number stimulated
mini strations .
• P+3 ultrasound evaluates
presence of corpus luteum or
a LUF HCG can also be used to mimic the LH surge. Generally
P + 7 Prog estero ne • Progesterone level should be
speaking, 10,000 units ofHCG are given when the fol-
and E, level 13-15 ng/ml or greater licle reaches 1.8 mm in size (mean fo llicu lar diameter by
• E2 level should be 12 ng/dl or ultrasound) and/or the endometrium is greater than or
greater
equal to 9 mm in thickness. Generally speaking, this will
be about two days prior to the onset of the Peak Day
and can be estimated from previous cycles.
Table 46-10: Various Uses of HCG High-dose Clomiphene Program --~

in Support of Ovarian Function:
lnfertile Women with Regular Cycles A " high-dose" clom iphene c itrate program is reserved
for those patients who have polycystic ovarian dis-
l odi cation Dos age ease. ln this group of patients, the initial starting <lose
Luteal phase support • 2,000 IU HCG P+3, 5, 7, 9 is 50 mg per day from day 5 through 9 ofthe cycle (the
standard starting <lose of clomiphene). Jf a menstrual
Follicular phase support • 100 - 200 1U SQ 7 days befo re
Peak Day through P+2
period <loes not occur by day 35 and the patient is not
pregnant, then 200 mg of progesterone is administered
Follicular rupture • 10,000 units IM when follicle lM to initiate a period (Tab le 46-11 ). Once the menstrual
triggering dese reaches 1.8 mm (M FD ) or
palien! is near Pea k Day flow begins, the dosage is increased to 100 mg by mouth
every day (QD) day 5 through 9 ofthat cycle. Ifa period
<loes not occur by day 35 and pregnancy or ovulation
Chapter 46 : Medicar Treatme nt of Ovarian and Target Organ Dysfunction 617
Table 46-11 : High-Dose C lo miphene Progression: Table 46-12: M o nito ring High-Dose
lnfertile W o m en wi th C lo miphene T herapy fo r W o men with
Long and Irregular M enstrual Cycles Long and Irregular M enstrual Cycles
Monitoring TechniqUé Importan! Observat.i on
lnitial dose 50 mg PO QD d. 5-9 of CrMS • Presence of a mucus cycle

e y ele with a Peak Day
lf no period by day 35 200 mg progesterone IM • Length of post-Peak phase
to initiate period • Presence of abnorma l bleeding
Then 100 mg PO QD d. 5-9 of • Other factors
cyc le
P + 7 Progesterone • When cycles become reg ular
lf no period by day 35 200 mg progesterone IM and E 2 level • Progesterone should be
to initiate period
13-15 ng/ml or greater
Then 150 mg PO QD d. 5-9 of • E2 leve! should be 12 ng/dl or
cycle greater
lf no peri od Then patient is clomi-
phene resis tan!
has not occ urred, then 200 mg of progesterone is once Table 46-13: P+7 Progesterone Levels
aga in given IM to initi ate a menstrual tl ow. The dosage with Higher-Dosage C lomiphene
is then increased to 150 mg by mouth every day (PO Before and with Treatment
QD) day 5 through 9 of the cycle. lf no menstrua l peri od
occurs, and/or no pregnancy occurs over a six-cyc le Befo re After
time frame (regardl ess of the dosage of clomiphene, so Mean Mean
Treatment Program ng/ml ng/rnl ·
long as regul ar ovul atory cyc les are occurrin g), then
the pati ent is considered to be clomiph ene res istant. Clomiphene 100 mg d. 5-9 5.6 14.9'
(n=5)
Clomiphene 100 mg or more d. 5-9 8.3 22.32
lt can be ofsome ass ista nce to admini ster a corticoster- with prednisone or dexamethasone
oid such as dexameth asone or predni sone. Thi s may (n=8)
enhance the effect of clomiph ene and decrease the inci - 1. p =.0 1 (Equal-va riance 1-test)
2. p =.0005(Equal-variance1-test)
dence of res istance. 4 However, whi le ovu lation rates
are fa irly hi gh with clomiph ene in patients who have
pol ycysti c ovarian di sease, the pregnancy rate remains
quite low. In additi on, Pea k + 7 progesterone and E2 leve Is are al so
drawn with the sa me param eters in mind as that previ-
Of course, these pati ents should also be eva luated fo r ously described fo r regul ar menstrual cyc les.
in sulin res istance and , if necessary, metformin should
be prescribed. At the sa me time, however, it must be The Peak +7 progesterone leve ls with a hi gher-dose
recognized that the best pregnancy rates ul timately come clomiphene both before and with treatment are noted in
as a res ult of ovari an wedge resecti on. Thi s surgica l Ta ble 46- 13. At 100 mg of clomiph ene from days 5
procedure, which was abandoned many years ago fo r through 9 of the cyc le, there is a significant increase in
reasons that no longer ex ist, is ultimately the very best the production ofprogesterone during the lutea l phase
treatment for these pati ents. Usually, even fo ll ow ing a ofthe menstrual cycle.
wedge resection , clom iphene is still used. The ova ri es
are much more recepti ve to the use of clomiphene under
those circum stances. Treatment of Amenorrhea _ _ _ _ _~
In monitoring patients on the " hi gh-dose" clomiphene In patients wi th amenorrhea, an adequate eva luation
program (Tabl e 46- J 2), the CrMS is used in the sa me for the underl ying cause of their amenorrheic state is
fa shi o n as it is w ith a li o th e r mo ni to rin g in necessary. Most cases will be related to hypothalami c
NaProTECHNOLOGY. lt is an essenti al too l to moni tor- ame norrh ea whil e oth ers may be related to hyper-
ing the type of cycl e th at is occurring and whether or pro lacti nemi a or even Kallm ann syndrome (Tabl e 46-
not there is an adequate mucus cyc le to defi ne fe rtili ty. 14). Th e medi ca ! support fo r ova ri an fun cti on in
618 The Med ical and Surgical Pract ice of NaProTECHNOLOGY
wome n w ith hypothalamic amenorrhea is to ftrst of ali, T he CrMS is once aga in used for its usual impo rta n!
use naltrexone up to a dosage of 150 mg per day (bui ld- fu nctio ns. Ovarian ultrasound, however, is used mo re
ing up very s low ly to that dosage). If this fa il s, then v igoro us ly to monitor the growth a nd development of
they are a candidate for ovarian and target organ stimu- the fo lIicles and th e number of fol Iic les present. Estra-
lation w ith the pul satile administration ofGnR.H by in- d io l leve ls during the preovulatory phase of the cycle
fusion pump .59 a re m eas ured d a il y to m o n ito r the potent ial fo r
overstimul atio n and Peak + 7 progesterone and E2 levels
In the case of hyperpro lactinemia, the presence of a are also monitored to insure adeq uate luteal function.
pituitary adenoma needs to be ruled out. The treatment
is to use either bromocriptine ( Parlodel) or cabe rgol in e
(Dostinex). lmplementation of Protocols ----~
In Kallmann syndrome (anovu lation with anosmia), the [n approaching a patient fo r the implementation of o ne
use of pul satil e GnRH by infus ion pump is a lso uti- o r more of the above protoco ls, an adequate eva luation
lized.56 is necessary and has been prev iou sly discu ssed . This
eva luatio n w ill determine w hether o r not afollicular
The ab ili ty to mon ito r the pul atile GnRH is shown in phase deficiency, luteal phase deficiency oran ovula-
Table 46-15. This monitoring i more extensive than what tion-related defect is present. lt wo uld also tell o ne
is used for any ofthe other ovul ation-related programs. whethe r or not there is a target organ dysfunction (en-
docrine receptor disorder) w ith the production of cervi -
ca l mucus or the endometrial lining. This is determ ined
Table 46-14: M edica! Support for O varian by the presence of dry or limited mucus cycles or ultra-
Functio n in Women with A m en o rrhea sound evidence of an endometrium that is too thin. T he
ab norma l bleeding th at shows on the CrMS chart (es-
lndication Dos age
pecial!y premenstrua l bl eeding and/or tai l-end brown
Hypothalamic amenorrhea • First, naltrexone to 150 mg per bl eedin g) is also ofs ignificance. Genera l medica! sup-
day
port fo r these women is also necessary and is described
• lf this fails, then GnRH by
pump below.
Hyperprolactinemia • Bromocriptine
• Dostinex
Fol/icular Phase Function
Kallmann syndrome • GnRH by pump
Once the endocrine profil e ofthe menstrual cycle has

been reviewed, it can be determin ed w hether or not the
wo man has Leve! AAA , AA, A, B , o r C fol licular phase
function. In Leve! A , fo llicular function is norm al and
Table 46-15: M o nito ring PulsatiJe GnRH Therapy

in M edica! Su ppo rt of Ovarían Functio n Table 46-16: aProTechnology
in Patients with H ypothalamic Amenorrhea M edica! uppo rt for DiHerent Levels
of Follicular Phase Deficiency
Monitoring Techni que lmpo rtant Obs ervation
(lnfertile Women with R egu la r M enstrual Cycles)
CrMS • Observe for regulation of the
cycle Level of Follicular
• Then for mucus intensity, Phase Defi ciency Medical Support
length of post-Peak phase and
abnormal bleeding Level A, B, or C • No treatment if above the
mean
Ovaría n ultrasound • Day 5 of cycle as baseline • Low-dose clomiphene if below
• Daily from P-5 through FR the mean: 25 or 50 mg PO QD
d. 3-5 of cycle
E, levels • Daily levels to observe for OR
over-stimulation (P-5 through • Low-dose menotropins days 3-
FR) 7 of cycle and mini-dose HCG
d. 8 through P+2
P + 7 P+E 2 • To observe for optimal luteal
fun ction Level AM. AA • No treatment
Chapter 46 : Med ical Treatment of Ovarían and Target Organ Dysfunction 619
there is no treatment necessary ifthe Peak leve! ofE 2 is optima! profile of progesterone is identified. Thi s is usu-
above the mean (26.0 ng/dL). However, ifthe Peak leve! all y assoc iated with a fo lli cular phase deficiency, so a
ofE 2 is below the mean , than the low-dose clomiphene combination of low-dose clom iph ene along with the
protocol is indicated starting at the 25 mg per day, day 3 post-PeakHCG protoco l is utilized .
through 5 of the cycle.
In a Type IIl tutea! phase defic iency, a defi ciency in
In a Levels B and C foll icular phase function , the peri- which the progesterone leve ls drop precipitous ly at the
ov ul atory E2 levels are substantially decreased. In this very end ofthe menstrual cyc le (usually the last seven
case, the low-dose clom iphene protocol beginning at days), HCG is admini stered to stimulate the corpus Iu-
the 25 mg dosage is impl emented. lfthat protocol does teum to produce more progesterone and E2 onl y on Peak
not work effective ly, it can be increased ora move to the +5, 7 and 9. The preovu latory E2 profile is usually nor-
low-dose menotropin protocol can be used with or with- mal and thus no fo llicul ar stimul ation is necessa ry.
out mini-dose HCG.
In a Type IV luteal ph ase deficiency, a defic iency in
In Levels AAA and AA follicu lar phase function , the E2 which the amount of progesterone being produced is
leve ls are higher than norma l and , so long as there is no significantly decreased earl y in the luteal phase, HCG is
ovu lation-related defect associated with it, preovula- administered on ly on Peak +3, 5 and 7 and if a follicu lar
tory treatment is generally not necessary. phase deficiency is present, it shou ld be treated.
In a Type V lutea l phase defic iency, a deficiency which

Luteal Phase Deficiency is an iso lated E2 defici ency, the patient is suppl emented
with E2 either in the form of 1 mg to 2 mg by moutl1 every
There are five di fferent types of tutea! phase deficiency day at bedtime (PO QD hs) Peak +3 through 12 or 5 mg
which have been described (see Chapter 35). Each of oftriestrogen mouth every day at bedtime (PO QD hs)
these approaches requires a sl ightly different implemen- Peak + 3 through 12 or one or the other of these used
tation oftherapy. HCG and/or clom iphene are the main- vaginally (in a non-susta ined-release form) fro m Peak
stays of treatment for th is aspect of the problem. + 3 through Peak + 12.
In a Type] tutea! phase deficiency where the luteal phase

is short and suboptima l, HCG in the dosage of2000 IU For Ovulation Defects
provided either IM or subcutaneous ly on Peak + 3, 5, 7
and 9, is used. Often, low dose clom iphene may also be Medica! support for the different types of ov ul ation
necessary. defects determined by ultraso und assessment is out-
lined in Table 46- 18. Ifa mature fo lli cle with a positive
In a Type 11 luteal phase deficiency, a significantly sub-
Table 46-18: M edica! Su pport for

Table 46-17: Medica! Support for Different Ovulatio n Defects
Different Types of Luteal Phase Deficiency as Determined by U ltrasound Assessm ent
(Infertile Women with Regular Menstrual Cycles) (lnfertile Women with R egular M enstrual Cycles)
Type of Luteal
Type of Ovulation
Phase Oeficiency Medical Support
Defect Medical Support
Type 1 • HCG: 2,000 IU IM or SQ
MF: + • No treatment needed
P+3 , 5, 7, 9
MF: - • Low-dose clomiphene
Type 11 • Low-dose clomiphene plus
HCG : 2,000 IU IM or SQ P+3 , • Low-dose monotropins and
5, 7, 9 mini-dose HCG
Type 11 1 • HCG: 2,000 IU IM or SQ LUF • Menotropins + 10,000 units

P+5 , 7, 9 HCG
• Menotropins + mini-dose HCG
Type IV • HCG : 2,000 IU IM or SQ
P+3 , 5, 7 IFS: +, - , Re
Type V
Possible follicular phase support
• Post-Peak E, support
PR : +, - , Re
AF
DRS: +, - , Re
} • Low-dose clomiphene
• Possibly low-dose menotropins
and mini-dose HCG
620 The Medical and Surgica l Pract ice of Na ProTECHNOLOGY
mucus cycl e and the ir use are outlined in Tabl e 46-20.

Table 46-1 9: Treatment fo r LU F Syndro me with
Gonadotro pins and H CG '
In F igure 46-1 2, the well -recogni zed, antago ni stic ef-
Total fec ts of c lomi phene citra te on the production of cervi-
Patients Treatment Ovulated Pregnant cal mucus is demonstrated . In the first cyc le, the muc us
N n n
cyc le score is 5.3 when clomiph ene is not being used . In
22 Serial HMG with 10,000- 21 15 the second cycle, when a low-dose c lomiphene citrate
15,000 JU HCG or 15,000
JU HCG mixed with 150 JU
protoco l was begun , the mucus cyc le score (M CS) was
HMG when follicle is mature O.O . T hi s observation can easily be made when women
1. From: Check JH, Diettrich C, Newroozi K, et al: Comparison of Various Thera-
are monitoring the ir cyc les using the CrMS . In orde r to
pies forthe Luteinized Unruptured Follicle Syndrome. lntJ Fert 37:33-40, 1992. be successful in imp lementing the u e of clom iphene,
coun tering not onl y its anti estroge ni c effects, but also
its effect on the pre-ex isting limi ted mucus cycles, is
critica!. T his effect has bee n prev iously recognized by
cumul us ooph orus is identified and there is no fo ll icular others (Fi gures 46-1 3 and 46- 14).50 -51
phase hormone defi ciency, th en no treatment is us uall y
necessary. A number of yea rs ago, it was demonstrated that Vita-
min 8 6 in a dosage fo nn of500 mg in a sustained-release
For ali ofthe other ovul ati on-re lated defects, e ither the fo rmat ta ken on a daily bas is could improve mucus pro-
low-dose clomiphene or low-dose menotrop in regimen
is in stituted. T hi s mayo r may not be w ith th e add ition
of the mini -dose HCG protoco l. Table 46-20: Medica! Su pport forD ifferen t
An omalies of Cervical M ucus
The one exception is LUF synd ro me where menotropins (lnfertile W omen with R egular Menstrual Cycles)
p lus a trigge rin g dose of 10,000 units of HC G o r
Type of Mucus
me notropins assoc iated w ith th e use of preov ulatory
Cycle Mucus Enhancement
m ini-dose HCG support is the approach of cho ice. A
progra m s uch as thi s has been reported by C heck, et Dry cycles • Vitamin 8 6 500 mg SR PO QD
• Amoxicillin 500 mg PO TI D
al,58 the result ofwhich are shown in Tabl e 46- 19. The P-4 through P
ve ry best trea tment fo r the LUF synd ro me was with a • Guaifenesin P-4 through P+2
combinati on of HMG and a tri ggering dose of ei ther • Prednisone (optional )
HCG ora combination o fH CG and HMG.
Limited mucus cycles • Vitam in 8 6
• Amoxicillin
• Guaifenesin
Mucus Enhancers
Regu lar mucus cycles • Vitamin 8 6 (optional)
• Amoxicillin (optional)
A key ingred ient in the approach ofNaProTECHNOLOGY • Guaifenesin (optional )
to th e treatment of in fe rtility is the use of mucus-en-
hanc in g age nt . These age nts, along w ith the type of
Figure 46-12 : Th e effects of clom iphene on mucus production. In the second cycle , a cycle in which clo miphene was used , the
cycle was dry and the mucus cycle score was O.O (Fro m: Pope Paul VI lnstitute research, 2004).
Chapter 46: Medical Treatme nt of Ovarian and Target Organ Dy sf unction 621
A - Untr. .t.<IOYUlal 04'YCOntrol•ubjKb

B - Untreated ovuJatory controlaubjects
- Subfect11rKeMng150mgCC - Subjec:lll ..ceMng 150 mg ce
onda'f'113lo7ofcycllr on day• 3 ~o 7 ol cycllr
1200
~ :>
w
"'.,
e
"'+I 1000
e
: 9
~ !_,
~ 8 800
~ 7 ~
g6 o
'O
600
"
]
5
~ 400
·~
~ 3
200
-3 ·2 ·1 PEAK +1 .3 -2 ·1 PEAK +1
e, e,
Oa ys Days
Figure 46-13 : Th e E2 co ncen trations and cervical mucus seores in wo men rece iv-
ing 150 mg of clo miphene on cycle day 3 th ro ugh 7 (red) and an untreated ovu latory
con trol subjects (blue). The number in parentheses is the number of observa tions
(From : Maxson WS , Pittaway DE , Herbert CM , et al: Antiestrogenic Effect of Clomi-
phene Ci trate: Corre lation with Serum Estradiol Concentrations . Ferti l Steril 42 :356-
359 , 1984).
- Untreated ovulatory contro l s ubjects
20 C=:J Subjects receiving 150 mg CC

on cycle days 3 to 7 duction . This is demonstra ted in Figure 46- 15. fn the
absence ofVi tamin 8 6, the MCS was 1.0. Wi th the addi -
e:"'
Q) tion ofYitami n 8 6, it increased to 5.7.
:; 15
...o
c.
In additi on to the above, it was also observed many
~ years ago by women who were charting their menstrual
..e 10
E and fert ili ty cyc les that when an antibi otic was taken,
:::1
z
especia lly amp icillin, the cerv ica l mucus disc harge in-
5 creased signi fica ntly. Thu s, the best mucus-enhancing
agent currently ava ilab le is one of the peni ci ll in antibi-
oti cs. Thi s is demonstrated in Figure 46-1 6 where the
POOR INTERMEDIATE GOOD mucus cycle score in the first cyc le without ampicilli n is
(1-3) (4- 6) (7-9)
O.O. With am picillin, it increases to 8.0 in th e second
Cervical Mucus Seores cyc le and in the third cyc le, when ampici llin was no
Figure 46-14 : Comparison of ce rvical mucus seores on the longer used, the mucus cyc le sco re once aga in de-
day of Pea k E2 concentration in subjects receiving 150 mg of creased to 1.0. These are th ree consecutive cyc les in
clomiphene on cycl e days 3 to 7 (gold) and untreated ovu la- th e same patient.
tory co ntrol subjects (blue) (From : Maxson WS , Pittaway DE ,
Herbert CM , et al: Anti estrogenic Effect of Clomiphene Citrate:
Corre lation with Serum Estradiol Concentrations. Ferti l Steril The effects of medication on the mucus cycle score are
42 :356-359 , 1984 ). outlined in Tab le 46-2 1. Clearly clomiph ene decreases
mu cus pro du cti on. However, either ampi cillin or
amoxici llin will signi fican tl y increase it as will Yitamin
Table 46-21: Effects of Medication on the
8 6 . Furthermore, guaife nes in has been shown to improve
Mucus Cycle Score (MCS)
mucus seores as we ll. Thus, th ese are the main ingredi -
MCS MCS ents to the enh ancement of cervica l mucus.
·Medication Before Rx After Rx:
Clom iphene citrate 4.9 4.11 The exact mechani sm as to why the antibi otics will im-
(n=20) prove mucus producti on is not entirely known. It is
Ampici llin/amoxicillin 4.0 9.0 2 thought that it may enh ance the utilization of estrogen
(n=11)
at the target organ. It is known, for example, that women
Vitam in 8 6 (pyri doxine HCI) 4.1 6.4'
(n=16) taki ng ora l contracepti ves ha ve a hi gher pregnancy rate
in the firs t cycle or two when they concomi ta ntly use
1. p=.5268 (Equal-variance !-test)
2. p=.0032 (Equal-variance /-test) an ti biot ics fo r vari ous reasons.52 -54
3. p=.05 (Aspin-Welch t-test )
31 32 33 34 35
NO VIT B•
MCS = 1.0
ON V!T B"
MCS = 5.f
L H
CAD OAO
""'º
Figure 46-15: In the second cycle, Vitamin 8 6 500 mg sustained-release was initiated . The mucus cycle score went from 1.0
to 5.7 (From: Pope Paul VI lnstitute research , 2004).
l l
Figure 46-16 : In the first and th ird cycle, no ampicillin was used . In the second cycle, ampicillin was used as a mucus enhancer
and the mucus cycle score increased to 8.0 (From : Pope Paul VI lnstitute research , 2004).
Table 46-22: Medica[ Suppo rt fo r Abnormal

Bleeding a nd Co ntinu o us Discharge
(lnfertile W o me n with R egular Menstrual Cycles) Table 46-23: Ge neral Med ica[ Suppo rt for
lnfe rtile Wome n with
R egular Menstrual Cycles
Medica! Support
lndication Types of Medica! Support
Abnormal bleeding
Premenstrual bleeding • HCG i ~-endorphins • Naltrexone
• Progesterone t Prolactin • Bromocriptine
• Antibiotics
t Androgens • Dexamethasone
Tail-end brown bleeding • HCG Maximize effects of • Dexamethasone
• Antibiotics clomiphene or menotropins • Bromocriptine
lnadequate nutrition • Diet and nutrition
Continuous discharge • Education
Cervical eve rsion sign s • Hyfrecation
Too much or too little • Moderate exercise program
exercise
Frequent "2W" • Antibiotics
observations
Chapter 46: Medical Treatment of Ovarian and Target Organ Dysfunction 623
Other medi cati ons that have been used to improve mu- Examples ------------~
cus producti on whil e usi ng clomi phene have incl uded
predni sone and ethinyl estradiol. 55 Predn isone is used A num ber of exampl es of pregnancies achi eved after
onl y sparingly, and our use of eth inyl estradio l has been the orga nic di sease ha been treated and th e ovarí an
too limited to comment. and target organ dysfun ction has been treated are illus-
trated. Each treatment is tail or-made to the indi vi dual
patient based upon thei r horm onal profil es, results of
Abnormal Bleeding and Discharge their ul trasound studies, CrMS charting and res ults of
laparoscopy.
The CrMS fe1tility chart may also show abnormal bleed-
ing pattern s such as premenstrual spotting or tail-end 1n Figure 46- 17, naltrexone is used in very low dose
brown bleeding. Each of these may be reflective of an a long with post-Peak HCG for lutea l phase support. Preg-
underl ying hormonal dysfunction, espec ially decreased nancy was established with feitili ty-foc used intercourse
progesteron e producti on. In addi tion, they may be a and she deli vered a full-term , hea lthy in fa nt.
sign ofa chronic endometriti s. Treating thi s with HCG
support during the post-Peak phase of the cyc le oran- In Figure 46-1 8, three examples of the use of clomiphene
tibi oti cs can be helpful. The recomm ended antib iotic citrate are presented. In two ofthe three pati ents, post-
would be either clarith romyc in or metron idazo le. lf a PeakH CG suppo1t was also prov ided. ln ali three cases,
continuous mucus di scharge occurs whi ch is consi - pregna ncy was established and a full-term , hea lthy in-
tent with the presence of a cervica l evers ion, then the fa nt was born .
cervix should be hyfercated.
In Fig ure 46-1 9, a tra diti ona l use of menotro pins
If"frequent 2W" observati ons are made, then a cervica l (Pergonal) was used from days 3 through 15 of the men-
infecti on may very well be present. Culturing the cerv ix strual cyc le with a tri ggering <lose of HCG on day 15.
for th e appropri ate bacteri a can be helpful and admini s- Pregnancy was establi shed and she had a fu ll -term de-
tering the bacteri a-spec iti c antibi oti c is impmtant. li very.
In f igure 46-20 , a sli ghtl y more restri cti ve use of

General Support menotropins wa impl ernented. In thi s case, the FSH/
LH was used on days 6 through 11 of the cyc le. The
Genera l support is also prov ided to the pati ents tryin g mucus cycle was identified and se lected fo r intercourse
to achieve a pregnancy. One of these is to implement and post- Peak HCG was implernented. Pregnancy was
naltrexone th erapy if thei r beta-endorphin levels are achieved and the pati ent had a normal, hea lth y preg-
decreased. altrexone can ha ve the effect of improv in g nancy.
the fun ction of the pituitary producti on ofFS H and LH.
Thi s, in turn , can have an effect on improv ing ovaria n In Figure 46-2 1, a low-dose menotropin protoco l was
fun cti on. used fro rn days 3 thro ugh 6 of the cyc le. Thi s patient
had a long-standing hi story of unruptured folli cles and
Ifthe pro lactin leve ls are elevated, then bromocriptin e had undergone rnultiple cyc les of clomiphene without
can be utili zed and if androgen leve ls are increased, success. In thi s case, FSH/LH , 3 amps, days 3 through
then dexamethasone should be used. Thi s is ali out- 6 of th e cyc le were impl ernented and then mini-dose
lined in Table 46-23. HCG was used. The HCG is used asa n LH substitute.
She had an exce ll ent mucus cyc le and achieved a preg-
3 4 35
A
8 0 IOSL B GY OAO OA.0 OAO OAO Qt\O OAO OAO OAO 00.0
IOKL IOSL x 1 IOSL w 1 (±)
Nol rex one a . Qid
"I
I HCG HCG H\..G HºG ~
Figure 46-17 : Pregnan cy achievement with the use of naltrexone and HCG (post-Peak) (From: Pope Paul VI lnstitute research ,
2004).
®
~ aw ~ ~ aw
~ ow ~ ~~~~ fff ~ 8
H H M M L VL OAO ClAO ClAO IOCL
" L ,,
L ,,IOKL
" L ...
IOCL IOKL IOKL SCL 4AO VG
AO
ClAO OAD 4P
•I
4G
"
,,
IOCL 4G
'1
OAO CAD CAD
e e e e f;-E MCG HCG I MCG MCG
e
se K>KL se IOC (,:,C IOC '4AD GK '4AD ~AD -'t-.::1 4 x-., 4 xl e.e IO K 4AO 4AO OAO 4xa
'111 1 1ta x;i, 11;3 x I •2 ><il • 1 •I
e e I I MCG MCG MCG MCG
Fig ure 46-1 8: Achieving pregnancy with the use of low-dose clomiphene progression (From: Pope Paul VI lnstitute research ,
2004).
JO 11 12 13 14 15 32 33 34 35
L
OAO
.,
aw aAD CIAD MO OAD MO CAD 00.0 DA.O OAO CAD CAD
(±) PG TE
Figure 46-19: The use of FSH/LH for the stimulation of ovulation and a triggering dose of HCG with pregnancy ensuing (From :
Pope Paul VI lnstitute research , 2004 ).
12 13 14 31 32 33 34 35
MCG HCG
Figure 46-20 : The use of low-dose FSH/LH and postovulatory HCG for pregnancy achievement (From : Pope Paul VI lnstitute
research , 2004 ).
Chapter 46: Medical Treatm ent of Ovarian and Target Organ Dysfunction 625
10 JI 12 13 14 15 16 17 18 19 20
H H M 1 IOCI< OAO IOKL 9KL 9KL IOKL

IC 1 JC 1 X/ ICI Jt 1 X1
PG
I I I I ST
HCG MCG HCG HCG HCG HCG HCG )..K.G MCG l-ICG HC0 HCG
Estradiol-17b (ng/dL) 1 Ultrasound '"""'

2.08 0
L•ft
1.93 1)
CR
CR
E2 5.7
p 12.5 1Progesterone (ng/mL)
27.2
16.2
- -------------15.0
12.5
-~-+--t-~-+--+-1 1-- ----10.0

5.7
5.0
Figure 46-21 : Low dose FSH/LH and mini-dose HCG for pregnancy achievement (From: Pope Paul VI lnstitute resea rch, 2004).
29 30 31 32 33 34 35
H H M L M
e
""º
H VL VL VL VL VL VL M M M M M L L M
880088""'° 8 8
OAD CAD OAO °'º OAO OAO OAO OA.D
The Use of Clomiphene

in PCOD
H H H M Vl ~O ()11.0 9 SL OA.O I06L OAO OAD IOl(L IOKL OA.0 !OKL

xi ,.; 1 11 I x I • t
o,or..o IOIC'L
11 I
°"'° ~ OAO
OAD
ccc
HHHHVLBB
OAD OAD OAO
H H H M
Fi gure 46-22: High dose clomiphene in a palien! with polycystic ovarian disease (From : Pope Paul VI lnstitute research, 2004).
nancy, delivering a healthy baby at ful! term . her ovulati on. In the second cyc le of treatment, she
achieved pregnancy and subsequently had a normal,
In Figure 46-22, a patient with polycystic ovary syn- hea lthy baby.
drome who has long and irregular cycles along with
dysfunctional uterine bleed ing is being treated with the In Figure 46-24, a patient with Kallmann syndrome is
high-dose clomiphene protocol. The extensive dysfunc- shown. With the use ofpu lsed GnRH, she achi eved this
tional uterine bleeding, whi ch is present prior to the pregnancy along with a second one and deli vered two
imp lementation of clomiphene, is replaced by regular healthy babies.
cycles, a reasonably good mucus cycle and ovu latory
cycles as we ll. In Figure 46-25, an experimenta l protocol using sma ll
doses of "booster" GnRH are shown. 57 In thi s case, the
In Figure 46-23 , a patient with hypothalamic amenor- GnRH dosage was 50 mcg subcutaneo usly, day 1
rhea is shown. She used the pulsatile adm ini stration of through 12 ofthe cyc le. The use ofG nRH in thi s fas h-
GnRH by the use ofa portable infusion pump to initiate ion wi ll stimul ate the endogenous production of FS H
t Hypothalamic Amenorrhea t
14 D:l s
H M
I I I I
t Pregnancy Achieved with t

Use of GnRH Pump
Figure 46-23 : The treatment of hypothalamic amenorrh ea with the pulsatile administration of GnRH (From : Pope Paul VI Jnstitute
research , 2004) .
12 IJ 14 15 16 17 18
VL L H M M SCG c;cG <.CG IOC IOK. aAO 9..xá\. MO ;.xi ~_,, ¡

x ól x ;!. xi .el 11 1
0 OAO
HCG
MCG
""' I I "<:G I l HCG I
e
,.. I
Figure 46-24 : Th e treatment of Kallmann syndrome with the use of pulsatile GnRH (From : Pope Paul VI lnstitute resea rch , 2004 ).
Chapter 46 : Medica! Treatment of Ovarían and Target Organ Dysfunction 627
Figure 46-25: The use of "booster" GnRH for pregnancy achievement (From : Pope Paul VI lnstitute research , 2004).
and LH from the anterior pituitary gland. In this way, it fied , it is prudent to discontinue the treatment and use
is used as a menotropin subst itute. HCG was used post- alternative approaches.
Peak to support the luteal phase and naltrexone, ampi-
ci llin and levothyroxine were al o used to support the The risk of multip le gestation has been reported to be
cyc le. In the second cycle, pregnancy was achieved approximately 8 percent. 60 Most ofthese are twin gesta-
and she delivered a normal , healthy baby. tions, but triplets and hi gher order pregnancies can oc-
cur, although rare. At the Pope Paul VI lnstitute, the
overall multiple gestation rate has been reduced to 3.2
Side Effects _ _ _ _ _ _ _ _ _ _~ percent.
There are a few side effects in the use of clomiphene Ovarían hyperstimulation syndrome can be observed
and/or the gonadotropins. In add iti on, sorne side ef- in patients with large doses. This conditi on can become
fects ofamox icillin, Vitamin 8 6 and HCG will also be very severe with massive ovarían en largement, progres-
reviewed. sive we ight gain , severe abdominal pain, nausea and
vomiting, hypovolemia, asc ites and oli guria. This is
generally considered to be a very rare complication of
Clomiphene Citrate clomiphene and is more likely with gonadotropins.
Th is medications is usually very well tolerated. About Endometrial thickness has been a concern with the use
1Opercent ofclomiphene-treated women will experience of clom iphene. 62 ·63 However, Check, et al. 64 ha ve shown
vasomotor flushes or hot flashes. Mood sw ings can be no difference in the mea n endometrial thickness during
common, but are alm ost always dose-dependent and the first six cycles oftherapy, nor did they show a trend
are much more severe in hi gher doses. In the low-dose for thickness to increase or decrease with successive
regimens typically used at the Pope Paul VI ln stitute, cycles either with or without the addition of ethinyl es-
mood sw ings are very uncommon. 60 tradiol. However, others have shown that ethinyl estra-
diol can reverse any de leterious effects that might be
Other side effects which were observed in less than 2 observed on endometria l development with clomi-
percent ofpatients include visual disturbances, blurred phene. 65.66
or doub le vision, scotomata and light sensitivity. These
are genera lly reversible, alth ough optic neuropathy has
been desc ribed. 6 1 When visua l disturbances are identi-
Gonadotropins We have observed, on occasion, sorne gastric upset or

nausea as a result ofVitam in B6 and th is is particularl y
With regard to gonadotropin stimul ation , the main two true if used in assoc iation with naltrexone. lf that oc-
side effects are ovarian hyperstimulation syndrome and curs, one or the other should be discontinued and the
multiple gestation. 67 patient will tolerate it much better.
The incidence of severe ovarian hyperstimulation syn-

drome (OHSS) ranges from an incidence ofless than .O1 Antibiotics
percent up to 3.9 percent. When severe OHSS is diag-
nosed, hospitalization may be necessary for control of We now ha ve over 25 years of experience with the use
fluid imbalances, maintenance ofvital organ perfusion, of antibi otics as a mucus-enhancing agent. During this
prevention of hypercoagulation, and control of pain. period of time, the main side effect that we have ob-
Hemoconcentration shou ld be avoided, maintaining the served, wh ich would be expected, is the finding ofyeast
hematocrit at less than 45 percent. 67 lt should be noted infections that occur periodically in women on this dos-
that in 25 years of experience with treating ovarian and age program. Otherwise, we ha ve seen no other effects
target organ dysfunction using NaProTECHNOLOGY including allergic reactions. However, we do make ita
techniques, severe ovarian hyperstimulation syndrome practice not to prescribe these antibiotics in patients
has never been observed. with previous history of allergic reaction of any type.
The multi-fetal gestation rate can be very high ranging 1f the patient does develop a yeast infection on
from 20 to 45 percent. This is associated with the prac- amoxicillin or amp icillin, we would normally switch her
tice ofsuperovulating the ovaries and trying to achieve to cefaclor (Ceclor) and that usually is well to lerated . If
8 to 1Ofollicles in each ovary at the time ofovulation. lt yeast infections continue to be persistent, treating the
is with the gonadotropins that the septuplet/octuplet- patient and her husband with Diflucan, 150 mg by mouth
type pregnancies have occurred. Gonadotropins are also (PO) at the end ofher course of antibiotic treatment can
used frequently in ART programs for superovulation of keep this under contro l.
the ovaries and harvesting of ova. In such situations,
with the practice ofimplanting multiple embryos, mul- We have seen no inclination towards increased resis-
tiple pregnancy is very high as well. Again , it is worth tance of organisms, although that is something which
stating that the multiple pregnancy rate at the Pope Paul needs to be conside red and followed close ly.
VI ln stitute is 3.2 percent.
Human Chorionic Gonadotropin

Vitamin 8 6
Human chorionic gonadotropin (HCG) is a well-to ler-
The use of pyridoxine hydrochloride (Vitamin 8 6 ) has ated injection which normally does not cause much in
been shown to be associated with a sensory neuropa- the way of side effects. However, on occasion, either
thy especia ll y when used in fairly high doses. 68· 70 In breast tenderness or nausea may occur as a result of
one report, the clinical picture ofa pure sensory central- the medication. Jn addition , ifthe woman develops an
peripheral distal axonopathy was consistent. The pyri- unruptured fo llicl e and then it is stimulated by HCG,
doxine dose was 200 to 5,000 mg per day, and in almost that may cause sorne pain or discomfort. This needs to
ali cases, the dosage was beyond one gram per day. Jn be adequately observed and if an ovarian cyst deve l-
our experience with the use ofVitamin B6 , we ha ve not ops, then the HCG should be discontinued. The best
observed this as a problem or difficulty. 1n 25 years we treatment for an unruptured follicle which is pai nful ,
ha ve seen one case of mild sensoty "tingling" as a re- either with or without the stim ulation ofHCG, is to give
sult of Vitamin 8 6 therapy. lt is thought that because intramuscular progesterone 100 or 200 mg. This will de-
this approach has consistent ly used a sustained-release crease the pain within a short period of time after its
fom1 ofVitamin 8 6 (500 mg sustained-release capsules) administration and will help its dissolution with the next
that the blood levels with such an approach would be menstrual cycle. Any person who has a consistent pat-
lower than with the standard Vitamin B6 tablets. As a tern ofdeveloping unruptured follicles (pers istent luteal
result, even though the dosage is higher, the blood lev- cysts), should not be considered a candidate for the
els would be expected to be lower and these side effects useofHCG.
should not be observed.
Chapter 46: Medical Treatment of Ovarian and Target Organ Dysfunction 629
Other Medications For Treating Ovarian tors acted locally in the ovary to make foll icl es more
Dysfunction sensitive to FSH. This might result in the accumu lation
of intra-ovarian androgens since inhibiting aromatase
A number of other medications ha ve been used to treat blocks the androgen substrate from being con verted to
ovulation-related abnormalities. One that has been tested estrogen .
rather extens ively is tamoxifen. 1 1· 81 The overall rate of
ovulation and pregnancy have been considered to be Mitwally and Casper believe that aromatase inhibitors
similar between tamoxifen and clomiphene and tamoxifen ha ve two main roles in the induction of ov ul ation. The
has been considered to be a su itable alternative to clo- first is to use it alone for the induction ofovulation and
miphene in the management of anovulatory infertility the second is to use it as an adjuvant in conjunction
(long and irregular cycles). lt has a chemical structure with other medications to improve the outcome of ovu-
which is somewhat similar to clomiphene anda mecha- lation induction, especially gonadotropins. 6 The dos-
nism ofaction which is simi lar as well. The Pope Paul VI age of the aromatase inhibitor has not yet been fully
lnst itute has used tamoxifen but empirica ll y found it established. Letrozole (Femara) has been used ata dos-
not to be as su itable as clomiphene. age of2.5 mg every day (QD) írom days 3 through 7.
Similar rates of ovarian stimulation ha ve also been ob-
Anotherdrug, avai lable in Europe, but not in the United tained with a single 20 mg dose of letrozole given on
States, is Cyclofenil. lt has been shown to be somewhat day 3 of the cycle when compared to the 5-day regi-
effective in women with infertility with normal ovula- men.95 M itwally and Casper believe that the single-dose
tory cyc les with perhaps less effect on the cervical mu- regimen holds sorne excitement beca use of its conve-
cus . 8~ · 83 Because it is not available in the United States, nience and simplicity. 86 The potential for administering
we have no experi ence with it. higher doses is being explored. The optimum dose and
regimen ofadministration, however, will most likely de-
Recently, a recombinant form ofHCG (r-HCG) has been pend on the indication and objective ofinferti lity treat-
studi ed .84 A single dose ofr-HCG 250 µg was found to ment. A single-dose regimen would satisfy two goa ls:
be at least as effective as a single dose of5,000 or 10,000 First, the achievement of maximum estrogen suppres-
JU of u-HCG but has apparently had sorne additional sion early in the menstrual cycle when it is desired; and
advantages which are typical of recombinant products. second, allowing clearing of the aromatase inhibitor
This includes less frequent and significant injection si te before the critica! final stage offertilization and embryo-
ad verse reactions with r-H CG as compared to u-HCG. genesis, to maximize safety and avoid any possible un-
desirable effects ofthe aromatase inhibitors. 84 A hypo-
Finally, the aromatase inhibitor, letrozole, has begun to thetical calculation ofthe total amount ofthe aromatase
receive increased attention. 85 -94 The aromatase inhibi- inhibitor letrozole in the body after sing le and multiple
tors, which block estrogen synthesis and lower estro- dose administration is shown in Figure 46-26.
gen leve ls are best known for their emerging role in
treating breast cancer and preventing its recurrence af- A second aromatase inhibitor is anastrozole (Arimidex).
ter tamox ifen therapy. The average percentage oftotal body aromatase inhibi-
tion with letrozole is greater th an 99. 1 percent and with
Aromatase cata lyzes the conversion of androstenedi- anastrozole it is 97.3 percent. 84
one and testosterone to estrone and estradiol respec-
tive ly. lt is present in the ovaries, brain, adipose tissue. Aromata e inhibitors are generally well tolerated with
muscle, liver, breast tissue and in malignant breast tu- only hot flashes and general gastrointestinal complai nts
mors. Third generation ora l aromatase inhibitors are ex- observed . In healthy, young women , aromatase inhibi-
tremely im portant in inhibiting aromatase without sig- tors appear to be very afe. 86
nificantly inhibiting other steroidogenesis enzymes.
They are reversib le, compl etely absorbed and rapidly
cleared from the body. 8 lt was hypothesized that block- Ovarían and Breast Cancer----~
ing estrogen production from ali sources by inhibiting
aromatization would release the hypothalamic-pituitary In the early l 990's two epidemiologic tudies were pub-
ax is fro m estrogenic negative feedback , thereby increas- lished which suggested that the risk of ovarian cancer
ing gonadotropin secretion and thus stimulating ova- might be increased in women exposed to various ovula-
rian fo llicles. tion-inducing medications. 96 ·9 7 Subsequent studies,
however, failed to corroborate these findings. 98 -100 A
A second hypothesi s suggested that aromatase inhibi- pooled analysis of eight case-control studies, published
in 2002, concluded that neither fertility drug use nor use been established and that no change in prescribing prac-
for more than 12 months was associated with invasi ve tices is warranted at the present time. This is especially
ovarian cancer. 10 1 In discussing this with patients they true with low-dose clomiphene and FSH/LH regimen
shou ld be cou nse led that no causal relationship be- where the ovaries are not superovul ated.
tween ovu lation-ind ucing drugs and ovarian cancer has
35 Letrozole Dose Remaining in Body
30
30
- 30 mg single dose
- 20 mg single dose
25 c::::J 1O mg single dose
2.5 mg/day for 5 days
20
20
mg
15
10
2.5
oL.-~~~~~~~!=!~.....,,........,...,._.
o 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Oays
Figure 46-26 : A hypothetica l calculation of the total amount of the aromatase

inhibitor letrozole in th e body after single and multiple dose administration
(From : Mitwally MFM , Casper RF: Aromatase lnhibitors in Ovulation lnduction .
Sem Reprod Med . 22 :61-78 , 2004).
1. Ki stner RW: Sequential Use of Clomiphene Citrate and Hu- 1O. La111111 EJ , Guderian AM : Clini ca l Effecls of Clomiphene in
man Me nopau sa l Gonad otropin in Ovulati on lndu cti on. An ov ulati on. Obste! Gy neco l 28:505 , 1966.
Fertil Steril 27:72-82, 1976 .
11 . MacG rego r AH, John on J E, Bunde CA: Further Clini ca l
2. Jewelew icz R, Gind o ff PR : Gyn eco l Obstet ln vest 26:89- Ex perien ce with Clomiph ene Citrate. Fertil Steril 19:61 6,
103, 1988 . 1968.
3. March CM: Ovul ati on lndu cti on. J Repro d Med 38 :335- 12. Puebla RA, Greenbl au RB: Clomiphene Citrate in the Man-
346 , 1993. agcment of Ovulatory Uterin e Bleedin g. J Clin End ocrin o!
24 :863 , 1964 .
4 . Kennedy JL, Adashi EY: Ovul ation lnducti on. Obstet Gyneco l
Clin No rth Am 14:83 1- 864, 1987 . 13 . Roy S, Greenbl att RB , Mahes h VB , et al: Clomiph ene Cit-
rate: Further Observations on its Use in lnduction of Ovul a-
5 . Greenblalt RH , Barfield WE, Jungek EC. et al: lnducti on of
ti on in the Human and on its Mode of Action. Fert il Steril
Ovulati on with MR L/41 . JAMA 178: 10 1, 196 1.
14: 57 5-5 94, 1963.
6 . Charles D: M.R.L. 41 in th e Treatment of Secondary Amen-
14 . Whitelaw MJ , Gra ms LR, Sta111111 WJ : Clomiph ene Citrate:
orrhea and Endometrial Hyperpl as ia. Lance! 2:278, 1962.
lts ses and Observa ti ons on its Pro babl e Acti on. Am J
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lati on. Am J Obste! Gyneco l 84:900, 1962.
15 . Adas hi EY: Clomiphene Ci1ra1e - lniti ated Ovul ati on: Th e
8. Jones GS, Moraes-Ruehse n M D: Clo miph ene Cit ra tc fo r State of the Art. In: Wallach EE, Zacur HA (Eds). Reproduc-
lmpro ve menl of Ovarian Functi on. Am J Obste! Gyneco l ti ve Medicine and Surgery. Mo by, St. Louis, 1995 .
99:8 14, 1967 .
16 . Kerin JF, Liu JH , Philli pou G, et al: Evidence fo r a Hypotha-
9 . Ki stner R: Further Obse rva ti ons on th e Effects of Clomi- lami c Sit e of Ac ti on o f Clomiph ene Citrate in Women. J
ph ene Citrate in An ovul atory Femal es. Am J Obstet Gyneco l Cli n End oc rin o! Metab 6 1:265 , 1985.
92 :380, 1965.
Chapter 46 : Medical Treatment of Ovarian and Target Organ Dysfunction 631
17. Greenbl att RB , Barfield WE, Ju ngck EC, et al: lnd uction of
38. Knobil E, Plant TM , Wi ldt L, et al: Co ntrol of th e Rhesus
O vul ati o n w ith MRL/41: Pre limin ary Repon. JAMA
Monkey Menstrua l Cyc le: Pe rmi ss ive Role of Hypo th a-
178: 127 -1 30, 1961.
lami c Go nadotropin-R eleas in g Hormone. Sc ience 270: 137 1,
18. Greenblatt RB: Chemical lnduction of Ovulation. Fertil Steril 1980.
12 :402 -4 04, 196 1.
39. Leyendecker G, Wil dt L, Hansmann M: Pregnan cies Fol-
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of Clomiph ene on th e Human Ovary. JAMA . 184: 122-130, Gn-Rh by Means of a Portab le Pump ("Zyk lomat") - A New
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20 . Nav ille AH , Ki stn er RW, Whea tley RE, et al: lndu cti on of
Ovul ation wi th Clomiph ene C itrate. Fert il Steril 15:290- 40. Dodge ST, Strickler, Kell er DW: Ovu lation lnducti on with
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22. Co un cil on Drugs. Ameri ca n Medi ca ! Associa ti on. Eva lua-
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3 1:620, 1979.
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ni enl Effective Meth od of Ovulat ion ln duction . Ferti l Steril
76 (S uppl 1):594-595 , 200 1.
Male lnfertility:
F ertility is a biological function of both a husband

and wife who, through sexual intercourse, unite their
gametes. When a woman has difficulty achieving a preg-
cal treatment is someth ing that the author usually un-
dertakes himself. Fam il y phys icians are better qualified
to undertake such exami nations since this is a part of
nancy, an evaluation for that problem must in vol ve not their standard ofpractice. For a gyneco logist, however,
only her but also her husband. This evaluation can be while it is nota comp lex or difficult examination, it is out
helpful at giving important infonnation to the couple so of their field of expertise . A urologist is also used for
they may better understand the future capability oftheir any surgical reconstruction that is necessary (for ex-
procreative potential. At the same time, it can be a com- ample, a varicocele repair ora vasovasostomy fo ll ow-
plex and diffícult area to work with. ing vasectomy).
In 1677, Anta ine van Leeuwenhoek, one of the inven- The most common diagnostic categories observed in
tors ofthe microscope, discovered the spermatozoa and the evaluation ofthe male w ill be varicoce le, idiopathic
described his findings in a letter to the Royal Society of oligospennia , or obstruction ofthe vas deferens. 2
London. He provided a detailed description ofthe liv-
ing spermatozoon and their movement. He was the first There are a variety of different fertility- impairing medi-
to hypo thesize that the sperm actually penetrate an egg cations that also need to be investigated. For examp le,
at the m oment of conception. 1 anabolic steroids, cimeti dine, steroidal antiandrogens
(DES), cyclosporine, and phenothiazine will suppress
Since that time, various attempts have been made to to sorne extent the hypothalamic-pituitary-go nadal ax is.
eva luate the male's fertility and also to develop ways of Such medications as ketoconazole, sulfasalazine,
treating it. Generally speaking this has been left up to va lproic acid, spironolactone and allopurinol are directly
the urol ogist, but experience would suggest that most gonadal toxic. In addition , calcium channe l blockers,
urologists have little interest in male infertility problems colchicine, nitrofurantoin and minocycline are known
and are quick to refer patients toan artificial reproduc- at least, on occasion, to impair fertilization. 3 Other fac-
tion technologist. Thus, the author usually recommends tors such as marijuana use or the large ingestion of
that patients see a urologist mostly for the purpose of a caffeine can also impair spermatogenesis.
physical examination. Any further evaluation and medi-
635
lt is also known that scrotal hypertherrnia can impair seminal fluid which <loes not violate one 's religious,
sperrnatogenesis in rnen. lt has been shown, for exarnple, moral or aesthetic beliefs while at the same time obtain-
that the scrotal temperature of infertile men is ignifi- ing reliable results. This technique is to use a perfo-
cantly greater than that observed in men who are fertile. rated sem inal co llection device (SC D). This col lection
The higher the scrotal ternperature, the more likely there device can be purchased from: Apex Medica] Technolo-
will be sperrnatogen ic alterations. 4 An exact etiology of gies, Inc. , 10064 Mesa Ridge Ct. , Suite 202, San Di ego,
the hyperthemia is not known but may result in up to a CA 92 121. Phone: 1-800-345-3208. The perforations need
0.5° e elevation in ternperature. to be placed by an assistant with a steri le needle be-
ca use the SCD does not come pre-perforated . In thi s
Varicocele, one ofthe more cornrnon findings in an in- fashion , however, the seminal fluid can be collected with
fertil e population, proves to be sornewhat complex be- an act of intercourse, at home, in a way which is not
cause it may also be observed in rnen who have normal contraceptive. When th e seminal fluid is collected in
ferti lity. In fact, studies on normally fertile rnen show this fas hi on, it needs to be brou ght to th e hospital orto
that 61 percent may ha ve sorne degree of a varicocele; the laboratory within 30 to 45 minutes after collection
although, most ofthese are subclinical. The su bel inical and it shou ld be kept warm during this time. lt is prefer-
varicoceles do not appear to have any impact on fertil- able for the sem inal fluid to be emptied from the collec-
ity.s tion device in to a clean plastic container prior to being
brought into the laboratory.
Seminal Fluid Analysis ------~ There have been a number of studies over the years
that ha ve shown this type of an approach to the co ll ec-
To assess rnale fertility, short ofa pregnancy, an analy- tion ofthe sem inal fluid to be very reliable. 8· 10 In fact,
sis ofthe semina l fluid is helpful. This can be accom - this technique has been fo und to be superior to mastur-
plished in a variety of different ways, sorne ofwhich are bation or coi tus inte1Tuptus fo r the collection of seminal
helpful and others which are not, whi le at the same time fluid. 11.12
sorne are acceptab le to patients wh il e others are not.
The work done at th e Pope Paul VI lnstitute, where the
The postcoital test (Sims-Huhner test) has been shown seminal fluid parameters using a perforated sem inal co l-
to ha ve only a poor to fa ir reproducibility among trained lection device were compared with same patient results
observers using a standardized scoring system .6 This where the seminal fluid analysis had been performed
particular test, whi ch eva luates an interaction of the elsewhere prior to coming to the Institute, compares the
semina l fluid with the cervical mucus, is enti cing be- two approaches (Tab le 47- 1). In this analysis, no statis-
cause it involves the natural act of intercourse and does tically signi fica nt differences were found in an eva lua-
not involve masturbatory activity; however, the overa!! tion ofthe fo ll owing semi nal fluid parameters: volume,
results are not very useful. viscos ity, moti lity, percent of normal sperm (morphol-
ogy), the total sperrn count and the effective sperrn count
The American Society for Reproductive Medicine has
the fo ll ow ing recommendation: "At least two semen
samples collected on separate days by masturbation Table 47-1: Sem.inal Fluid Parameters using a
are recommended ." 7 Thus, encouraging mento mastur- Perforated Semin al Collection Device (PPVI) and
bate becomes a pa1i ofthe standard medica! eva luation Sam e Patient P erformed Elsewhere
for inferti lity; however, this approach to semen co ll ec- (Matched Pairs)
tion is dehumanizing and humiliating. Menare usually Result
placed in a washroom with pornographic literature and Parameter n PPVI Elsewhere p
asked to masturbate. Having spoken to many men about Volume 45 3.4cc 3.4cc NS'
this over the years, it is not well received by most, though Viscosity 21 0.9 0.6 NS
they often do not object because it is sort of the "ma-
Motility 20 47.2% 47 .6% NS
cho" thing to do. It is not something that settles well
Percent normal morphology 19 52.1 60.4 NS
with most of the mal e patients the author has seen. 1n
TSC' 25 173.9 133.5 NS
fact, there are many men who refuse a seminal fluid analy-
ESC' 23 17.6 22.8 NS
sis thinkin g that this is the only way that seminal fluid
can be collected. 1. NS = not statistica lly significa nt
2. TSC = total sperm count
3. ESC = effective sperm count (counUccx % motility x % normals)
There is however, an excellent alternative way to collect

Chapter 47 : Male lnfertility: Evaluation and Treatment 637
- ESC (the count/cc x percent motility x percent norrnals).

Table 47-3: Male Status Evaluation of Pope
Also, at the Pope Paul VI lnstitute, a simple classifica- Paul V1 lnstitute
tion systern of oligospermia and azoospermia has been lnfertility Population (N=538)
developed. This is noted in Table 47-2. In this classifi-
Classification n %
cation system , differences can be determined by evalu-
ating the sperrn count (per ce), motility and the percent- 1 Normospermic 226 42.0
age ofsperm that are normal (morphology). 11 Oligospermic 306 56 .9

11 36 6.7
lla o O.O
ln a review of538 patients who were investigated in this
llb 86 16.0
fashion (Table 47-3) it was found that 226 (42.0%) ofthe lle 62 11 .5
men were normospermic . On the other hand , 56.9 per- lld 13 2.4
cent were ol igosp ermic and 1.1 percent were lle 102 19.0
azoospennic. The most common variety of oligosper- llf 7 1.3
mia was Class lle where the count was greater than 20 111 Azospermic 6 1.1
mi Ilion per ce but the motility and the percent ofnormal

sperm was less than 60 percent. The second most com-
mon was the Class llb where only the percentage of
motile sperm was less than 60 percent ( 16.0%) . The third
most common was C lass lle where the percentage of
normal sperm was less than 60 percent. The rernaining Table 47-4: Semen Analysis
breakdown can be identified in Table 4 7-3. Mínima! Standards of Adequacy
Parameter Adequate Values

This brings us to a discussion of what should be con-
On at least two occasions
sidered a normal sperm count. The standard sperm
Ejaculate volume 1.5-5.0 ml
count parameters are identifi ed in Table 47-4. In these
Sperm density > 20 million/ml
parameters, if the count is greater than 20 mi Ili on, the Motility > 60%
motility is greater than 60 percent and the morphology Forward progression > 2 (scale 0-4)
reflects greater than 60 percent normal sperm, a long with and
the additional factors noted in Table 47-4, the seminal No significan! sperm agglutination
fluid analysis can be considered normal. No significan! pyospermia
No hyperviscosity
More recentl y, the World Health Organization has is- From: Sigman M, Lipshultz LI. Howard SS: Evaluation of the subfertile
male. In: Lipshultz LI. Howard SS (Eds): lnfertility in the Male, Ed 3. St.
sued a different set ofreference values. In this case, the Louis. Mosby-Yearbook. 1997. p 1?:>-193.
sperm concentration of greater than 20 mi 11 ion is sti 11
Table 47-2: Pope Paul V1 lnstitute

present, but motility is considered normal ifit is greater
Classification of Oligosperma
than 50 percent and the morphology is normal if greater
Classification <20 million <60% motility <60% normal than 15 percent. The World Health Organization criteria
for normal semen reference ranges reflects an introduc-
1 Normospermic >20 million > 60% motility >60% normal
tion ofthe strict Kruger criteria for sperm morphology.
11 Oligospermic
11 X X X
lla X 1n January 1988, Kruger introduced the concept that

llb X the sperm morphology of patients could only be con-
ll e X sidered normal ifthe morphology assessment was based
lld X X
on his "strict" criteria. 13 Unfortunately, this approach to
lle X X
evaluating the seminal fluid has now been incorporated
llf X X
into most laboratories around the country. This pro-
111 Azospermic no sperm
duces seminal fluid testing results that, for example, may
1. NS= not statistically significan! show a count of98 mi Ilion with a rnotility of80 percent
2. TSC =total sperm count
3. ESC = effective sperm count (counVccx % motility x % normals) but a morphology of only 5 percent. Such an analysis is
possible only with the utilization ofthe Kruger criteria.
638 T he Medica l a n d Surgical P ra ctice of N a ProTECHNOLOGY
achiev ing pregnancy with natural intercourse and thus

Table 47-5 : Wo rld Health Organization have little or no application in that setting. The mo ve of
Reference Criteria for Semen Analysis 1 many laboratories toward the adoption of these criteria
is another example ofthe insens itivity that the medica!
Param eter Ref ere nce Values
community has shown to many patients who refuse to
Volume ::::_ 2.0 ml o r greater participate in any !VF or ART-type program . Further-
pH 7.2-7 .8 more, it is another exa mple ofhow they have been aban-
Sperm concentra ti on ::::_ 20 million /ml doned by those in reproductive medi cine.
Total sperm count ::::_40 million
Motility ::::_50%
Morphology' > 15% normal fo rm s Treatment: lntrauterine lnsemination
1. From: WHO Laboratory Manual far the Examination of Human
andlCSI ~~~~~~~~~~~~
Semen and Sperm-Cervical Mucus lnteraction. World Health
Organization. 4th Ed . Cambridge University Press. NewYorl<,
1999. It has been suggested that, ifthe indi v idual male is iden-
2. Adapted from Kruger. tified as having male factor infertility (keep in mind that
the strict morphology tends to encourage such a di ag-
nosis), treatment should include intrauterine insemina-
tion and , ifthis fa il s, in vitro fertilization wi th intracyto-
Most patholog ists have fallen into the trap that has plasmic spenn injection (ICSI). Very little attempt i made
been set by these criteria. In fact, this criteria was spe- at further identifyin g the underly ing causes orto treat it
cifically established to determine who wo uld be a bet- medicall y. Little attempt is made at tryin g to ass ist
ter candidate for in vilro fertilization , and th e criteri a couples at ac hieving pregnancy naturall y.
has little to do with the natural procreative act. As a
result, man y patients are now getting ve ry odd results And yet, the success rates for intrauterine in seminati on
from their patholog ists or the ir laboratori es and the re- for " mal e factor infertility" are very poor. When [Uf is
sults often do not legitimately make sense. used in natural cycles (Table 47-6), the pregnancy rate
ranges from O.O to 9.0 percent. When lUl is used in
Thi s idea of strict criteria has been further developed clomiphene citrate-stimulated cycles for ma le factor in-
by the National Cooperative Reproductive Medicine fertility, the pregnancy rates range from 0.1 to 16.0 per-
Network. 14 These strict criteria have had no eva luati on cent (Table 47-7) and with HMG -stimulated cycles, the
in the group ofinfertility patients who are interested in pregnancy rate ranges from 1 to 15 percent (Table 4 7-8).
Thus, intrauterine insemination , with its very low suc-
cess rate and patients with male factor-assoc iated fertil -
Table 47-6: Studies of ity probl ems (as determined by the Kruger criteri a), are
lntra uterine lnsemination for primed to be directed into the artifica l reprod uctive tech-
Male Factor lnfertility in Natural Cycles 1 nologies. A very high percentage ofthese patients will
No . of
eventually ha ve that recommendation presented to them.
No. o f Preg na n c i esl Pregnancy
S tudy Patients No . of Cycles Rate (%)
Glass and Ericcson (1978) 19 0/67 o Table 47-7: Studies oflntrauterine

Domowski et al (1979) 27 4/90 4.0 lnsemination for Male Factor lnfertility in
Harris et a l (198 1) 20 3/120 3.0 Clomiphene Citrate-Stimulated Cycles 1
Kerin e t al (1984) 35 8/39 2.1
Confino et a l (1985) 27 01- o No . of
Byrd et al (1987) 15 3/36 2.2 No. of Pregnanci es/ Pregnancy
Study Pat ients No . of Cycles Rate (%)
Hughes et a l (1987) 20 0/32 o
K evin and Quinn (1987) 26/296 9.0 Hewitt et a l (1985) 36 3/64 8. 0
Ho et a l (1989) 47 0/114 o B lumenfeld and Nahhas 13 5/43 3.8
TeVelde et al (1989) 30 3/112 3.0 (1989)
Francavilla et al 68 15/335 4.0 Bollan et a l (1989) 29 5/158 1.7
Friedman et al (199 1) 81 18/276 6.0 Martinez et al (1990) 17 2/12 16.0
Kirby et al (199 1) 188 24/397 8.0 Shalev et al (1995) 52 21223 0.1
1. Adapted from : Ringler GE, Marrs RP, Stone BA: lntrauterine lnsemination 1. Adapted from: Ringler GE, Marrs RP, Stone BA: lntrauterine lnsemination
forthe Treatment of Male Factor lnfertility. In: Werthman PE (Ed ). lnfertility far the Treatment of Male Factor lnfertility. In: Werthman PE (Ed). lnfertility
and Reproductive Medicine Clinics of North America. 10:555-567, 1999. and Reproductive Medicine Clinics of North Ame rica. 10:555-567, 1999.
Chapter 47: Male lnfertility : Evaluation and Treatment 639
origin, then surgery can be helpfu l. For those peopl e

Table 47·8: Studies of who are azoos permi c (w hi ch is qui te ra re), coun se ling
lntrauterine for M ale Facto r lnfe rtility in should be prov ided to encourage th em to adopt. That is
HMG-stimulated Cycles 1 part ofthe approach in NaProTECHNOLOGY.
No. of
No. of Pregrlanc i es/ Pregnancy Wi th those patien ts w ho have o li gospermi a, the most
Study Patjents Nq. of Cycles Rate (%) common medi cation used to help sti mulate the sperm
C ru z et a l ( 1986) 48 7/96 7 count is clomiph ene citra te. 17 •18 Approx imate ly 55 per-
Ke m man et al (1987) 76 9/105 2 cent of patients w ith o li gos permia can expect an im-
Sande et a l (1988) 40 8/56 15 provement in their sperm coun t w ith the use of clomi-
Yovich and Matson (1988 ) 55 9/ 109 1 phene.
Horva th et a l (1989) 39 6/ 175 3
Dodson a nd Ha ney (199 1) 39 13/85 15
The most recommended dosage of clomiphene is 25 mg
Martinez et al (1991) 16 2/28 7
Chaffkin et al (1991 ) 17/111 15 per day fo r 25 days fo llowed by a rest period of five or
Na n et al (1994) 11/84 10 s ix days ; however, at the Pope Paul Yl lnsti tute we ha ve
fo und that lower doses of clomiph ene are, at least e m-
1. Adapted from: Ringler GE. Marrs RP, Stone BA: lntrauterine lnsemination
forthe Treatment of Male Factor lnfertility. In : Werthman PE (Ed). lnfertility p ir ica l ly, m ore s uccess ful. O ur sta nd a rd dose o f
and Reproductive Medicine Clinics of North America. 10:555-567, 1999.
clomp ihene in ol igos permia is 5 mg by mouth two times
a day (PO BID). Thi s can be p repared th ro ugh a co m-
poun ding pharmacy.
IC S I has also been recommended fo r treatment of ma le In Tab le 47-9, a representa ti ve gro up ofstudies are cited
factor infe rti lity and the obstructi o n of the vas defe rens where clo miphene therapy has been utili zed ve rsus a
(obstructive azoospermia) . However, a rece nt cost-ben- placebo or another med ication. Ge nerall y speak ing, there
efi t an a lys is d e m o ns tr ate d th at m icros urg ica l a re good data to support th e effecti ve ness of clo mi -
vasovasostomy was mo re effi cac io us and cost-effec- phe ne in improv ing the sperm coun t, 19 at least in sorne
ti ve than JCS I fo r post-vasecto my infertil ity (a cost of patients.
$25,470 versus $72,52 1 per live birth). Furthermore, con-
cerns have been raised abo ut expos in g wo men to the Human chorionic gonadotropin (HCG) has been shown
ri sks a nd compli catio ns w hi ch may be assoc iated w ith to have a hi gh grade of pred ictab ili ty concernin g the
lCS l. T here is sorn e concern abo ut the tra nsmi ss ion of restorati on offertility. Whil e it is not nearl y 100 percent
abnorn1al geneti c materia l in thi s procedure. 15 The over- effective, it does help the majori ty of men. When admin-
a !! compl eted pregnancy rate in patien ts be ing treated istered intra muscularly, HCG has a long circulating half-
w ith JCS I ra nges o nl y fro m 15 to 19 percent. 16 li fe (about 30 to 40 hours), significan ti y increasing plasma
testostero ne leve ls 24 ho urs afte r HCG applicati on. Hu-
ma n cho ri onic gonadotro pin has been used w ith suc-
Medical Treatment _ _ _ _ _ _ _ __, cess in pati ents w ith pers iste ntl y low motili ty, and dos-
age forms have ranged fro m 10,000 JU biweekl y to 2,500
Azoos pern1i a has no known treatment unless thi s con- IU every five days fo r 75 to 90 days or 2,5 00 lU give n
diti o n is secondary to obstructi on. lf it is obstructi ve in twice week ly overa period of six to eight weeks. 18 Thi s
Table 47·9: Cont rolled Studies of C lomiphene Therapy
Duration No . of Semen
Study Drug Dose (months) Patients lmprovement
Paulson (1979) 25 mg/day 6 20 70%

Cortisone 6 20 40%
Ronnberg (1980) 50 mg/day 3 27 78%
Placebo 3 29 21%
Abel et al (1982) 50 mg/day 9 98 0%
V itamin C 9 89 0%
M ici c and Datl ic (1985) 50 mg/day 6-9 56 32%
No treatment 6-9 45 7%
Adapted from: Jarrow JP: Nonsurgical treatment of male infertility: Empiric therapy. In: Lipshultz LI .
Howards SS (Eds): lnfertility in the Male, Ed 3. St. Louis, Mosby-Yearbook, 1997, pp 410-422.
has also improved pregnancy rates w Attempts have Vaginal Lubricants --------~
been made to combine HCG treatment with various forms
of FSH ( either human menopausal gonadotropin or re- lt has been shown in various studies that lubricants
combinant human FSH). However, results from this ha ve used to assist intercourse are, to varying degrees, sper-
not been encouraging. 21-23 matocidal.30-34 Raw egg white is the only one that has
been shown not to be deleterious to the sperm. How-
A variety of other approaches have also been utilized . ever, the use ofraw egg w hite is not recommended be-
For example, clonidine w ill improve spermatogenesis in cause ofthe potential to have a foreign protein allergic
patients who have maturation arrest. Clonidine is an reaction from placing this in the vagina. 32 ln a study of
alpha-adrenergic agent which stimulates growth hor- 15 substances which have been used over the years as
mone secretion. A dosage of0.075 mg was given orally vaginal lubricants, petroleum jelly and glycerine have
at bedtime. Patients with azoospermia did not respond, had the least detrimental affects on motility and were
but oligospermic patients responded overa two to three considered , at the time, to be the lubricants of choice. 31
month period oftime and severa! patients became preg- lt should be specifically noted that substances such as
nant.24 Prostaglandin inhibitors have been used 25 and K- Y®Jelly or Surgilube®are especially spermicidal.
pentoxifylline has proved beneficia! in oligospermia. 26·27
Glutathione, in a dosage of 600 mg by intramuscular CREIGHTON MODEL FertilityCare™

injection every other day overa period oftwo months, System and NaProTECHNOLOGY_ _
demonstrated a statistically significantly positive effect
on sperm motility. G lutathione has a number of physi- The CREIGHTON MODEL System plays a specific role
ological and pharmacologica l qua li ties that tend to act in patients who have difficulty achieving pregnancy
against lipid peroxidation of the cell membrane . This when the seminal fluid parameters are abnom1al. In such
has recently been found to be involved in sperm dam- circumstances, identifying the time offertility with ac-
age, resulting in a reduced fert ilizing potential. 28 curacy will assist couples with severe oligospermia to
achieve pregnancy. In Figures 47-l and 47-2, four ex-
Finally, vitamin E has also been used asan antioxidant amples of successful pregnancies in these circum-
to treat reactive oxygen species associated with male stances are shown. In Figure 47-1 , the patient's hus-
infertility.29 An oral administration ofvitamin E signifi- band had a sperm count done on day 1O of the preg-
cantly improved the in vitro function ofhuman sperma- nancy cycle. H is effective sperm count (ESC) was
tozoa. l 89,666/cc. This was not this patient's first pregnancy,
it was her fourth ; however, they had more difficulty
achieving this pregnancy than the others. Nonetheless ,
the only treatment eventua lly implemented after she had
been evaluated and found to be within normal limits,
""' ge ge 8C 9'C IOC (,iC, 4)(a 4xl

1(/ X1 X1 JC I lf l IC 1 IC f
I l
33 y/o G4 P2 SAB1
SFA X=
Count 771 ,000/cc =
Motility 30%/10% =
Normals = 82%
WBC's 10-15/hpf =
ESC 189,666/cc =
Figure 42-1: Patient whose husband has severe oligospermia . Effective sperm count (ESC) was 189,666/cc at time of
pregnancy using natural insemination and properly timed intercourse (From : Pope Paul VI lnstitute research , 2004).
Chapter 47 : Male lnfertility : Evaluation and Treatment 641
wasfertility-focused intercourse throug h the CrMS . the entire cycle. The coup le used this day and success-
fully achieved a pregnancy. Later, w ith an ultraso un d
In Figure 47-2 , severa! similar examples are presented. performed approximately four weeks fol lowing the esti-
1n patientA, the etfective spe1111 count was 30,000/cc, in mated time of conception , verification of thi s concep-
patient B the ESC was 1 16,850/cc and in patient C , the tion date was ac hieved. T he due date as estimated by
ESC was 50,000/cc. These examples are presented to ultrasound and the due date estimated by the Peak Day
show that the CrMS and NaProTECHNOLOGY can be were identical within one day.
used to assist couples achieve pregnancy even when
there is severe oligospermia. Over the years of our involvement in the treatment of
infertility patients, we have consistently seen extraord i-
In Figure 47-2 , pregnancy cycle B, there are other addi- nary successes in patients who have severe o ligosper-
tional findings. This patient's Peak Day occurred on mia . The results ofthis are shown later in th is textbook.
day 30 ofthe cycle with an observation of "tacky clear" These results equal or exceed the success rate of ali of
(8K x 1). This was the only peak mucus observation of the artificial reproductive technologies.
12 13 14
I I I I I I
r I I I
.... ,
'111ld
Pregnancies in
Severe Oligospermia
Figure 42-2: Patients with severe oligospermia and successful pregnancy using properly timed intercourse and natu ral
insemination : A) effective sperm count = 30 ,000/cc, B) effective sperm count = 116,850/cc, C) effective sperm count = 50 ,000/
ce (From : Pope Paul VI lnstitute research , 2004).
1. Howa rds SS: Antoin e va n Leeuwenh oek and the Discovery 20 . Mehan DJ, Chehva l MJ: Human Chorionic Go nadotropi n in
of Sperm . Fertil Steri l 67:8 16-1 7, 1997. th e Trea tm ent o f th e ln fe rtil e Man. J Uro l 128:60-63 ,
1982.
2. Si gman M, Lipshultz LI , Howa rd s SS: Eva lu atio n of th e
Subfertile Mat e. In: Lipshultz Ll , Howards SS, eds: lnfertil- 2 1. Knuth UA , Honi gl W, Bals-Pratsch M, et al: Treat111 en t of
ity in th e Male (3 'd ed.) Mosby Yearbook, St. Loui s, 1997. Severe Oli gospermia with Hum an Chorionic Gonadotropin/
Hum an Menopausa l Gonadotrop in: A Pla cebo-Co nt ro ll ed ,
3. Spit z A, Ki m ED, Lipshultz Ll: Em piri c Med ica l Th erapy Doub le Blind Tria!. J Clin Endocrino! Metab 65 :108 1-1087,
for Ma le ln fe rtilit y. In We rthrn an (e d): Ma le lnfert il ity. 1987.
In fe rtil e Repro Med Cl ini cs of NA 10:569-586, 1999.
22. European Metrodin HP Stud y Group. Efficacy and Safety of
4 . Mieusset R, Bujan L, Mondinat C, et al: Association of Scro- Hi ghl y Purifi ed Urinary Follicle-Stimulatin g Hormon e with
tal Hyperth emia with Irn paired Spermatogenesis in lnfertile Hu111an Chorionic Gonadotropi n for Treatin g Men with Iso-
Men. Fertil Steri l 4 8:1006-1011 , 1987 . late d Hypogo nadotropic Hypogo nadi sm. Fertil Ste ril
5. Kursh ED: What is th e lncid ence of Varicocele in a Ferti le 70 :256-262 , 1998.
Populati on9 Fe rtil Steril 48:5 10-511 , 1987. 23 . Kam isc hke A, Behre HM , Bergmann M, et al: Recombinan!
6. Glatstein IZ, Best CL, Palumbo A, et al: The Reproducibility Human Follic le Stimulating Hormone for Treatment of Mal e
of the Postcoi tal Test: A Prospective Study. Obstet Gynecal ldiopathi c lnferti li ry: A Randomized, Doubl e-B lind, Pl acebo-
85:396-400 , 1995. Co ntro ll ed, C linical T ria!. Hum an Reproduction. 13 :596-
603 , 1998.
7. American Society for Reproducti ve Med icin e. Fact Shee t:
Di agnosti c Te tin g for Ma le ln fe rtili ty. Birmingham , Ala- 24 . Terada H, Suzuki K, Fujita K: Oral Clonidine lmproves the
bama , 1997. Sperm atoge nes is of Pati ents with Maturat ion Arres!. (Ab-
strac t 77 2) American Urolog ica l Assoc iation (AUA) 93 rd
8. Mehan DJ , Cheh va l MJ: A C lini ca l Eva lu at ion of a New An nual Meeting, Jun e 1998 .
Sil astic Seminal Fluid Co ll ection Device. Fertil Steril 28 :689-
69 1, 1977 . 25 . Barkay J, Harpaz- Kerpe l S, Ben-Ezra S, et al: The Prostag-
landin and lnhi bitor Effect of Antiinfl ammatory Drugs in
9. Schoenfe ld C, Amelar RD, Dubin L, et al: Eva luation of a the Therap y of Ma te lnfertility. Fertil Steril 42:406-4 11 ,
New Silasti c Se111inal Fluid Co ll ecti on Dev ic e. Ferti l Steri l 198 4.
30:319-321, 1978.
26 . Mer in o G, Chequer JCM, Baraho na E, et a l: Effects o f
1O. Za vos PM: Semin al Parameters of Ejacu lates Co llected frorn Pentox ify llin e on Sperm Motility in Norm al Gonad otropi c
Oli gospe rrni c and No rmos permic Pat ien ts via Masturbati on Asthenozoospermic Men. Archi ves o f And ro logy. 39 :65 -
and at lntercou rse with the Use of a Si last ic Seminal Flui d 69, 1997.
Co ll ecti on Dev ice . Fertil Steril 44: 5 17-520, 1985.
2 7 . Tesarik J, Thebalut A, Testan J: The Effect of Pentoxifyll ine
1 1. Zavos PM , Good Pasture JC: Clinica l lmprovements of Spe- on Spenn Movemen t Characteri sti cs in Normosper111ic and
cific Se 111in al Defic iencies via lntercourse with a Seminal Ast he nozoos per mi c Speci mens. Hum a n Repro du cti on.
Col lecti on Dev ice versus Ma sturbati on. Fertil Steril 5 1: 190- 7:1257- 1263 , 1992.
193, 1989 .
28. Lenzi A, Cul asso F, Gandi ni L, et al: Pl acebo-Contro ll ed,
12. Zavos PM, Kofina s GD , Sofikiti s V, et al: Di ffe rences in Doubl e- Blind, Cross-O ver Trial of Glutathione Th era py in
Semin al Para meters and Specimens Co ll ected by lnterco urse Male lnfertilit y. Hum an Reprodu cti on. 8: 1657- 1662, 1993.
and lncompl ete lntercourse (Co itus ln terruptus). Fert il Steril
61: 11 74-11 76, 1998. 29. Kesso poul ou E, Powers HJ , Sharma KK, et al: A Doubl e-
Dash Blind Randomi zed Placebo Cross-Over Controll ed Trial
13. Kruger TF, Acosta AA , Sim111ons KF, et al: Predi cti ve Valu e Us ing the Antiox id ant Vitami n E to Treat Reacti ve Oxygen
of Abno rma l Sper111 Mo rph o logy in In Vitro Fert ili zation. Species Associated to Mal e lnfertility. Fertil Steril 64:825-
Fert il Steri l 49: 11 2-11 7, 1988. 83 1, 1995.
14 . Gu zick OS , Overstreet JW, Factor-Lit va k P, et al: Spe r111 30. Ta gatz GE , Okaga ki T, Sc iarra JJ : The Effect of Vag in a l
Morph o logy, Moti lit y and Co nc en tra tions in Ferti le an d Lubricants on Sperm Motility and Viab ilit y. A111 J Obste!
lnfertil e Men . N Engle J Med 345:1388-1 939, 200 1. Gyneco l 11 3:88-90, 1972.
15. Pa v!ov ich C P, Schlegel PN: Fertility Options After Vasec- 3 1. Go ld enberg RL, White R: The Effect of Vagin al Lubri ca nts
to111y Reversa l. Fertil Steril 67 : 133 , 1997. on Sperm Moti lity. Fertil Steril 26:872-873 , 1975.
16. Hade J, Daneshmand S, Surrey M W: Cons idera tion of Fe- 32. Tulandi T, Mc ln nes RE: Vaginal Lubri cants: Effect of Glyc-
ma le Fac to rs in the Treat111ent of Ma le ln fe rtilit y. N: eri n and Egg White on Sperm Motility and Progress ion In
Werth111 an PE, Ed ln ferti lity and Reproductive Medi c in e Vitro. Fertil Steril 4 1:151- 153, 1984.
C lini cs of No rth A111eri ca: 10:607-619, 1999.
33. Boyers SP, Co rrale s MD, Hu sza r G, et al: Th e Effec ts of
17. Ronnberg L: Th e Effect of Clomiphene C itrate on Di ffe r- Lubrin on Sper111 Motilit y In Vitro. Fertil Steril 47:8 82 -
ent Sperm Pa rameter s and Serum Ho rm o ne Leve ls in 884, 1987.
Prese lected ln fe rtile Men: A Controll ed Doubl e-Bl ind Cross-
Over Stu dy. lnt J Androl 3:479-486. 1980. 34. Mill er B, Klein TA, Opsah l MS: Th e Effect of a Surgical
Lubrican! on In Vivo Sperm Penetration of Cervical Mucus.
18. Mi cic S, Dotli c R: Eva luation of Sperm Para meters and Fertil Steril 6 1: 1171 -1 173 , 1994.12. Sanderson SK, Dubrow
Clinica l Trial with Clo111iphene Citrate of Oli gosper111ic Men. J: Fertility Dec line in th e Modern World and th e Origin al
J Uro l 133: 22 1-222 , 1985. Demographic Transitio n: Test in g Three Th eo ries wi th
19. Schill WB: Recen! Progress in Ph annaco log ica l Therapy of' C ross-Nat io na l Data. Po pulation and Env iro n111ent 2 1
Male Subfert ility - A Review. Andrologia 11:77-107 , 1979. (6):5 11-5 3 7, 2000.
Fecundity and the Mucus Cycle Score
in Couples using the CrMS
Joseph B. Stanford, M.O.
T he understanding and cooperative management of

fertility is based on the fundamental biologic real-
ity that conception (fertilization) is possible for relatively
Barrett-Marshall tudy based on a British population of
couples using basal body temperature for natural fam -
ily planning (NFP), 20-22 a study ofwomen in North Caro-
few days of the fertility (menstrual) cycle u Because lina who were trying to conceive and who co llected
ovum v iabili ty is less than 24 hours after ovulation , the daily urine specirnens to identify hormones of ovula-
number of days during which conception can occur is tion and conception, but had no specific knowledge of
ba ed on the viability and transport of spenn , which in their own feti ili ty,223 anda larger European fecundabil ity
turn is based on estrogenic (type E) cervical mucus .3-5 study of couples using the sym ptothermal method of
Effectiveness stud ies ofvarious methods ofnatura l fam- NFP. 24 Each of these studies has resulted in multiple
ily planning have established that prospective identifi- analyses and publications, sorne ofthem compari ng the
cation of days of fertility (also called the fecund win- di fferent data sets. 25 Importantly, each ofthese data sets
dow) is accurate for avoiding pregnancy 6- 10 and achiev- excluded coup les with any history sugges ti ve of
ing pregnancy. 11 • 12 The Peak Day of vaginal discharge subfertil ity.
( defined as the last day on which a woman observes
vagina l discharge whi ch is lubricative, clear, or stretchy) This chapter discusses the first stud y to examine fe-
has been shown to be a reliable indicator ofthe timing cundity and the fecund window specifica lly from the
of ovu lation, occurring +/- 2 days of the date of ovula- point of view of a standa rdized mucus-only system of
tion in about 95 percent of menstrual cycles. 13- 19 understanding fert il ity, the CREIGHTON MODEL
FertilityCare™ System (CrMS). lt is the first study to
Despite the fundamental biologic importance ofthe fer- look systematical ly at the quality of mucus discharge
tility cycle, few studies ha ve investigated the exact prob- and the probability ofconception (fecundity). lt is a lso
abil ities of pregnancy for specific days in relation to the first study to include couples with subferti lity.
ovulation, or how the quality ofmucus affects the prob-
ability of conception. Three studies have been used to The CrMS has a number of essential characteristics that
estímate the probabilities of pregnancy for given days made this study possible. First, th e observation of mu-
relative toan estimated ovulation day identified by basal cus was standardized in its teaching and app lication ,
body temperature or urinary hormones: the original allowing for an acc urate comparison ofthe fertility chart-
643
ing between different women. 26 •27 Second , an objective tified in the CrMS chart is genera lly 9 to 1Odays.
mucus cycle score was developed by Hilgers that can
be used to examine the quality of estrogenic cervical Cycle fecundity:
mucus discharge for a given cycle. 28 This study builds Refers to the probability of conception in a specific
upon classic foundational work by Hilgers, et al ., which ferti lity (menstrua l) cycle, assurning that intercourse
demonstrated that the standardized observations of occurs during the complete ly optimum time, such as
vaginal discharge by women using the CrMS correlate on the Peak Day.
very closely with the changes in the biophysical param-
eters ofthe mucus secreted by the cervix. 29 This earlier Daily fecundity:
work demonstrated that biologically, the quality of mu- Refers to the probabi 1ity of conception if intercourse
cus discharge and the Peak Day could identify the po- occurs on a specific day of the fertility cycle, de-
tential for conception on any given day. The study dis- fined in relation to the Peak Day (that is used as the
cussed in this chapter represents an extension and clini- estimated day of ovulation). For example, the daily
cal validation ofthat work, by assessing actual clinical fecundity of Peak minus 2 (P-2) refers to the prob-
conception in relat ion to mucus observation , according ability of conception if intercourse occurs only on
to the CrMS. the second day before the Peak Day, and on no other
day during the fecund window.
The results presented in this chapter come from the
CREIGHTON MODEL Multicenter Fecundity Study. This
study was launched over a period of severa! years The objectives of this study were:
through discussions at the America n Aca de my of
1. To estímate the day-specific probabilities of concep-
Fertili tyCare P rofessionals (known at the time as the
tion in the menstrua l cyc le based on the biomarkers
American Academy of atura! Family Planning). Par-
that are clinica lly assessed with the CrMS .
ticipating centers and the Practitioners responsible for
study participation are acknowledged at the end ofthis 2 . To assess the cycle-specific probab il ity of concep-
chapter, along with other persons who have contrib- tion associated with the CrMS mucus cycle score.
uted to this research. Many ofthe results presented in
3. To assess the variation in fecundity among couples
this chapter have been reported previously. 30 The pri-
using the CrMS .
mary purpose ofthe CREIGHTON MODEL Mu lticenter
Fecund ity Study was to answer the question outlined
above and addressed in this chapter; however, other We undertook this study among a group of new users
analyses have been reported from this study 31 and fur- ofthe CrMS in six different CrMS centers in the United
ther analyses are ongoing. States (as detailed in the acknowledgments) . We in-
cluded couples with a history of difficulty achieving
In this chapter, the fol lowing definitions are used: pregnancy, whom we analyzed separately.
Conception:
Refers in principie to fertilization. However, in this Methods of the CREIGHTON MODEL
study, there was no way to directly assess fertiliza- Multicenter Fecundity StudY ----~
tion , so for the purposes of this chapter, it refers to
clinically identified pregnancy (i .e., prolonged post- We conducted a retrospective coho1t study using data
Peak phase with positive pregnancy test). extracted from existing standard teacher and user
records ofthe CrMS . Ali new users ofthe CrMS for the
Fecundity: years 1990-1996, were considered potentia lly eligible for
Refers to the probability of conception. this study. lnitially, approximately 80 CrMS centers in
the USA were contacted and asked to consider partici-
Fecund window: pating in this study. The fina l selection of CrMS centers
Refers to the consecutive period of days during was based on wi llingness to participate, estimates of
which conception is possible. lfit were possible to pregnancy rates at each center (higher pregnancy rates
measure th is time period exactly, it would be about were preferred), and logistical considerations. A detai led
five to six days. 24 ·25 However, because the mucus description ofthese new users has been published pre-
symptom has sorne variability in onset and the Peak viously.31
Day can vary up to three days in relation to ovula-
tion ,13 the clinically estimated fecund window as iden- We reviewed ali descriptive variables that were avail-
Chapter 48 : Fecun d ity and the Muc us Cycle Score 645
abl e to us fro m screening data fro m the CrMS partici - and ma ny of these ac hi eved pregna ncy. Thi s a ll owed
pating centers, based on the General lntake Form (G IF), us to esti mate pregnancy ra tes for intercourse on di ffe r-
w ith th e inte nt to select two coho1ts far study: normally e nt days thro ughout the cycle fo r thi s gro up ofwomen
fe 11ile couples, and infe rtile co upl es. We fo und that the ofapparentl y normal fe rtili ty.
most rel iable ind icato r offertili ty sta tus that was ava il -
a ble fro m coupl es at the time of entry into CrMS in-
structi o n was their own stated inte ntion far lea rni ng the Subfertile Couples -------~
CrMS o n the G lf : whether they we re curren ti y tryi ng to
ac hi eve pregnancy, or not. (Thi s crite rion was more re- Most (7 1%) couples who indi cated at e ntry to CrMS
li able than a couple-des ignated history of infe rtili ty or a in truction th at they were try ing to ac hieve pregnancy
Reproducti ve Category of in fertili ty.) We used this key gave ev idence of prev ious diffi cul ty in ac hi ev ing preg-
c rite rion to deve lop two d istinct cohorts. A cohort of nancy, although not ali hada fo rma l di ag nos is of infe r-
appare ntl y no rmal fe rt ility cou pl es was generated fro m tili ty. We therefore des ignated ali coupl es who ind icated
the poo l of coup les who indi cated th at they we re not at entry that they were try ing to ac hi eve pregnancy as
try ing to achieve preg nancy, a nd a co ho1t of subfe rtil e subfertile. We app lied the fo ll ow ing add iti o na l se lec-
coup les was generated fro m the poo l of couples w ho tio n cri teria to thi s g roup : wo ma n 's age at entry be-
indi cated that they were tryi ng to ac hieve pregnancy. tween 18 and 39 years, sexua ll y acti ve w ithin two men-
st ru a l cyc les of e ntry, not preg na nt a t e ntry, not
breastfee ding, and records ava il abl e fo r rev iew. Fa r thi s
Normally Fertile Couples - - - - -...., gro up, we had no exc lusio n fo r numbe r of fo ll ow- up
vis its com pleted, because we w ished to include preg-
Co uples w ho we re not try ing at e ntry to ac hieve pregnancies that mig ht happe n in the fi rst two mo nth s of
nancy indi cated that they were learning the CrMS wi th try ing to ac hi eve pregna ncy. In thi s gro up, there was
a curre nt intention of avo iding pregnancy, o r of moni - a lso no exc lus ion based o n di sease or surgery.
tori ng their ferti li ty w ithout specifi c re producti ve inten-
tions. We app lied add itio na l se lecti on criteria to this
g roup in a rder to se lect fo r coupl es th at we re of a ppa r- Study Procedures --------~
ent ly no rmal fe rtili ty: age at entry between 18 and 39
yea rs, sex ua lly acti ve within two me nstrual cycles of Each eligibl e coupl e began contributing data to the study
entry, not pregnant at entry, not breastfeedi ng, no hi s- fro m when the wo man first sta rted c harting he r da ily
to ry of di sease or surgery that mig ht impair ferti li ty. In vagina l di scha rge, whi ch o rdin aril y occurred immedi -
additi on, the records had to be ava il abl e for rev iew. ate ly after she fir t attended an introd uctory teaching
Ba ed on previo us wo rk, we restricted the e ligibili ty of sess ion fa r the CrMS . Each co uple conti nued contrib-
thi s gro up to those who had co mp leted fo ur or mo re utin g data to the study until any o ne of the fo llo wi ng
fo ll ow-up instruct io nal vi s its (72 pe rcent of a ll new us- condi tions occurred : 1) the woma n became pregnant; 2)
ers in these ce nters ove r thi s time peri od), in order to the co upl e stopped c harting th e CrMS o r no fu rthe r
optimi ze the qua lity of the clini ca l data from the couple 's CrMS c ha11ing was ava ilable; 3) the wo ma n bega n the
cha rting.3 1 According to CrMS procedures the first fo ur use of ho rmo ne therapy; 4) the coupl e compl eted o ne
fa ll ow-up visits usuall y occur in the first two mo nth s of yea r of c ha rting w ith th e CrMS. A n add itio nal ex it con-
use, and during thi s time the coupl es learn how to pre- d ition fo r the couples w ith a pparentl y no rma l fe rtili ty
c ise ly o bserve and cha1t th eir m ucus discharge. was the occ urrence of a reproductive surgery o r proce-
d ure (such as cryo therapy of the cerv ix) .
lt is important to recogni ze that sorne coupl es that be-
gin use of the CrMS w ith the intenti on to avo id preg- Four sta ndard CrMS fo rm s se rved as data sources fo r
na ncy c hange their intenti o ns or behav ior th ro ug hout thi s study: 1) the Genera l lntake Form; 2) the Fo ll ow-up
th e first yea r of use (a nd beyond ). ln structi on in the Form; 3) th e CrMS da ily c hart; and 4) the CrMS preg-
CrMS emphas izes that a coupl e may at any time choose na ncy eva luati on fo rm . C harts we re photocopi ed by
to use the CrMS to avo id pregnancy (by a bstine nce each ofthe CrMS centers, w ith ide nti fiers removed, and
from genita l contact during the days offerti li ty) or consent to the Uni ve rsity of Uta h. Researc h ass istants who
ve rse ly to achi eve pregnancy (by intercourse duri ng we re forma ll y tra ined in the CrMS (by attending th e
the days offert ility). 6 Consiste nt with this, a substantia l same Ed ucati onal Progra m as FertilityCare™ Practi-
propo1t ion of coupl es w ho indicated at entry th at they tioners) abstracted data fro m the charts based on pro-
we re avoiding preg nancy later c hose to have intercourse toco ls deve lo ped by th e in vestigato rs. Data abstracted
during days identifi ed as fe 1tile (fecun d) by th e CrMS , for each co up le included de mogra phi c ite ms and med i-
646 The Med ic al and Surg ical Pract ice of NaProTECHNOLOGY
cal hi story. Fo r each CrMS fo ll ow-up visi t, data were compete independently in attempt ing to fert ili ze the
abstracted on the CrMS in structor 's assessment of the ovum .22 However, the Schwartz, et a l. , model can pro-
compl eteness of the wo man 's daily chartin g and the duce biased estimates because it assu m es that a li
concomitant use of barri ers o r wi thdrawa l. For each coupl es have equa l fec undi ty, i.e., that ali coupl es are
menstrual cycle, data abstracted included medication eq ua ll y like ly to get pregnant ift hey have interco urse
use or other ci rcum stances, and whethe r or not there o n the same days relative to ovulation. Our analysis
was c lini ca l evide nce of conception. For each day of was based on a Bayesian mode l proposed by Dunso n,
the me nstrual cycle, the fo llow ing data were recorded : which acco unts for couple-speci fi c a nd cyc le-spec ific
the vaginal di scha rge record ing system (V DRS) obser- fac tors predicting a unique cou ple 's fecundity, wh ich
vations, interco urse, and any spec ial circumstances. Key may be diffe rent from that of another couple.32 The model
data we re do ubl e-entered for a li cases. The Peak Day accom pli shes this by us ing a " cycle viability" term ,
for each men strua l cyc le was identified independently whic h has a multiplicative effect on the day-specifi c
by two research assista nts and by the principal in vesti- pregnancy probabi liti es. The model a lso req uires the
gator (JBS). Us ing recorded dates, we corre lated data daily fecundity to in crease (or stay constant) up to the
o btained from th e Follow-up Form wi th data from the unkn own most fec und day of the cyc le a nd decrease
CrMS dail y cha rt. ( or stay constant) thereafter. In other words, the model
ass um es there can be on ly o ne most fec und day, and
The unit of analysis for this study is the menstrual cycle. that fec undi ty rises before that day and fa lls afterwa rds.
For th e purposes ofthis analysis, menstrual cycles were This ass umptio n is consisten t w ith data from prev ious
excluded if any of the following was present: co ncur- studies, and it increases the statistical power of the
rent use of honnonal medi cati on (i ncluding oral contra- model. This model has been used previous ly in exp lo r-
ceptives) o r a ny othe r medicatio n that might affect ei - ing re lati onshi ps between male and female age a nd the
ther fertility or muc us o bse rvatio ns (s uch as clomi- day-specific pro babi 1iti es of conceptio n from the Euro-
phene) ; incomp le te data for muc us observati o ns on pean fecun dability study. 33
days in the cycle; incomplete data fo r acts of intercourse
in the cyc le; o r any use ofbarriers or w ithdrawa l during
the cycle. Mucus Cycle Score _ _ _ __ _ _~
Cycles were excluded from th is analysis ifthe Peak Day T he standardized daily vaginal di scharge recording sys-
could not be re liabl y identified. The Peak Day was conte m of the CrMS is based on stretch , color, and sensa-
si dered not reliabl y identified ifthe research personnel tion ofthe discharge as recorded by the V DRS .29 This
could not reach a consensus o n the Peak D ay, inc lud- recording system is converted to a dai ly numerica l score
ing consultation with stud y consultant Dr. Hilgers. This ranging fro m O to 16. 28 A n average of the daily score
occurred in 3.7 p ercent ofcycles. lt is impo rtant to note from th e Peak Day and the 5 days precedin g the Peak
that not reliably identifying the Peak Day could occur Day yields a summat)' mucus cycle sco re for each men-
for a number of reasons, includin g cyc les w ith ab no r- strual cycle. This 6-day w indow correlates w ith the ap-
m al or absent ovulation. Even without identify ing a Peak prox imate 6-day fecund w indow found in earli er stud-
Day, the couple can still used the CrMS to identify days ies, as described previous ly. 24 ·25 Th e score can range
of potential fert il ity a nd infertility for th e purposes of fro m O to 16 . A score ofO indicates a dry cycle w ith no
avoiding preg nancy o r trying to conceive . However, in Peak Day, so that ali seores included in this study were
most cases of not identi fy ing the Peak Day, further evalu- above O. lt is currentl y unknown exactl y what a norma l
ation by a medi ca! consul tant would be adv isab le fo r score wou ld be, but clini ca ll y, a regular mucus cycle
couples. score has been designated as 7 .6 or greate r. 34 We used
the mucus cycle score as a variable to predict fecundity,
along wi th age and recent use of oral contrace pti ves.
Statistical Model --------~
The stud y protocol was approved by the Uni versity of
B eca use intercourse can occur on multipl e days during Uta h lnstituti ona l Review Board as exem pt (not requir-
the fecund window, statistical models need to be used ing subj ect consent), since it in vo lved the use of exist-
to estimate dail y fecu ndity. 2 ·2º· 24 •25 A deta iled summary ing c lini ca l data with a li unique subject identi fiers re-
of statistical model s has been given elsewhere. 25 The moved.
m ost co mmo nl y used model was ada pted by Schwartz,
et al. , under the ass umption that sperm introd uced into
the re productive tract on different days m ing le and then
Chapter 48 : Fecund ity and the Mucus Cycle Score 647
Results - - - - - - - - - - -- -----, graduates), of the Roman Cath oli c reli gion (7 1%), and
nulliparou (67%). The most common meth ods of fam -
Of 1278 new users ofthe CrMS at the six FenilityCare™ ily pl anning ever used in th e past were ora l contracep-
Centers, 184 were excluded because they were breast- tives (66%) and barrier methods offamily planning (46%).
feeding or pregnant, 72 beca use they were less than 18 There were systematic differences between the group
years or over 39 years of age, and six were exc luded of norma ll y fe rtil e and subfe rtile coupl es in thi s study
because their intenti on status at entry was unknown. fo r a number of characteristi cs. These included the pro-
Thi s res ulted in a poo l of 8 16 couples who were not porti on fro m di ffe rent CREIGHTON MODEL teachin g
seeking pregnancy at entry and 200 subfertil e co upl es centers, marital status ( ub fe rtile much more likely to be
who were seekin g preg nancy at entry. Of th e 8 16 married), and religion (normally fe rtile couple more likely
coupl es not seekin g pregnancy at entry, 94 were ex - to be Catholi c). The normal fe rtili ty gro up had more re-
cluded beca use of a h istory of gyneco logic surgery that cent users of ora l contraceptives. Subfe rtil e coupl es had
could affect fe rtili ty or mucus observations (including higher pro porti ons of th ose with a hi story of previous
cryotherapy or cautery of the cervix), 15 were exc luded pregnancy and spontaneous abortion, and co uples who
because th ey had a hi story of use of Depo-Provera or had previ ously used a natural method of fa mily plan-
the intrauterine dev ice, and 139 were excluded beca use ning, most commonl y basa l body temperature (whi ch
they completed less than fo ur fo ll ow-up CrMS in struc- often may have been used to try to achi eve pregnancy).
tional visits. This left 568 coupl es of apparently nom1al Subfe rtil e co upl es in thi s study were also older than
fertility eligible for the study. Of these, 259 charts (46%) normally fe rtil e coupl es (both men and women) and on
could not be obtained fo r review, leaving 309 normall y average entered CrMS in stru cti on about one year later.
fertile coupl es with charts avai labl e for analysis. Of the
200 couples with subfertili ty, 83 (43%) charts could not Among the 11 7 subfe rtil e coupl es, 59 coupl es had been
be obtained, leav ing 11 7 subfe rtil e coup les with charts trying fo r over one year to get pregnant, 6 couples had
avail abl e for analys is. been try ing fo r less than one year to get pregnant, and
52 couples had no avail able info rmation on how long
The dem ographic and reproducti ve characteri sti cs of they had been trying to get pregnant. The average tim e
th e 309 normall y fe rtil e couples and 11 7 subfe rtil e spent trying to conceive before leaming the CrMS was
coupl es are given in Tabl e 48-1 . In genera l, the sampl e 3.0 years; ra nge 0.25 to 11 years (n=65).
was predominantly white (93 %), marri ed (7 1%, an addi-
tiona l 19% were engaged), wel1educated (65% college From the 309 normall y ferti le couples we obtained infor-
X Normal fertility couples

0.5 4 Subfertile couples
>-
g 0.4
~
e:
Cl
Q)
-
5_0 .3
o
~
!
i
= 0.2 1 ¡
.e
~ i i t
! __,,-)
fj ---*: :!/~~
¡ ¡¡\ ¡¡
.e
o
a: 0.1
¡/ ........... * :¡
1
: i
1 1- t 1 1
¡ ........_
, _ :
, ___ * ·-·
_..-- , 1 1 t - :i:--- .
1 "'-- ' "'- ·
0 . 0+-a.-_,_;i..==-:1'------------..;._-&.;-
=~
-6 -4 -2 o 2 4
lntercourse day • Mucus peak
Figure 48-1: The probability of preg nancy from interco urse on a single day in the men-
strual cycle {daily fecundity) relative to th e peak mucus day, plotted separatel y for normally
ferti le co uples and subfertile co uples. The dotted lines are th e 90% confidence interval s for
the normally fertile couples (From : Stanford JB , Smith KR , Dunson DB : Vulvar Mucus
Observati on and the Pro bability of Preg nancy. Obstet Gynecol 101 :1285-1293, 2003).
Table 48-1: Characteristics of Snidy Subjects by Fertility Status
Percent of p·value for

Percent of apparently Percent of normal fertility
total sample normal fertility subfertility vs. subfertility
Characteristic n (N=426)1 (n=309) (n=1 17) by chi-square1
Creig hton Model A 193 45.3 40.8 57 .3 .001

teaching center B 20 4.7 2.9 9.4
clusters' e 158 37 .1 40.8 27.3
D 55 12.9 15.3 6.0
Woman's race' Caucasian 396 93 .0 92 .9 93.2 .91

Other5 30 7.0 7.1 6.8
Marital status Not married 122 28.6 38.8 1.7 .0001

Married 304 71.4 61 .2 98.3
Woman 's education' Less than college graduate 151 35 .5 35 .1 36.8 .75
College graduate 274 64.5 64 .9 63 .3
Yearl y household income $40 ,000 or less 236 55.4 56 .0 53.8 .69
Over $40 ,000 190 44.6 44.0 44.2
Woman 's religion' Catholic 299 70.5 78.8 48.7 .0001

Other" 125 29.5 21 .2 51 .3
Woman employed? No 67 15.8 14.9 18.0 .45

Yes 357 84 .2 85.0 82 .1
Any previous No 284 66.7 73 .5 48.7 .001

pregnancy? Yes 142 33 .3 26.5 51 .3
Ever hada No 384 90. 1 96 .8 75 .2 .0001

spontaneous abortion? Yes 42 9.9 4.2 24.8
Ever had an elective No 409 96 .0 95 .8 96 .6 .71

abortion? Yes 17 4.0 4.2 3.4
Eve r used oral No 143 33 .6 65.9 27.3 .095

co ntraceptives? Yes 283 66.4 64 .1 72 .7
Ever used barrier No 232 54 .5 56.0 50.4 .30

methods? Yes 194 45.5 44.0 49 .6
Ever used a natural No 347 81 .6 88.6 62.4 .0001

method of fam ily Yes 79 18.5 11 .3 37 .6
planning?
Contraceptives most No 298 69 .9 62 .5 89.7 .0001

recen! method of Yes 128 30 .1 37 .5 10.3
family planning?
Mean for
Mean for total apparently Mean for p-value for
sample normal fertility subfertility normal fertility
(Range) (Range) (Range) vs. subfertility
n (N=426) (n=309) (n=1 17) by t-test
Woman's age (years) 426 27.9 27.0 30 .30 .0001
(18-39) (18-39 ) (21-39 )
Man 's age (yea rs) 413 29.7 28.8 31 .9 .0001

(19-49) (19-49) (23-49) .0001
When ente red program 426 3.18 2.91 3.92 .0001

(Years since 1/1/90) (0.04-0.96) (0.04-6.96) (0.04-6.96)
1. Far a few ilems, percentages are calculated excluding cases wilh missing data far that item. Percentages may not total 100% dueto rounding .
2. Ali p-values less than or equal to .001 are shown as .001 .
3. The eigh t Creighton Model teaching centers in this study were clustered into four groups based on similar continuation rates within each group.
4. Far these categories, the distribution of men's responses were very similar to that far women's responses .
5. Other race includes Hispan ic (3.3%), African American (0.2%), Asian or Pacific lslander (2.4%). Native American (0.2%), and others (0.9%).
6. Other religion includes Protestan! (21 .8%), other religion (6.3%), and no religion (1 .2%).
7. Natural methods inctudes calendar mythm (2.8%), basal body temperature (11 .3%). symptothermal (1.6%), ovulation method (2.3%). and other (4.0%).
Chapter 48: Fecundity and the Mucus Cycl e Score 649
mati on fo r 2142 menstrual cyc les. After exc lusion of daily fecundi ty was greater than O.O 1 for normally fertile
cycles with use ofprobl emati c medi cations, use ofbarri- coupl es from day-5 to day +4, and for subfertile couples
ers or withdrawa l, or incomplete recording of mucus fro m day -4 to day +3.
observati ons or intercourse, 168 1 cyc les were eli g ibl e
fo r analys is, among which were 81 pregnancies. From We used a multivariab le model to adju st for the effects
the 11 7 subfe rtile coupl es we initia lly had 600 menstrual of age, mucus cyc le score, and fe1iility statu s as addi-
cycles recorded. After the sa me exc lusion of cycles, 373 tio11al covariates intluenci11g the cycl e fecu11dity. 32 .3 3 (l11i-
cycles were eligibl e for analys is, among whi ch were 30 ti ally we adju sted also for recent oral contraceptive use,
pregnancies. All pregnancy cyc les thus identifi ed had but since tbi s vari able had no effect on the model , we
at least one act of intercourse within the interva l from 6 exc luded it from subsequent an alyses.) Fertility status
days pri or to the Peak Day through 3 days after the was significa11t in the model , as was mucus cycle score
Peak Day. For both n01mally fe rtile couples and subfe rtile amo11g normal ly ferti le coup les (posterior pro bab i1ity >
coupl es the median Jength of menstru al cycl es entered 0.95), but mucus cycl e score am o11 g subfe11ile couples
into the study was 29 days, wi th 80 percent of men- was not. There was a trend towards decreasi11g cycle
strual cyc le lengths fa lling between 25 and 38 days long,
inclusive. The total numbers of acts of intercourse that
occurred in th e a11alyzed cyc les in the window from 6 __.... -
~ - Normal fertility couples .... ····
days befo re to 4 days after th e Peak Day were as fo l- C 0.8 - - - Subfertile couples
lows: 3 16 acts of intercourse on day -6, 295 on day -5, .
""'
Q)
D.. ...... ··
...··
276 011 day -4, 240 on day -3 , 220 011 day -2, 2 1Oon day e:
o 0.6
....·······
-1 , 22 1 on day O(the Peak Day) , 209 011 day + 1, 174 on ~
day +2, 197 on day +3, and 524 on day +4. .
e:
e:
g> o.4
et ---
Figure 48-1 gives the estimates of the probabili ty of
>. ..,... ...:::.: _____ _ --- ---
---- -·;;:_.'--·-·········
pregnancy for a single act of interco urse during the ~ 0.2

...-··
_....·······
fec und window relati ve to the mucus Peak Day, des ig- .
:e
.o
,.-,., -_·:: __ -- --- -- -- - -- ----- -- -- --- ------- -- -- ----- - --- ---
nated as day O. The hi ghest dail y fec undity was fo und e
D.. o.o
to be on the Peak Day (0.38 for normally fe rtile couples,
and 0. 14 fo r subfe1iile coupl es). By constra int of the o 5 10 15
Mucus Cycle Score
model, the dail y fec undity on the most fecund day (as it
turns out, the Peak Day), is also equal to cyc le fec un- Figure 48-2: Correlation between mucus cycle score and
th e probability of pregnancy from intercourse on the peak
dity. Thu s, the mea n cycle fec undity was 0.38 for nor-
mucus day of the menstrual cycle (cycle fecundity) far cycles
mally fertile co uples, and O. 14 for subfertile co upl es. from normally fertile couples and subfertile couples. The finely
Daily fecu11dity (point estim ate) was greater th an 0.05 dotted lines are the 90% confidence intervals far the normally
fo r normally fe1iile coupl es from <lay -3 to day +2, and fertile couples (From : Stanfard JB , Smith KR , Dunson DB :
Vulva r Mucus Observation and the Probability of Pregnancy.
fo r subfe rtile couples fro m day - 1 to day + 1. Si milarl y,
Obste! Gynecol 101 :1285-1293, 2003).
Table 48-2: R esul ts from the Multivariable Analysis of Fecundity
Estimate so 90% CI
Peak probabi lity' 0.38 0.08 (0 .26 , 0.52)
Fecundity ratio
1. 5-year increase in woman 's age 0.95 0.15 (0 .72 , 1.21)
2. normal fertility vs . subfertility 0.35 0.16 (0 .14, 0.66)*
3. mucus cycle score among normal fertility 1.50 0.63 (0 .99 , 2.75)*
(average vs. low) 2
4. mucus cycle score among normal fertili ty 2.51 2.06 (0 .98 , 6.58)*
(high vs. low)
5. mucus cycle score among subfertility 1.05 0.4 1 (0 .69 , 1.88)
(ave rage vs. low)
6. mucus cycle score among subfertility 1.15 1.25 (0 .26 , 3.71)
(high vs. low)
1. Probability of pregnancy far a oouple of average fecundity in a cycle with interoourse on the Peak Day.
2. low=O, ave rage=5.67, high=16 formu cus soore
• significan! (posterior probability >.95)
650 The Medical and Surg ical Pract ice of NaProTECHNOLOGY
~ 1 · 0 -r;:====
A=11n=o=
rm=a=11y=f=
ert=il=
e=co=u=
p1=
es:::;---------, Discussion ------------~
~ -- - All subfertile couples
., O ur res ults demonstra te that the standardi zed clini ca l
t:.. 0.8
e / observati on o f vag inal di scha rge at the vulva, as made
by wo men trai ned in the CrMS, can be used to accu-
iº·'
~
Qj
0.4 //
,'
,/ rately identify the fecund window of the menstrual cycle,
i.e. , the days when intercourse i like ly to result in preg-
nancy. The changes in vaginal di scharge are prospec-
tive, occurring a number of days in adva nce of the Pea k
b /
=0.2 ------- Day 13 · 16•35 (rather than afterwa rds as occurs with the basal
~ ------------------------------ body temperature shift) , and such observations are eas-
ily leamed and interpreted by women of ali socioeco-
a: O.O '-r----~--~--~---~---.-J
O.O 0.2 0.4 0.6 0.8 1.0 nomic bac kgro unds. 36 While it has been know n fo r sorne
Percentile of couples, distributed by fecundity yea rs that the fe rti lity charting ofvaginal di scharge ac-
Figure 48-3 : The probability of pregnancy from interco urse curately identifi es days offe rti li ty and infe11i li ty, corre-
on the Peak Day (cycle fecundity), in relation to the distri bu- sponding to the bi ophys ica l changes of cerv ical mucus
tion of fecundity for normally fe rti le co uples and subfertile and the " bi o logica l va lve," th i i the first study to pro-
couples (From: Stanford JB , Smith KR, Dunson DB : Vulvar
vide quantitati ve estimates of daily and cycle fec undi ty
Mucus Observation and the Probability of Pregnancy. Obste!
Gynecol 101 :1285-1 293, 2003). based on standa rdi zed observation ofvaginal di scharge.
fec undi ty w ith age, but it did not reach stati sti ca l sig- The max imum daily fec undi ty in our stud y in coup les of
nificance. The detailed parameters ofthe model are given apparently normal fe rtili ty (from intercourse on the Peak
in Table 48-2. Based on thi s mode l, Fi gure 48-2 illus- Day) is 0.38, whi ch is slightl y lower than estimates fro m
trates the relati onship between mucus cyc le score and th e British study, and slightly hi gher than res ults from
the cycle fecundity. The mean mucus cyc le score in the th e North Ca rolina and European stud ies .24 •25 Variation
total sample was 7.6, w ith a ra nge 1.2 to 15.0. There was in the und erl ying reproducti ve potential of the respec-
no significant difference in the mucus cyc le score be- ti ve amples may acco unt fo r thi s va riation .
tween the nom1ally fertile couples (7 .5) and the subfe rtil e
couples (7 .8), (p=0.36 by /-test). There was a near linear The durati on of the fec und window identifi ed in our
positive relat ionship between the mucus cycle sco re study for normall y fert il e coupl es (6 days for proba bili-
and cycle fec undity fo r fertil e coupl es, w ith a hi gher ties greater than 0. 05 ) is comparab le to that fou nd in
m ucus cyc le score correlating to a hi gher cyc le fec un - prev ious studi es. 2·24 ·25 Our results indi cate that the du -
dity. Thi s re lati o nship wa not fo und in s ubfe rtil e ration ofthe fec und window is less fo r subferti le couples
coupl es. (3 days fo r probabi liti es greater than 0.05 ).
We fo und wide va riabili ty between coupl es in their abil- O ur results de part significantly from prev iou s ana lyses
ity to conceive, even among coupl es w ho have no hi s- of da ily fecundi ty in suggesting that the hi ghest prob-
tory of infertili ty (F igure 48-3). For example, coupl es in a bility of co ncepti on occurs on the peak m ucus day
th e 95 th percentil e (in other wo rds, out of 100 cou pl es rather than one or two days pri or to the Pea k Day (i n
of apparently nonnal fertili ty, the 5 percent most fec und users of symptothermal FP)24 or the estimated day of
couples), have cycle fec undi ty ofover 85 percent if they ovul ation by hormonal measures or the last day oflower
have intercourse on the Peak Day. O n the other hand , temperature.25 T here are sorne potenti a l reasons fo r this
coupl es in the 5th percentil e (in other wo rds, out of 100 apparent di screpancy. A li studi es of the fec und win-
coup les of apparentl y normal feii i1ity, the 5 least fec und dow ha ve used imperfec t markers of ovu lation that have
coupl es), ha ve cyc le fec undi ty of less than 5 percnt if sorne va ri ability aro und the ac tual time of ovu lati on.
they have intercourse on the Peak Day. Sim ilarl y, couples Studi es re lating the Peak Day to the estim ated day of
at the 75th percentile ha ve cyc le fecundi ty over 60 per- ovulation (meas ured hormonall y or by ultrasound) have
cent and coupl es at th e 25 th percentil e have cyc le fe- shown that the Peak Day i di stributed w ith in a ra nge of
cu ndi ty ofa littl e less than 20 percent. However, among +/- 3 days relati ve to ovul ation. However, th e curve is
the subfertil e coupl es, even those at the 75 th percentil e somewhat skewed, w ith the Peak Day more like ly to
have a probability of pregnancy of no more than 25 occu r pri or to ovul ati on than afterwards. ln contrast,
percent, and those at the 25 th percentil e have cycle the basa l body tempera tu re shi ft is more likely to occur
fec und ity of less th an 5 percent. afte r ovul at ion. 14 · 18 .3 7 Th i mi ght in part accoun t fo r thi s
apparent di screpancy, at least in comparing the present
Chapter 48: Fecund ity and the Mucus Cycle Score 651
study with the two studi es that relied on basal body Clini ca ll y, it has been observed that subfertile couples
temperature. 24 ·25 In additi on, the Peak Day is when bi o- have lower mucus cycle seores th an norma lly fertile
physica l characteristics ofmucus are most favo rab le to couples. 34 However, in this study, the mucus cycle seores
sperm survival and transpo1t and thus may identi fy the were about the same (7.8 and 7.5 respectively). There
day when sperm are most likely to survive in vivo, even are at least three poss ible explanations for this. First,
with underl ying va ri ab ili ty in the subseq uent time of this study only included cycles where a Peak Day was
ovulation .5·29 Further studi es with both mucus observa- identified, which meant that dry cyc les (cycles with no
ti on and a hormon al marker of ovul ation are needed to mucus Peak Day) were excluded . Dry cyc les are much
clari fy this issue. more common among in fert il e patients, and thi s exclu-
sion would arti fi ciall y ínflate the mucus cycle score for
Other studi es have suggested that recent use of ora l these patients. Second as discussed further bel ow, sorne
contraceptives may reduce the probability of concep- coup les in the subfertility group may not have had clinical
tion ,38·39 and that older age of the woman is assoc iated inferti lity. Third, one-third ofcouples in the normal fer-
with a lower fecundity (even within the age range of tility group had recently used oral contraceptives, wh ich
this sampl e). 24 ·33 .4° However, these variab les were not lower the quality of the mucus cycle score for at least
signi fica nt in our multivariate model. lt is possible that severa! cyc les after di scontinuation. 44 (Those in the
with a larger sam ple size and with more women of subfertility group who had di scontinued ora l contra-
younger ages, we may have found a significant effect ceptives mostly did so much earlier, given th eir inter-
for age, since there was a trend to decreasing probabil- vening time attempting to conceive).
ity of pregnancy with older age. We also did not ha ve
adequate sample size to fully exami ne the possible in- Our results agree with previous analyses of the Euro-
tluence ofrecent use of oral contraceptives , since rela- pean multicenter fec undability study in suggesting that
tively few cyc les in the analysis happened soon after there is a great variabil ity among couples in terms of
discontinuing ora l contraceptive. their fecun dity.33 ln other words, sorne coup les really
are more fecu nd (fe rtil e) than others, eve n among
Our study is the first to show a correlation between the couples ofapparently nonnal fe rtility (Figure 48-3). Simi-
mucus cycle score and the cyc le-specific probab ili ty of larly, sorne subfe1tile couples will be more fecund than
conception (cycle fecu ndi ty). Ana lys is from the Euro- others, though most will have much lower fecundity
pean multi center fecundability study has also shown than most "normall y fertil e" couples.
that the presence and quality mucus discharge is asso-
ciated with a higher fecundity, independent of timing Our findings must be interpreted in li ght ofsome uncer-
relative to ovulation. 4 1.4 2 A cycle-specific effect ofm u- tainty in the actual fertility statu s ofthe couples in the
cus cycle quality that we found in our study is consis- study. The majority ofthe couples of apparently norma l
tent with a day-specific effect fou nd in the analyses of fertili ty were nulliparous , and ali but two ofthe unmar-
the European multicenter fecundabi lity study. Mucus ried couples in the study were in th e normally fertile
discharge serves as a marker for the likelihood ofsperm group. Therefore, this group probab ly included sorne
surv iva l. In additi on, the quality and quantity ofmucus coup les with unrecogni zed subfertility, who had no pre-
discharge in the menstrual cycle is dependent on the vious opportunity to test their fertility. The hi gher pro-
estrogen leve Is and therefore may reflect the hormona l portion ofmarried couples within the subfertility gro up
status ofthe menstrual cycle, which in turn may be re- simp ly reflects the fact that married couples have had
lated to the viability of the ovum. 43 The mucus cyc le the opportun ity to try to conce ive and to lea rn whether
score identifies a spectrum of cyc le viabi li ty with in or not they were fertil e.
couples ofapparently normal fertility, with the mucus
cycle seores and cycle viabi li ty on the lower end ofthe The coup les in the normal fe rtility gro up began using
spectrum approaching those found in subfertile coup les. the CrMS stating they wished to avo id pregnancy, but
E ven days without mucus di scharge that fall with in the many of them later chose to ha ve intercourse on days
six-day window contribute infonnation on the lower prob- offertili ty. We also exc luded co upl es with known con-
ab ili ty for sperm surviva l, and possibly lower estrogen ditions likely to reduce fertility. Hence, our nonnal fe rtil-
levels on those days. However, within the group of ity group is reasonably similar to two ofthe other three
subferti le couples the mucus cyc le score lacks discrimi- stud ies of day-specific probabilities of conception (the
natory power to differentiate cycle viability. Among British and European studies ), which also studied couples
these subfertile couples other factors that impair fertil- who initially avoided, and later achieved pregnancy. 2º· 24
ity (s uch as anatomic factors or male factors) may be
more common and have more influence. On the other hand, the subfertil e group is notas clearly
de fin ed . U nfo rtun a te ly, a re li a ble indi ca tor as to avo iding pregna ncy at study e ntry, we beli eve that this
subfertility stah1s was not availabl e fo r ali coupl es. We bi as sho uld be minima l. In the subfertile gro up, we did
chose to use a se nsiti ve meas ure that was ava il able fo r exclude co upl es based o n nurnbers of follo w-ups com-
ali coup les at stud y entry and should inc lude nearl y ali pl eted, because we suspected that thi s wo uld excl ude a
coupl es with kn own in fe rti lity, but had the di sadvan- number of concepti ons in thi s g roup . In fact, a substan-
tage of pro babl y including a few couples w ith no rmal tia l p ro po rti o n of con cepti o ns (9 o f th e 30) in th e
fertili ty: we des ignated ali co uples who began use of subfe rtil e gro up occurred w ithin the first fo ur fo ll ow-up
the CrMS to achi eve pregna ncy as subfe rtil e . A no ted, CrMS instructi o nal vis its in thi s group. Therefore, an
in fo rmati o n on length of time spent try ing to ac hi eve exclusio n based on number of fo llow-up instructional
pregnancy pri or to leaming the CrMS was often absent. vis its wo uld have introduced bi as underestim ating the
It is poss ibl e that sorn e coupl es learning the CrMS w ith pro babi 1iti es of concepti on fo r subferti le couples . Other
the initi a l intent to ac hieve pregnancy in fa ct had nor- than numbers of fo ll ow-up visits, the same c riteria for
ma l fe rtility (particularly a mo ng the nine couples that cycle quali ty we re applied to both no rmall y ferti le and
becarn e pregnant w ithin the first fo ur fo ll ow-up ses- subfe rtile gro ups (i. e. , cycl es were exc luded for the use
s io ns) . However, based o n di scuss ions w ith eac h of the offertili ty-related rnedi cati o n, inadequate mucus o bser-
CrMS centers, the vast majo ri ty of coupl es seeking to va ti o ns, the use of barrie rs o r w ithdrawa l, o r the incom-
conce ive w he n th ey first lea rn the CrMS had sorn e prio r pl ete recording of intercourse).
diffí culty achi eving pregnancy. At a minimum, two-th irds
of the subfe rtil e coupl es had well -docurne nted infett il- A n additiona l weakness of thi s stud y is the lack of an
ity. In the extreme case, up to o ne-thi rd ofthe subfetti le indepe ndent marke r of ovul ation . Mo re ins ight into the
coupl es may have actua ll y had normal fe rtili ty. ro le of the rnuc us di scha rge would be poss ibl e from a
stud y th at in clud ed both vu lva r o bservati o ns a nd a
Becau se of the retrospecti ve nature of this stud y, we hormonal marker of ovul ation, such as urinary hom1o nal
we re una ble to locate and enter over 40 pe rcent ch arts a nalys is. As noted, such a stud y is necessary to ad-
fro m potenti ally eligibl e co upl es. lt is poss ibl e that thi s dress the questio n of w hy we found the hig hest prob-
influenced the reproducti ve potentia l ofthe sample . Be- a bili ty of conception o n the Peak Day, whe reas othe r
cause we had bas ic demographic infonnation fo r couples studi es fo und th e hi ghest probabi lity of conception o ne
fo r w hich we did not have charts, we expl o red thi s issue or two days pri o r to the Peak Day, o r othe r estimated
furt he r. As assessed by chi-square analys is, the re was day of ov ul atio n.
no signifi cant differe nce betwee n coupl es in the stud y
and co upl es w hose charts we re not located fo r the fo l- Strengths ofthi s study include the standard ized o bser-
lowing characteri stics: ferti lity status, wo man 'sor man 's vatio n and recording of rnucus di scha rge, the inclus ion
age, race, educatio n, income, reli g ion , pari ty, hi story of of subfe rtil e co up les, and the rigorous procedures for
spo nta neous or e lecti ve abortio n, CrMS teac hing cen- chart abstrac ti o n and identifi cation of the Peak Day.
te r cluste r. However, there were signifi ca nt di ffe re nces The stud y is based o n the standardi zed gro und wo rk of
in marita l status (7 1% of those in the study were mar- the CrMS , a nd prov ides an importa nt c linical va lidatio n
ried, as o pposed to 49% of those whose c harts coul d of the clini ca l re levance of the Pea k Day and the rnu cus
not be located (p<.000 1 by c hi -sq uare). lt also seems cyc le score.6.21.3 1.44.45
likely that c harts we re more ava il abl e fo r th ose co uples
who became pregna nt, w hich might bi as the res ults of Future studi es should be done prospecti ve ly, w ith ri g-
the overall probabiliti es of conception upwards, depend- orous criteri a fo r subfe1tility o r in fe rtili ty, and w ith pro-
ing o n whethe r the un ava il abl e cha1ts included addi- cedures to make enrollme nt and foll ow-up as compre-
ti o nal cyc les wi th inte rcourse in th e fec und w indow, hensive as possible. Lo ng itudinal studies ofmuc us cycle
but w ith o ut concepti on. Unfo 1tunately, we did not have qu ali ty, bl eeding patterns, fecundity, fe rtili ty, and other
acc urate data o n pregna ncy rates amo ng th ose whose hea lth outcomes wo uld be of great inte rest. The CrMS
charts were not ava ilabl e to assess thi s issue. offers an idea l pl atfo rm for thi s kind of inquiry.
A related potentia l fo r bi as is that we exc luded co uples In conclusion, the present stud y prov ides evidence that:
in the no rma ll y fe rtile g roup w ho compl eted fewer than
fo ur fo ll ow-up visits (genera ll y the first two mo nths of l. The CrMS can be used by both norrnall y fertile and
CrMS in structi o n) . lfthere we re ma ny concepti ons that subfe rtile co upl es w ishing to optimally time inter-
were excluded during thi s fLrst two mo nth s, thi s could course to conceive.
artifici all y reduce the probabiliti es of pregnancy arno ng
2. The Peak Day is th e day w ith the hi ghest fec undi ty
th e no m1 ally fe rtil e coupl es. G ive n that coupl es were
Chapter 48 : Fecundity and the Mucus Cycle Sco re 653
(probab ility of concept ion). even among only those coup les of apparentl y nor-
mal fertility.
3. The CrMS accurately identifi es the fecu nd window
from the couple's perspective for cooperatively man- 6. The CrMS should be consid ered a first-line inter-
aging their fertility. vention for timing intercourse to conce ive.47
4. The mucus cycle score correlates strongly with cyc le 7. Stud ies that seek to identi fy dail y or cyc le fecundity
fecundity (probabili ty of conception) for coup les are likely incomplete with out an assessment ofmu-
without a hi story of infertility. cus discharge qua lity. The CrMS has a standardized
vaginal di scharge recording ystem and mucus score
5. There is a wide variability in fecundity in co upl es,
that is we ll su ited for this type of assessment.
Acknowledgements - - - - - - - - - - - - - - - - - - - - - - - - - -
This chapter is based on work from the Multicenter • Mary Schurk, RNC, CFC P, and Jeanne Stoll, RN, CFCP
CREIGHTON MODEL Fecundity Study. The principal in- SSM FertilityCare™ Services, St. Maiy's Heal th Cen-
ves ti ga tor was Jo se ph B. Stanford , MD , MSPH , ter, St. Louis, MO
CNF PMC. Ken R. Smith, PhD, Department ofFami ly
• Rosemary Clements, CFC P
and Consumer Studies, University of Utah, was a co-
Natura l FertilityCare™, Linco ln , NE
investi gator for the study. David B. Dunson, PhD, Bio-
statistics Branch, National lnstitute of Env ironmenta l • Rebecca J. K.napp, RN, CFC P
Hea lth Sciences, conducted statistica l ana lysis. Tho- The FertilityCare™ Services, Di ocese of Wi chita, KS
mas W. Hilgers, MD , and James Trussell , PhD served
• Victoria A. Delucchi , CFCP, and Jenny Perez, CFCP
as cons ul tants to the study. Bec ky Croc kett, Mary
Seton FertilityCare™ Center, Daly Ci ty, CA
Bishop Stone, and Juli e Fryer were research ass istants.
We thank th e following CREIGHTON MODEL • Funding for the Multicenter CREIGHTON MODEL Fe-
FertilityCare™ Practitioners and Centers for parti ci- cundity Study was provided by the Robert Wood
pating in thi s study: Johnson Foundation through the General ist Physi-
cian Facul ty Scholars Program, and also by the Health
• K. Diane Daly, RN , CFCE, and Ann Prebil, RN, CFCE
Sn1dies Fund, Department of Family and Preventive
St. John 's Merey Medica! Center, Department of
Medicine, Un ivers ity ofUtah.
FertilityCa re™ Services, St. Louis, MO
• Elizabeth Minnini, CFCP
SSM FertilityCa re™ Services of St. Joseph Hospi-
ta l, Kirkwood Sate ll ite Center, Kirkwood , MO
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26. Hilgers TW, Daly KD, S.K. H, Prebil AM. Creigh ton Mode l
ti on Method of Natural Family Pl a nn ing: A Standardized,
Fertil ity Care Sys tem: A Standardized, Case Management
Case Management Approach to Teachi ng, Book 1. Omaha,
Appproach To Teaching, Book 1. Omaha , NE: Pope Paul
E: Creighton Universi ty Na tu ra l Family Pl ann ing Educa-
VI ln st irute Press; 2002.
tion And Research Cen ter; 1982 .
27. Hil gers T. The CREIGHTON MODEL FertilityCare™ System :
46. Hilgers T, Prebil A, Daly K, Hil gers S. The Picture Dictionary
An lntroductory Book let for ew Users. 5 Ed. Omaha, NE:
of the CREIGHTON MODEL FertilicyCare'" System : Teacher 's
Pope Paul VI ln sti tute Press; 2001.
Ed iti on. Omaha, NE: Pope Pa ul VI lnstitute Press; 1999.
28. Hil gers TW. The Objective Assessment of the Vu lvar Mucus
47. Stanford JB, White GL, Hatasaka H. Timing lntercou rse to
Cyc le. lnt Rev Of Na t Fam Pl an 12(3)Fa 11 :250-6, 1988.
Ac hi eve Pregnancy: Current Ev id ence. Obstet Gynecol
100(6): 1333-4 1, 2002.
NaProTECHNOLOGY and lnfertility:
A Family Physician 's Approach
Dr. Phil C. Boyl e
he family phy s ician has a central role in th e Patient ca n begi n to record their medi ca ! information
T medica! mana ge ment of co upl es who are try-
in g to co nceive with atura! Pro creat ive Tech-
on this standardi zed form pri or to the initial consulta-
tion. This helps them to focus on their past medica!
nology (NaProTECHNOLOGY - NPT). Consultations history, maki ng it easier to accurately recall previous
are, ofnecessity, longer th an for most other spec ialties. in vestigati ons and treatments. A referral letter fro m the
An average consu ltation wi ll last between 40 to 45 min- couples ' fa mil y doctor can be a useful source ofaddi-
utes. Each consultation is part of an ongo ing process tional medi ca! infonnation for the initial consultation.
of education, support and couple empo werment. Fol-
lowing the initial training, it takes tim e for NPT phys i-
cians to adapt their consu ltat ion sty le in order to meet ConsentForm ________ _ _~
the needs ofthose who present for eva luation and treat-
ment. lt i rarely poss ibl e to compl ete the cons ultati on lt is critica! fo r physicians working in Natural Procre-
in a shorter time, unless sorne aspects can be delegated ative Technology (N PT) to keep precise medica! records
to nur es or supporting staff. NPT phys icians review of each patient so th at accurate success rates can be
coupl es every three to fo ur months for a follow up con- determined with this exc iting new approach . Many may
sultati on. On average coupl es are seen between three wish to co llect their data in a prospective fashio n and
to fo ur times per year. participate in an international co llaborative research
project under the auspices ofthe lnternati onal ln stitute
of Restorative Reproducti ve Medi cine 2 (llRRM ). ln ar-
lnitial Medica! Consultation ----~ der to use pati ents ' data fo r research purposes it is ad-
visab le to obtain written conse nt from eac h couple. Ali
lt is essent ial to obtain an accurate medi ca ! history. To identifying deta ils are removed frorn the fina l grouped
ensure consistent and comp lete data co ll ection in each ana lysis, so that patient confidential ity is not breached.
case it is recommended that medi ca ! consultants use a A copy ofthe consent form is ava ilabl e from the 1IRRM .
standardized forrn 1, to obtain the couples ' history and Pati ents are asked to provide written consent to have
record medica! progress with treatment. th eir de- identifi ed data used in the ca lculation of out-
comes and success rates if they ha ve decided to enter
655
the fertility treatment program. The consent fonn is u u- " How old is too old ?" lt is difficult to give an absolute
ally signed following the initial consultation. cut off age after which conception and successful preg-
nancy is impossible. Although women can have suc-
cessful pregnancies even up to 50 years old, it is rare to
The Consultation Process _ _ _ __ ~ have a successful outcome for women with primary in-
fert ility after 45 years of age. Out of over 1,400 couples
Coup les often begin NPT treatment with speci fic ideas, treated in general practice so far we have not had a
concerns and expectations 3 regarding their own fertil- successful pregnancy for any females aged 45 years or
ity and how investigations and treatment may proceed. greater. Couples are usually advised not to pursue treat-
lt is important for doctors to address each couple's in- ment at this stage because ofthe low likelihood of con-
dividual situation a every couple is unique and will ceiving (< I % ) and a high probability of miscarriage 5
have different fears , worries and misperceptions about (over 50% ) or Down syndrome (3 % ) should conception
what lí es in store for them during the process ofNPT occur. lt is the couple who .final/y decide whether or
fe1tility treatment. 110110 pursue treatmenl based on the informa/ion they
receive. Many derive a certa in sense ofsatisfaction from
The entire program can last between 18 to 24 months entering the program and "giving ita go" for a time-
before treatment wou ld be discontinued and deemed even six to 12 cycles so that they can have a sense that
unsuccessful. Many couples achieve successful preg- at least they tried and reach a point where they come to
nancies before reaching the end ofNPT treatment and accept their infe1tility.
pregnancy is possible as soon as couples begin to track
their biological markers offertility. Overall succes rates PT helps couples to adjust to and accept involuntary
can be surpris in g ly high even despite long standing childlessness, which may be the final outcome despite
infertility, adva nced female age and previous unsuc- our be t attempts at fertility treatment. Successful treat-
cessful attempts with artificial reproductive technology ment is much more than helping a couple to conceive
(A RT). Results from an lrish NPT practice wh ich treated and de li ver a healthy ch il d. Our goa l is to offer the best
123 9 couples over fo ur years between Feb. 1998 and medica! treatment ava il able in order to achieve a preg-
Jan. 2002 yie lded an overall live birth rate of25 .2 per- nancy . .... but not at any price. We do not want to reach
cent, rising to 44.7 percent for those who successfully our goal at the expense of the couple's health, relation-
completed the program 4 . Although there is a reasonable ship or psychological well being.
chance of having a succe sful live birth with PT it is
important to emphasise that about 50 percent or so may
not succeed in achieving that goal. A key point is to Health
encourage coupl es to persist with treatment until the
program is compl eted so that they give themselves the Remarkably, many women feel better while receiving PT
best possible chan ce of success. fertility treatment. This is in stark contrast with many
ferti li ty treatments which often lea ve the woman fee ling
A primary goa l is to make treatment couple-centered. quite unwell. During NPT, PMS w hi ch may have been
The husband and wife attend medica! consu ltations previously severe often disappears with treatment. Dys-
together and work on this project as a team , hoping to menorrhoea and bowel compla ints are recti fied through
realize their ultimate goal of achieving a successful preg- surgical diathermy of endometriosis. Abnormal men-
nancy. While we dearly wish that everybody would strua! function associated with PCOD or
conceive, unfortunately a significant number will not. oligomenorrhoea is corrected, resulting in regular men-
This is not to be pessimistic but realistic and honest strual cycles. This reduces the lifetime risk of endome-
with each couple. O lder coupl es, where the fema le age trial cancer to that of the normally fertile population ,
is greater than 40 years, and those with severe pelvic provided progesterone support is continued on a long-
adhes ion s or severe endometriosis ha ve a reduced 1ike- term basis.
lihood of success.
Treatment is reserved for married couples to protect Re/ationship

the best interests of the chi ld and promote a secure
family life. This infom1ation is made available to couples NPT is a process which involves the husband as an
prior to booking the initial medica! consultation . active participant. The man 's role is to record the bio-
logic markers of fertility according to specific instruc-
Regarding advanced fema le age, man y ask the question tions using the CREIGHTON MODEL FertilityCare™
Chapter 49: NaProTECHNOLOGY an d lnfertility: A Family Physician 's Approach 657
System (CrMS). This is taught by a specially trained so that the NPT physician can gain insight into their
FertilityCare™ Practitioner (FCP). Each day the man primary concerns.
asks his wife what markers of fertility were observed
and he records the most fertile sign on their chart. There This initial medica! consu ltation is primarily an informa-
are severa! important reasons for the man to be involved. tion gathering session for the NPT physician as we ll as
First, he becomes actively involved in the process, rein- the coup le. The doctor tries to assess the coup les' suit-
forcing the reality that it is their ferti li ty as a couple ability to enter the program, based on the informati on
whi ch we are treating, notjust her fe1tility alone. Sec- which is collected. At the same time the couple try to
ondl y, we find that when menare in volved in the chart- decide ifthe NaProTechnology (NPT) approach appea ls
ing process, the recordings are more precise because to them or not. There are advantages and disadvan-
the observations are discussed and considered in more tages to N PT e va luation and treatment, and not every-
detail pri or to recording. ln addition, the couple commu- body wishes to fo ll ow th is approach , although most do
nicate on a dail y basis about their fertility. This often find it very appea ling.
all ows them to discuss their feelings about subfertility,
the treatment and possible success or failure . This en-
hanced dialogue often helps them to recognize many of 2. Teaching and Explanation
the unspoken stressors whi ch may arise with ferti lity
treatment. Husbands need to affirm their wives that, as Having col lected a detailed medica! history and being
a couple, they va lue her health , her well being and their aware ofthe coupl es' primary wo1Ties and concerns, the
relationship. Then, ifthe couple are to remain childless, NPT physician can proceed to expla in how NPT works.
they will be a ble to cope with that together. We encour- lt is helpful to set goals for th e couple, both with in each
age coup les to discuss adoption as a very positive op- consultation and for the treatment programas a whole.
tion should NPT not result in a pregnancy. They should be told that each consultation will take 40-
45 minutes in total. Consultations involve active dia-
logue with the doctor. This leads to coup le empower-
lnitial Medical Consultation ----~ ment through ongo in g education and sharing in the
decision making process regarding further in vestiga-
The initial medi ca! consultation is divided into two main tions and ongo ing treatment.
parts:
A guiding principie for the physician is to actively in-
1. Co llection ofi nformation vo lve coup les in the decision making process fro m the
beginning and througho ut the months of treatment.
2. Teaching and exp lanation about NPT
Ultim ately coup les are responsibl e for deciding which
3. Physical exam ination treatment they wou ld like to pursue at different times
throughout the program based on information which
the doctor shares with them. The NPT physician out-
1. Collection of lnformation lines the principies, expl aining why a particular inter-
vention may be recommend at any given time. NPT pro-
The coupl e are greeted with a handshake and allowed tocols are useful guidelines as to when various treat-
to sett le comfortably before the consu ltation begins. ments and interven ti ons wo uld be appl ied, but these
The docto r begi ns by tak ing a detai led medical/fertility protocols are far from rigid and may vary widely from
hi story to understand their present situation as clearly one couple to the next depending on their history, un-
as possib le. They may have filled out the medica! con- derlying diagnosis, fema le age and the coup les ' prefer-
sultation fo rm in advance, so the NPT physician can ence - always gu ided by the physicians clearly explai ned
clarify the information and obtain further detai ls ifthey rationale. The coup le entera genu ine pa1tnership with
ha ve a referral letter from the fami ly doctor or other medi- the NPT physician in managing their own unique fe1til-
ca! correspondence. ity condition. They ultim ately treat their own ferti li ty in
consultation and discussion with the NPT physician.
A very usefu l fina l question whi ch often yields surpris-
ing ly pe1ti nent in formation is the fo llowing: " Is there
anything el se important regarding your fertility history 3. Physical Examination
which I didn 't ask you ?" [n addition to obtaining fur-
ther medica! information this open ended question al- lf the coup le have never had a physical examination
lows the couple to express what they are worried about, previously, it may be conducted at the initial medica!
consultation or subsequently at the first medica! review. report this is a far more acceptable method of co llecting
It is ad visable for the woman to have the usual gy neco- the samp le compared to othe r a pproac hes. The NPT
logic exam. The man should a lso be assessed for a vari- physician gives the man written in structions which
cocele and tender prostate if his semen ana lysis is sub- clearly exp lain how to prepare and co ll ect the sample
optimal. (F ig ure 49-1 ). Co ll ecting semi nal fluid in th is fash io n
provides accurate results, is genera ll y more acceptable
tomen and is consistent with ful 1respect for men 's sexual
Male FertilitY---------~ dignity. The results should be available for the next con-
sultation at which point severa! interventions may be
If the man has had a recent normal semen ana lysis he recommended ifthe analys is is subo ptimal.
may not require further eva luation at this point. lfhow-
ever he has never been assessed, he should be advised lf previous results are known to ha ve been poor, blood
to produce a semen a nalys is prior to the next review tests wou ld be taken at this stage for FSH, LH, thyroi d
consultation w hi c h is usually 12 weeks fo llowing this function , testosterone levels and ful ! b lood count. T his
initial appo intrnent. is to try and determine ifwe are dealing with an underly-
ing medica! comp laint, normogonadotrophic o li gosper-
Men a re advised to co llect the seminal fluid samp le mia or primary testicu lar fa ilure. The latter wo uld be less
through a us ual act of intercourse while wearing a per- like ly to respond to further med ica ! interventio ns. The
forated non-spermicidal silastic sem inal fluid co ll ecting man can be exam ined for a varicoce le and referred to a
device. 6 Thi s allows for the ful! sample to be co ll ected. uro logist for furt her assessme nt if necessary. lt is im-
Pre-ejaculatory fluid wh ich contains a hi gh concentra- portant to find a urologist who is interested in eval uat-
tion of sperm is not mi ssed as may occur with samp les ing and treating the underlyi ng problem caus ing a sub-
collected during rnasturbation. ln addition many men optima l semen ana lysis. Unfortunately many refer fo r
lnstructions for Seminal Fluid Collection

Please find enclosed a perforated seminal fluid co llecting device , which is essentially a special type of
condo m. lt is free of spermicide so that seminal fluid ca n be collected without contami nation or harm.
1. Prior to co llecting !he sample, you are advised to avoid intercourse for 72 hours (3 Days) to allow
the count to build up to maximum levels.
2. You should have a shower prior to collection, as this will minimize contamination of the sample.
3. lt is recommended to collect the seminal fluid through a natural act of intercourse.
We have found this has a higher level of acceptability co mpared to masturbation . In addition the seminal
flu id collecting device allows all of the seminal flu id, including pre-ejaculatory flu id to be collected. Pre-
ejaculatory flu id can be difficult to collect through masturbation , and if missed may give the appearance
of a low sperm count.
4. Please transfer the seminal fluid directly to a conta iner immediately after collection and dispose of the
seminal fluid collecting device (condom). Do not send the condom into the laboratory.
5. Remember the sample must reach the laboratory within one hour and the container must be kept
at body temperature prior to and after collection of seminal fluid . Place !he container into your
pocket to keep it warm .
Figure 49-1 : lnstructions for Seminal Fluid Collection form

Chapter 49: Na ProTECHNOLOGY and lnfertility : A Family Physician's Approach 659
artificial insemination or IVF without attempting to re- Female FertilitY ---------~

so lve the man's problem.
When it comes to the evaluation and treatment of fe-
ma le fertility, NPT differs widely from standard infertil-
Lifesty/e Changes ity approaches. Even if a male factor is present it is
common to find an additional female component con -
Men are adv ised to reduce alcohol 7 intake and stop tributing to the couples ' subfertility. This fema le factor
smoking, to wear loose fitting clothing and to reduce is usually not identified prior to NPT. The two main
lifesty le stresses. These interventions can produce sur- areas where NPT finds new problems are with the
prising improvements in semen parameters. The cycle woman 's cervical mucus quality or suboptimal levels of
of sperm production from sertoli cell to ejaculate can progesterone and estradiol-17~ in the luteal phase of
take 72 days. We usually recommend a repeat analysis the menstrual cycle. Of course there are many other
three months fo ll owing any particular intervention to factors which are found and treated, but these would be
assess the effectiveness of treatment. the main two.
Medica] treatrnents that NPT physicians may recom- We have found it helpful to have the initial consultation
mend incl ude a tria! ofantibiotics such as clarithromycin for infe1tility with the NPT physician prior to the couple
or ciproxin alone or in combination for two to three weeks beginning FertilityCar e™ charting. NPT begins by giv-
or longer to treate a chronic prostatitis, tamoxifen cit- ing the couple a detailed explanation ofhow the woman 's
rate (Tamox ife n) 1Omg twice daily8, clomiphene citrate cycle should function under normal physiologic condi-
(Clom id) 25mg da ily, indomethacin 25 mg BD, l-carnitine9 tions. lt is important to use diagrams from the Picture
1 gram daily or pycnogenol 1º 30 mg twice daily. Although Dictionary 12 while explaining how the no1111al menstrual
at times improvements may be dramatic, generally im- cycle should work. We explain that in order to evaluate
provements are moderate in about 20 to 25 percent of fema le fe1tility the couple must first learn how to record
men. lft he count remains consistently below one mil- the biologic markers ofthe menstrual cycle in a precise
li on it is less li kely (though not impossible!) that con- and ordered fashion using the CrMS. The NPT physi-
ception will occ ur. cian can give a useful overview, explaining how to be-
gin recording the signs offertility from the first day of
Another condition in the male that deserves a separate the menstrual cycle. The physician uses the
mention is when ant i-sperrn antibodies 11 are present in FertilityCare™ chart to explain how the couple can
high concentrations. This can be treated by suppres- record their observations for the next two weeks prior
sion ofthe ma le immune system with prednisolone 20 to attending their FCP . They will need to see the practi-
to 40 mg twice da ily for 1Odays beginning on day 4 or 5 tioner every two weeks for individual instruction over
ofhis wife's menstrual cycle. The high dose ofsteroid the following two months. The couple are giyen a vid-
treatment is genera lly well tolerated. lt is not recom- eotape or DVD 13 presentation ofthe lntroductory Ses-
mended formen over 50 years old, those with high blood sion, together with the user manual , FertilityCare™
press ure, diabetes ora previous exposure to TB. Men chart and stamps so that they can begin to record their
are screened with appropriate blood tests , blood pres- biologic markers of fertility immediately. The woman
sure measurement anda chest x-ray prior to commenc- observes her markers throughout the day whenever she
ing treatment. goes to the bathroom and her husband records the most
fertile observation on the chart at the end of each day.
The treatments that we recommend for male infertility
are certa inly not unique to the N PT physician. How- The FCP is central to further evaluation at this point. lt
ever, wi th the advent of ART many infe1tility specialists is essential that practitioners are well trained and par-
omit these approaches in favor of artificial insemina- ticipate in ongoing cont inuing education in order to
tion, in vitro ferti lization (JVF) or intracytoplasmic spern1 provide a quality service to each couple who comes
injection (ICS I). Experience from NPT shows many under their care. Practitioners should receive written
couples can conceive without reso1ting to ART. Fur- correspondence fo ll owing each consultation with the
thermore when ART has been previously unsuccess- N PT physician so that they are informed of the per-
fu l, NPT can still be an effective treatment option for sonal needs and clinical situation regarding their couple.
many couples. The practitioner is an allied health care professional who
can make the process offertility tracking an enjoyable
and worthwhile experience for the couples they see. A
caring and sensitive practitioner will establish a sound
660 The Medical and Surg ical Pract ice of NaProTECHNO LOG Y
therapeutic relationship, ensuring accurate cha1ting and An effective cycle is one w here:
practica! support to encourage couples to continue with
l. Peak + 7 blood results fo r progesterone and es-
the program until its comp leti on. Practitioners can re-
tradiol are in the norma l range
mind couples when to have blood samples drawn on
" day 3" and " Peak + 3, 5, 7, 9 and 11 " during th e initial 2. Cerv ica l mucu s seores are satisfactory
hormonal eva luatio n an d " Peak + 7" fo r each treatment
3. lntercourse occ urs frequently during the ferti le
cyc le. The practitioner can offer valuab le support to the
d ays
couple and confirm that they are adhering to the
physician's plan oftreatm ent. The practitioner is often 4. Stress/tirednes is kept to a minimum
available to answer phone queries regarding cha1ting
difficulties or simpl e problems regarding medica! treat- Coup les may conce ive on the first or twelfth effecti ve
ment. The practitioner is nota physician or coun e ll or, cycle or at any po int in between. lt may take 15 to 18
but can readily recognise when further assistance may total cyc les to ac hi eve 12 effecti ve ones. Cycles are
be required in these areas. Suffice it to say that a we ll - onl y counted ift he conditions for an effective cycle are
tra ined FCP is worth their weight in go ld ! met. A cycle can sometimes be counted as a " half effec-
ti ve" if the NPT phys ician feels a pregnancy was pos-
Before the coup le leave the initial consultation to begin sibl e, but the cycle was not used to it ful! potenti al. For
recording their ferti lity they are gi ven an overview of examp le if on ly one "fertil e day" was used for inter-
our " goa ls" with treatment. course or cervical mucu flow was more limited than
usual or ifthe monthly blood results fa ll below the tar-
get normal ra nge these cycles could be recorded as " half
Overview of Treatment Course _ __ ~ effective". The enti re treatment program can take up to
24 month s or two yea rs to co mpl ete. lt is important to
The first six months are the lead in time before effective tell coupl es this information before they beg in treat-
cycles of fertility trea tment begi n. Couples generall y ment. N PT is nota "quick ti x" so lution to in fertility,
spend three month s lea rning how to track their personal rather it is a process of eva luating and correcting ab-
biologic marke rs offertility. During the first cycle they normalities which interfere with normal reproductive
lea rn how to confidentl y identi fy the Peak Day. On the function and thi s process takes time! Many peopl e wa nt
second cycle they have timed hormonal blood tests to to be pregnant yesterday and the poss ibility that they
see what abnormal ities may be fou nd . Treatment is com- may ha ve to wait up to two years is not appealing. They
menced during the third or fo urth cycle and it often need to know that at times pregnancy may occur very
takes a futther three cycles before hormone deficien- quickl y, injust a few months, but ifthey are to give PT
cies, limited cerv ica l mucus flow or other problems are their best shot they should compl ete the program . The
corrected w ith medications. longer couples stay in the program, the mo re likely they
are to concei ve. Of co urse treatment cannot conti nue
Most couples do not conce ive during these first six indefinitely, so an end po int must be chosen. lf a preg-
cycles. Those with a hi story ofprevious mi scarri age are nanc y has not occurred by abo ut 12 effective cycles it
advised to avoid conception until monthly Peak + 7 seems unlikely that continuing for longer will prove ef-
blood resu lts for progesterone and estradio l have fect ive, but sorne cou pl es ha ve conceived on the ir l 4th
reached the normal range. Couples who conceive with and l 5th effective cycles. This is more li kely to occur in
sub-optima! hormone leve ls still ha ve a signifi cant ri sk cases where stress was interfering with treatment dur-
of miscarri age. In additi on they seem to require ongoing the earlier cycles ora surgical intervention perforn1ed
ing progesterone support for longer during pregnancy in the middle of th e program gave a better chance of
compared to those who conceive with optima! hormone subsequent concepti on. lf a urg ical interventi on re-
leve ls. After three cycles of treatment PMS symptoms su lted in a rnajor improve rnent in prognosis, it may be
have genera ll y improved, Peak + 7 blood results are in we ll to re et the co unt fo r 12 effective cyc les fo llowing
the normal range and the fertility chart returns to a nor- the treatrn ent.
mal looking pattern. lnteresting ly we have found that
PMS can be a littl e worse for the fir t and second cyc le Because treatrnent rnay take sorne time we encourage
oftreatment before symptoms are controlled in the third coup les to live their li fe as norma ll y as poss ible while
cyc le oftreatment. treatment proceeds in the background. We encourage
holidays and fun activ ities wh ich can g ive a certain di s-
From this point onwards we begin to enter into " effec- traction from the process oftry ing to conceive. " Cycle-
tive cycles" w here a pregnancy is more li ke ly to occur. gazi ng," where couples becorne too focused on their
Chapter 49 : NaProTECHNOLOGY and lnfertility : A Family Physician 's Approach 661
fertility cha11 is a very counterproducti ve acti vity. lt days is commonl y associated with progesterone defi-
adds to the stress of treatment and frustrati on bui lds ciency. Typica l symptoms include irritabili ty, breast ten-
for each cycle th at passes without concepti on occur- derness, bloating, weight ga in, sa lt/sweet cravings, teari-
rin g. Coupl es are advised to think more long term after ness, depress ion, headach e, fa ti gue and insomnia.
they have passed through the initi al six month s of evalu-
ation and corrective treatm ent. We say " hopefull y by Ma ny women have these symptoms fo r two or three
thi s time next year you will be pregnant" and " If it hap- days pre-m enstruati on and th at is normal. lfsy mptom s
pens sooner than one yea r, consider ita bonu s." Thi s are present fo r fo ur or more days, that is abnormal and
long-term approach is necessary to keep people moti- may indi cate a progesterone defic iency. In true PMS,
vated for the durati on of treatment. lf these goa ls are the symptoms are relieved with th e onset of menstrual
not set in the beginning, couples tend to dro p out too fl ow.
early and miss out on a poss ibl e successful outcome.
During the hi story ta kin g we reco rd whi ch symptoms
are present, their ave rage durati on each cycle and se-
Subsequent Medica! Consultations===l verity out of 1O, with a score of 1O indi cating maximum
severi ty.
At the econd medica! consultati on (first review) th e
PT physician rev iews the FertilityCare™ chart to- lt ca n be interesting to compare PM S seores before and
geth er with ali of th e bl oo d test res ults and the during treatment. Usually women fee l much better while
husband 's seminal fluid analys is. A base line ultraso und th ey are rece iving treatment.
examination is performed at thi s consultati on, or pri or
to the consultation if an ultraso und is not ava il able in
the practice. If a diagnos is has been established, treat- 3. Signs
ment can be commenced to correct the underlying ab-
nonnality. Th e FertilityCare™ch art will often indicate the status
of a wo man 's reproductive and gy neco log ic health.
NPT adheres to time-honoured medi ca! principi es in Typ ica l abnorm al features whi ch may be ev ident from
evaluating and treating infertili ty and recurrent mi scar- the cha rt include:
riage. • Dry cyc les
l. H istory • Limi ted mucus
2. Symptoms • Premenstrual spotting
3. Signs • lntermenstrual spotting
4. l nvestigati ons • Ta il -end brown bl eeding
5. Diagnosis • Short post-Peak phase
6. Targeted medica l/surgica l treatment • Long post-Peak ph ase
• Long cyc les
1. History Th is is where the CrMS rea ll y exce ls. Thi s system be-
ga n as a mea ns of understanding norm al fe rtili ty in
As ex pl ained earlier PT phys icians are advised to co l- hea lth y co upl es fo r fa mily pl an nin g purp oses.
lect the hi story using a standardi zed medi ca ! consu lt- FertilityCare™ has been used by ever increasi ng num-
ant form . Suitable pati ents may ha ve a hi story of: bers of coupl es since 1976 so that we know what a "nor-
• Jnfertility mal" chart looks like. !f a coupl e have abnormal repro-
• Mi scarri age ducti ve fu nction it is often evident from the fe11ility chart
• Ectopic pregnancy even before bl ood tests or ultraso und studi es ha ve been
• Prematurity performed. As many as one coupl e out ofs ix today ex-
• Low birth we ight peri ence infe rtili ty pro bl ems whi ch require medica! in-
• Placenta! abrupti on terventi on. lt is very reassuring fo r coupl es who have
• Pregnancy-induced hypertension made the decision to postpone hav ing children for a
few yea rs to see they have a norm al appearing fe rtility
chart, and would be likely to conce ive qui ckl y and eas-
2. Symptoms il y at a later date. Simil arl y, if abnormal signs are seen, a
tra ined FCP can advise the coupl e to seek medica! at-
Premenstrual syndrome (PM S) lasting fo r fo ur or more tenti on for in vestigat io ns and treatm ent to correct any
ab normaliti es even before they try to conce ive. This

No rmal Ranges (For lre land)
has the advantage ofrestoring normal reproductive func-
Pre Peak P- 3, P-1 , P+ 1
tion in order to reduce the likelihood of infertility or Estradiol on ly - Over 370 pg/ mL (1000 nmol/ L)
miscarriage ata later date.
Peak Plus 7
Progesterone ( 18.5-3 1.0 ng/ m L) (60- 100 nmol / L)
Estrad iol ( 145-300 pg/ mL) (400-800 pmol/ L)
4. lnvestigations
At this point, the PT physician usually has a reason- Mucus Enhancing Medications
able clinical impression regarding the couple 's fertility 1f mucus enhancing medications are req uired they are
potential. Appropriate investigations must be performed commenced immediately if mucus flow is very poor.
in order to establish a diagnosis and proceed to specific Usually mucus enhancers can be withheld until after
treatment. Symptoms and signs alone cannot estab li sh hormonal correction is achieved. In this way we can tell
a diagnosis, which is critica! with the PT approach. for certain whether or not mucus improves as a result of
treatment. In addition it is unhelpful to fac ili tate con-
ception with suboptimal hormones, as the risk of mi s-
Investigations - Leve/ 1 carriage is likely to be increased when P+ 7 progester-
Targeted Hormone Eva/uation one and E2 are too low.
The following pre-treatment blood tests are taken dur-
ing the second cycle oftracking and interpreted by the In vestigations - Leve/ 2
PT physician during the third cycle oftracking.
U/1rasound Studies
Blood tests are taken on day 3 ofthe cycle for FSH , LH, A. Structural Assessment
prolactin, thyroid function , vitamin B 12, 16 rubella, com- A baseline ultrasou nd sea n is very usefu l for
plete blood count and testosterone (if indicated ). couples who undergo infertility treatment. Ul-
trasound is a minimally invasive procedure which
PT physicians are advised to take a complete hor- can provide a structural assessment of the fe-
mone profile for estradiol 17-~ pre-ovulation on Peak male reproductive organs. lt is best to perform
-3 , -1 , + 1 anda combination of estradiol 17-~ (E, ) and an abdominal ultrasound with a ful! bladder for
progesterone on Peak + 3, 5, 7, 9 and l l. Anything less the initial assessment, fol lowed by transvaginal
than this ful! pro file will give an incomplete picture and ultrasound for subsequent scans. Large ovari an
limit the accuracy ofthe diagnosis. cysts may be missed ifthe abdominal sean is not
performed. The fo llowing abnormalities may be
lffor some reason it is not possible to take the ful! profound:
fi le, a Peak + 7 (P+ 7) test for both progesterone and Uterus - fibroids, polyps, adenomyosis,
estradio l 1 7~ is a reasonable compromise. If either of retroverted lie
these results are low we know that the corpus luteum is Tu bes- hydrosalpinx
not functioning as it hould . This could be because of Ovaries-cysts, endometrioma, PCOD.
inadequate fo lli cular function or corpus luteum insuffi-
ciency. // is no! possible to tell which unless the fi1/I B. Follicular Tracking
hormone profile is taken. In this situation it is wise to Ultrasound follicle tracking can be perfo rmed as
correct the luteal phase ofthe menstrual cycle first, for an initial assessment to establish a diagnosis of
three cycles. HCG 2000 units on Peak + 3, 5, 7 and 9 will abno m1al ovarian function. Another approach is
usually correct corpus luteum insufficiency, except for to defer this investigation until afte r hormone
heavier women who may require a higher dose 2,500 or abnorma lities have been corrected and then ar-
3,000 units. lf monthly P+ 7 blood results for progester- range for fol licle trackin g to confirm th at ovula-
one and E2 fa il to reach the normal range after three tion is occurring normally as monthly blood tests
cycles, ovulation induction with clomiphene should be on P+ 7 for progesterone and E, wou Id suggest.
added to the treatment. The dose required varies from Often normal rupture is confi~ed but at times,
25 mg (one-ha lftablet) daily for three days up to 150 mg despite having normal P+ 7 blood results, we may
(3 tablets) daily for five days starting on Day 2 ofthe still find:
menstrual cycle. The dose is gradually increased until Small follicles
monthly P+ 7 progesterone and E2 ha ve reached the • lncomplete (partial) rupture
normal range. Luteinized unruptured follicle.
Chapter 49 : NaProTECHNOLOGY and lnfertility: A Family Physician's Approach 663
Treatment is adjusted as necessary. The dose of A. Functional A bnormalities

clomiphene is increased if the fo lli cles are too Severa! functiona l abnorma li ties may be fo und as fol-
sma ll. HCG 5,000 or 10,000 units on P- 1, Peak lows:
Day or P+ 1 can help to facilitate fol licul ar rup-
a. Ovarian hormone defici ency- di agnosed by full
ture if incomplete rupture or LUF is found.
hormone evaluation
i. Follicular phase- inadequate foll icular
In vestigations - Leve/ 3 function. Small fo llicles, producing inad-
equate leve ls of estradio l-1 7 ~ preovu la-
Surgical Evalualion
tion.
The NPT family physic ian tries to be as minimally inva-
ii. Luteal ph ase defect- the re are three
sive as possib le and is rel uctant to refer for surgica l
types recognized by PT as described
assessment. Many couples can conceive without the
by Hil gers- Types 1, ll and III.
need for a general anesthetic and surgery. lf it is likely
from the coup le's hi story that they would benefit from b. Ovu latory defect- diagnosed by ultrasound fo l-
surgica l interventi on, early referra l is made. This wou ld licle tracking
be where a coup le have pronounced symptoms cons is- i. Anovu lat ion
tent with endometrios is such as severe dysmenorrhoea, ii. Small follicle
deep dyspareunia or pronounced bowe l sym ptoms dur- iii. Empty Follicle
ing the menstrual flow. l fthe female is 38 years or older iv. Partial fo lli cularrupture
and has never had previous surgica l eva luation, earl ier v. Luteinized Unruptured Follicle Syndrome
referral may be necessary.
c. Polycystic ovari an di sease (PCOD) can be mild ,
moderare or severe. The severe and moderare
Usuall y surgica l assessment can wait until six effective
forms are easier to di agnose. Mild PCO D can be
cyc les of med ica! treatment ha ve been com pl eted. The
difficu lt to confirm with only one or two of the
advantage of postponing surgery is th at an unneces-
abnormalities bein g present. Typ ical ly women
sary invas ive procedure may be avo ided. The disad-
ha ve long irregu lar cyc les, hirsu tism and obesity.
vantage is that optima! fertility treatment may not be
Blood tests show a reversa! ofthe FSH : LH ratio,
achi eved unti l after surgica l correction of an underlying
elevated testosterone leve ls and increased in su-
abnormality has occurred . lt is good to explain the risks
lin resistance. Ultrasound shows large ovaries
and benefits, the adva ntages and disadvantages of sur-
with multip le small fo llicles measuring 0.5 to 0.7
gery and in vo lve coupl es in the decision-making pro-
mm in diameter. A laparoscopy shows pearly white
cess to dec ide when they would like to pursue the more
ovaries. A biopsy of the ovaries and hi sto logy
invas ive surgica l in vestigations and treatment.
can confirm the di agnos is.
Surgical in vestigations that may be recommended in- d. Limited ce rvica l mucu s tlow- diagnosed by
clude: FertilityCare™ chart onl y.
• Laparoscopy and dye test - with diathermy/ la-
e. Chronic stress- The effects of stress can often
ser of endometriosis
be seen on the FertilityCare™ chart. Recogniz-
• Hysterosco py
ing that stress is present and hav ing an abi lity to
• Hysterosa lpingogram
monitor its impact cycle by cyc le is very helpful
• Transcervical catheteri zation of fallopian nibe
in understanding and managing li fe 's stresses.
(USA only)
f Male factors- described earli er
g. ln fection-C hroni c low-grade endometritis
5. Diagnosis
h. lmmunological- Anti-ovarian antibodies 15 ... (and
There are two main di agnostic categories in NPT (a) others to be di scovered)
fu nctional reproductive abnonnalities or (b) strucniral
problems. Often the two categori es co-ex ist. Of course
ifadd itional med ica! problems are fo und with day-3 blood B. Structura/ Problems
tests show ing anemi a, abnormal thyroid function etc. These are diagnosed by ultrasound or one of the surgi-
these probl ems are corrected first. ca l techniques li sted above. Common diagnoses include:
• Endometriosis
• Polycystic ova ri an di sease (PCOD)
• Pelvic inflammatory disease (PI D) rng nightly) or oral micronized progesterone (200
• Uterine fibroids mg by mouth two times a day [PO BID]) fo r 1O
• Endometrial polyp days, starting on Peak + 3 ofthe cycle.
• Uterine septum.
d. Mucus Enhancers- Yi tam in B6 , mucolytics and
amp icillin are added as necessary. lt is good to
assess the effectiveness of these medications by
6. Targeted Medica//Surgical Treatment
documenting the mucus cycle score before and
during treatment. lfmucus does not improve af-
Treatment is targeted and directed at speci fic abnor-
ter three cycle , the mucus enhancer is discon-
malities. lfwe cannot fínd a problem, we cannot treat it.
tinued. Up to 50 percent of women may get an
lfit is not broken we do not need to "fix it"!
improvement in mucus quality with these treat-
ments.
As one proceeds along the investigative process, ab-
normalities are found at various different levels. Wher- e. Stress Management- The adverse effects of
ever the problem lies treatment is directed to correct the stress can be monitored on a cycle-by-cyc le ba-
abnormality and restore normal physiologic function. sis. The effectiveness of intervention s to modify
This is complete] y different from contemporary practice stress can be assessed with the FertilityCare™
which will often conclude that everything is normal ac- chart. lf necessary, coup les can be referred for
cording to the day 21 blood test for progesterone, but counseling or prayer to help in managing more
will give a three to six-month tri al of clomiphene,just in difficult situation .
case it might work!
f PCOD- cases of increased insulin resistance
should be treated with metformin HC1 18 500 mg
A. Functiona/ Abnorma/ities (Medica! treatment)
three times a day (T ID). lt is best to start with
a. Ovulation lnduction- lf an ovulatory defect is either half to one tablet daily and gradually in-
confirmed, treatment is targeted init ial ly with - crease the <lose until the ful! treatment is reached.
clomiphene to correct the abnonnality and restore Sorne women cannot tolerate metformin HCl be-
normal function. In cases of clomiphene resi - cause ofbowe l-related symptoms. Rosiglitazone 19
tant anovulation , where ovulation <loes not oc- 4 mg daily is a useful alternative. Most women
cur despite maximum doses ofclomiphene, many will require ovulation induction with clomiphene
women will ovulate ifprednisolone 5 mg daily is and luteal phase support with vaginal progester-
added to the treatment. 16 lfthis is not effective ( 1 one 400 to 600 mg for 1Onights commencing on
to 2% ofthe time) patients may require FSH injec- P+ 3 each cycle. ln terestingly, the majority of
tions in order to achieve ovulation. Very rarely women with PCOD do not require mucus enhanc-
(<0.1 % of the time) patients may ha ve hypotha- ing medications and experience minimal side ef-
lamic amenorrhea, which can be treated with pul- fects from clom iphene.
satile GnRH.
g. Chronic Endometritis- This can be di fficu lt to
b. lfultrasound shows incomplete rupture or lutein- diagnose. Often an endometrial biopsy will fai l to
ized unruptured follicle (LUF) - HCG 5,000 or identify any organisms. lfthe fertility chart shows
10,000 unit is given on P- 1, Peak Day or P+ 1 to persistent premenstrual, intermenstrual or tail-end
facilitate follicular rupture. In addition, adjusting brown bleedi ng this may be dueto a chronic en-
the <lose of clomiphene to 25 mg daily for 1Odays dometritis. lf a low-grade infection is presenta
starting on day 1 of the cycle can be effective. two-week tria] ofmetronidasole 400 rng three times
LUF may also be a side effect from NSA!Ds 17 if a day (T ID) and cephradine 500 mg th ree times a
they are taken on a long-term basis. These should day will usually cause the unusual bleeding pat-
be discontinued, ifpossible. tern to disappear.
c. Corpus luteum insufficiency is usually treated h. [mmunological factors as a cause for subfertility
with HCG 2000 IU on Peak + 3, 5, 7 and 9 ofthe are still the subject of research and there are no
menstrual cycle. Couples are taught how to in- clear guidelines as yet in this area . A possible
ject themselves and can usually do this confi- immunological factor may be present in cases of
dently following instruction and practicing for a clomiphene resistant anov ulati on 15 •16 that re-
few cycles. Progesterone can also be used in the sponds after adding prednisolone 5 mg daily.
luteal phase as vaginal suppositorie (400 to 600
1. Male Treatment- as described earlier.
Chapter 49 : NaProTECHNOLOGY and lnfertility: A Family Physician 's Approach 665
B. Structural Problems (Surgical treatment) ii. Hysteroscopy

Surg ical interventions are specifically applied to cor- iii. Other eva luation as indicated .
rect structura l abnormalities:
• Endometriosis- Diathermy, laser2° or microsur- 12. Continue until 12 fully effective cycles have been
gery as required completed . If significant abnonnalities are de-
• Polycystic ovarian disease (PCOD)- Laparos- tected surg ica ll y, re-start count for 12 cyc les af-
copy with ovarian diathermy 21 or laparotomy and ter surgical correction .
ovarian wedge resection 22 are required ifsuccess- 13. Set goa ls and targets with couple. Discuss op-
ful ovu lation induction cannot be ach ieved with tions ART/adopti on/acceptance with their pros
medica! treatment alone. and cons - ifNPT does not result in conception.
• Pelvic inflammatory disease (PID)- Microsurgi-
cal reconstruction of pelvis
• Uterine fibroids- Myomectomy
Conclusion - - - - - -- -------.
• Endometrial polyps- Polypectomy
• Uterine septum- Hysteroscopic resection. 23
NPT cooperates with the couple's natural procreative
potential to ach ieve optimum function. The entire treat-
NPT physicians need to have access to well-trained
ment program is built aro und the CREIGHTON MODEL
gyneco logists who are confident in offering skilled sur-
FertilityCare™ chart. The chart is important fo r the ini-
gica l treatments for the patients who require surgical
tial evaluation of a coupl e's fertility potential, for the
intervent ion. The NPT physician should continue to
timing of blood tests and to monitor the response to
manage the couples' medica! treatment after surgery.
treatment cycle by cycle. The beneficia! effects of medi-
ln summary the treatment plan is as follows:
ca ! and surgical treatments can be seen as the chart
1. Set goa ls for the couple. Moti vate them to con- changes from an abnormal to normal pattern. In addi-
tinue the program for 18 to 24 months. tion if stress is an issue th e beneficia! effects of coun-
sel ing and stress management can be seen from improved
2. Begin to record s igns of fertility with
cha11ing patterns.
FertilityCare™ chart.
3. Blood tests in second cycle. Many of the medica! treatments used in NPT are not
new. What is new is the way treatment is targeted with
4. Medica! review with ultrasound in third cycle.
respect to a very preci e fe11ili ty charting system and
5. Estab lish a diagnosis. tailored to each couple's indiv idual cyc le.
6. Correct ovarian fünction/ recommendations to
We have not yet reached the end point in the growth
improve male fertility.
and development ofN PT as a specia li zed program of
7. Monitor P+ 7 bloods monthly, semen analysis - fertility treatment. The FertilityCare™ chart continues
three monthly if suboptimal. to challenge us to correct physiologic abnorma lities that
do not always improve with hormona l manipulation. We
8. Enhance cerv ical mucus flow if necessary after
are beginning to discover the role of antibiot ic treat-
P+7 is optima l.
ment for chronic low-grade endometritis to treat persis-
9. Confinn ovulation with ultrasound follicle track- tent tail end brown bleeding and suspect that immuno-
ing. Adjust treatment if necessary. logical factors wi ll be significant in treating resistant
cases ofrecurrent miscaiTiages. An in-depth understand-
!O. Continue to aim for 12 fully effective cycles:
ing of indi vidual charting patterns allows for new in-
i. Optima! P+7 P and E2
vestigations and treatments to develop to try and opti -
ii. Satisfactory cervical mucus quality
mize reproductive function .
iii. Freq uent intercourse during mucus days
iv. Adequate stress management (counsel-
NPT is a revolutionary new approach to understanding
ing/prayer ifrequired).
and managing reproductive and gynecologic health. It
11. lfthe coup le have not conceived after five to six is just waiting to be discovered and embraced by the
fully effective cyc les, it may be time to refer for greater medica! commu nity. The advantages this new
surgica l evaluation system offers to doctors and couples are astounding!
1. Laparoscopy (in iti al or repeat with an ex-
pert in endometriosis)
1. Standardi zed Medical Co nsultant form de ve loped th rough 12. Hilgers TW, Prebil AM , Da ly KD, Hil gers SK. The Pictu re
the lnt ern ation a l lnstitute o f Restorative Reprodu cti ve Di ctionary - 2"d Editi on Pope Pau l VI lnstitute Press, Omaha,
Medicine (11 RRM ) and di sse rninated to its members. The NE, USA, 1999.
forrns were spec iall y deve loped for those who participate in
13. A vid eotape or DVD prese ntat ion of th e standardi sed intro-
ongoing prospective clini ca l tri a ls and are use ful for NPT
ductory sess ion is ava il ab le fo r NPT Ph ys icians.
Ph ys ician's data co ll ection.
14. Bennen M. Vitam in B 12 Deficiency, lnfe rtility And Recur-
2. The lnternati ona l lnstitut e of Res tora tiv e Reproductive
ren! Fetal Lo ss. J Reprod Med 46:209-212, 2001 .
Med icin e (llRRM ) is an lntern ati onal resea rch organisati on
wh ich was fo rmed in 2002 to promote research into in fe r- 15. Luborsky J, Pong R. Pregnancy Outcome And Ova ri an
ti lit y treatments wh ich are not invasive, destructive or Anti bodies In ln fe rtilit y Pati ent s Unde rgoi ng Co nt ro ll ed
c ircu mve ntive in nature. Furth er in formatio n on reg ister- Ovar ian Hyperstimulati on. Am J Reprod lmmun o 44:261-
in g wi th the ll RRM is ava il ab le via e mail: 265 , 2000.
ma i l@ ferti 1ityca re. net
16 . lsaacs JD Jr, Lincoln SR, Cowa n BD. Ex tended Clom iphene
3 . Tate, P. The Doctor 's Cornrn uni cation Handbook - Radcliffe Ci tra te An d Prednis one For Th e Trea tm e nt Of Chroni c
Medica l Press, ISBN 1-85775-011 -X Anovu lation Res istant To CC Alone. Fertil Steril 67:64 1-3,
1997.
4. lri sh NPT C lini c patient record s from 1998 - 2002 inclu-
sive, Dr. Phil C. Boyle, 6 Clifton Crescent, Newcastl e, Ga lway, 17. Stone S, Kh amashta MA, Ne lso n-Pi ercy C. No nstero idal
lreland . Paper 2 of a se ries of 3 papers written and submit- Ant i- lníl am matory Dru gs And Reve rsible Female lnfertil-
ted for publication. ity - Is There A Lin k? DRUG SAFETY 25:545-551, 2002.
5 Andersen, AM; et al. Maternal Age And Fetal Loss : Popu- 18 . Seli E, Duleba AJ. Should Pati ents With Polycysti c Ovarian
lati on Based Reg ister Linkage Study. Br Med J 320 : 1708- Syndrome Be Treated With Metformin ? Pro ve n And Po-
17 12, 2000. tenti al Benefits. Hum Reprod 17:2230-2236, 2002.
6. Mal e Factor Pak™ Apex Medical Techno logies, !ne ., 10064 19. Ghazeer i G, Kutteh WH , Bryer-Ash M, Haas D, Ke RW.
Mesa Ridge Co url, Suite 202, San Di ego, CA 92 12 1, USA Effect Of Ro siglitazone On Spontaneous And C lomip hene
Ph. (00 1) 858 535 00 12 Citrate- lnduced Ovulation In Women With Polycystic Ovary
Syndrome. Fertil Steri l 79: 562-566, 2003.
7. Vicari E, Arancio A, Gi uffri da V, D' Agata R, Ca logero AE. A
Case Of Reversible Azoospermia Following Withdrawal From 2 O. Sutton CJG, Jones K. Laser Laparoscopy For Endometri osis
Alc oho l Co nsumption. J En doc rin o! ln ves t 25 :473 -4 76, And Endometri oti c Cysts. SU RGICA L EN DOSCOPY AND
2002. OTHER INTERVENT!ONAL TECHN !QUES , 16: 15 13-
15 17, 2002.
8. Kadiog lu TC, Koksa l IT, Tun e M, Nane 1, Tellalo glu S.
Treatment Of ldi opathi c And Pos tva ricocelectomy Oligo- 21. Takeuchi S, Futamura N, Takubo S, No da N, Minou ra H,
zoos permia With Oral Tamoxifen C it ra te. Br J Uro ! lnt To yo da. Po lycys tic O va ry Syndrome Treated With
83:6 46- 8, 1999. Laparoscopic Ovari an Drillin g With A Harmonic Sca lpel - A
Prospe cti ve, Rand omi ze d Stud y. J Reprod Med 4 7:816-
9. Len zi A, Lombardo F, Sgro P, Salacone P, Ca ponecch ia L,
820 , 2002.
Dondero F. Use Of Ca rnitine Therapy In Selected Cases Of
Male Factor lnfenility: A Double-Blind Crossove r Tr ia!. 22. Yildirim M, Noya n V, Tiras. Ova rian Wedge Resection By
Fertil Steril 79:292-3 00, 2003. Min il aparato my In lnfertil e Pati ent s With Po lycyst ic Ova-
ri an Synd rorne: A New Technique. Europ J Obstet Gynaeco l
1O. Roseff SJ. lrnprovement ln Sperrn Quality And Fu nction
Bio 107:85 -87 , 2003.
With Fre nc h Ma ri time Pin e Tree Bark Extract -
( Pyc noge nol). J Reprod Med 47:82 1-824, 2002. 23. Oppelt P, Siebo ld J, Sta hl er J, Plath ow D, Kaufmann M,
Baum ann. Hysterosco pi c Septa l Resecti on, The Treatment
1 1. Bates CA. Antisperm Antibodies And Ma le Subfen ility. Re-
Of Choice In Patients With Subse ptate Uteru s: Pos topera-
view Arti cle. Br .1 Uro. 80:69 1-697, 1997.
tive Pregnancy Rates. Gynaecol Endose 11: 123- 126, 2002.
NaProTECHNOLOGY and Pregnancy
following Failed ART
Dr. Phil C. Boyle
nfertility is a significant problem fo r many coup les in need for ART in many cases. NaProTECHNOLOGY is a
I the deve loped world today. Up to one in five coup les
experience difficulty conce iving in the United States 1 •
couple-centered, disease-based approach to investigate,
diagnose and treat infertility. The term " natural" refers
In Europe one in six coup les have difficulty conceiv- to the method of conception through a natural act of
ing2. Current infertility protocols usually advise blood intercourse as opposed to any artificia l interventi on
tests on day 3 to 76 of the menstrual cycle to assess which replaces intercourse. Clinica l experience and ret-
go nadotropin and prolactin leve ls, thyroid function, rospective studies 3 show great promise, however fur-
hemoglobin , rubella status and testosterone levels- if ther prospective studies are needed to determ ine present
clinically indicated. In additi on bloods tests are usually day success rates and conv ince the greater medica! com-
taken on day 2 ] or 22 ofthe cyc le to measure progester- munity ofthe va lue ofNPT fert ility treatment.
one leve ls in the probabl e mid-luteal phase ofthe men-
strual cyc le. Most specialists would agree that ovula- Idea ll y coup les should learn how to track the signs of
tion is probab ly occu1Ting ifprogesterone leve ls exceed fertility and understand their fertility potential , even
30 nmol/L (9.5 ng/mL). After a sem inal fluid analy is , befare attempting concept ion. Coup les who use
postcoital test, ultrasound exam ination, laparoscopy and CREIGHTON MODEL FertilityCare™ System~ (CrMS)
dye test and possibly a six to nine-month trial ofclomi- for family planning have a distinct advantage over non-
phene citrate (Clomid), those coup les who have not users. They can tell , even before they try to conceive, if
conce ived face the prospect of artific ial reproductive they may be at risk ofm iscarri age or infertility based on
technology (ART) ifthey wish to continue fert ility treat- their CrMS cha11ing pattern. This is very usefu l infor-
ment. Occasionally ovulation induction with FSH (with mation to help them make an informed dec ision abo ut
or without intrauterine insem ination) may be given for a managing their ferti lity in a way which is appropriate to
further three to six cycles before embarking upon in them. lf couples experience infei1ility or miscarriage NPT
vitro fe rtilization (JYF) with or without intracytoplasmic should be their first choice to identify and treat what-
spenn inj ection (ICSI), which we refer to as ART through- ever abnormal iti es may be found.
out thi s chapter.
But what about coup les who were unaware ofthe NPT
NaProTECHNOLOGY (NPT) is a new, safe and effective approach and ha ve tried ali of the medica! treatments
means oftreating inferti lity that can avoid the perceived ava il able to them , including artificial reproductive tech-
~~~~- ~ ~~~~~ 667

668 Th e Med ic al an d Surg ica l Pra c t ice of Na ProTECHNOLOGY
nologies (A RT) without success? Is it worth trying NPT

at this point orare they simp ly wasting their time? Table 50-1: Profile of Entire Gro up -
95 Couples
Experience fro m a fa mily practice in Galway, lreland has
Average Range
shown that 20 percent to 30 percent of couples with (y ears) (years) Total
prev iousl y un successfu l ART will have a successfu l
Female age 36 .8 28-47
pregnancy with NPT. This chapter wi ll look at that se-
Years trying to conceive 6.1 2-13
lect group of pati ents who have succeeded with NPT
Attempts al ART 1.85 1-7 176
afterfa iledART.
Attempts at embryo transfer 1.84 0-5 175
N PT has been ava ilable to Iri sh patients since February

1998. lt was not known at that time how effective thi s average age ofthe woman per conception was 36.8 years,
treatment would be for infertile couples who had other- with a range from 28 to 47 years. Th e couples had been
wise finished with fe rtili ty treatment. Patients were told trying to conceive for an average of 6. 1 years and had
that because NPT was a new approach we could not 176 fai led attempts at ART, with 175 un successful em-
predict what the probability of success would be. bryo transfers. There was an average of two un suc-
cessfu l attempts at ART per coupl e (Tabl e 50- l ).
This chapter will focus on the number of couples who
ha ve conceived with NPT, despite previously fa iled ART.
We will look at six years of clinical practice in a fa mily Results with NPT Treatment _ _ _ _~
phys ician 's office from the beg inning of February 1998
until February 2004. The percentage success rate is only There were 123 conceptions from 95 coup les, res ulting
ava ilabl e for the first fo ur years ofpractice and will be in 89 successful pregnancies from 74 of the couples.
presented in a life-tabl e analysis. Fourteen out ofthe 74 coupl es had a second successfu l
pregnancy and one hada th ird success with PT. There
lt is importan t to bear in mind that the effecti veness of were 21 who did conceive, but either hada mi scarri age
PT improved over time a the physicians offering treat- ( 17) or ectop ic pregnancy (4) as the final outcome (Table
ment gained greater experience and it is likely to be even 50-2.) There were three tw in pregnancies, giving a mul-
more effective th an present results would indi cate. Al o, tiple pregnancy rate of3.4 percent per live birth or 2.4
a key factor in giving coupl es the best chance of suc- percent per concepti on .
cess is for them to co mplete 12 effecti ve cyc les of treat-
ment which can take fro m 18 to 24 month s after beg in- A life-table analysis showin g the success rate of treat-
ning the progra m. Unfortunately, many coupl es gave ment fo r the first four years ofthe programare shown in
up prior to reaching this desired end point, large ly be- Table 50-3. This table shows th e adjusted proporti on
cause the goa ls of treatment were not clearl y outlined
by their physicians from the outset.
Table 50-2: Outcome of Patients Pregnant
with NaProTechnology after Failed ART
Study GrOUP· ---------~
Ali patients with prev iously un successfu l ART who Total number of conceptions 123
conceived with N PT treatm ent throu g h a fa mil y Total number of couples conceiving 95
physician 's practi ce in Galway, Ireland were included in Total number of live births 89
thi s study, between February 2, 1998 and February 1, Total number of couples with al leas! one live birth 74
or ongoing pregnancy
2004. Four pati ents were exc luded from the study be-
Total number of couples with al least two live births 14
cause two were already pregnant at the initi al medica!
Total number of couples with al least three live births
consultat ion and a further two previously had a suc-
Number of couples ectopic/miscarriage 4+17 =21
cessfu l pregnancy with IVF prior to conceiving with
NPT. Total number of twins 3
Twin rate per live birth (%) 3/89=3.4 %
There were 95 patient who conce ived 123 tim es. The
Chapter 50: NaProTECHNOLOGY and Pregnancy following Failed ART 669
Tab l e 50-3: Life-Table Analysis-Success Rates of NPT Treatment for First Fo u r Y ea r s ( 1998-2002 incl u ded)
Couples with co nceptlons resultlng In first Continu lng Final outcome

Number Couples withdrawing live births or first ong.o lng pregnancles treatment w/o mise. or
starting Cumulative Cumulative Adjuste<l proportlon llve birth at ectoplc
Stage of 1n évent Cumu lative crude %of Cumu lative crude % of achievlng end of study without
treatment category Number number ali subjects Number number all subjects pregnancy follow-up live birth
0-2 months 351 8 8 2.3% 7 7 2.0% 2.0% o o

3-6 months 336 72 80 22.8% 17 24 6.8% 7.6% o 5
7-11 months 242 79 159 45.3% 16 40 11.4% 15.0% o 2
12- 17 months 145 62 221 63.0% 15 55 15.7% 26.2% o
18-25 months 67 29 250 71 .2% 4 59 16.8% 32.6% 11 2
26-36 months 21 7 257 73.2% 2 61 17.4% 43.8% 10
>36 months o 257 73.2% o 61 17.4% 43.8% o
Total numbers 351 257 61 22 11
ach ieving pregnancy is 26.2 percent at 12 to 17 months, The profil e of this group shows that 55 (58% ) of the
rising to 32.6 percent for 18 to 25 month s in the program. coupl es had a n initial diagnos is, prior to coming into
the PT program , ofunexplained infe rti lity (F igure 50-
1). Twenty-two couples had endom etriosis, 1O had low
An alysis of Pregnancies - - - -- - - . progesteron e, l O were deemed not to be ovulating, 11
had an abnormal sem ina l fluid a na lysis, seven had at
Ana/ysis of 95 Patients Who Conceived least one blocked fa ll op ian tu be, e ight had pe lvic adhe-
s ions and 13 were in sorne oth er di agnostic category.
The previous obstetrica l hi story fo r the 95 couples who The sum of diagnoses exceeds 95 a sorne couples had
conceived is outlined in Table 50-4. a combinatio n oftwo or more di ag noses.
There were 42 couples who had never conce ived natu- None of the coup les had a di agnosis of unexp lained
rall y before. Ofthese, 29 did conceive but never hada infe11ility following PT eva luation . The principa l dif-
live birth and 24 couples hada previous li ve birth . ferences w ith N PT diagnoses are th e elimination ofun-
explained infe11ility anda large increase in the catego-
T he average d uration of inferti 1ity was 6. 1 years, with a
ran ge from two to 13 years (Table 50-5).
Tabl e 50-5: Average D u ratio n of lnfertilicy
Women aged 33 years and yo unger acco unt for o nl y 15
B efo re First PT Live Birth (N =95)
percent ( 18/J 23) of conceptions, while those aged 40+
yea rs account for 21 percent (26/ 123). The majority of Years trying to Number of couples out of
women were 34 to 39 years old , ma kin g up 64 percent conceive 61 live births
(79/ 123) of conceptions (Tabl e 50-6). :': 2 years 4
3 years 8
4 years 13
5 years 21
6 years 19
Tab l e 50-4 : Obst etric History
7 years 6
(N=95)
8 years 9
9 years 7
Past Obstetric History n %
10 years 1
Nulligravida 42 44 11 years 2
12 years 4
Nulliparous 29 31
13 years
Secondary infertility 24 25
Ave rage = 6.1 yea rs
largely unchanged except far a new co lumn - conceived

Table 50-6: Women's Age at Conception pre-in vestigations. T here were 15 coup les w ho actually
123 Conceptions from 95 Cou ples with conceived befare investigations were completed, w hil e
Previous Failed IVF they hadjust started tracking their s igns offertil ity. Of
Age(years) Number of Conceptions these, 1O of the 15 had a previous di agnos is of unex-
plained infertility.
~30 5
31-33 13
There were 55 percent of co upl es who conce ived be-
34-35 25
36-37 26 yond s ix months into th e program and 10 coupl es who
38-39 28 required more than 20 months befare concepti on oc-
40--41 15 curred. Sorne had taken a break fa r a time befare res um-
42-43 7 ing treatment, whic h was fi nall y successfu l. Others had
44+ 4
a delay in pursuing surg ical eva luation and conceived
Average= 36.8 years
when medica! treatme nt was resum ed fa ll ow ing surg i-
ca l intervention (Figure 50-3.) In genera l most coupl es
have comp leted treatme nt by 24 mo nths into the pro-
gram.
ries of low progesterone, low estradio l and un favorable
mucus. The e horrnone deficiencies we re faund because A ummary of the treatrnent w hi ch couples rece ived is
ofthe timed blood tests with respect to ovul ation, which ou tlined in Figure 50-4. Coup les often hada combina-
are more precise and, therefare, use a higher reference tion of different treatme nts, w hic h is why the sum of
range than standard day 2 1 ranges. Estradiol measure- medica! interventions is greater than 95. Fifty-one women
ments are usuall y not c hecked at ali on day 2 1 in a con- had ovul ati on induction w ith c lom iph ene and 48 hada
ve nti o nal fert ility eva luation. Un favorable mucu s was series of HCG injections of2000 units o n days 3, 5, 7
identified w ith the FertilityCare ™ c hart w he re cervica l a nd 9 afte r ovu latio n acco rding to the fert il ity cha1i.
mucus seores were faund to be below accepted normal Forty-nine had sorne fo rm ofmucus enhancing med ica-
ranges. 4 ·5 The rest of the di ag no st ic categories are ti o ns and 1O coup les had other medica! treatme nt in-
55
95 Couples ART Diagnosis
Figure 50-1 : lnfertility diagnosis prior to coming into NPT program .
100.0
95 Couples NPT Diagnosis
73
23
Figure 50-2 : lnfertility diagnosis after being evaluated by NPT.

Chapter 50 : NaProTECHNOLOGY and Pregnan cy following Failed ART 671
cluding bromocriptine, thyroxine and cyclofenil During pregnancy 84 women had progesterone sup-
(Neoc lym) . One couple with a diagnosis of hypotha- port andan additiona l 17 also had HCG in an attempt to
lami c amenorrhea required treatment using a GnRH reduce the ri sk ofm iscarriage. This was usually recom-
pump. They conce ived on their third cyc le ofpulsatile mended in cases oftwo or more previous miscarriages
GnRH fo r their first NPT pregnancy. or ifthe hormone levels were found to be very Jow on
the cyc le of conception. There were 1 1 coup les who did
Seven men required ferti li ty treatment. Four had not have any hormone support during pregnancy.
tamoxifen, two had prednisolone and one had antibiot-
ics, vitami n and minera l supplements. Fifteen women
conceived followi ng surgical interventions, 1O follow- Outcomes of A/1123 Conceptions
ing diathem1y of endometriosis, two post myomectomy,
one post polypectomy and two had successful micro- Ofthose who conceived and were aged 3 7 years or less,
surgica l reconstruction of blocked fa ll opian tu bes. 84 percent had a successfu l outcome, with 16 percent
ending in miscarriage or ectopic pregnancy. But for
women aged 38 years or greater, on ly 57.4 percent had a
successful outcome, with a 42.6 percent risk ofunsuc-
10
10 10 Month s of Treatment to First Conception
95 Couples Previous Failed ART "
9 cessfu l pregnancy. The ri sk of an ad verse outcome was
more than twice as high for older women . The overa ll
risk of miscarriage or ectopic pregnancy for al l age groups
was 27.6 percent (Tab le 50-7). These fig ures are also
plotted on a bar chart to show the correlation of ad-
3 3
verse pregnancy outcome with advancing female age.
Of women aged 42 years or greater, 55 percent had an
adverse outcome to their pregnancy (F igure 50-5). The
4 5 7 8 9 10 11 12 13 14 15 16-20 2{}t
Months twin pregnancy rate overa ll was (3/89) 3 .4 percent per
Figure 50-3 : Months of treatment to first conception in 95 live bi11h.
co uples who had previous failed ART.
Outcomes for A/195 Couples

100.0
95 Couples Medical/Surgical Rx
Looking at ali 95 couples, sorne had a miscarriage on
their first pregnancy, but subseq uently went on to ha ve
a successfu l pregnancy on their second or third attempt.
The fina l outcomes for the 95 coup les show that 74
50.0
eventuall y had at least one successfu l "take-home" baby
and 2 1 did not. Fourteen of the 74 successful couples
went on to ha ve another successful pregnancy and one
had a third success.
o.o
.:::-.,..,,,,. .,.,. ~ <>""'..,....,..... ,,... """" ..-;;,.. .,...,..
Finally, ifwe look at all ofthe couples with a hi story of
Figure 50-4: Summary of medical and surgical treatment previous failed ART between 1998 and 2002, it appears
coup les received after failed ART. that a higher number ofpast IVF attempts is associated
Table 50-7: Pregnancy Outcomes from Ali 123 NPT Conceptions

from 95 Couples witb Previo usly U nsuccesshtl ART
Number of Ongoing Successful Total adverse

Age(years) conceptions Uve births pregnancy pregnancies outcome Miscarriage Ectopic
.:: 37 69 53 5 58 (84.0%) 11 (16.0%) 8 (11 .6%) 3 (4.4 %)

~ 38 54 29 2 31 (57.4%) 23 (42 .6%) 21 (38.9%) 2 (3.7%)
Ali ages 123 82 7 89 (72 .4%) 34 (27 .6%) 29 (23.5%) 5(4.1%)
672 The Medical and Surgical Practice of NaProTECHN OL OGY
Discus s i on ------------~
6()0/o Risk of Miscarriage with Advancing Maternal Age
123 Conceptions Following Previous Failed ART 55%
There are man y different ways to analyze the results of

50%
N PT fe rtili ty treatment, but w hi chever way we look at
the figures , we ca n confidentl y say that a signi fica nt
number of couples will conceive w ith thi s approach.
30%
Everybody knows of dra matic stori es abo ut couples
that had been trying to conceive for years without suc-
200/o cess, w ho spontaneously ac hi eve a pregnancy after fin -
ishing with ferti li ty treatment or following a successful
adoption. C líni ca! consensus is that abo ut 5 percent of
couples with fa il ed fVF will conceive subsequentl y with-
O"/o out any intervention . For the first four years of treat-
37 years or less 38 to 41 years 42 years or greater
ment, we ha ve a success rate of up to 32.6 percent or
more, depending on how we interpret the results ofNPT
Fi g ure 50-5 : The ri sk of m iscarriage with advancing maternal
age in 123 conceptions foll owing previously failed ART. treatment. There we re 12 couples within thi s group w ho
conceived with fert ili ty-foc used intercourse alone with-
out medi ca! treatment. Thi s represents a success rate of
with a lower N PT li ve birth rate. This effect <loes not 3.4 percent, which is comparable to the expected spon-
appear to be related to the wo man 's age. A lthough those taneous pregnancy rate fo ll owing failed IVF.
with three and more previous attempts with ART are a
little o lder, the average age is still below 38 yea rs. Ifa We ha ve observed that the process of lea rning how to
coupl e had one prev ious attempt atART, the PT crude track the bi o logic markers of fertility leads to coupl e
li ve birth rate was 28.9 percent. This fe ll to l 8.4 percent empowern1ent, stress reduction and often to restora-
with two prev ious ART attempts and was just 13 .3 per- ti on of normal reproductive functi on. Thi s is especia lly
cent if there we re three or more previous attempts with the case w here couples have been under a lot of stress
ART (Table 50-8 and 50-9). prior to commencing N PT. There is a temptation to count
pregnancies whi ch ha ve occurred pri or to the introduc-
tion of medica! treatment as " non-N PT pregnancies,"
however the process offerti lity track ing itse lf is an in-
tervention , central to our program, which improves preg-
Table 50-8: Final Pregnancy Outcomes from All 95 N PT Couples with Previously Failed ART
One or more Ongoing Successful Total adverse

Live births pregnancy pregnancies outcome Miscartiage Ectopic
Ali 95 couples 69 5 74 (77 .9%) 21 (22 .1%) 17 4

Average age 36 years 39 years
Table 50-9: NPT Pregnancy Success Rates according to Num.ber of Previous Failed
ART Attempts including Ali Conceptions and Ali Live Births for Four Years, 1998-2002
Number of Average Number Total number Total number of liv.e Live birth
IVF attempts female age of couples of conceptions births or ongoing preg. rate
36 .5 82+5+34 =121 47 35 28.9%
2 36 .2 94+9+22 =125 24 23 18.4%
3+ 37 .5 81 +8+16 =105 22 14 13.3%
A ll 36 .7 351 93 72 20.5%
Chapter 50 : NaProTECHNOLOGY and Pregnancy foll owi ng Failed ART 673
nancy rates even in the absence of medications. Most ferti li ty rates 6 . Furthermore we have had two live births
couples who did conce ive in this way also had proges- fo llowing myomectomy7 . The fibroids were prev iously
terone support 10 · 11 usua lly for 12 to 16 weeks gestation deemed insignificant by the ART spec iali st, but in the
in an attempt to reduce the risk of subseq uent miscar- opini on ofa micro-surgeon they were regarded as prob-
nage. lemati c and subsequently removed, restoring normal
ferti lity. lt is important for NPT Phys icians to have ac-
Thi s gro up of patients had reached the end of avai lable cess to skill ed co-operati ve surgeons to maximize the
conventional infertility treatment options, includingART chances of successfu 1 treatment.
but had not yet tried NPT. Despite advanced female
age, long-standing in fertility and previous un success- lf a co upl e did achieve fe1tilization with NPT, the prob-
ful attempts with ART, a remarkable 32.6 percent suc- ab ili ty of successful maintenance of impl antati on was
cess rate with PT treatment was achi eved. lncreasi ng 72.4 percent for ali age groups. Women aged 37 years or
numbers ofpast IVF atte mpts were associated with de- younger had an 84 percent probability of successfu l
creasing live birth rates with NPT treatment. Thi s can- pregnancy ifthey managed to conceive. Remember th is
not be accounted for simpl y because of advancing fe- is a popul ation of patients where most of them did
ma le age, and one mu st suspect that the process of achieve successful fertili zation previously with ART,
ART itse lf may have an ad verse effect on the coup le's but the embryos fa iled to implant in ali of them. Embryo
fertility potential, making future pregnancies less likely. wastage and fa il ed implantati on is generall y accepted
We feel it is crucial for couples to consider NPT before by th e medica! community to be very hi gh in the nor-
ART, especia ll y because of the poss ibl e negati ve im- mall y fertile population 8 . lt is often stated that implanta-
pact of ART against future PT success. However, as tion success rates from TVF cycles are comparable to
the above fi gures show, NPT can still be effective, even what occurs in nature. These data would contradict th at
after multiple failed attempts at TVF. assumption. Clearly the vast majori ty of embryos, re-
sulting from NPT successfull y implanted and concluded
NPT aims to find out why couples ca nn ot conce ive and with a li ve birth , especia ll y in younger women. The
then tries to correct the identified abnormalities - hor- higher pro bab ili ty of mi scarriage in the older women is
mone defici ency, un favo rab le mucus, anovu lation , en- most likely related toan in creased incidence ofembry-
dometriosis, male factor, and so fort h. When a func- onic developmental abnorm alities whi ch were incom-
tiona l or structural abnormality is identified and cor- patible wi th li fe 9 . Hormon e support with progesterone
rected we expect a restoration of norm al reproductive and HCG may also have pl ayed a significant ro le in
fun ction. lt is interestin g to look at our group of 95 reducing the risk of mi scarriage fo r these patients 1º· 11 •
couples who did conceive and compare the diagnoses
pre and post PT eva luati on. We had a dramatic in- Achieving a li ve birth is not the only parameter by which
crease in the categori es of low progesterone, low estra- we judge successfu l treatment with NPT. Couples are
dio l and unfavo rab le mu cus. The gro up of un ex pl ained clearl y in fo rm ed at the outset that they may not suc-
inferti lity was practically eliminated. This retlects a sho11- ceed, but we do wa nt to give them the best chance
coming in the present eva luati on process for couple possib le before reaching the end ofthe program. Whil e
with infe11ili ty. The timed hormonal blood tests for both every effort wi ll be made to help each couple to con-
progesterone and estradiol5 help us to identify subtle ceive, we do not want to reach thi s goa l at the expense
defic iencies that are impl y not diagnosed with a day 2 1 of th eir hea lth, the ir sa nity or rel at ion ship . Many
blood test that does not pay any attenti on to the time of coup les report fee ling hea lthi er and say th at NPT has
ovulation. In addition, the CrMS can di agnose abnor- helped them to accept involuntary childl ess ness in a
rnal mucus tlow and abnormal bl eeding pattems that way whi ch ART co uld never do. Restorati on of gyne-
otherwise pass unnoti ced . co logic hea lth and a strengthenin g of the re lati onship
are also successfu l outcomes which have not been mea-
The surg ical interventi ons are worth em ph asizi ng as sured in the figures reported. This is the experi ence for
well. Many couples with a diagnosis of endometriosis the majority of coupl es and makes the process a re-
ha ve not had effective surgery to correct this . We have ward ing and fu lfilling one fo r the phys ician and pa-
had sorne couples, who were ori ginall y deemed to have tients ali ke. Adopti on is also viewed as a very positive
a normal pelv is fo llowi ng laparosco py and dye test. A outcome for th e coupl e if it is not poss ib le for them to
second look laparoscopy through our program , fo ll ow- ha ve a chi ld oftheir own.
ing referral to a known ski ll ed gyneco logist frequently
found pre viou sly undiagnosed endometrios is. Ad- PT pregnancies are very di ffere nt from ART pregnan-
equate detection and remova l of endometriosis improves cies in many respects. The imm edi ate and most striking
di ffe rence is that we have a very low incidence of twin s, lt i likely th at a signi ti cant number of previously unex-
and in th e lri sh program have not yet had triplets. The plained infertil e couples may have ubtle hormonal or
incidence of multipl e births is ju t 3.4 percent, compared mucus abnormaliti es which can be detected using the
with a multipl e birth rate of 1.2 percent without fertili ty CrMS and N PT techniques. ldenti fy ing these abnor-
treatment, nin e percent with clomiph ene in general use maliti es will surely lead to estab lishing a di agnosis fo r
and an average of 53 percent fo r ART progra ms in the in fe11ility in more cases. When medica ! and surgical in-
USA 12 . Multiple births are more prone to prematuri ty, terventi ons are appli ed in cooperati on with a system
whi ch increases the incidence ofcompli cati ons uch as whi ch empowers th e coupl e through edu cati on and
cerebral pal sy, respiratory and gastro-intestin al prob- stress management, hi gher pregnancy rates do occu r,
lems. Premature delivery often res ults in a pro longed espec iall y if treatm ent is extended o ver a two-year pe-
stay in the Spec ial Ca re Baby Unit to dea l with the ri od of time.
newborn 's medi ca ! problems 13 • Obv iously thi s places
an increased burden on hospital resources as treatm ent Evidence is accumul ating in favo r of PT as the method
ca n be prolonged and ex pensive. PT ca n signi ticantly ofc hoice in pro moting fe rtility awareness, maintaining
reduce these prob lems. gynecol ogic hea lth and treating couples with infe rtility
and recurrent miscarriage. lt is an uncomp licated com-
Another striking di ffe rence with PT is that once a mon sense approach to understand and treat nearl y
couple have had a succes ful pregnancy, their chances every cause of infe rtili ty. Thi s chapter has shown the
of subsequent successful pregnancies are excell ent. effecti veness of NPT, even in ca es of long standing
NPT is a correcti ve treatm ent whi ch restares norm al re- infe rtili ty, advanced fe ma le age and prev ious fa iled at-
producti ve fun ction. Hav ing identifi ed and corrected tempts at IVF. The tragedy in medi cine today is that
the abnormality which prev iously prevented a success- phys icians often adopt high-tech, in vasive approaches
ful pregnancy, fu ture pregnancies occur qui te eas ily in with out adequ ately investi gatin g underlyin g patho-
most cases. A minority of couples wil 1 not conceive aga in, physio log ic cause , and simpler treatment options fo r
usually due to advanci ng female age, but many will suc- in fertil ity.
ceed with future attempts. Fou11een of our coupl es did
ha ve a second successfu l pregnancy and one of tbem Doctors need to lea rn how to think aga in ! Remember
even bad a third success. On e woul d ex pect thi s fig ure how to be a phys ician that uses your medica! know l-
to increase furth er with time as more coupl es return fo r edge as a mea ns of appl ying new approaches in a sen-
anoth er attempt. Thi s is not the case with ART whi ch is ib le manner. As the old Latin dictum goes " Primum non
circum ve ntive and not corrective in nature. lnfe rtil e nocere - First do no harm! " Most of the med ication s
couples genera ll y remain in fe11il e, even after they ha ve used in PT are currentl y used in many inferti lity pro-
had a successfu l IY F pregnancy.14 grams. PT di ffe rs primari ly in the way this treatment is
appli ed with res pect to the CrMS in a meth od ica l and
meas ured fa shion to restore normal reprodu cti ve fun c-
Conclusion ------------~ ti on. Trying to apply these treatments without using
the FertilityCare ™ System is worse th an trying to find
Remarkabl y, 42 percent of coupl es who attempted IVF your way around a new city without a map .... .you sim-
in the United Kingdom in 1998-1 999 had a di agnos is of pl y get lo t!
unexplained inferti lity2. Thi s must ca l! into questi on
co nventi onal in fe rtili ty eva luation protoco ls. How is it The N PT approach is new and exci ting. This chapter
possible with ali of the recent advances in modem medi- provi des evide nce that NPT is superior to conventi onal
cine that th is aspect of hea lth is so poorly understood? medi ca! approaches in the area of infertili ty. lt ques-
Obviously something is preventin g these 42 percent of tions current practi ce when a relati ve ly sim ple, mini-
coupl es from conceivin g - but thi s someth ing is not mally invas ive, fa mily physici an-based program can help
fo und with current diagnosti c techniqu es. 95 co upl es to achi eve 89 successful pregnancies de-
spi te a hi tory of prev iously fa iled ART.
Chapter 50 : NaProTECHNOLOGY and Pregnancy following Failed ART 675
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MG, Sap ienza F, Ma rtin ez F, eo be lli s L. lmp lan tati on In
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Pat ien ls Over 40 And Rai sin g FSH Leve ls- A Review. Pla-
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Effectiveness of NaProTECHNOLOGY
in the Treatment of lnfertility
T he surgical and medica! approaches to the treat-

ment ofinfe1ti lity using NaProTECHNOLOGY can
be assessed using sta nda rd statistical techniques . How-
beca use it does not acco un t fo r ali of those who mi g ht
ac hi eve pregnancy after being lost to fo ll ow-up. lts ac-
c uracy is directl y rel ated to the ability ofthe program to
ever, that can make it difficult to compare its results with maintain c lose short- and long-term fo ll ow-up .
the way that success rates are expressed for the a1tifi-
cia l reproducti ve techno logies. Thu , thi s chapter wi ll
beg in by reviewing the bas ic ways in which infertili ty Table 51-1: Ways to Evaluare Success
s uccess can be stati stica lly presented . of lnfertili ty T reatment
Statistical Techniques
Measuring Effectiveness _______, 1. Kaplan-Meier Survival Curves

- The most common ly used for all types of
infertility assessment
There a re two standard ways in w hi c h success has bee n - Presumes pregnancy will occur in patients
ex pressed over the yea rs . The most common ly used is who discontinue treatment
- Probably overestimates success
the Kap lan-Meier Surviva l Curve 1 (Tabl e 51-1 ). This is a
life-table approac h that has been the most common ly 2. " Per-Woman " Pregnancy Rates : Number of
used means of expressin g success of treatment, but it pregnancies observed/total number treated
- Does not account for those who achieve
does have tl aws. It presumes pregna ncy will occur in pregna ncy alter LFU
patients who discontinue treatme nt a nd/or are lost to - Significantly underestimates success
fo ll ow- up at the same rate as those who stay in treat-
3. Fecundability Rates
ment. The Kapl an-M eier Curve most li ke ly overestimates
- The number of pregnancies + Tota l number of
success as a result. exposure months
4. Cycle-by-cycle Success Rates

A second approach is to publi sh the "per woman" preg-
- Uniquely used for ART
nancy rate. Thi s is the number of pregnanc ies o bserved
di vided by the total numbe r ofwomen treated . This ap-
proach tends to s ignifi ca ntl y underestimate success
677
A third means of eva luating success is to calculate the

fecundibility rate. This is the number of pregnancie Table 51 -3: Data R eq uired fro m an ART Program
to Determ.ine Per·Woman Success R ates
divided by the total number of exposure months and
and Disco ntinuation Rates
expressed as a rate or percentage.
Lastly, the cycle-by-cycle success rate was uniquely

Cycle number of treatment, in numerical order
developed for use with the a11i ficial reproductive tech-
• Establish the number in the study popu lation
nologies of in vitro fertilization , ICSI, GTFT, etc. lt has Attempts per cycle for ART, in numerical order
been adopted by many peop le who have stud ied artifi- • Births per cycle of attempt
cial insemination procedures as well. 2 The cycle-by-cycle Discontinuations per cycle of attempt
uccess rates used in ART do not give an accurate evalu- • Number entering treatment in subsequent cycle
ation of what success an individual woman might ex- Percentage of cancellations
Continuation of such data collection over a
pect from the approach to treatment. lt is commonly period of at least six cycles
acknowledged that " per woman" conceptio n rates are
often not reported in IVF programs because th e drop-
out rate from these approaches is so hi gh. 3
The standard data collection and reporting data points A

that are necessary for presenting and assessing ART 9 p
effectiveness are identi fied in Table 51-2. 4 From these
data points, it is impossible to calculate the " per woman" ...
8
7
• p
o
Q)
success rate. The national report for the ART programs .e L
E 6
states that it is not possible to calculate "per woman" ::i
L
-
z 5
success rates because in the data co ll ection system ,
the woma n 's name is not avai lab le to the investigators.
eQ):
:.::;
4
3
• p
o
nl
However, that could eas il y be resolved in a way which a.. 2 o
maintains confidentiality. p
In order to ca lcu lare "per woman" success and discon- 1976 1977 1978 1979 1980
tinuation rates, it is necessary to have the information Calendar Period

presented in Table 51-3. However, the actual number of
B
women in the basic study population is often not re- p
9
ported. lt is, nonetheless, impo11ant because this is ulti-
... 8 o
mately th e most meaningful statistic to the individual Q)
p
.e 7
woman approaching infertility care. E
::i 6 L
Table 51-2: Standard Data Collected and

Presented to Assess ART Effectiveness 1
-
z
eQ):
:.::;
5
4 p
L
a..
nl
3 o
Standard Data Points·ART Ca lculation 2 o
p
Number of cycles
• Percentage of cycles resulting in pregnancies 2 3 4
Percentage of cycles resulting in live births lnterval Since Entry (Years)
Percentage of retrievals resulting in live births
Figure 51 ·1 : A graphic representation ot data needed tor a
• Percentage of transfers resulting in live births
lite-table analysis ot nine hypothetica\ patients treated for
Percentage of transfers resulting in singleton live births intertility. The darkened ci rcles are the time ot treatment; P,
• Percentage of cancellations pregnancy; L, los! to tollow-up; O, no! pregnant al !he termi-
• Average number of embryos transferred nation ot the study. A - patients are treated at variou s points in
• Percentage of pregnancies with twins time and patients who become pregnant do so after varying
• Percentage of pregnancies with triplets or more periods ot observa tion . B - patients are displayed after re-
• Percentage of live births having multiple infants coding the time of entry into the study (i.e ., the time ot treat-
ment) as time zero. While the actual start time ot treatment is
1. From: 2001 Assisted Reproductive Technology Success Rates: Na- different for each ot !he patients, in lite-table analysis , they
tional Summary and Fert ility Clinic Reports. U.S. Dept. Health and
Human Services, CDC, Atlanta and American Society of Reproductive can all be adjusted to a standardized starting point (From:
Medicine, December, 2003. Janes HW, Rock JA: Reparative and Constructive Surgery ot
!he Female Generative Tra e!. Williams and Wilki ns , Baltimore/
London , 1983, p. 27) .
Chapter 51: Effectiveness of NaProTECHNOLOGY in the Treatment of lnfertility 679
Kapl an- Meier curves use a li fe-tab le approach (Figure In assess ing the " per cycl e" success ra te as is ofte n
5 1- 1) and from that, a cum ulati ve pregnancy rate over a used in A RT approaches , it pres umes th at that preg-
pe ri o d of tim e ca n be ca lc ul ated ( Fig ure 5 1-2). nancy rate w ill be mainta ined in each subsequ ent cycle
Fec undability rates ca n be used to com pare o ne ap- of treatment, however, in most cases, th e cyc le-by-cycl e
proach to another beca use th ey ca lcul ate the number of success rate decreases apprec iabl y from one cycle to
pregnanci es that mi ght occur di vided by the total num- the next. Thi s is true, not o nl y in the artificial reproduc-
be r of exposure month s o r ex posu re cycle.5·6 ti ve technologies but a lso in natu ra l co ncepti on as well .
100
Results of NaProTECHNOLOGY_ _~
90
In thi s chapter, data w ill be presented in a va ri ety of dif-

80
fe rent ways on a tota l of 1,045 pati ents who have been
.~
a:,.. 70
treated fo r infe rtili ty by way of N aProTEC HNOLOGY .
The breakdown of data o n th ese patients is found in
.u
o
o
• • • • • • • • • • ;o:~
Tabl e 5 1-4 . Thi s po pul ati on of pati ents represents vari-
..
O>
~ 60 g~p
o us pati ents who have been treated a nd have, as or-
.
.-·
----
~
ga ni c causes of in fe rtili ty, endo metri os is, tuba! occlu-
....
>
.
'5
sio n, polycys ti c ovarian di sease, pelvic adh es ive di s-
u
§ 50
.
,.
. ease, anovulati on (amenorrhea), azoospermia, or in sorne
cases, unkn own causes . In additi on, thi s populatio n of
,.
40
,,
pati ents has been broken in to a number of diffe re nt sub-
, groups and these are identi fi ed in Tabl e 51-5. Thi s in-
30 , c ludes pati e nts di vided by differe nt types of ovul ation
•
20
.
,
•• defects, the presence or absence of a c umulu s oophorus,
10
Uncurved Table 51-5: N aProTechnology:
group
T he Va rious Subgroups used in Assessments
12 18 24 30 36 42 -----
48
Months of Follow· UP
54 60 66 72
Subgroups n
Fig u re 51 -2 : A schematic descriptio n of a cumulative preg- Ovulation Defects 249
nancy model. Relative proportions of patients in th e "cured " MF, AF, DRS = 176
and "uncured" groups ove r time are represe nted by the cali - IFS , LUF, PRS = 73
ber of the line (From : Guzick OS : Clini cal Epid em iology of En- Cumulus Oophorus 211
dometriosis and lnfertility. In : Roc k JA (Ed ): Endometriosis. +e.o . = 141
Obste! Gynecol Clin North Am 16 :4 3-60 , 198 9). - e .o . = 70
Mucus Cycle Seores 150
Regular= 34
Limited = 100
Dry = 16
Table 51-4: NaProTechnology Stages of Endometriosis 491
lnfertility Study Populatio n Stage 1 = 223
Stage 11 = 144
(N = 1045)
Stage 111 = 75
Stage IV= 49
Conditi on n %
Type of Luteal Phase Deficiency 275
Endometriosis 643 61 .5 Type 1 = 30
Type 11 = 99
Tubal occlusion 158 15 . 1 Type 111 = 26
PeOD 107 10 .2 Normal = 120
Pelvic ad hesive disease 34 3.3 In Town vs. Out of Town 874
In town = 713
Anovulation 11 1.1 Out of town = 161
Azoospermia 10 1.0 Age 874
Unknown 82 7.8 :ó 27 yea rs = 252
28-37 years = 561
Tota ls 1,045 100 .'.'. 38 =61
mucus cycle score calculations, the various stages of had an ovulation-related disorder, the presence or ab-
endometriosis, the presence or absence of a Type 1, ll or sence of a cumu lus oophorus, the type of luteal phase
IIl luteal phase deficiency, whether the patient is from deficiency andan age breakdown. The ana lysis wi ll be
" in town" (within 150-mile radius ofthe Pope Paul VI comp leted with an evaluation ofoverall " family bu il d-
ln stitute) or from "o ut oftown ," and also broken down ing."
by various age groups.
In Figure 51-3 , the cumulative pregnancy rate fo r the
This study population hadan average age of30.4 years infertility population treated with NaProTECHNOLOGY
(Table 51 -6) and an average length of time trying to is shown. ln this ana lysis, over 60 percent of patients
achieve a pregnancy of 3.42 years. Many of them had became pregnant by 24 months and nearly 70 percent
previous infertility testing prior to being seen in the by 36 months. This includes pregnancies from ali com-
lnstitute (Table 51-7) and many ofthem also had previ- ers including those who had severe ol igosperm ia, vari-
ous unsuccessful infettility treatment (Table 51-8). ous stages of endometrios is, tuba! occlus ion , etc. lt does
not, however, inc lude those patients whose husbands
These various groups are evaluated using Kaplan-Meier were azoospermic. ln the NaProTECHNOLOGY model
curves, " per woman" pregnancy rates and fecundability of infertility evaluation and treatment, azoospermic
rates. ln sorne cases, they will be compared, as best as couples are encouraged to look seriously at adoption
possible to various artificial reproductive approaches. as the solution to their family building.
lncluded in this analysis w ill be cumulative total preg-
nancy rates, pregnancy rates related to the use of the Early in the work ofthe CrMS , we fo und that some pa-
CREIGHTON MODEL System (CrMS) prior to medica! tients would become pregnant overa period of time if
evaluation and treatment, success rates relative to en - the only treatment they received was from the app lica-
dometriosis, polycystic ovarian di sease, pelvic adhe- tion ofthe CrMS itself. Furthermore, it was leamed that
s ion s, tuba! occlusion , oligospermia and anovulation. the type of mucus cycle mattered with regard to overall
In addition, the data will be evaluated from the point of pregnancy rates. The data in Table 5 1-9 was obtained at
view of the type of mucus cycle the woman had at the that time. In 40 patients who had limited mucus cycles
point of entry of the study program , whether or not she andan average length of infe1tility of 3.2 years, 16 of
them achieved a pregnancy in an average of5.4 months.
However, those patients who entered with dry cyc les
Table 51-6: Demographic Data
had significantly lower pregnancy rates with on ly 20
on All lnfertility Patients
percent (n = 1O) overa period of 12.0 months. Th is was
Data Point Mean the first indication that there was a distinction between
the capability of achieving pregnancy in women with
Age 30.4 years
different types ofvulvar mucus cycle pattems. The only
Gravidity O. 7 pregnancies
treatment that this group of patients received was
Length of time no IUP 3.42 years
supp lementation with Yitamin 8 6 and fertility-focused
Length of time on BCPs 3.22 years
intercourse.
Days of TEB ' 2.4 days
1. TEB; tail-end brown bleeding .
Table 51-8: Previous lnfertility Treatment

NaProTechnology Study Population
Table 51-7: Previous lnfertility Tests Treatment %

NaProTechnology Study Population
Birth control pills 76.7
Fertility drugs 38.9
Test %
Major surgery 20.4
Seminal fluid analysis 69.4 Laser surgery 11.4
BBT 68.4 Artifical insemination 7.3
Hysterosalpingogram 61.4 Cauterization 6.2
Laparoscopy 50 .2 Danazol 3.4
Endometrial biopsy 50 .2 Lupron 2.7
Hormone testing 47 .0 IVF 0.9
Ultrasounds 40.1 GIFT 0.6
Chapter 51 : Effectiveness of NaProTECHNOLOGY in the Treatment of lnfertility 681
Cumulative Pregnancy Rate of lnfertile Patients

t reated with NaProTECHNOLOGY
1.0-1-......._ .......+....._-....._+......._._.......-+-.......- .......-+-.......- .......,..
0.9 ------,-------r------1-------r------
1 1 1 '
' 1 1 1
0.8 ------~------- ~ ------~---- ~ ------

.s
"'
! 1 -r---:::
______ ,, ______ _ 1
O:: O.7
>-
u
•
e:
~ 0.6
Cl
e
c.. 0.5
Cll
>
-.;::;
..!!! 0.4
::::1
E
::::1
u 0.3
0.2
1
1 1 1 1
0.1 -----1-------r------,-------r------
o.o-J-......-.-......+ ......-.-......+ ......-.-......+""""'.....""""'+-""""'..,...""""'"'1-

o 12 24 36 48 60
Months of Follow-up
Figure 51 -3: The cumulative pregnancy rate of a large group of infertility
patients treated with NaProTECHNOLOGY (From : Pope Paul VI lnstitute
research , 2004). Th e light blue lines represen! 95-percent confidence inter-
vals .
Table 51-9: The Creighton Model System

Cumulative Pregnancy Rate of lnfertile
Outcome of Patients with Vulvar Mucus Anomalies
CrMS Users till Time of Evaluation
and lnfertility- No M edica! Treatment 1 by NaProTECHNOLOGY
Follow-up at Least Six Months lf Not Pregnant 0.4 +-.............-..._,,¡,,,........,_..._........................_.......................................,..
(N=SO)
Limited
Mucus Dry
Cycles Cycles ~
o:"' 0.3
Number of patients fol lowed 40 10 >-
u
... with primary infertility 24 9 e:
... with secondary infertility 16 1 "'e:Cl :·
Mean age
Range
28.3 yrs
20-37
27.5 yrs
22-35
e:
Cll
0 .2
Cll
>
+:;
Length of time trying to achieve
prior to comi ng to center "'
"5
Mean 3.2 yrs 3.6 yrs
E
::J 0. 1
Range 7 mos-10 yrs 1.5-6.0 yrs (.)
Number of pregnancies 16 2'

Percent 40.0 20.0
Length of time to achieve 6 12 18 24

Mean 5.4 mo 12.0 mo Months of Follow-up
Range 2.9 mo 10.14 mo
Figure 51-4: The cumulative pregnancy rate of infertility pa-
1. Sorne patients did receive supplementation with Vitamin 86. tients using only the CrMS up until the time of evaluation by
2. In the pregnancy cycles. the dry cycle pattem oonverted to a limrted mucus cyde.
NaProTECHNOLOGY (From : Pope Paul VI lnstitute research,
2004) .
More recent ly, we have followed those patients who Figures 51-6 through 51-12 : Cumulative pregnancy
began to cha1t their cycles, but achieved a pregnancy ra tes fo r patients with endometriosis trea ted wit h a
NaProTECHNOLOGY-driven approach to infertility. Patients
without direct medica! intervention . This is shown in with endometriosis. Data presented according to the AS RM
Figure 51 -4. Sorne patients do becorne pregnant as a stage classification of endometriosis (From : Pope Paul VI ln-
result of sirn ply charti ng their cyc les, knowing their time stitute research, 2004).
of ferti lity and uti li zing that inforrnation. This graph
shows those pregnancy rates up until the time that they
may ha ve been entered into the NaProTECHNOLOGY
prograrn.
In eval uating the success of NaProTECHNOLOGY in

patients with inferti li ty and endornetriosis, the tirst pre-
sentation of data is a comparison bet\veen the resu lts of
treatrnent with NaProTECHNOLOGY to the classic study
---
publ ished by Rock, et al. , in 1981 7 (F igure 5 1-5). Th is
study of the effect iveness of conservative surgery for
endometriosis has been used as the gold standard for - -- ----
- Stoge1
pregnancy rates associated with the surgical treatrnent .... _ Stage 2
- - - Stoge 3
- - Stoge4
Cumulative Pregnancy Rate of Endometriosis
36 42 48 54
Patients treated with NaProTECHNOLOGY
compared to Conservative Surgery
(Patients with Normospermic Husbands Only)
1.01+-----+----+----+------i----+-
0.9 - - - - - - -:- - - - - - - ~ - - - - - - - •' - - - - - - - •' - - - - - - - ·-' - 0 .9 Log RankTesl

' ' p ...9421
.
.! 0 .8
..
0.8 '
- - - - - - -:- - - - - - - ...' - - - - - - - ~' - - - '
--- L -------~------
' IX
>. 0 .7 ::."- --:------ ----:.·-- -- ------
' o
e
~ 0 .6
,! O.7 · - - - - - - -:- - - - - - - ~ -. - -
:
- - -~-------
'
L -------~-- --- -
' ' .
CI
"'
Q'. '' ''
o ' '
.
~ 0 .5
>. ~
. 0 .4
o
e:
"'
e:
Ol
~
0 .6
' •
. •
- - - - . - - - - - - - - - -: - - - - - - - 1-
:
t 1
3
e o.3
u"
0.2 ~
o..
CI>
.:!:
0 .5 . - - - - - - -:. - - ~- - - 1. - - - - - - f ------- ~ -------:-------. 0. 1
~
o.o~ ...................,....,........,......,_....,....,....,...,..,.....+
<V o 12 18 24 30 36 42
~ 04 - - - - ,
'
- - - - - - - 1 - - - - - - - r - - - - - -
'
-1- - - - - - -
::s ' '

o ' '
' '
0.3 - _,_ - - - - -- ~ - -- - - - - ~ ---- - - - . - -- - - - -·----- - -
' ' '
' ' '
~
1---+------~ -------i-------~ ------

: 1 1 :
0.2 _¡_- - - - - -
' ' • N•ProTECHNOLOGY
..
Pope Paul VI lnstitute
0.1 - - - - - -·- - - - - - - J - - - - - - -
' Conservative Surgery
' ' Johns Hopkins
'
' ' - Non-linear Regressíon
12 24 36 48 60 72
Months of Follow-up
Figure 51-5: Cumulative pregnancy rate of patients with en-
dometriosis treated with NaProTECHNOLOGY compared to
conservative surgery only. Patients with normospermic hus-
bands only (From : Pope Paul VI lnstitute research , 2004 and ~
Rock JA, Guzick OS, Sengos C, et al : Th e Conservative Sur- ~
gical Treatment of Endometriosis: Evalua ti on of Pregnancy
Success with Respect to the Extent of Disease as Catego-
rized Using Contemporary Classification Systems. Fertil Steril
35:131-137, 1981).
Chapter 51 : Effectiveness of NaProTECHNO L OGY in the Treatme nt of lnfertility 683
of endometriosis over many years. While the curve far

success in NaProTECHNOLOGY wou ld appear to be
significantly higher, statistical significance could not
be calculated because the raw data from the original
Johns Hopkins study was no longer ava il able far com-
parison. In both groups, on ly normospermic husbands
were included.
The success rates of NaProTECHNOLOGY in en -

dometriosis are also broken down by theASRM classi-
fication of endometriosis stage in Figures 51-6 through
~ 51-12 . In Figure 51-6, the cumulative pregnancy rates
~ for patients in ali faur stage of endometriosis, are
shown. Clearly those patients with stage 111 and stage
IV endometriosis consistently have lower pregnancy
rates. This is compared statistically far the various
stages of endometriosis in the remaining figures. There
was no statistically significant difference between stage
1 and stage 11 endometriosis or even stage 1 and stage
111 endometriosis. However, there was a statistically sig-
nificant difference between the success rates in stage 1
and stage IV endometriosis. In addition , there was a
statistically signiticant difference between the success
in stage 11 versus stage IV endometrios is and it carne
close to statistical s igniticance in comparing stage 111 to
stage 1V endometriosis.
Cumulative Pregnancy Rate of Patients with

Polycystic Ovarían Disease
Treated with NaProTECHNOLOGY
compared to Surgical Wedge Resection Only (N=48)
1.0
~ 08
a:
~ 01
0.9
i::: o.e
~ 0.5
Q) 0.8 --,
Q.
1V
~ a::
... .
0.4
3 >-
o
0.7 ---,----
§ 03
u e: ! 1 ' - :
' ' ''

~
"'e:
Cl
0.6
:--:----:--.-.~ :----,-- '
-, - - - - - - - -
~ ~
..-·
1
'
'
'
' ' •
c.. 0.5 -:- ---:----~--- • f----~----:---
t
Q)
> ' '
~ - '
__ , _ _ _ _ .J _ _ _ _ l _ '
0.4
:~ '
::::i
E
::::i 0 .3 L - - -1
u
0 .2
+ NaProTECHNOLOGY
0 .1 - -1 - - - - j -
Wedge Resection
' ' Johns Hopkins
- Non-linear Regression
. .,,
,,,,.,.,,.---- o.01~-.;...........;.....,.....;........;........,.~1w;---""'-""";;;¡;;¡.,.._
o 12 24 36 48 60 72 84 96 108 120
~ 04
./ Months to Follow-up
/.//-------
.Y
3
§ 0.3 ~ . Figure 51-13: Cumulative pregnancy rate for patients with
u polycystic ovarían disease treated with NaProTECHNOLOGY
~
0.2
~i./. compared to surgical wedge resection only. (From : Pope Paul
o 1 ~... .. .
~ VI lnstitute research , 2004 and Adashi EY, Rock JA, Guzick D,
et al : Fertility Following Bilateral Ovarían Wedge Resection: A
Critica! Analysis of 90 Consecutive Cases of the Polycystic
Ovary Syndrome. Fertil Steril 36:320-325, 1981 ).
In F ig ure 51-1 3, a comparison between the a pproac h of abi li ty to be successfu l with po lycystic ovarian disease.
NaProTECHNOLOGY and ova ri an wedge resection is
compared to the class ic descripti on fo r ovari an wedge In Figu re 5 1-1 4, res ults ofa group ofp ati ents with tuba!
resecti on in po lycysti c ovarian di sease by Adas hi and occ lu sio n are shown. Thi s presentati on includes ali
Rock, et al.,8 publi shed in 198 1. Cumulati ve pregnancy fo rms oftubal occ lusion including prox ima l, as well as
rates to ju s t a b ove 80 pe rce nt were see n in di sta l tuba! occ lusion. Cumulative pregnancy rates of
NaProTECHNOLOGY by the 36th month post ovaria n o ver 50 percent were observed at 30 months. The curves
wedge resecti on. A stati sti ca l compari son could not be fo r those patients w ith severe pe lvic adhesive disease
made because data fro m the ori g ina l John s Hopkins treated wi th Go re-Tex and tuba! occ lu sion treated with
stud y were no longer avail able. No netheless, it appears tuba! re-impl antation and Prolene stents are shown in
that the approach ofNaProTECHNOLOGY improved our Figures 5 1- 15 and 5 1- 16.
Comparing the cumu lati ve pregnancy rates in a genera l

NaProTECHNOLOGY
Cumulative Pregnancy Rate for Patients gro up of patients w ith infertility by looking at the fe rtil-
with Tuba! Occlusion ity po te nti a l of th e hu s b a nd a nd di v ide d b y
1.0
normospermia, and mild, moderate and severe oligosper-
0 .9 mi a, are shown in Fi gures 5 1-1 7 th ro ugh 5 1- 19 . There
.
.!
o::
0.8 . •. . . was virn1all y no di ffe ren ce between the gro up of pa-
ti ents w hose husbands had either mild or moderate oli-
>. 0.7
.
u
e
e
C>
0.6
gosperm ia (see Chapter 4 7). There was, however, a de-
crease in the cum ul ati ve pregnancy rate in those hus-
~ bands who had severe o li gos penni a (a lthough in our
o. 0.5
"'
.~
¡¡¡ 0.4
analys is, it was not statisti ca ll y significant). Nonethe-
:; less, it is di ffic ult to look at thi s presentation and not
E 0 .3
::1 see it as clini ca lly sign ifi cant. It should be po inted out,
u
0 .2 however, that even with severe o li gos permi a, reason-
0 .1
abl e pregnancy rates can be obta ined .
6 12 18 24 30 36 42 48 54 60 T hi s was looked at in a different way by foc using on a

Ordinal Months spec ific aspect ofth e semina l fluid analys is. We looked
Fig ure 51 -14: Cumulative pregnancy rates for pa- at nonn ospermi c husbands versus pati ents whose hus-
tients treated for tubal occlusion with
N aProTECHNOLOGY (N=158) (From : Pope Paul VI bands had ei ther a sperm count of S 1Omi lli on/cc, motil-
lnstitute research , 2004). ity _:::: 30 percent or the percentage of sperm that were
NaProTECHNOLOGY Patients NaProTECHNOLOGY Patients

Treated with a Gortex Graft Treated with a Prolene Stent
--·-·-+--·--t. ·-----t---+---t···--- :::-----t-----+--·- --~-----+--·

~ ----t--·---·f---l--+-·--t---·
O.S
0.8 -----r----¡---···--1--+------¡--- ~ o.8

o:: 0.7 _______ [______ i ____ j_ _
___ _l ____L---·-
~ ---+---t-----
---+----t-·-J-----+-----r-
~ ·-------·~- -·-i----···-t-----~---- ~-- --~--11__,___ _j__ --;-
0.7
0.6 ..-- .. ~ 0.6
! --·+·-·----t-----..·+-----11,__. :. -·+----·
~
0.5 .....-- ..
0.4 --·--+---.. . . t----+---· • ----+---

"'
il:
>
;"' o4
1
1
-----+---·
______ ¡_ ______
1
o.s ----L-·----·L- - - ,----
1 1 '
_i-...·-- ----- -----+----
•
3E 0.3 ----¡----+ 1 1
----+t
.. 1 1 1 1
~ º·3 ------r----·1----+--~- t---1---· 8
1 1
----+·---r--
----r·1 -¡·1 ---+--¡
1 1 1
u:: =t:~t::· 1
0.2
0.1
•
o.o~.........,...,1
l
--¡----¡
-¡-1----1----¡--¡- ! 1
......~...+~......+...--¡..,....~-+-~-+
O.O
o 6 12 18 24 30 36 o 6 12 18 24 30 36
Months of Follow-up Months of Follow-up
Figure 51-15: Cumulative pregnancy rates for pa- Figure 51-16: Cumulative pregnancy rates for pa-
tients with severe pelvic adhesions treated surgi- tients with proximal tubal occlusion treated surgi-
cally with Gore-Tex (From : Pope Paul VI lnstitute re- cally with tubal re-implantation and Prolene stents
search , 2004). (From : Pope Paul VI lnstitute research , 2004).
Figure 51-17 through 51-19: Cumulative pregnancy rate of Figures 51-20 through 51-22: The cumulative pregnancy
inferti lity pa ti ents whose husbands have mild , moderate or rate of infertility pa tients with normospermic husbands ver-
severe oligospermia compared to !hose patients w ith sus husbands with less than 10 million sperm/cc, s 30 per-
normospermia (From: Pope Paul VI lnstitute research , 2004). cent motile sperm or s 30 percent normal morphology (From :
1.0
0.9
.
.!!
e;
0.8
0.7
."
e:
e: 0.6
"' 0 .5
E
"-
"
.?
;;; 0.4
:;
E 0.3
"
(.)
0.2 Mild Oligospermia
Normal
0.1
o.o
o 12 30 36 42 48 54
41 o.e
;;;
o::
>- 0.7
"~
e:
0.6
.t""' 0 .5
.~ 0 .4
;;;
:;
E
"
(.)
Moderata ollgospermia
Normal
O.Q - - --.- Log Rank Test

p= .1766
41 0.8 m o.a
;;; ;;;
o:: o::
>. 0.7 >. 0.7
"e:~ 0 .6 "e:~ 0.8
il:""' 0.5 "'E

Q. 0 .5
~
."
:;
0 .4
E o.3
"
(.)
Severe Ollgospermla
Normal
normal in appearance .'.S 30 percent (us ing standard mor-

phology eva luation, not Kruger 's). The cumulative preg-
nancy rates for this group of pati ents are shown in Fig-
Tabl e 51 -10: Ca u ses of A n ovulati o n
ures 51-20 through 51-22 . Wh en looked at in thi s fas h-
NaProTechno l ogy Stu dy Popul ation
ion, the di stinctio ns appeared to be mo re prominent and
(N=ll )
most likely clinically s ignificant, although they did not
approach statistical s ignificance. Total Total
Cause n Pregnant %
In our population of pati ents, we had 1 1 patie nts w ith Kallmann syndrome 100.0
anovu lation. In thi s group, one had Kallmann synd rome, Hyperprolactinemia
one had a pituitary adenoma assoc iat e d w ith (pituitary adenoma) 100.0
hyperprolactinemia and nine pati ents had hypothalam ic Hypothalamic amenorrhea 9 7 77.8
ame norrhea. Ofthese 11 patients, 9 succeeded in achiev-
Total 11 9 81 .8
ing pregnancy (8 1.8%) (Table 5 1-10). Thi gro up of pa-
tie nts showed the overa!! best success rate of any popu-
lation of patients that we ha ve observed.
In F ig ures 51-23 through 51-25 , the cumul ative preg-

nancy ra tes in a g roup of patients w ith e ndometri osis
Cumulative Pregnancy Rate of Endometriosis Patients treated with NaProTECHNOLOGY

By Mucus Cycle ~lassification
p=0.8513 (log Rank)
; 0 .8
"'il'
~
~ 0 .6
!"'
o..
~
~ 0.4
:;
E
- Regular Mucus Cydea(n•34)
8 02 - Regular Mucus Cycles (n=J-4) - Limrted Mucus Cydes (n,. 100)
- Regular mucus cycles (n=34 ) - Limited mucus cycles (n=100)

- Dry cycles (n=16) - Dry cycles (n=16)
36 48 60
Figures 51-23 through 51-26 : Th e cumulative pregnancy rates far patients with endometriosis treated with
NaProTECHNOLOGY divided according to the classifica tions of the mucus cycle . All three types of mucus cycles are shown
in Figure 51-23 and various compa risons of regular mucus cycles , limited mucus cycles and dry cycles in the remaining
presentations (From : Pope Paul VI lnstitute research, 2004) .
are broken down by the mucus cyc le classification. A li Figures 51-27 through 51-29 : Th e cumulative pregnancy
rate for infertility patients with various types of ovu lation -
three c lass ifi cations are presented in Figure 5 1-23 and re lated defects. In Figure 51-29, the combination of the two
in the remaining figures , they are ali statistically evalu- groups are shown together. The difference is statist ically
ated . There are two things that are striking. First ofal l, significantly different (From: Pope Paul VI lnstitute research ,
the overa! ! pregnancy rate between regular mucus cycles 2004).
a nd limited mucus cyc les is not s ign ificantly different
one from the other. Keep in mind , however, that this
includes the treatment of these and in many cases, the
limited muc us cycle group were converted to more regu-
lar mucus cyc les with the use of mucus enhancers and
their ovulatio n abnormalities and foll icular and lutea l
phase deficiencies were also treated (and , of course, ~ 0 .8
~
their endometriosis was also treated- surgica lly). There ~ 07
o
is, however, a statistica lly significant difference between e
~ 0 .6
the cumul ative pregnancy rates in patients who have .Cl
regular mucus cycles vers us dry cyc les (Figure 51-25) ..

o:..
~ 0 .4
0 .5
and limited muc us cyc les and dry cycles (Figure 51-26).
This sig nifi cant decrease in pregnancy rates assoc iated ~"' 0.3
w ith dry cyc les is extreme/y importan/ and has not pre- o" 0 .2 - Mature Folicle
. .._ Affolicularism
vious ly been reported . Delayed Rupture
1n Figures 5 1-27 through 51-29, a comparison of the

cumulative pregnancy rate in infertility patients by type
ofovulation-re lated defect is identified. In Figure 5 1-27,
no s igni ficant d ifference ex ists in the pregnancy rates
in patie nts with mature fo llicles, afo lli c ul arism ora de-
layed rupture pattern. In Figure 5 1-28 , the pregnancy
rate in patients with immature fo llicles are very similar to .! 0.8
the previous gro up but those pregnancy rates with par- "'
~ 0.7
o
e
tial ruptures o r lute inized unruptured fo lli cles are lower ~ 0.6
and when the three types of ovu lation defects are com- ~"'
bined into two groups and co mpared in Figure 5 1-29 , ~
. 05
the gro up conta ining the unruptured fo ll icle group has ~

0 .4
0.3
---
a statistica ll y significantl y lower cum ul ative pregnancy o" 0.2 - Inmaturo Folicle
rate (p=.023). -- - Partial Rupture
Lutenized Ulruptured Foi cle
ool : ...........,......:;;;,;;;:;:;;;:;;;;;:;:;;;:;;;;;:;:;;;:;;;;:;;::;;:;;:..J
The next assessment is comparing those w ith pre-exist- o
ing fo llicu lar ultrasound stud ies that show either a posi-
tive or negative cumulus oophorus. The pregnancy rates
for these two groups ofpatients were basically the same
as shown in Figure 5 1-30. Again, keep in mind that these
patients were treated with ovu lati on-inducin g medi ca-
tions. This data suggests that with appropriate treat-
.., o 8
.!
ment, by stimulati on of the foll icle, one can obtain a o::
,., o 7
o
secondary effect of further development of the cumu- e
~ 06
lus oopho rus and maturation ofthe ovum .
~"'
.
~
..,
0.5
04
In Figure 5 1-3 1, the cumulati ve pregnancy rate in a group :;
E o.3
of patients with endometriosis w ho were treated but
o"
also had luteal phase deficienc ies are compared. The - COO"boAF, MF, DRS
overa ll cumul ative pregnancy rate fo r a Type l, 11or111 COO"bo IFS, PRS, L~
lutea l phase deficienc y (a li of which were treated) is o.o. -.....................--------~

o
indistinguishab le from those with normal lutea l func-
tion .
688 The Medica! and Surgi ca l Pra ct ice of NaProTEC HNOLOGY
Cumulative Pregnancy Rates for lnfertility Three different age categori e were also compared. Thi s
Patients with Positive vs. Negative included those pati ents who were S 27 years of age, 28
Cumulus Oophorus to 37 years ofage and 2: 38 years of age. The cumulative
1.0 - - - - - - - - - - - - - - - - - -..........
pregnancy rates for these patients are shown in Fi gures
0 .9 ¡-
, --,-- --,- -1- 5 1-32 through 51-35 . There are differences between the
th ree different age categori es and in each case, the di f-
Q) 0 .8
~ fe rences are stati sti ca ll y significa n!. However, the great-
a: ' '
>-
(,)
0 .7 - - - J.. - - - L. - - - -·- - - - _._ - est di ffe rence is seen in the age group 2: 38 years. Thi s
e: is typi ca l of presentati ons of simil ar data by others.
:g 0 .6
Cl
a:
Q)
Q)
0 .5 The pati ents were al so class i fi ed by geograph ic cat-
.:!:: 0.4 egory (f igure 51 -36). They were either cl ass ified as " in
~ town" which mea nt that they were within a 150-mile
"3
' - -- --
u
E
::::1
0 .3
0 .2 -- ~ _ ~
;- - -
_..__......__..._
Positil.€ Cumulus oophorus
__ _..__....._....,
radiu s of the Pope Paul VI ln stitute or "out of town"
whi ch meant that th ey were outside ofth at rad ius. Th e
ln stitute sees a large number of pati ents from outs ide of
0 .1
Negatil.€ Cumulus oophorus
a 150-mile radius at thi s time. In thi s case, the cumul a-
ti ve pregnancy rates in both ca tegori es were very simi-
O.O
o 6 12 18 24 30 36 42 48 54 60 lar, although the "out-of-town" group was sli ghtly lower
Ordinal Months than the " in-town" gro up. The di stincti ons between th e
Figure 51-30 : The cumulative pregna ncy rate for infertility two groups were not stati stica ll y significant and most
patients with positive or negative cumulus oophorus (From: likely not clinica ll y significan!.
In NaProTECHNOLOGY, if medical treatment is not suc-
cessful , then support fo r adoption as afa mily -building
technique is incorporated into the overall pl an of ac-
ti o n. Ado pti o n is not see n as a "fa ilur e" of
NaProTECHNOLOGY or a fa ilure ofmedical treatment.
Cumulative Pregnancy Rate of
Endometriosis Patients with Luteal Phase lt i recogn ized as a rea li sti c mea ns of build ing on e's
Deficiencies of Progesterone vs. Normal fa mil y when medi ca ! treatment fa il s, keeping in mind
1.0- i - -............................._......_._......._ _ _.....___._................ that there is no system of in fe rtili ty eva luati on and treat-
ment whi ch comes clo e to approaching 100 percent
0.9 - - - - - - - - - - - ,. - - - - - - - - - - - ' - - - - - - - - - - - -r - • - - - - - - - -
success rates. Eva luati on of a large group of pati ents
~ 0.8
who were treated fo r endometriosis, looking at both the
a:
111 cumul ati ve pregnancy and adopti on rates, is identifi ed
>- 0.7 -< - - - - - - - - - - • - - - - - - - - - - - -t- - - - - -
in Fi gure 5 1-37. Ass isting coupl es in achi evin g such a
(,) ' '
e: ' '
:g 0 .6
hi gh rate offamil y build ing is acknow ledged as a ve ry
Cl s ig nifi ca nt acco mpli s hm e nt of th e wo rk in
~
a. 0.5 NaProTECHNOLOGY.
Q)
>
~ 0.4
111
"3 The fecun dabili ty rate in NaProTECHNOLOGY can be
E
::::1
0.3
Type 1 Def.(n=30) compared to conventional approaches oftreatment and
u ------ Type 11 Def. (n=99) to in vitro fe rtili zati on in pati ents who ha ve endometri o-
0.2 ;'-- - -:- - - -----
1-
___ J_ _ _ _ _ _¡' _ _ _ _ _ _ _ - -- Type 111 Def. (n=26) sis and polycystic ovarian di sease. Thi s is shown in
_
0.1 - - Normal ( n= 120) Tabl e 5 1-11 . When comparing the fecundabi lity rate in
endometriosis using NaProTECHNOLOGY approaches,
O.O
o 12 24 36 48 th e rate is 3.11. Thi s compares to 1.82 in the ori ginal
Ordinal Months Rock analys is. NaProTECHNOLOGY is significantl y
Figure 51-31 : The cumulative pregnancy rate for patients hi gher (Table 5 1-11 ).
with endometriosis who have either a Type 1, 11 or 111 luteal
phase deficiency vs. normal luteal function (From: Pope Paul In a similar fashion, NaProTECHNOLOGY was compared
VI lnstitute research, 2004). to the Adashi , Rock work in polycysti c ovaries. The
fec undabili ty rate with NaProTECHNOLOGY was 4.38
vs. 1.34 and , aga in , thi s is signifi cantl y different.
W hen comparing the overa ll fecundabi li ty rate and centon average, wi ll discontinue therapy. IVF is a treat-
NaProTECHNOLOGY to in vitro ferti li zation , however, ment w hi ch is on ly successful if it is used. Thus, with
the fecundabil ity rate is signifi cantl y less. The rate in discontinuation, comes a lower "per woman" pregnancy
NaProTECHNOLOGY is 3. 13 vs. 13.3 9 and 14.3 .1º rate.
While the fec undabi li ty rate in NaProTECHNOLOGY is This is summarized in F igures 5 1-38 and 5 1-39. ln Figure
lower, the overa ll "per woman " pregnancy rate contin- 5 1-38, the " per wo man" pregnancy and family-b uilding
ues to be higher when compared to the artificia l repro- rates by different organi c ca uses ofinfertility, are com-
ductive technologies. One ofthe reasons for this is the pared to the results of severa! different eva luations of
sharp dropout or di scontinuatio n rate in patients who in vitro fe rtili zation. lt is diffi c ult to ma ke these com-
undergo IVF treatment (Tab le 51-12). T hree different parisons because so few studi es in IYF a llo w for the
gro ups of data for IYF are compared and by the third calculation of " per wo m a n" s uccess ra tes. Thus , the
cyc le, of th ose who are not yet pregnant, nearly 90 per- studies quoted range from the yea r 1986 through
~~:~-~-·~----------·--:---------
..... -- - s Age 27
··• - Ages 28 - 37 - s Age27
-·• ·· Ages 28 - 37
2 Age 38
0.0.-....,,....,....,....,_ _...,...........,.....,.....,............+- 0.0--....,,-............................- .........................
o 12 18 24 30 36 42 48 54 60 o 12 18 24 30 36 42 48 54 60
Ordinal Months Consecutive Ordinal Months
0 .9
..
.!
a:
0.8 0 .8
log Aank Test
p = .0119
~ 0.7
..
e
e 0.6
"'e
.
11. 0 .5
>
~ 0 .4
:;
§ 0 .3
u ---
2 Age 38
o . o ~...,......,.......,....,..,........,.........,.........,......,........,.....,.f-
o 12 1B 24 30 36 42 48 54
Consecutive Ordinal Months
Figures 51-32 through 51-35 : The cumulative pregnancy rate for all infertility patients treated with NaProTECHNOLOGY
divided according to age ca tegories- 5.27 years , 28 to 37 years , ~38 years (From : Pope Paul VI lnstitute research , 2004).
NaProTECHNOLOGY
Table 51-11 : Co mparison of Fecundity Rates
Cumulative Pregnancy Rate of
All lnfertile Patients N aProTechnology vs. Conve ntional Therapy vs. IVF
Treated in Town vs. Out of Town Endometriosis/ PCOD
1.0
Fecundabiiity . Odds rátio
Melhodól.ogy rilté (OR) \ .pcvalue•
0.9
Log Rank Test
CI> 0 .8
p =.2644 Rock
¡;; (Endometriosis/CS E)' 1.82 1.0
a: NaProTechnology
~ 0.7 (Endometriosis) 3. 11 [ill <.0001
e:
CQ Adashi , Rock (PCOD/WR)3 1.34 1.0
e: 0.6
CI NaProTechnology (PCO D) 4.38 l 3.27 1 <.0001
....CI>
fl.. 0.5 NaProTechnology (ALL) 3.13 1.0
CI>
> IVF (Hogan)' 13.3 l 4 25 1 <.0001
~ 0.4
~ IVF (Guzick) 5 14.3 l 4 571 <.0001
;::¡
E
;::¡
0.3
1. Fecundability Rate - Number of Conceptions/Patient Months of Exposure.
(.)
2. Rock JA, Guzick DS, Sengos C , et al: The Conservative Surgical Treatment of
0.2 ~ lnTown
Endometriosis: Evaluation of Pregnancy Success with Respect to the Extent of
···<>··-Out Of Town Disease as Categorized Using Contemporary Classification Systems. Fertil
0 .1 Steril35:131-137, 1981 .
3. Adashi EY, Rock JA, Guzick D, et al: Fertility Following Bilateral Ovarian Wedge
Resection : A Critica! Analysis of 90 Consecutive Cases of the Polycystic Ovary
O.O Syndrome. Fertil Steril 36:320-325, 1981 .
o 6 12 18 24 30 36 42 48 54 60
4. Hogan, JW: ldentifying and Addressing Data-Analytic Challenges in IVF and
Months of Follow-up ART lntemational Symposium: Frontiers in Reproductive Endoclinology. March
27-31 , 2001 , Washington , DC.
Figure 51-36 : Th e cumulative pregnan cy rate for ali infertility 5. Guzick DS, Wilkes C , Jones HW: Cumulative Pregnancy Rates for In Vitro
patients divided according to whether they are geographi - Fertilization. Fertil Steril 46:663-667, 1986.
cally "in town " or "out of town." 6. Chi-square analysis.
NaProTECHNOLOGY and Family Building

Combined Cumulative Pregnancy and
Adoption Rate for Endometriosis Patients
0 .9
-
Q)
co
a=:
1/)
1/)
0 .8
0 .7
~ 0 .6
u
::::1
(/)
0.5
Q)
>
:;;
.!2 0.4
::::1
E
::::1 0 .3
(J
0 .2
0.1
o.o -fitr.,.,.;.,,.,.,.,¡.,.,.,,.,.,.,,.,.;.,,.,.,.,~""""""",.,.,.,~Tl""l'TT'l.,.,,......Tl""l'TT'l.,.,,......'f-
o 6 12 18 24 30 36 42 4 8 54 60 66 72 78 84 90
Ordinal Months
Figure 51-37: The combined cumulative pregnancy rate and adoption rate
fo r endometriosis patients treated with NaProTECHNOLOGY. This graph
in dica tes the o ve ra ll fa mil y-bui ldin g rate asso c iated wi th
NaProTECHNOLOGY (From: Pope Paul VI lnstitute research, 2004 ).
Chapter 51: Effectiveness of NaProTECHNOLOGY in the Treatment of lnfertility 691
20 02. H o w ever, in fi ve categories of a ppl ication in

Table 51-12: Discontinuation of Therapy Rates
NaProTECHNOLOGY, the " per woman" pregnancy rates
in IVFTrea tment
a nd fa mil y-building rates are stati stica ll y hi gher than
Curnulative percent the comparable " per woman " pregnancy rates in TVF. 1•3 ·9
discontinuéd treatrnent
Hogan 2 Güzick' Sharrna'
In the case ofth e study by Sharma, et al .,3 different "per
After the ... 2001 1986 2002 wo man" success rates can be identified. These range
First cycle 43 .0 52.0 64.5
from a high of 47.2 percent to a low of 23 .5 percent.
Second cycle 70 .2 73.3 89 .5 Howeve r, the uppe r range is obtained by transferrin g
Third cycle 84 .7 87.0 97 .6 more than two e mbryos. When :::; 2 embryos are trans-
Fourth cycle 92.2 94 .0 fe rred, the n the rate decreases to 23. 5 percent. This lat-
Fifth cycle 96. 1 96.7 te r stati sti c is more comparabl e to the ove rall o utcome
1. The percent of patients not pregnant who disoontinue treatment . of NaProTECHNOLOGY w he n lookin g at suc h factors
2. Hogan, JW: ldentifying and Addressing Data-Analytic Challenges in
IVF andART. lntemational Symposium: Frontiers in Reproductive En- as the multiple gestation rate and is co ns istent w ith the
docrinology. March 27-31 , 2001 , Washington , DC.
3. Guzick DS, Wilkes C, Janes HW: Cumulative Pregnancy Rates for In
c urrent effort to promote:::; 2 embryos per tra nsfer. 11· 13
Vitro Fertilization. Fertil Steril 46:663-667, 1986.
4. Sharma V, Aligar V, Rajhowa M: Factors lnfluencing the Cumulative
Conception Rate and Oiscontinuation of In Vitro Fertilization Treat- These same " per woman" pregnancy and fa mi ly-build-
ment for lnfertility. Fertil Steril 78:40-46, 2002 .
in g rates a re conve rted to odds rati os in F ig ure 51-3 9
a nd are co mpared to wh at has been kn o wn as the
Figure 51-38 : The "per woman "

" Per Woman " Pregnancy and Family Building Rates
pregnancy and fami ly-building rates
comparing NaProTECHNOLOGY NaProTECHNOLOGY and IVF
81.8
and in vitro fertilization (From : Pope
Paul VI lnstitute research, 2004 and
the listed references) .
e:
~
Ql
50
a.
o
Anovulation Family PCOD Ende- Tubal IVF IVF IVF IVF IVF
NaPro Building NaPro metriosis Occlusion Tubal General General General Endometriosis
1 ~8~b~ 1
NaPro NaPro Occlusion 1986 2001 s 2ET 1986
1<0001 1 l <.0001 1 ~ 1986 (Guzick) (Hogan) 2002 (Guzick)
(Guzick) (Sharma)
Figure 51 -3 9: Comparison of the

Comparison of Odds Ratios of " Per Woman "
odds ratios of "per woman " preg- 3.52 Pregnancy and Family Building Rates
nancy and family-building rates
NaProTECHNOLOGY vs. IVF
comparing NaProTECHNOLOGY to
in vitro fertilization (From : Pope Paul 3.0 2.80
VI lnstitute research , 2004 and 2.67
stated references ).
.Q
~ 2.0
:g"'
o
1.0 --- --------IVF

,-.0------·---
o.o Family Family Endometriosis PCOD Tubal

Building 1 Building" Na Pro Na Pro Occlusion
Na Pro Na Pro NaPro
l<.0001 1 1<0001 1 l <.00011 l <.00011 1 .0216 J ~. g:::;::~:~~= ~=(~~~J';uzidl)
fertility rate and the hi gh discontinuation rate wh ich

Table 51-13: Success of Treatment for ultimatel y lowers the overall " per wo man" pregnancy
Endometriosis-related lnfertili ty: rate.
A Meta-Analysis of Diffe rent Approac hes-
per Woman Success Rates Th is ana lys is , which has attempted to present mul -
Per woman
tiple different aspects of the questions re lated to
Treatment program pregnancy rates NaProTECHNOLOGY and provides a framework u pon
which fuh1re stud y and evaluation can be cond ucted,
IVF 9.9
appears to show that NaProTECHNOLOGY exceeds the
IVF total s 17.6
conventio nal means of treating in fe1ti li ty by surviva l
IVF + GnRHa 32.4
curve analys is, " per woman" pregnancy rates and fe -
Surgery 55.3
cundab ili ty rates. In addi tion , it exceeds the artific ial
From : Campbell JS, Pasta DJ, Adamson GD: Preliminary Meta-Analy- reproductive technologies in treating infertility whe n
sis Comparing in Vitro Fertilization with Surgical Treatment far Mod-
erate and Severe Endometriosis. J AM Assoc Gynecol Laparosc 2:56- eva luated by surviva l curve analysis a nd per woman
57, 1995.
pregnancy rates. However, when looked at from a fe-
cundabili ty point of view, the artificial reproductive tec h-
nologies show higher rates than NaProTECHNOLOGY.
" gold standard " in the treatment of in fertility over
the last 25 years , IVF. In eac h case , once aga in , the There are severa! important points that need to be kept
NaProTECHNOLOGY rates are higher than the IVF rates. in mind relative to this d ata. First of a li, in
NaProTECHNOLOGY, the number of women who will
This should not be considered terribly surpris in g. A eventual/y achieve a pregnancy is higher than the
randomized contro ll ed tri a! of either IVF ora sta ndard number of women who will achieve a pregnancy with
infertility treatment algorithm wa published in 1999 by the artificial reproductive technologies. While it is true
Kara nde, et al. 14 In this case, the use of a stand ard infer- that it may take lo nger to achieve that pregnancy, the
tility treatment algori thm resulted in a higher pregnancy actua l goa l of ac hi ev ing a pregnancy is hi g her with
rate a nd lower cost than IVF. A s imil ar comparison was NaProTECHNOLOGY.
made by Campbe ll , et al. in 1995 15 (Table 51- 13). Agai n,
traditional forms oftreatment fo r endometriosis-re lated Seco ndl y, in NaProTECHNOLOGY, the underlyi ng
in fert ili ty revea led hi gherpregnancy rates tha n the a rti- causes of infertility are investigated and, in man y cases,
ficial reproductive tec hnolog ies. identified and treated. In ART, these are neither in vesti-
gated nor adequate ly treated.
Conclusions __________ __~ Thirdly, the s uccess rates c ited here for
NaProTECHNOLOGY are expected to improve even fur-
The abil ity to eva luate success rates in infertility treat- ther in the years ahead as surgi cal techniq ues ad vance
ment can be very complex and difficult. In fact, sorne and our abi lity to treat ovarian and target organ dys-
have wondered wheth er or not sorne a uthors under- function (OTOD) progressively improves .
stand their own data . 16 Survival c urve ana lys is, " per
wo man" pregnancy rates and fecundability rates can Finally, in NaProTECHNOLOGY, the multiple pregnancy
be used to cond uct th is type ofan eva luatio n. In addi - rate is onl y 3.2 percent, wh ich is mo re than 10 times less
tion , cycle-by-cycle pregnancy rates can be utilized as than w hat is seen in mostART programs. So, while the
well and have been used almost exclusive ly by the ad- speed to pregnancy may be somewhat higher for those
vocates ofthe artificial reproductive technologies. What wome n who actua ll y ac hieve a pregnancy in the ART
is often overlooked is the decreasing, cycle-by-cycle programs, the pregnancies are much mo re compl icated.
1. Kapl an EL, Meier P: No n- Para metr ic Es timati on from In- 9. Hoga n JW: ldenti fying and Add ressing Data-A nal ytic Chal-
comp lete Observati ons. J Am 5tal Assoc 53:457-48 1, 1956. lcnges in Studies of IVF and ART. In: lntern ati onal Sympo-
si um on Frontiers and Reproducti ve Endocrin ology. 5erono
2 . Oli ve DL, Ha ney AF: End ometrios is-Assoc iated ln ferti li ty: Sy mposia USA., Washington DC March 27-31, 2001.
A Crit ica! Rev iew ofTh erapeutic Approaches. Obstel Gyneco l
Surv 41 :538 -553, 1986. 1O. Guzick DS, Wilkes C, Jones HW: Cumul ati ve Pregnan cy
Rate s for In Vitro Fertili zati on. Ferti l Steril 46:663-667 ,
3. Sharma V, Ali gar V, Rajkhowa M: Factors ln íluencing the 1986.
Cumu lat ive Conception Rate and Discontinuati on of In Vitro
Fe rtili zation Treatment for lnfertilit y. Fertil 5teril 78:40- 1 1. Jones HW, Schnorr JA: Mut liple Pregnanc ies : A Ca ll to Ac-
46 , 2002. tion. Fertil 5te ril 75: 11 - 13, 200 1.
4. 2001 Assi sted Rep rodu cti ve Technology 5uccess Rates: Na- 12. Rebar RW, DeCheney AH: Ass isted Reproductive Tec hn ol-
tional 5ummary and Fertiliry Clini c Reports. Ameri can 5o- ogy in th e United States. N Eng l J Med 350: 1603- 1604,
ci ety for Reprodu ctive Medicin e and Ce rner fo r Di sease 2004.
Co ntro l, Atl an ta and Birmingham, December 2003. 13. Jain T, Missmer SA, Horn ste in MD: Trend s in Embryo -
5. Cramer DW, Walker AM , 5chiff 1: Statistical Methods in Tra nsfer Practice and in Outcomes of the Use of Assisted
Eva luatin g the Outco me of Fertility Therapy. Fertil 5teril Reproduct ive TEc hn o logy in the United States. N Eng l J
32 :80-86, 1979. Med 350: 1639- 1645, 2004.
6. O li ve DL: Anal ys is of C linical Fertility Trial s : A 14 . Karande VC, Korn A, Morri s R, et al: Prospective Random-
Methodol og ic Re view. Fen il Steril 45 : 157-171, 1986 . ized Trial Co mp arin g th e Outcome and Cos t o f In Vitro
Fertilization wit h that of a Traditiona l Treatmen l Algo-
7 . Rock JA , Guzick OS , Sengos C, et a l: The Co nservat ive rithm as First-Line Therapy for Coup les with lnfertilit y.
Surgical Trea tm ent of Endometriosis: Evaluation of Preg- Ferti l Steril 7 1:468-475 , 1999.
nancy Success with Re spect to the Exte nt of Di sease as
Ca tegorized Using Contemporary C la ssification Sys tems. 15. Ca mpb ell JS , Pasta DJ , Adamson G D: Pre liminary Meta-
Fertil Steri l 35: 13 1-1 37, 198 1. Analys is Comparin g In Vitro Fenili zati on with 5urgica l Treat-
ment for Mod erate and 5evere Endometrios is. J Am Assoc
8. Ada shi EY, Rock JA, Guzick D, et al: Fertility Following Gynecol Laparosc 2:56-57, 1995 .
Bil atera l Ovarian Wedge Resecti on: A Critica! Ana lysi s of
90 Co nsec uti ve Cases of the Polycys ti c Ovary Syndrome . 16. Dri sco ll G L, Ty lcr J PP : What is th e Best 5trategy fo r Pre-
Fertil 5teril 36 :320-325, 1981. sentin g A RT Res ults? A Co nt roversia! Comment. J Ass ist
Reprod Genet 16:463-467, 1999.
Part V:
p~
NaProTECHNOLOGY
Th omas Hilgers, M.O. "lt is true that a cervical mucus discharge is nota 'high tech '
Chapter 53
idea .. .Everyone concemed with prenatal care needs to
recognize the accuracy of this bioassay system and the
ease with which such information is obtained so that its
benefits can be better incorporated into obstetrical practice."
695
696
Three-dimensional Ultrasound:
Putting a Face on the Unborn Human Person
A num ber ofyears ago, it was predicted that ultra-

sound tec hn ology would advance to such a de-
gree that it wo uld a llow everyone to see, more and more,
and her husband an opportunity to bond at an earlier
stage of development with the baby they are abo ut to
have. This is a very human connection ' It is at times
the hum an be ing in its earliest stages of growth and profound and at ali times unique and inspiring. The im-
deve lop ment. 1 Since then , advances have been extraor- ages in this collection transpire nearly the entire time
dinary and, with the advent ofthree-dimens ional (volu- span ofpregnancy from 9-weeks gestational age through
metric) ultrasound, it is possible to take a photograph of 40 weeks (Figures 52-1 through 52-25).
the baby in utero show ing its uniquely human features
and personal ity. Ultrasound during pregnancy has been studied exten-
sively over the years and has been found to be safe.
Ultraso und technology is used med ically to monitor and The following official statements on safety are prov ided
evaluate th e fetus and to protect it. However, more and for the reader's benefit.
more, ul traso und technology is being used to detect
fe ta l ab norma li ties so that abortions can be performed. TheAmerican lnstitute for Ultrasound in Med icine has
At the same time, feta l ultrasound showing the uniquely a bioeffects committee and their last officia l statement
hum an features ofthe fetus with 3-D ultrasound, is of- dated December 2002 reads : "There are no known harm-
ten criticized and ca ll ed a "nonmedical application ." fu I effects associated w ith the medica] use of
sonography. Widespread clinical use of diagnostic ul -
In thi s chapter, sorne ofthe work which has been ongo- trasound for many years has not revea led any harmful
ing at the Di v ision of Reproductive Ultrasound at the effects . Studies in humans ha ve revea led no direct link
Pope Paul Vl lnstitute is compiled. lts speciflc purpose between the use of diagnostic ultrasound and any ad-
is to show the growth and development of the fetus verse outcome. Although, the possibility exists that bio-
fro m the facia l perspective. Ali ofthe images in this chap- logical effects may be identified in the future, current
ter are th ree-dimensional ultrasound images taken dur- information indicates that the benefits to patients far
ing the various stages of pregnancy at no harm to either outweigh the risks, ifany. "
the mother or the baby. Such examinations are used fre-
quently at the Pope Paul VI l nstitute to allow the patient The Mayo Clinic has the following statement with re-
697
gard to the effects ofultrasound: " There is no evidence danger to hearing" (www.mayoclinic.com , April 2004).
of harmful effects to the fetus through the use of ultra-
sound during pregnancy. Un like x-rays, ultrasound does The images contained in this chapter are not the end of
not involve potentially ham1ful radiation. fnstead , it uses the in-utero ultrasound story. Indeed, four-dimensional
high-frequency sound waves, which bounce off body ultrasound has now become available 2 and will show
structures to create images. These sound waves are at the embryo and fetus in real-time, motion picture-type,
frequenc ies that the ear cannot perceive and pose no 3-D ultrasound.
Figure 52-2: Also at 9 weeks , a side profile showing the

umbilical cord coming in from the right (From : Pope Paul VI
lnstitute , Divisan of Reproductive Ultrasound , 2004).
Figure 52-1 : The gestational sac, yolk sac and early fetus
with arms , legs, and ears clearly visible at 9-weeks gestation
(Courtesy Medison lnc.).
Figure 52-3: ldentical twins at 10-weeks gestation (From: Figure 52-4: A side view at 11-weeks gestation (From : Pope
Pope Paul VI lnstitute , Divisan of Reproductive Ultrasound, Paul VI lnstitute, Divisan of Reproductive Ultrasound , 2004).
2004) .
Chapter 52: Three-dimensional Ultrasound: Putting a Face on the Unborn Human Pe rson 699
Figure 52 -6: A lateral view at 12-weeks gestational age with

the umbilical cord coming from the right (From : Pope Paul VI
lnstitute , Divison of Reproductive Ultrasound, 2004).
Figure 52-5: A frontal view at 11-weeks gestational age. The
umbilical cord is seen coming in at mid-abdomen (From : Pope
Paul VI lnstitute , Divison of Reproductive Ultrasound , 2004).
Figure 52-8: At 17-weeks gestational age, the facial and arm

features are identified (From : Pope Paul VI lnstitute , Divison of
Reproductive Ultrasound , 2004 ).
Figure 52-7 : Facial features at 15-weeks gestation . The left
hand is covering the left eyebrow (From: Pope Paul VI lnsti-
tute, Divison of Reproductive Ultrasound , 2004).
Figure 52-9 : At 22 weeks the facial features are shown

(From : Pope Paul VI lnstitute, Divisan of Reproductive Ultra- Figure 52-1O: At 24 weeks, the anterior fontanelle is clea rly
sound, 2004). visib le and the facial features are clearly shown (From: Pope
Paul VI lnstitute, Divisan of Reproductive Ultrasound , 2004) .
Figure 52-11 : Facial featu res at 26-weeks gestation (From :

Pope Paul VI lnstitute, Divisan of Reproductive Ultrasound ,
2004).
Figure 52-12: Facial features at 27-weeks gestation (From :
Pope Paul VI lnstitute , Divisan of Reproductive Ultrasound ,
2004).
Chapter 52: Three-dimensional Ultrasound: Putting a Face on the Unborn Human Person 701
Figure 52-13: Facial features again at 27-weeks gestation

(From : Pope Paul VI lnstitute, Divison of Reproductive Ultra-
sound , 2004).
Figure 52-14: Facial features at 28-weeks gestation (From:
Pope Paul VI lnstitute, Divisan of Reproductive Ultrasound ,
2004).
Figure 52-15 : The forearms , hands , and fingers covering Figure 52-16: Facial features at 28-weeks gestation (From:
the left side of the face at 28-weeks gestation (From : Pope Pope Paul VI lnstitute , Divisan of Reprodu ctive Ultrasound ,
Paul VI lnstitute, Divison of Reproductive Ultrasound , 2004). 2004).
Figure 52-17 : The left si de of the face with the left hand and
fingers seen at 28-weeks gestation (From : Pope Paul VI lnsti- Figure 52-18 : Facial features at 32-weeks gestation (From :
tute, Divison of Reproductive Ultrasound , 2004). Pope Paul VI lnstitute, Divisan of Reproductive Ultrasound ,
2004).
Figure 52-19: Facial features at 33-weeks gestation (From : Figure 52-20 : Facial featu res at 34-weeks gestation (From:
Pope Paul VI lnstitute, Divison of Reproductive Ultrasound , Pope Paul VI lnstitute, Divison of Reproductive Ultrasound ,
2004 ). 2004).
Chapter 52 : Three-dimensional Ultrasound : Putting a Face on the Unborn Human Person 703
Figure 52-21: Facial features with the eyes open at 35- Figure 52-22: Facial features at 35-weeks gestation (From :
weeks gestation (From : Pope Paul VI lnstitute, Divisan of Re- Pope Paul VI lnstitute , Divisan of Reproductive Ultrasound ,
productive Ultrasound , 2004). 2004).
Figure 52-23: Facial features at 36-weeks gestation (From : Figure 52-24: Facial features at 36-weeks gestation (From :
Pope Paul VI lnstitute, Divisan of Reproductive Ultrasound , Pope Paul VI lnstitute, Divisan of Reproductive Ultrasound ,
2004). 2004 ).
Figure 52-25: Facial features at 40-weeks gestation (From : Pope Paul VI

lnstitute, Divisan of Reproductive Ultrasound , 2004).
1. Hil gers, TW: Li vin g Proof: A Visua l Enco unter w ith th e 2 . Go nca lves LF, Romero R, Espinoza J, et a l: Four-Dimen-
Unborn . Pope Paul V I ln stitute Press. Omaha, NE, 1990. siona l Ult raso und of th e Feta l Hea rt Us in g Co lo r Doppler
S pa ti o te mp ora l lm a ge C orr e la tion . J U ltrasou n d Med
23: 4 78-48 1, 2004.
Chapter 52 : Three-dimensional Ultrasound : Putting a Face on the Unborn Human Perso n 705
The Human Connection

Sta ges of prenatal life (clockwise from
left) starting at nine-weeks gestation
and followed by 11-weeks gestation ,
15-weeks gestation , 24-weeks ges-
tation , 28-weeks gestation , 32-weeks
gestation and 35-weeks gestation.
Dating the Beginning of Pregnancy
ne ofthe most important aspects of obstetrica l care the pregnancy in this fashion , it wi ll be 38 weeks lon g
º is to date, as precisely as possible, the beginning

of pregnancy so that the estimated time of arrival (ETA)
can be ca lcu lated (sometimes referred to as the E DC -
estimated date of confinement). The standard textbook
or 2 weeks shorter than the gestational age dates. The
fetal age, of cour e, is the actual age ofthe pregnancy.
H istorically, the obstetrician has focused on the first day

in obstetrics, Williams Obstetrics, states vigoro usly that ofthe last menstrual period for two reasons. First ofa ll ,
"precise knowledge ofthe age ofthe fetus is impera- the menstrual tlow itse lf is a fairly dramatic symptom
tive for idea l obstetrical management!" 1 ( emphasis which the woma n can be expected to remember. In ad-
in the original). And yet, even with ali ofthe availab le dition , it is easy to teach her to record the first day of
technology, one of the puzzles of modern obstetrics, is the last menstrual period so that when that information
that the obstetrici an has not yet learned how to accu- is elicited by the phys ician, ata later time, it is ava il-
rate/y date the beginning of a pregnancy. able.
Pregnancy can be measured in two different ways. The However, in the midst of al 1 ofthis, the obstetrician and
most common and most often used in clinica l obstetrics many women have missed the point that the cervical
is the measurement of the gestational age of the preg- mucus discharge is ve ry much ajlow in the same fash-
nancy. The gestati onal age ofthe pregnancy is measured ion as the menstrual tlow. In sorne cou ntri es , they refer
from the first day of the last menstrual period. In this to menstruation as the redjlow and the mucus discharge
way of dating the pregnancy, it is 40 weeks in duration as the whitejlow. Unfortunatel y, modern obstetrics has
(on average) instead of the actual 38 weeks . In other paid little attention to the white jlow.
words, it dates the pregnancy, on average, 2 weeks longer
than it actually is. When one is c harti ng the CREIGHTON MODEL
FertilityCare™ System (CrMS), however, one can date
The other way of measuring the dates ofthe pregnancy th e pregnancy accurately from the actual or estimated
is to meas u re the f etal age. The fetal age of the preg- time of conception. Therefore, one can date the preg-
nan cy is measured from the time of conception or the nancy according to its true date (or true beginning) or
estimated time of conception (ETC) . When measuring in fetal age terms. This is measured by evaluating the
707
708 The Med ical and Su rg ical Practi ce of NaProTECHNOLOG Y
acts ofintercourse that occur during the time offertility When one identifies the ETC, one can then ca lcu late
and establishing an estimated time of conception through the duration of the pregnancy at the time of the preg-
this approach. nancy and the estimated time ofa rri va l (ETA) (the due
date). Tn calcul atin g the ETA with the use ofthe CrMS,
In determining the estimated time ofconception (ETC), the fo ll owing fo rmula is used:
one looks at both a range and a midpoi nt. The ra nge is
obtai ned by looking at the earli est act of intercourse . ETA= ETC - 3 months - 7 days.
during the time of fertility and the last act of intercourse
during th e time offertility (genera ll y speaking). lfthere
is on ly one act of intercourse during the time offertility At first g lance, the ca lcu lation of the ETC seems aw k-
and it is during the pre-Peak time, then the range is from ward and comp li cated. Once known and understood,
that act of intercourse through and including the Peak however, it becomes less cumbersome and easy to use.
Day. lf there is only one act of intercourse during the
count of Peak + 1, 2 and 3, then that act of intercourse is If one act of intercourse occurs during the pre-Peak
the estimated time of conception (ETC) (Tabl e 53- 1). phase of the cycle, there is a natural tendency to think
that act of intercourse resulted in the pregnancy and th us
1n ca lculating the midpoint, one takes the middle point the ETC shou ld be the date of that act of interco urse.
between the earliest act of intercourse and the last act However, in an exam pl e ofan intercourse occurri ng on
ofi ntercourse during the time offertility. In fact, there Peak-4, it is unlikely that concepti on actuall y occu rred
may be no acts ofintercourse on the particular day called on that day, since it is un li kely for ovulation to have
the " midpo int" and eventually identifi ed as the estimated occurred so early in the cycle. Thu , using the Peak Day
ti me of concepti on. Of course, the un known here is the as " outer end" ofwhen ovul ati on may take place, pro-
actual time of ovul ation which can not be determined v ides a reasonab le estimate of the range u pon which
w ith certainty. However, thi s w ill g ive a very good and conception may have taken pl ace. Th e midpo int then
c lose estimate of ovulation. lf a true midpo int cannot beco mes a good way of estimating the time of concep-
be determ ined, th en one se lects the even numbered day tion in an example such as that.
between the two points. The midpoint becomes the es-
timated time of concepti on (ETC). During the post-Peak phase ( durin g the count of three),
T able 53-1: Calculation of th e Estimated Time of Conception (ETC)

and lts Range
Date 1/1 0 1/1 1 1/1 2 1/13 1/14 1/15 1/1 6 1/1 7

EXample P-4 p .3 P-2 P-1 p P+1 P+2 P+3
A 1 1
B 1
e 1
o 1 1
E 1 1
F 1 1 1 1
G 1 1
H 1
1 1
1= lntercourse
Answers~~~~~~~~~~~~~~~~~~~~~~~-
A. Range = 1/ 10 - 1/ 16 D. Range = 1/ 11 - 1/ 14 G. Ra nge = 1/15 - 1/ 16
ETC= 1/13 ETC = 1/12 ETC= 1/ 16
B. Ra nge = 1/10 - 1/14 E. Range = 1111 - 1/ 16 H. Ra nge = 1/ 16

ETC = 1/12 ETC = 1/14 ETC= 1/16
C. Rang e = 1/11 - 1114 F. Range = 1/ 10 - 1/ 16 Ra nge = 1/17

ETC= 1/ 12 ETC = 1/ 13 ETC = 1/17
Chapter 53: Dating the Beginnin g of Pregnancy 709
it is mo re like ly th at a s ingle act of inte rcourse may The di stinctio n between ways of identi fy ing a nd ca lc u-
ha ve resulted in conception because ofthe sho rt pe riod lating the dates of a preg nancy a re furth e r elaborated
of time in w hich ovul ati o n wo uld have had to occ ur u pon in Table 53-2 fo r each of the three pregnancy cycles
during thi s phase of the cycl e. Thus, w ith a single act o f in Figures 53- 1throug h5 3-3 . ln each ofth e three cases,
interco urse, during th e co unt of three, that sing le day us ing the last menstrual peri od approach (Naegele 's
ca n be used as th e estimated time of conceptio n. a pproach), the ca lcul ated due date is April 8th (based
u pon a las t menstrual pe ri od of Jul y 1st). However, by
It is not always poss ibl e to ca lcul ate a spec ific mi ddle esti mating the actual time of conceptio n or the true be-
point between two dates. Thi s occurs, most specifica lly, g inning of the pregna ncy, the re is a co rrelation between
when there are an even number of days betwee n th e th e two dates onl y in the pregnancy of Fi gure 53-1 . In
two po ints. In this ca e, there wo uld be tec hni ca lly no Figure 53-2, the due date is ca lculated from the CrMS
middl e po int, but rather two po ints th at wo uld occ ur in as April 20th (a 12-day di ffe rence from Naege le's rule)
" the middl e." Thus, a convention has been estab lis hed a nd in Figure 53 -3, April l 7th (a 9-day di ffe rence from
for selecting a speci fi c date w ith rega rd to whi ch o ne Naegele's rul e).
would be calcu lated as the midpo int. If two days a p-
pea r as middl e points, the n the even num bered day is We have studi ed 173 pati ents in a co nsecuti ve fashi o n
conside red the middle po int. who ha ve been charting the CrMS at the time of con-
ception. The ETC and the ETA were ca lcul ated in thi s
Thi s is deta iled in Tabl e 53 -1 w ith a series of examples fas hi on. In thi s group of pati ents, earl y ultrasound dat-
that allow fo r one to practi ce the calcul ati on o f the range ing ofthe pregnancy was also o btained . Thi s dating was
and the midpo int. Thi s acti vity is do ne, in deta il , at the obtain ed by the measure ment ofth e crown-rump length
tim e o f a pregn a ncy eva lu a ti on co ndu c te d by a of the e mb ryo or fe tus. Most of the exa minati ons were
FertilityCare™ Practitioner ( o ne of the services pro- perfo rmed during the first trimester of pregnancy w hen
vided in the array o f services through a FertilityCare™ the dating of the pregnancy is thoug ht to be accurate
Center) 2 . It ca n a lso be calcul a ted eas il y in th e w ithin plus o r m inus three days .
physician's office w ith the ava ilability ofthe CrMS chart.
Exa mpl es ofpregnancies occurring wi th the CrMS are In Tabl e 53 -3, the results of th at eva luati o n are shown .
present in Fig ures 53- 1 thro ug h 53-3. An acc urate date fo r th e beginning of pregna ncy can be
Figure 53-1 : A pregn ancy occurring in a fairl y regular length cycle where the Peak Day occurred on day 17 of the cycle (From :
H VH H H M M VL
+x.3
4 x. 3 4,ca. QA.O °"'º °"° CAD 0-.0 IOK IOKL IOKL IOKL \OKL SKL IO&l
KI -:a. xea. ic. a K.il. lt,1. lt l,
toSL IOSL IOSL .... -... ()AD OAD
KI •I KI
°"º °'º OAO O'<O OAO °"° OAO OAO
I I
Figure 53-2 : A pregnancy occurring in a longer cycle where the Peak Da y occurred on day 24 of the cycle (From : Pope Paul VI
710 The Medical and Surgical Practice of Na ProTECH NO LOGY
establi shed with the use of the CrMS . Thi s corre lates wo me n ta ke their basa l body te mperature and w ith the
we ll w ith the ultrasound dates a nd the estimated due po int of tbe shift in the basa l body temperatu re, one
date o r ETA. In fact, the CrMS dating correlated, on could estimate the poss ible time of concepti on. How-
ave rage, in th e fo ll ow ing way: CrM S E TA= U/S ETA ever, thi s wo uld not be expected to be as accurate as the
+ 1.97 da ys (Table 53-4). T he CrMS dates were highl y CrMS because the shift in the te mperature is not as ac-
acc urate with the two being w ithin 10 d ays of each c urate a predicto r of ovulati on as the occurrence of the
othe r in 100 p erce nt of cases . Peak Day 3A. A compari son of th e lo ngest le ngth esti-
mate to the ETA for the CrMS, BBT and the LM P is
There are other w ays in w hi c h to establi sh a n acc ura te shown in Table 53-5.
date for the beg inn ing ofpregnancy. One way is to have
lt is generall y recogni zed that ultraso und is the meth od
of c hoice fo r dating pregnancy5 . The data in thi s c hap-
Table 53-2: Calculation of ETN (EDC 2) te r o n Peak Day corre lati on to ETC ve rify that. And
using Exa mples from CrMS Charts3 yet, the Pea k Day data are eas ily availa ble a nd more
cost effe cti ve. C learly the use of the LMP for dating
Due Date Calculations
Naegele's CrMS pregnancy carries w ith it a hi gh degree of erro r6. W hile
Chart in ... Calculation• Calculatlon5 ultraso und a nd the Peak D ay were w ith in 1O days of
Figure 53-1 April 8 April 8 each other in 100 percent of cases studi ed, it has been
Figure 53-2 April 8 April 20 shown that the LMP is greate r than 1Odays di ffe re nt in
Figure 53-3 April 8 Apri l 17 o ver 16 perce nt of cases 7•
1. ETA ; Estimated time of arrival

2. EDC ; Estimated date of confinement Acc urate ly dating th e beginning of preg nancy is recog-
3. In this series of examples, far simplicity sake the fi rst day of the last
menstrual period (LMP) is stipulated to be July 1.
ni zed to be o ne of the most impo rtant things that can be
4. EDC ; LMP - 3 month s + 7 days acco mpli shed in the earl y days of prenatal care. The
5. ETA; ETC - 3 months - 7 days (where ETC ; esti mated time of
conception) mo re accurate the dates are, the less obstetrical inte r-
fe rence o ne can anti cípate during the course of the preg-
nancy. For exampl e, a decreased use of amni ocentes is
fo r fe ta l lung maturi ty pri o r to re peat cesarean secti o n
24 25 26 27 28 29
MHML L~~~~~~~~~~~~~=m=m~~~~=~~m~~m~=
-. 1 "ª
I I I I
Fi gu re 53-3 : A pregnancy occurri ng in a longer cycle where the Peak Day occurred o n day 26 of the cycle (From : Pope Paul VI
Table 53-3: Relationsh ip of Estimated Time of Arrival (ETA) Calculated from Estimated Time of
Conception (ETC) by Creighton Model and Early U ltrasound (U/ S) Dates (N=173)
.Days .before U/S Date ETA by Pays after U/S date

CrMS early U/S CRMS
>7 -7 -6 -5 -4 -3 -2 -1 o +1 +2 +3 +4 +5 +6 +7 >7 Totals

Number 2 2 7 8 17 26 23 17 16 14 9 7 6 16* 173
Percent 0.6 0.6 0.6 1.2 1.2 4.0 4.6 9.8 15.0 13.3 9.8 9.2 8.1 5.2 4.0 3.5 9.2 99 .9
• Longest was +1 0 days

Mean: CrMS ; U/S + 1.97 days
Range: CrMS to U/S ETA ; 0-10 days in 100% of cases
0-7 days in 90.2% of cases
Chapter 53 : Dating the Beginning of Pregnancy 711
can be anticipated ifthe dates are more accurate. This

Table 53-4: Creighton Model
is because a repeat cesarean section ca n be scheduled
FertilityCareT" System
beca use of true confidence that the dates are accurate.
Estimating the Due Date (ETA)
In the author's own practi ce, amn iocentesis or fetal lung
CrMS vs. U ltrasound
maturity has been performed once in the last 18 years,
and yet, neonatal outcomes have been exce llent.
ETA by CrMS = ETA by U/S + 1.97 days
By having accurate dates, one can also better assess
ETA by U/S .:!:. 3 days = 82 .0% ETA by CrMS
the normal progression of the pregnancy and also de-
ETA by U/S .:!:. 5 days = 94 .0% ETA by CrMS termine both pre- as well as po t-maturity conditions.
lf induction of labor is a consideration, that decision
can be made without added obstetrical manipulation .
lt is well recognized that increased adverse pregnancy
outcomes can be expected if the dates are not accu-
rate8·9.
When labor ensues, an accurate judgment can be made

Table 53-5: Relationsh ip of the ETA (EDC) to with regard to whether th at labor is beginning prema-
the Three Systems of ture ly. If premature labor has started, then aggressive
Calculating the Due Date management can be instituted to halt that labor and de-
lay its onset until ful! term. Again , acc urate dates al-
Longest length
Method N Estlmate to ETA lows for improved judgrnent in the management of preg-
nancy, labor and deli very along with the management
CrMS ' 173 10 days
of a who le variety of medi ca ! and obstetri ca l compli-
BBT' " 26 14 days
cations of pregnancy.
LMP'" 26 18 days
LMP 5 44,623 > 1O days =16.6% of cases lt is true that a cervica l mucus discharge is nota "high
1. Based on 173 consecutive pregnancies where ETA b CrMS and early
ultrasound (U/S) were compared: mean CrMS ETA - mean U/S ETA+ tech" idea. However, it is an incredibly good bioassay.
1.76days Everyone concemed with prenata l care needs to recog-
2. Based upon a study of 26 deliveries using the Prem Rule: EDC = first
day of overall thermal shift - 7 days + 9 months (from Kippley'). nize the accuracy ofthis bioassay system and the ease
3. Kippley JF and Kippley SK: The Art of Natural Family Planning . with which such information is obtai ned so that its ben-
Fourth edition. Couple to Couple League. Cincinnati, OH 1996,
pp300-301 efits can better be incorporated into obstetrical prac-
4. Based upon a study of 26 deliveries using Naegele's Rule: LMP - 3 tice.
months + 7 days (from Kippley' ).
5. Yang H, Kramer MS , Platt RW, Blondel B, et al : How Ooes
Ultrasound Sean Estimation of Gestational Age Lead to Higher Rates
of Preterm Birth? Am J Obstet Gynec 186: 433-437 , 2002.
1. Cunningham FG, Gant NF, Leveno KJ , Gilstrap LC, Haulh JC , 5. Gardosi J, Geirsson RT: Routine Ultra ound is the Method of
Wenstrom KD: Williams Obstetrics. 21 " Edition, McGraw-Hill, Choice for Dating Pregnancy. Br J Obstet Gynaecol 105:933-
New York, p. 226, 2001. 936, 1998.
2. Hi lgers TW, Hi lgers SK, Prebil AM , Daly KD: The CREIGHTON 6. Kramer MS, McLean FH, Boyd ME, Usher RH: The Validity of
MODEL FertilityCare'" System: A Standardized Case Manage- Gestationa l Age Estimation by Menstrua l Dating in Term,
ment Approach to Teaching. Book 11- Advanced Teaching Ski li s. Preterm and Post-term Gestations. JAMA 260:3306-3308, 1998.
Pope Paul VI lnstitute Press, Omaha, NE 2003 , pp 118-119.
7. Yang H, Kramer MS, Platl RW, Blande! B, Breart G, Morin 1,
3. Hil gers TW, Abraham GE, Cavanagh D: Natural Family Plan- Wilkins R, Usher R: How Does Early Ultrasou nd Sean Estima-
ning. l. The Peak Symptom and Estimated Time of Ovulation . ti on ofGestational Age Lead to Higher Rates of Preterm birth?
Obset Gynec 52 :575, 1978. Am J Obstet Gynec 186:433-437, 2002.
4. Hil gers TW, Bailey AJ: Natura l Family Planning JI - The BBT 8. Nguyen TH, Larsen T, Engholrn G, Moller H: lncreasedAdverse
and Estimated Time of Ovulation. Obste! Gynec 55:333-339, Pregnancy Outcomes with Unreliable Last Menstruation. Obste!
1980. Gynec 95:867-873, 2000.
9. Taipale P, Hiilesmaa V: Predicting Delivery Date by Ultrasound
and Last Menstrua l Period in Early Gestation. Obstet Gynec
97: 189-194, 200 l.
Assessing Progesterone during Pregnancy
uch of the work that has been acco mpli shed on sorne of these pati ents also had a hi story of previous
M the assessment of serum progesterone in normal
pregnancy was done fro m the earl y l 950s through the
spontaneous abortion and, in sorne cases, recurrent spon-
taneous abortion.
l 970s 1- 11 • Furthermore, most of the a sessment of
progesterone in pregnancy as it relates to vari ous com- During the course of these pregnanci es, progesterone
plications of pregnancy was accomplished fro m the early was adm iniste red using progesterone in sesame seed oil
l 960s through the early l 980s9· 12-24 • In spite of improve- either 100 mg or 200 mg intramuscularl y every three to
ments in the accuracy and precision of progesterone four days during the course ofthe pregnancy. The fírst
assays since that time anda better ability to date preg- progesterone leve! was drawn usually l 6 to 18 days af-
nancy and establish more accurate gestational ages, very ter the estimated time of conception. Conception was
little subsequent work has been accomplished in this est im ated us in g th e Peak Da y esti mat e of th e
a rea. CREIGHTON MODEL FertilityCareni System which
was being charted by most of th e patients in this study.
lt is the purpose of thi s chapter to pre ent data on the This day has been shown to be close ly assoc iated with
leve! of progesterone in norma l pregnancy andas they the time ofovu lation (plus or minus two days in 95 .4%
relate to a variety of pregnancy-related comp licati ons of cyc les 25 ). In cases where the pati ent was not using
and features of prev ious reproductive history. Modern the CREIGHTON MODEL System, the pregnancy was
means of progesterone assessment with improved ac- dated by the use of ea rly ultrasound measurement of
curacy and prec ision were used along with more pre- the crown rump length or the gestationa l sac obtained
cise mea ns of dating the pregnancies. genera lly between th e 6th and the 9th week of preg-
nancy. The progesterone leve ls were drawn every two
This study was undertaken between the years 1980 and weeks just prior toan inj ection of progesterone - 72 to
200 1 in a group of 6 1O patients through 830 pregnan- 96 hours following the previou progesterone inj ection
cies and 8,545 progesterone levels. These patien ts were - at the expected trough of the exogenously admi nis-
primarily infertili ty pati ents who were receiving proges- tered progesterone.
terone supp lementation during the course oftheir preg-
nan cy. ln fe rtility was either primary or secondary and Pregnancies were then reviewed fo r the occurrence of
713
previous pregnancy complications, intrapregnancy com- mature delivery (n= 11 ).

plications or specific postpartum problems. In those
pregnancies in which there was no history of previous 1n addition, current pregnancy compl ications were ide n-
spontaneous abortion, prematurity, or any other type of tified. These included: first trimester spontaneo us abo r-
pregnancy-related complication (or the patient was a tion (n= 75); seco nd trim ester spontaneo us abortion
primigravida) and the pregnancy itselfproceeded with- (n= 12); pregnancy-induced hypertens ion (n=3 l ) and
out complication and delivered without difficulty at full toxemia of pregnancy (n=22). In add ition, middle tri-
term, those pregnancies were considered nonnal and mester abruption of the placenta or subchorion ic hem-
their progesterone levels were pooled to estab lish the orrhage identified by ultraso und (n=23), ad herent pla-
norma l curve . centas observed at the time of del ivery (n=8), pl acenta]
abruptions (n=4) and low-lyi ng placenta and early pla-
Patients with a pregnancy history ofa documented com- centa previa (before the 20th week of pregnancy and
plication ora previous pregnancy history of problems identified by ultrasound) (n=28) were ali separate ly
were identified. Each ofthese pregnancies were evalu- categorized . Pat ients who threatened premature labor
ated separately for the progesterone profile during the were separate ly eva luated as we ll . T hese incl uded pa-
course of pregnancy. Those with a previous pregnancy tients who were receiving on ly ora l Terbutaline (n=77);
history that were tudied included the following: previ- patients who received cervical cerc lage (n=44); patients
ous history ofpolycy tic ovarian disease (n=26) ; previ - who had spontaneous rupture of membranes prior to
ous history of one spontaneous abortion (n=87); previ- the 37th week of pregnancy (n= 29) (P ROM) and pa-
ous history ofthree or more previous spontaneous abor- tients who received intrave nous antibiotics for low-grade
tions (n=2 l ); prev ious history of at least one induced chorioamnionitis (n= l09) and patients who de livered
abortion (n=53); a previous history of at lea tone pre- prematurely ( prior to the 3 7th week of pregnancy)
lmmunoassay Methods
Blood was co ll ecled by venepuncture into red stoppe red so lid phase 125 1 radioimmunoassay kit was used for progeste r-
vac utainer tubes and allowed to clot. The serum was then de- one ana lyses from May of 1988 to August of 1995 . The Coat-
canted and analyzed immediately after collection for progest- A-Count progesterone procedure is a solid phase RIA proce-
erone . Serum sa mp les that were not ana lyzed immediate ly were dure wherein labeled 125 1-progesterone competes for a fixed time
frozen at - 20º C until the assay was perfom1ed. Frozen seru m with progesterone in the palient sample for ant ibody sites (an-
samp les we re ana lyzed within a few days of co ll ecti on. tibodies) wh ich are immobilized to the wall ofa po lypropy lene
rube . The supern atant is then decanted, which terminales the
competition berween the m 1-labeled antigen (progesterone) and
Progesterone ana lyses were perfonned using three immunoas- the patient progesterone. The tube (bound fraction) i then
says: the Pantex Rad ioimmunoassay (R IA ) Kit (Sa nta Monica, counted. The sensi tivity of this RJA method is 0.05 ng/mL.
CA 90404), the Coat-a-Count Proges tero ne Kit, Diagnostic Within-run precis ion averaged 7 percent and the between-run
Products Corporation (DPC) (Los Angeles, CA 90404), and precision is 8 percent.
lmmulite Progesterone (sol id phase, chemiluminescent enzyme
immunoassay) usi ng the lmmulite ystem which is a continu- lmmulite progesterone, which is a sol id phase, ligand-labeled
o us random access immunoassay analyzer [Diagnostic Prod- competitive chemiluminescent enzyme immunoassay, was used
ucts Co rporation (DPC) Los Angeles. CA 90045). Ali RLA from August of 1995 until the end of the study. In this proce-
ana lyses were perforrned in duplicate. Single analyses were dure, the solid phase, a polystyrene bead which is enclosed
performed on the lmmulite System as recommended by the within an
manufacturer. lmmulite test rube, is coared with polyclonal rabbit antibody
which is specific for progesterone. The patient sa mple and
The Pantex RIA Progesterone Kit was used from the beginning ligand-labeled progesterone are sim ultaneo usly introduced into
of the study through May of 1988. This kit in vo lves an ex trac- the test tube and incubated for approximately 30 minutes with
tion step which is then followed by RIA using a double anti- intermittent agitati on. During this time, progesterone in the
body teclmique. Progesterone which is extracted from serum is samp le competes with li gand-labeled progesterone for antibody-
evaporated to dryness. The residue is then preincubated with binding sites on the bead. The bound from free fraction is then
anti -progesterone antiserum. 125 1-labeled progesterone is added separated by washing. An alka line-phosphatase-labeled anti-
which compeles with progesterone in the patient ample for ligand is introduced, incubated, washed and then the substrate
the antibody sites. A fter incubation for a fixed time, separat ion is added. After incubation the chem il uminescent substrate is
o fbound from free fra ct ion is achieved w ith antiserum and the mea ured by a luminom eter. The photon output or chemilumi-
antibod y-bound fraction is precipitated and counted. The sen- nescence is inversely proportional to the progesterone concen-
si tivity of the method is 0.75 ng/mL. Within-run precision is tration . The sens itivity of the lmmulite method is 0.2 ng/mL.
8.6 percent while between run preci sion is 8.9 percent. Within-run precision is 5 percent and the between-run prec i-
sion is 8.6 percent.
The DPC ( Diagnostics Produ cts Corporation) Coat-A-Cou nt
Chapter 54: A ssessi ng Progeste rone during Pregnancy 715
Correlation Studies
Correlation studies between the different kits were ca refu ll y co uld be established.
performed in order to be ab le to convert betwee n the different
progesterone assay results. For Pantex RIA (x) and DPC RIA The conversion for ali Pantex levels to the DPC-RIA , based
(y), least sq uares ana lys is (n =289) gave a slope of 1.42, y- upon these correlati on studies, were obtai ned with the use of
intercept of- 1.11 and correlation coeffici ent of0.96. For DPC the following fo1mulae: for levels 0.1 through 26.0 ng/mL, DPC
RIA (x) and lmmulite (y) least squares analysis (n= J84) gave a leve! = 1.2098 (Pantex va lue) - 2.5965; for Pantex levels 26. J
siope of 0.942, y-inte rcept of- 1.35 and correlation coefficient throu gh 227.0 ng/mL: DPC leve ! = 1.388 1 (Pan tex value) +
of 0.988. 2.60. Ali conversions were rounded to one decimal point.
Very little difference is observed in pati ent progesterone re- For lmmulite conversions to th e DPC-RIA standard va lue, the
sults between DPC RlA and lmmulite. A large difference is fo llowing conversion formu lae were developed and used :
observed in patient results between Pantex R.IA and DPC RJA lmmulite value 0.1-2.3 ng/mL: DPC-RIA leve! = lmmulite +
progesterones. Pantex RIA patient results are approximately 0. 1; J111111ulite va lue 2.4-7.5 ng/mL: DPC-R!A leve! = Jmmulite
40 percent lower than DPC RIA results. Th is is dueto the ex- + 1.0; lmmulite va lue 7.6-12.5: DPC- RIA leve! = lmmuli te +
traction step whi ch is used in the Pantex RIA procedure. 1.5; lmmulite va lue 12.6-20.0: DPC-RJA leve! = l111111ulite +
3. 1; lmmulite va lue 20.1-30.0: DPC-R.JA leve! = lmmulite +
Because ofthese differen ces between assays, we used correla- 3.0; lmmulite value 30. 1 - 50.0: DPC-RIA leve! = lmmulite +
tion studi es to co nvert ali progesterone Jevels to the DPC- RJA 1. 7; lmmulite va lue 50. 1-75.0 ng/mL: DPC-RJA = l111111ulite +
method. Us ing conversion factors, we ca lculated ali patient 0.7; lmmulite value 75 .1- 100.0: DPC-RJA leve! = l111111ulite -
progesterone Jevels relative to DPC-RIA so that ali level s were 1.1 ; J111111ulite va lue 100.1-150.0: DPC-RIA leve! = Jm mulite
sta ndardized to DPC-RIA . ln-house comparisons for serum +2. 1; lmmu lite va lue :'.:: 150. 1: DPC-RJA leve! = J111111ulite -
progesterone Jevels at ali ranges of progesterone were carried 3.8.
for each of the assays so that ca re ful and accurate correlations
(n=24). There were 26 sets oftwins a lso eva luated . tibiotics for threatened prematurity and (3) the feta l dis-
tress gro up (n=44) whic h included patients with low
Patients who had pregnancies where fetal distress was biophysical profiles, meconium-stained amniotic fluid ,
identified were also evaluated. These included: patients fetal distress during labor and low Apgar seores. For
with low Apgar seores (seores less than 7 at 5 minutes) each of these groups, the data were pooled by trimes-
(n=22); patients with fetal distress during labor (usu- ters and for six weekly intervals for comparison to the
ally identified by late decelerations as defined through contro l group.
intrapartum fetal monitoring) (n=39); patients who de-
livered babies with meconium-stain ed am niotic fluid The number ofpatients and pregnancies outlin ed above
(n= IO) and patients with low biophysical profiles (8 or exceed the tota l of 830 pregnancies that were involved
less on a sea le of 12) (n= 13). In addition, patients who overa ll in this study because, in sorne cases, pregnan-
had oligohydramnios (n= 19), intrauterine growth restric- cies were represented in vario us different categories and
tion (IUGR) as identified by ultrasound parameters are thus duplicated because ofbe ing represented in these
(n=25) and patients who were identified as smokers different groups. However, when pooled into the ab-
during tbe course oftbeir pregnancy (n=3 I) were sepa- normal placenta! group, the threatened prematurity
rately eva luated . During the postpartum phase of the group and the fetal distress group, duplication was elimi-
pregnancy, patients who suffered from postpartum de- nated.
pression (n= 18) and patients who had postpartum hem-
orrhage ( estimated blood loss greater than 500 ce at The data were then stat istically evaluated using Student
time of delivery) (n= 14) were al so separately evaluated. t-test with the assistance of th e NCSS 2000 statistical
system 26 . Statistical comparisons were made on a point-
ln addition to the above, three major groups were fur- by-point basis comparing individual levels on an every
ther identified and the pregnancies and their progester- two week basis as we ll as poo led data based upon the
one data were pooled. These included: ( 1) ab normal pooling of data overa six-week period oftime between
placenta] groups (midtrimester abruption ofthe placenta, the different groups and then finally by pooling the data
adherent placenta, placenta! abruption and low- lying in the control gro up and comparing it to the pooled data
placenta and early placenta previa as identified by ul- on a trimester basis. T he latter two methods of assess-
trasound) (n=63), (2) threatened prematurity group ment are the subject ofth is chapter. The former assess-
(n=226) (patients who received only oral Terbutaline, ments are presented in detail in the Appendix of this
cervical cerclage, premature rupture ofmembranes, pre- book .
mature delivery and patients receiving intravenous an-
,.., .. lmmulite
/",,,.. 172.2
Progesterone Levels in // 166.0 DPC

160 /
Normal Pregnancy ¡
I
153.0
'
140 136.8
,
:::::J
E
,, Pantex
--
~
O>
e
120
- - DPC (ng/ml)
- - - lmmulite (ng/ml)
- - - - - - Pantex (ng/ml) 103.9
118. 1
/
/
/
'/
<ll
e 100 V
o
,_
.....<ll
(j)
~
A 90.3
81.2
<ll 80 74 .3
O>
o
,_
65.9
(L
60 55.5
E
::::¡
53.5
,_ 48.6
7/
,..
<ll
40.4 /,..
(j)
40
22.4
20 :;.--".'.".
o
4 6 8 1o 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestati on
Figure 54-1: A co mparison of the means of three different immunoassay systems for evaluating
progesterone in normal pregnancy: DPC (RIA}, lmmulite (Chemilumi nescence), and Pantex (RI A)_
Figure 54-2: A comparison of primigravidas to multigravidas with their mean progesterone levels by week
of gestation in normal pregn ancy (DPC-RIA}.
Chapter 54: Assessing Progesterone during Pregnancy 717
The progesterone level s in normal pregnancy are iden- subsequent pregnancy in al i three trimesters was a his-
tified in Figures 54-1 and 54-2. In Figure 54-1, the mean tory of polycystic ovarian disease. Patients who had a
progesterone level s based upon the different fom1s of hi story of a previous induced abortion, one spontane-
assessment - Pantex , DPC-RIA and Immulite/Chemi- ous abo1tion ora previous premature birth had sign ifi -
lumin escent immun oassay (Tmmulite) are compared. cantly decreased progesterone leve ls in the second and
There was very little difference in the DPC-RIA and third trimesters ofpregnancy. A history ofthree or more
Chemiluminescent techniques during the course of preg- spontaneous abortions was associated with significantly
nancy. However, the Pantex leve ls were observed to be decreased progesterone levels only in the second tri-
significantl y lower throughout the entire course ofpreg- mester ofthe subsequent pregnancy.
nancy.
First Trimester Second Trimester
In Figure 54-2, the comparison of the mean progester- Control X= 31 .5 140.0 Control i = 62.8
one levels in no1mal primi gravid (n=55) and multigravid

120.0
(n=54) pregnancies are shown. Except for the level at ::;
E
16 weeks gestation , no other levels were statistica lly o, "';Ji ~
sign ificantly different from each other. The general pro- .s "'< ~
100.0 "'
"' ;¡¡
files were considered to be the same and the data for

Qi
>
Q)
_J
Q) 1
....
~
~
so.o
~
"!?
*~
the primigravida and multigrav ida populati ons we re e:
pooled and accepted as the control gro up.

e
Q) ~
1ií
Q)
O>
so.o
e
CL
In Figures 54-3 through 54-8, the pool ed data by tri- E 40.0
2
mester for the various previous pregnancy historical Q)
en
events and current pregnancy events are presented . The 20.0
mean progesterone leve l for the control gro up during • p-value < .05
t p-value < .025
the first trimester was 3 1. 5 ng/mL (n=48 8), the second *
p-value < .01
trimester 62.8 ng/mL (n=5 l l) and the third trimester i p-value < .001
11 p-value < .0001
11 8.4 ng/mL (n=3 24). When looking at previous his-
Figure 54-4 : Pooled trimester data for progesterone in
torical events (Figure 54-3), the one condition which
pregnancy: first and second trimester spontaneous abortion
had significantly lower progesterone leve ls during a (SAB) vs . normal pregnancy.
First Trimester 85.o Second Trimester Th ird Trimester

Control x = 31 .5 Control x = 62.8 150 Control x = 118.4
80.0 145
:z:.
·e: 140 :z:.
·e:
:::¡- 40.0 CD :::J CD :::J
75.0 <(
<;; <(
<;;
E en 135 en
o, CD E
"'o:::J
E
-S "'o:::J <(
en ~
a.
~
a.
70 .0 ·;;: 130 ·;;:
~
Qi
> 35.0 o o ~
a.
o
E
"'o
:::J
·;;: o ~
a. "'o
:::J
·;;:
Q)
_¡ o o Q)
5
125 o Q)
u u CD e: ~ CD u e: ~
Q)
e
Control CL 65.0 CL ~ o (") CL
120
~ CL o CL
o
(¡¡ Mean
1i5 30.0 60.0
Q)
Ol
113.4.
110
e
a_ 55.0 56.2 t 105 106.9 t 106.6 §
E 55.0 § 54 _3 11
25.0 25.9 t
2Q) 53.2 t 52.6 § 100 101 .8 t
(/)
so .o
95
45.0
20.0 90
• p-value < .05
t p-value < .025
t p-value < .01
§ p-value < .001
11 p-value < .0001
Figure 54-3 : Pooled trimester data for progesterone in pregnan cy: normal pregnancy vs. previous history
of abnormal reproductive events (PCOD = polycystic ovarian disease ; IAB = induced abortion ; SAB =
spontaneous abortion) .
40.0 First Trimester 80.o Second Tri mester Third Trimester

Control i = 31 .5 Control i = 62 .8 150.0 Control lC = 118.4
c.
~
::::r
E
e,
.s
.
"O
e
g ·ª
1i
c.
o
~
140.0
~
~
c.
~
g
.
"O
e
a;
>
"'
3S.O 34.6 70 .0 B~
-[g'.i
~
l ~
c. 130.0
~
l
¡¡
~
11
B-"
~~
O>.
i
_J
"'e<::
Conlrol 31 .9
~~
3-[ i
;¡
i"
:¡
~
f.
~~
~!
"'
1ií 1
120.0
e"'
O>
a.
E
::>
Q; e
.~ 110.0
(/) j ~
56.6
56.0 105.6 10S.O
:¡
i 100.0 102.2
2S.O ;¡ so.o 51 .3
"'p-value < .05 90.0

t p-value < .025
*p-value < .01
§ p-va1ue < .001
11 p-value < .0001
Figure 54-5 : Pooled trimester data fo r progesterone in preg nancy : abn orm al
placentae vs. normal preg nancy.
First Tri mester Second Trimester Th ird Tri mester

Control X= 31.5 Control i = 62.8 Control i = 118.4
c.
8S.O
e
¡.s 40.0 80.0
145.0
140.0
"'
:E'
a;
135.0
¡¡
s ~ ~
~
c. g
>
130.0 ~
"'
_J
Q) j .g
l -~
"§ ~ ::;
12S.0 .2
~
<::
€ ~ oo:
e
Q)
~
u 120.0
"'~ ~ c3 a.
1ií
Q)
O>
e
a.
E
"'
Q;
(/) su ll
105.0
2S .O so.o
100.0
* p-vatue < .05

t p-value < .025
t p-value < .01
§ p-value < .001
u o-value < .0001
Figu re 54-6: Pooled trimester data for progesterone in preg nancy: threatened
prematurity vs . normal pregna ncy (PROM = Premature Ru pture of Membranes).
Flrst Trimester Second Tri mester Th ird Trimester

Control i ,. 31 .5 Control i = 62.8 Control X = 118.4
so.o so.o u:
<. c. 160.0
45.0 ~ ~
i.s 40.0
75.0
70.0
-~
i~ 1
'6
~
.3 35.0
Con•""
¡!! Level
e 30 .0
~
e
o..
25.0
E 20.0
2Q)
(/)
15.0
10.0
• p-value < .05

so.o
t p-value < .025
; p-value < .01
§ p-value < .001
np-value < .0001
Figure 54-7: Pooled tri mester data fo r progesteron e in pregnancy: miscellaneous

current preg nancy events vs. norm al pregnancy.
Chapter 54: Assessing Progesterone during Pregnancy 719
First Trimester Second Trimester Third Trimester

Control X = 31 .5 Control X = 62.8 Control i = 118.4
59.4 11
60.0
200 .0
:;
11 0 .0
j 183.2 11
E f e
-~
~
180 .0 ~
ii'
~
'É
"'
.s
Qi
>
8
~ ~ 1'
160.0 ~
1'
E
~ ~
i
Q)
_J il
~o
Q)
e::
e
2
~
Q_
~
-¡¡
Q_
E
"'
~
Q_
140.0
1
"' f
120.0
"'
Q)
a:"'
~
o e
~ 100.0
E
::i
(¡;
(fJ 40.0 80.0
• p-value < .05
t p-value < .025
* p-val ue < .01
§ p-value < .001
!I p-va1 ue < .0001
Figure 54-8: Pooled trimester data for progesterone in pregnancy: fetal distress vs.
normal pregnan cy (BPP = Biophysica l Profile; IUGR = lntrauterine Growth Restri ction ).
ln Figure 54-4, the progesterone leve Is from the poo led tal distress in labor, low apga r seores, low biophysical
first trimester data ofthe control group versus first and profiles (BPP), intrauterine growth restriction (IUGR)
second trimester spontaneous abo11ion and in the sec- or oli gohydram ni os ali had signifi cantl y lower levels of
ond trimester for those patients who had second trim es- progesterone observed during both the second and third
ter spontaneous abortions is shown . In ali cases, the trimester ofpregnancy.
progesterone level s were significantly lower in these
two groups. In Figure 54-8, a variety ofdifferent pregnancy events
are presented. Twin gestation s had signifi cantly higher
Those patients who had abnormal pl acentae are shown progesterone leve ls during the first, seco nd and third
in Figure 54-5 . The patients who had adherent pl acen- trimesters of pregnancy. Patients with postpa11um de-
tae had elevated progesterone leve ls during th e first tri- pression had significantl y increased leve Is of progest-
mester ofpregnancy but they beca me significantly de- erone during the first trimester of pregnancy but they
creased in the second trimester. Those patients who had were decreased in the second trimester. Pati ents who
a low-lying placenta and a placenta prev ia (as identi- had toxemia of pregnancy had significantly elevated
fied by early ultrasound) and a midtrimester abruption leve Is of progesterone in the fi rst tri mester of pregnancy.
or subchorionic hemorrhage (a lso identi fied by ultra- They were noted not to be significantl y di fferent from
sound) had signifi cantl y lower progesterone levels both the control group in the seco nd or third trimesters of
in the second and the third tri mes ter of pregnancy. pregnancy. Those patients who had pregnancy-induced
hypertens ion, however, had significantly lower proges-
In Figure 54-6, those who experienced various presen- terone leve Is during the second trimester of pregnancy
tations of threatened prematuri ty are presented. The and patients who were smokers had significantly lower
progesterone levels were significantl y decreased dur- leve ls in both the second and third trimester of preg-
ing the second and third trimester in those patients who nancy. Those who experienced a postpartum hemorrhage
had rece ived only Terbutaline as a tocolytic agent, anti- also had significantly lower progesterone leve ls during
biotic treatment for the treatment of a subclinical the second and th ird trimesters of pregnancy.
chorioamn ioniti s, an occurrence of premature rupture
of the membranes (PROM ), or a cervica l cercl age be- The progesterone leve Is pooled by six-weekl y intervals
cause of cervical insufficiency. This trend continued sig- for the control group and the abnorma l placenta, threat-
nifi cantly in to the third trimester of pregnancy. ened prematurity, and the feta l distress groups are shown
in Figures 54-9, 54- l O and 54-11 respectively. For the
In Figure 54- 7, conditions or events associated with fetal abnormal placenta and threatened prematurity groups,
distress are shown. While patients who exhibited meco- th e progesterone leve ls are stati st ica ll y significantl y
nium stai ned amni otic fluid had higher leve ls during lower for eac h of the last four 6 week ly intervals of
the first trimester, they were significantly lower in the pregnancy. For the feta l distress groups, the leve ls are
seco nd trimester. Patients who were identifi ed with fe- stati sti ca ll y lower in the last three 6 week ly intervals of
720 The Med ica! and Surgical Practi c e of NaProTECHNOLOGY
pregnancy. progesterone during the course of th e pregnancy. In the

early days ofthis program , it was n 't entirely known what
A summary, by trirnester, as to the variation in progest- leve ! of progesterone wo uld be consi dered normal. As
erone leve! from the control group fo r each of th e con- a result, progesterone was administered to patients who
ditions studi ed is presented in Table 54- 1. had normal pregnancies.
T he coefficient of va ri ation (CV) for the progesterone However, that is of sorne va lue when it comes to the
assays conducted during the co urse of this eva luat ion design ofthi s partic ul ar stud y because in both the stud y
range from 5.0-9.5 percent throughout the entire range and the control popul ation, progesterone was be ing ad-
of pro geste ro ne leve! assess ment. ministered so that the inj ection of progestero ne should
not infl uence the res ults of the interpretation of the
In thi s study, both the study and contro l populations progesterone assays. fn addition , it has been shown that
were receiving intramuscular progestero ne during the by 72 hours fo ll ow ing intramuscular progeste rone ad-
course of the ir assessment. The progesterone was administration the serum progesterone leve] fa ll s gener-
ministered because of a prev ious hi story of infe rtili ty a ll y below 1 ng/mL2 7• Thus, by 72 to 96 hours after
and with the purpose of decreas ing the incidence of admini strati on, when the subsequent serum progester-
spontaneous aborti on. At the same time, progesterone one was drawn , this wo uld not be expected to affect the
leve ls we re being monitored to assess the need for progestero ne assessment. It wo uld have reac hed its
trough. Furthermore, it has been observed that the ad-
mini stra tion of progesterone-like s ub stances during
Table 54-1: Summary Table of Statistically pregnancy does not di sturb the metaboli sm of progest-
Significant Changes in Progesterone Levels erone w ithin either the maternal or fetop lacenta l com-
by Condition or Event partm ents. 28
Trimester
Co ndition or Event Fitst Sec ond Third
lt has been kno wn fo r a lon g time that progesterone is
decreased du ri ng the first tri mes ter of pregnancy in pa-
Previous history tients who ha ve spontaneous abo1iions. lt has also been
PCOD J. J. J.
IAB NC J. J. thought that the placenta takes over for the production
One SAB NC J. J. of progesterone during the second and th ird trimesters
Three or more SAB NC J. J.
Prematurity NC J. J. ofpregnancy29 . This study shows that the leve! ofproges-
terone in first and second trimester spontaneous abor-
Cu rren! pregnancy
First trimester SAB J. tions are indeed stati stically decreased. ln fact, th is ob-
Second trimester SAB J. J. servation supports the structure of this study. ln spite of
Ad herent placenta t J. NC
Low lying placenta & NC J. J. receiving exogenous progesterone, these changes, which
placenta previa were observed by others, were a lso observed here.
Midtrimester abruption NC J. J.
Terbutaline on ly t J. J.
Antibiotic Rx NC J. J. Howeve r, a decrease in progesterone producti on, pre-
PROM NC J. J. sumab ly by the placenta , durin g the second and third
Cerclage NC J. J.
Twins t t t trimester of pregnancy in a va ri ety of different p reg-
Postpartum depression t J. NC nancy-related co mp lication s and previous pregnancy
Toxemia t NC NC
PIH NC J. NC hi storica l events was also observed. Th is suggests that
Smoker NC J. J. the role of progesterone as an indi cation of place nta!
Postpartum hemorrhage NC J. J.
Meconium stained AF t J. NC function may be more significant than what had been
Fetal distress NC J. J. prev iousl y appreciated and is especiall y importa nt into
LowApgars NC J. J.
NC J. J.
the second and third trimesters of pregnancy. This stage
Low BPP
IGR NC J. J. of pregnancy has onl y been m inimally studied in the
Oligohydramnios NC J. J.
past.
Groups
Abnormal placentae t J. J. While it is not new that a variety of pregnancy-re lated
Threatened prematurity NC J. J.
Fetal distress NC J. J. comp lications are assoc iated w ith decreased progester-
one production, in thi s study, there is an expanded eva lu-
NC = no statistically significan! ch ange ation of that very type of assess ment. For examp le, it
t = statistically significant increase
J. = statistica lly sign ifican! decrease has been shown previously that serum progesterone lev-
e Is have been noted to be decreased in intrauterine fetal
Chapter 54 : Assessing Progesterone during Pregnancy 721
Comparison of Progesterone Levels

Means of All Levels at Six-Week lntervals
Study Group
Abnormal placenta! 148.4
150.0
_J groups {N=63)
E
e;, - Normal controls
e
<ll D Abnormal placenta! groups
e
~100. 0
-¡¡;
<ll
e
c.
E
~ so.o
(/)
o.o
2-6 weeks 8-12 weeks 20-24 weeks 26-30 weeks 32-38 weeks
p-value NS' NS 1 .0056' 1 CQQIEJ
1 Not stat1sllcally s19nifican1 Mean Progesterone - Six-week inlervals
2 f.lest (equal variance)
3 Mest (unequal variance)
4 Mann-Whllney U test
Figu re 54-9 : Pooled six weekly data for progesterone in pregnancy: abnormal
placenta! groups vs. normal pregnancy.
Study Group
150.0 Threatened Prematurity
_J Group {N=226)
E
e;, • Normal coritrols
e
<ll CJ Threatened prematunly group
e
~ 100.0
e
<ll
c.
E
~ 50.0
(/)
o.o
2-6 weeks 8-12 weeks 14- 18 weeks 20-24 weeks 26-30 weeks 32-38 weeks
p-value NS' NS 1<0001' 1 1<.0001'1 1<.0001'1
1 No1 sta11sbcalty significan!
2 1-test (equat variance)
Mean Progesterone - Six-week intervals
3 /-tes t (unequal variance)
4 Mann-WMney U test
Figure 54 -10 : Pooled six weekly data fo r progestero ne in pregnancy :

threa tened prematurity group vs. normal pregnancy.
Study Group
150.0 Fetal Distress-
Current Preg nancy {N=44)
~
Cl
e • Norma l controls
<ll O Fetal distress group -currenl pregnancy
e
~ 100.0
-¡¡;
<ll
Cl
ec.
E
2 50.0
<ll
(/)
o.o
2-6 weeks 8-1 2weeks 14- 18 weeks 20-24 weeks 26-30 weeks 32·38 weeks
p-value NS ' NS NS l .00581 l .02451 1 04081
1 Not statistically silJnrl'icant
2 t-test {equal variance)
3. 1-test (unequal vanance) Mean Progesterone - Six-week intervals
4 Mann-Wh1tney U test
Figure 54-11 : Pooled six week ly data for progesterone in pregnancy: fetal
distress group vs . normal pregnancy.
death ,6·9· 13 pre mature labo r, 17 threatened premature la- The data in thi s ve ry la rge a nd systematic asses me nt
bor, 16 · 17 pre m a tu re rupture of t he m e mbra nes, 17 of progestero ne in pregnancy suggests that the more sig-
amni o niti s, 17, and abrupti o n ofthe pl ace nta . 1' lncreased nifican/ progesterone de.ficient time period in pregnancy
levels ofproges terone have al so been obse rved in tw in is actua/(¡1after the .first tri mes ter and in to the second
º
preg na nci es, 2.5· 14•2 Rh izoimmuni zati o n9 and hydatid i- and third trimes ters .
fo rm mol e24 . The las t two condi tio ns were not a compo-
nent ofthi s stud y. In the earli er publi shed studies, a very wid e range o f
proges terone was co n ide red to be no rmal. In rev iew-
Progeste ro ne has been freq ue ntly assessed in toxemia in g those studies, o ne ees a c lea r pattem of decreased
o fpregna ncy and fo und to be va ri o us ly decrea ed 6· 12· 13 , progeste rone producti o n in such conditions as threat-
increased 9 or not changed 15 . In thi s study, no significant ened prematurity, premature birth, toxemia of pregnancy,
c hanges were o bse rved in toxemi a a ltho ugh th e levels pregnancy-induced hype rte ns io n, and so forth . In fact,
we re genera ll y o bserved to be hi g he r. We d id find de- had stati stica l eva luati o ns o f progesterone gone beyond
c reased leve ls of progestero ne in the second trim este r a generall y s impl e desc ripti ve presentation in these ea r-
of patients with pregnan cy-indu ced hype rte ns io n. Oth- li er studies o r the sampl e s izes had bee n larger thi s ma y
e rs have made imil a r o bserva tio ns, 14 whil e still o th e rs have been better identifi ed.
ha ve o bserved no s ignifi ca nt di ffe rences 15 .
The question of how to determine the normal fo r proges-
As early as 195 1, the urina ry excreti on ofpregnaned io l, te rone in pregnancy is probl emati c. In o lder studies, the
the main urina ry metabo li te of progesterone was ex ten- mean ± 2 sta ndard dev iati ons from the mean (95% con-
s ive ly eva luated in no rma l and abno rma l pregna nc ies 30 . fide nce limits) we re co ns ide red no rm al or th e no rma l
In these studi e , decreased leve ls of pregna nedi o l we re ra nge. Thi s is a co mmo n a pproach w hen loo kin g at es-
o bserved in a va ri ety of pregna ncy-re lated co mpli ca- tablishing normal va lues fo r a who le ran ge ofbiochemi-
tio ns som ewhat s imil ar to th e studi es on progeste ro ne. ca l marke rs. However, we fo und that stati stica lly s ig-
Decreased le ve ls o f preg na nedi o l we re o bse rved in nificant (eve n p< .0001 ) progesterone leve Is were fo und ,
spo ntaneo us a bo rti o n, mi ssed a bortion, in tra ute rin e fe- when analyzed o n a po int by po in t bas is, to ofte n fall
tal death , premature labor, pl ace nta previa and accidental we ll within th at ra nge.
hemorrhage and intra uterine growth restriction30- 34 . Preg-
na nedio l leve ls we re a lso consisten tl y observed to be In additi o n to the above, automated assays fo r progest-
decreased in pa ti e nts w ith toxemi a of pregnancy and e rone in mode rn medi c ine are much more preci se tha n
pregnancy-induced hype rte ns ion 3º· 3 1.3 2·34 . they were 25 to 40 yea rs ago. Fo r exa mpl e, wh il e the
coefficie nt ofvari ati on in the curre nt study is only mod-
In thi s stud y, we a l o o b erved a decrease in second erate ly improved w hen the progeste rone leve ls are be-
and third trimeste r progesterone leve ls in pati ents w ith low 50 ng/mL, they a re s igni fica ntl y impro ved beyond
certa in types ofa bn o rm al reproductive hi sto ri es. These th at. Lindbe rg, et a l,9 re ported C V (%) of 15.3 to 17.4
ha ve inc luded: a hi story of po lycystic ova ri an di sease pe rce nt in progesteron e assays g reater than 50 ng/mL .
(a lso decreased in the first trim ester), induced abo rti o n,
o ne prev io us spo nta neous abo11ion, three o r mo re spon-
taneous a bo rti o ns a nd pre mature bi rth . T he data wou ld Table 54-2: Coeffi cient of Variatio n (%) for
suggest th at pati e nts w ith these hi sto ri es houl d be con- Se rum Progeste rone Assessment -
idered at ri sk fo r pl ace nta! insufficiency in subseq uent The Precisio n of Assay at Diffe re nt Ranges of
pregna nc1es. M easurem ent: 1974 vs. 2001
PPVI
Al so, a number of new, current pregnancy probl ems were Progesterone level 19741 2000 2
ng/m l CV(%) CV(%)
observed in thi s stud y to ha ve dec reased progesterone
producti o n. These conditi o ns, not prev io us ly reported, 10.0 8.3 6.3
include: pati ents with adhe rent pl ace ntae, low- lying pl a- 25.0 8.3 5.0
33.0 8.3 5.8
centae o r pl ace nta prev ia (observed by ul trasoun d),
73.2 17.4 9.5
midtrim este r a bruptio ns (observed by ultraso und ), 121.4 15.3 6.6
smo ke rs, postpa11u111 he morrh age, fe tal di stress, low
1. Lindberg BS , Nilsson BA, Johansson EDB: Plasma Progeste rone
Apgar seo res, meconium- sta ined am ni oti c fl ui d. de- Levels in Normal and Abnormal Pregnancies. Acta Obste! Gynec
creased bi ophys ica l profiles, intra uterine growth restri c- Scand 53: 329-335, 1974.
2. Data from Diagnostic Products Corporation and Pope Paul VI
ti o n oli go hydra mni os a nd pati en ts who deve lop post- lnstitute , 2001 .
partum de press io n fo ll ow in g deli ve ry.
Chapter 54 : As sess ing Progeste ron e during Pregnancy 723
In our laboratory, this ranges from 6.6 to 9.5 percent The older studies also relied upon a woma n's reco ll ec-
(Tab le 54-2). This signiti cant improvement in the coef- ti on ofthe tirst day ofher last menstrual period to date
fi cient of variation indi cates a more prec ise assay. the gestational age ofthe pregnancy. Ultrasound dating
during the l 960s through l 970s was ra rely, if ever, uti-
Modern progesterone assays also offer a di stinct im- li zed. Additionally, Peak Day information was not ava il-
provement in cross reacti vity over the older assays . For able when those earlier studi es were done . lt has shown
exa mpl e, Ottesen and Lebech , 11 in 1979, reported that th at the Peak Day is equal to the ultrasound date + 1.97
their assay had a 31 .0 percent cross reactivity with 5a- days in dating the gestational age of th e pregnancy with
pregnane 3, 2 dione. The DPC-RI assay used in thi s a range of O to l O days in 100 percent of 173 consecu-
study cross reacts only 0.8 percent with thi s metabo- tive cases 38 (see Chapter 53). In additi on, early ul tra-
lite.36 Previous studi es 11•37 have shown the presence of sound to date pregnancy is now we ll accepted as a more
signiticant amounts of circul atin g 5a-pregnane 3, 2 accurate dating technique than recallin g the first day of
di one in blood of pregnant wo men. Co ncentrations the last menstrual period (LM P). 39
ranged from 3 to 46 ng/mL during pregnancy with higher
concentrat ions, 20 to 40 ng/mL, being observed later in When the progesteron e data were evaluated on a po int-
pregnancy or the week be fore term . These substanti al by-point, every-two-week basis fo r each of the above
5a-pregnane 3, 2 dione concentrati ons in blood make it conditi ons and when th e data were pooled and eva lu -
very important that clinician and laboratori es use as- ated on an every-six-weekl y basis as opposed to a tri-
says that have low cross reactivity to 5 a-pregnane 3, 2 mester bas is fo r each of th e conditions li sted, similar
dione in their progesterone assays in order to obtain identiti ab le pattern s were observed . Whi le the vo lu me
true blood progesterone determin ations during preg- of th at data is ex tensive, it is reproduced in the Appen-
nancy. Th is cross reacti vity with 5a-pregnane 3, 2 dione di x.
may also be concentration dependent whi ch would make
the use of a se lective progesterone assay even more Thi s comprehensive look at progesterone in pregnancy
important during pregnancy. The present study used new, rai ses a number of questi ons with rega rd to the ro le of
improved, more prec ise, accurate and se lecti ve immu- progesterone during pregnancy and the ab i1ity of proges-
noassays. The overall effect is that more precise and terone to be used to assess placenta! functi on and as a
accurate blood progesterone leve ls were obtained when monitoring device for the use of progesterone supple-
compared to assays which we re used in previous stud- mentation during pregnancy. lt is hoped that it wi ll lead
1es. to further investigation along these lines.
J. Zandcr .1 : Progesteronc in Hu man Blood and Tissues. Na turc 8. Tu lchinsky D, Hobe l CJ, Yeagcr E, Marshall JR : Plasma Es-
(Lond ) 174: 406-407. 1954. tronc, Estradi ol, Estriol, Progestcronc and 17- Hydroxyprogest-
cronc in Human Pregnancy. l. ormal Prcgna ncy. Am J Obslel
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onc Lcvels in ormal and Abnormal Pregnanc ies. Acta Obstel
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1O. Parkc r CR, Evercll RB, Quirk JG, Wha ll cy PJ , Gant NF: Hor-
4. Ya nnonc ME: Pl as 111a Progcsterone Leve Is in No r111al Pregnancy, monc Producti on During Pregnancy in Jhe Primi gravi da Patienl.
Labor and th e Puerperium : l. Mcthod of Assay. Am J Obstet l. Pl as ma Leve ls of Progesterone and 5 Alpha- Pregnan e-3, 20-
Gynec 1O1: 1054-1 057, 1968. Di onc Throughout Pregnancy of Norma l Wo 111en and Women
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Levels in Normal Prcgnancy, Labor and the Puerperium. 11. Clini- Gyncco l 135: 778-782, 1979.
ca l Dala. Am J Obstct Gynec 1O1: 1058- 1061. 1968. 11. Oncscn B, Lcbech PE: Pl as ma Progesteronc, Seru m Estrio l and
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Measurcd by a Rapid Competiti\ e Protcin Binding Technique. tcct Changcs Befare Spontaneo us Labor. Acta Obstet Gyneco l
Acta Endoc rin olog ica 61: 607-6 17, 1969. Scand 58: 423-427, 1979.
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Pl asma Progesteron e Leve ls Durin g Human Pregnancy and La- Pregnanedi ol and Oestrogens in Foetal Death from Seve re Prc-
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Oestriol with Uri nary Tract Oestrogen Levels in Cl ini ca l Ob- Medroxyprogesterone Acctate Does Not Perturb the Profile of
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Using Progesterone Support
during Pregnancy
rogesterone support in pregnancy has been in use This idea has received a considerabl e boost from recent
P for nearly 60 years , having received its start with
publications dating back to the l 940s u lts initial use
widespread publicity given to two papers which both
showed a sign ificant reduction in pre-term deli very rates
was in pati ents who had habitual spontaneo us abor- with the prophylactic admini stration of either progest-
tion caused by lutea l phase deficiency. Luteal phase erone14 or 17 a-hydroxyprogesterone caproate. 15While
defic iency is dueto a fa ilu re ofthe function ofthe cor- this was portrayed as a " major breakthrough" by the
pus luteum and the production of progesterone from national media, in rea lity, data on the use of progester-
the corpus luteu m is indi spensable during the first seven one (or 17 a-hydroxyprogesterone ca proa te) for the pre-
weeks of pregnancy. Surgical remova l of the corpus vention ofpreterm labor ha ve appeared in the literature
luteum during thi s period oft im e, results in pregnancy for nearly 30 years. 16-22
loss 3 and progesterone replacement ca n help maintain
the pregnancy. 4 There is ev idence to support the con- Progesterone itse lf, rather than any of its metabolites,
cept that progesterone given in ea rl y pregnancy may appears to be the active natural progestational com-
be useful in so rne women with recurrent miscan-iage5 pound in the uterus. In co njun ct ion with estradio l,
and that the measurement of serum progesterone lev- progesterone has the fo ll ow in g important fu nctions:
els in early pregnancy can be an adjunctive marker for
• It sti mul ates the growth of th e uteru s
th e further assessment of pathologic pregnancies. 6·7
• 1t causes "maturati on" ( i.e. di fferentiation) of the
endometrium converting it to a secretory type.
The adm ini stration of progesterone later in pregnancy
• It st imulates the decidualization of th e en-
has been considered to be justified because of an ob-
dometrium required for impl antati on.
se rved decrease in circulating progesterone with the
• And it inhibits myometri al contracti ons. 23
onset of labor,8 an association of premature labor with
decreased progesterone co ncentrations 9 and the obser-
vation that progesterone has a tocolytic effect 10·13 · lt is The corpus luteum is the maj or source of progesterone
thought that the ad mini stration of exogenous progest- during the first 9 to 1O weeks of pregnancy. There is,
erone mi ght therefore reduce uterine contractions and however, a shi ft in progestero ne producti on from the
help prevent preterm labor. corpus luteum to the placenta between the 6th to the
725
l 2th week ofpregnancy. During the 2nd and 3rd trim es- progesterone needs to be taken in to considerati on when
ter of pregnancy it has genera ll y been thought th at the determining the dosage of proge terone support.
placenta is the maj or source of progesterone produc-
tion. However, it has also been shown th at the corpu s In women who ha ve preterm labor, both serum leve ls
luteum of pregnancy continues to produce progester- of progesterone and 17 cx-hydroxyprogesterone are sig-
one24during this peri od of time. Progesterone concen- ni fi ca ntl y decreased durin g the seco nd and the third
trations in the periphera l vein of women at term were the tri mester of pregnancy. 17Since progesterone has an in-
same as the progesterone concentrati on in the ovari an hi bitory effect on uterine musc le contractility,26·30 thi s
ve in comin g fro m the ovary where there was no co rpu does not appea r to be un ex pected. The effect of proges-
luteum. The progesterone concentrations from the ovary terone on uterine contractility may be med iated thro ugh
in whi ch a co rpus luteum was present, howeve r, were th e inhibiti on of prostag landin-induced myo metria l ac-
more th an twi ce that of the progesterone leve ls in th e ti vity whi ch is inhibited by progesterone 13·31 and proges-
periphera l vein (Figure 55- 1). terone may decrease th e number of gap j unction fo r-
mati ons in the myometrium. 32 Progesterone is al so fo und
Th e de novo synthesi of progesterone by the placenta in very large concentrati ons in th e myo metrium of the
is limited . Thi s is mainl y because progesteron e requires pregnant uteru s33 and th at conce ntrati on ca n be in -
LDL cholestero l and the syncyti otro ph obl ast, where creased further with the ora l admini stration of micron-
progesterone synthes is occurs, has very littl e choles- ized 1M H progesterone. The ob ervation that there is
terol. Matern al pl as ma LDL cholestero l is used to an increased freq uency of uterin e contracti ons associ -
bi osynth es ize progesterone beginning at 6 to 8 week ated with an increased li ke lihood of pretem1 deli very, is
of pregnancy and progesterone producti on continu es further ev idence of th e important assoc iati on of these
after thi s peri od of tim e e ven if the ova ri es are refi ndings. 34
moved.25
Other mechani sms by whi ch progesterone may wo rk
Progesterone is produced in very large amounts during in pregnancy in clude its kn own immu nosuppressant ef-
pregnancy (Tab le 55-1 ). ln th e nea r-term pregnant fect in humans.35 For exa mpl e, it has been suggested
woman progesterone is produced in the amoun t of250 that an important role fo r progesterone in mainta inin g
mg/day and up to 600 mg/day in women wi th multi ple pregnancy is its regul ati on of cellul ar immuni ty at the
pregnanci es. Thi s extraordin aril y large producti on of maternal-fetal bed. Lymphocyte proliferation at the ma-
ternal-fe tal interface during pregnancy may be under
the speci fi c regu lati on of progesterone. 36 Progesterone
300 maya lso be an important regulator of gelatinase-B pro-
du cti on at th e fe tom atern al interface . Gelatinase-B (92
kd type IV co ll agenase) is in vo lved in bl astocyst im-
250
pl antati on and troph oblast in vas ion. Progesterone ca n
decrease co ll agenolyti c acti vity in uterin e cervica l fi -
200 brob lasts by decreas ing co ll agenase producti on and in-
E
e, creas ing tis ue inhi bitor of metall oprotein ase activity,
.E.
Q) thus preventing th e di lation of the uterine cervix .37·38
e:
e
~
150
lt is the purpose ofthi s chapter to describe the auth or's
"'
Q) nearly 25 -yea r ex peri ence in the use of progesterone
"'e
o.. support in pregnancy and th e protoco ls currently used
100
at th e Pope Paul VI lnstitute. Th e indi cati ons fo r the
use of progesterone, the protoco l fo r progesterone sup-
50 po1t, th e observed effects ofpro gesterone suppo1t, will
ali be rev iewed a long with th e safety of progesterone
use in pregnancy.
Periph eral Ovarian vein Ovarian vei n
ve in without with
corpus luteum corpus luteum
(NS) (p = <.01 )
lndications for the Use of
Figure 55-1 : Plasma progesterone levels in the peri pheral
vei n and the ovarían vein s with and without a corpu s luteum
Progesterone in PregnanCY ----~
in pregnancy at term (Adapted from: LeM aire WJ , Conly PW,
Moffett A, Cleveland WW: Pl asma Progesterone secreti on by One can onl y pecul ate as to how common progester-
th e corpu s luteum of term pregnancy. Am J Obste! Gynec one support in pregnancy is utili zed at the present time.
108: 132-134 ,1970).
Chapter 55 : Using Progesterone Support in Pregnancy 727
Table 55-1 : Progesterone Concen trations

in Vario us Compartments in Pregnancy
Steroid Concentration
Maternal serum level - 1O weeks 30 .0 ng/ml

Maternal serum level - 24 weeks 75 .0 ng/ml
Maternal serum level - 36 weeks 153.0 ng/ml
Retroplacental blood pool 600.0 ng/ml

Fetal serum levels 7X maternal levels 3
Progesterone production - midpregnancy 75.0 mg/day
Progesterone production - late pregnancy 250-600 mg/day
100 mg progesterone IM - peak serum level 30.3 ng/ml

200 mg progesterone IM - peak serum level 99 .9 ng/ml
1. Kumar D, BarnesAC: Studies in Human Myometri um during Preg nancy. V I. Tissue progesterone profile of
the various compartments in the same individual. Am J Obstet Gynec. 92: 717-719, 1961 .
2. Hawkins DF: Sex Hormones in Pregnancy. In: Obstetric Therapeutrics. Hawkins DF (Ed). London:
Bailliere Tindall, 1974, pp. 106-141 .
3. Ryan KI : Placenta! Synthesis of Steroid Hormo nes. In: Tulchinsky D, Ryan KJ (Eds): Materna l-Fetal
Endocrinology, W B Saunders Co., Philadelphia, PA 1980, pp. 3-16.
4. Klo pper A , Fuchs F Progestagens. In: Fuchs F, Klopper A( Eds). Endocrinology of Pregnancy, 2nd Ed.,
Harper and Row, Hagerstown, M.O. 1977, pp. 99-122.
5. Pearlman W H: [1 6-34 ] Progesterone in oophorectomized-hysterectomized women. Biochem J. 67:1. 1957.
There are no stud ies to show the frequency of its use. pregnancy reaches 13 weeks of gesta tion , the progest-
Simpson and Kauffman have suggested that the expo- erone is di scontinued. Other protoco ls in vo lve the vagi-
sure to progestational agents ofa ll kinds has decreased nal administration of90 mg dail / 4or 50 mg given daily
significantl y over the last 20 to 30 years39 and thi s is by intramuscul ar injection. 45.4 6
consistent with trends previously identifi ed by Wi seman
in the United Kingdom. 40 lt has recentl y been pointed While the u e of progesteron e during the second and
out that this may be th e result of the significant late third trimesters of pregnancy may increase in the next
sequelae that were docum ented fo ll ow ing the in u/ero few years beca use of the recent publication of artic les
ex posure of the fetus to the potent stero id di ethyl stil- suggesting its benefit in the prevention of pre-term la-
bestrol (DES) and that thi s bad ex peri ence has cast "a bor,1 4·15 it is ge nerally not used during the second and
long shadow. " 41 ln spite of thi s, the use of progester- third trimester of pregnancy. Thi s is perhaps best ex -
one, at least in ea rl y pregnancy, does appea r to be wide- pressed by Yazigi, et al, when they sa id:
spread in artifici al reproducti on programs. 42-46
"The use ofprogesterone in ongo ing pregnancy
. . . is a thornier prob lem . Whil e it is clear that
Keep ing perspective, the use of progesterone during
sorne viabl e pregnancies are characteri zed by
early pregnancy (the first 1O to 12 weeks) has been in
lower serum progesterone leve ls than others, it
use for nearly 60 years. Indi cati ons fo r its use have
is un clea r whether or not thera py is beneficia!
included a documented lutea l phase deficiency, hi story
or even necessary for th eir continued we ll be-
of recurrent pregnancy loss, or vaginal bleeding during
ing." 47.
the first 6 to 8 weeks of pregnancy.
Various progesterone support protoco ls ha ve been di s- This com ment and the attitude toward the use of proges-
cussed in th e li terature. Often, progesterone is suppli ed terone in the seco nd and third trimester in pregnancy is
by vag inal su ppos itory ata starting dose of25 mg tw ice troubling. For some reason, tlie intensive investiga-
daily beginning 3 to 4 days after the mi ssed menstrual tion of the role ofprogesterone in pregnancy during
period. The pregnancy is then followed by ultrasound th e second ami third trimester has gone virtual/y
to estab li sh viabi lity. A serum progesterone leve! may unapproached over the last 20 to 25 years. And yet, a
or may not be measured (and usually is not). Once the con iderab le amount of data suggest that progester-
proges terone leve! exceeds 20 to 25 ng/mL or when the one production is clearly sub-optima ! in a va ri ety of
728 The Med ic al and Su rg ical Practice of NaProTECHNOLOGY
pregnancies w he re obstetrica l complications exist (see additio n, serum proge terone leve ls during the co urse
C hap ter 54) . What is troubling is that further research of pregnancy we re further shown to be decreased in a
has not been forthcoming an d investigation ofthi s im- variety of pregna ncy-re lated complicati o ns (see Chap-
portant area has been left unattended. The recent pub- ter 54) . Whi le th e progesterone leve! was fo und to be
lication of the effective ness of progesterone in the de- decreased in women who had spontaneo us abortion (a
crease in prem aturi ty 14 · 15 has led to such comm ents as " I finding th at others had previous ly ide ntiti ed), a n exten-
think it's go ing to awake n people to an o ld idea that s ive data base was estab li shed which docume nted the
kind ofs lipped away." While promi si ng studies in this decrease in progesterone production during the sec-
a rea ha ve ex isted s in ce the l 970s, it has been di fficu lt to ond and third trimester of pregnancy in a va ri ety of
inte rest pharmace uti ca l compani es or govem ment agen- patients who had various obstetri ca l compli catio ns (see
c ies to fund mo re compre hens ive experi mentation. lt Chapter 54 and Appendix). As a result ofthi s project, a
has litera ll y been " sitting o n the pharmacists ' he lffor spec iti c set of indi cati o ns for the use of progesterone in
more than 30 yea rs."48 A nd yet, it is an ed ict ofcontem- pregnancy could be identified and are enumerated (Tab le
porary reproductive medi c ine that progesterone sho uld 55-2).
not be administered after the first trimester. In thi s day
of " evidence-based med icine," the re is no evülence Those patients who have a previous pregna ncy histo1 y
upo n w hi c h to base thi s ed ict. In fact, most evid ence of spontaneous abortion, stillbirth, preterm delive1 y,
that does ex ist actua ll y supports its use. premature rupture of the membranes, pregnancy-in-
duced hypertension ar toxemia, ar abruption of the
For the last 25 years, the a uth or has been suppl ement- placen ta a re co nsidered ca ndid ates for the use of
ing pregnanc ies w ith progesterone. This project began progesterone in pregna ncy through the Po pe Pa ul V I
with the use of progesterone in early pregnancy in paln stitute protocol for progesterone s upport in preg-
tients with in fertility o r a prev ious hi story of mi scar- nancy. In additi on, those patients who, during the course
riage. The goa l of progesterone therapy was to decrease of their pregnancy, develop s ig ns o r symptoms of
the incide nce of mi scarr iage in subseq ue nt pregnan- threatened premature labor o r objective s ig ns of cer-
c1es . vica l dilatation a nd effaceme nt to whi ch a cervical cer-
clage is necessa ry, a re al so provided progesterone sup-
As this project began to grow, it was difficult to deter- port. A 11 mu/tiple pregnancies o r pregnancies with a
mine the dosage of progesterone that shou ld be given majar congenital uterine anomaly are supported
a nd an objective mea ns by w hic h the pregnancy could throug hout the e ntire cou rse of their pregnancy. Pa-
be mo nito red. This led to the measurement of serum tients w ith a documented hi story of infertility are also
progesterone leve ls during the course of pregnancy. supported . In so rne cases, progesterone is monitored
Eventuall y, a standa rd c urve fo r progesterone in preg- as a matter of ro utin e to assess Further the poten tial use
nancy (a norm ogra m) was developed and the abili ty to of proge terone in a g ive n pregnancy. Fo r exa mpl e,
obj ecti ve ly assess progesteron e became poss ibl e. In wome n w ho ha ve a hi story of prem enstrual sy ndrome
where there is a documented luteal phase deticiency of
progesterone during t he postovulatory ( post-p eak)
phase of the menstrual cyc le, even tho ug h they ha ve
Table 55-2: lndicatio ns of th e Use of
not had prev io us pregnancy difficulties, would be a
Progesteron e in Pregnancy - candidate for assessment of seru m progesterone in early
Pope Paul VI lnstitute P ro tocol pregnancy. That i then plotted on the normogram and
a determination is made w ith regard to the use of the
progesterone.
Previous SAB
Previous stillbirth
Previous prematurity (<37 weeks)
Previous PROM (<37 weeks ) Pope Paul VI lnstitute Progesterone
Previous pregnancy-induced Support Protocol _ __ _ _ _ _ _~
hypertension (or toxemia )
Previous abruption of placenta
Patient with threatened premature A number of vario us approac hes to the use of progest-
labor or cerclage
Multiple pregnancy erone support in pregnancy have been utili zed. These
lnfertility support programs are noteworthy in thei r lack ofuni for-
Congenital uterine anomaly (majar)
Low progesterone level mity. The two hormones th at have been genera ll y used
are 17-hydroxyprogesterone caproate ( 17 OHP-C) and
progesterone (P).
Chapter 55: Using Progesterone Support in Pregnancy 729
With 17 OH P-C, the dosages ha ve generally ranged rrom Progesterone ha bee n se lected as the horm one of
250 to 1000 mg given 1M on a weekly basis. 15 - 19•21 .-1 2 choice for th e support of pregnancy over and abo ve 17-
Progestero ne has been used eith er by vagina l supposi- hydroxyprogestero ne ca proate, 17-h ydroxyprogester-
tory (25 mg to 100 mg), 14ora l administration (200mg/ one hexonate ( 17-0H P-H ) or medroxyprogesterone ac-
400mg),20- 22 ·33 .4 48% vagin al ge l,46or by intramuscular etate (MPA). The selecti on of progesterone is based
inj ection (50mg !M dail y).44.45 What is particularly note- upon the fo ll ow ing fac tors:
wo11hy about ali ofthese programs for the adm ini stra-
l. Progesterone is the main suppo rt hormone of
tion of progesterone is the absence of an objective
pregnancy.
means to monitor admin istration of the dosage of
progesterone that is being provided and the ability to 2. 17-0HP-C, 17-0HP-H and MPAarea ll syntheti c
decide whether th e progesterone shoul d be continued ana log ues of 17- hydroxyprogestero ne and
or di scontinued. progesterone and are thus chemi ca lly different
from natural progesterone and this likely de-
The Pope Paul VI lnstitu te Progestero ne Suppo11 Pro- creases their abil ity to bind to myometrial proges-
tocol now has nearly 25 yea rs of ex peri ence support- terone receptors. 49
ing its use. There are severa ! important feat ures with
3. 17-0HP-C, l 7-0HP-H are genera lly not ava il-
regard to this protoco l:
able.4117-0HP-C, th e most commo nly used and
• First and fo remost is its abi lity to obj ectively the subj ect of one of th e recent rev iva ! papers, 15
monitor the dosage of progesterone being pro- was manufactured under the trade nam e
vid ed based upon the erial monitoring of se- Delalutin (Bristo l-M eyers-Squ ibb Company), but
rum progesterone leve ls during pregnancy. its man ufacture was discontinued in 1986 dueto
a dec lining market share. 50
• 1ts se lection of progesterone o ver the use of 17-
hydroxyprogestero ne caproate. 4. While 17-0HP-C can be considered safe in preg-
nancy (as is progesterone), MPA has sti ll a few
• lts use during the co urse of pregnancy where
lin ge rin g question s remainin g wi th regard to
suppl ementati on of progesterone can be objec-
safety.
tively quantified. Thus, it is not limited to use in
onl y the first trim ester of pregnancy, but often 5. Progestero ne is a compl ete ly natura l hormone.
exte nds into the second and th ird trimesters. Tha t is, it is a hormone manufactured in abun-
dance by the hum an body durin g pregnancy,
• lts proven safety.
150 ..-~~~~~~~~~~~~~~~~~~~.......,..
, ~~-,1,
- 2~~--.
/
166.0
Progesterone Levels in
160
Normal Pregnancy
(N=109)
140
Patient's Name:
G P LMP
..... Er e - - - - ETA
E 120
o,
.E.
DPC
"'e:~ 100
RIA
~
"'"'en 80
~
Q.
E
2 60
"'
(/) . '
40
--
20
National Hormone Laboratory
~
o
6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gesta tion
Figu re 55-2: Progesterone levels in norma l pregnancy with the mean and one
standard deviation shown (DPC-RIA).
whil e the others are ali fore ign to the body and mea n. By plac ing that marker to fl ank the mean proges-
not manufac tured by it. tero ne leve! during pregnancy (by gestati onal age at 2
weekl y interva ls), the hom1one leve! that is drawn on an
The key to the obj ecti ve suppl ementation of progester- indi vidual patient ca n be plotted in a gestation al age-
one durin g pregnancy is the ava ilabili ty ofa mea nin g- spec i fíe way and the curve can be broken up in to f our
ful standa rd curve (or normogra m) fo r the producti on zones (Zone 1 through Zone 4). Thi s is illu strated in
of progesterone during th e co urse of pregnancy. These Figures 55-4 and 55-5 (for RI A and chemiluminescence,
curves are not ava ilabl e in most laboratories. The a- respectively).
tional Horm one Laboratory ofthe Pope Paul VI In ti -
tute, however, has developed such a curve in the many In usi ng progesterone in pregnancy, onl y human iden-
years of its work in th e use of progesterone-supported tical progestero ne is uti 1ized, and , over the Iast 25 years,
pregnancy (see Chapter 54). The standard curves fo r the intra muscul ar inj ection of progesterone has been
nonnal pregnancy fo r radioimmunoassay (DPC- RI A) and the main route ofadmini strati on. The ori ginal protoco l
chemiluminescence ( Immul ite- DPC) are shown in Fig- fo r thi s was pub lished in 199 1,51 Progesterone should
ures 55-2 and 55-3. Whil e standard curves such as thi s be admini stered to the indi cated popul ations as earfy
are somewhat di fti cult to compile, they are not at ali out as possib fe at the beginning of pregnancy. Thi s is best
of th e reach of most laboratories. lt does require a co n- accompli shed in those wo men who are charti ng the
sistent effort to moni tor erum progesterone leve ls in CREIGHTON MODEL System (CrMS). As a matter of
patients whose pregnancies are completely norma l and ro utin e, when the woma n reaches 16 days po t-Peak
to do that with the assay whi ch is being used withi n the (Peak + 16), a pregnancy test can be perfo rmed and, if
laboratory. There are di ffe rences between assays fro m necessa ry, progesterone support can be initi ated.
laboratory to laboratory (even if it is the same assay sys-
tem) and , of cour e, diffe rences between di ffe rent assay During the course of pregnancy, progesterone leve ls
systems. In sorne cases, these may be qu ite signi ticant are drawn on an every two-week bas is and progester-
di fferences and these need to be accounted fo r in the one is suppl emented based upon the progesterone leve!.
clinica l utilizati on ofsuch assessments. The dosage ofprogesterone admini stered is determined
based upon th e zone that the progesterone leve! is in.
These standard curves are fla nked by two dotted lines When the progesterone leve! is drawn , it shoul d al-
whi ch represe nt one tandard deviation away from the ways be drawn immediately prior to the administra-
180 I
176.
I
169.8
.'
Progesterone Levels
156 .8
160 in Normal Pregnancy
(N=109)
140 ,,
Patient's Name: , ,,
G p
- -- LMP ,,
~ 120 ETC ETA
.:."' lmmulite
CP
e
e
~
100
91,•
lfl
CP
"'e
Q..
80
.·
E
::J
Q; 60
rJ)
40
20 .. National Hormone Laboratory

~ Pope Paul VI lnstitute
o
4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-3 : Progesterone levels in normal pregna ncy with the mean and on standard
deveation shown (DPC-lmmulite).
180
ZONE 3 1722
Zones of Progesterone 166.0
160 in Pregnancy 1530
(N=109) ZONE 4 ,'
140 Patient's Name:

G
--- p
- - - - LMP ,,
,'
,,
ETC ETA
120 ,
"E DPC
• '°'ZONE 3
e,
..=.., 100
RIA
103.9
e: 903
.,e ZONE 4 812

.,
iií
Cl
80 7' 3
ZONE 2
'
e
D.. ZONE 3
65.9 ZONE1
E
:J
:;;
60 ZONE4
... 53.5
55.5
ZONE 1
en <10.4
.....
ZONE 2
....
.. . . -
40 # •ZONE 3 35.0
20
22.4
ZONE 2
..... ZO NE 1
National Hermane Laboratory

-
· i:o N E1 ~~ Pope Paul VI lnstitute
6 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-4 : The four zones of progesterone shown using the DPC-R IA assay.
180
1 ' ZONE 3
176.0
Zones of Progesterone 169.8
160
in Pregnancy
(N=109) ZONE4
140
Patient's Name: ---~o--------
G_ _ _ P _ _ _ _ LMP _ _ _ _ _ __
"E
e;,
..=.
120
ETC ETA,_ _ _ _ _ __
lmmulite
. Z~NE.· 3 '1S.O
e"'
j
e • • , 101 .8
100
• 91.4
.2l
"'"'
Cl
ZO NE 4 ,...,
~ 82.3
ZONE2 ,.
e 80 73.6
D.. 65.2 ,. ZONE 1
E
~ 60
en"' ZO NE 1
40
20
ZONE 2 • .•
.•;o:~"··· Pope Paul VI lnstitute
o
4 6 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-5: The tou r zones of progesterone shown using the DPC-l mmulite assay.
732 The Med ica ! an d Su rgical Practice of NaProTECHNOLOGY
-------
!ion of the subsequenl progesterone dose . In this way, progesterone is decreased to 100 mg twice week ly and
the proge terone leve! is drawn at the bottom of the ifin Zone 3, the admin istration ofprogesterone ca n be
natural absorption pattern ofthe exogenously adminis- discontinued but a progesterone leve! is repeated in
tered progesterone and is thus drawn at its trough. 1n two weeks to see that it ma in ta ins itself. lf it begi ns to
thi s way, a best estimate ofthe baseline production of decrease again , then progesterone ca n be restarted
progesterone during the course of that pregnancy can (Table 55-5).
be obtained and an objective decision can be made
relative to the next dosage of progesterone to be ad- Between the 34th week ofpregna ncy and fu l! term, if
ministered. The goal of treatmenl is to see that the se-
rum progesterone leve/ during pregnm1c\' reaches ei-
ther !he mean leve/ or is in Zone 3 or Zone 4. Table 55-3: Progesterone u pplementatio n -
First 12 Weeks of P regna ncy
lfthe woman is taking either oral progesterone or vagi-
nal capsules or suppositories of progesterone, she
should not use those the night before she gets her Starting dose 200 mg IM
progesterone leve! drawn. Again, with the monitoring lf <20 nglml 200 mg IM twice weekly
of progesterone levels every two weeks, an objective
assessment ofthe dose ofprogesterone can be obtained. lf Zone 1 Consider adding progester-
one oral or vaginal capsules
The supplementation protocol is outlined in Tables 55- lf 20-25 ng/ml 100 or 200 mg IM twice
weekly
3 through 55-6 and is illustrated in Fi gure 55-6.
lf >25 ng/ml 100 mg IM twice weekly or
discontinue (lf discontinued ,
The startin g dose of progesterone is 200 mg given in- continue to monitor serum
tramuscularly (IM). lf the progesterone leve! contin- progesterone levels.)
ues to run less than 20 ng/mL, then progesterone is
continued ata dosage of200 mg 1M twice weekly. 1fthe
leve! is in Zone 1, additional oral or vaginal progester-
one can be considered. 1fthe leve! is between 20 and 25
ng/mL, then the dosage ofprogesterone is either 100 or
Table 55-4: Progesterone u pplem entatio n -
200 mg given t:vvice weekly. lfthe leve! is greater than 25
12 to 24 Weeks Gestatio n
ng/m L, the progesterone may be continued at 100 mg
1M twice weekly or di scontinued (Table 55-3 ). 1f it i
discontinued, a progesterone leve! should be drawn
twice at two wcckly intervals and ifit is maintained at Zone 1 200 mg IM twice weekly consider
progesterone oral or vaginal capsules
the mean or abovc, the progesterone can be perma-
nently discontinued unless other conditions warrant Zone 2 100 mg IM twice weekly
its continuati on. Zone 3 100 mg IM weekly for 2 levels then
discontinue
During th e l 2th through the 24th week of gestation,
progesterone is continued at 200 mg IM twice weekly
and either oral or vag inal progesterone supplementa-
tion ca n be considered if the seru m progesterone con-
tinues in Zone l. lf the leve! is in Zone 2, then the
progesterone is continued at 100 mg IM tw ice week ly. Table 55-5: P rogestero ne Su pplem entatio n -
Once Zone 3 is reached , then the progesterone leve! is 24 to 34 Weeks Gestatio n
decreased to 100 mg IM on a weekly basis unt il two
leve ls have been maintained in Zone 3 and then it may
be discontinued (Table 55-4 ). Zone 1 200 mg IM twice weekly +
progesterone oral or vaginal capsules
During the 24th through th e 34th week of pregnancy, i f Zone 2 100 mg IM twice weekly
the progesterone leve ! continues in Zone 1, then Zone 3 Discontinue progesterone and repeat
progesterone is adm ini stered at 200 mg IM twice weekly level
and consider adding either oral or vaginal progester-
one. 1f the progesterone leve! is in Zone 2, then the
the progesterone leve! is in Zone 1, then progesterone vious dosage form (at least at one administration time).
should be continued at 200 mg IM twice weekly or 100 And secondly, progesterone is ad mini stered when the
mg 1M twice weekly with the addition of either oral or progesterone leve! is still within one standard deviation
vagi nal progesterone. In addition, it is recommended of th e mean.
that week ly biophysical profi les and/or non-stress tests
(NSTs) be perform ed to monitor for the appearance of With rega rd to the first point, this dosage ofprogester-
feta l di tress . lf the proges terone leve! is in Zone 2, one has been empiricall y utili zed ove r a 25-year period.
then progesterone at a dosage of 100 mg 1M weekly lt is we ll within the range of the amount ofprogesterone
should be continued until at least 3 7 weeks (Table 55-6). actuall y produced during the course or pregnancy (see
Table 55-1) and is fully consistent with the anticipated
1f either oral or vaginal progesterone is administered as needs of progesterone based upon serum monitoring,
a suppl ement to the intramuscul ar progesterone, 200 the absorption patterns of progesterone and th e known
mg ora l sustained release progesterone is usually cho- effects of progesterone on uterine cont racti 1ity. 1º·"º
sen fororal administration . Thi s is then given two times
a day (BID). lfvaginal progesteron e is used, a 300 mg
micronized vagi nal capsule is u ed per vagina either
every day at bedtime (QD hs) or two times a day (81 D). Table 55-6: Progestero ne Supple mentatio n -
34 Weeks to Term
With the use ofthis protocol , progesterone leve ls will ,
on occasion, fall into the upper half of Zone 2 (upper
Zone 2). In this case, the intramuscul ar progesterone Zone 1 Begin doing weekly biophysical profile
and/or NST + progesterone
may be eliminated and oral progesterone can be adm in- 200 mg IM twice weekly, or 100 mg IM
istered. In those cases, we would recommend 200 mg of twice weekly with either oral or vaginal
progesterone
ora l microni zed, susta ined-releasc progesterone.
Zone 2 Progesterone 100 mg IM weekly
There are a couple of question s which come up with
regard to this particular protoco l. First of ali, the amou nt
of intramuscular progesterone given is larger than pre-
lndications for progesterone

Zones of Progesterone ZONE 3 1722
monitoring and supplementation:
in Pregnancy 166.0
160
Patient's Name: - - - - - - - - - - 1. Previous SAB
G P LMP_ _ _ _ __ ZONE4 ,'
2. Previous infertility
ETC ETA _ _ _ _ __
140 3. Previous sti llbirth
,, 4. Previous prematurity
1st dose ;; 200 mg Zone 1 =200 mg/2x/Wk IM ,, (.'.".37 weeks)
progesterone
.,, , '
+ cons1der add1ng
120 in 011 IM prog. vag capsules 5. Previous PROM
Zone 2 = 100 mg 2x/'wk IM
<20 ng/ml = prog 200 mg (.'.':37 weeks}
Zone 3 = 100 mg 1x/Wk IM
2x/Wk IM 103.9
far 2 levels then D/C 6. Previous pregnancy-induced
100 lf zone 1, cons1der add1ng hypertension
prog vagina l capsules 90.3
20·25 ng/ml =prog 200 or
7. Previous abruption
ZONE4 812
100 mg 2x/Wk ZONE 2 , 8. Congenital uterine anomaly
80 74.3
>25 ng/ml = prog 100 mg 9. Palien! with cerclage
2x/Wk IM ZONE 1
65.9 10.Low progesterone
' ZONE 3
60 53.5 55.5
Zone 1 =Begm doing
ZONE 4 weekly biophys1cal
48.6
.. ZONE 2
ZONE 1
Zone 1 :;: 200 mg 2xlwk IM
profiles and/or NST
+prog 100mglM
2xlwk
40 • ZONE 3 or 100 mg 2x/Wk +
27 .7 28.7 prog vag caps Zone 2 =prog IM
Zone 2 =100 mg 2x/Wk IM 100 mg 1x/Wk
22.4
ZONE 1 Zone 3 = O!C prog and
20 repeat level
ZONE 2
~
- ZON E 1·.
o -'r-~--r---r-..--+-,...--,--,--,--r--r--r-,---.--.--,--r-...--r-,---l
4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-6 : The progesterone support protocol of th e Pope Paul VI lnstitute.

734 The Med ica! an d Surgi cal Practi ce of NaProTECHNOLOG Y
With regard to the supp lementation of progesterone tration ofthe progesterone. Progesterone is loca ll y irri-
when the serum progesterone is with in one standard ta tin g. However, i f the progesterone is drawn up with
dev iation ofthe mean , that would appear to be justified one need le and ad mini stered w ith a second needl e, and
on severa! grounds. First ofa ll, w hen se rum progester- the progesterone is given very slow ly (o ver 2 to 3 min-
one levels are ana lyzed a long a who le host of various utes by the clock) in the hip and according to instruc-
obstetrical complications, there are statistica ll y signifi- tions, th ese sid e effects can be greatly reduced. In th e
cant differences in serum progesterone between the com- nearly 25 years of our experi ence, we ha ve never seen
plicated pregnancy and the normal pregnancy, gesta- an abscess e ither infected or steril e, with the admin is-
tiona l age fa r gestati ona l-age, even w hen the serum tration of progesterone. We have, on occasion , how-
progesterone leve! far the overa ll population ofpatients ever, seen induration andan intlammatory reaction. This
fa li s w ithin that one standard deviation (see Chapter 54 has a lmost always responded to the local admin istra-
and the Appendix). Secondl y, and this is really the most tion of heat and time. On occasion, the injections ha ve
important feature , the assessment of progesterone in to be di scontinued and then e ither oral or vagina l or a
pregnancy must be done serial/y . In this fas hi on, one combination of the two are usecl . Aga in , it cannot be
can identify the pro.file of th e progesterone production stressed enough, however, th at the !M ad mini strati on
during the pregnancy and it does estím ate, to sorne ex- ofprogesterone mu t be g ive n properly. In the majority
tent, the total progesterone output (the area under the of cases, we instruct the husba nds to give these inj ec-
curve) durin g the course ofthat pregnancy overa par- tions to their wives and they come in far a specific shot
ticular period oftim e. In that way, it is simi lar in concept instruction given by registered nurses. That protocol i
to the integrated proges terone leve! previou ly de- described e lsewhere but <loes need to be attended to
scribed far the a sessment of progesterone during the (see Chapter 86). lfth ere is localized itching at the site
lutea l phase of th e menstrua l cyc le. 52 ·53 ofthe injection , vi tam in E o il app li ed to the site can be
very help ful in relieving those sympto ms.
When progesterone is administered intramuscularly, it
can on occasion , create loca l irritation, red ness and
swelling (a long with assoc iated pruritus). These side
effects can be greatly reduced with the proper adminis-
Table 55-7: Observed Effects of Progesteron e Suppo rt in Pregnancy

Published Standards vs. Po pe Paul VI lnstitute Protocol
Observed lncidence (%)

Co nditi o n Published Standa rd PPVI Protocol
Gestational hypertension 5.9 54 5.0

10.0 55
12.556
Toxemia 6.354 4.0

18.156
Low Apgar seores 1.757 0.9
Postpartum depression 10.9 58 2.2

10.25 '
10-1560
Meconium-stained amniotic fluid 16.061 6.1

16.662
Nausea 73 .863 8.2
Vomiting 37 .563 6.9
Headache "Frequent""' 4.5
Postpartum hemorrhage
(>500 ce)
Vaginal delivery 3_9ss 3.2
C-section 6.465 6.5
Chapter 55: Usi ng Progestero ne Su ppo rt in Preg nancy 735
Observed Effects of all much more common compli cations in thi s situation.70
Progesterone Support ------~
Fina ll y, one of the mo re remarka ble pos iti ve e ffects is
With the use o f proges tero ne support in pregnancy, a seen w ith th ose wome n w ho have nausea, vo miti ng or
number of pos itive effects have been observed over headache du rin g the course of pregnancy. These are, at
the years. These are o utlin ed in Tabl e SS- 7 and com- th e minimum , a nui sance and ve ry annoyin g and , at a
pa red to pu bli shed standards. T he incide nce of both maximum , very probl emati c. They were fo und to be sig-
gestati o nal hypertens ion and toxemi a ofpregnancy are ni fica ntly reduced w ith progesterone suppo rt. While
quite lo w w ith the use of progesterone w ith the PPV I progesterone leve ls were fo und not to be decreased in
protocol as compared to publi shed sta ndards. W hat is the first trimester in these cond itions, they we re mark-
pe rhaps even mo re dra mati c, however, is th e ap pare nt edl y decreased in th e second trim ester.
decrease in the in cide nce of mild forms of gestati o nal
hyperte ns ion a nd toxe mi a (Tabl e SS -8). Such an impact Postpartum hemorrhage w ith bo th vag ina l deli very and
of progeste rone on these conditi o ns has bee n prev i- cesarea n sectio n was eva luated and fo und to be the
ou s ly observed and it was noted that this effect was sa me incidence as the pub lished standard. Th e use of
observed only when the progesterone was admini stered progeste ro ne in th ese two ci rcum sta nces wo uld not be
no later th an mid-pregnancy. 66 When compared to pla- expected to have a ny parti c ul a r va lue and that is w hat
cebo, progeste rone has been observed to cause a s ig- was observed.
nifi cant reducti o n in bl ood press ure suggesti ng that
progesterone has a n a nti-h ypertens ive action.67·68 ·69 Progestero ne suppo rt is a ma instay ofth e Po pe Pa ul Vl
ln stitute Prematurity Preventi o n Pro gra m . Thi s w ill be
A pgar seores ofS o r less at five minutes ha ve also been di sc ussed in deta il late r (see Chapter S6).
o bserved to be decreased in th e PP V I progra m, how-
ever, this particular data point is mo re diffic ult to assess
beca use Apgar seores can be somewhat subj ecti ve . Safety of Progesterone Use in
Pregnancy ~~~~~~~~~~~~
The incidence of postpartum depress io n, however, is
signifi cantly reduced in the progesterone-supported pro- G reen has po inted o ut that the p ro blems id entifi ed w ith
gram protocol. The genera l incide nce of postpartum the use of di eth y lstilbestro l ( DES) has cast " a lo ng
de press io n is co nsidered to be in the 1O to 1S percent shadow" o n the use of horm ona l s uppl e mentati o n in
ra nge. However, with the PPV I Protoco l, on ly 2 .2 per- pregna ncy. 41 In additi on, there a ppears to be an extrao r-
cent of suppl emented pati ents had postpartu m depres- dinary amo un t of confus io n related to the use of proges-
sio n (see Chapter 30). terone support in pregnancy. Furthermo re, the Food and
Drug Admini strati on (F DA), whi ch is qui te capa bl e of
In additio n to the a bove, meconi um-stai ned amni oti c reli ev ing thi s confu sion, has instead continued the con-
fluid was fo und to be reduced in the PPVJ program w ith fusi ng sto ry and sorn e of this needs to be addressed .
a n in cid ence of 6. 1 percent compa red to abo ut l 6 per-
cent in publi shed studi es. Meconium-stain ed a mniot ic In the recent labeling of progesterone products fo r th e
fluid is a probl em beca use cesarean sectio n, instrumen- FDA, o ne of the contra indi cati o ns to th e use of oral
ta l delivery, feta l di stress and meconium asp ira tion are progesterone is li sted as " known or suspected preg-
Table 55·8: lnciden ce of Mild and Seve re Gestatio nal H ypertensio n and Toxemia,
Patients o n P roges teron e, Po pe Paul Vl lnstitute vs. Publisbed Stand ards
Gestational h~eerten s i o n Toxem ia

Site Mild Severe Total Mil d Severe Total
% % % % % %
Pope Paul VI lnstitute 4.0 1.1 5.0 3.4 0.6 4.0

Patients on progesterone'
Pre-eclampsia prevention 16. 6 0.7 217 5.0 2.5 3.3

study group 2
1. lncludes singeltons, twins, nulliparas and multíparas (Total N=933)

2. Hauth JC, Ewell MG, Levine RJ, et al: Pregnancy Outcomes In Healthy Nulliparas Who Developed Hypertension. Obstet
Gynec 95:24-28, 2000.
na ncy. " 71A nd yet, no such contra ind icati o n is ide nti- thi s type may induce mild masc ulini zation ofth e exter-
fie d for th e use of progesterone ge l. 72 In fac t, w hil e ora l na ! geni ta li a ofthe fe ma le fe tus, as we ll as hypospadias
progesterone has been spec ifí ca ll y contra indi cated in in the ma le fe tus, it is w ise to avo id us ing th e drug
" kn o wn o r suspected pregnancy," progeste rone ge l is durin g the fírst trimester of pregnancy." 73
indi cated fo r progeste rone suppl e me ntati on or re pl ace-
me nt as a pa rt of a n ass isted reproducti ve tec hno logy Thi s ro le ofthe FDA in perpetuatin g thi s confus io n is
(A RT) treatm ent fo r in fe rti le wo me n w ith progeste rone unn ecessa ry. In th e past, th e Obstetri cs a nd Gyneco l-
defi c ienc y, and progeste ro ne is recomm e nded to be ogy Ad visory Committee to the FDA has recommended
continu ed in a dosage of 90 mg o nce da il y a nd treat- that the restri cted use ofpro gesterone a nd 17-0HP-C in
ment is co ntinued fo r th e fírst 1O to 12 weeks of preg- ea rl y pregnancy be lifted.74 U nfo rtun ate ly, w hil e thi s
na ncy. In an odd tw ist, whil e the oral progesterone is recomm endation was made in 1984 , it has never been
co ntra indi cated in " kn own o r suspected pregna ncy," compl etely heeded.
its offíc ial la belin g also sta tes that thi s o ra l progester-
o ne "should be used during pregnancy o nl y if indi - M uc h of th e confu sio n s urrounds a user-unfriendly
cated (see contraind icati o ns)." 71 nomenclature as it spec ifí call y relates to progestational
agents. Th e te rm " progesterone" is ofte n used loose ly
The oral progeste rone pre paration is recogni zed as a to refer to any progestatio na l age nt in cluding both C 21
pregna ncy Category B substa nce by the FDA and , "sev- a nd C 19 agents. But progesterone is progesterone and
era ! studi es in wo men exposed to progesterone have nothing more. 75 lt is produced naturall y in the hum an
not demonstrated a ny s ig nifí ca nt increase in fe ta l mal- body along w ith other naturall y occun-ing progestational
fo rm atio ns." 71 age nts suc h as 20 a-dih ydroprogesteron e, 20 ~-dih y
d ro progeste ro ne, and 17-hydroxyp roges te ro ne. Proges-
The confu s ion wo rsens w he n o ne looks a t the la be ling terone is the o nl y know n natural progestationa l agent
for progesterone inj ecti o n, US P in sesa me o il. He re th e w ith maj a r bio logic s ignifícance and 17-hydroxyproges-
la belin g becomes fri g htenin g a nd it is wo1ih quoting : terone is virtuall y ine1i. There is one intermedi ate proges-
tati onal agent, 20 a -dihyd roxyprogesterone, which does
" WARNINGS: The use of progestati onal drugs possess, a lbe it weak, " progestatio na l" acti vity. But the
durin g the fírst four months of pregnancy is not re lati ve potenc ies of progestati o nal agents have been
recomm ended . Progestational agents ha ve been ass ig ned primaril y o n th e bas is o f the ir ability to pro-
used begi nning w ith the fírst trimester of preg- du ce secreto ry c han ges in th e es trogen-pri med e n-
nancy in attempts to prevent a bo rti o n, but th ere do metrium .75 Poss ibl e effects o n the mothe r and con-
is no ev ide nce that such use is effecti ve. Fur- ceptu s have not been sati sfacto ril y a na lyzed or studi ed
thermore, the use of progestatio nal age nts, w ith fo r th eir potential be nefít.
thei r uterine-re laxant properti es, in pati ents w ith
fe rtili zed defecti ve ova may cause a de lay in To he lp c la ri fy the no menclature, those progestatio nal
sponta neous a bo rti o n. age nts w hi c h are natural to the human body, i. e. , a re
Severa! re ports suggest an assoc iati o n be- actua ll y manufac tured phys io logica ll y w ithin the body,
tween intra uterine exposure to progestati o na l a re best referred to as hormon es a nd by the ir spec ifí c
drugs in the fírst trim ester of pregnancy a nd na me. Those progestati o nal agents w hich are artijlcial
genital abnormalities in male and female fe tuses. to the body, i.e. , are not manufactured phys iol ogicall y
Th e ri sk of hypos padi as (5 to 8 pe r 1000 ma te in the body, are best referred to as artimones (artifi c ia l
bi1ihs in the general population) may be approxi- substitutes fo r natura ll y occurrin g hormo nes) . In thi s
mate ly doubl ed with ex posure to these drugs. way, o ne ca n beg in to di sting ui sh betwee n those com-
There are in suffíci ent data to quantify the ri sk po unds w hi ch a re naturall y occurring to the body and
to exposed fem a le fe tuses, but insofar as sorne those w hi ch are fo re ign to it. Thi s becomes im porta nt
ofth ese drugs induce mild virili zatio n ofth e ex- as o ne looks at the overall questi o n of sa fety. Progest-
terna! genitali a of the fe ma le fe tus and because ero ne is a C11 steroid de ri v ing fro m th e pregnane
of the increased associ atio n of hy pospadi as in nucleus. Th e re are certa in artimo nes that a re also C 21
the male fetus, it is prude nt to avo id the use of co mpo und s. Th ese in clude 17-h ydro xy progesteron e
these drugs durin g the first trimeste r of preg- caproate ( 17-0HP-C) and medroxyprogesterone acetate
nancy." 73 (M PA) (Fig ure 55-8).
In the " Warnin g fo r Wo me n" secti on of thi s FDA-ap- Th ere are also C 19 stero id s de ri ved from the androstane
proved labeling, it states: "Th erefore, s in ce drugs of nuc le us. Testosterone is th e pro to typi ca l C 19 stero id.
12 18 17
21
C,,-Steroid Tes tos tero ne

C..-Steroid Progesterone (Androstane)
(Pregnane)
C-19 Progestins
C-21 Progestins
OH =e
o o
0-g{CH,), - CH , 0 - C -CH,
o
Ethiny l testosterone 19-nor Ethinyl testosterone
o O (Ethisterone) (Norethindrone)
Hyd roxyprogesterone caproate Medroxyprogesterone acetate
Figure 55-7 : Th e C 21 pregnane nucleus and the chemica l

structure of progesterone and the C 21 artimones 17-0H-
progesterone cap roate and medroxyprogesterone acetate.
Norgestrel Norethynodre l
While testosterone is a naturally occurring C 19 steroid Figure 55-8 : The C 19 androstane nucleus and the chemica l
structure of testosterone and C 19 artimones ethinyl
with obvious androgenic prope11ies, there are a number testosterone (ethisterone) , 19-nor ethinyl testosterone
of ai1ificia ll y derived C 19 compounds which are less an- (norethindrone) , norgestrel and norethynodrel.
drogeni c, but also have progestational activity. These
includ e compounds such as norethindrone ( 19-nor
ethinyl testosterone), norethynodrel , norgestrel and ethis- dence that this can al o exert a masculinizin g intlu-
terone (ethinyl testosterone) (F igure 55-9). These 19-nort- ence. 78.79.so.
estosterone derivatives unequivocally can masculinize
thef emalef etus if given in high doses at susceptible times In an extensive review of the fetal effects ofprogesta-
of embryogenesis. 39·74 -76 ti onal agents (both natu ra l and artific ial), Simpson and
Kaufman concl uded that despite many coho11 and case
The confusion or lack ofu ndersta nding ofthe pharma- contro l studies, there sti ll remains little reason to sus-
cology involved is still producing erroneous conclu- pect that progestogen ex posure in u tero exerts a del-
sions regard in g progesterone as a teratogenic agent. eteriou s effect on fetal development. The so le excep-
Progesterone is an antiandrogen , notan androgen . The tions are the 19-nortestosterone derivatives, which in
C 19 artimones do have and rogenic potential. The C21 high doses ( 1Oto20 mg daily) can ca use genital viri li za-
artirnon e rnay show long-actin g progestational effects tion. 39 They co nclud ed that the evidence i cons ider-
because they are not rapidly removed to the circu lation ab le that ora ll y ingested progestogens do not ca use a
and metabolized like proge terone. 76 general increase in birth defects, are not cardiac terato-
gens , do not cause limb reduction defects, do not ca use
The effect ofthese 19-nor compounds was recogni zed neural tu be defects or hydrocephalus, the frequency of
by Wi lkins and Janes, et al, in 1958 and this study con- esop hagea l atres ia has not been increased in any ofthe
tinues to be cited and is a cau e for confusion n Thi s studi es, and in utero ex posure is unlik ely to result in
study, frorn Joh ns Hopkin s Univers ity, presented 2 1 abnorma l development of the male gen itali a. Other re-
cases offemales that showed evidence ofmascu li ni za- views ha ve come to simi lar conc lusions.81.82 ·83
tion ofthe externa ! geni tali a. In 12 ofthese cases there
was in utero ex posure primarily to the C 19a11imone ethis- A detailed summary of anima l and hum an terato logy
terone (ethinyl testosterone). In 3 cases, no steroid studi es with regard to the use of progesterone and th e
were used in pregnancy and in the remaining 6 cases C 21 artimones 17-0 HP-C and M PA are li sted in Tables
IM progesterone was used. However, ofthose 6 cases, 55-9 and 55- 1O. With specific reference to MPA , anima l
3 were also exposed to ethi sterone and one to methylt- studies have suggested an increased risk offac ial clefts
estosterone exp laini ng the defect. In the other 2 cases, and masculinization offema le fetuses and feminiza ti on
the women also rece ived stilbestrol. There is now evi- ofma le fetuses. These effects were observed, howeve r,
only at hi gh doses (8 mg/kg/day and 1Oto40 times the feta l tissues appear sa turated with progesterone and
human dose) . No similar increased ri sk was fo und far probably do not ha ve the capac ity far additional proges-
eith er progesterone or 17-0HP-C. lt should be noted terone uptake. 115
that when early mouse and rabbit concepti were cul-
tured with mega-doses of progesterone (2,000 and 10,000 In our own experi ence w ith the use of progesterone in
ng/mL) they failed to undergo further c leavage until pregnancy, the incidence of fetal anomaiies in patients
cultured in a progesterone-free medium . Scialli has noted on progesterone (2.2%) ve rsus those who were not tak-
that thi s findin g is nonspecific and does not bear on the ing progesterone (2.7% ) was actuall y lower (a ltho ugh
likelihood that progesterone w ill ca use birth defects in the differe nce was not sta t ist ica lly s ign ificant-
intact animals. 75 Furthermore, it is noted that these con- p = .6088). The breakdown of the observed anomalies is
centration s do not appear in nature. In human teratol- shown in Tab le 55 - 11. We observed one mal e infa nt
ogy studies, both 17-0HP-C and MPA 107 genera lly ha ve with hypos padi as wi th an inc idence of0.2 percent. But
shown no in creased risk in anoma lies w ith the poss ibl e thi s is significan tl y lower than the quoted incidence of
exception of one case o f transient clitora l e nl argement 5 to 811 000 (0.5 to 0.8% ) and even more signifi canti y
with M PA (in 166 cases) and retrospective reports of di ffe rent than the claim th at progesterone ma y be asso-
hypospadi as with 17-0HP-C and MPA. In the hum an ciated wi th a doub ling of that frequency. 73 We al so ob-
studi es on progesterone, no increase in anoma li es has served one female in fa nt with mild labi al fusion treated
been observed incl udin g cardiovascular anoma lies . effecti vely with estrogen crea m (incide nce of0.2%). But
this, too, is much lower than the reported incidence of
Asan interesti ng aside, the fetal umbilical ai1ery bl ood 1.8 percent. This series of patients is one of the Iargest,
level s of progesterone ha ve been noted to be higher in ifnot the large t, ever re po11ed for progesterone supp le-
male infants than in fema les . The fema le umbili ca l vein mentation in pregnancy. Furthermore, nearl y ali of these
leve ls were the sa me. Thus, the di ffere ntia l between the patients had exposure to progesterone during the first
two is greater in fema le fetuses suggesting that they four months of pregnancy and no increase in any ofthe
metabo lize more progesterone than the ma le. 108 anoma lies was observed.
lt has aiso been suggested that the ad ministration of lt ha been ob erved in animals that progesterone at
progesterone may accelerate earl y childhood deve lop- five times th e daily endogenous leve! had no ap parent
ment and enhance academic perfo rmance. 109-110 However, effect on feta l weight. 116 In our own ex perience, we fo und
this has not been confirmed 111 and others have argued no statistica ll y significant difference in the birth weight
against it. 112 of th ose babies born afte r exposure to progesterone
support (Tab le 55-12). The mean weight for those ex-
As has been noted earli er, progesterone is produced in posed to progesterone support was 7 .82 pounds and
Jarge quantities during the course of pregnancy increas- fa r th ose not on progesterone support 7.81 pound s.
ing as th e pregnancy advances . During the last trimes-
ter, the pl ace nta! production ofprogesterone is approxi- In conc lu sion , speci fica ll y as it relates to the natura lly
mately 250 to 300 mg/24 hours. While mate rna l plasma occurring hormone progesterone, th er e is no cr edibl e
tota l progesterone Jeve ls a lso in crease during thi s pe- evidence to suggest th at its use to support pregna ncy,
riod of time, fetal serum levels are nearly seven- fa ld w heth er th a t s uppor t be in the ea rl y d ays or months
higher than mate rnal serum Jevels. 113 ln addition, proges- of th e pregn a ncy or la ter in the pregnancy, is in an y
terone is relea ed in to the retropl ace ntal blood pool and way ter atogenic or responsible for a ny genital ma lfor-
concentrati ons are in the arder of 600 ng/m L, w h ich is m a tions. ln fact, a li ofthe ava ilab le evidence strongly
severa ] times hi gher than materna l serum leve ls 114 (even suppo11s its safety when used in pregnancy.
w ith exogenously-administered intramusc ul ar progest-
erone). Thus, the fetu s is ex posed natura JI y to very hi gh In this report, over 2000 pregnancies ha ve been reviewed
leve ls of progesterone , even higher than w hat one or reported with the use of progesterone support in
would anticípate with exogenously ad mini stered proge - pregnancy w ith no increase in birth defects or genital
terone . anoma lie . Progesterone support in pregna ncy can b e
consider ed completely safe!
The question of whether excess progesterone may af-
fect neural deve lopment can be ra ised and has been
studied . Essentiall y no conjugation or meta bo li sm of
these stero ids occurs in nervous tissue . Furthem1ore,
Tab le 55-9: Summa ry of A nimal Teratology Studies:

Progesterone vs. C 21 Artimones
Progesterone C,, Artimones
Concepti fail to grow when cultu red with mega MPA may increase fa cial clefts at higher doses 8990
doses: 2,000 and 10,000 ng/ml"' 85 (see text)
MPA increased mascu linization of female fetus al
No increased masculinization of female fetus at high doses (8 mg/kg/day)88
high doses (40 mg/kg/day) 88
17-0 HP-C: no increased masculinization of
No increased genital anomalies at high doses (12- female fetu s at hig h doses (20 mg/kg/day)88
90 mg/kg/day)
MPA: increased feminization of male genitalia al
No effect on maternal, fetal or placenta! weight at high doses (10 to 40 times human dose) 919293
high doses (12-90 mg/kg /day)
MPA: no genital anomalies al 3 times human
No increase in cardiac anomalies - embryos dose 94
cultured at high doses (1000-3000 ng/ml) 88
MPA: no increase in non-ge nital birth defects al
any dose"·94
17-0HP-C: no increased congenital anomalies at
200 times the human doses (833 mg/kg/day) 95
MPA; Medroxyprogesterone acetate 17-0HP-C ; Hydroxyprogesterone caproate
Table 55-10: Summary of Human Te ratology Studies:

Progesterone vs . C 21 Artimo nes
Progesterone C 21 Artimones
Collaborative Perinatal Project: no increase in any MPA, 17-0HP-C: Collaborative Perinata l Project.
birth defect (527 cases).96 No increase in birth defects _,._,,
No increase in ca rdiovascular effects.97 ·98 MPA Mayo Clinic: No increase in anoma lies (60
cases). 101
West German collaborative study: no increase in
congen ital anomal ies (186 cases).99 MPA - Hig h doses in human s (5-50 mg/day) - one
case clitoral enlargement in 166 cases .103
Johns-Hopki ns: no increase in congenital
anomalies (93 cases).100 MPA. 17-0HP-C: No increase in total brith defects
or genitourinary anomalies (1 ,608 cases) .'"'
Mayo Clinic: No increase in congenital anomalies
(244 cases).'º' West German Collaborative Study: no increase in
birth defects (462 cases)."
No increase in anoma lies (198 cases) .'º'
17-0HP-H: no increase in congenital anomalies
(150 cases).'º'
17-0HP-C: no increase in congen ital anoma lies
(189 cases).'º'
MPA: no increased risk in 366 cases .108
MPA = Medroxyprogesterone aceta te 17-0HP-C; 17-hydroxyprogesterone caproate

17-0HP-H; 17-hydroxyprogesterone hexonate
740 T he Medical and Surg ical Practice of Na ProTECHNOLOGY
Table 55-11: Specific Ano malies Observed in Patients o n

Progesterone (N =933) vs . ot on Progesterone (N=405 )
Pope Pau l Vl l nstitu te
On Not on
Anomaly Progesterone Progesterone Publish ed
Observed (N=933) (N=405) Frequency
n % n % %
Renal anomaly 4 0.4' 0.2 0.7•

Down syndrome 4 0.4' 1 0.2 0.1•
Cardiac anomaly 3 0.3 2 0.5 0.9•
Cleft lip and/or palate 3 0.3 1 0.2 0.2'
Other chromosomal 2 0.2 2 0.5 0.2•
anomalies
Omphalocele 0.1 1 0.2 0.03'
Polydactyly 0.1 o o.o 0.08'
Clu b feet 0.1 o o.o 0.4'
Labial fusion 1 0. 1 o O.O 1.8•
Hypospadias 1 0.1 o O. O 0.5-0.8'
GI anomaly o O.O 2 0.5 0.02'
Dandy Walker Malformation o o.o 0.2 0.09'
Totals 21 2.2• 11 2.7
a. Chi-square =0.2507 (p=.6166) when compared to those not an progesterone.
b. March of Dimes Perinatal Data Center, 2000. March of Dimes Birth Defects Foundation. www.marchofdimes.com. 2003.
c. Nyberg DA, Mahoney BS, Pretorius OH : Diagnostic Ultrasound of Feta l Anomalies. Yea r Book Medica l Publishers,
C hicago, 1990, p. 22.
d. National Vital Statistics Reports. Department of Hea lth and Human Services, National Cen ter far Hea lth Statistics, Feb.
12, 2002.
e. Leung AKC, Robson WLM , Tay-Uyboco J: The lncidence of labial fusion in children . J Paediatr Child Hea lth. 29: 235-326,
1993.
Food and Drug Administration official labeling : Progesterone far injection. USP, in sesame oil, 2001 .
g. Chi-square =0.2619 (p=.6088) when compared to !hose not on progesterone.
Table 55-12: Birth W eigh ts -

Babies Exposed and N o t Exposed to P rogesteron e
Suppo rt in Pregnancy (F ul l-term l nfants On ly)
Mean We ight
N in lbs . s.o.
Exposed to progesterone support 166 7.82 1.04
No progesterone support 106 7.81 ' 0.99
1. Not statistically significan !.
Examples of Progesterone Support in a nationa l reg istry be created to document feta l out-
Pregnancy~~~~~~~~~~~~ come following progesterone support therapy. 100 Such
a registry was ne ve r undertaken to the author 's know l-
In Fi gures 55-9 through 55-12 a number of examples are edge, however, it c lea rl y makes sense that a national
g ive n of the assess ment of progesteron e during th e registry of thi s ty pe, or at least a collaborative reg istry
course of complicated pregnancies and th e outcomes hould be undertaken fo r the ongo ing assess ment of
of those pregnancies are de cribed. thi s issue beca use of its overa !! importance. lt is now
time to make a concerted comm itment to see that thi s
A number ofyea rs ago, Rock , et a l. , reco mmended that gets done and is acco mpli shed .
I 1722
I
166.0
160
Normal Pregnancy 1 53 ~
(N=109)
: 13 8.8
140
Patient's Name· _ __ __ _ _ _ __
G_ _ _ P~~~LMP _ _ _ __ _
::¡-
ETC ETA._ _ __ _ _ 118.1
E
e, 120 ..
e:
Q)
e:
o 100
DPC
103.9
.·
.. º 104.2
~ 903
89 .6 /
tíQ) 812 ~:
Cl
o
et
80 743
,. ·',
65 .9
E .... -• s1.a
::i
~ 60 54.2
53.5 55.5 ' ..... "6"1.2
en ~-
.· 40 .4 • • •• j_~ .•
40 • 40.8
20
. . ...... .· Pope Paul VI lnstitute
4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-9 : A progesterone curve of a 34-year-old , gravida 2, para 1, who had a
history of having had an emergency cesarean se ction at term for severe fetal
distress which ended in a neonatal death . She was an infertility patient with en-
dometriosis and polycystic ovarian disease and was a heavy smoker. In the above
pregnancy, her progesterone production was clearly suboptimal after looking quite
favorable during the first trimester. She was supplemented with progesterone and
had a healthy male infant at 38 weeks gestati on by repeat cesarean section .
180 ------------------------,,~
, ---,,-
,2--~
166.0
160
Normal Pregnancy 1S3.0
(N=109) ..
136.8
140
--'
e,
E 120
Patient's Name. - - - - - -- - - -
G
ETC
P~~~ LMP _ _ _ _ __
ETA_ _ _ _ __
...
.
:' 124.0
118.1
.:.
Q)
e: DPC
e
Q)
100
1'03 1
103.9 .·
tíQ)
Cl
o 80
812
75.9 .
.r·
., .. • ..78.6
et 71 .2
~---
65.9
E
2Q) 60
en ...,f.; 53 .5 55.5 56.9 '
555
~ .·
.. .. 48.6
.· .
.,¡
-··
47.3
40
..
41 .6
... 38.0
20 . .... National Hermane Laboratory

....... .. .· Pope Paul VI lnstitute
6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-1 O: This 36-year-old , gravida 4, para 2 with one previous miscarriage
developed severe IUGR during the above pregnan cy. At birth , the baby weighed 4
lbs . 14 oz. She was supplemented with progesterone and her levels in the 2nd and
3rd trimester were mostly Zon e 1 and lower Zone 2. The placenta! weight at
delivery was 197.0 grams (<10th percentile) . She delivered spontaneously at
38 weeks a small but healthy infant with Apgars of 9 and 9.
180 , 1722
/
166D
160
Normal Pregnancy t53.0
(N=109) :
: 136.8
140
Patient's Name:
::::; G_ _ _ P_ __ LMP
E ETC ETA 118.1
e, 120
.s., 1039
e DPC
~
e 100
90.3 .·
.,"' 81 2
87.0
•
Cl
o
et
80 74.3
73.3 , .·
¡&-.._ •• ..- _.
E ~68.2 70.8
::i ... ' 66.6
O; 60
(/) ·' .(
. '' . 47.8
~
.J·
40 42.9
2~
18.7 • ; . :22.2 24.7
20
--••~--
15.5 18.2 ..__,
17.0 National Hormone Laboratory
. ~. Pope Paul VI ln st~ute
6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-11 : This 42-year-old gravida 1, para 1 achieved a pregnancy seven months
after evaluation and treatment with NaProTECHNOLOGY. Prior to coming to the Pope
Paul VI lnstitute, she had two failed attempts at IVF. In !hose attempts , her endometrio-
sis and hormone dysfunction was left undiagnosed. In her pregnancy she had a
suboptimal progesterone profile usually in Zone 1 or lower Zone 2. With progesterone
supplementation , she delivered a healthy female infant at 39 weeks.
1 80 ~-----------------------_,~
, ---17-
22--~
166.0
160
Normal Pregnancy
(N=109) :
140
,
Pat1ent's Name: - - - - - -- - - -
G P LMP _ _ _ _ __ ,,
Er e - - - - ETA _ __ __ _ ,,
120 114.0 ."
DPC
103.9 t
100
90.3 , •••
80
659
74.3
812
7v 76.3
I "·º
• 55.S
60 53.S .... ...,.,
40
. 48.6
~
55.2
. . ···
~··
li
43.0 4~-2.... 42.8
20
13.3
• National Hormone Laboratory
Pope Paul VI lnsfüute
6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 55-12: This is a 39-year-old , gravida 4, para 1 who had an intrauterine fetal
demise at 26 weeks associated with very severe hypertension . She also had one
previous miscarriage. In this pregnancy, which was supported by progesterone, she
had a healthy female infant at 38-weeks gestation. She weighed 8 lbs. 15 oz. Apgar
seores were 8 and 9. She wa s normotensive throughout the course of her preg-
nancy.
Chapter 55: Using Progestero ne Support in Pregnancy 743
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Prevention of Preterm Birth:
A Comprehensiva and lntegrated Approach
he prematurity rate in the Un ited States is a national While modern obstetri cs has most ly been interested in
T tragedy (F igure 56-1 )! While the American Co ll ege
of Obstetricians and Gynecologists says the incidence
the severely premature infant born at le s than 32 weeks
gestation , even those in fants born from 32 through 36
of preterm birth ha "changed 1ittle o ver the last 40 weeks gestation are at increased risk . The relative ri sk
years," 1 it actually increased from 6.7 percent in 1967 to for infant death from ali causes among sing letons born
12. 1 percent in 2002 .2-6 It represents the leading cause of between 32 and 33 gestational weeks in the Uni ted States
neonatal mo1tality7 and the second leading cause of in- is 6.6 and among those born from 34 through 36 weeks,
fant mortality (death during the first year of life) and, for the relative risk is 2.9. 8
the first time since 1958, there has been an increase in
the infant morta lity rate between 200 1 and 2002. 6 The lt is estimated that the nati onal hospital bi ll for prematu-
increase was concentrated in the neonatal period . rity tota lled $ 13.6 bi llion in 200 1.6 ln addition to increased
mortality, there are any number of med ical and deve lop-
mental problems that are associated with premature birth
Prematurity Rates In the
(Table 56-1 ).9- 16 There is an in creased rate of intraven -
United States: Births < 37
12.o
W eeks Gestation 1967-2001
111 llS HI lll tricular hemorrhage, respiratory di stress, cerebra l palsy
11.0 - 101·"º110110110 and visual and hearing impairment. In fact , the rate of
108101 'º 7
'ºº102102
cerebral palsy in neonatal survivors who weigh between
- 100
500 and 1500 grams at the time ofb irth is 1Oto50 tim es
~
o. 9.0 hi gher than fo r full-term infants. 17• 18 Developmentally,
80
abnorma l cogn itive function , academic skili s, poor vi-
sual motor, gross motor and adapti ve function are also
7.0
associated with preterm birth. In additi on, mental retar-
.J j i!l!!!i!!!!!!!!!i!!li
dation and developmenta l de lay are more frequent in
infants born prior to 37.0 weeks gestation.
Vear
Figure 56-1: The prematurity rate in the United States (birth

less than 37.0 weeks gestation) 1967-2001 .'"'
Ali in ali , prematurity caiTies with it enormous risks along
with the extraordinary utilization of hea lthcare resources.
747
gra ted stra tegy to prom ote optima! development of

Table 56-1: Summary of Medica( and
women 's reproductive hea lth in order to prevent preterm
Developmental Probl ems Associated with
birth and low birth we ight deli very.
Premature Birth 11 · 1i
At the Pope Paul VI In stitute, a com prehensive and in-

tegrated strategy fo r the prevention of preterm birth
Medical
Responsible for 70% of fetal , neonatal and infant
has been de ve loped, impl emented and tested. lt has
deaths resulted in a 7 1.4 percent decrease in the overa ]] prema-
lncreased ra tes of intraventricular hemorrhage turity rate with deli veri es at .:::; 36 .9 weeks anda 142. 1
lncreased ri sks of respiratory distress percent decrease in the delivery of infants at .:::; 34.9
lncreased risk of cerebral palsy, and visua l and
hearing impai rment weeks gestation and a 200 percent decrease in del ivery
at .:::; 33.9 weeks . lt is the purpose of thi s chapter to
Developmenta l
di scuss thi s approach to the prevention of prematurity
Abnormal cognitive function
Abnormal academic skills
a long with th e overal l context within whi ch such a pro-
Poor visua l motor function gra m ex ists loca ll y, as we ll as its potenti al app lication
Poor gross motor function on a wider leve!.
• Poor adaptive function
Mental retardation and developmental delay
The Prematurity Prevention Program of

the Pope Paul VI lnstitute - - - - --.
For over 25 yea rs, th e author has been interested in the

And yet, its causes have been complex and difficult to question of preve ntin g preterm labor and deli very. For
pinpoint. Clearly, the increased rate of multipl e preg- the last 18 yea rs, a specific protoco l for the prevention
nancies secondary to the utili zati on of the a1tificial re- ofpreterm labor and del ivery has been instituted. This
productive techno logies, has added to the prematurity protocol is out lined in Tab le 56-2.
rate. It is quite poss ibl e that the epidemic of sex ually-
transmitted diseases and induced abo rtion has also had The program begins by identifyi ng those patients who
an impact on thi s situation. are at high risk for going in to preterm labor. These pa-
tients are then taught how to se/f-monitor their uferine
The current sta tus of th e approach to preterm birth ap- contractions. When indi cated, supp/ementa! intramus-
pears to be an acceptance of its inevitability, then prepa- cular progesterone is provided while monitoring serum
rati on for early deli ve ry. 19 While vari ous ri sk factors are progesterone leve ls and tocoly tic therapy (usuall y with
recogni zed, program s are recom mended to anti cí pate Terbutaline) is used fo r symptoms ofuterin e irritability
the delivery ofthe prem ature in fa nt. The recommenda- (contractions).
tion s often made are the timely admini strati on of corti-
costeroids, hei ghtened surveillance with monitoring of In addi ti on to th e above, antibiotic therapy is provided
maternal and fetal well-being, refe rral to a perinatologist
or neonatologi st on a non-em ergent bas is, preparing
the patient and her fam il y, arranging for deli very at a Table 56-2: Prematurity Prevention
terti ary care center (if necessary) and "i n sorne cases" Program of the Pope Paul Vl lnstitute
undertak ing in terventi ons that may de lay or preve nt
preterm delivery. 19
1. ldentify patients who are at high risk
2. Uterine contraction self-monitoring (patient
Any number ofattempts ha ve been made to implement education)
programs for the prevention of preterm birth. Often, these 3. Supplement with IM progesterone while monitoring
have either not been successfut 20 or ha ve been on ly serum levels
4 _ Tocolytic therapy (usually Terbutaline) far symptoms
minimally successful. 21 While prenata l ca re has been of uterine irritability (contractions)
shown to improve infa nt mortality rates,2 2 more and 5. Antibiotic therapy when palien! breaks through
more, th ere is a recognition that neither preterm birth toco lytic therapy
nor intrauterin e growth retardation can effecti ve ly be 6. Ultrasound assessment of cervix when dictated by
risk criterion , symptoms or pregnancy cond ition
prevented by pren atal care in its present form. Lu, et al23 7 _Cerclage when indicated by ultrasound assessment
have recen tiy ca ll ed for a re-conceptua li zati on of prena-
tal careas pa1t ofa longitud inall y and contextu all y in te-
Chapter 56: Prevention of Preterm Birth: A Compre hensive and lnteg rated Approach 749
to those patients who brea k through their tocolytic

Table 56-4: Additional Proven Risk Factors for
therapy. Ultrasound assess ment of the cervix is also
Prete rm Labo r and D elivery2 5· 38
used according to ri k criterion, symptoms or pregnancy
condition. 1f ultrasound assessment of the cervi x indi-
cates, cervical cerclage is placed. Eac h of these will be
• lnfertility • Maternal age >35 years
taken individua lly.
• Abortion • Mother born al <37 weeks
• Adolescence • Smoking
• Multiple pregnancy • Exposure to DES
/dentifying Patients at Risk • Prematu re cervical dilatation • Cervical incompetence
• History of previous stillbirth • Placenta previa
Many risk fac tors may precede th e onset of premature • Malpresentation • Cervical cone biopsy
labor and deli very (Tab le 56-3 and Table 56-4). The
N ICHD maternal fetal medicine network has carried out
a preterm pred ict ion stud y, which found that fetal
fibro nectin anda sho11 cervix doc umented by ultrasound lap,39·4 º various approaches to monitorin g thi s in creased
examination to be strong predi ctors of preterm labor. uterine activity have been uti lized.
Other predictors in c lud ed previous spo ntaneous
preterm birth, uterine contractions, vagina l bleeding, U ing tocodynamometry, even by long di stance and at
pelvic infection and bacteri a! vagin os is. 24 home, sorne suggested that thi could be a reasonable
mean for monitoring thi s activity. 41 -44 There appeared
Additional risk factors include such conditions as in- to be sorn e ea rl y enthus iasm for thi s approach and it
fe rtility, abortion, adolescence, multipl e pregnancy, pre- appeared to be somew hat effecti ve in identi fy ing early
mature cervica l dilatation, hi story of previous stillbi1th, the woman who mi ght go into preterm labor. 45-47 Re-
malpresentation , maternal age of greater than 35 year ports were then publi shed which showed th at this mea-
and a gestat iona l age at which the mother was born of urement was not cli ni ca ll y useful for th e predicti on or
at less than 37 weeks (Table 56-4). 25 »8 When one of prevention of preterm de livery. 48·49 Thi s approach also
these ri sk factors are identi fied at the initi al intake at the began to utilize nursing interventi on. The initia l reports
new obstetrical visit or during the course of the preg- were hopeful 5º but it was show n to result in no better
nancy, the patient is entered into th e nex t phase of the outcome than those who have less frequent nursin g
program. contact.5 1-54 .
The bulk ofthis work brou ght to th e surface a seri es of

Uterine Contraction Self-Monitoring symptoms that were associated with uterine contrac-
ti ons and the possibility th at th ey may hera ld the onset,
lt see ms quite clear that women who are destined for sorne time in the future, ofpreterm labor.55 ·56 While there
pre-term de li very ha ve more uterine activity on average was co ntinued con troversy with rega rd to these signs
than do other women of co mparable gestational age. and symptoms, because of their low pos iti ve pred icti ve
Although there may be a considerab le amount of over- va lu e, their use fo r the purposes of sc reening for the
possibiliry of pre-term labor was defended. 57 This ali
Tab le 56-3: Recogni zed Risk Fac tors for presented certain chall enges. As obstetricians, it has
Preterm Labo r and D elive ry' been thought that " Braxton Hicks contracti ons" were
N ICHD Maternal Feta l M edicine Network norm al, but there was a cal! fo r th e discontinuation of
the term "Brax ton Hi cks contracti ons." 5K
Risk Factor %
Positive fetal fibron ectin 29.4 At the Pope Paul VI Jnstitute, pati ents are in structed on
Cervical length :<: 25 mm 26.9 the symptoms of uterin e contractions during pregnancy
Previou s spontaneous preterm birth 23.4 (Tab le 56-5). These include pelvic pressure, low back-
Contractions 16.2 ache, the uterus knotting up like a ball. uterine con-
Vagi nal bleeding 14.9
tractions (or cramps), a vaginal discharge (especial/y
Pelvic infection 12.2
Bacteria! vaginosis 12.3
the "2 W " discharge) and vaginal bleeding which is
otherwise unexplained. Th ey are in stru cted in the fol-
1. From: Goldenberg RL, lams JO, Mercer BM, et al. : The Preterm Pre- lowi ng fas hi on:
diction Study: The Yalue of New vs. Standard Risk Factors in Predicting
Early and Ali Spontaneous Preterm Births. Am J Pub Hlth 88: 233-238,
1998.
Pelvic pressure:
Sometimes uterine contractio ns are fe lt s impl y as a Table 56-5 : Sympto ms o f U te rine
s ig nifi ca nt press ure in the pe lvis w hich te nd s to Co ntrac tio ns during Pregnancy55· 56
co me and go. Sometimes wo men w ill describe thi s
fee ling as "so mething fallin g o ut. " Sometim es they
a re rh ythmi c, occurring two to th ree times a n ho ur, Pelvic pressu re
Low backache
or pe rh aps o nl y two to th ree tim es a day. In o rde r to
Uterus knots up into a ball
be impo rtant, they do not have to be occurring ev- Uterine contractions (or cramps)
e ry three to fi ve minutes . Vagina l discharge (2W)
Vaginal bleeding otherwise unexplai ned
lmv backache:
Low backac he is a nothe r s ig n of uterin e contrac-
ti o ns, espec ia ll y if it is pe ri odi c. Sometimes ute rine
contractions are best fe lt in the bac k and are not fe lt
in th e fro nt. Aga in , o ne 's awa reness that thi s may Vaginal discharge (2 W) :
occ ur can be ve ry helpful. Genera ll y, there is no di scha rge during th e course of
pregnancy, altho ugh on occas io n, a mucu s di scharge
Uterus knots up like a ball: mi g ht occur. When a wa tery di scharge (wet w itho ut
Som etimes the o nl y sympto m of contracti o ns is the lubricati o n) beg ins to occ ur, it is impo rtant to be
ti ghtening of th e uterus in whi ch th e ute ru s seems notifi ed . lt may be a sign of a low-grade infecti o n
to " kn ot up like a ba ll." In a s ituati o n like thi s, it is a nd these infec ti o ns can be the ea rl y stimulu s to the
easy to to uch the ute rus thro ugh the a bdomina l wa ll develo pment of pre mature labo r.
and to dete rmine its firm ne s. Again , if the e are
rh ythmi c, they are impo1tant. Vaginal bleeding, othenvise unexplained:
Th e re should be no vag inal bl eeding durin g th e
Uterine contractions (cramps): course of pregna ncy until a wo man goes into labo r.
The uteru i a mu ele a nd when it contracts, there O n occasion, however, bl eeding ma y occu r some-
mayo r may not be a fee ling that the woma n wi ll per- time du ri ng the seco nd o r third trimeste r of preg-
ceive as a contraction . Whe n the wo man is in labor, nancy. lt may be the o nl y s ign of th e uterus con-
the contracti ons are eas ily identifi ed. However, in the trac ting and ofte n is a ign of low-g rade in fec tion. 1f
earli er stages o fpregnancy, they may eas il y go unno- a wo man observes thi s, it sho uld be repon ed to her
ticed un les she develops an aware ness of these con- physicia n.
tracti ons and a rea li zatio n ofthe ir impo1ta nce. Uter-
ine contractio ns cause the ute rus to tighten and re- The pati ent is educa ted in mo nito rin g these sympto ms
lease in a periodi c fashi on. Uterine co ntracti ons are of uterine contractio ns during pregnancy. Most impo r-
not co nstant (generall y spea kin g) and occas ional and ta ntl y, she is encouraged to notify the phys ician :S of-
irregul ar contracti ons are o f less significance. fi ce when they occur. A uterine contraction se lf-mo ni-
to rin g fo rm is prov ided to the pati e nt so that s he ca n
Th e wo man ca n a ppreciate the presence ofut e rine co n- mainta in thi s mo nito rin g during th e co urse of th e ec-
tractions by s imply reali zing th e importa nce ofthi s kind o nd a nd third trimeste rs ofhe r pregna ncy. T his fo rm is
of tig htening that occurs in he r a bdo me n whi c h comes show n in Tabl e 56-6. With the use o fthi s form , she ca n
a nd goes over a peri od of time. Th is ca n also be identi- be encouraged to monito r these symptoms. 1f the symp-
fi ed by ly ing on o ne 's left s ide w ith fi ngertips pres ing toms a re essenti a ll y the same from o ne day to th e next,
aga in st th e ute ru s. 1f the ute rus inde nts softl y a nd eas- they a re most lik ely not importa nt. However, o nce they
il y, then the re are no contracti ons. Once the ute rus ti ght- c hange or become mo re se vere, it is extreme/y impor-
e ns, it will fee l mo re firm and that firmn ess is a contrac- tan! th at th e ph ys ic ian 's offi ce be notiti ed . Su ch 111-
ti o n w hethe r o r not the wo man inte rprets it as a contrac- struc tion is prov ided to the pati ent.
ti o n o r not. On e ca n time these contracti o ns wi th thi s
type ofmonito rin g. 1f th ese symptoms are the sa me fro m one day to the
next, they are most like ly not ve ry re levant. Howe ve r,
1n sorne wo me n, th e uterin e contracti o ns fee l clo e to o nce the patte rn changes, it is important to pay atten-
me nstrua l- lik e cra mpin g that is inte rmitte nt. Wh e n ti on to it. lt is also impo rta nt to allow the woman not
c ramps occur durin g the course of the pregnancy, they onl y to decide the ·e issues, but also provide he r th e
s ho uld not be ig no red. free dom to ca l1 the o ffi ce a nd ha ve the o ffice nurses,
Obstetrical Health Maintenance
Uterine Contractions Self-Monitoring System

Due date: _ _ _ _ _ _ _ _ _ _ _ __ _
Month : - - - - -- - - - - - - - -
Date of Month
Sign 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
1. Pelvic pressure
2. Low backache
3. Abdomen knots up like a ball
4. Cramps or contractions
5. Vaginal bl eeding
6. Vaginal discharge (2 W)*
7. Generally not fee ling right (+ or - )
I s today the same a yesterday? (Y or N)

)>
()
Total score o
3
"O
• Use Vaginal DischargC' Recordmg System from )OUr CREIGHTON MOOEL ~ Carl''" ~
¡;;
:¡-
et>
:::i
"'et>
<"
"'c.
:::i
:;
Prepared by o not present (absent) íD
+1 occasional or irregular ~
for the Study of Human Reproduction
+2 more regular, more intense "'íDc.
+3 rhythmic (come and go), stronger )>
2004
"O
"O
o
Table 56-6: Form for recording the uterine contractio ns (self-mon itoring ). "'o
:¡-
who sho uld be properly trained in eliciting and inter- The Use of Progesterone
preting these symptoms , to assess them and report to
the physician. The assessment and utilization ofprogesterone in preg-
nancy is reviewed in detail in C ha pters 54 and 55 ofthi s
A Prematurity Preventi o n Office Yisit Assess ment Form textbook. lt wil l not be reviewed aga in at thi s time. How-
is also utilized. This makes it easy at the time of the ever, it sho uld be reinforced that the ab ility of proges t-
prenatal visit to review the patient's self-mon itoring (Fig- erone to effectively treat threatened premature labor has
ure 56-2). No prenata l vis it shou ld be comp lete without been in the medica! literature s ince at least 1956 .59 lt was
reviewing these symptoms with the patient. Funhermore, reinforced in 1979 w he n decreased progesterone a nd
the patient sho uld be told that prenatal vi its can only 17-hydroxyproge terone levels were observed in those
occur o n an every-o th er-week to four-week basis, and patients who delivered premarurely (Figure 56-3 and 56-
yet these symp toms may occur at other times. Thus, 4).60 Subsequent ly, a number of additi o na l studi es ha ve
when they do occ ur a nd when they worsen , it is impor- reinforced these findings. 61 •63
tant for the patient to ca ll the oftice because interve n-
ti o n occurs based on thi s interacti o n. More recently, in 2003 , th e use ofe ithe r progestero ne 64
or 17 a- hydroxyprogesterone caproate 65 we re shown to
be effective in the prevention ofpreterm labor. And yet,
e ve n befo re the second of these two latter stud ies was
publi shed , it was declared that it was " too soon to adopt
progestero ne fo r the prevention ofp reterm delivery"66
PREMATURITY PREVENTION PROGRAM

OFFICE VISIT ASSESSMENT FORM
Patient's Name:_ _ _ _ _ __ _ _ _ _ _ __ _ _ __ __ ETA by CrMS: _ _ _ __ __ _ _
U/S: _ _ _ _ _ _ _ __
Physician 's Name: _ _ _ _ _ __ _ _ _ __ _ _ _ __ __ LMP: _ _ _ _ _ __ __
DIRECTIONS: Please complete the following form at each prenatal visit.
Date
Gestational Age
1am experiencing:
1. Pelvic Pressure
(Yor N)
2. Low Backache
(YorN)
3. Abdomen Knots up Like a Ball

(Yor N)
4. Cramps or Contractions
(YorN)
5. Vaginal Bleeding
(YorN)
6. Vaginal Discharge
(Yor N)
7. Generally not Feeling Right

(Y or N)
Treatment Plan
lm lemented
To be completed by the physician or the nurse: These Symptoms are: (Put symbol in lower right triangle of box)
These Symptoms are: (Put number in upper New: New since the last visit
O. Absent outer triangle ol box) NC: The same intensity as the last visit
1. Mild lfl: lncreased frequency, intensity or severity
2. Moderate since the last visit
3. Severe
Prepared by: Pope Paul VI lnstitute fer the Study ol Human Reproduction , 6901 Merey Road, Omaha, NE 68106
ppplorm Copyright, 2001
Figure 56-2 : A prematurity prevention program office visi t assessment form used al the Pope Paul VI lnstitute .
Chapter 56: Prevention of Preterm Birth: A Comprehensive and lntegrated Approach 753
200 -
-
Control group
Treated palients delivering at term
and the American Co llege of Obstetricians and Gyne-
O Trea ted and untreated patients delivering preterm co logists (ACOG), in their May 2003 Practice Bulletin
180 on the prevention of preterm labo r did nol even men-
tion progesterone. 1 In November 2003, the use of proges-
160 terone to reduce preterm birth was finally assessed by
theACOG, but then only with a caution that it should be
restricted in its use on ly for women with a documented
hi story ofa prev ious birth at less than 37 weeks ofges-
tation. TheACOG Committee on Obstetric Practice cites
" unreso lved iss ues" and these include "optima! route
n •6
/j
/ ¡n•6
n• 2
of drug delivery and lon g-term safety of the drug." 67
And yet, progesterone has been used in pregnancy for
over 50 yea rs with no known short or lon g-term safety
issues. The ACOG approach to pre-term birth appears
to be without urgency. To them , a patient first needs to
60 n •5
n • 10 su ffer through a preten11 bi11h and its known neo natal
1 Gpl>Gp3 Gp2 >Gpl
and lon g-term problems before th ey can be cons idered
a ca ndi date for supplementation with a hormone wh ich
P< .05 p< .05 is normally produced in large quantitie in pregnancy
Gp2 >Gp3 Gp2>Gp3 Gp2 > Gp3
p<: . 05 P< .025 P< .025 and where it has been shown that patients who go into
preterm labor have suboptimal progesterone levels. Not
onl y does progesterone qui et th e uteru s, but also
16 24 32 40
WEEKS' GESTATION progesterone may cause the narrowing and lengthen-
in g of th e cervix in a somewhat similar fash ion to its
Figure 56-3: The mean plasma progesterone levels as mea-
sured at 16 to 24 weeks , 24 to 32 weeks and 32 weeks to e ffects in the postovulatory phase of the norma l men -
term . The solid circle equals group 1 (controls); the open strual cyc le. 68 lt is troub ling that a hormone that is pro-
triangles equals group 2 (treated patients delivering at term ); duced in as large a quantity as progesterone is in nor-
the solid triangles equals group 3 (treated and untreated pa-
mal pregnancy and can-ies with it virtuall y no known
tients delivering preterm) (From: Johnson JWC , Lee PA ,
Zachary AS, et al: High-Risk Prematurity-Progestin Treatment maternal or fetal side effects, is so roundly ignored or
and Steroid Studies. Obste! Gynecol 54:418 , 1979). de-cmphas ized.
Further study of the integrity of the corpu luteum in

12 - Control group
- Treated patients delivering at term
the cyc le of pregnancy achi evement has also shown
c:::::J Treated and untreated patients delivering preterm th e importa nce of progesteron e. Chec k, et al., have
10 shown that those patients with luteal phase deficiency
who did not rece ive progesterone in the pregnancy that
occurred a her a known hi story of lutea l phase deficiency
had a sign ifi ca ntly hi gher prematurity rate including
severe prematu rity at less th an 32 wee ks gestation 69
(Tab le 56- 7). This has been reproduced by Sik los i, et
al. ,70 who showed that premature labor occurred in pa-
4
n=5
ti ent who had s ignificantl y lower progesterone levels
n•IO l Gpl > Gp3 durin g the lutea l phase oftheir menstrual cycle (p< O.O 1)
P< .01
Gp2>Gp3 Gp2 > Gp3 than th ose who delivered at full term . Taking this infor-
p < .025 P< .005 mation and co mbining it with the knowledge of serum
o 16 40 progesteron e levels during the course ofthe pregnancy
24 32
WEEKS' GESTATION in certain types of lutea l phase defi ciency and in those
Figure 56-4: The mean plasma 17 alpha-hydroxyprogester- pati ents with known types of infe rtility due to en -
one levels (17 a-OHP) levels as measured at 16 to 24 weeks, dometriosis , fo r example, shows the importance of
24 to 32 weeks, and 32 weeks to term . The solid circles are progesterone in these situation s.
group 1 (controls); the open triangles equal group 2 (treated
patients delivering at term ); solid triangles equal group 3
(treated and untreated patients delivering pre-term) (From: More recently, HCG has also been show n to have very
Johnson JWC , Lee PA, Zachary AS , et al: High-Risk Prematu- potent toco lytic effects.7 1 In a placebo-controlled tria!,
rity-Progestin Treatment and Steroid Studies. Obste! Gynecol the use of HCG (one single dose ofHCG 5,000 units IV
54:418, 1979).
754 The M ed ic al an d Surg ic al Practice o f Na ProT ECHNOLO GY
outcomes and have potentially adve rse affec ts o n

Table 56-7: lncid ence of Severe Prematurity women in preterm labor.
(<32 weeks) by Progesterone
Supplem entation Status-Patients with At the Pope Paul VI lnstitute, a s li ghtl y different ap-
History of Lu tea! P hase Deficiency 1 proach has been taken. The drug chosen for use is the
~-mim etic agent terb uta line. Thi s drug is provided to
Delivery at Oelivery at
<32 weeks <37 weeks patients w ho have positive ign or sym ptoms of ute r-
(%) (%)
ine contractions (uterine irritability) because it will qui et
Grou p 1 (n=32 ): uterine activity. lt is used in a dosage of2 .5 mg every
Did not receive progesterone 12.5 31.2 fo ur hours around the clock. Rare ly is a highe r dose
Grou p 2 (n=39): ever used and then on ly o n a ve ry short-term bas is.
Patients taking progesterone 2.6 10.3
~6 but <1O weeks Thi s drug, in higher doses, can be assoc iated w ith sig-
Group 3 (n=469): nificant side effects. However, at thi s lower dose, the
Progesterone therapy 1.3· 13.7' o nl y id e effects obse rved usua ll y are edginess or
~ 12 weeks
jitteriness whi ch usually di ss ipates within seven days.
1. Check JH, Lee G, Epstein R, et al. : lncreased Rate al Preterm
Delive ries in Untreated Women with Luteal Phase Deficiences:
Preliminary Report. Gynecol Obste! lnvest 33:183-184, 1992. Terbutal ine is provided as a mea ns of both quieting the
p<0.01 versus Group 1 (by Fisher exact test) uterus wh il e, at the same time, testing it. ln rnany cases,
the treatrnent of the uterine irritabili ty stops w ith the
use of progesterone and terbuta line. Howeve r, if the
pat ient 's contracti ons or irritabi lity begi n to " break
and 10,000 units of HCG in 500 ce of dextro e as a drip of through" the terbutaline and proge terone, then a move
20 drops/minute) resulted in a delay in delivery of28.8 toward th e use of antibi otics is initi ated.
days versus only 15 days for the placebo-treated group .
Thi s suggested that human chorionic go nadotropin ex-
hibited potent toco lysis w ith no fetal side effects n The Use Of Antibiotics
Up to 80 percent of early preterm births are associated

Tocolytic Therapy w ith an intrauterine in fect io n th at precedes the rupture
ofmernbranes.89 ·90 While there ha ve been many tria Is of
Over the last 40 years, there has been an effo11 made to antibiotic therapy in wo me n w ith preterrn labor, most
identi fy a pharmacologic agent which would stop uter- have found that such therapy does not prevent prema-
ine contractions and prevent preterm birth. The litany ture birth .90 Go lde nbe rg a nd Ro use question whethe r
of pharm aco log ic age nts includes the fol low in g : thi s fa ilu re is due to th e se lection ofinappropriate a nti-
isoxs uprin e, ethanol , rno rphin e s ul fate , terbutaline, biotics, the initiation of treatrnent too late in the cas-
rito drin e , ind o rn e th ac in , mag nesium su lfate a nd cade of events leading to sponta neo us preterm labor or
atosiban .73 · 74 Extens ive eva luation ofthese agents, alone other factors which are un know n.9 1
or in comb in ation ha been conducted over this period
ofti me. 75 -86 By 1993 , the three rnost common ly used drug A c lue to possible identification of those women who
were ritodrine, te rbutaline and magnesium sul fate. 87 have " silent c horioam ni o niti s" as a ca use of preterm
labo r was published in 1984 92 (Tab le 56-8). Harneed, et
In a critica! and co mpre he ns ive review of the e fficacy a l. , showed that those wo me n who were ref ractm y to
a nd safety of these age nts, in 1993 , Hi gby, et al. 88 con- toco/ysis wi th ritod rin e, had a pro mine nt presence of
cluded that "The o nl y tocolytic drugs that might be indicators suggesting a si/en! chorioamnionitis. Th e e
effective are the prostag landin inhibitors . Tocolytic included an elevated maternal e-reactive pro tein , posi-
age nts should o nl y be used between 24 a nd 32 co m- tive amniotic fluid gram stain, greater than 100 mrn 3 white
pleted weeks of gestati o n. Magnesium sul fa te shou ld blood cells in the amni otic fluid , positive bacter ia! growth
not be used to treat premature labor. Oxytocin antago- a nd histopathologic evidence of c horioa mni o nitis at the
ni sts sho uld be used o nl y in experimental clínica! tria Is. ti me of delivery. This study, and other w hi ch po inted to
Ca lc iurn c hanne l blockers and beta ad re nergic receptor imil ar findings ,93 -95 provoked the a uthor to begin to
ago ni sts inhibit ute rin e contract ions but do not pro- use the c lini ca l s ign of a breakthrough in ute rin e activ-
lo ng gestat io n for longer than 48 ho urs. " A lth ough ity whi le on tocolytic age nts (specifically terbutaline)
tocolytic agents were shown to prolong pregnancy, they asan indication of s ilent c horioam ni oniti s.
ha ve not been shown to imp rove perinatal or neo natal
Chapter 56 : Prevention of Preterm Birth : A Comprehensive and lntegrated Appro ach 755
hi gh in tra-amn iotic fluid leve ls, cefoperazone sodium

Table 56-8: Silent Chorioamnionitis as a Ca use (Cefobid) was chosen fo r use.98 At the tim e thi s antibi-
of Preterm Labor that is otic was initi ated, the concept of "p ul sed antibi oti c
Refractory to Toco lysis 1 therapy" was ini tiated. Once th e pati ent had brea k-
Successful Failed
thro ugh contractions on terbuta lin e, she was consid-
Tocolysis Tocolysys p-value ered a candi date fo r the initi ation of pul sed cefoperazone
Source & Test Results n % n % th erapy. The therapy began as an outpati ent intrave-
Maternal blood nous appl ication giving 2 grams IV every other day fo r
e-reactive protein th ree doses over a course oftwo to three weeks (usu-
+ 2 33.3 4 66 .6 <.005
29 93.5 2 6.4 all y Monday, Wednesday and Friday). Once there was
Amn iotic fluid symptomatic improve ment, the anti bioti c therapy was
gram stain decreased to 2 grams IV tw ice a week. 1futerine contrac-
+ o O.O 2 100.0 <. 025
ti le activity increased symptomati ca lly aga in , the anti -
31 88 .6 4 11.4
W BC
biotic therapy was increased aga in to three times a week.
> 100 mm' 2 28 .6 5 71.4 <.00025 Thi s continued until 37.0 weeks when it was di scontin-
s 100mm 3 29 96 .7 1 3. 3
ued.
Bacteria! growth
+ 1 25.0 3 75.0 <. 01
29 96 .7 3. 3 Cefoperazone has a very broad spectrum of acti vity,
Histopathologic one whi ch will cover most of the aerobi c and anaerobic
chorioam nionitis bacteria often foun d in th ese situati ons. A compari son
+ 2 28.6 5 71.4 <.01
27 96.4 3.6 co ul d be made betwee n the ea rl y deli ve ry rate pri or to
the introd ucti on of cefoperazone into the reg im en and
1. Hameed C, Tejani N, Verma, UL, Archbald F: Silent Chorioamnionitis as
a Cause of Preterm Labor Refractory to Tocolytic Therapy. Am J Obstet aga in afterwards. In Tabl e 56-1 O, the in cidence of pre-
Gynec. 149: 726-730, 1984.
mature deli very _:: : 35 .9 weeks gestati onal age after initia-
ti on of cefoperazone therapy was 2.8 percent. Pri or to
that time, it had been 6.6 percent (p=.O 1, chi-square analy-
sis).
When one rev iews the types of mi croorga ni sms that
have been identified in chorioam nioni tis, one sees a In Tabl e 56- 11 , a simil ar compilation of data is presented
great va ri ety. These are ide ntifi ed in Tab le 56-9 . Whil e for patients who deli vered at _:: : 34.9 weeks gestati on.
antibi oti cs ha ve not usually been successfü l, it is like ly Here the diffe rence was even more striking as the in ci-
that th ey have eith er been started too late, or the choice dence pri or to cefoperazone therapy was 4.9 percent
of antibi oti c has not had a broad enough spectrum. and afterwa rds, 1.7 percent (p=.O 12 chi -sq uare analy-
sis).
Prior to ini tiating any antib iotic therapy, urine cul tu res
and sensiti viti es need to be done because of th e possi-
bility th at an asymptomati c bacteriuria may be present.
These asymptomati c bacteriu rias have been shown to Table 56-9: Type of High-viruience
be assoc iated wi th both preterm deli ve ry and low birth Microorga nisms Recovered from Amniotic Fluid
we ight in fa nts. Antibi otic th erapy in th ose situ ations in Preterm Labor and PROM 1
directed spec ifically at the causative organ ism, is effec-
tive in reducing the occ urrence of low birth we ight.96
Aerobic Organisms An aerobic Orga nisms
Group B streptococci Peptococcus
Whil e many anti bioti c tri als have not shown satisfac- Enterococci Bacteroides
tory res ults, th e use of a combin ati on of am pici lli n- Strep viridans Peptostreptcoccus
Staphlococci aureus Fusobacterium
su lbactam has shown to be effective in prolongi ng preg-
Gardnerella C/ostridium
nancy in the presence of prematu re rupture of mem- Coliform
branes.97Thi s combinati on anti biotic has a broader spec- E. coli Genital
Klebsiella pneumonia Mycoplasma
trum than many used in the past. Proteus mirabilis Chlamydia
Citrobacter freundii
Enterobacter aerogenes ... and others
The antibi oti c program of the Pope Paul VI ln stitute
was begun in December 1985. At that time, the thi rd 1. Hillier SL, Krohn SL, Kiviat NB , Watts HB , Eschenbach DA:
Microbiologic Causes and Neonatal Outcomes Associated with
generati on cephalosporin s were j ust becoming ava il - Chorioamnion lnfection. Am J Obstet Gynec 165: 955-961 , 1991.
ab le. Beca use of a long half-l ife, broad spectrum and
Th e pati ents also ex hi bited superb symptomati c im-

Table 56-12: Subj ective Assessmen t of
provement in the presentation of their symptoms of uter-
Overall l mprovemen t in P atien ts'
in e contract ion irri ta bil ity. In a stud y of 82 consecuti ve
Symptoms with P ulsed Cefo perazo n e
patients rece iving cefo perazo ne therapy, 69 of them had
(N= 82)
good to exce ll ent symptomati c improvement (84.1%)
(Table 56-1 2). In th ose who had improvement, the mean How Patient Feels n %
number of days required until improvement was atta ined Excellent 46 56.1
was 10.3 (Table 56- 13). Good 23 28. 0
Minimal improvement 3 3. 7
In additi on, the incidence of the premature ruptu re of No improvement 10 12. 2
rn embranes prior to 3 7. O weeks gestation dec reased Totals 82 100.0
from 4. 9 percent prior to the introduction of cefoperazone
th erapy to 2.3 percent afterwa rds (p=.04, chi-sq uare
analysis) (Table 56- 14).
Another ex peri ence was also obta ined with eight pa- Table 56-13: W h en Sym pto ms lmproved
ti ents who had pro longa ti on of th ei r pregna ncy fo r H ow Lon g After Star t of T herapy was
greater th an seven days after spontaneo us rupture of l mp rove m en t N oted ? (N= 72)
membranes prior to 37 .O weeks gestati on. With the use Number of days after
of cefop erazone, the pregnancy was pro longed on an antibiotic s sta rted n %
average of 11.8 weeks. Without cefoperazone, the pro- 1- 7 42 58 .3

longati on was onl y 5.9 weeks (p=. 11, eq ual va riance /- 8--14 15 20.8
test) (Tabl e 56-15). In one case, the patient's rnem branes 15--21 8 11 .1
ruptured at 16 weeks ges tati on and w ith pul sed ?.22 7 9. 7
Mean number of days until 10.3
improvement
Totals 72 99.9
T able 56-10: Delivery at s3 5.9 Weeks Befo re 1. Antibiotic was pulsed cefoperazone.
and After U se of Cefoperazo ne

Po pe Paul Vl lnstitute Protocol
Cefoperazone Table 56- 14: Ru pture of M em bran es

Befo re After Totals
prior to 37.0 Weeks Gestatio n
Delivery at n % n % n %
Before and After U se of A n tib iotics
:::35 9 weeks 15 6.6 16 cm 31 3.8
?.36.0 weeks 211 93 .4 565 97.2 776 96 .2 Before use of After use of
antibiotics antibiot ics
Totals 226 100.0 581 100.0 807 100.0 n % n %
1. p =.01. chi-square analysis Membranes rupture 11 ' 4.9 182 123'1

before 37.0 weeks
1. Of 226 patients
2. Of775patients
3. p= .04 , chi-square analysis
Table 56-11 : D elivery at s34.9 Weeks B efo re

and After U se of Cefoperazo ne
Po pe Paul Vl l nstitute Protocol Table 56-15 : Prolongatio n of P regnancy'
After P ROM Prior to 37.0 Weeks
Cefoperazone
After Totals
With and W ith out Antibiotics
Befo re
n Mean
:::34.9weeks 11 4.9 10 Lill 21 2.6
With antib iotics 4 11 .8 weeks
?.35.0 weeks 215 95 .1 571 98.3 786 97 .4
Without antibiotics 4 5.9 weeks2
Tota ls 226 100.0 581 100.0 807 100.0 1. Pregnancies where the extension of pregnancy was
greater !han seven days.
1. p =.012. chi-square analysis 2. p= .11 , equal varia nce t-test
Chapter 56 : Prevention of Preterm Birth : A Comprehensive and lntegrated Approach 757
cefaperazone, she deli vered a fu ll -term, hea lthy ma le in- Use of Cervical Cerclage
fant. Ln another case, with ru ptured membranes at 26 weeks
gestat ion and fa ilure of Augment in therapy by the In 1986 , M ichae ls, et al. , 104 reported th e use of ultra-
perin ato log ist, she was given pul sed cefaperazo ne so und to eva luare the length of the cervix and fa und
therapy and within fa ur weeks sea led her membranes and that pretenn deli very was stati sti cally signifícantly higher
eventually deli vered at 38 weeks. Since thi s data is not yet in those pati ents who had a shortened cervix. Ea rl y in
statistically signifí cant, furth er eva luation is needed. th e study, they rea li zed that ul traso und- obse rva bl e
changes of cervica l incompetency, when left untreated,
Unfa rtun ately, cefa perazone was removed fro m the co ul d resul t in seco nd-trimester losses. The study de-
market approx imately two years ago. Si nce that time, sign, therefore, could not incorporate a randomi zed treat-
the lnsti tute's protoco l has used ceftriaxone (Roceph in) ment and non-treatm ent gro up. Nonetheless, thi s study
as its main antibi otic treatment. Thi s anti bioti c is sim ilar began our interest in the eva lu ati on of the cervix by
to cefaperazo ne in that it has a long half- li fe (24 hours) ultraso und assoc iated with the use of cervica l cerclage.
and a simil ar spectrum of activity. Beca use th e half-life
is so long, th e regimen was also changed. lt is given In 1996, Iams, et al. , reporting fo r the Maternal Feta l
intravenously fa r 1Oto 14 days at 2 grams per day. Thi s Medi cin e Unit Network showed that the ri sk of sponta-
can ali be done on an outpatient bas is. In a few cases, neo us preterm deli very is increased in wo men who are
we ha ve used intravenous metronidazo le or ampici lli n- fau nd to have a short cerv ix by vagin al ultrasonogra-
sulbactam, with similar effecti veness, but not as the fi rst- phy du ring pregnancy 105 (Fi gure 56-5 and 56-6) . ln the
line approach. meantime, indi cations fa r a cervica l cerclage were being
expa nded beyond th e tradi tionall y accepted diagnos is
To our kn ow ledge, there have been no neonata l side of classic cerv ica l incontinence (docum ented by a pre-
effects fro m th e use of thi s thera py. So rne have ca u- vious pregnancy loss during the middl e trim ester). Its
ti oned th at drug res istance co uld deve lop when mater- use has been reco mmended in pl acenta previa, 106 uter-
nal antibiotics are utili zed. 99 - 100 Wh ile thi s is a legitimate ine malfar mati ons, 107· 108 prev io u DES ex pos ure or cer-
concern , no drug res istance has been observed in th e vica l cone bi opsy with cervica l changes in pregnancy. 109
I 8 years of appli cation of thi s protoco l. Furthermore, Jn spite ofthese ex pansions, concern continued to ex ist
th e overa ll neonatal morbidi ty and morta ii ty is signi fí - with regard to the overa JI safety of cervica l cerclage and
cantl y reduced beca use of the adva nced gestational w het he r o r not it mi g ht be assoc iated w ith
age at the time of deli very. In addi tion, the use of outpa- chori oamni oni tis, premature rupture of membranes, pre-
ti ent parentera l antibi oti c th erapy has been fa und to be mature labor or other concerns th at might be avo idabl e.
safe and economi ca l. 10 1- 103 There was, in fac t, th e classic ra ndomi zed contro l tri a!
e:- 800 of cervica l ce rclage whi ch suggested that there is no
Q)
.~
14 700
Qi
o 12 Relativa No . of women 600 e - Estimated probability of spontaneous preterm
~ 10 risk Q)
0.5 delivery befare 35·weeks gestation from logistic
500 E e:- 1
::J
ro / o Q) 1
reason analysis
E 8 400 s: .~
Qi 0.4
1
\ - Observed frequency of spontaneous preterm
~ o o \ delivery according to cervical length measured
-
Q_
o
,;;,(,
en
6
4
300
200
ci
z 2
E
~
0.3
1
1
1
\
by transvaginal ultrasound al 24 weeks
o:: 2 \ 100 Q_
1
\
Q)
.~
o o
o 0.2 \
ro o 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68
g
Qi
~
:.oco 0.1
Le ngth of Cervix (mm) .o
5 10 25 50 75 e
Q_
Percentile O.O
Figure 56-5: The distribution of subjects among percentiles o 20 40 60 80
for cervical length measured by transvag inal ultraso nog ra-
phy at 24 weeks of gestation (solid line) and relative risk of Cervical Length (mm)
spontaneous pre-term delivery before 35 wee ks of gestation Figure 56-6 : The estimated probability of spontaneous preterm
according to percentiles by cervica l length (bars). The risks delivery before 35 wee ks of gestati on from the log istic-re-
among women with values at or below the 1st, 5th, 1Oth, gression analysis (blue dash line) and observed frequency
25th , 50th and 75th percentiles for cervica l length are com- of spon taneous preterm delivery (red solid line) according to
pared to the risk among wo men with val ues above the 75th cervica l length measu red by transvaginal sonography at 24
percentile. (From : lams JO, Goldenberg RL, Meis PJ , et al: The weeks (From: lams JO , Goldenberg RL, Meis PJ , et al: The
Length of the Cervix and the Risk of Spontaneous Prematu re Length of the Cervix and the Ri sk of Spontaneous Premature
Oeli very. N Engl J Med 334, 567-572, 1996). Oelivery. N Engl J Med 334, 567-572, 1996).
evi dence that cerc lage either prolonged gestat ion or the Royal Co ll ege's Multicenter Tria! , no special tests
improved surv iva l. However, a major methodological or specia l follow up vis its were requ ired .
flaw in the study inc luded the inelig ibility ofmost ofthe
high-risk groups includin g recurrent spo ntaneo us abor- When comparing the u e of cervica l cerc lage w ith and
tion , multiple preg nancy, congenita l anomalies, uterine w itho ut proph y la ctic antibiotics (cefo perazo ne), the
fibroids, previo us s urgery o n the cerv ix, or a short or a uth or found a much hi ghe r ri sk of premature birth in
dilated cervix (Tabl e 56-16). This tria! , in effect, showed patients who did not receive prophy lactic antibiot ics
that the use of cerv ica l cerclage for the prevention of (p= .00 18) (Tab le 56- 17). When eva luated further (Table
pretem1 labor in individuals who were not at high risk 56-18), the mean gestationa l age at delivery with cer-
and who did not need a cerc lage, resulted in a higher c lage and prophy lactic cefoperazone was 38 .5 weeks.
incidence of problem in the study group. However, it The mean gestationa l age at delivery ofthose pati ents
did not address the actual populati o n of patients who who received cervical cerc lage prior to the use of pro-
might be in need of cerv ica l cerclage. 110 A simi lar study phylactic antibiotics (cefoperazone) was 34.7 week
from France had si mil ar results and sim ilar flaws . 111 The (p=.00 1).
final report ofthe Medica! Re earch Counci l/Roya l Co l-
lege of Obstetricians and Gynecologists Multicenter lt was also identified that pa ti ents had diffi c ul ty adjust-
Randomized Tria! ofCervica l Cerclage 112 showed that it ing to the cerclage ift hey were mobilized too quickly
had a beneficia! effect in a small number of cases but fo ll owi ng the surgery. Thus, a protocol was developed
was associated with puerperal pyrexia. In none ofthese for ali patients who receive cervical cerclage. This in-
three studi es was ultrasound used to assess the cervix volves the fo ll owi ng:
or were prophylactic antib iotics used. Fu11hermore, in
l. The cervix mu t measure less than 3.0 cm o r exhibit
grea ter than 6 mm of e ndoc e rvica l funneling
Table 56-16: Randomi zed Controlled Tria! of (n ippling) on ultrasou nd exam ination.
Cervical Cerclage 1 2. These changes must be present pri o r to the 28th
week of pregnancy.
No evidence that cercl age eilher prolonged gestation

3. Prophy lactic a ntibi otics are g iven prior to the time
or improved surviva l of surgery in preop holding [currently 2 grams
But most high-risk gro ups were ineligible for th e ceftriaxone (Rocephin) IV].
study
• Recurren! SAB
4. The cerclage i performed (see below).
• Multiple pregnancy
, Congenital anomaly
, Uterine fibroids
5. The patient is kept at total bedrest except fo r bath-
• Previous surge ry room privileges fo r the first 36 hours fo ll ow in g the
• Short or dilated cervix
place ment ofthe cerc lage.
1. Rush RW, Isaac S, McPherson K, Janes L, Chalmers 1, Grant A: A
Randomized Controlled Trial of Cervical Cerclage in Women at High 6. Ceftriaxone ( Rocephin ) is continu ed at 2 grams, in-
Risk of Spontaneous Preterm Delivery. Br J Obstet Gynaecol 91 : 724-
730, 1984. travenously, every 24 hours for three doses .
7. After the 36-ho ur quiet period , the patient is all owed

to be up and around but not at complete activ ity far
another 7 days.
Table 56-17: Cerclage Patients Treated

With and With out Prophylac tic Cefoperazone Surgical Technique
Cefo pe razone
In doing a cervica l cerc lage, a 5-mm Mersi le ne band is
Gestational age Befo re After Totals
at delivery n % n % n % placed in a modified McDonald-type procedure (F ig-
ures 56-7 through 56-14). The band is pl aced at 12, 9, 6,
:::35 .9weeks 7' 35 .0 3 ~ 10 12.5
3 and 12 o'clock positions in a purse-string-like fashion
:c:.36 .0weeks 13 65 .0 57 95 .0 70 87.5
as hi gh up on the cervix as possible. The band shou ld
Totals 20 100.0 60 100.0 80 100.0 be placed deep into the fibro us ti sue of the cerv ix,
1. lndudes four patients delivered befare 26.0 weeks and three patienls between being carefu l not to penetrate the endocervical cana l. 1t
32.1 and 35.9 weeks.
2. p ; .QQ18, Fisherexacttest
is then tied tightly in the anterio r position with e ight
knots so that it ca n be fo und easi ly at 36 to 37 weeks
when it is remo ved .
Chapter 56: Preventi on of Preterm Birth: A Comprehensive an d lntegrated Approach 759
Figures 56-7 through 56-1 4 : The placement of a cervical

cerclage using a 5-mm Mersilene band . The cerclage is placed
at 12 o'clock, 9 o'clock, 6 o'clock, 3 o'clock, and tied at 12
o'clock positio n (From : Pope Paul VI lnstitute research , 2004).
760 The Med ic a! and Surgical Practice of NaProTECHNOLOGY
The cercl age is re moved by pl ac ing a ring fo rceps on fo ll owing the pl ace ment ofan emergency cerclage. They
the knot and pulling gentl y so that the loop of the cer- also noted an improved sonogra phi c status of tbe cer-
clage ca n be ide ntifi ed. Us ing a long, steril e sc issors, vix and the in crease in the le ngtb of the cerv ix corre-
that loop is c ut a nd the cerclage is removed . Thi s can be lated w ith improved pregnancy o utcome.
done, usually w itho ut di ffic ulty, in the office and is per-
fo rmed at 36 wee ks if the re is no prev io us hi sto ry of Funa i, et al. , 114 meas ured the cervix w ithin 72 ho urs of
cervica l in compete nce a nd at 3 7 .O weeks if there is a the cerclage p rocedure. They noted an increase in length
previo us hi sto ry of pregnancy loss. ofthe cervix fro m 2.7 +/- 0.9 cm to 3.6 +!- 0.9 cm. Others
have observed s imil ar fi ndin gs. 115 · 11 6
The length ofth e cervix as measured by ul traso und in
pati ents w hose ce rv ix was initi a ll y less tha n or eq ual to A fte r cons idera bl e ex peri en ce w ith evaluating the cer-
3.0 cm, both befare and after cerv ica l cerclage, is identi- vica l le ngth, it is usuall y recomm ended th at the cerv ix
fied in Tabl e 56-1 9 . The mean length ofthe cerv ix was be measured by tran svagina l ultraso und .11 1- 120 At th e
2 .27 c m pri or to the cerc lage and 3.32 c m afte r the cer- Po pe Pa ul V J ln stitute, we ha ve co ns istentl y used a
clage (N= 14) (p=.000 1). " partia ll y fu ll b ladder" techniqu e and transabdom inal
ul traso und s imil a r to tha t o ri g in a ll y descr ibed by
The endocerv ical nippli ng, as meas ured by ultraso un d, M ichae ls, et a l. 104 · 12 1 We have a lso assessed th e cerv ix
was 14.2 mm pri o r to th e cerclage and 7.0 mm afte r th e by tra nsvagin al sonograp hy, and ha ve used it o n occa-
cerc lage (N = 30, m atched pa irs, p = .0047) . G uzman, et sio n, but have not yet fo und it to be as helpful as th e
al. , 11 3 has studi ed the sonographi c status of the cerv ix tra nsabdomina l approac h w ith a parti ally full bl adder.
By " partially fu ll bladder" we mean that by the subj ec-
tive accoun t, the pati ent empties he r bladder to " half-
Table 56-18: Patients Treated With and
fu ll. " At the tim e of ultraso und examinatio n, thi s can be
Without P ro phylactic Cefoperazone
eas il y verified.
at Time of Cervical Cerclage
Gestational Age at Delivery:
Genera lly speakin g, we have had no diffic ulty in identi-
Singleton Pregnancies Only (N =SO)
fy ing the cervix, although the re are sorne pi tfa ll s that
Proeh~lactic Cetoeerazone need to be cons ide red in do ing thi s typ e of ultraso und
Gestational age Befo re After examin ati o n, th ese wo uld include overdi stension of the
at delivery n % n %
bl add e r a nd m yo m e tr ia l co ntrac ti o n s. Th ese ca n
.'.020.0weeks
20. 1-26.0 weeks
26. 1-32.0 weeks
1
3
o
5o 1
15.0 :
O.O
o
1
1
ººI
1.7
1.7
a rti fact ually le ngthen the cervix o r el iminate the obser-
vati o n of the endocervica l nippling 122 - 126 (Tabl e 56-20).
32.1-35.9 weeks 3 15.0 1.7
36 0-36.9 weeks o O.O 4 6.7
~37 . 0 weeks 13 65 .0 53 88 .3
The Pope Paul Vl lnstitute progra m considers the pro per
pl ace ment of a cervica l cerclage to prov ide exce ll ent
Tota ls 20 100.0 60 100.1
reinfo rcement to the cervix in an appro priately identi-
Mean gestationa l age 34.7' weeks 38.5 weeks fie d po pul ati o n using ultraso und param eters, w ith the
at delivery use of prophy lacti c anti bioti cs and short- term bedrest
1. p;.001 fo ll owing the procedure. In most cases, the patient even-
tually w ill res ume norma l ornea r no rma l activ ity. Ex-
ampl es of ultraso und im ages befare and afte r cerclage
are shown in Fig ures 56-1 5 th ro ugh 56-1 9.
Table 56-19: Length of Cervix as M easured by

U ltrasound 1 in Patients whose Cervix was Table 56-20: Length of Endocervical N ippling
lnitially s3.0 cm Before and After Cervical (Funneling) as Measured by Ultrasound 1
Cerclage (N =14) Befo re and After Cervical Cerclage (N=30)
N so Range
N so Range
Befare cerclage 14 2.27 cm 0.50 1.07-2.93 cm
2
Befare cerclage 30 14.2 mm 6.2 7.00-32.0 mm
Alter cerclage 14 3.32 cm 0.70 1.40-4.27 cm
Alter cerclage 30 7.0 mm ' 11.8 0.0-44 2 mm
1. Measurement done with transabdominal ultrasound and partially full
bladder. 1. Measurement done with transabdominal ultrasound and partially full
2. p;.0001 (Studentl-test) bladder.
2. p; .0047 (Student t-test)
Figure 56-15: Transabdominal ultrasound measurement of the length of the cervix wi th a fu ll

bladder (left) and a partially-full bladder (right) . The cervical length with a full bladder is 3.87 cm and
a partial of 2.91 cm .
Figure 56-16: The cervical measurement with a full bladder (left) is 4.29 cm. The same cervix with
a partially full bladder measures 2.75 cm (right) .
Figures 56-17 : On the left, the endocervical nippling measures 17.1 mm and the cervix measures
2.01 cm . This is prior to cerclage with transvaginal measurement. On the right, the same cervix with
a partially-full bladder post cerclage, measures 3.97 cm . The hyperechoic linear striations in the
cervical ultrasound are the cerclage.
762 The Medica! and Surgica l Practice of NaProTECH NOLOGY
Figure 56-18 : The cervix prior to cerclage (the left) measures 2.23 cm and after cerclage 3.85 cm
(rig ht}.
Figure 56-19 : An example of one of !he pitfalls in assessing !he ce rvix. This example shows
pseudo-nippling of 17.2 mm in depth secondary to a uterine contraction .
Twin Pregnancies _________ Results of the Program ------~
In twin pregnanci es, it has been found that su ppl emen- The results ofthe Prematurity Prevention Protoco l out-
tation with progesterone is he lpful in pro long in g the 1ined in this cha pter are presented in Tables 56-2 2
length of the gestation. In those patients w ho had through 56-2 7. The overa ll prematurity rate (deli ve ry at
progesterone during the course of their pregnancy, the S 36.9 weeks) using the Pope Paul VI lnstitute P rotocol
average gestationa l age at the time of delivery was 36.5 was 7.0 percent (n=775). In a compari son gro up of pa-
weeks. In those patients w ho did not have progester- tients w ho also received their prenata l care at the Pope
one, the average gestational age at the time of de li ve ry Pau l Vl ln stitute, but where the protoco l was not uti -
was 34.6 weeks (p=.03, Wilcoxon Rank-Sum test) (Tab le li zed , the co rresponding prematurity rate was 12 .0 per-
56-21 ). So it is now routine w ith the lnstitute's Prematu- cent (s imilar to the national average) (p = 0.0032, chi-
rity Preve ntion Program to supplement a li twin preg- square ana lysis). Overall , this represents a 7 l .4 percent
nancies with intramuscul ar progesterone throughout the decline in the prematurity rate usi ng this protoco l.
co urse of the pregnancy. If indi cated by ultrasound or
other parameters, the use of cerclage or intravenous A simil ar ana lysis w ith regard to delivery rates at S 35.9
antibiotics, as previously described, wou ld also be uti- weeks,S 34.9 weeks, or S 33.9 weeks is outlined in Tables
li zed, but ofte n is not necessary. 56-23 through 56-25 , and a summary is placed for ali
gestational ages in Table 56-26.
C ha pte r 56 : Prevention of Prete rm Birth : A Comprehens ive and lntegrated Approach 763
Table 56-21: Gestation al Age at D elivery Table 56-24: D elivery at .$34.9 Weeks
T win Pregn ancies With and W ithout Pope Paul VI lnstitute
P rogesterone P rematurity Prevention P ro tocol
Mean (;~$tation al Age Comparison . PPVI
at Oelivery Groug Protocol Tota is
1
Twi ns on progesterone (n=26) 36.5 weeks
Twins not on progesterone (n=13) 34 .6 weeks

.::34 9weeks 20 4.6 15 ~ 35 2.9
?.35.0 weeks 415 95.4 760 98 .1 1,175 97 .1
1. p=.03, Wilcoxon Rank-Sum test
Tota ls 435 100.0 775 100 .0 1,210 100.0
1. p=.008 , chi-square analysis
Table 56-2 2: D elive ry at .$36.9 Weeks Table 56-25: D elive ry at ~33 . 9 W eeks
Pope Paul VI lnstitu te Prematurity Pope Paul VI lnstitute
Prevention P rotocol Prematurity Prevention P ro tocol
Comparison PPVI Cornpa r ison PPVI

,,.Gro up Protocol · Total.s grQYI:! fr2!21<2! Totals .
n % n %- n % Delivery at n % n % n °lo·
.::36 .9 weeks 52 12.0 54 ~ 106 8.8 .::32 .0 weeks 17 3.9 10 LJd'.l 27 2.2
?.37.0 weeks 383 88 .0 721 93 .0 1,104 91 .2 ?.32 .1 weeks 418 96 .1 765 98 .7 1,183 97.8
Totals 435 100.0 775 100 .0 1,21 0 100.0 Tota ls 435 100.0 775 100.0 1,210 100.0
1. p=.0032, chi-square analysis 1. p= .0031 , chi-square analysis
Table 56-23: D elivery at .$3 5.9 Weeks Table 56-26: Summary of D elive ry R ates
Pope P au l VI lnstitu te Pope Paul VI lnstitute Prematurity
Prematurity Preven tion P rotocol P revention P ro tocol vs. Comparsion Gro u p
Co mpariso !'J PPVI Cornparison PPVI

g rQYI:! f rQ!Qs;QI Totals Delivery at Group' Protocol'
..
Delivery at n % n % n % (weeks gestation ) % % p-value3
.'.035 .9 weeks 28 6.4 28 ~ 56 4.6 .::36.9 weeks 12.0 7.0 .0032

?.36 .0 weeks 407 93 .6 747 96 .4 1,154 95.4 .::35.9 weeks 6.4 3.6 .025
.":34.9weeks 4.6 1.9 .008
Totals 435 100.0 775 100.0 1,210 100.0 .":33.9 weeks 3.9 1.3 .00 31
1. Total N=435 deliveries
2. Total N=775 deliveries
3. Chi-square analysis
The most significant reduction in prematurity rates oc- Biochemical lndicators of Preterm Birth
curred at the lower gestati ona l ages; 96.4 percent of
babies were born at 36.0 weeks or greater. At :S 34.9 There is a great need to develop biochemical in dicators
weeks, there was a 142. 1 percent decrease and at :S 33 .9 whi ch w ill identify those pati ents who are like ly to go
weeks, a 200 percent decrease in delivery rates . into premature la bor and deli ver. A good dea l of wo rk
has been done in thi s area with still va ri ed results. The
The cornpari son gro up used in thi s ana lysis is not a most pro minent of these is feta l fibron ectin, 126· 127 a pro-
stri ct contro l gro up matc hed for age, grav idity, parity tein located at th e choriodecidual interface. lt is fo und
and other factors. However, a comparison between thi s in cervicovagi nal secreti ons and is pred icti ve in preterm
gro up and th e stud¡1group wo uld suggest th at the study birth in more than half of th e preterm bi1ths at less than
group was overa ll , at higher risk because of th e pres- 28 weeks (when tested at 22 to 24 weeks).
ence of a much higher percentage of patients w ith pre-
vious infe1tility (Table 56-27). At the Pope Pau l V I lnstitute, serum hi gh sensi ti vity e -
reactive pro tein (hs-e RP) has been used asan adj unc-
An estimate of the frequ ency with whi ch progesterone, tive a id in a gro up of pati ents. e -reacti ve prote in (e RP)
antibi otics and cercl age we re used to obtain these re- is an ac ute-phase protein that was di scovered in 193 0.
su lts is shown in Table 56-28 . Jn the most recent 192 e RP was the first ofa gro up ofprote in s that was fo und
consecuti ve hi gh-ri sk pregnanc ies managed with this in th e ac ute phase of in fec tion . The ac ute-ph ase re-
protocol , 126 received progesterone (65.6%), 47 received spo nse, i.e., th e changes in co ncentrations ofthe ac ute-
antibi ot ic suppo1t (24.5 %) and 8 hada cervica l cerclage phase proteins , is a non-specifi c innate defense mecha-
(4.2%). lt wo uld be anticipated that the freq uency of ni sm of the host. There are many other conditi ons be-
use of these techniques would be proport ionall y de- sides bacteria! infecti ons th at lead to an acute-phase
creased in a lower-risk population (and perha ps even response inc ludin g infl ammati on, necros is, ma li gnan-
hi gher, ifth e population was at hi gher risk) . cies, burns, surgery, trauma, childbirth , strenuous exer-
cise, stress and psychiatri c di sease. 128
e -reactive protein is a co mpl ex g lyco protein fo und in

the a 2 globulin fraction ofserum . The ability to measure
eRP has changed over the years and has created sorne
degree of confus ion. 129 However, with th e recent ava il-
Table 56-27: Comparison Gro up and ability ofan autornated hi gh-sensitiv ity e -reactive pro-
PPVI Prematurity Prevention Gro u p tein assay, the sensitivity fo r identify ing this protein
Comparison PPVI
has in creased significantly in the last few yea rs u º· 13 1
ltem Group Protocol p-value
e -reactive protein has been studied in pregnancy over
Age(x) 270 29 .8 <. 0001
Gravida (x) 3.16 2.96 NS
the last 20 to 25 yea rs. Most of these studies ha ve been
Para (X) 1.34 1.18 .026 performed usi ng earli er assay models which were notas
lnfertitity (%) 16.5 39 .8 <.0001 sensiti ve. 132- 145 In additi on, va lues in norm al pregnancy
Mean hs-CRP Levels Before and After the Start of Cefoperazone Therapy (N=6)
Preliminary Resulls
35 .0
~ 30 o 27J
..
E
a: 25 .0
Table 56-28: Th e Use of Progesterone, 9
2 20 .0
A ntibiotics and Cerclage in 192 Consecutive
15 o -----------
16 1
High-Risk Obstetrical Patients 13.0
10.0
10.2
8.2 8.4 7.7 73
5 .0 6.9
Use of ... n % 5.6
Progesterone support 126 65.6

Weeks pnor Cefoperazone Weeks al'ler cefoperazone
to cefoperazone started
Antibiotic support 47 24 .5
Cerclage 8 4 .2 Figure 56-20: Preliminary res ults of serial measurement of
hsCRP befare and after the use of cefope razone therapy
(N=6) . The horizontal dotted line represents the division be-
tween normal and abnormal levels of hsC RP in pregnancy.
Chapter 56: Prevention of Preterm Birth : A Comprehen sive and lntegrated Approach 765
have rarely been studied. 146 - 147 In these limited evalua- Special Case Examples _ __ __ _ ~
ti ons, the median CRP va lues fo r women not in labor
range from 0.7-0.9 mg/dL (or 7.0-9.0 mg/L using the newer The work presented in thi s chapter is summarized with
hi gh sensiti vity assays), depending somewhat on ges- the fo ll ow in g case presentation s:
tati onal age; 95 percent ofthe va lues were 1. 5 mg/dL or
lower ( 15.0 mg/L usin g the hsC R.P assay) . No consis- Case1
tent change in CRP levels was found when women were
serially samp led throughout the course of their preg- This is a 26-year-old , gravida 3, para 2, who ex hibited, in
nancy and when they were not in labor. However, the her first pregnancy, preterm labor, uterine irri tability and
median CR.P value for women in labor at term increased premature changes in her cervix . She was at bed rest for
to 1.3 mg/dL ( 13.0 mg/L) and 32 percent ofva lues were the last 2- 1/2 months ofher pregnancy and deli vered at
over 1.5 mg/dL (15.0 mg/L). In add ition, the median CRP 36 weeks gestation, whi le being cared for elsew here.
va lues in norma l pregnanci es appear to be hi gher than
sta ndardized va lues for non-pregnant individuals ( usu- In her second pregnancy, her cervix measured 2.89 cm
all y li sted at :::; 2.5 mg/L). at 14. 1 weeks without endocerv ica l nippling. A cervical
cerclage was pl aced, she was mana ged with ora l
A very preliminary view ofthe first six cases evaluated Terbutaline, progesterone and eve ntuall y pulsed
by seri al hsCR.P leve ls and subsequentl y treated with cefoperazone. Her hsCRP decreased from 9. 1 mg/L to
cefoperazone is shown in Figure 56-20. This shows an 4.1 mg/L. She continued to work full time throughout
in crease of hsCR.P prior to the introduction of antibi ot- the course ofthat pregnancy and delivered at 41 weeks.
ics anda subsequent decrease into what would be con-
sidered the normal range after the cefoperazone was A simil ar management scheme wa u ed for her third
in stituted. pregnancy. She deli vered at term a~e r working up to the
time of deli very. Her cerc lage is noted in Figure 56-21 .
CR.P is impacted by a variety of other intl ammatory con-
ditions such as periodontal di sease, sinusiti s and per-
haps even the intramuscul ar admini stration of progest- Case2
erone. Thus, its role is far from clear. However, working
toward the deve lopment of a biochemical parameter Thi s is a 36-yea r-old , grav ida 6, para 2, who had three
whi ch would identi fy subclini ca l infection pri or to the previous spo ntaneous aborti ons. She was given proges-
rupture ofmembranes so that antibi otic treatment could terone and HCG support during th e course of her preg-
be instituted, would make a huge impact on the prema- nancy. At 12 weeks gestati on she began having severe
turity rate. The work in th is chapter shows that that can menstrual-like cra mps and vaginal bleeding. Her hsCRP
be accompli shed. Jn addition , others have now shown was 8.5 mg/L. She was given 1O days of Rocephin 2
that patients with premature contraction s and elevated grams IV. Her symptoms di sappeared; her hsC R.P de
CR.P values seem to benefit from antibi otic therapy dur-
in g pregnancy. 148
Many other factors ha ve been eva luated wi th the same

goa l in mind. These include such things as corticotro-
pin-releasing hormon e, 149 amniotic fluid cata lase activ-
ity, 150 AF adrenomedu llin , 15 1- 152 AF ma tri x
metalloproteinase-9, 153 AF cytok ines, 154- 155 interleukin-
6, 156- 158 •16 1 interl eukin -8, 159- 160 neo pterin, 161 seru m tumor
necrose facto r-a lpha. 158· 159 · 162 Even procal citonin, which
has been shown to be enhanced by chori oa mnioniti s in
premature newborns, 163 sa livary estri ol , whi ch is in-
creased in preterm birth, 164 and placenta! growth fac-
tor, 165 which has recen ti y been shown to be increased in
acute coronary syndrome, are logica l targets of future
in vestigation. one ofthese, to date, has become promi-
nent. But to make future progress, such a biomarker
mu st be identified, must be reasonably non-in vas ive
and must be deve loped for these purposes. Figure 56-21: The cervical cerclage is identified by the ar-
rows in this palien! from Case No. 1.
766 The Med ical an d Su rg ica l Pract ic e of NaProTECHNOLOGY
at the Pope Paul VI Institute is 82.6 percent. Thi s com-

Table 56-29: Midtrimester Separation of the pares to a term delivery rate of 44.4 percent as presented
Placenta (Diagn osed by U ltraso und) in the medica! literature (Tabl e 56-29).
and the Use of P rogesteron e
Sauerbrei
&Pham ' PPVI' Case4
n % n %
Del ivered al term 8 44.4 19 82.6 This is a 44-year-o ld, grav ida 8, para 1, who had had six
Delivered prematurely 10 55.6 4 17.4 prev ious spontaneous abortions. Her one and onl y chi ld
was delivered by emergency cesa rean secti on at 36
Tota ls 18 100.0 23 100.0
weeks gestation because of a pronounced decrease in
1. Sauerbrei EE , Pham OH : Placental Abruption and Subchorionic Hemor- fetal heart tones. She was evaluated and found to have
rhage in the First H a~ of Pregnancy: US Appearance and Clinical Outcome.
Radiology 160:109-1 12, 1986.
suboptimal progesterone production during the luteal
2. Besides progesterone, bed rest was prescribed for all patients. Three oflhe phase of her menstrual cycle and also endometri osis.
patients also had cervical cerclages and three had pulsed cefoperazone. The endometri os is was laser vapori zed and her luteal
phase defi ciency was trea ted with HCG.
Durin g the course of her pregnancy, she was managed

creased to 5. 1 and she deli vered at fu l! term with a re- with progesterone and HCG suppl ementation. An ultra-
peat cesarean section. so und at 22.4 weeks, after severa! epi sodes of symp-
to ms ofuterine irritabi li ty, showed a cervix whi ch mea-
sured 2.45 cm with 12.5 mm of endocervical nippling
Case3 and dilatation ofthe interna! cerv ica l os of 16.9 mm . A
cerv ica l cerclage was placed and at 27.6 weeks, her cer-
This is a 26-year-old, gravi da 2, para 1 who began hav- vix was now 3.63 cm with no endocerv ical nippli ng. She
ing signifi cant uterine irritability at about 14 weeks ges- was a lso tr ea te d w ith ter buta line a nd p u lse d
tation. At 16 weeks, a large retropl acenta l hematoma cefoperazone. She delivered at 38 weeks a hea lthy fe-
was identifi ed on ultraso und . She was managed w ith ma le infa nt by repeat cesarean secti on. Her progester-
intramuscular progestero ne and complete bed rest for one profil e du ring the course of her pregnancy is shown
six weeks and the hematoma reso lved. She went on to in F igure 56-22. For much of the pregnancy, her proges-
deli ver a fu ll -te rm , hea lthy baby. terone levels were in low zone 2 or high zone 1.
In a series of23 such pati ents, the ful l-term deli very rate
180
Progesterone in Pregnancy
Case #4
160 ....._. Normal mean
_._ Paüent
? 140
°'
.s
Q)
e
120
e 100
2en
e
Q)
Q._
80
E 60
::;¡
~ 40
20
o 2 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figure 56-22 : Th is is the serum progesterone profile of Case No. 4 of a patient

who had had six previous miscarriages , but ca rried th is pregnancy to term with
prematurity prevention protocol.
Chapter 56: Prevention of Preterm Birth : A Comprehensive and lntegrated Approach 767
Cases amox icillin and guaifenes in for mucus en hancement, T3 ,

naltrexone 16 mg by mouth two times a day (PO BID)
Th is is a 24-year-old, gravid a 5, para 1, who had one and estradiol -1 7 ~ , 1 mg by mouth every day at bedtime
previously induced aborti on, one ectopic pregnan cy, a (PO QD hs) Peak + 3 through 12. She had also been tried
stil lborn at 19 weeks and a delivery at 24 weeks with for many months on low-dose Clomid , but its effect on
spontaneou rupture of membran es at labor. With the the mucus was so poor, it had to be stopped.
last delivery, she was sent home by the perinatologist
until she went into labor. With thi s treatment program, she did achieve a preg-
nancy, but at 16. 7 weeks gestation, she began hav ing
With her fifth pregnancy, she was fo ll owed carefu ll y symptom s and her cervix measured 2.65 cm with 19. 1
and by 10.2 weeks, airead y had ev idence of endocervi- m111 ofnippling and dilatation ofthe interna] cerv ical os
ca l nippling. Because of her ex tremel y poor obstetrica l at 15. 7 111111. She underwent a cervical cerclage and four
history, she was given three days of cefoperazone prior weeks later, her cervix was 3 .1 3 cm with no endocervical
to placement ofthe cervical cerclage. This was followed nippling and the interna! os was closed . She al so had, at
by an additional 1Odays . The cerclage, in her case, was 22 weeks, a recurring probl em with uterine contractions
placed at 10.2 weeks. While this is un usual , beca use of and was treated with ceftriaxone 2 grams 1Y x 14 days. A
her poor obstetrical hi story, it was thought to be justi- great many ofher sympto111s di sappeared. At the time of
fied. publication ofthis textbook, her pregnancy is progress-
in g norm all y, she is without symptoms and doing well.
In this pregnancy, she had spontaneous rupture of th e She is also being suppl e111ented with progesterone dur-
membranes at 38.1 weeks, and eventually hada cesar- ing the cou rse ofthi s pregnancy. Her progesterone curve
ean section for failure to progress. She had a 6-pound, is shown in Fi gure 56-23 with her levels consistently
7-ounce baby boy with Apgar seores of7 and 9. being subopti111al.
One of the important fea tu res of thi s case is her CrMS

Case6 chati, which prior to her pregnancy, is shown in Figure
56-24 . Thi s chart shows mul tipl e signs of infec tion
The final case presentation is a 41-year-old , grav ida 2, present in advance of her pregnancy. The prolonged
para O, who had one previous spontaneous aborti on epi sodes of premenstrual brown bleeding, the "frequent
along with a long hi story of infe rtili ty. At the tim e of 2W" observations and the tail-end brown bleeding can
evaluation, she had endometrios is, severe bil atera l sa l- ali be signs oflow-grade infecti on whi ch are otherwise,
pingitis isthmi ca nodosa with bilateral occlusion ofthe asymptomatic. A focus ofresearch in th e future will be
fal lop ian tubes, decreased pre-Peak and post-Peak es- the eva luation ofthe CrMS and its standardi zed vulvar
tradiol levels and a normal progesterone profile. Her observati ons with th e subsequent outcome of pregnan-
T3 :rT3 ratio was 3.7 and her ~-endorphin leve! was less cies. lf, in fact, much of prematurity is caused by low-
than 8.8 pg/mL. She was treated with post-Peak HCG, grade infec ti on, which is, ofand by itse lf, very difficult
180
Progesterone in Pregnancy
160 Case #6
_._ Normal mean
__.,_ Patient
~
E
140
o,
.s
QJ
120
e
e 100
2
.·
"'
~ 80
e ... ...
Cl.
E 60
::J .·
~ 40
20
o 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40
Weeks Gestation
Figu re 56 -23: This represents th e progesterone cu rve in preg nancy of a patient

with threatened premature labor, low-grade chori oamnionitis treated with proges-
terone , ceftriaxone , terbutaline and ce rclage (Case No. 6).
768 The Medica! and Su rgical Practice of NaProTECHNOLOGY
15 16 17 18
p. 15_q
P+7 E.a: .5.s
SCK IOK
><I • I
Clr'D MO OA.O 0-.0 OAO 0-.0 °"'º VL
•I
VL
xi
oa.D OAO OAO
""""""
Figure 56-24: This is the CrMS chart from the patient in Case No. 6. This is her chart leading up to the time of her pregnancy.
Noteworthy is the presence of prolonged premenstrual spotting, tail-end brown bleeding and "frequent 2W" observations. Ali
of these observations are consisten! with a low-grade infection being present prior to the onset of her pregnancy. Further
research is necessary to determine the ability of this type of prospective tracking of vulvar observations to be helpful in the
identification of low-grade infection prior to the onset of pregnancy and , hopefully, subsequently treated (From: Pope Paul VI
to diagnose, the best of ali worlds wou ld be to identify dressed. Most ofthe effort can be accomplished through
this in advance of pregnancy, treat it effectively and an outpatient effort. lt is not common for a Pope Paul V I
prevent the entire spectrum of uterine irritability, uter- lnstitute patient to be managed in the hospital and when
ine contractions, premature labor and premature birth. it doe occur, it is usuall y onl y for one or two day ,
enough time to give adose ofsubcutaneous Terbutaline
(0.25 rng SQ), hydrate the patient and give her one dose
Cónclusions ------------~ of ceftriaxone.
This work has shown th at it is possible to make a sig- This chapter began by pointing out that the prematu-
nificant impact in reducing the esca lating incidence of rity rate in the United States is a national tragedy! Un-
preterm births. lt does require, however, a pecific com- fortunate ly, it does not yet get enough publicity to
mitment to see that it is accomplished. This particular arouse the public to greater action. Sorne ofthe increase
program has worked because it uses a comprehensive is iatrogenic (especia ll y with the increase in multiple
and integrated approach. lt is also made possible by pregnancies from A RT) and sorne is se lf-imposed by
incorporating the pregnant woman, through pregnancy- what appears to be pregnancy-assoc iated in fectio n,
related education, in to the role ofa meaningful partner in sorne ofwh ich is most ce1iainly secondary to sexua lly-
her own healthcare and that ofher new baby. Patients wi ll transmitted diseases. Sorne of it, too, is undou btedl y
respond when given this opportunity and without them , related to the widespread use of first trim ester induced
it is not possible. lt should be pointed out that others abortion by the medica! profession to solve what ulti-
have used successfu ll y, a somewhat simi lar approacli. 119 mately is a soc ial problem. But most of it appears to
result because ofa lack ofwill on the pa1i ofthe medica!
In addition, the ph ys ician and others in the prernatu- profession and the commun ity to make a defined im-
rity-prevention program cannot accept pretem1 labor and pact. lt is hoped that the work presented in thi chapter
birth as a.fait accompli. lt mus! be viewed asan inten- wi ll stimulate others to develop meaningful program
sive care situation and mus! be corresponding ly ad - for the prevention ofpreterm birth.
Chapter 56 : Prevention of Preterm Birth : A Comprehensive and lntegrated Approach 769
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Chapter 56: Prevention of Preterm Birth : A Comprehens ive and lntegrated Approach 771
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Recurrent Spontaneous Abortion:
pontaneous abortion is defined as the spontane- nal age (Figure 57-1 ). 7 We are slow ly comi ng to recog-
S ous loss of pregna ncy prior to the 20th gestationa l
week. Pregnancy losses which occur during this period
ni ze that no miscarriage can be considered normal. Ali
miscarriages are the result ofa pathophys iologic repro-
oftime are said to occur in about 15 percent ofpregnan- ducti ve event. lt is the current cha ll enge of medicine to
cies. 1At the same time, the ri sk ofmiscarriage increases find those underlying ca uses and, in sorne cases, un-
proportionately to the number of previous mi scarriages derlying causes that are common occurrences are
experienced (Table 57- 1).2 Unfo1tunately, a definite cause often overlooked.
has been difficult to determine. Over the years, mi scar-
riages have been observed as a somewhat "normal" find- This chapter w ill foc us on th e ro le of
ing. Often it has been thought to be "nature 's way" of NaProTECHNOLOGY, the CREIGHTON MODEL
ending a pregnancy which was doomed to fail in any Fertility Care™ System , end ometri os is, hormona l
regard. However, there has developed a somewhat more
aggress ive approach over the past five to ten years to-
wards evaluation and management ofwomen with spon- Table 57-1 : Rate of Spontaneous Abortio n
taneous abo11ion. lt is now we ll recognized that a defini- (SAB) Relative to N umber of Previous SABs'
tion of recurrent pregnancy loss includes two or more ( =7, 399)
consecutive spontaneo us miscarriages 1 and that thi
Number of Previous Percent Subsequent
warrants a full eva luation. 3 Furth ermore, it is becoming Spontaneous Abortions Spontaneous Abortions
more and more recogn ized that there appears to be an
assoc iati on between in fert ility and sponta neous abor- o 12.3
tion.4·6 23 .7
2 26.2
3 32 .2
A variety of fac tors underlie the occurrence of mi scar- 4 25.9
riage. These inc lude genetic, endocrinologic, anatomic,
immun ologic and microbiologic variations. 1One ofthe
1. From: Warburton D, Fraser FC: Spontaneous Abortion Risks in Man:
Data from Reproductive Histories Collected in a Medica! Genetics Unit.
Hum Gene! 16:1-24, 1964.
we ll-recogni zed features ofspontaneous abo1tion is its
in creased frequency associated with advancing mater-
775
776 The Medica! and Surgi ca l Practice of NaProTECHNOLOGY
c hanges a nd othe r facto rs which are importan! to the

un de rly ing cause of spontaneous aborti on. 50
45
The CREIGHTON MODEL Syste m ==l 40

e:
A large nu mber of patients w ith a history of sponta ne- e: o 35
o ·-
o us abo1t io n ha ve been fo ll owed w ith the CREIGHTON :e c.
o u
.e "'
MODEL System (CrMS). With a history of at least one "' g 30
"' u
-e
prev io us mi scarriage (N= 14 1), the incidence of limited :l
o
Cll "'
N 25
mucus cycles and d1y cycles totalled 74.5 percent (Tab les e: ·-
"'e:
-e: oOl
57 -2 and 57-3). There is no t a large di ffe rence in the o u 20
di stributio n of the muc us cyc le based u po n the prev i- ena. "'
~
e!? ~ 15
o us history of o ne, two, th ree or mo re m iscarri ages. For
the w ho le group, whe n co mpa red to a gro up of no rmal
10
fe rti lity co ntro ls (Tab le 57-3), th e mucus cyc les were
markedl y mo re limited (p<.000 1, chi-sq uare ana lys is). 5
In Tab le 57-4 a num ber ofbio markers ha ve been Further 15 20 25 30 35 40 45 50

evaluated. The mucus cycle score (5.43), menstrual score
Maternal age in years
(5.78), length and variability ofthe post-Peak phase ( 13.04 Figure 57-1 : Spontaneous abortion ve rsus matern al age
+/- 3.52) we re ali hi g hly s igni fica ntly differe nt from the (From : Newcom WW, Rodriguez M, Johnson CWC : Repro-
no rma l ferti lity contro ls. The day in which the Pea k Day duction in th e Older Gravida: A Literature Revi ew. J Reprod
Med . 36:839-845, 1991).
occurred, however, was virtuall y identica l (Table 57-4).
Table 57-2: C reighto n Model FertilityCarern System

T ypes of M ucus Cycles-Patien ts with H isto ry of
Spontaneous Abortion
History of Spontaneous Abortion

Classification Qng IYlQ ;¡ or more ~
of Mucus Cycle n % n % n % N %
Dry 5 5.5 4.2 3.8 7 5.0

Li mited 64 70.3 14 58.3 20 76.9 98 69 .5
Regular 22 24 .2 9 37.5 5 19.2 36 25 .5
Totals 91 100.0 24 100.0 26 99.9 141 100.0
T able 57-3 : T ypes ofMucus Cycles

C reighton M odel Fertili ryCar ent System
P atien ts with History of Spo ntaneous Abortio n vs.
No rmal Fertili ty Co ntrols
History of Normal Fertil ity

Classification One or more SABs Controls
of Mucus Cycle n % n %
Dry 7 5.0 o O.O

Limited 98 69.5 19 30.6
174.5 11 l30 .6 J
Regular 36 25 .5 43 69.4
Tota ls 91 100 .0 24 100.0

1. p<.000 1, chi-square analysis
Chapter 57 : Recurren! Spontaneous Abort ion : Evaluation and Treatment 777
In Figure 57-2, a hormonal corre lation during the co urse tradio l pro fil e. The only horm one whi ch appeared nor-
of a cyc le in whi ch the pati ent beca me pregnant and mal during the course ofthi s cyc le was th e LH surge.
subsequently mi sca rried, is shown in associati on with
the tra cking ofth e fertility cyc le and th e tracking of the The risk of mi scarri age is kn own to be increased in
ovarían fo lli cle. The mucus cyc le was markedl y limited women who have an inadequately short luteal phase. In
(MCS= l .7). In additi on, the fo lli cle was immature at the Figure 57-3, a woman with a short, ft ve-day, post-Peak
time ofrupture (MFD= 1.62 cm). Thi s coi ncided with an phase is shown in associati on with her peri ovulatory
ex tremely suboptim al preov ul atory es t radi o l - 1 7 ~ pro- estradi ol and postovul atory progesterone and estradiol
ftl e and a suboptim al post- Peak progesterone and es- pro fi les. Thi s ft ve-day post-Peak phase pro vides an ex-
Follicle < 1.0 1.18 1 . ~ 7 l.~ FR CLC
diameter LAP Spontaneous

(cm) Abortion
U/S
LH
Progesterone
Estradiol-17
Figure 57-2: Conception in a limited mucus cycl e leading to spontaneous aborti on. An ultrasound study of the fo llicle revealed
an immature folli cle. Preovulatory E2 levels are suppressed and postovulatory P and E2 levels are suppressed. The mucus cycle
is limited. The LH leve! is normal (from Pope Paul VI lnstitute research, 2004 ).
Table 57-4: C rMS Bio m a rkers

Nor m al P atients ( =22) vs. P atie nts Ex periencin g
Spo ntaneous Abo rtio n (N=31)
Normal Fertility Spontaneous

Controls Abortion p-value
n Mean n Mean
Mucus cycle seo re 22 10.35 31 5.43 <.0001 1

(+/-3 .4 3) (+/-3 .77)
Menstrual score 22 6.18 31 5.78 .0068'
(+/-1 .06) (+/-1.86)
Day of the Peak 22 16.9 28 16.5 NS*
(+/-4 .0) (+/-4 .0)
Post-Peak phase 22 11.48 28 13.04 .0003'
(+/- 1.63) (+/-3 .52)
1. /-test
2. F test of equal variances
The re was no sig nifican t difference noted between the two groups in their ages.
1 2 3 4 5 6 7 8 1 9 l 10 1 u l 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 JO 31 3 33 34 35
~!, f f ~ f ~ ~ ef t
!~ ~
·~
J .ól n·
.
H H O<L IOKL IOKl IOKL IOKL IOK.L lOKL >.AO
""º ~g
Estradiol-17P
1 Short Post-Peak Phase 1 Progesterone
• ... •
-
1 1
40.0 ng/dl
1
Regular Mucus Cycle
1 1 1
20.0 ng/m L.
-
""'° 30.0 ng/dl ... 15.0 ng/ ml-
-
...
""'° 20.0 ng/dl 10.0 ng/ml_
-
~ 10.0 ng/dl
... - 1 5.0 ng/ml-
-
l ~EM NO! bRD 'Rf EW Ht R . > A li!PS
IMK
R:
A~POI HM FNT FO ·"
ANI
- 1 •
... 1
• 1
Figure 57-3 : A CrMS chart showing a short post-Peak phase (five days) correlated with its hormone profile wh ich shows a
very short luteal phase (seven days) . Pregnancy in thi s situati on should universall y lead to spontaneous abortion (From : Pope
Paul VI lnstitute research, 2004 ).
ce ll e nt estimati o n of w hat is also an extreme ly short sta bl e length of the post-Peak ph ase in wome n w ho do
luteal phase as dete rmined hormonally. The preovu latory not mi scarry. In Ta bl e 57 -5, the length of the post-Pea k
estradi o l profil e is reasonabl y normal. In a cyc le such as phases of the previo us 19 cycles prior to a concepti o n
thi s, pregnancy may occur, but the likel ihood of sus- w hi ch ended in mi scarri age a re shown. The range in
ta ining it is extremely low. length of the post-Peak pha e in thi s wo man was 7 to 14
days during th e course of that period of observa ti on.
Th is condition is pe rha ps th e first o ne w hich can now Thi s is a hi ghl y unstable post-Peak phase (whi ch esti-
be eva luated and treated before a wo man even becomes mates a hi ghl y un sta bl e lutea l phase) a nd is kn own to
pregnant, thu s eliminating the need altogethe r fo r mi s- be associated w ith signifi cantl y suboptimal progeste r-
ca rri age. Th e evaluatio n begin s w ith track ing the fe rtil - o ne and estradi o l leve ls. Thu s, w hen she did become
ity cycle w ith the CrMS, identi fy ing the short post- Peak pregnant, it was not urpri sin g w hen she miscarried.
ph ase and obta inin g ho rmo nal suppo rt thro ug h sti mu- Thi s ty pe of variabili ty in th e length of the post-Pea k
la tion ofth e corpus lute um w ith HCG (HCG 2000 IU phase or instabili ty in its length is an important biomarker
intramu scul arl y o r ubc uta neously Peak + 3, 5, 7 and 9) . of decreased proges tero ne and estradi ol prod uctio n
A nother bi o marke r whi c h is ve ry he lpful is the pres- Table 57-5: Variation in Length of Post-Peak
ence ofpremenstrual spotting. ln Fig ure 57-4, a wo man Phase Prior to Co nception Leading to SAB
w ith fo ur prev io us mi sca rri ages began tracking her fer- (One Patient's History)
tility cycle and obta ining her ho rmone levels. Her pre- Length of the post-Peak phase in days
menstrual spotting began seven days pri o r to the o nset
14 11 10 9
of menstruati on. She had a very suboptimal lutea l phase 13 11 11 8
progeste ro ne and estradi o l profile and a moderately de- 9 13 11 11
8 7 7 10
pressed pe rio vul ato ry estradi ol profil e. 11 6 12
The post-Peak phase in wo me n w ho eventuall y m is- Range = 7 - 14 days (7 days)

carry is highly variable in compari son to the relative ly
Chapter 57 : Recurrent Spontaneous Abortion : Evaluation and Treatment 779
during th e lutea l phase of the menstrual cycle and its has been well documented for pregnancies that mi s-
assoc iated long-term medica! effects. carry during the first trimester (Figure 57-5) and for preg-
nancies that miscarry between 12 and 20 weeks of ges-
tation (Figure 57-6). lt has been tempting to suggest
Endocrine Parameters ------~ (and many treatments take thi s approach) that it is the
decreased progesterone w hich is the cause of th e mi s-
lt is wel l recognized that the production of progester- carriage and subsequent support ofthe pregnancy with
one in a pregnancy which ends in mi scarriage is signifi- progesterone sho uld be th erapeutic. Unfortunatel y, it
ca ntl y decreased. 8• 10 At the Pope Paul VI ln stitute, this is undoubtedly more complex than that.
12 13 14 15 16 32 33 34 35
Progesterone
Limited Mucus
Cycle
40.0 ng/dL-+.....,l--+--+-l-+--+-__,-+--+-~1-..--.-......---.-......-11--+--+-I--+--+__,-+--+~ 20.0 ng/mL
30.0 ng/dL-+.....,1--+--+-l-+--+-__,-+--+-~l-+--+--+-+--+--+-l--+--+-I--+--+__,-+--+~ 15.0 ng/mL
20.0 ng/dL-+---+-+-+-+__,1--+--+--+__,•+--+--+__,I--+--+--+- -+--1111-t-+--+--+-+--+--+- 1O.Ong/mL
5.0 ng/mL
Figure 57-4 : A woman with premenstrual spotting , a history of four consecutive misca rriages , her CrMS chart and her
hormone profile. Her postovulatory progesterones are remarkably decreased (From: Pope Paul VI lnstitute resea rch , 2004).
Comparlson of Progesterone Levels Comparison of Progesterone Levels

Means of All Levels at 6-Week lntervals Means of All at 6-week lntervals
Sludy Group
141.4 Study group
150.0 1st Trlmester SAB- 148.4
-'
'""º Mldtrlmester
~ Current Pregnancy
(N=75)
l spontaneous
! 100.0 • Norm•I control•

c::J Fl1'9t trimHIM SAB-current pregn•ncy
103.4
~ 1000
abortion group
(N=18) 103.C
l 52.4
73.1
l
- NOl'll'Wllcontrolt
c:::::J Mknrlmetier 1pont.1n9CHl1 • bonk>n grou p
73.8
...
~ ""·º
cll
35.3
o.o ,... 8-12 14-18 20-24 29-30 32-38

week1
WHk• weeks WHkl WHkl WHkl
~va!Ue NS' 1<0001'1
1 Not1tatl:llleally'9'11fant
2 MM! (equal vartlince) Mean Progesteron•-'·week lntervals 1 N0111M1111Ca11yllgnlftcM!t
3 Mffl (unequal vartanc:.) 2 1·""4 (~"tall9nclt) Mean progesterone-6-week lnterval1
JHHl (~Vlllet'a l
-' Mann-WhitneyU!ftl
• Menn-~UMll
Figure 57-5: A comparison of progesterone levels at six Figure 57-6 : A compa ri son of progesterone levels at six
weekly intervals in a group of patients (n=75) that ended in weekly intervals in a group of patients who had middle tri-
spontaneous abortion during the first trimester. Comparison mester spontaneous abortion (n=18). Comparison is made to
is made to a group of normal controls (n=109) (From : Pope a group of normal controls (n=109) (From : Pope Paul VI lnsti-
Paul VI lnstitute research , 2004) . tute research , 2004).
riages (F igure 57-9A through 57-90). The most remark-

Table 57-6: P-HCG Levels Early in Pregnancy abl e decrease in the progesterone production by th e
Fu ll Term vs. SAB 1 corpus luteum was observed , fo ral! catego ri es o n Pea k
Full-term Spontaneous + 7, Peak +9 a nd Peak + l J; although in sorn e categori es
Time following pregnancy abortion th e decrease started as earl y as Peak + 5.
Peak Day (P) 2 n Mean n Mean p-va lue'
P+11 - P+17 32 1,303 .7 16 479 .2 <.02 This hormone pattern stro ng ly suggests that there is
P+18-P+24 25 2,205 .1 23 643 .2 <.0001
an underl ying fea ture of abnormal fo llicul ogenesis w hich
is a n underly ing fea ture to the cause ofmiscarriage. In
P+25-P+32 9 15,320 .6 13 5,859 .3 <.006 fact, the finding th at mucus cycles are s ignifi cantl y lim-
1. From: Pope Paul VI ln stitute research, 2004 . ited , as a genera l rule, in this catego ry of patients and
2. Number of days post-Peak in women using the CrMS
3. Mann-Whitney U test
that this find in g is seconda ry to both suboptimal estra-
diol prod ucti on a nd recepto r formation , the prevalence
of these endocrine findin gs suggests strong ly th at ab-
normal fo ll iculogenesis is at th e root of many mi scar-
riages. This is a find ing w hich , too, could explain sorne
O ne reason for th e decreased progesterone production ofthe underlyi ng genetic abnormali ties which have been
co uld be the decreased production of P-HCG in the de- prom oted as ca uses to the prob lem of mi scarriage. t 1- 13
ve loping tro ph ob last (Tabl e 57-6). T he re is a sign ifi -
cant decrease in the amou nt of P-H CG produced in those
pregna nc ies w hi ch eventua ll y miscarry ve rs us those Premenstrual Symptoms - - - - ----.
pregnanci es which go o n to full term a nd thi s starts
very earl y in the pregnancy. However, that too is overl y With this degree of lutea l ph ase dysfun ctio n, o ne wo uld
simplistic. expect that patients who ha ve mi sca rri ages wo ul d ha ve
an increased rate of pre me nstrual symptom s. In fact,
At the Pope Paul V I lnstitute, we ha ve eval uated a la rge that has been studi ed a nd in Tabl e 57-7 th e incidence of
g ro up of wome n w ith a hi story of one, two, three o r vario us premenstrual sympto ms in 300 wo men w ho have
mo re mi sca rri ages . Thi s endocrine eva luation in vo lved previous ly ex perienced a spontaneous abortio n are iden-
a look at the pe ri ovul ato ry estrad iol levels a long w ith tifi ed . While the incide nce of the premenstrual symp-
the postovulatory progesterone and estrad io l levels. toms is somew hat less th an that o bserved in e ither pre-
These data are shown in Figure 57-7, Fig ures 57-7 A-E, menstrual syndrome or in women w ith infertility, clearl y,
Figures 57-8A-D, and Figures 57-9A-D. the spectrum of those symptoms is consiste nt wi th a
physio logic linkage to these condition s. Th ese symp-
The pe ri ovu latory estradi o l production by the develop- to ms, in thi s grou p of pati ents, do a ppea r to be some-
in g fo lli c le is significa ntl y decreased in those wo me n w hat less severe beginning on ly an average of7.7 days
who ha ve had a prev io us hi story of spontaneous abor- pri o r to the o nset of menstruati o n (Tabl e 57-8). No ne-
tion. lt is more suppressed in those wome n who have
had three or more miscarriages (F igure 57 -7C), but when
Table 57-7: lnciden ce of Prem enstrual
eva luated the three-va lue sum s and means ofthe peri-
Symptoms-P atients with PMS, lnfertility
ovu latory estrad iol profi les (an estimate ofthe integrated
and Spo ntaneous Abortion (SAB) 1
estradi ol profil e), a nd the estradi o l profile was sup-
pressed fo r al! categories ofperiovulatory estrad iol pro- Patients with
du cti on in patients who had mi carriages as compared PMS lnfertility SAB
% % ,%
to the normal ovu latio n control group . Symptoms (N=147) (N=252) (N=300)
lrritability 92 .6 90 .5 73 .3
The postovulatory estradi o l leve ls, o n th e other hand ,
Bloating 91 .7 85.3 81 .6
showed no statisticall y s ig nifi cant va ri ation from the Crying easily 90 .2 80 .2 63 .6
no rm except fo r sorne late decrease in estradio l produc- Fatigue 89 .1 67 .3 55.2
Depression 88 .0 74 .1 62 .8
tion in th ose wo men w ho had a history ofthree or more CHO cravings 83 .7 75 .1 64 .6
miscan-iages (F ig ure 57-8C). Breas! tenderness 82 .7 85 .7 74.4
Weightgain 75 .6 69.4 60.3
Headache 64.4 50 .8 42.0
On the other hand , the progesterone producti o n by th e lnsomnia 49.2 29 .0 9.9
corpus lute um in this gro up of patients was markedl y 1. From : Pope Paul VI lnstitute research , 2004 .
decreased for a li categories of patient's w ith mi scar-

Periovulatory Estradiol-17P Levels Periovulatory Estradiol -17P Levels

History One SAB Three or More Previous SABs
26.0 - Control (n=21 ) 26.0 - Control (n=21)

- Study group (n=62} - SAB (n=21 )
-' 20 -' 20
~e ~
e
17 9
=
.... ~
i
~
14.8
'O 14 . ~ 14.8 n
12 8 12.8
~
w w
~ 11 .1
10 10 o 10 10.1
p-vatues .0721 p-values .0999
Peak Er 2 Peak Er 2
Days ± Periovulatory of Peak E2 Levels Oays ± Penovulatory Peak E2 Levels
Figure 57-7A Figure 57-7C
Periovulatory Estradiol -17P Levels Periovulatory Estradiol-17P Levels

Two Previous SABs Previous SAB (ali)
26.0 - Control (n=21 ) 26.0 - Control (n=21)

- SAB (n=23) - SAB (n=106)
-' 20 -' 20
~ ~
~ 15.6
~
.'O
~ 14.8 i 14.8
13.B
12.B ~;;;
~
12.8
w 10 w 10
9.7
8.5
p-values NS NS p-values .0556
Peak Er 2 Peak E2 Peak Er 2 Peak E,
Days ± Penovulatory Peak E2 Levels Days ± Penovulatory Peak E2 Levels
Figure 57-78 Figure 57-70
Periovulatory E, Profiles
3 Value Sums and Means
Patients with Previous SAB
SUMS MEA NS
80
p-vatues 1 OOJJ j j .0344 j j .001s 11 ooos j
70
-' 60 20
536 17 9
~
:::- 50
-§
~ 40
w
30 10
20
10
Control One Two Three Ali Control One Two Three All
(N=21) SAB SAB SAB SAB (N=21 ) SAB SAB SAB SAB
(N=49) (N=17) (N=14) (N=84) (N=49) (N=17) (N=14 ) (N=81 )
Figure 57-7E
Figure 57-7A through 57-7E : The periovulatory E2 levels in control patients

with normal ovulation patterns by ultrasound and patients who have had one,
two , three or more spontaneous abortions in addition (57-?E) !he three value
sums and means far !he periovu latory E2 profiles are compared to a group of
normal contro ls (From : Pope Paul VI lnstitute research , 2004).
Post-Peak Estradiol -17P Levels Post-Peak Estradiol -17P

History of One SAB Sums and Means 90
One SAB
80
- Control(n•57) - Control (n:57)
- SA8 (n-127} - SAB(n-92)
,,,~'"
,,.
:: : 120
'º' i8
u ae
30
20
10
NS NS NS
P•3 P•5 P•7 P+9 P+11 Sum Mean

Days Post-Peak
Figure 57-8A
Post-Peak Estradiol-17P Levels Post-Peak Estradiol-17p

Hlstory of Two SABs Sums an d Means 90
Two SABs
80
- Conlrol (n•57) - Control(nz57)
- SAB(n&39) - $AB(n•20)
NS
30
20
10
P•3 P+S P+7 P+9 P+11 Sum Mean

Oays Posl·Peak
Figure 57-88
100
Post-Peak Estrad i ol-17 ~ Levels Post-Peak Estradiol -17p
History of Three or More SABs Sums and Means 90
Three or More SAB s
80
- Control (n"'57) - Control (ns57)
- SAB(n•38) - SAB(n•20)
70
NS m
~
.. .. 532
60
50
40~
~
~
30
20
10
NS
P+J P+S P+7 P•9 P+11 Sum Mean

Days Post-Peak
Figure 57-8C
100
Post-Peak Estradiol-171} Levels Post-Peak Estradiol-17P
History of All SABs Sums an d Meaos 90
All SABs
BO
- Conlrol(n=57) - Control (n=57)
- SAB(n-199) - SA8 (n><135)
70
~ 12.0 120
¡ 532
NS
60 w
i!l.
= "'
~10
i
UJ
..
'º' ••
••
50
40~
~
~
,
30
20
10
p-va!Ue• ~ NS NS NS NS
P+J P+S P+7 P+9 P-+11 Sum Mean

Days Post.Peak
Figure 57-80
Figure 57-8A through 57-80 : Post-Peak estradiol levels in a group of

patients who have had one , two , three or more spontaneous abor-
tions. They are compared to a group of women with normal ovulations
by ultrasound . The five-value sums and means are located on the right
sid e of the graph (From : Pope Pau l VI lnstitute research, 2004).
Chapter 57 : Recurren! Spontaneous Abortion : Evaluation and Treatment 783
20 ~~~~~~~~~~~~~~~~-.-~~~~~~~~~~-. 100
Post-Peak Progesterone Levels Post-Peak Progesterone
History of On e SAB Sums and Means 90
On e SAB
- Control (n-=57) - Control(n"'57) 80
- SAB (n,.129) ~ - SAB (n,. 101 )
70
'" 60~
"
501
40i
30
20
10
P+3 P+S P•7 P-t9 P+11 Sum Mean

Oays Post-Peak
Figure 57 -9A
100
Hlstory of Two SABs Sums and Means 90
Two SABs
.... -
-
Control (n=57)
SAB (n-26)
80
70
"' 60~"
..
'" 501
40i
30
20
10
P+3 P+S p ...7 P+9 P•11 Sum Mean

Oays Post-Peak
Figure 57-98

History of Three or More SABs Sums and Means 90
Three or More SABs
"' - Control (n=57) 80
- SAB (n:23)
70
!!
60~
..
"º 501
401
30
20
10
NS
P•3 P+S P•7 P+9 P+11 Sum Mean

Oays Post-Peak
Figure 57-9C
Post-Pea k Progesterone Levels Post-Pea k Progesterone

History of Ali SABs Sums and Means 90
Ali SABs
"' - Control(n~7) 80
- $AB(rµ:149 )
70
60~"
11
50
40~
1
il-
30
20
10
P+3 P+S P+7 P+9 P+11 Sum Mean

Days Post-Peak
Figure 57-90
Figure 57-9A through 57 -90 : Post-Peak progesterone levels in

pa ti ents with a history of one, two , three or more spontaneous
abortions. They are co mpared to a group of normal controls. The
five-value sums and means are located on th e right side of the
graph (From : Pope Paul VI lnstitute research , 2004) .
784 The Medical and Su r g ical Practice o f NaProTECHNOLOGY
Table 57-8: Number of Days Prior to Menses Symptoms Start

PM vs. SAB 1
Number of Days Symptoms Start Premenstrually Averag e
Entity 4-6 7-9 10-13 14 or more Number of Days
PMS 8.7% 37.4% 29.6% 24 .3% 9.4 days

SAB 18.6% 59 .3% 13.6% 8.6% 7.7 days
theless, th at wo uld still be considered a fa irl y marked Rol e of Endometriosis - - - - - - - - ,

premenstrua l symptom comp lex.
Endometri os is has been shown to be a link to sponta-
neo us aborti on. Daya has conducted a meta-a nalys is
Ovulation Disorders _______~ of studi es whi ch showed an increased rate of sponta-
neous aborti on rates befare treatment and a decreased
With these hormone protiles, one would also anti cipate rate ofspontaneous abortion fo ll owing treatment (F ig-
an increased risk of ovulati on-related dysfun cti on in ures 57-1 O, 57- 11 , and 57- 12). 14
women wh o have undergone a mi scaiTi age. In Tabl es
57-9 and 57- 1O, the incidence ofvarious types ofovul a-
tion-related abnormalities is identifi ed. The incidence is
Table 57-10: lncidence of Ovulation Defects
also divided in to those women who have had one, two,
Se rial U ltrasound Evalu ation of Patients with
three or more mi scarri ages . Anatomi ca lly abnorma l ovu-
Spontaneous Abortion (N =143)
lati on pattern s by ultrasound were identi fied in 40.6
vs. Patients wich lnfertility ( =460)
perce nt of th e women who were stud ied with prev ious
mi scarriage (N = 143). Thi s is less th an in a group ofp a- SAB lnfertility
Entity n % n %
ti ents who experi ence infe rtili ty (56.5%) and it i stati s-
tica lly significantly different (p=.0008) chi-sq uare analy- Anatomically normal 85 59.4 200 43 .5
ovulation by U/S
is. We have been able to show previously that imma-
Anatomically abnormal 58 40 .6 260 56 .5
ture fo lli cles are associated with miscarri age, and thi s ovulation by U/S
parti cular defect is the most co mmon abnorm ality ob-
served in women who ha ve prev ious mi scarriages. How- Totals 143 100.0 460 100.0
ever, other ovulation-related abnormalities also ex ist and 1. p=.0008, chi-square analysis
2. From: Pope Paul VI lnstitute research , 2004 .
are tabul ated in Tabl e 57-9.
Tab le 57-9: Types of Ovu lation Patterns

Serial U ltraso und Evaluation of Patients
with History of Spontaneo us Abortion 1
Ultrasound History of Spontaneous Abortion

Ovulation Qng Two ;¡ or more ~
Classification n % n % n % N %
MF: + 55 61 .8 14 58 .3 16 53.3 85 59.4

MF: - 7 7.9 5 20.8 6 20.0 18 12.6
LU F 7 7.9 2 8.3 o 00 9 6.3
IFS 16 18.0 2 8.3 6 20.0 24 16.8
PR 4 4.5 4.2 2 6.7 7 4.9
Totals 89 100.1 24 99 .9 30 100 .0 143 100.0
1. From· Pope Paul VI lnstitute research , 2004.

Chapter 57 : Recurren! Spontaneous Abort ion : Evaluation and Treatment 785
Table 57-11 : Diagnosis of Endometriosis in Patients

wi th History of Sponta neo us Abo rtio n (N=l92)
History of Spontaneous Abortion

One Two 3 or more Totals
Endometrios is n % n % n % N %
Present 104 61.8 34 89.5 26 76. 5 164 85.4

Absent 16 7.9 4 10.5 8 23.5 28 14.6
Tota ls 120 100.0 38 100.0 34 100.0 192 100.0
Within our own studi es of 192 patients with a previous defect finding of that in endometrios is itse lf.
hi story of spontaneous abortion , endom etriosis was
fo und in 85.4 percent of patients (Table 57-1 1). Thi s lt is thought that the peritonea l fluid fro m patients with
percentage is much hi gher than usuall y reported, most endometriosis may ha vea n ad verse affect on the repro-
li kely because of the "near contact" laparoscopic ap- ducti ve process and be ca usat ive to both inferti li ty and
proach used at the Pope Paul V I lnstitute. Noneth eless, miscan-i age. 14 A wide asso11rnent of peritonea l fluid tox-
it is, in our view, a significant finding and correlates we ll in s ha ve been investigated. These wo uld include estra-
with the endoc rin e, mucus cyc le and ov ul ation-related diol , progesterone, prostaglandin s, com plement co m-
po nents, cytoki nes and growth fac tors. 15 Interl eukin-1
Devereux 1963 ~ (1L-1) and tumor necros is factor-a lpha (TNF-a) are se-
Petersohn 1970 r---+----1 creted by activated macrophages . When T- lymphocytes
Na ples 1981 are stimu lated by 1L- 1, they produce lL-2 . Th is contin-
Rock 1981 ues a cascade of cytok in e production by indu cing in-
Olive 1982 i-----i
Wheeler 1983 ~
Groll 1984
Metzger 1986
Fitzsimmons 1987
~ 80
10 20 30 40 50 60 70 80 90 100 o-;$?.
.........
Spontaneous abortion rate (%)
Figure 57 -10: A meta-analysis of spontaneous abortion rates

in patients with endometriosis prior to treatment (from Daya S:
-Q)
co
.....
e
70
60
Endometriosis and SpontaneousAbortion . lnf Reprod Med Clin o
North Am 7 :759-77 3, 1996). :eo
.o 50
co
(f)
::l 40
Petersohn 1970 i-.-,
oQ)
e
co 30
Spangle r 1971 1--+---i
e:o
Naples 1981 l--+-----1 a. 20
(f)
Rock 1981 f-+-1
10
Rock 1981
Groll 1984 1--+----1

Befo re After
Metzger 1986
treatment treatment
10 20 30 40 50 60 70 80 90 100 9 studies 6 studies
Spontaneous abortion rate (%) Figure 57-12 : A summary of the effects of treatment of en-
Figure 57-11 : Spontaneous abortion rates following treat- dometriosis on the rate of spontaneous abortion both before
ment of endometriosis (From: Daya S: Endometriosis and Spon- and after treatment (From : Daya S: Endometriosis and Spon-
taneous Abortion . lnf Reprod Med Clin North Am 7:759-77 3, taneous Abortion . lnf Reprod Med Clin North Am 7:759-773 ,
1996) . 1996) .
Table 57-1 2: Treatment of Endometriosis in Patients

with History of Spo ntaneous Abortion 1 (N= l92)
HistO !)( of Spontaneous Abortion

One Two 3 or more Totals
Type of Trea tment n % n % n % N %
Laser laparoscopy 59 48.8 18 48.6 19 55.9 96 50.0

Laser laparotomy 40 33.0 13 35.1 6 17.6 59 30.7
No treatment 22 18.2 6 16.2 9 26.5 37 19.3
Tota ls 121 100.0 37 99.9 34 100.0 192 100.0
terfero n-gamma (IFN -y) production by other T-l ym pho-

cytes and also causes acti vation of natural k ill er (NK ) Table 57-13: Sac Size Discrepancy ~ 7 D ays
cell s. Th ese ce ll s have been shown to cause a lys is of in Duration (S mall Sac)
tro phobl asti c ce lls. 16 ln fac t, these cytok ine leve Is ha ve Spontaneous Abortion R ate
been shown to be decreased in peritonea l fluid in wome n 5.0-8.9 Weeks vs. 9.0-11.9 Weeks
w ho have e nd o metr ios is th at has been med ica ll y History of Sponta neous Abortion
treated. 17 Thi s reduces emb ryotox ic ity. O ne wo ul d an - Normal
pregnancy SAB Totals
ti c ipate th at surg ica l correction and remova l of th e en- Type of Treatment n % n % N %
dometriosis wo uld produce simil ar res ults.
5.0-8.0 weeks ' 47 68.1 22 31.9 2 69 100.0
1
It is thought that the ad ve rse effects of endometri os is 9.0-11 .9weeks 22 100.0 O O.O 22 100.0
may very we l1occur during fo l Iicular deve lopment and 1. Man y of these pregnancies were treated with progesterone.
2. p= .0024 (chi-square analysis)
res ult in abnormalities in the morpho log ic deve lopment
of th e emb ryos. 14 Thi s wo uld a lso be consistent with
the endocrine para meters whi ch have been shown to
ex ist in these situati ons.
Surgical treatment is considered the treatment of choice

fo r endometri os is at the Pope Paul V I lnstitute. Most of
these pati ents can be treated by lase r laparosco py with
a smaller percentage being treated with excision of their
endometri os is via laparotomy (Tabl e 57 - 12). With en-
dometrios is being so preva lent in thi s series, laparoscopy
is considered an important part of the overa ll eva lua-
tion and treatment fo r pati ents w ith recurre nt mi scar-
riage (two or more) .
Ultrasound Findings - - - -- - ----,
It has been shown that ultraso und can ident ify a certain
group of patients w ho are at a very high risk fo r mi scar-
riage. Th is is parti cul arl y seen in those pregnancies in
w hich th ere is a lag in the size of the gestati onal sac
re lati ve to the size of the embryo. In those pati ents w ho
have very little d iscrepancy in sac size (F igure 57- 13), Figure 57-13 : A n ea rly pregn a ncy ultrasound e xa minati o n
(tra nsvag ina l) w he re the c row n-rump le ngth measu res 1.17
the mi scarri age ri sk is very low. 19 However, w hen the
cm (7 weeks 1 day) and th e gestatio nal sac measures 2.44
sac size is markedly red uced and not in keeping with the cm (7 weeks 1 day). T his was a 30-ye ar-old , gravid a 2 , para
size ofth e feta l pole (F igure 57-1 4) then there is a much 1 w ho had a no rmal pregnan cy o utco me (Fro m : Pope Paul V I
hi gher ri sk of mi scarriage . Thi s is shown in Tabl e 57-1 3 ln stitute Division of Reprod uctive Ultra so und , 2004).
Chapter 57 : Recurren! Spontaneous Abortion : Evaluation and Treatment 787
where th e mi scarr iage risk in patients where the sac size time, we have identifie d no treatment whic h can specifi-
di screpa ncy is g reater than o r equa l to seven days is ca ll y save that pregna ncy.
3 1.9 percent when o bserved between 5.0 and 8.9 weeks
(as determined by a measurement of the crown-ru mp T he ro le of e ndometri os is a nd its treatme nt is demo n-
length). lf such a sac s ize di scre pancy ex ists after the stra ted in Figures 57- 15 a nd 57- 16. These lapa roscopi c
ninth week of gestation, no mi scarriages we re observed. ph otograph s a re in a patie nt who had six prev io us mi s-
Thu s, thi s is a findin g whi ch is unique to a short w in- carri ages . E ndo metri os is was identifi ed in the crease
dow in the earl y stages of pregnancy. A t the present between the prox ima l porti on ofthe right fa ll o pi an tu be
and th e latera l po rti on of the ri ght posterio r uterine fun-
du (F ig ure 57- 15). Jt was a lso o bserved as a small su-
pe rfi cia l les ion on the medi o latera l as pect of the left
ovary (F igure 57-1 6). In both cases, the surgery was
lase r va po ri zati o n and subseque nt pregna ncy occurred
and we nt full term with adequate progeste rone and HCG
s uppo rt.
Role of Progesterone _ __ _ _ _~
The ro le of1proges teron e in sustaining pregnancy has

been known fo r a number of yea rs, sin ce luteecto my
perfor med in ea rl y pregnancy was shown to res ult in
spo nta neous abo rti o n (F ig ure 57- 17). Wh en progester-
o ne was prov ided to support the pregnancy, the preg-
na ncy co uld be sa lvaged eve n in th e prese nce o f
luteectomy. 19 With thi s evide nce, it has been tho ug ht
that progesterone support wo uld be a viabl e o ptio n fo r
the treatm ent of pati e nts with recurrent spo ntaneous
Figure 57-14: The crown-rump length in th is tran svaginal
ultrasound examination mea sures 0.67 cm (6 weeks 2 days) abo rt io n. Un fo rtunately, it is a fa r more compl ex ques-
and the gestational sac 0.94 cm (4 weeks 6 days). A positive ti o n a nd iss ue than that.
heartbeat at 132 beats per minute was identified . At the next
ultrasound sean at seven weeks, the fetal heart had stopped
lt has bee n shown that progestero ne suppo rt can cor-
and a diagnosis of missed spontaneous abortion wa s made.
This was a 29-year-old , gravi da 3, para O with a previous rect and maintain the endometrium 20 a nd that progest-
history of two spontaneous aborti ons (From: Pope Pau l VI erone support ca n reduce the ri sk of mi sca rri age in a
lnstitute Division of Reproductive Ultrasound, 2004).
Figure 57-15 : Thi s patient with six previous misca rri ages has en dometriosis between the proximal portian of th e right fallopian
tube and th e posterior surface of the uterus (left) . On the right, thi s is shown followi ng laser va porization . This patient
eventually conceived and had a full-term preg nancy.
Figure 57-16: Thi s pati ent with three previous misca rriages had endometriosis on her left ovary (left) w hich wa s laser
vapo rized (right). She subseq uently had a norm al heal th y pregnancy.
subsequ e nt preg na ncy. 2 1- 3 1 On the othe r ha nd , other

studi es have shown progesterone to have no effect. 32 - 35
- et.nges ... JÑsmll progesterone oonoennuon
ol 1 P91*"5-.0 ~ llft9f lutMCIOmy
~ Evo1u11onol~Pfessur9l'lU1ne7pillllf\ll
Trans.en.ÓllC:JNM..-d~n:r-se111~111
ln wo rk do ne at th e Pop e Pa ul V I lnsti tute, progester- -
5 palllll'll$ ....ni- pregnancy . . . nol lemWIBted by luteeaomy
~ Laekof~ol.......,_pressure111_,.Sl*ll!lr'Q
o ne levels we re fo ll o wed in subseq ue nt pregna nc ies in Luteectomy Abortion
pati ents w ho had a prev io us ly diagnosed lutea l phase

defect. Th e Type 1, 11 a nd 111 lutea l phase deficie nc ies
• ' 100
were studied. In thi s gro up of patients, there was a mark-

edl y decreased progestero ne pro tile in those pati e nts
w ith a preex isting Type 1 lutea l pha e de fi ciency. Whil e
the re w ere so me stati stical differences a lso observed in 50 3
3
the Type II lutea l phase defi cie ncy, th e Type III lu tea l :r
<O
phase defic ie nc ies showed no statisti ca l diffe re nce fro m

the normal contro ls. These data may offer sorn e clues 25
as to who mig ht best benefit fro m progestero ne suppl e-

Progesterone
menta ti o n in pregnancy.
o 1 11 13 15
Days afl'er Luteectomy
ft a ppears cl ear that those w ith a preex isting Type 1
lutea l ph ase defi c iency not o nl y need progestero ne Figure 57-17 : The luteectomy-induced changes in plasm a
support during the lutea l phase of the menstrual cyc le progesterone, intra uterine pressure and clinical progress in
(th e post-Peak ph ase) , but they also need progesterone abortion. A summary of th e results of 12 studi es. The dark
red ci rcles and lines illustrate changes in plasma prog ester-
suppo rt during the course of th eir pregn anc ies. ln Ty pe one co ncentrati on of se ve n pati ents who aborted after
ll lutea l phase defi c iency, it is like ly that progestero ne luteectomy. The light red stars and lines indicate th e evolution
su ppo rt w ill also be necessary; altho ug h, in some cases of intrauterine pressure in the same seven patients. Th e dark
blu e circles and lines ill ustrate th e transient decrease and
it may prove othe rw ise. In Type lll lutea l ph ase defi-
subsequent increase in progesterone in five patients whose
c ie ncy, it is li ke ly that progesterone suppo rt w ill be un- preg nancy was not terminated by luteectomy. The light blu e
necessa ry. stars and lines indicate the lack of evolution of intrauterine
pressure in the same five patients. Two patients in the first
group and one patient in the second group had ovariectomy
Thi s makes fo r a reasonab ly ra tiona l approac h upon instead of luteectomy (From : Csapo Al , Pulkinen MO , Ruttner
w hi ch progeste ron e th erapy ca n be based . However, in B, et al: The Significance of the Human Corpus Luteum in
actua l impl eme ntati o n, it is stil 1somewhat diffi c ul t be- Pregna ncy Maintenance . 1 Preliminary Studies. Am J Obste!
ca use not in a ll cases is it known w heth er o r not the Gyneco l 112:106 1-1 067, 1972).
wo ma n has a preex istin g lutea l phase defi cie ncy to be-

g in w ith . Secondl y, th ere w ill be sorne deg ree ofva ri a-
Chapter 57: Recurren! Spontaneous Abortion : Evaluation and Treatment 789
150 1'8 •
ti on around thi s rati ona le; and thu s, the onl y approac h Type 1 Luteal Phase Oeficiency
Progesterone Levels at Six Weekly lntervals
whi ch appears to be workab le is to provide progester- _ Con,,..
125 i::::J T~ l klt..i ph.JIM~
one supplementati on to those patients with a hi story of 1131
prev ious pontaneo us abo rtion and mo ni to r thei r 103'
progesterone levels during th e course ofthe pregnancy. 87 3
Foll ow ing th e progesterone supplementati on protoco l 738
outlined in thi s tex tbook; that ca n be done, and when

52'
progesterone is no longer needed, it ca n be discontin-
389
353
ued. Thi s is the approach taken at the Pope Pa ul VI ,..
25
lnstitute (Figures 57-1 8, 57-1 9, 57-20).
2-6 14 - 18 20·24 25 . 30 32-38

NS ~ [§] ~ ~
Role of HCG - - - - - - - - - - - - - . Weeks of Pregnancy
Figure 57-18: Progesterone levels at six wee kly intervals in

patients with a definitive endocrine diagnosis of type 1 luteal
Human chorioni c gonadotropin (HCG) is a glycopro-
phase defi ciency co mpared to norm al pregnancy controls
tein horm one composed oftwo di ss imil ar subunits, al- (From: Pope Paul VI lnstitute research, 2004).
ph a and beta, joined noncova lently. lt i prod uced by
troph oblast ti ssue in normal pregnancy and trophob las-
ti c di sease and at low leve ls by poorl y-differentiated 150 Type 11 Luteal Phase Deficiency 1484 146 4
cancers. The alpha-subunit of HCG in normal pregnancy Progesterone Levels at Six Weekly lntervals
- Control
and troph obl astic di sease is composed of92 amino ac- 125 TJpt1 ll lutNJ pNIM deflc'9ncy
ids. lt has two N-late oligosaccharide side chain s at-

-'
tached at amin o ac id res idues 52 and 78, whi ch are 100
bi antennary and monoantennary types. The beta-sub-

~.e
unit in normal pregnancy and trophobl astic disease i i
75 738
.,.
composed of 145 amin o ac ids. The beta-subunit con- .e 50
52.•
•••
tains two -l ate oli gosaccharide side chain s attached
353 332
to res idues 13 and 30, whi ch are of a bianten nary type. 25
A hi gh proporti on of tri antennary oli gosacc hari des is
found on beta-subunit in pati ents with persistent tro-
phobl asti c di sease.36
Weeks of Pregnancy
Serum levels of bi olog ica ll y active HCG ri se ex ponen- Figure 57-19 : Progesteron e levels at six wee kly intervals in
ti all y in the first trimester ofpregnancy, doub ling every patients who had a definitive endocrine diagnosis of type 11
luteal phase defi ciency co mpared to norm al preg nancy co n-
two days, and ri sing to a pea k at about 1O weeks gesta- tro ls (From : Pope Paul VI lnstitute research, 2004).
ti on. The HCG leve ls decrease from the 1Oth to the 20th
week of gestation, reaching approx imately 20 percent of
peak leve ls and remain at thi s co nce ntra ti on unti l fu ll
150 1484
Type 111 Luteal Phase Deficiency
tenn . Progesterone Level s at Six Weekly lntervals
1457
- Control
125 c=J Ty1>9 111 lute.I ptwise deflc6ency
HCG has a well-known effect on the corpu s luteum. lt
will stimulate the producti on of both progesterone and E 100
103 4 103 3
estradi ol. Recent ev idence suggests th at it also may act .

g.
e
as a growth and differenti ati on factor during pregnancy. j 75
738 74 2
According to ex perim ental results, its mode of acti on e 4

a..
may be di vided into three sequenti al phases. 37 50 52. 51 1
25
During th e first ph ase, whi ch beg in s shortl y after con-
cepti on and lasts until its occurrence in the seru m, HCG
acts preferentiall y in a juxtacrine manner. lt has been 2-6 8 . 12 14 • 18 20-24 26- 30 32 · 38
NS NS NS NS NS NS
shown that HCG admini strati on provokes profo und ef- Weeks of Preg nancy
fects on paracrine parameters ofdi ffe rentiati on (IGFB P- Figure 57-20 : Progesterone level s at six weekly intervals in
1, prol actin) and impl antati on (LI F, M-CSF). YEGF, a patients with a defin itive endocrine diagnosis of type 111 luteal
cytok in e important fo r neoangiogenes is, is also si gni fi- phase deficiency com pared to norm al pregnancy co ntrols
(From : Pope Paul VI lnstitute research, 2004).
ca ntl y stimul ated by HCG suggesting th at HCG has a signifi cant differences were fo und between the two
role in endometria l vasculari zation and pl acen tati on. lt therapies in terms of deli very weight, placenta! weight
has also been shown th at lutea l rescue with HCG is or neonatal Apgar core and ubsequent outcome. 42
assoc iated with a second wave of angioge nes is and This was fo ll owed aga in by a report from Harri son in a
vascular stabili zation .38 group ofwomen who had threatened spontaneous abor-
tion (a different pop ul ation of patients). In thi group,
The second ph ase is an endocrin e one and is marked by the use of HCG was used in a similar fas hi on but those
an appearance of HCG in the paternal serum . Ri sing with a history of hab itu al spontaneous aborti on were
leve ls of HCG cau e a very rapid elevati on of serum exc luded. Only those patients with a hi story ofvaginal
progesterone refl ecting the resc ue of the corpus luteum. bl eedin g pri or to the 8th gestation week of a viab le in-
Other endocrin e functions of HCG include its in trin sic trauterine pregnancy were included. [n this popul ation,
thyrotropic activity as well a a modulation offetal tes- the supplementation with HCG was fo und to be statisti -
ticular, ovaria n and adrenal function. 37 ca ll y improved over that of bedrest alone.43At the same
time, he reported that the difference between HCG and a
The third phase may be characteri zed by the ex press ion pl acebo was not significantly different. He co ncludes
of HCG/ LH receptors on the trophoblastic ce ll s them- by uggesting that it would not be inappropriate to con-
se lves. Before the ninth week of gestati on, human vil- sider the HCG therapy regimen empl oyed in the study.
lous trophob lasts ex press a truncated HCG/LH recep- Other studi es have also suggested that it can be used
tor isoform and are probabl y not responsive to HCG. in recurrent pregnancy loss. 44 .4 5
Later, the expression pattern is witched to the fu ll length
receptor, allowing HCG also to modulate the di ffere ntia- While th e reports on HCG use in recurrent spontane-
ti on ofthe trophoblasts themselves. A specia l feature is ous abortion have been rni xed, the weight of the evi-
the self-regul ation of HCG biosymphysis which may in dence is in the direction of it being of sorne va lue. In
part ex pl ain the unique secretion profil e ofthe hormone addition, there are no known side effects to the admin-
with peak levels during the first trim ester fo ll owed by a istration of HCG eith er to the woman or to her baby
rapid dec line after the 1Oth week of gestation. Thus, (o utside of perha ps sorne local irritati on at the site of
overa ll , HCG seems to ha ve a va ri ety of local and sys- injection - alth ough, these inj ections are genera ll y very
temic functions in and outside the embryo-endometrial we ll tolerated). Thus, it seerns reasonab le to use HCG
microenvironment. 37 asan additi onal part of the approach to the trea trn ent of
women with recurrent spontaneous aborti on.
A number of investigator ha ve studi ed the effects of
HCG admini stration in th e treatment ofrecurrent spon-
taneous abortion. These trials have had somewhat mixed Genetic and Autoimmune Studies _ _~
results. lni tially, Sv igos 39 treated a group ofwomen with
recurrent spontaneou s aborti on and low progesterone While it has often been recommended that karyotypin g
levels wi th HCG and found a sign ifican! decrease in the the biologic mother and father in cases ofhabitual spon-
mi scarriage rate. In an rvF population, lutea l phase sup- taneous abort ion, such karyotyping is often unproduc-
port with HCG also seemed to improve pregnancy out- ti ve. lt is ex pen ive and most often comes back normal.
come40 and HarTison publ i heda placebo-controlled tria! Thus, it is not a facto r unl ess a bas ic eva luation and
of patients with habitual spontaneous aborti on (a hi s- treatment prograrn is unsuccessfu l.
tory of the three prev ious pregnancies endin g in spo n-
taneous abortion). An ini tial dosage of 10,000 1U was With regard to imrnunologica l facto rs, thi s is a very com-
ad min istered at the earli est diagnosis of pregnancy and plex area.
was followed up with 5,000 IU tw ice weekly up to the
l 2th week of pregnancy and then once weekly up to the Ant iphospholipid antibodi es (lupus anticoagul ant and
l 6th week. On ly two ofthe 32 patients mi scaJTied (6.2%). anti cardi olipin antibodie ) are the only validated irnrnune
In a fo llow-up tria! , pati ents were random ly all ocated in causes of recurren! miscarriage. However, the overa ll
a double-b lind fas hi on to either HCG or placebo. The ro le that this pl ays in the evaluation and treatment of
results were stati sti ca lly much poorer with the pl acebo- patients with recurren! spontaneous abortion is not yet
controlled group .4 1 clear, particularl y in view of the data presented in this
chapter.
In a fo llow-up to that study, Harrison fa il ed to confirm
the previous pl acebo-controlled data wh ich all ocated Antiphospholipid syndrome (A PS) is characterized by
th e use of HCG in habitu al spontaneous abortion. No the presence of ci rcul atin g antiph ospholip id antibod-
Chapter 57 : Recurrent Spontan eou s Abortion : Eva luati o n and Treatment 791
ies in association with specific clinica l features, which soc iated with mi scarriage. These events include the ap-
may include thrombo is (either arterial or venous) or pearance of short post-Peak phases, variability in the
ad verse pregnancy outcomes, most often feta l loss. Preg- length ofthe post-Peak phase, and limited mucus cycles.
nancies which are affected by APS but do not result in Thus, when these events are shown to occur in a pro-
fetal loss can be complicated by severe pregnancy-in- spective identification, it poses a un ique cha llenge to
duced hypertension, fetal growth restri ction or placen- both the FertilityCare™ Practitioner as well as the
ta! insuffic iency requiring preterm delivery. The term FertilityCare™ Medica! Consultant.
antiphospholipid antibodies describes a fam il y of au-
toantibodies which likely invo lve a range oftarget speci- lf the patient has never experienced a miscarriage be-
ficities and affinities but ali ofwhich recogni ze va rious fore , th en these patterns become even more challeng-
combinations of phospholipids and/or phospholipid- ing. lfthe wo man also experiences significant premen-
binding proteins. 46 strual symptoms or premenstrual spotting, thi s also in-
creases the potentia l that a luteal phase progesterone
The most common ly detected antiphospholipid antibod- deticiency mi ght occur and an interventi on mi ght be
ies are lupus anticoagulant, anticard iolipin antibodi es necessary.
and anti-~ 2 -g lycoprote in 1antibodies. Because there is
no definiti ve association ofspec ifi c cl ini ca l manifesta- In the case of a short post-Peak phase, that interven-
tions with a particular antiphospho lipid antibody, mul- tion shou ld detinitely be made. In these cases, clínica!
tiple tests (most commonly lupus anti coagulant and lgG observation has shown that mi scarriage occurs univer-
and lgM anticardio lipin) should be used in seeking the sa ll y in situations such as thi s. The treatment for this is
APS diagnosis.46 simpl e. Admini stering HCG, 2000 units IM (or subcuta-
neous) on Peak +3, 5, 7 and 9 will appropriately lengthen
The treatment for APS involves supplementing with low- the post-Peak phase and support the luteal phase,
dose aspirin (75 mg per day) and poss ibl y the use of progesterone and estradiol production. ln thi s fashion,
subcutaneous unfractionated heparin (5000 units ev- the pregnan cy chances can be signifi cantly enhanced.
ery 12 hours). In one study, the combination of these Once pregnancy is achieved , then progesterone shou ld
two therapeutic agents signifi cantl y improved the li ve be monitored and progesterone supplementation be-
birth rate.47 In that tria! , the heparin was used every 12 gun.
hours. In a second randomized controlled tri a!, the add i-
tion of low-mo lecu lar weight heparin did not signifi- In pati ents with limited mucus cycles, variab le post-
cantly improve pregnancy outcome; although , a hi gh Peak phases, premenstrual spotting and/or premenstrual
success rate was achieved when low-dose aspirin was sym ptoms, the challenge is more complicated. Here it
used for APS. In thi s study, the heparin was used onl y seems reasonable to at least screen the lutea l phase
5000 units subcutaneous on a daily basis. 48 (presu ming no previous miscarriages ha ve occurred)
with a Peak +7 progesterone and estradiol level. lfthey
are low, then implementation of a honnonal support such
Evaluation and Treatment Protocol ==l as HCG seems reasonable. The aim in treatment is to try
to reduce and elim inate the potenti al fo r miscarriage al-
In approaching women with spontaneous aborti on, the together; although, that i not at ali uni versa ll y pos-
Pope Paul VI Institute takes a so mewhat different ap- sible at the present tim e.
proach. First ofall , it identifies miscarriage asan abnor-
mality rather than simply a frequently occurring norma l In a patient who has experienced one spontaneous abor-
reproductive event. Furthermore, it recognizes that there tion, she should be asked to begin charting the CrMS
are underlying causes to each mi scarriage even though and observi ng for the above biomarkers. After charting
we may not always know what they are . Finally, it rec- has begun, then at least a limited hormone profi le wou ld
ognizes that th ere is a significant sense of loss that be reasonab le. ln thi s way, the underlying endocrine
both the mother and the fa ther may experi ence as the events can be better understood a.nd appropriate suppl e-
resu lt of such an event. Spontaneous abortion is thu s mentation begun. When two or more spontaneous abor-
not taken li ghtly as a med ica! event. tions have occurred, th en a more complete evaluation
should be undertaken. The plan of eva luation is shown
[n FertilityCare™ Centers throughout the United States in Table 57-14. The pati ent 's history is taken, she tracks
and in other countri es, women are now beginning to her fertility cyc le fo r two cyc les and return s fo r a phys i-
track their fertility and identi fying, in a prospective fas h- cal exam ination. At that time, a ful 1series menstrual cycle
ion, certain types of events which are k.nown to be as- hormone profile, follicular ultrasound series, and diag-
792 The Medica! and Surgica l Practice of Na ProTECHNOLOGY
Once pregnancy is estab li shed, these pat ients are sup-

Table 57-14: NaP roTechnology Evaluation
ported with progesterone using the progesterone pro-
Protocol for Patients with Two or Mo re
tocol outl ined in this textbook. In additi on, th ose pa-
Spontaneous Abortions
tients w ho ha ve had two or more mi scarri ages are a lso
supplemented w ith HCG in the dosage of 5000 IU two
Take the patient's history (upon entry)
times weekl y throug h at least the l 6th week of gesta-
Chart CrMS for two cycles ti on.
Return for physical examination and order the
following :
• Seminal fluid analysis
• Full series menstrual cycle hermane profile Results of Treatment -------~
• Screen for APS
• Follicular ultrasound series
• Diagnostic laparoscopy, hysteroscopy, and The resu lts oftreatment can be eva luated in a number
selective hysterosalpingogram
Comprehensive management review ofdifferent way . First ofa ll , whil e others have shown
that the treatment of endometri os is does decrease the
subsequent ri sk of mi scarri age, the data from the Pope
Pa ul V I ln stitute can now be added to th at. In Tab le 57-
16, the number of patients with a history of spontane-
nostic laparoscopy is undertaken. A sem inal fluid analy- ous abortion pri or to treatment and after treatment is
sis is considered optiona l de pending upon the length shown. Prior to treatment, 46.2 percent of patients had
ofti me that th e patient has been tryi ng to ac hi eve preg- spontaneou abo1iions in their previous pregna ncies .
nancy. Follow ing treatment, thi s was reduced to 23.7 percent
(p=.0065 , ch i-sq uare analys is and p=.0077 Fisher exact
Thi s approach w ill all ow the full details of the various te t).
endocrine parameters offo lli cu lar phase and lutea l phase
deficien cy to be identified along with any anatomi c ovu- In review in g th e pregnancy outcome in a gro up of pa-
lation-related abnormaliti es. In additi on, endometri os is ti ents who had had three or more prev ious spontane-
will be fo und and can be appropriate ly treated . ous abortions (Table 57-17), treatrnent duriJ1g their preg-
nancy wi th proge terone a lone or with progesterone
The treatment approac h in pati ents such as thi s in vo lves and HCG are shown. The mi scarriage rate was lower in
a simil ar ap proac h to the treatment ofpati ents with in- the group of wo men who had progesterone and HCG,
fe rtility. Th e com pl ete treatment approac h is outlined in but it was not statisti ca lly signifi ca nt (Tabl e 57-18). ln
C hapter 45 w here the treatment of ovaria n and target th e gro up of 1 19 patients , at th eir first atte mpt at preg-
organ dysfu ncti on is outlined. In additi on , the patient nancy, 68 .9 percent had a pregnancy success. ln fo l-
sho uld be screened fo r AP as previousl y described. low-up attempt to treat this sa me group of patients, an
additi onal 12 pati ents had li ve-bo rn in fa nts, resul ting in
Testing for chromosome ab norm aliti es and other more an overa ll s uccess ful pregnancy rate of79 .0 percent.
complex autoimmune abnorma liti es are not conducted
at this po int; however, iftreatment fa il s, then such an sing life table analys is, the pregnancy rates in patients
eva luati on can be considered and undertaken. who had either two or three previous un successfu l preg-
nancies is compared in Figure 57-22. The li fe table shows
Table 57-15: Full Series M enstrual Cycle
H ormone Profile
T able 57-16: Spontaneous Abortio n Rate
Foll owing Conservative Surgery for
• Day 5: FSH , p-end o rphin
Endo metriosis and NaP roTechnology 1
• P-5 through P+2 (every other day): E, Befo re After
P+ 3, 5, 7, 9, 11 : P+E, Treatment Treatment
Number of patients ... n % n %
P+5 , 7, 9: P-endorphin
• P+7: Testosterone FSH Total T, withoutSAB 43 53 .8 45 76.3
Free testosterone LH Free T, with SAB 37 46.2 14 12372 1
Androstenedione pro lactin TSH
DHEAs Total T3 Totals 80 100.0 59 100.0
Reverse T3
T3 :rT 3 ratio 1. From: Pope Paul VI lnstitute research. 2004 .
2. ¡r.0065 (chi-square =7.415) and p=.0077 (Fisherexact test)
Chapter 57: Recurrent Spontaneous Ab o rti o n : Evaluation and T reatment 793
a virtuall y identica l success curve, reaching nearly 80

percent at 24 month s, for both situati ons. In addit io n, a Table 57-18: Pregnancy Outcome Summary in
re lati vely new program fo r us, treating thyroid system P atierJ.ts with 3 o r Mo re Spo ntaneo us Abo rtion
dysfun ction (T SD) with sustained-release T 3 , has shown Progeste rone Only vs.
promi se (Chapter 36) . In the first 27 pregnancies there Progesterone and HCG 1•2
have bee n onl y two mi scarri ages (7.4%). T hi s is clearl y Progesterone Total ·
an area fo r fu11h er resea rch. Progesterone and HCG Group
n % n % N %
Preg nancy success 38 65 .5 44 72.13 82 68 .9
Table 57-17: Pregnancy Outco m e Summary Pregn ancy loss 20 34.5 17 27.9 37 31.1
in Patients with 3 o r M ore Totals 58 100.0 61 100.0 119 100.0
Spo ntaneous Abo rtio ns 1 (N=119)
1. From: Pope Paul VI lnstitute research. 2004.
2. Of the total group (N=11 9), 94 eventually hada successful pregnancy
Progesterone (79.0%).
Progesterone and HCG 3. p=.4359
Outcome Measure n % n %
Full term 32 55.2 40 65.6

34.0- 36.9 weeks 3 5.2 2 3.3 70 70
s. 33.9 weeks 3 5.2 2 3.3 60 60
Mid-trimester SAB 2 34 4 6.6
50 50
First trime ster SAB j 15 25.9 12 19.7 I' 40 40
Ectopic p reg nancy 3 5.2 1 1.6
30 30
Tota ls 58 100.1 61 100.1 n ·_.;,..-6-...--· 0
20
o---_..,a..--
,..,, - 20
1. From: Pope Paul VI lnstitute research, 2004 . 10 10

2. In this group of 27, 12 subsequently hada live birth (44.4%).
10 11 12
Weeks gestation
Figure 57-21 : Th e salid lines show the growth in th e gesta-

ti onal sac size (GSS) in patients having a normal pregnancy.
Th e dotted lines show the GSS in pati ents who end ed up
miscarryi ng (From : Cunningh am DS, Tichenor JR, Opsahl MS:
Ultrasonographic Ch aracteri sti cs of First-Trimester Gestations
in Recurren! Spontaneous Aborters. J Re prod Med 40 :565-
570 , 1995).
Cumulative Pregnancy Rates of Patients

with Histories of Two or Three SABs
1.0
1 1 -
0.9
! Logrank Test p-value=0 .5978 ! -
0 ----·
~
2
0.8
0.7
./ ,,,
---
._.......
/
•
-~
~
; 0.6
~
e:
~
¿ t;
o.. 0.5
"
.2: { ·
10
-•,..
:; 0.4
E
"
u 0.3
.,• •.
0.2
1·
0. 1 -1-1 --•-- -
Two Previous SAB (n=41)
Three or More Prevlous SAB (n=36)
-
1\1
o.o
o 6 12 18 24 30 36 42 48
Ordinal Months
Figure 57-22: A Kaplan-Meier life tabl e curve co mparing
the cumulati ve pregnancy rates of patients with histories of
either two or th ree spontaneous abortions. The pregnancy
rates are not statisti ca ll y significantl y differen t (wi th treat-
ment) (From : Pope Pau l VI lnstitute resea rch , 2004).
794 The Med ical and Surgica l Pra ct ice of NaProTECHNOLOGY
1 2 J 4 5 6 7 11 9 IO ll 12 13 IJ 15 16 17 18 111 ?0 21 21 2J ?J 25 26 ] 21 I 28 ?9 JO JI 32 33 34 JS
11,1111111! I!! 1! ! ! !, ~ ! ! ! ~ 111.c J1111111111M~

B & 6 e 8 _, xa .1 ICI '" "' . La •! •.i·a .a. .. a •• ,.a "''
=
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r ... r r r
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Es fud¡ 1- 17~ raid ~ ""º Frbae fie r ne nglnl
5 v Dl'-"' sun 3~
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EM NO! R: DRD RrEW HI RT. STA~PS ANI
'™
ti: -
AK. A~ l>OI NT 01 fO LOW·U
- ,, - f--f-
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Figure 57-23 : This is a 34-year-old , gravida 11 , para 4, who had six previous spontaneous abortions.
Four of these were in the first trimester and two of them were in the second trimester. They were
associated with subchorionic hemorrhage , and bleeding at the time was ve ry heavy. She underwent
evaluation at the Pope Paul VI lnstitute and was found to have endometriosis, an anatomically normal
ovulation by ultrasound , andan extremely suboptimal periovulatory estradiol and suboptimal progester-
one and E2 profile du ring the postovu latory phase of the cycle. She was treated wi th low-dose
clomiphene mucus enhancers, pre-Peak HCG (200 IU) and sustained-release T 3 . When she became
pregnant, the pregnancy was supported by progesterone and HCG. At 18 weeks, she had contractions
which broke through Terbuta line and was given a course of Rocephin . She eventually delivered a
healthy baby at full term without any further complications (From : Pope Paul VI lnstitute research , 2004).
1 2 3 4 S 6 7 8 9 10 U 1Z 13 14 IS 16 17 111 I 191 20 121 12? 123 / 24 1 25 ?6 27 28 29 30 31 32 JJ 34 35
U!S MFC 1. 58 UIO /,Q; a .~ ;l.4P.! C R

e.o. + + + +
.,,,., Fr¡;q d erc ne lncyl inl
5 'IJOI P., m 4L~
-
11. S
12.9
20.5
,_ - .,
-
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'"
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"
IQ.O
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-
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~ ¡ii.....--
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1~AK Al POI HM >NT FOI FC LO .., ]
--
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1
Figure 57-24: This is a 44-year-old gravida 7, para 1, who had six previous spontaneous abortions .
These miscarriages were ali in the first trimester of pregnancy. She was eva luated and found to have
endometriosis , a suboptimal periovulatory estradiol profile and a significan! decrease in her 5-value
progesterone sum , postovulatory. Ovarian ultrasound series was normal. Both her and her husband's
karyotypes were normal. She was treated with low-dose clomiphene , post-Peak HCG and mucus
enhancers . She received progesterone and HCG when she was pregnant. At 22.4 weeks , after
having contractions, her cervix was 2.45 cm on ultrasou nd , with 12.5 mm of endocervical nippling ,
and the interna! os was dilated 16.9 mm . She underwent a cerclage. She also received Terbu taline and
cefoperazone. At 38 weeks, she had a repeat cesarean section with a healthy full-term infant (From :
Pope Paul VI lnstitute research, 2004) .
1. Reprodu cti ve Endocrin o logy Prec is, 2"d Editi on: Rec urren! 20. A kse l S, Jo nes G S : Effec t o f Proges te ron e a nd 17-
Pregna ncy Loss . Am er ica n Co ll ege of O bstetri cians and Hydroxy progesteron e Caproa te on Nor111al Corpu s Luteum
Gyn ecol og ists, Was hin gton DC 2002. Fun cti on. A111 J Ob stet Gyneco l 118:466-472, 1974.
2. Wa rburton D, Frase r FC: Spo nta neo us Aborti on Ri sks in 2 1. Bishop PMF, Richard s NA: Habitu al Aborti on: Prophylac-
Ma n: Dat a from Re produ cti ve Hi sto ries Co ll ec ted in a tic Value o f Progestero ne Pell et lmpl antati on. Brit Med J
Medica! Genetics Unit. Hum an Geneti cs. 16: 1-24, 1964 . 130- 133, Jul y 15, 195 0.
3. Kutteh W H, Carney G L: Eti olog ic Factors in Women with 22. Co pe E, Emelife EC : Habitu al Aboni on Treated with 17
a H isto ry o f Recurre nt Pregnancy Loss. Obstet Gy neco l Alph a- Hyd roxy proges tero ne Ca proa te. J O bs tet Gyneco l
42S, 1999 . Brit Co111111 72 :1 035 -1 037, 1966.
4 . Co ulam CB: Assoc iati on betwee n ln fe rtility and Spontane- 23 . Gerh ard 1, Gwinn er B, Egge rt-Cruse W, et al: Double-Dash
ous A borti on. Am J Re prod lmmun o l 27: 128- 129, 1992. Blind Co ntro ll ed Tri a ! o f Proges terone Substituti o n in
Threa tened Abort io n. Bi o Res Prcg 8:26-3 4, 1987.
5. Regan L: Endocrin e Fa ctors in Recurren! Mi sca rri age. lnf
Re prod Med C lin No rth Am 7:72 1-743, 1996. 2 4 . Morga n J, Hac ken WR, Hunt T: The Pl ace of Progesterone
in th e Treat111ent of Abort ion. J Obstet Gyneco l Brit Emp
6. Joffe M, Li Z: Associati on of Tim e to Pregnancy and th e
323-324 , 1960.
Outco me o f Pregnancy. Ferti l Steril 62:7 1-75, 1994.
25. Check JH , Chase JS , Wu C-8, et al: The Effi cacy of Proges-
7. Newco m WW, Rodr ig uez M, John so n JWC: Reproducti on
terone in Achi ev ing Success ful Pregnancy: l. Prophylacti c
in the O lder Gravida: A Litera ture Rev iew. J Reprod Med
se Du r ing Lut ea l Ph ase in Ano ulatory Wo me n. lnt J
36:83 9- 84 5, 199 1.
Fe rt il 32: 135-138, 1987.
8. Klopper A, MacNaughton M: Horm ones in Rec urren! Abor-
26. Chec k JH , Adelso HG : Th e Effi cacy o f Proges teron e in
ti on. J Obstet Gyneco l 1022- 1028 . 1966.
Ac hi ev in g Success ful Pregnancy: 11. In Women with Pure
9 . Corkcr CS, Michi e E, Hobson B, et al: Horm onal Pattern s Lutea l Ph ase Defects. ln t J Ferti l 32: 139- 141 , 1987.
in Co nceptua l Cycles and Ea rl y Pregnancy. Brit J Obstet
2 7 . C hec k Jl-I , Chase J S, Nowrooz i K, et a l: Proges teron e
Gy naeco l 83:489-494, 197 6.
The ra py to Dec rease First-Tri111 es te r po nt a neo us Ab o r-
1O. Daya S, Ward S, Burrows E: Progesteronc Pro files in Lutea l ti ons\ in Prev io us Ord ers. ln t J Fe rti l 32 : 192 - 199, 1987.
Ph ase Defects and Outco me o f Progestero ne Trea tme nt in
28. Daya S: Effi cacy of Progesterone Support fo r Pregnan cy in
Patients with Recurren! Spontaneo us Aborti on. Am J Obstet
Wo111en with a Recurren! Mi scarri age. A Meta-an alys is of
Gyneco l 158 :225 -232 , 1988.
Co ntro ll ed Trials. Brit J Obste! Gyneco l 96 :275-280, 1989.
11. Kutt e h WH: Re c urre nt Pr eg na ncy Loss . N :Ca rr BR ,
29 . Prietl G, Di ed rich K, Van Der Ven Hl-I , et al: The Effect of
Blac kwell RE (Eds). Tex tboo k of Re produ cti ve Medi cin e.
17 Alph a- 1-i ydroxy proges tero ne Ca proa te/Oestradi o l Val er-
2"d Editi on. Appl eton and La ngc, Stamford , CT, 1998.
ate on the Deve lop111 ent and Outco111e of Earl y Pregnancies
12. Boue J, Bo ue A, Lazar P: Retrospec ti ve an d Prospec ti ve Fo ll ow in g In Vitro Fe rtili za ti o n and E111bryo Tran sfer: A
Epide mi o log ical Studies of 1500 Karyotyped Spontaneous Prospective and Randomi zed Contro ll ed Tri al. Hum Reprod
Human Abortion s. Terato logy. 12: 11 -26, 1975 . 7: 1-5 , 1992 .
13 . Ha sso ld T, Che n N, Funkh ouse r J, e t a l: A Cy toge neti c 30. Poul y JL , Bass il S, Frydm an R, et al: Lutea l Support After
Stud y o f 1000 Spont aneo us Abo rti ons. Ann Hum e Genet ln- Vi tro Fe rtili zati o n: Crin one 8%, A Su stain ed-Re lease
Lo nd 44: 15 1-1 78 , 1980. Vag in al Proges terone Ge l, Versus Utrogestan a n Ora l Mi-
cro ni zed Progesteron e . Hu m Reprod 1 1:2085-2089, 1996 .
14. Daya S: Endometriosis and Spontaneous Aborti on. In : lnf
Re prod Med Clin No rth Am 7:759-773, 1996. 3 1. Propst AM, l-lill JA , Gin sburg ES , et al: A Rando111ized Study
Co 111pa rin g C rin o ne 8%, An lnt ra 111u sc ul a r Proge st e ron e
15. Ramy JW, Archer DF : Peritonea l Fluid : lt s Re leva nce to
Suppl eme ntati on in ln-Vitro Fertili za ti on - E111bryo Tra ns-
th c Deve lo pment of Endo metrios is. Fe rtil Steril 60 : 1- 14,
fer yc les . Fe rtil Ste ril 76 : 1144- 11 49, 20 01 .
1993.
32. wyer G IM, Daley D: Progestero ne lmpl ant ati o n in Ha-
16 . Daya S, Gumby J: lmmu nos uppress ion in Human Dec idua
bitu al Aborti on. Brit Med J 1073- 1077, May 16, 2953.
Agai nst Natural Ki ll er Ce lls. Proceedin gs of Ca nadi an Fer-
tilit y and Andrology Soc iety Annu al Meetin g 1988 . 33. Go ld ziehcr JW: Doubl e-Dash Bli nd Tri al of a Progestin in
Ha bitual Aborti on. JAM A. 188 :65 1-65 4, 1964 .
17. Taketami Y, Kuo T-M , Mi zun o M: Compari son of Cyto kine
Levels and Embryo Tox icity in Perit onea l Fluid in lnfe rtil e 34. Mo ll er KJ A, Fuchs F: Doubl e- Das h Blind Contro ll ed Tria l
Wo111e n w ith Untreat ed or Trea ted End o metri os is. A111 J of 6- Meth yl, 17-Acetoxyprogesterone in Threate ned Abor-
Ob stet Gy neco l 167 :265-270, 1992. ti on. J Obstet Gyneco l Brit Co mm 72: 1042-1044 , 1968 .
18 . Cunningham DS, Tichenor JR , Opsa hl MS: Ultrasonographi c 35. Shear111an RP, Garren WJ: Doub le- Das h Blind Study ofthe
Characte ri sti cs o f First-Tri111 es te r Gestati ons in Rec urrent Effect o f 17-l-l ydro xy proges tero ne Ca pro at e o n Abo rti o n
Spontaneou s Abort ers. J Reprod Med 40: 454-570, 199 5. Rate. Brit Med J 292-295, February 2, 1963.
19. Csa po A l, Pulkkin e n MO, Ruttn e r B, et a l: The Signi fi- 36. Co le LA : hCG lts Free Subunits and lts Metabo lites: Ro les
ca nce o f th e Human orpu s Luteu111 in Pregnancy Ma inte- in Preg nancy a nd Tro ph obl as ti c Di sease . J Re prod Med
na nc e . l. Pre li111inary Studi es. Am J Ob ste t Gy neco l 43:3- 10, 1998.
11 2 :106 1-1 067, 1972.
3 7. Licht P, Ru ssu V, Wildt L: Th e Role or Human Chori onic 43. Harri so n RF: A Co mpara ti ve Stud y of Hum an Chor ionic
Gonadotropin (hCG) in lh e Embryo-Endometrial Mi c ro Go nadotropin, Pl acebo, and Bedre sl fo r Women with Early
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plantati on. Se min Reprod Med 19 :37-47 , 200 1.
44. Blumenfeld Z, Ru ac h M: Ear ly Pregnancy Wastage: The
38. Wulff C, Di ckson SE, Du nca n WC, el al: Angiogenesis in Role of Repetili ve Hum an Chori oni c Gonadotropin Suppl e-
th e Hum an Corpu s Luteum: Simul ated Ea rly Pregnancy by me ntation Durin g the First Eight Weeks of Geslation. Fen il
hCG Treatme nl is Assoc iated with Both Angioge nes is and Ste ri l 5 :19-23, 1992.
Vesse l Stabi li za ti on. Hum Reprod 16:25 15-2 524, 200 1.
45. Quenby S, Farqu harso n RG: Hum an Chori oni c Gonadotro-
39. Svigos J: Pre li minary Experience with the Use of Human pin Supplementati on in Recurring Pregnancy Loss: A Con-
Chor ionic Gonadotrop in Th erapy in Wome n with Repea ted trolled Tria l. Fertil Steril 62:708-7 1O, 1994.
Abo rti on. Clin Reprod Feni l 1:131-135, 1982.
46. Branch DW, Porter F, Paid as MJ , et a l: Obstetri c Uses of
40. Yov ich JL: Assess ment and Horm ona l Trea tm en l of th e lnt ravenous lmmun oglobu lin: Successes, Failures, and Prom-
Lutea l Phase in In Vitro Fe nili za ti on Cyc les. Ausl NZ J ises. J Alle rgy Clin lmmun ol 108:5133-8, 200 1.
Obstel Gynaec 24: 125 -1 30, 1984.
47. Rai R, Co hen H, Dave N, el al: Rand omized Contro lled
4 1. Harri son RF : Treatment of Habitua l Abonion with Hu man Tria! of Aspirin and Aspirin Plus Heparin in Pregnant Women
Chor ion ic Gonado tropin : Results of Open and Pl acebo- with Recu rren! M isca rri ages Assoc iated with Ph ospholipid
Conrroll ed Stud ies. Europ J Obstet Gynec Reprod Bio 20: 159- Antibodies (o r Antiphospholipid Ant ibodies). Brit Med J
168, 1985. 3 14: 253 -257, 1997.
42 . Harri son RF: Hum an Chori oni c Gonadotropin (hCG) in thc 48. Farquharson RG, Que nby S, Greaves M: Antiph ospholipid
Managemenl of Recurren ! Abo n ion: Resu ll s o f a Multi- Sy nd rome in Pregnanc y: A Randomi zed, Co nt rolled Trial
Ce ntre Pla ce bo-Co ntro ll ed St ud y. Europ J Obstet Gy nec of Trea tm ent. Obstet Gyneco l 100:408-4 13, 2002.
Reprod Bio 47: 175- 179, 1992.
Early Pregnancy Loss:
Challenging Current Paradigms
ve r the years, there has been a n asse rtion in repro- "ova" that we re recovered free-l ying in the ute rus a nd
º ducti ve medicine that the natu ra l was tage of hu -

man embryos is extreme ly hi g h. lt has been estim ated,
fo r exampl e, that at least 73 pe rcent of natura l sing le
conce ption s ha ve no rea l c hance of surviving six-weeks
tubes, we re ever fe rtili zed . lt is now we ll kn own that
clea vage alo ne is not e no ug h to esta bli sh the occur-
re nce offe11ili zati on, since unfe rtili zed mammalian ( in-
cludin g huma n) ova often exhibit degenerati ve changes
gestati on. 1 Furth enn o re, that wastage is noted to occur w hi c h rese mbl e c leavage (pa rthogeneti c c lea vage). 5
" prior to clinical recogniti o n." Often, thi s type of data is S hettles has aspirated un fe 11ilized ova from perfectl y
used to j usti fy in vitro fe rtilizatio n beca use, as noted by in tact ovari an fo lli cles that were c leaved to the mo rul a
some a uthors, "IVF concepti o ns do nearl y as well as and ea rl y bl astocyst stages .6
natura l pregnancies afte r el inica l recogniti on." 1
T he cla im that a hi gh numbe r of conceptuses were lost
The di scuss ion o n earl y huma n was tage began w ith earl y in the ir deve lopme nt was e ncouraged by a hypo-
studi es by Hertig a nd Rock in 1956. T hese in vestigators theti ca l a na lys is presented by Roberts and Lowe. 7 Their
studi ed 34 " human ova" w ithin the first 17 da ys of de- estimate that 78 pe rcent o f conceptuses we re lost was
velopm ent obtained fro m 2 11 pati ents w ho had had a based o n a seri es o f presumpti o ns whi c h we re unte n-
hys te rectomy after be in g enco uraged to have inte r- abl e, including an estim a te of the number o f a nnual acts
course pri o r to the surgery. Depending upo n whic h of of co itus a nd a nnual ac ts of unprotected co itus.
their papers you beli eve, 13,2 10,3 11 ,4 of the "ova" were
abno rmal. Their wo rk is essentiall y one o f a kind s ince it Th e natura l e mb ryo loss has been di ffi cult to determine
has never been repeated. Fro m thi s stud y, the claim was becau se of the compl ex nature ofobtaining reli a bl e in-
made that 50 perce nt of ea rl y e mbryos are lost. Thi s form atio n. In gene ral, the best data ava il a bl e, howe ver,
comes from a s ub-secti o n of the He rti g-Rock stud y in ha ve come fro m a numbe r of in vesti gati ons w hic h ha ve
whi ch 4 o ut of8 (50% ) o f "ova" recovered pri o r to im- been conducted in va ri ous a nimal species. 8• 12 ln a li of
plantatio n were cons ide red to be a bno rma l. Thi s small these studi es, control animals were eva luated in an ap-
series and its evaluati o n is probl e mati c. prox imated natural state. In these mammals, the sponta-
neous fe tal loss was cons iste ntl y less than 15 percent
The re is a seri o us questi o n as to w hether o r not the a nd the preimpla ntati on loss , 1 to 3 pe rcent.
797
798 T he Medical and S urgical Practice of Na ProTECHNOLOG Y
More recentl y, Wil cox, et a l. , 13 using dail y urine speci - Pope Paul VI lnstitute Evaluations _ _ ~
mens to evaluate P-H CG in 22 1 hea lthy wo men attempt-
ing to conce ive, identifi ed 198 pregnancies by an in- Thi s iss ue has been examin ed at th e Pope Paul Vf Insti-
crease in the P-H CG leve! near the expected time of im- tute in a couple of di ffe rent way . First of all , the overa!!
pl antation . Ofthese, 22 percent ended before pregnancy incidence of pregnancy loss pri or to the 20th week of
was " detected clin icall y." 13 pregnancy has been eva luated fo r 1,704 consecutive
pregnanc ies (Tabl e 58- 1). Thi s shows an overall preg-
[n 1999 , Wil cox, et a l. , furth er in vestigated thi s is ue. 14 nancy loss rate of2 l .4 percent w ith 15. 5 percent rep re-
In 189 pregnancies where dail y urine samples were aga in senti ng early mi scarri ages (within the first 12 weeks of
analyzed fo r P-H CG, 75 percent !asted at least six weeks pregnancy, 3.8 percent in the middl e trimester of preg-
in du ration past the last menstrual pe ri od and the re- nancy, a 1.9 percent incidence of ectopi c pregnancies
mainin g 4 8 pregnanc ies (2 5% ) ended in earl y loss . and a 0.2 percent inc idence of indu ced a borti on.
A mong the pregnanc ies th at !asted six weeks or more,
the first appearance of chorioni c gonadotropin occurred In furth er evaluating thi s more spec ifica ll y, an eva lu a-
6 to 12 days after ovul ati on. One of the interesting find- ti on was made of3 63 cycles in whi ch the earl y eva lua-
ings in thi s particul ar study was the relationship of earl y ti on ofserum P-H CG was perfo m1ed. Thi s included 185
pregnancy loss to the timing of impl antati on. Us in g an in which the result was pos iti ve and 178 cyc les in w hi ch
endocrine parameter fo r the timing of ovul ati on, their th e P-HCG was negati ve. These were quantitative P-
data suggested that the ea rl y loss increased as the ti me HCGs (Tabl e 58-2). O ne of the questi ons asked was
of impl antati on was delayed. 1f impl antati on occurred whether or not "clinica l signs of pregnancy" were present
by the ninth day, 13 percent ended in earl y loss. Thi or absent. Thi s is very poo rl y defin ed in those studi es
pro porti on rose to 26 percent wit h implantation on day which have previously been done. lt was fo und that in
l O, to 52 percent on day 1 1 and 82 percent after day 1 1. a li cases in whi ch there was a pos iti ve P-HCG, c lini ca l
Thi s is a unique contributi on and should be the subj ect sign of pregnancy were present. In those patients w ho
of furth er in vesti gati on. 14 had a negati ve P-H CG, the clini ca l signs of pregnancy
we re a bsent (Table 58-3). Beca use these patients were
These latter two studi es by Wilcox, et al. , seri ously chal- chartin g the ir menstrua l and fertili ty cycl es with th e
lenge the earl y estima tes of 50 to 78 percent earl y preg- CrMS, they could identify clini ca l signs of pregnancy,
nancy loss. These studi es we re we ll des igned and used
a very precise measurement fo r P-HCG. And yet, even
more recentl y, the claim that human reproduction is " rela- Table 58-2: R esults of Serum ¡3-HCG Testing
ti vely ineffi cient w ith a presentati on th at 75 percent of Pope P aul VI lnstitute
pregnancies repre ent a fa ilure of impl antation and, are (N=363 cycles)
th erefore, not clinicall y recogni za bl e" continues to be
made. 15 Result n %
Positive 185 51.0

Negative 178 49 .0
Totals 363 100 .0
Table 82-1: Pregnancy Loss Prior to

20 Weeks Outcome D ata
Po pe P aul VI lnstitute
Table 58-3: R esults of ¡3-HCG Testing and
Total Pregnancies - 1, 704
Presence o r Absence of
Outcome n % Clinical Signs of Pregnancy -
Pope P aul VI lnstitute (N=363)
Spontaneous abortion 264 15.5
Mid-trimester SAB 65 3.8 Clinical Signs of Pregnanc:t
Result Total Present Absent
Ectopic 32 1.9 n %
~ -HC G n n %
1nduced abortion 4 0.2
Positive 185 185 100.0 o o.o
Tota ls 365 21.4 o.o
Negative 178 o 178 100.0
Chapter 58 : Early Pregnancy Loss : Challenging Curren! Pa radigms 799
which before thi s time would have gone unnoti ced. In undergo in g analys is of their post-Peak hormone pro-
Figure 58-1 , an example of a pati ent who had a pos iti ve fil es were furth er exa mined. In rev iew ing th ese, the
~-H CG on Peak +22 of27.7 fo llowed by a decrease to 7. 1 progesterone leve ls on Peak + 11 were observed . lt has
on Peak +24 and a heavy menstrual peri od on Pea k +25 been shown that serum progesterone exh ibits a very
shows that this prolonged post-Peak phase was clini ca l rapid response to th e presence of increas ing levels of
ev idence of pregnancy. This has been referred to as a ~- H CG. 1 6 An exampl e of a no1111al pregnancy with rising
"ch emical pregnancy." However, the exact eti ology of leve ls of progesterone is shown in Figure 58-2.
such an event is not known. For exa mple, does a true
conception occur in cycl es such as thi s? Is there rea ll y By look ing at th e post-Peak progesterone profiles and
an early embryo, or thi s the result of a co mpl etely ab- identifying increas ing Peak + 11 progesterone levels, one
normal phys iologic event to whi ch trophobl astic ti ssue can obtain indirect evidence of an ex isting pregnancy
is present, ~-H CG is produced and the post-Peak pha e at its very earliest stages. ln additi on, tho e cycles in
del ayed? The answer to th ese que ti ons are not yet whi ch the Peak + 11 progesterone was seen to increase
known, but should be pursued to be better und erstood.
In the author 's experience with these types ofpregnan-
cies, almost invariably, the post-Pea k phase is prolonged Table 58-4: Outco1ne of Positive ~-HCG Tests
and thi s prolongation is almost always 18 days or greater Hisk-Risk Pregnancies
in duration . (Table 58-3). Po pe Paul VI lnstitute (N=185)
This evaluation of~-H CG was conducted in a very high- Outcome n %
risk population. The results of the 185 pos iti ve ~-H CGs Norma l pregnancy 139 75.1
are tabulated in Tabl e 58-4. Th e overa ll pregnancy loss Overt spontaneous abortion 38 20.5
rate was 24.9 percent and fo ur of the 185 pregnancie Ectopic preg nancy 4 2.2
cou ld be considered early losses that were either subtle
Ea rly spontaneous abortion 1 4 2.2
or "subclinical" (2.2%) but ali with prol onged post-Peak
ph ases . Totals 185 100.0
1. But clinical signs of pregnancy were present.

A different approach has also bee n undertaken to ana-
lyze thi s. In thi s approach, a group of in fertili ty patients
9 10 u 12 13 14
r r
SCV 8C.Y <oc.. 8CY IOCY 8CY SCY

1(.,, ic .;I. )1:3 .a. " 1 ica. •el.
~·
;n . 7
Figure 58-1 : In the first case, a positive pregnancy test was obta ined on P+16 and her period started on P+23. This 22-day post-
Peak phase (prolonged) is a common finding in early pregnancy loss and is, de facto, a "clinica l sign of pregnancy." In the second
case, a positive pregnancy test was observed on Peak+25. A period started on Peak +26 and her ~ -HCG decreased to 7.1. This
is another example of an early pregnancy loss with "clinical sig ns of pregnancy" observed when charting the CrMS .
800 The Med ical and Su rg ica l Pra cti ce o f NaProTECHNOLOGY
15 16 17 35
L
OAO
llH L VL VL
OAD OAO OAO
""° ""°
I
0-.0 OAO OAO 0.JCcil a.:a IOKL IOOL
ltl .,,,
aA.O <..e
...
P+3 P+7 p.q P+ll
Figure 58-2: In this example, progesterone assessed during the cycle of pregnancy shows an increase on both Peak +9 and Peak
+11 . lt has been shown that the progesterone respon se is very ra pid when stimulated by the production of ~ -HCG in early
pregnancy.16
were furth er evaluated by perfom1ing seru m ~-H CG lev-

els on that blood sample. Not ali of these have po itive
~-H CGs . Thus it can be concluded that in those cycles
in which the progestero ne leve ls are decreas ing or in
th ose cycles in which the progesterone leve! has in - Table 58-5: Estimated Early Pregnancy Loss
creased but the ~-H CG is abse nt, no pregnancy existed. B ased u po n Analysis of
These data are summarized in Table 82-5. Rising P+ 11 Progesteron e Level in
Profiles of ln fe rtility Patients
In this series, there were 590 menstrual cycl es in 590
n %
patients that were exami ned using the post-Peak proges-
terone profile. Ofthese, 36 cycles exh ibited a ri si ng leve! Number of profiles examined 590
of progesterone on P+ 1 1 (6. 1%). The percent of posi- Number and percent with rising 36 6.1%
tive ~-HCGs observed in the presence of an elevated P+11 progesterone level
Peak + l l progesterone leve! was determined to be 1 1. 1 Percent positive P-HCG in 11 .1%

presence of rising P+11
percent. Thus, the overall estim ated early pregnancy progesterone level'
wastage in thi s eva luation was 0.67 percent.
Estimated early pregnancy 1 0.67%1
wastage (6 .1% x 0.11)
When one combines these two types of eva luation, the
1. Based on analysis of P-HCG on nine patienls with rising P+11
use of early ~-HCG leve ls and an eva lu ation of rising progesterone levels. One of the nine had positive i}-HCG on P=1 1
(25.1).
leve ls of progesterone late in the lutea l phase for a total
of 775 cycles, an earl y pregnancy loss rate in th e ra nge
of0.67 to 2.2 percent was identified. This has been more
consistent wi th the stud ies that were done in studies of
mammals which sho wed an early pregnancy loss ofone
Chapter 58 : Early Pregnancy Loss : Challenging Current Parad igms 801
to three percent. In additi on, these patients who have In our own data analys is, using a somewhat imil ar and
ea rly pregnancy losses, almost in variably ha ve clini ca l yet very different approach, and with exce ll ent monitor-
signs of pregnancy. in g ofthe menstrual cyc le with the abi lity to see "clini-
ca l signs of pregnancy" in their earliest stages, no preg-
nancies were observed in whi ch some defacto evidence
Final Note ----------~ of pregnancy was not ev ident. In add iti on, usi ng serum
~-H C G leve ls andan analysis of ri si ng levels ofproges-
Ever since the ori gi nal work of Hertig and Rock in 1956, terone late in th e lutea l phase, the estimated earl y preg-
it has been claimed that the human reproductive system nancy loss in stud ies at th e Pope Paul VI lnstitute ha ve
is ex tremely inefficient because there is a very high rate shown a range of 0.67 percent to 2.2 percent which is
of early pregnancy loss. As studi es ha ve become more much more consistent with mammalian studies performed
and more refin ed, it appears that the origi nal claims of on an imals in which pregnancy occurred in a state which
50 to 78 percent ea rl y pregnancy loss are not compat- approx imated the natural environment.
ibl e with current studi es. Wilcox , et al. , 14 has shown
much lower rates than previously presented.
References
1. Bokl age CE: Surviva l Probab il ity of Hu111 an Co ncc pt io ns 1O. Bl andau RJ , Youn g WC: Th e Effcc ts of Delayed Fenili za-
fro111 Fcrti li zati on to Ter111 . ln t .1 Fe rtil 35 :75-94, 1990. ti on on th e Deve lop111 en1 o f th e Gui nea Pi g Ovu111. A111 J
Anal 64 :303 -329, 1939 .
2. Herti g AT, Roc k J, Ada111s EC: A Descri plio n of 34 Hu111 an
Ova Wilhin the Firsl 17 Days of Dcve lop111en1. A111 J Anal 1 1. Marston JH , Chang MC : The Fe rtili zab le Li fe of Ova and
98 :435-493, 1956. th eir Morph ology Fo ll ow in g Delayed ln se111inati on in Ma-
ture and l111mature Mi ce. J Ex peri111ent Zoo 155:237-252,
3. Hertig AT, Rock J, Adam s EC, el al: 34 Fertili zed Ova, Good,
196 4 .
Bad and lndifferenl, Recovered fro111 2 1O Women of Kn own
Fertilil y. Pediatrics 23:202 -2 11 , 1959 . 12. Fugo W, Butcher RL: Ova Ripeness and th e Ma111111a li an
Ova 1: Ova Ripene ss and Ea rl y Embryo nic Deve lopm enl.
4 . Herti g AT: Hu111an Troph obl as ts: No r111 a l and Abn or111 a l.
Fertil Steril 17:804-8 14, 1966.
A111 J Clin Path 47:249-268 , 1967.
13 . Wilcox AJ, Wei nberg CR, O'Conn or JF, et al: Jnc idence of
5 . Mastro iann i L, ori ega C: Obscrvati ons on Hu111an Ova and
Earl y Loss of Pregnancy. Engl J Med 3 19: 189- 194, 1988.
th e Fertili zati on Process . Am J Obste! Gy neco l 107 :682-
690, 1970 . 14 . Wi lcox AJ , Baird DO, We inberg CR: Ti111 e o f l111plantat ion
o f th e Co nce ptus and Loss of Pregnanc y. N Eng l J Med
6. Shettl es LB: Perso na l Co m111 uni ca ti on , eple111ber, 1976.
340: 1796-1 799, 1999.
7 . Roberts CJ, Lowe C R: Wh ere Have Ali th e Co nce pti ons
15. No rwitz ER, Sc hu st DJ , Fi sher SJ: lmp lantati on and lh e
Gone? Lancel, pp 498-499, March 1, 1975.
Surviva l o f Ea rl y Pregnancy. N Engl J Med 345: 1400-1408,
8 . Braden AWH : Are Non-Geneti c Defects of Ga111eles l111por- 200 J.
1ant in th e Eti o logy o f Prena tal Mo rt a lit y? Fe rti l Ste ril
16. Licht P, Russu V, Wildt L: On the Role of Hu man Chori oni c
10 :285-298 , 1959 .
Gonadotropin (hCG) in th e Embryo- End o111e1rial Mi croen-
9. Hunter RHF: The Effects of Delayed ln se111inati on on Fer- viro nm enl : lmpli ca li ons for Differenti ati on and lmp lanta-
tili zati on and Ea rl y C leavagc in lh e Pi g. J Re pro Ferti l ti on . In : Carr BR (Ed): Semin ars in Reproduc ti vc Medi ci ne
13 :1 33 - 14 7, 1967. 19:37-47, 200 1.
Fertility, Conception, and Childbirth in
Women of Mature Reproductive Age:
New Hope through NaProTECHNOLOGY
Tracey Parnell , M.O.
omen in their thirties or forties who wish to achieve norma li ties and restore normal reproductive function ,
W a successfu l pregnancy may well face cha ll enges
not ex peri enced by their younger co unterparts. Sorne of
offer new hope for coup les ofmature reproductive age
who wish to achi eve th eir dreams of a successful preg-
the diffi culti es encountered by these women may in- nancy an d hea lthy child.
clude difficulty conceiving and infertili ty. 1 Once con-
ception has occurred these women may then experience This chapter wi ll seek to outline the scope ofthe prob-
signifi cantly higher rates of mi scarriage,2 medica! com- lem and the ev idence that NPT can address some ofthe
plications during pregnancy 3 and perinatal problems physiolog ic abnormaliti es th at contribute to infertili ty
such as premature delivery and infants with low birth and perinatal difficulties encountered by the mature
weights. 4·5 The imp lications of such complications are grav idae, in particular, premature bi1ih and deli vering
fa r reaching,6·7 both in terms ofthe medica! and soc ieta l low birth we ight infa nts. A bri ef review of sorne of the
needs of the child and the fami ly. For many coup les theories ofreproductive aging will provide a background
hoping to achi eve successful pregnancy and childbi rth , for understand ing why NPT may be more effective in
the only option presented to them has been to emp loy dea ling with this issue than ART.
artifi cial reproductive technologies (ART) aimed at cir-
cum venting what has been seen as the unavoidable and
irreparable effects of time on the hum an reproductive Review of the Problem _ _ _ _ _ _~
system.
The latter hal f ofthe 20th century heralded fundamental
ew and exciting research in to atura! Procrea ti ve Tech- societa l changes in the developed world ; changes wh ich
nology (NaProTECHNOLOGY - NPT), however, brings have seen a signi fica nt demographi c shi ft in the aver-
into question the inev itability of these outcomes and age age ofwomen wishing to achieve pregnancy8 . Dur-
the reproductive theories underlying them. In fact, N PT ing and after World War 11 , women bega n working out-
research would suggest that perhaps many of these side the home in record numbers. For many women, the
women are actua ll y suffe ring from correctab le disease focus shifted from marriage and fa mily to educati on and
and dys fun ction of the reproductive system, not simple career adva ncement. 9 Changes in sex ual norms and re-
aging. NPT, which seeks to diagnose reprod uctive ab- productive health that occurred in the l 960s and ea rl y
803
l 970s further contributed to this demographic shift. 10 ofover $585 mi Ili on dollars for twins born through !VF
As a result, more women than ever before are trying to andan additional $346 mi Ilion dollars for in-hospi tal care
conce ive in their 30s and 40s. Many find , however, that of tripl ets. Th i does not take into acco unt ongoing
becoming pregnant is increasing ly difficult. hea lth care issues , including the in creased risk of cere-
bral palsy or blindness.21 As we ll , so rne studi es are now
The Ameri ca n Society for Reproductive Medicine esti- suggestin g that these children are at increased risk of
mated that nearl y 20 percent ofwomen wait until after rare diseases such as retinoblastoma 22 and congenital
age 35 to start their families. 11 In terms offe1tility and ca ncers,23 possibly secondary to problems with genetic
maternity, patients aged 35 and older are considered to imprinting that occurs during initial fe1tilization and early
be of advanced maternal age. Women of this age are embryo deve lopm ent under conditi ons that arise from
often noted to be at hi gher ri sk for in strum ented or cae- ex pos ure to artifici al culture medi a.
sa rean delivery, 12 medi ca ! prenata l comp lications, pre-
mature deli very and the delivery of low-b irth weight Whether at ri sk or not, man y parents are willing to ac-
infants. 13 In pa1ticular, the delivery of a preterm, low- cept the chance of twin or higher a rder pregnancy in
birth we ight in fa nt is associated witb significa nt short order to ha ve a child. Few, however, are made aware of
and long-term hea lth complications that may have last- the in creasing evidence to suggest that si ngleton preg-
ing consequences not onl y for the child and fa mil y, but nancies are also at ri sk of seri ous perinatal complica-
the hea lthcare system and soc iety at large . 14 ti ons. umerous recent studi es have demon strated that
the risk of premature labor and of ha vin g a low-birth
For coupl es who are ex perienc in g difficulties concei v- we igh t in fa nt are not restricted to those oftwin or hi gher
ing, the use of ass isted reproductive technology (A RT), order pregnancies. 24 •25 In 2004, th e British Medica! Jour-
in particular in vitro fertilization (IVF), has become the nal pub! ished a systematic review of al1control led stud-
recommended treatment of choice by in fert ili ty specia l- ies of ART peri natal outcomes between 1985 and 2002.
ists. For women of advancing reproductive age, so rne lt concluded " .. . that sin gleton pregnancies from as-
reproducti ve spec iali sts even recom mend IVF as the sisted reproduction have a significantl y worse perina-
first step in dea ling wi th infertility. 15 The reasons be- tal outcome than non-assisted pregnanc ies." 26 What is
hind thi s advice lie large ly in the fac t that, the older the sti 11 unclear, however, is whether NaProTECHNOLOGY
patient, th e less likely the success of ART. IVF is not, offers greater hope of successful pregnancy and deliv-
however. parti cul arl y successfu l in treating women age ery of a healthy child for women of advancing repro-
38 and older (Tab le 59- 1) 16 and it is not without its own ductive age.
ri sks.
umerous studi es on IVF conceptions and births have NaProTECHNOLOGY and Perinatal
documented the high incidence of twin and hi gher or- Outcomes - - - - - - -- - - - - --,
der pregnancies that re ult from th is procedure. 17· 18 Sorne
cou ntri es are even moving towards restrict ing the num- In 2002, researchers with the lnternational ln titute of
ber of em bryos that can be tran sferred in order to de- Restorative Reproducti ve Medicine (llRRM ) began a
crease thi s serious co mplication. 19 A 1997 study by rev iew process to examine outcomes of pati ents pre-
Hild eba ugh, et al. , estimated the cost of peri natal in- senting far N PT treatment in Irel and. Thi s info rmation
hosp ital ca re for twins at $37,94 7 and tripl ets at $ 109, was an alysed from ex isting databases. The resu lts of
765 .2º Us ing data from the C DC Reproductive Hea lth these studi es clea rl y demon strated that N PT was an
ART database for the year 2000, this ca lcul ates to a cost effecti ve option for couples experiencing infertility, with
an overa ll success rate of 43.1 percent, calculated by
Table 59-1: Live Birth Rate per Treatment Cycle 24-month li fe- tab le anal ys is.27 What though of those
by Age women in the advanced reproducti ve age category?
Live birth ratel

treatment cycle % Success
Separate analys is (Tabl e 59-2) shows that women 38
and older, who had not prev iously undergon e lVF are
All ages 9,139 / 37,469 24.4 a ble to achieve rates simi lar to th e overall success rates
Age ~ 37 years 10,528 149,518 21 .3 ach ieved in the study population. Those women , how-
Age ~ 38 years• 1,389 112,049 11 .5 eve r, who had undergone IVF, had lower success rates
• lndicates calculated from HFEA data. wi th 15.1 percent achi ev in g li ve birth.
From: Human Fertilisation and Embryology Authority Provisional National
Data Statistics IVF from 01/0411999 to 3110312001with 68 ctinics reporting.
Although notab ly lower then th eir non-IVF co unter-
Chapter 59 : Fertility, Conception , and Childbirth in Women of Mature Reproductive Age 805
pa rts, thi s numbe r still co mpares favora bl y to the ave r-

Table 59-2: Live Births by Age Categories and
aged two -yea r s uccess rate q uoted by the Hu man
History of Previo us IVF Attempts
Fe1ii li sation and Embryo logy A utho rity (Table 59-3). 28
(Ireland D atabase)
A lth ough success rate are quoted per treatment cyc le
Uve and thus a re di ffic ult to compa re to th e N PT program
birth rate
for th ose success rates, other studi es have shown s imi lar poor
continuing
upto
results fo r thi s age category. What is of more important
No. of Crude 24months cons ide rati on in Tabl e 59-3, however, is the overall high
No. of treatment live birth of NPT
Patient category patients episodes rate treatm ent
ra te of multiple pregna ncy repo rted .
No previous IVF 296 301 20.3 43.8

Here too research is prov iding new hope. A review of
Age 38 years and older
wo men seeki ng to achi e ve s uccessfu l pregnancy us ing
Previous IVF 161 161 15.1 25.3
Age 38 years and older PT examined the inc ide nce of multip le pregnancy,
prete1111 de li very, low bi1ih weight and admission to N1 CU
• Calcu lated using life-table anaylsis
a nd neo natal co mpli cati o ns in wo men who were age 37
or o lde r in the yea r of deli very. The res ults wo uld sug-
gest th at wo men of th is age category who conceive
us in g N PT are at no greate r ri sk fo r ex peri encing th ese
compl icati o ns then the ge nera l po pul ati on.29
An addi tio nal ana lys is of the databa e for wo men aged
Table 59-3: Selected Pregnancy Outco mes, IVF 35 and a bove also revea led similar trends (Tab le 59-4).
Ali ages Age ~ 38 years•

A more in-de pth rev iew ofth e data, from Februa ry l 998
Live birth rates/ 10,528 149 ,518 1,3891 12,049 until May 2003 , reco rd s 4 13 co ncepti ons in th e lrish
treatment cycle
database, 230 of these to 19 1 wo men age 35 o r greate r at
Percentage live births per 21.3% 11 .5%
treatment cycle the time of co nception. Ofthese, 190 were tirst conce p-
Singleton 8810 ti o ns, 34 we re second co nceptio ns a nd 6 we re third co n-
Twi n births 308 1
Triplet births 235
Table 59-5: Characteristics of Pregnancies
% of multiple births/ 27.3%
live birth s* Among Women Age 35 and Older
% of twin births/live birth s* 25.4% (lreland Database)
• lndicates calculated from HFEA data.
From: Outcomes of IVF in Human Fertilisation and Embryolog y Authority Provi-
siona l National Da ta Sta tistics from 01/04/1999 to 31/03/2001with68 clinics Number of couples 191
reporting .
Conceptions 230
Number of live births 151
Twin pregnancies 5
Number of miscarriages/ectopic pregnancy 77
Mean number of weeks on hormone support 18.4
during preg nancy
Table 59-4: Rates of Preterm Birth,

Low Birth Weight, and Multiple P regnancy Rate in
NPT P regnancies for Wo men
Age 35 and O lder and fo r the General Populatio n Table 59-6: Characteristics of Women Age 35 or
(lreland D atabase) Older Co nceiving with NPT
Population
(lreland Database)
NaProTECHNOLOGY Norms (UK)
Rate of prete rm birth 5.9% 7.0%

Average age of woman (range 35-44 yea rs) 37.9
(<37 wee ks)
Number of cycles of previously failed IVF 42
Rate of low birth weight 4.6% 6.0%
Mean number of years of inferti lity 4.6
infants
Average nu mber of mo nth s of NPT treatment 9.0
Multiple preg nancy rate 3.3% 1.0% prior to conceiving
806 T he Medica! and Su rg ical Pra ctice o f NaProTECHNOLOGY
Table 59-7: Population Smdies on Risk of Preterm Birth,

Low Birth Weigh ts, and Multiple Pregnancies
after Conception with IVF
Friedler,
Beral , Doyle Schieve , Saunders & Mashiach,
& Maconochie 32 et al. 31 Lancaster'2 and Laufer"
Population size 1267 987 3 3503 1149

Yea r of study 1978-1987 1996-1997 1986 1982-1989
Study location United Kingdom United States Australia Israel
Rate of preterm 24% n/a• 17.8% 28.6%
birth (<37 weeks)
Rate of low birth 32% 26.2%.. 36.4% 23. 8%
weight infants
Multiple pregnancy rate 23.0% 56 .0% 22.0% 23.6%
Not noted in study

- Sing leton pregnancies o nly
ceptions. From thi s there were 15 1 live births, 77 misca r- studi es in wo men of ali a ges, this data was restricted to
riage or ectopic pregnancies (Table 59-5), with one preg- a pop ul ation ofwoman at hi gh ri sk for these comp li ca-
nancy on-goi ng and one with an unknown outcome. Of ti ons by reason oftheir adva nced maternal age (35 - 44,
th e 151 live births, birth we ight data was ava ilable fo r average 37.9) and lengthy hi story of infertility (4.6 years
109 infants and gestational age was know n in 1 16 ca e . on ave rage) (Table 59-6).
Numerous studies have highli ghted th e increased ri sk Table 59-8 shows the di stribution of gestationa l age at
of multipl e pregnancies, prematu re birth s and the birth birth in pati ents treated with NaProTECHNOLOGY. lt
of low birth we ight in fa nts after 1VF. Table 59-7 shows shows that in PT conceived pregnancy the majority
the results from four large sca le internationa l popula- of in fants (94. 1%) were born at 37 weeks or beyond .
ti on studi es examining the outcom e of IVF birth s. A l- There were no in fa nts born earlier than 35 weeks. Thi s
th ough the A merican rev iew by Schi eve, et a l. , foc used g ives a prematurity rate of5.9 percent. In addition, there
largely on the incidence of multipl e births in the data were onl y 5 of 109 recorded birth weights that were
recorded by the Center fo r Di sease Contro l (C DC), the <2500 grams, for a low birth we ight rate of 4. 6 percent
in cidence of preterm birth s wou ld be expected to be (5/109) ; with the incidence of very low birth rate (< 1500
hi gh , particularly in li ght ofa 56 percent multiple birth grams) being 0 .9 percent ( 1/ 109).
rate. These results are for ali pati ents, and a li ages who
have undergone ART. Thi s is a triking contrast to the These numbers compare favo rably to the nationa l ave r-
corresponding PT data for multiple birth s, premature age of the genera l pop ul ation fo r the United Kingdom
deli very and low birth weig bt infants as li ted in Table
59-4. lt must be remembered that unlike the prev ious
Table 59-9: Summary of Peri natal Outcomes
Comparing ART to NaProTechnology
Table 59-8: Distribution of Gestational Age at Birth
(N=lül ) (Ireland Database) ART' NaProTECHNOLOGY 2
% %
Weeks of gestation Number born Percent
Multiple pregnancy rate 22.0-56.0 3.3
37 weeks or > 95 94 .1 Rate of preterm birth 17.8-28.6 5.9
36 weeks 3 3.0 (<37 weeks)
35 weeks 3 3.0 Rate of low birth weight 23.8-36.4 4.6

infants
34 weeks o O.O
1. These are the range ofthe outcomes cited in Table 59-7 for ART pregnan-
33weeks o O.O cies.
32 weeks o O.O 2. Women of mature reproductiva age o nly (35 and older, average age 37.9
years}.
Chapter 59: Fertility, Conception , and Childbirth in Women of Mature Reproductive Age 807
during this tim eframe. Although further studi es are the periconceptual hon11ona l mi 1ieu, stri ving fo r the idea l
needed and currently on-going, this wou ld certainly conceptual environment. Thi s wou ld hopefu lly avoid
support the notion that NPT is ab le to reduce the risk of any adverse chem ica l impact on not on ly the ga metes,
premature labou r and delivery and improve low birth but on the developing embryo, particularly in the cru-
we ights in hi gh risk women over the age of 35 with a cia l and frag il e early stages of development.
hi story of infertility.
There is no denial that there are changes seen in the
A summary of these peri nata l events compari ng ART fema le reproductive system with age, including in-
with NaProTECHNOLOGY is presented in Table 59-9. creased risk of infertility, pregnancy and peri natal com-
There is no question that the peri natal outcomes in this plications, andan increased risk of genetic abnormali-
group of women of mature rep roducti ve age is signifi- ties.35 The question though is whether these changes
cantly better than those outcomes reported in the litera- represent the nOJm for th is age gro up ora population in
ture through a representative se lection of reports. The whom physiologic abnorma liti es are present. A review
multipl e pregnancy rate, rate of preterm birth and the of the concept of reproductive potential and the theo-
rate of low birth weight in fants is sign ificantly lower in ries of reprod uctive system aging may help to better
those women treated with NaProTECHNOLOGY. exp lain PT research outcomes, which seem to large ly
suppo11 the latter theory.
NPT and ART Perinatal Outcomes:

Why the Difference?_ _ _ __ _ _ _, Reproductive Potential _ _ _ _ _ _~
lt wou ld appear that NPT may decrease the risk ofhav- Why is it that sorne women in the thirties and early
ing a low birth weight infant or premature delivery. The fort ies are able to achieve pregnancy with littl e diffi -
risk ofthese comp li cations is known to be increased in cu lty or comp li cation s and others are not? Is the timing
ART conceptions, either directly through the procedure of the inev itab le aging process pre-programmed or a
itse lf or by the fact that ART does not address the un- result of a eries of complex interactions between inter-
derlying phys iologic abnormali ties th at cause inferti l- na! and externa! facto rs? lfso , can these factors be iden-
ity, particularly in women over age 35. tifíed and modifi ed to allow the individual to max imi ze
their fertility until reach ing the limits of th eir bio logic
There are a number oftheoretical reasons why this would potential?
be so. Many infertili ty ex pe11s be lieve that the fa ilure of
!VF in older women is a result of increased risk of lt is well accepted that there is a natura l tendency to
aneupl oidi c or geneticall y abnon11 al embryo format ion, decreasing fert ility with age. 36 Evidence to support thi s
secondary to instabi li ty in the older oocyte harvested. exists both in the animal kingdom and in populati on
In order to overcome thi s, ART may offer pre-implanta- studies in commu niti es in which confo unders such as
tion genetic screening or oocyte donation . eith er of contraceptive use and steri li zation procedures are not
these techniques claims to correct other underlying fou nd .37 They do not, however, assess changes in fre-
physio logic co nditi ons that may contribute to th ese quency of intercourse, nor do th ey assess des ire fo r
abnormaliti es. These techniques do, however, resu lt in children and use of such practices as co itus interrup-
sorne improvement in the li ve birth rates in the mature tus . We are also limited, however, in drawing conc lu-
grav idae. They do not change, however, the risk of peri- sions from these studi es as many of them were con-
natal complications. ART is also associated with a marked ducted prior to the sweep in g changes that have oc-
increase chance of tw in or higher order pregnancies, curred in the la t few decades. lt does though provide
another well documented risk fo r premature delivery, sorne baseline for discu sion.
low birth weights, and perinata l co mpli cations. 34
One such oft-quoted study was done on Hutterite com-
NPT however, seeks to non11a li ze the physiologic con- munities in the l 950's.38 Women in the community wou ld
ditions under which concepti on takes place . During the usua ll y only have one marri ed partn er and wo uld not
critica! times of ovulation, fertilization and implantation , active ly use any form of fam il y plann ing. The rate of
the ova and subseq uent embryo are bathed in a com- infertility for women in their twenties was about 3.5 per-
plex and intricate array of biochemical sa lts and pro- cent; but increased to 7 percent for women at age 30
teins, each playi ng an essentia l ro le in ens uring the suc- and 11 percent for women at age 35. After the age of35,
cess of the biologica l processes underway. By nom1al- there was a significa nt increase in infert ili ty (33 % at age
izing phys iologic parameters, NPT hopes to maximize 40) until by the time they were 45 , 87 percent ofwo men
were co nsi de red infertile. By age 50, 100 percent of mo ne (FSH) initiate oocyte maturation and ovu lation, in
wo men were infertil e. lt wou ld seem that at least a s ig- a complex feedback loop in vo lvi ng the ovarian hor-
nifica nt propo rti o n ofthe fe male po pul atio n ho pin g to mones estrogen and progesterone. The preov ul atory
conceive in th eir 30s o r earl y 40s should be a bl e to do LH surge resta1ts the process of me iotic de ve lopment
so . for the oocyte. Thi s process is th o ught to be med iated
by severa ! protein compl exes, which play a role in the
T he conce pt of a woman 's reproducti ve potential thu inhibition or initi ation ofthe meiotic deve lopment of the
in corporates w hat should be th e no rma l ab ility to conce ll. Following the LH surge a number ofnew biochemi-
ce ive in the absence of specifi c condition . This con- cal signals are produced by the cell. Thi s phase of growth
cept ofreproductive potential should help delineate what in vo lves th e production a nd sto rage of s ig ni fica nt
a re li ke ly inevitable age related changes from those ab- a mounts of metabolic substrates, prote ins a nd mR.J"\JA.
no rmal reproductive conditions that are mo re like ly to An alteration o r a bnormali ty at this stage may we ll ad-
occur in the re producti ve mature woman. verse ly affect the proces of fertilization and eventual
e mbryo develop ment.·w
Reproductive Aging Theories _ _ _~ A RT ex perts wo uld a rg ue that the fl aw is a result of

agin g of the oocytes the mse lves, as is ev idenced by
However, before we ca n assess th e reproduc ti ve poten- the increased risk of genetica lly abnormal emb ryos, most
tial of the indi vidua l, it is necessary to ha ve a funda- often mi scarried, and the improvement in ART li ve birth
me ntal understanding of the processes invo lved in the ra te noted wi th egg do natio n from yo unger women.41
aging ofthe reproducti ve system. The fema le reproduc- Thi s improve ment, however, does not necessaril y mean
tive system is the result of the complex interaction be- that the origi nal primary oocyte itse lfwas flawed. Alter-
twee n numerous bioche mica l pathways, intricatel y co- native ly, once it was ex posed to the environment in-
ordinated by severa] target and response organs within duced by the procedure of oocyte retri eva l it cou ld ha ve
th e huma n body. There are a numbe r of theories as to become dysfun cti o nal. Could thi s dys function ali ty in -
how s ig nifi can t the contributi o n is ofeach of the com- dicate inhere nt age related instability? Yes, perhaps.
po ne nts o f the syste m to the dec lin e of ferti lity seen A lth o ug h the question that must then be asked give n
with ag in g. The two main th eorie center aro und the the comp lex ity ofthe inte raction s of th e oocyte a nd its
contribu tio n of the aging of the oocyte itse lf vers us env iro nm ent is, ifthese degenerati ve changes ex ist, are
c hanges seen in the hypothala mi c- pituitary access. they in fac t a res ult of abnormal micro-environmental
changes th at adve rsely affect th e initi a l meioti c reacti-
The first th eory is that the agin g process is inevi ta bl y vatio n process o r the production of ce llul ar hormo nal
ti ed to the deteriorati o n of the oocytes stored in th e s igna ls? Perhaps, like many things that are agin g, the
ovary. Oocytes are initi a ll y formed in utero and have oocyte merely becomes le s tolerant of cha nge a nd di s-
undergone their first me iotic di vis ion at aro und the fifth rupti o n in its e nvironment over time. Aga in, N PT spe-
mo nth of gestatio na l age. lt is in this stage of develop- c ifi ca ll y seeks to ensure an id ea l periconceptua l envi-
me nt that th ey are stored as prima ry oocytes, sorne ro nme nt, a nd , as such , if th ese a re in fac t post-ov ul a-
200,000 at pube1ty, awaiting the biochemi ca l "on" sw itch ti o n o r post-fertili zation effects, PT may we ll prevent
that sig na Is th e o nset of me narc he a nd that repeatedl y some of these abnormalities from occurring.
occ urs th ro ug ho ut th e re produ c tive lifespan of the
woman .39 The qu estion remains, is decreased fert ili ty in the o lder
reproductive woma n so le ly a product of inhe rent de-
How, thoug h, is it determined which primary oocyte w ill generation of the genetic material of the oocyte, which
unde rgo furthe r growth a nd ovulati on, whi ch wi ll be- may have been produced fo1ty yea rs prior, or are s ig-
come atretic and whi ch w ill never respo nd to stimuli? n ificant chan ges a lso attributab le to c han ges in th e
This question is o ne of the great my teries ofthe fema le hypotha lam ic-p ituitary control mechan isms? It must be
re producti ve cycle, and certainl y an area fo r research in remembered that the hypothalamic-pituitary system also
the future . 1f it we re poss ibl e to determin e what trigge rs seems to play a n impo1ta nt ro le in ea rly, and on-go in g
ovul ation rather the n quiescence o r atresia it may be pregnancy and pregnancy o utcomes. 42 The poor results
possible to further rec ruit primary oocytes we ll in to the ac hi eved with A RT and the o utco mes seen wi th PT
late r re prod uctive yea rs. wo uld su ppo rt th e theory that abnorm al hypotha lamic-
pituitary fu ncti o n contributes sig nifi cantl y to these ad-
As it is unde rstood c urre ntl y, the pitu itary ho rmones, verse o utcome .
luteini zing hormone ( LH ) and fo lli cle stimu lating hor-
Chapter 59 : Fertility, Conception, and Childbirth in Women of Mature Reproductive Age 809
The compl ex hormonal environ ment in whi ch ovulation compl etion and synchro ni zation of ali process in-
and fertili za ti on takes place is contro ll ed by the hypo- vo lved: although an ove rview is emerging, many
th alami c-pi tuitary axis, which also shows increased aspects still remain to be elucidated. Thus it is im-
changes with age. 43 The initi al process of ovul ation and poss ible to assess and ga uge th e co nsequ ences of
fertilizati on is criti ca ! not onl y fo r th e ea rl y stages of manipul ati ons durin g a sisted reproductive prac-
deve lopment and impl antati on but the events that oc- tice .... "48 (p27)
cur during these phases actuall y set the stage for suc-
cess of the rest of the pregnancy. Like much of bio- The defi ned pu rpose of ART is to attempt to achi eve
chemi stry, th e bi ochemi ca l signals produced earl y are pregnancy by circum venting the underl ying di fficulti es
beli eved to intluence eac h subsequent action; an error that preventi on conception. lt is not curati ve nor cor-
early on may well have profound and devastating ef- recti ve in nature. The process does not attempt to cor-
fec ts. rect any un derl ying phys iolog ic abn ormaliti es; in fac t,
ovu lation induction and oocyte retrieva l often require
Work ori gin all y done by Barker correlating low birth suppression of ex isting hypothalami c-pituitary function
weights and prenatal maternal nutriti on with subsequent in order to be successfu l. 49 lt could be th eori zed that
adult offspring hea lth compli cati ons has proven con- thi s may, in fac t, worsen any pre-ex isting hormone ab-
troversial.44 Ev idence is mounting, however, to sugge t norrna li ties. PT on the other hand , acknow ledges that
that the events th at occur duri ng preimp lantation may hypoth alam ic-pitu itary dysfun cti on may be a signifi-
well have an impact not onl y on the pregnancy, but cant contributor to age related in fe11ility and perinatal
throughout the remainder ofthe indi vidual's li fes pan. compli cati ons and the improved outcomes are a result
Within ART there is also animal resea rch to support of foc using on cooperating with and restoring norm al
concern s regarding th e artifi cial periconceptual envi- reprod ucti ve fu ncti on.
ronm ent in whi ch fertili zati on and early deve lopment
takes pl ace. 45 Mi ce whose onl y difference was in vitro
fertili zation in artificial culture medi a showed subtle but Summary _ _ _ _ _ _ _ _ _ _ _~
signifi ca nt differences in learning ability and anx iety a
adults.46 Although it is diffic ult to directl y compare outcomes of
ART and NPTstudi es, it would certa inl y seem that PT
ART ex perts do not claim that they know the long-term treatm ent is more favora ble or at th e ve ry least compa-
effec ts of th e in vitro proce s: rab le to ART. NPT does not increase the risk of twin or
hi gher ord er pregnancies, and, fo r hi gh ri sk women, it
" .. . we know nothing yet about the ag ing ofadul ts would appear to decrease the ri sk of having preterm
born after ART, whi ch is easy to understand be- labour or the deli very of a low birth we ight in fa nt. As
cause the first in vitrofertilization (IVF) child was NPT foc uses its attenti on to ensuring effecti ve ovul a-
born in 1978. Therefore, fin al co nclu sions with retory para meters and peri conceptual hormonal param-
spect to the hea lth effects of ART trea tm ents on the eters, not on alterin g the oocytes or the ea rl y embry-
children thus co nce ived ca nn ot be made" 47 (p 127). onic geneti c makeup, it would suggest that the hor-
monal mi lieu in whi ch th e conception takes pl ace is at
"A new pharmaceutica l is introduced accordin g to least as impo11ant as the oocyte age . Unlike ART, whi ch
very well-defined protoco ls and pharmaceuti ca l com- attempts to circum vent th e underl yin g reproducti ve
pani es are responsible fo r the unfo reseen side-ef- dysfun cti on, NPT foc uses on correcting or curing th e
fec ts. ART procedu re have not been and are not underl ying abnormaliti es.
being introduced according to we ll-defined proto-
co ls and are introdu ced with out know ledge of the Furth er research should foc us on im prov ing the under-
ri sks"(p 135). standing of th e compl ex processes ofov ul ati on, fe11ili-
zati on and pregnancy, and on identi fy ing normal repro-
" Fertili zati on marks the creati on of a new and unique ductive phys iology from abnormal. Continued research
indi vidual .. ..(p2) There is no doubt that the process on the appli cat ion of N PT to correcting these abnor-
of oocyte growth and matu ra ti on is a hi ghly com- maliti es sho ul d enab le th e NPT medi ca ! consultant to
plex process . ... The fin al evo luti on ofa mature oo- max imi ze and restore reproducti ve potenti al to many
cyte whi ch has th e potenti al fo r fe11ilization and fur- women hopin g to ha ve chi ldren in their thirti es or early
ther deve lopm ent is dependent upon the co rrect fort ies.
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49 . Mas hiach S, Dor J, Goldenberg M, Sha lev J, Blankstein J,
44 . Kh an IY, Laka in g L, Pos ton L, N ic olaid es KH. Fetal pro- Rudak E, Shoa m Z, Fin elt Z, Nebe l L, Goldman B, et al.
gra mm in g for ad ult di sease:where nex t? .1 Matern Feta l Neo- Pro toco ls fo r in duct ion of ovu lati on. Th e co ncept of pro-
nata l Med. 13:292-299, 2003. gramm ed cyc les. An n N Y Acad Sci 54 1:3 7-45, 1988.
Lethal Congenital Anomalies:
Prenatal Diagnosis and the
Management of Pregnancy
P renatal di agnos is is aso ld as obstetri cs and hav in g

babi es . Beginnin g with s uc h obse rva ti ons as
Chadwick 's Sign to the regular externa! measurement of
Over the last 20 to 25 yea rs, there has been an ex plosion
in techn ology whi ch now all ows fo r th e appli cati on of
testing fo r th e eva luati on of different ge neti c abnor-
the growth ofthe uterus during pregnancy and the aus- maliti es. At least 20 di ffe rent chro moso me anomali es
cultation of the fetal heartbeat, prenatal diagnos is has can now be identified and 700 to 1000 di ffe rent bio-
had a spec ial rol e to pl ay in the ongo ing eva luation and chemi ca l or molecul ar conditi ons with a geneti c bas is
management of pregnancy and th e fetus. can also be eva luated. Thi s is accompli shed through a
vari ety of di ffe rent systems, often technologica ll y quite
As sci ence has adva nced, pre nata l di ag nos is has di ffe rent, which have as th eir major foc us the eva lua-
evo lved into th e eva lu ati on of fe tal di stress th ro ugh ti on of the normal and the abnormal fe tus.
contracti on stress and non-stress testing, nippl e stim u-
lati on testing and the ultrasound eva luati on of the bio- Historica ll y, prenatal di agnos is ha had as its major fo-
ph ysical profile. Durin g labor, amni oscopy is used to cus the di agnos is or assess ment of conditi ons which
eva luate the amniotic fluid by peering th ro ugh th e in- by way of such di agnos is and assessment wo uld ass ist
tact membranes. Continuous in trapartum surve ill ance th e physician in helping thef etus to a more norma l and
ca n be accompli shed th ro ugh electronic mon itoring of hea lthy li fe. Such an obj ecti ve has carried with it an
the fe tal hea1tbeat and uterin e co ntracti ons. obj ective mora l good fo r whi ch the ethical phys ician
res ponded by see ing such di agnos is as not onl y a duty
As thi s work towards di agnos ing vari ous prob lems and but a very spec ial res ponsibility.
condition s in pregnancy has technologica ll y advanced,
the assessment of fe tal lun g maturi ty has been benefit- Un fo rtun ately, the tated obj ecti ve of prenatal di agno-
ted by the measurement of the lec ithi n/sphingomye li n sis at the beginning of the 2 1st century is "to offer the
rati o (the LIS ratio) or the levels of phosphatidylglycero l. widest range of in fo rmed choice to coupl es at ri sk of
Thi s uses an amni ocentes is tec hnique whi ch was first hav ing children with an abn ormality, and to all ow such
populari zed in th e man age ment of erythrob lastosis couples the opportunity to achi eve a hea lthy fa mily by
fe talis by Professor Sir William Albert Lil ey of New avo id ing the bi1t h ofaffected children th ro ugh se lected
Zea land. aborti on." 1 Such an attitude is cl ea rl y at odds with the
813
814 The Medical and Surgic al Practic e of NaProTECHNOLOGY
long he ld practice of making a di agnosis to he lp the be used for feta l meas urements, the eva luation of fe ta l
indi v idua l in restoring health w hil e not using the infor- abn ormalities, echocard iography and the evaluation of
mation to depri ve the indi vidual of li fe. Thi s more recent bl ood fl ow w ithin the uterine and fe ta l-pl ace nta! units.
approach clearl y has signifi cant impl icati ons.
Beca use it is used in pregnancy, its safety is an impor-
It has been proc la imed that such in fo rmation "should ta nt co ncem . There are no confinned ultraso ni ca lly in-
prov ide accurate genetic info rmati on yet di ctate no par- duced adverse effects in humans that have, to date,
ti cul ar co urse of action ," 2 a fo rm of non-directi ona l or been re ported w hen d iagnostic leve Is of ultraso und are
non-judgmental coun seling. It is also admitted w hat we utilized.4
have kn own ali a long, "of co urse, comp letely non-di-
recti ve counseling is pro babl y unrea li stic. For example, When ultraso und is used as a prenata l d iag nostic too!,
a coun se lor 's unwitting facia l ex press ions may ex pose it is effecti ve beca use it is abl e to eva luate morph olog ic
hi s or her unstated opini ons. Merely offering antenata l changes in various structures. In this case, in pregnancy,
di ag nosis serv ices implies approva l. Despite the di ffi - the techn ology is abl e to eva luate the ge neral phys ica l
culti es ofbeing trul y obj ecti ve, one should attempt to parameters of the pregnancy, the cervix, p lacenta, amni-
prov ide in fo rmati on and th en support the co upl e's de- otic fluid , feta l anatomy in rather signifi cant deta il , ges-
c ision."2 Such non-directive counseling, it should be tatio na l age param eters, fe tal growth para meters, and
pointed out, is an aberration in medicine since pati ents Dop pler wave fo rm assess ments of va ri ous pregnancy
come to the phys ician not onl y fo r an eva luation and related blood vesse ls. With regard to fe ta l anatomy, ul -
di agnosis but a lso fo r the phys ician' info rmed and expe- traso und is quite capa ble of evaluatin g the centra l ner-
rienced counse l with rega rd to the appropriate remedy. vous system, the face , neck, heart, lungs, a bdo mina l
wa ll , gastro intestina l tract and fe tal intraa bdom ina l or-
l t is the purpose ofthi s chapter to eva luate those too ls gans, the urinary tract and adre na l g lands, th e genita l
w hich are currentl y be ing used fo r the prenatal and pre- tract, ske leta l dyspl as ias, the umbili ca l cord and other
implantatio n evaluati on of geneti c abnorma lities. Thi s anoma lies. 5
chapter w ill limi t it elf to the use of ul traso und, amnio-
centes is, chori oni c villus sampling, the eva luati on of ln the case of spina bifida, ultraso und is an extreme ly
serum markers such as alpha-fetoprotein , the Tripl e Test, good and non-in vas ive means of assess ing th is poten-
percutaneous umb ili ca l bl ood samplin g ( PUBS) , fetal tiall y compli cated abnormality. l n va ri ous stud ies, ul tra-
skin bi opsy and the preimp lantati on di ag nosis of ge- so und was able to identi fy 87 percent,7 9 1. 1 percent,5
netic di sease. The impact of thi s techno logy, w ill then and 98 percent 2 of affected cases.
be di scussed with spec ial emph as is on th e support of
fa mili es, fro m diagnosis ofa letha l anomaly th ro ugh the At the Pope Paul V I lnsti tute, we have been study ing
natu ra l occurrence of death . the growth rate of the gestati ona l sac and the crown
rump length of the fetal pole. When there is wh at we ca l!
a "sac d iscrepancy" of seven or greater days (the ges-
The Use of Ultrasound _ _ _ __ _ _,, tati onal sac is lagging by seven or more days in its
growth pattern fro m th e gestati ona l age as judged by
Ultrasound is an adva ncin g techn ology w hich utilizes crown ru mp length) then there is at least a 40 percent
hi gh frequ ency sound waves fo r the eva luati on of morri sk of mi scarri age. Thi s eva luation must be performed
ph ologic changes in interna! ti ssues. Wi th adva nc ing betwee n 6.0 and 9 .0 weeks gestati ona l age. In such cir-
ultraso und technology, espec iall y with adva nci ng co m- cum stances, we can identi fy an embryo or fetus that is
puter techno logy, the c lari ty of these pi ctu res has im- at hi gh risk.
proved significantl y and , in fac t, three-dimensiona l ul-
traso und technology has now come into c linica l prac-
tice. Amniocentesis ______ ____----.
Di agnostic ultraso und has been ava il abl e fo r over 30 A mni ocentes is is a techn iq ue that has been used fo r
yea rs and has now become a widely acce pted c lini cal abo ut forty yea rs. It utilizes a needl e introduced into
too! in a lmost ali branches of medi cine. lt has been esti - the amni oti c fluid and a syri nge that is used for the
mated that more than one-h alfofa ll pregnant wo men in withd rawa l ofthe fluid . Thi s fluid becomes a too! upon
the Uni ted States are exa mined by ultraso und .3 Thi s w hi ch one ca n do chro mosoma l or bi ochem ica l assess-
widespread acceptance is dueto its c líni ca ! utili ty, con- ments. The needle, is in troduced w ith the ass istance of
ve nience and non- invas ive nature. The techno logy can u ltraso und g u idance.
Chapter 60 : Lethal Congenital Anomalies 815
With amniocentes is, skin ce ll s from the fe tus can be rors ofmetabolism usuall y transmitted in an autoso-
cultured and chromosomal analysis of the ce li s can be mal recess ive fas hi on, th at can now be identified.
acco mpli shed. Results usually take three to four weeks
to return . Thi s will allow for the di agnos is of such things 7. Others
of tri somy 13 , 18, and 2 1; Turner 's syndrome; and tri p- There are many oth er poss ibiliti es for eva luation in
loidy. However, it <loes carry wi th it sorne di stinct risks. thi s fas hion including the assessment of amniotic
For exa mple, the pregnancy loss rate is considered to fluid alph a-fe toprotein analys is.
be approximatel y 0.5 to 1 percent in ex perienced hand s
because of either trauma from the needle in sertion or
infection which occ urs as the res ult of it. With those The Triple Test _ _ _ _ _ _ _ _ _~
less experienced, the loss rate may be hi gher.
lni tia l tudies with maternal serum alpha-fetoprotein
Amniocentesis for thi s purpose is usuall y performed at (MSAFP) revea led that, in co mbinati on with maternal
about 16 weeks of gestation although on occas ion it is age, this test could enhance the estab li shment ofDown
performed between the 11 th and the l 4th week. While it syndrome to about 40 percent of ali cases. By adding
is not considered appropriate to perfo1m amniocentesi s the serum marker of HCG (and to a les ser extent serum
in every pregnancy, the follow ing is currently consid- estrio l) and measuring it at around the l 6th week of
ered a list of the "accepted med ica ! indi cati ons" for pregnancy, identification can now be made of Down
amni ocentes is for geneti c diagnosis. 2 syndrome in approx imately 60 percent or more of cases.
Both AF P and HCG increase in Down syndrome while
l. Advanced maternal age estri ol decreases. False pos iti ve rates range from 3.8 to
lt is now general medica! practice in the United States 7.2 percent. 8
to offer prenatal clu·omosomal diagnosis to ali women
who at their expected delive ry date will be 35 yea rs A meta-analysis of prospective studies for the Triple
of age or over. The des ignati on of35 years is, how- Test sc reening for Down syndrome among women ofa ll
ever, quite arbitrary and is based generally on the ages is presented in Tabl e 60-1. Very imil ar results have
increas ing incidence of Down syndrome. been reported fo r the AF P!H CG/Estri ol/ Age combina-
ti on.9
2. Previous child wi th chromosomal abnorma li ty
Whi le the ri sk ofsuch recurrence is often no greater These data revea! that fo r every posi tive result in which
than 1 percent, most medica! authorities still recom- a Down syndrome fetus is present, their are 54 normal
mend antenatal studies of the am ni oti c fluid. fet uses with a fal se positive res ult (98.2%). lfone takes
into acco unt an adjustment based on ultraso und find-
3. Parental chromosoma l rearrangements ings, there will be one Down syndrom e affected fet us
A balanced translocation is th e usual indication but for eve ry 35 otherwise unaffected fetuses with false
inversions and other chromosomal abnormalities ex-
ist although these are ali quite uncommon.
4. lncreased ri sk ofaneuploidy Table 60-1: The R es ults of a Meta·Analysis

Beca use of low matern al erum alpha-fetoprote in , of the Prospective Studies for the
low estrí o!, and elevated hum an chorion ic gonadot- Triple Test Screening for
ropin. In thi s case, ifthe ri sk is greater than or eq ual Down Syndrom e
to that assoc iated with a 35-year-old woman (i.e. l/ N %
270) counseling for potenti al am ni ocentes is is con-
Pregnancies 57 ,676 100.0
sidered by the medica! profess ion to be appropriate.
Number of Down synd rome 103 0.18
(1:555)
5. Prenatal diagnosi s of mendelian disorders
Down syndrome detected 67 65.0
The use ofmetabolic eva lu ations, enzyme analysis (1:862)
and D A analys is can lead to an understanding of lnitial false positives 3,638 6.3
various mendelian di sorders uch as hemog lobino- False positive alter ultrasound 2,347 4.1
pathi es and hemophilia. False positive: true positive ra tio 54 .3 : 98 .2
Alter ultrasound 35 .0 : 1 97.2
6. lnborn Errors ofMetabolism.
There are an ever increas ing number of inborn er-
pos itive res ults (97.2 % ). ln othe r wo rds, a pos itive re- abn ormal. ln other words, CYS is less reliab le than am-
sult ca rri es with it o nl y a 1.8 pe rcent ac tual in cide nce of niocentesis. lt also carri es w ith ita 1. 72 to 4.60 percent
Down syn d rome, and, afte r ult rasound assess me nt, 2.8 miscarriage ra te (Tab le 60-2) .
percent. These pregnanc ies are then further subj ected
to the ri sks of a mniocentesis as a fo ll ow-u p to clarify
these posi ti ve results. In this case, one must add a mini- Percutaneous Umbilical Cord Blood
mum 0.5 to 1 pe rcent feta l loss ra te to the eq uati o n. This Sampling _ _ _ _ _ _ _ _ __ _ --.
means that at least 0.5 to 1 fetus is sacrifi ced for eve ry
1.8 or 2.8 Downs babies that are identified. Umbi lica l cord blood either from the umbili ca l artery or
vein is obtained in thi s technique through the perc uta-
A recent stud y of 69 1VF pregnanc ies revea led th at 2 1 neous use of a lo ng needl e. Acces to the arte ry o r ve in
(30 .4% ) screened pos itive fo r Down ynd ro me, 4 (5.8% ) w ill va ry depending upon the placenta! locati o n and the
for neural tube defects, and 3 (4.3 % ) for both condi- po iti on of the cord in se11io n.
ti o ns. Howeve r, at bi11h , no ne ofthe infa nts had a neu-
ra l tube defect or Oown syndrom e. Th e rate of pos iti ve A. With a n anteri o r pl ace nta, th e needl e goes thro ugh
screens for Down synd ro me wa abo ut twice the ex- the placenta a nd to the vesse l.
pected rate fo r wome n of thi s age. The screen-pos iti ve B. With a posterior pl acen ta, the needle passes through
rate for ne ural tube defects was as ex pected. 10 the amniotic fluid the n pe netrates the vessel.
C. With a late ral o r funda ! placenta, the needl e passes
Further use ofthe Triple Test has been promoted for the thro ugh a portian of the pl ace nta and th e am ni otic
prenatal detecti o n ofTurner 's yndrome, fe ta l non-im - fluid before e nte rin g th e bl ood vessel.
mune hydrops, feta l demi se, multipl e gestati o n, inaccu-
rate gestati o nal age estim ati on and other patho logies. By obtaining blood in this fas hi o n, thi s bio logica l fluid
It is po inted out that s uc h mate rn al serum testing is can be used to do chromosome anal ys is, bi ochemica l
o nl y a sc reenin g procedure and is, by itse lf, not di ag- and mo lecul ar assess me nt, and DNA ana lysis in asome-
nost ic. what s imil a r fas hi on as o ne does w ith amniotic fluid .
There i noted a 1. 1 percent feta l death rate and a 0.8
Often , the maternal se rum alpha-fe to prote in screen is pe rce nt aborti on rate w ith thi s tec hnique. 12
done during the co urse of pregnancy. In the United
States, this is often a routine, sometimes mandated pro-
cedu re. lt sho uld be noted that there is a considerab le Table 60-2: Chorio nic Villus Sampling
degree ofoverlap betwee n materna l serum AF P in nor- R ecently Published Risks of
ma l pregnancies and maternal serum AF P in pregnan- po ntaneo us Abortio n
cies characteri zed by neural tube defect. In fact, ofwomen
hav ing unex pl ained elevations of serum A FP levels, onl y Sponta neous
Number Abortion
1 of 15 will prove to have a fetus w ith a neural tube Author Year cvs n %
defect ata late r po int.
Borrel A. et al' 1996 335 11 3.28
Sundberg K. el al' 1996 579 27 4.66
Yang Y H. el al' 1996 750 18 2.40
Chorionic Villus Sampling -----~ Cederholm M. et al' 1997 174 3 1.72
Brambati B. et al• 1998 10,000 258 2.58
C horionic Yillus Sa mpling (CYS) all ows fo r prenatal ge- Total 11 ,838 316 2.67
netic di ag nos is to be made during the first trim ester of a Borre! A . Costa D , Delgado RD . Transcervical Chorionic Vi llus
Sampling Beyond 12 Weeks of Gestation, Ultrasound Obste! Gynecol.
pregnancy. lt is prom oted as a means w hi c h, because of 6:416-420, 1996.
its a bility to obtain earl y di agnos is, also wo uld " protect b. Sundberg K, Bang J . Smidt-Jensen S, et al. Randomized Study of Risk
of Fetal Loss Related to Early Amniocentesis Versus C horionic Villus
patient pri vacy" a nd " permit pregna ncy te rminati on
Sampling, Lancet350: 697-703, 1997.
earl y in gestatio n." 11 c. Ya ng YH , Park YV, Kim SK et al. C horionic Villu s Sampling: C linical
Experience of the lnitial 750 Cases, J . Obste! Gynaecol. Res. 22: 143-
149, 1996.
CYS offers s imilar in fo rmati on wi th regard to chromo- d. Cederholm M, Axelsson O. A Prospective Comparative Study of
somal status, e nzyme levels, D patterns, etc. as does Transabdominal Chorionic Villus Sampling and Amniocentes1s
Perforrned at 10-13 Weeks' Gestation, Prenat. Diagn. 17: 311 -317, 1997.
th e eva luat ion of a mnioti c fluid . However, there is an
e. Brambati B, Tulu t L , Cislagh i C . Alberti E. First 10.000 Cho rionic
increased ri sk in CYS that th e c hro moso me eva luati o n Vi llus Sampling Pe rformed on Singleton Pregnancies by a Single
Operator. Prenat. Diag n. 18: 255-266, 1998.
may actually be different from the baby, either abnorma l
when the fetus is norma l o r normal whe n the fetus is
Chapter 60: Lethal Congenital Anomalies 817
Fetal Skin Biopsy _ _ _ _ _ _ _ _--. ing to accept. This entire issue is further explored in
Chapter 82 ofthis textbook. Those who might " benefit"
Skin disorders that may be suspected in the fetus are fro m preimplantation diagnosis are identified as the fol-
diagnosed by directly study ing the feta l ski n. U nder lowing: 14
ultrasound guidance a fetal skin biopsy fo rceps is in-
1. Women who are already steri/ized
serted through a small trochar. The fo rceps has a diam-
Ifthey wished a subsequent pregnancy, they would
eter of 1mm and severa] sampl es of fetal sk in are ob-
be consi dered candidates fo r in vitro fertili zation
tained . The optimum site for fetal skin bi opsy is the fetal
and would thus be candidates fo r preimplantation
back, buttocks or thi ghs.
genetic diagnos is (PGD).
This particular technique is quite ra re and thus the loss 2. Women with a moral objection to termination of
rate due to fetal skin biopsy is not known although it pregnancy
does seem reasonable to consider it in the same range In a contorted sort of way, it is often stated that
as fe toscopy (2.5% to 6%). " moral or reli gious objection to termination of an
establi shed pregnan cy need not exc lude the poss i-
lt is often said about these types of invas ive tests that bility of manipulation ofunfertilized oocytes orear-
they carry with them "a n inherent, albeit small , ri sk to li er preimplantation em bryos." Such thinking does
the fetus ... ." 13 Thi s is language w hi ch can be very mi s- not indi cate either a sensiti ve assessment of those
leading because while the overal l risks, in percentage with re ligious va lues or a basic concept ofwhat these
term s alone, mi ght be quite low (and thus acceptable in reli gious va lues hold to the indiv idual.
general medica] terms), the risk to the ind ividual fetus is
3. Women who are infertile and at risk
usua lly fatal and thus the relative proportion of that
Thi s appli cation would be limited to the relative ly
risk is very high and significan/.
few w ho actuall y opt for in vitro fertilization.
4. "Genetic disaster families"

Preimplantation Diagnosis -----~ These fa milies, by way of th eir rather ugly classifi-
cation , become candidates for PGD .
The preimplantation di agnosis of inherited disease has
grown out ofthe technology of in vitro fe rtili zation and lt is suggested that laboratori es establi shed for the pur-
the challenge to clinicians and investigators to improve poses of PG D must offer a range of techniques in IVF,
the "take home baby rate." Here genetic diagnosis is be- emb ryo logy and molecular biology. Since most ofthese
ing applied to embryos prior to the time of implantation. methods are labor intensive and w ill need skilled staff
and very clean rooms, the cost in da llar terms alone is
There are two distinct so urces of human embryos for anti c ipated to be hi gh.
those choosing preimplantation diagnosis as a means
of averting the birth of afflicted children. The most ob- The methods that are avai lable to achi eve diagnosis
vio us and common approach is w ith the use of embryos with PGD include the fo llowing:
coming from in vitro fertilization. Thi s has led to a sig-
1. Embryological methods
nificant amount of embryo experimentation. The other
These approaches include the evaluation of the first
alternative is to flush embryos from the uterus, so-call ed
polar body, the " non-in vas ive" di agnosis of em-
uterine lavage, after natural or induced ovulation to
bryos, or tbe excis ion of one or more cel Is fro m them
obtain embryos in thi s fash ion and then reimpl ant them
for typing (b lastomere bi opsy).
in someway.
2. DNA techniques
Part of the justification fo r this type of prenatal diagno-
3. Chromosome analys is
sis, which wi ll carry with it a significant loss of human
embryos, is what is often consi dered to be a very hi gh
rate ofnatural embryo loss in norma l human reproduc- To date, PGD has not increased the success rates fo r in
tion . The presumption that 50 to 75 percent ofpreim- vitro fert i1ization.
pl antation embryos are lost natura ll y is one wh ich has
cemented itse lfinto the reproductive literature. Unfo r-
tunate ly, closer observation of this suggests that the
human procreative system is considerably more effi-
c ient than w hat investigators and clinicians are wan t-
818 The Medical and Surgical Pra ct ice of NaProTECHNOLOGY
Supporting the Family and the Fetus=J loss rate, cannot be med ica ll y or ethi call y justified .
There has been a technological exp losion with regard Di ag nostic ultraso und, on the other hand, w hi ch is a
to prenatal diagnosis and specifica lly wi th its appli ca- non-in vas ive procedure, is proba bly underutil ized. This
tion to those diseases which are genetica ll y inherited . technique can be extreme ly he lpfu l in the manageme nt
Th ere are a numbe r of ways to obtai n tissue a nd vari - of pregnan cies but the examination s mu st be carefu lly
ous fluid sam pl es to do c hro mosomal ana lysis, eva lua- and skilljúlly performed by indi viduals who are well
tion of biochem ica l prod ucts and DNA ana lys is. This trained to look at the specific aspects of feta l growth
technology has now moved into the spec ifi c eval uation and deve lopme nt and anatomica l structure. Unfortu-
of the e mbryo and has been the subject of this chapter nate ly, such ultrasound eva luati on is not uni ve rsa ll y
up to th is point. ava ilab le a nd, in fact, is, in many ways, s ig nifica ntl y
und erdeve lo ped .
ln a rece nt review on thi s subj ect, Ja uni a ux 14 made the
following state me nt w hi ch appears to summ ari ze the lt is clear that th e predominant attitude w ithin med icine
cun-ent attitude of Weste rn medi cin e with rega rd to pre- has q uickl y deve loped, in an abortion environment, to
nata l diag nos is: "The adva ntages ofever-earli e r prena- presume th at thi s in fo rm ation will lead to the decision
tal testing seem obv ious: The sooner a problem is de- by the woma n to abo1t the child if the ba by turns o ut
tected , the ooner therapy or termination ca n be under- ab no rn1al. In fact, the a utho r has encountered women
taken ." While lip service is given to "therapy," it is w ho have told their phys ic ians that they would not con-
clear that "terminal ion, " or abortion is the majar ap- sent to such prenatal di agnosis because of such rea-
proach utilized as a result of these programs. In other sons and th ei r physicians have had angry and e mo-
words, over the last 35 yea rs, we have moved , in prena- tional o utbursts towards th e pati ent.
ta l diagnos is, from making a di agnos is for the purposes
of ass isting the patie nt ( in thi s case the fetus), to mak- What is often not considered by hea lthcare prov ide rs
ing a diag nos is so that the patie nt ca n be elimin ated. is the psycholog ical and spiritua l benefit that comes
Thi s shift has already take n place and , to a great ex te nt, with a moth er anda father reaching out of them se lves
has taken a stro ng ho ld in medi ca! practice. toward a child w ho is geneticall y impaired . The author
has persona ll y had the o pportuni ty to wo rk with a num-
It sho uld be pointed o ut that di agnostic information , of ber of such pati ents a nd in eve1y case both the mother
and by itse l f, is not mora ll y corrupt altho ug h the mea ns and fa ther have, o n their own acco rd, indi cated that
by whi ch it is acco mpli shed must be carefu lly eva luated they have been enri ched by the ex pe ri ence. Th is en-
and questi o ned fro m a medica! perspecti ve. Any tech- richment is both emotio nal and psychological as well as
nique that carries with it a direct interven/ion in the spi ritua l. Often, it helps bond th e spouses togethe r es-
lije of the embryo cannot be considered moral/y ac- pecia ll y if this occurs with in the context of a suppo rt-
cep table. T hose techniques w hi c h carry with th em a ive environment, an environme nt w hich, qu ite frankly,
ri sk ofan embryocidal o utco me must be carefull y eva lu- is often missing from man y late 20th and early 21 st cen-
ated from a medica ! perspective to see w hether or not tury ph ys ici a n 's office.
they a re at ali justified . Ultimate ly, thi s de pends u pon
the va lue system upo n whi ch such dec is ion maki ng is In these circumstances, the a utho r counsels hi s patients
built. that in hi s ex pe rie nce every c hi ld is conceived for a
particular reaso n and purpose. lfthis c hild is conce ived
Far the most part, invasi ve procedures whichjeopar- w ith a sig nifi cant chromosomal abnormality w hich is
dize the emb1y o and f etus are medically unnecessary fa ta l u pon bi1th or before bi 1th , for examp le, then it is
within the context of a medica/ practice in which the the natural role of that baby to extractfrom its parents
physician and the patient do not wish abortion. The re and !hose around them the !ove, concern and prayer
are few se lect cases in which havi ng adequate ad va nee that only a human being,falling into the grips of such
knowledge of a part icu lar conditi o n will be helpful in a mishap, can extrae/. Those parents who abort thi s
g uiding appro priate management at the ch ild 's birth. In problem , and thus cover it up psychol ogica lly and spiri-
those circ um stances, w ith very careful technique a nd tua ll y, w ill never have the opportunity to experience
app li cation ofthe principies ofprocedure so as to lower this potenti al growth. And , by not dea ling openl y with
the ri sks to the lowest possib le, such intervention could the problem they subject the mse lves to the risk ofpsy-
be co ns ide red justified. However, in a case suc h a the cholog ica l regret and emotio nal an d spiritual detac h-
"Triple Test" where 54 in 55 pos itive results are fa lse, ment.
a mni ocentes is, wi th its minimum 0.5 to 1 pe rcent fe tal
Chapter 60 : Lethal Congenital A nomalies 819
As abortion advances in our societies, the gap between 35 years ofage and two ofwhom were approximately 30
those who are psychologically and spiritually retarded yea rs of age. In ali cases, the patients would not ha ve
and those who are becoming psychologically and spiri- aborted the ir abnormal babi es and the use of amniocen-
tually enriched is widening ever more. It is, in the author's tesis in such circumstances would ha ve been observed
view, a tremendous challenge to the Church to enab le as meddlesome.
ministries to reach out in special ways to these particu-
lar kinds ofproblems witnessing to the very fundamen- While this is distinctly against the general trend of ob-
tal beauty ofhuman li fe and the supreme gift that chil- stetrics in the United States, it also shows that overa
dren are to the marriage whether normal or not. Much of prolonged experi ence ofti me, one can practice success-
the effect of such a renewal of these values, however, fully within the context of one's Catholic fait h to the
needs to begin directly with physicians beca use of the ultimate health benefít of the patient a nd her unborn
important ro le that they play. child . Furthermore, in such a practice, support for these
mothers and their fami li es should be ava ilable from the
Hoeldtke and Cal houn 15 ha ve recen ti y reported the de- physician , nurses and office staff. This support shou ld
velopment of Perinatal Hospice. Their thought, which be not only medica! but a lso psychological/emotional
parallels the a uthor's, is that the pregnancies associ- and sp iritual.
ated with letha l abnormalities are somewhat analogous
to that of fam ilies with a terminally ill child and that their
management is we ll served with a coherent and sensi-
tive end-oflife approach. Their approach is one of com-
prehensive structu red care for these families. This sup- There are a number of ways in the fu tu re where prob-
port is fro m the time of diagnosis through the birth and lems related to these difficulties can be addressed in a
death of the in fant well into the postpartum period . Of positive way. Sorne examp les are:
31 patients reported, 27 (87%) chose to participate in
The Peri natal H osp ice Program.
Study ofthe Cumulus Oophorus
It shou ld also be noted that prenatal diagnosi s can be
used to ass ist the embryo and in such cases, depend- In ultrasound studies ofthe cumu lus oophorus, a num-
ing upo n its effectiveness and associated risk factors , ber of poss ibilities ex ist. One case involved a woma n
ca n very much be of assistance. ln fact, the author be- who had five pregnancies with fou r ending in miscar-
lieves that there is a huge opportunity ahead for the riage . Genetic stud ies revealed an abnormali ty in the
successfu l treatment of those infants who are curren ti y parents that suggested th eir every-time risk of a nother
unable to be helped. spo ntaneou s abortion was 67 percent. On ultrasound
ln the author's practice of obstetrics now

for over 34 years (including years in train-
ing) a mate rnal serum a lpha-fetoprote in
leve! or a "Tripl e Test" has never been
obta ined. Durin g this period of time, the
autho r has never seen a baby born with
spina bifida and only recently a baby born
w ith meningo mye loce le. A lso, during this
period oftime, on ly three genetic amnio-
centeses ha ve been done, in spite of the
fact that this practice deals with a high risk,
older po pulation ofwomen. These women
ha ve ex perienced a variety of other repro-
ductive ab normaliti es including infertili ty,
repetitive miscarriage, previous ectopic
pregnancy, previous stillborn infants, pre-
vio us prematurity, and so fort h. In th is
group of patients over this period of time Figure 60-1 : This follicle shows the presence of two cumuli within th e same
fo ur patients have had babies w ith Down foll icle. On the left, a planer view and on the right, a 3-D view of the same
follicle . Follicles with up to three cumuli , have been observed (From: Pope
syndrome, two ofwhom were greater than Paul VI lnstitute Division of Reproductive Ultrasound, 2004).
examination, it was not possible to identify a cumulus size of the CO shows that it a ppears to be large in some
oophorus (CO) (an empty fo llicle). Suspecting the pos- ovu latory defects (Table 60-3). Thi s suggests the need
sibi li ty that this may be a retlecti on of the underl ying for more research into the role of ultrasound, the ap-
genetic abnormality, we counse led (with no guarantees) peara nce ofthe CO and the poss ibility that such could
for her and her husband to wait until a normal CO was be used to identi fy genetically hea lthy cycles.
identified and then atte rnpt pregn ancy. In the fifth cycle
of ultrasound, she had a norrnal-appearing CO . They
attempted and did achieve pregnancy, deli vering, at tem1, Evaluation ofthe Mucus Cyc/e
a healthy baby.
Worne n who chart the CrMS and have limited rnucus
In severa! other cases, fo llicles ha ve been observed w ith cycles do have a significantly increased incidence of
rnultiple COs (two or three) and this raise interesting ovulation-related abnom1a lities. These abnormalities are
questions of etiology and whether or not it repre ents a the precursors to inferti li ty, miscarriage, ectopic preg-
healthy ovu lation (Figure 60-1 ). Further study of the nancy and possibly sorne ano mali es. It can be suggested
that wornen , to screen their own cyc les, should chart
their menstrual and fert ility cycles using the CrMS . If
Table 60-3: Size of the Cumulus Oophorus in abnom1a lities are identified, then preconception treat-
P atients with Sonograp hically ldentified rnents could be irnplemented to decrease the incidence
Ovulation-related Defects ofthese problems (Figure 60-2). The full context ofthese
types of cyc les and their con nection to fetal anoma lies
Size of CO
Ovulation Descrl ption n (mm) is not yet understood. But, it should be considered for
further research because ofthe possibility that anorna-
A. Mature follicle , complete rupture 112 2.83
lies could be identified and treated prior to pregnancy.
B. Luteinized unruptured follicle 23 3.17 1
C . lmmature follicle 16 2.62 2
D. Partial rupture 6 2.67 3
Fetal Therapy
1. LUF compared to A, C, and D. Respective p-values:
p=.035 (Equal variance /-test)
p=.032 (Wilcoxon Rank-Sum test) While sti ll in the research stages, feta l surgery does
p=.03 (Aspin-Welch unequal variance /-test)
ho ld sorne hope for treating such cond iti ons as open
2- Not significan tly differe nt for A or D.
spina bifida. In addition , with further study, the poss i-
3. Not significan tly different ror A or C.
bility c learly ex ists for the fe tus to be treated medicall y
for other biochemical and ph ys iological abnorm alities.
16 17 18 19 20 21
M0 <.CK ~K 9CK CioCK 0AD OAO O.O.O OAO CIAD OAO OAO CAD 0-.0 OAO OAD MO OAO CAD 0A0 OA
1( f X 1 ~el XI
I I
= 5.3
MO OAD Ql\C ()11.0 a-.D OAD CAD VL ~ OAD OAO OAO

OAO
Figure 60-2: Two cycles from two differe nt patients where conception resulted in a major fetal anomaly. In the first cycle, the
baby had Down syndrome (MCS=5 .3). In the second , co ngenital hydrocephalus (MCS=4 .0). Both we re limited mucus cycles .
Chapter 60 : Letha l Congenital Anomalies 821
Concluding Case Studies - - - - - - - , of love was remarkable. One week Jater, in conversa-
tions with the author, the coupl e told him th ey had " no
Thi s chapter is concluded with the presentation of sev- regrets" for approach ing their baby 's care in thi s way.
era! case studies, so me in their own words, of patients '
care in the presence of a lethal congenital anoma ly.
Case2
Case1 This patient had had multiple previous mi scarriages and

in the current pregnancy, a fa tal lethal anomaly was iden-
T hi s patient, in her seventh pregnancy, had the sponta- tifi ed. They too we nt to abo ut 33 weeks before the baby
neous rupture ofmembranes at 20 weeks. Her obstetri- was born . The baby died sho11Jy thereafter. A number of
cian ca ll ed in a peri nato log ist for consu ltation . His rec- the staff at the Pope Paul V I ln stitute atte nded the fu -
ommendation was to induce labor and abort the baby. neral and the patient speaks today, severa! yea rs after
The patient was v iol ated by thi s advice and, with no- the event, about ho w special it was to ha ve been ab le to
where else to turn, sought the assistance of th e Pope g ive birth to thi s child . Throughout the pregnancy, her
Paul VI Institute. and her husband were supported by ali the hea lthcare
providers they carne into contact with .
Even though she was a long distance away, the preg-
nancy was supported medica ll y, emotiona ll y and sp iri-
tuall y. At 32 to 33 weeks, the baby was born by emer- Case3
ge ncy cesa rean sectio n because of depressed heart
tones. The baby had a lethal trisomy anomaly and died In thi s case, the In stitu te's support was by long di s-
in hi s parents' arms shortly after birth. The parents had tance. The coup le, age 26 and 30, had a baby di ag-
taken th e position that the responsibl e a pproac h was to nosed wi th tri somy 18 and chose to give ali ofthe Jife to
parent thi s baby to the best of the ir ability before, as thi s baby that was poss ibl e. At term, the baby died , in
well as afte r birth. u tero. Her mother wrote a long reflection on their expe-
riences and it is worth quoting, in her own wo rds, sorne
Two hundred peop le attended thi s baby's funeral. The ofwh at she felt:
baby's li fe had touched many peopl e. The outpouring
Case 3: In Her Own Words
"She weighed 4 pounds, 4.5 ounces and was measured at 16 support us and to honor Jordan. We we re so pleased th at she
inches long. Despite ali her outward di fferences, she was so received the remembrance and dignity that she deserved. And
precious and beautiful. She had dark hair just like her Daddy on tha t day, we could really see how her life had inspired
and a littl e button nose just li ke her Mommy. She mostly others - the way they talked about her and were interested in
looked li ke her Daddy th ough. Andas we sa t there and gazed her pictures. lt was amazing to see how such a little girl that
at our daughter's sweet little face, we fell her spirit ali around li ved onl y a short amount of tim e had ignited so many hearts.
us. We knew she was tel li ng us that she loved us, thanking us We were, and always will be, very proud to be her parents.
for doi ng everythin g we could for her and not to be sad, for
she was in a wonderful place free from any harm. Life ha a new meaning to us now. Our ex peri en ce with Jordan
has inspired us to rethink ou r priorities and goa ls and retlect
When lhe priest was finished , our family, who was wa iting so on what is truly importa n! in li fe. And althoug h there has
pati ently, carne in. They gathered around u and our priest been an enormous amount of stra in put on ou r marriage, we
continu ed to say more prayers. We took sorne ini tial pictures have ente red into a much hi gher leve! of !ove, respect and
with him and her Godparents. Then everyone had the chance co mmitment with each other than we ever thought imag in-
to hold her, have pictures taken with her and say their hello's able. We have matured so much Iogether and have learned to
and good-bye's. Seeing our fami ly and her Godparents hold be strong for each other. There couldn 't possibly be anything
her so lovingly and cheri sh every second they had with her in life that we wou ldn 't be ab le 10 get through together.
touched our hearts so deeply. We will never forget that pre-
cio us time we al l spent together with her. We look back and not once (do we] regret any decisions that
we made for Jordan, nor at any point did we conside r her life
Jorda n 's service was very sacred. There had to ha ve been to be a choice. She was a real person who made a real differ-
about 150 people gathered that day in her memory. We were ence.
so touched and gra tefu l fo r ali the people who were there to
Case4
And, finally, a mother of a baby affl icted with Potter 's

syndrome describes in her own words, the experience:
Case 4: In Her Own Words
Therese Lucille Wagner is our third chi ld . She was bom and Over the next severa! months 1 had num ero us ul trasound s to
died on June 21, 1999, having li ved 35 weeks. This story is monitor Therese's health . Each ultrasound was almost sur-
about her life and its impact on others. real. There was the baby - strong heart beat, ten finger , ten
toes, trying to move arou nd, safe inside my wo mb. Each week
At the 14-week ultrasound for Therese, the technician was passed as ifshe were li ving ou t her en tire li fe .
unable to find kidneys and remarked that the vo lume of am-
niotic fluid around th e baby was unu sua ll y low. She was uncer- At 24 weeks we began to make plans for a live birth . My
ta in what other probl ems might be present. Lack of amniotic mother made small white gowns and matchin g blankets of
fluid indicates poor kidney development, which negatively various sizes to dress our sweet innocent little sou l fo r her
impacts lung development. lt seemed the best plan of action burial. She also made gowns and blankets from soft baby flan-
was to wait for Therese to mature to better determine th e nel prints we had chosen, to dres her at birth. We wa nted
exact cause and extent of her diffi culties. something persona l and respectful for our time with her in
the hospital. We chose readings and music fo r the funeral and
We had always prayed for healthy chi ld ren withou t a second asked our family priest to travel to my hometown for the
th ought. Our prayer now was for a "special child" to help funera l Mass. Finally, we purchased a burial plot next to my
teach us and our other children the true meaning ofsacrifi cia l sister, who passed away 18 years ea rlier. Being prepared in our
!ove. hearts and in the details to co me was therapeutic and gave us
more opportuni ti es to parent. We made plans for Therese as
The 18-week ultrasound confirmed our worst fears. Our baby we made plans for all our children. The only difference - her
was large enough now that even underdeveloped kidneys shou ld li fe outside th e womb wo uld be meas ured in hours, not yea rs.
be vis ible but none were found and the amniotic fluid sur-
rounding our little one had decreased from the 14-week ultra- We spent each day loving this child without fear of the future.
sound! Therese wa diagnosed with Potter 's Syndrome, an Our prayer now was fo r a li ve birth. Please God, allow us to
anoma ly in which the kidneys are either completely missing, hold our sweet child, naming and baptizing her.
as they were in our case, or extremely underdeveloped. This
meant certain death at birth if we did not miscarry. As our baby grew, many que ti ons arose rega rding her ca re.
We are forever gratefu l to have received the support from Dr.
We wanted as much time wi th this chi ld as God wou ld give us. Hilgers and hi s staff to cheri sh our unborn child and allow her
Our prayer now was to carry her long enough to know her and to grow naturally in our hearts as well as in my womb. This
prepare a place in our hearts for her. was alife giving decision that has also helped us to hea l.
Those long months 1 never left Ornaba, even to go to my Dr. 1-lilgers treats eac h pregnancy as if it were " normal." He
parents, whic h would have been a comfort for ali of us. But and his staff treat every child, regardless of its health, with
the risk of miscarriage hung too heavil y over me. 1 could not respect and dignity. Through the moth er, they offer every
allow strangers tocare for us - people who did not know the child the same " medica! opportuni ty." Their uniqu e approach
sacredn ess of the moment. 1f th e wo rst happened, 1 wanted to involves the parents, medi ca! staff and the Faith.
be in my own home to grieve, not in a strange or far off place
and certain ly not wi th a Doctor who did not share our under- By 35 weeks there was no topping nature. Our fin al hours
standing of the fragile , but precious gi ft of Ji fe 1 carried. were quickly com ing. With mi xed emotions we prepared for
both a birth and a death. But more importantly - a feast day.
Our chi ld ren , then nea rl y 3 and 1 Yi, prepared their hearts by The day a soul uniqu e from all others, brought into being
naming it the "angel baby" who was growing bigger and tron- through our sayi ng yes to God 's divine plan fo r marriage,
ger inside Mommy's tummy until it was ready to go li ve in en ters eternity and becomes a special intercessor for our fa m-
heaven with Jes us. How cou ld this chi ld continue to thrive ily.
inside of me and yet be so close to death?
At 7:29 a.m. on June 21 , 1999, Therese Lucille Wagner, our
This pregnancy was very different from my previous two. precious little fl ower, was born and li ved independently for 93
Most noticeably, the baby's movement decreased as the am- minutes. What a miracle! She changed th e hearts and li ves of
niotic fluid continued to deplete, until she was unable to change a ll she met th at morning. Born by cesarean sect ion, her
positions at al!. 1 also seemed to expend more energy as 1 Daddy's dark brown eyes open and alert, she was quickly
cared for th e baby inside ofme. Amazingly my body compen- cleaned and swadd led, placed on my chest, nu ggling close to
sated for the baby's condi ti on, helping to sustain this precious my cheek. Mark baptized her, aw kwardl y spi lling holy water
li fe. over her head, his hands shaki ng with exci temen t.
cominued on next page...

Chapter 60 : Lethal Congenital Anomalies 823
Case 4 cont'd: In Her Own Words
Such a blessing to us, her soft sk in, her new baby smell , her Of course these comments hurt, but onl y to a point. We pray
dark curly ha ir, her kitten like sounds, her perfect fingers and for these peo ple. Praye r, in its many forms is very powerful.
toes. We took it ali in for each of minute of her painfully Maybe Therese 's life gives them somethin g to think abo ut. A
short li fe outside my womb. We wept at th e imperfections of successful, we ll ed ucated, healthy you ng couple chose to par-
this life on earth and from her we ga ined new hope for eter- en! a child such as Therese. Th is sa me coup le celeb rates her
nity in heaven with her. li fe rather th an moums it. God only know s whom she touched.
Wh ile she lived, Therese was cuddled and held close in tum by Therese, to us, is not a past experience. She is a member of
her godparents, Dr. Hilgers and Dr. Ann Russell, her Pediatri - our family that we !ove, pray to fo r intercess ion and active ly
cian . These two doctors did ali in their power to help us to include in our family activities and celebrations. She hada life
realize our dream ofa li ve birth and to ensure that our short time well li ved to its ful! potenti al. Our respect for her life facili-
with her wou ld be unencumbered by our medica! care. They tated her success. Her success is perfecti on ach ieved in Christ's
made this time with her as sacred and intimate as poss ible. prese nce - eternal happiness. The rese is a treasure that be-
longs to our fa mil y and to God. By our fa mil y's exa mp le, the
During our pregnancy, we received praye rs and support from selfish, ex ped ient options fo r endin g her life ea rl y are shown
fami ly, frie nds, nei ghbors, acquaintan ces, and many we never for what they truly are - selfi sh and ex pedient.
knew. Losing a close loved one had been a normal life ex peri-
ence for both of us, but our own chi ld? At first it so und ed 1 know th at our daughter li ved and was loved from th e mo-
imposs ible! The praye rs and offe rs of help and encouragement of her conception even wh ile she remained hidden from
ment li fted us up as we faced the unim ag inable. us. From within the silent confin es of her place beneath my
hea rt, she proclaimed her presence and worth . She taught us
The response of so me others shocked and sadd ened us. "Why to hold life more preciously, to cherish the li fe God gives us
wou ld you do it?" "Wh y is yo ur doctor makin g yo u carry thi s and to treat others with di gnity and respect. As parents andas
baby?" "What a lot for nothin g." There we re even those who people we are changed for knowing her .. . for knowing and
would not acknowledge me or Therese while 1 was pregnant. receiving our precious daughter, Therese.
Somehow, we made them uncomfo rtable by lovi ng and cher-
ishin g her.
Final Note ______________, being accom pli shed very effectively. The current abor-
tion climate has created an underl y ing fear and pro-
Prenatal diag nosis does indeed have a place in pre natal duced a mentality that effective ly says, "Life is on ly an
care. Over the last 20 to 30 yea rs, however, it has taken option; the decision to abo ti must be penultimately pro-
on the ro le of estab li shing a diagnosis so th at th e ba by tected. " But this does not serve our patients well. We
can be aborted. This is not the best that medi cin e has to as medica! practitioners must be willing to share in sorne
offer. of the pain , experience sorne of the sadness and gri ef
and challenge a li of us to someth ing beyond that. Our
As human be ings, hea lthcare providers ca n ve ry much experi ence should lead peop le to human and sp iritual
share in both the ecstasy ofa norma l health y deli very, growth. Such shou ld never be denied eithe r the patient
as we ll as, the ago ny and strugg le of a baby s lowly or the health care provider. Programs such as Perinata l
dy ing ofa letha l congenital a no maly. Thi s is where ou r Hospi ce and the su pport provided at the Pope Paul VI
hearts must be c ultivated a nd a ll owed to mature. Mod- ln stitute must be allowed to ex pa nd and grow, serve
ern medicine can do this well if allowed to and i f nur- and del iver, support and , yes, even !ove. Rea l !ove fo r
tured to. Unfortunately, in today's world, neither are rea l people both born and unborn!
References
1. Penketh R: The Scope of Pre impl antation Diagno s is. In: 8. Chard T, Maclntosh , MCM: Screening for Down Syndrome.
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Cambridge, United Kingdom , 1993, p. 82 .
o f the RCOG Workin g Party on Bioc hemical Markers on
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Adenomatoid Malformation : Prenatal Di agnos is and Natu-
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Preconceptional Care and the
reconceptional counseling has become increasingly contro l pri or to the onset of pregnancy. Such condi-
P a part of preven ti ve obstetrical care in the past 1O to
15 yea rs. 1•2 The preferred strategy is one of primary
tions as diabetes, epi lepsy, renal di sease, heart disease
and hyperte nsion are ali exampl es of conditions which,
prevention which is the avoidance of causal factors. if managed effectively pri or to the beginning of preg-
U nfortunate ly, secondary prevention is still promoted. nancy and during the course of pregnancy, will pro-
This identifi es and terminates affected pregnanc ies. duce a much better outcome for both mother and baby
durin g the course of the pregnancy. Such management
With th e a d ve nt of the CREIGHTON MODEL will be directed by the patient 's physician and is not the
FertilityCare™ System, one can envision a future w hen top ic of this chapter.
ali women wi ll be encouraged to chart th eir menstrual
and fertility cyc les prior to ac hi evi ng pregnancy. This
will be the primary prevention strategy as it wi ll not onl y Lifestyle Behaviors - - - - - - - - - - .
allow for avoidi ng causal factors but will also allow fo r
the identification and eventual treatment of these fac- Jf certain li festy le changes can be implemented pri or to
tors pri or to becoming problematic. the beginning of pregnancy and during pregnancy, it
can also offer an improved outcome far the pregnancy.
This chapter rev iews sorne of the basic principi es of Such factors as smoki ng, alcoho l intake, caffeine intake
preco nception a l care along with the ro le of the (in large amounts may decrease the chances of estab-
CREIGHTON MODEL System (CrMS) in implementing lishing a pregnancy and may increase the chance of
such a strategy. mi scarriage), recreationa l drug use, over use ofvitamin
or herbal supplements, and the use of va rious medica-
tions can ali be reviewed and changed if necessary.
Medical Conditions - - - - - - - - - - . There are certain types of medi cations which can be
quite harmful to pregnancy. Information on drugs that
There are a variety ofmedical condi tio ns whi ch do much might be harmfu l can be obtained from the Physicians
better iftreated properly during the course ofpregnancy. Desk Reference (www.pdr.net) o r from Reprotox
ln fact, they do their very best if they are under good (www. reprotox.org).
825
Diet and exerc ise are also important to manage prior to in the area of preconceptional cou nseling, the concept
and during the course of pregnancy. As a genera l rec- th at " potenti al pregnancy ri sks and strategies to pre-
ommendati on, wo men should be encouraged to main- ve nt them must be provided before conception" 1 is com-
ta in a balanced di et of fruits, vegetabl es , breads, meat pletely agreed to. While th e emphasis is often then placed
and dai ry products. Foods with a hi gh fa t content hould upon reducing the number of " intended pregnancies",
be reduced a long w ith a limited ca lori c intake so that a in NaProTECHNOLOGY the emphas is is p laced on se-
pregnancy-related body we ight can be attained. A n idea l lective intercourse and responsible parenthood. Se-
weight ga in of 20 to 30 pounds over the entire preg- lecti ve intercourse allows the coupl e to choose the best
nancy is a reasonable goal. time fo r ha ving intercourse during the course of the
fe rtility cycl e. In such situations, w ith adequate know l-
edge of the natura l procrea ti ve system, the coup le can
Supplementation Programs _ _ _ _~ actually begi n to make intelli gent decisions with regard
to their future procreati ve deci sions.
Ne ural tube defects such as spin a bifida, meningomy-
e locele and anenceph aly occur in about one to two per Th e CrMS provides an extraordinary set of bio log ica l
1000 1ive b irths. Th ey are seco nd on ly to the cardi ac markers (b iomarkers) w hi ch allow fo r the body to speak
ab nonn aliti es in fre que ncy. However, a 60 to 100 per- to the indi vidual. In effect, the CrMS is "an authentic
cent reducti on in the freq uency of these defects can be language ofa woman 's health andfertility. " The chal-
obtained in wo men who supplement their diet daily with lenge in NaProTECHNOLOGY is to educate wo men and
at least 0 .4 mg offo li c aci d. 2 The United States Publi c their husbands on the signifi cance of the messages or
Hea lth Serv ice has recommended the fo ll owi ng: signa ls that the body is sending to them. What other-
wise has fo r fa r too long been "asy mptomati c" and ig-
A li women of child bearing age who are capabl e of be- nored bi omarkers now become keys to the imp lementa-
coming pregnant shou ld consum e 0 .4 mg of fo lic ac id ti on of the plann ing fo r a hea lth y pregnancy.
per day for the purpose of reducing the poss ibi lity of
hav ing a fetus affected with spin a bifida or other ne ura l As wo men learn the CrMS from their FertilityCare™
tube defect. Practitioner (FCP), there are severa! things that are im-
portant. F irst of ali , they must recogni ze th at the chart-
The routine suppl ementati on of fo li e acid should ining of the vari ous biomarkers of their menstrual and
c lude at least 0 .4 mg per day. lf the wo man is obese, fe rtili ty cycl es is extreme ly important notjust fro m the
then 1.0 mg per day i recommended and if there is a " avoi ding pregnancy" po int of v iew. Thi s is, unfo rtu-
previous history or fa mil y history of ne ural tu be defect nately, the limited view of the contracepti ve mentali ty.
then 4.0 mg per day of fo li e aci d is recommended. lt The CrMS cha ll enges coupl es to think beyond contra-
should be started at least one month prior to conce p- cepti on ("o utside the contracepti on box" ). It challenges
ti on and continued during th e course of the pregnancy. them to th ink also in terms of the woman 's health and in
term s of achievin g pregnancy.
Genetic Diseases - - - - - - - -- -. The FCP can be extreme ly helpful to th e wo man w ho

has questions about w hat she is observ ing. The FCP
There are a va ri ety of di ffe rent genetic and inherited can guide her and instruct her with regard to its signifi-
biochemica l abnormaliti es which can occur. These are cance and its mean ing. When a bnormalities are ob-
rev iewed in the chapter on prenata l di agnos is. How- se rved , th e n a ph ys ic ia n s pec ifi c all y t ra ined in
ever, research needs to co ntinue not only on the pri- NaProTECHNOLOGY is the one to see so the best strat-
mary preve ntion of th ese conditi ons but al so th eir ap- egy fo r improving e ither the wo man 's health or the sub-
propriate treatment w hen they do occur. Th e person sequent pregnancy can be imp leme nted .
affli cted w ith th e di sease must be the primary concern
of these research efforts.
The CREIGHTON MODEL System in
Primary Prevention - - - - - - - ----.
Responsible Parenthood lnstruction=l
The Peak Day has been studied extensively w ith regard
W hil e it wo uld seem that there is often not mu ch phil o- to its association wi th the timin g of ovul ati on. These
sophical agreement between the current approach to re- studi es have been co ndu cted with the use of indirect
producti ve health care and that ofNaProTECHNOLOGY, honnonal para meters as we ll as observing the follicul ar
Chapter 61 : Preconceptional Ca re and the CrMS 827
growth , development and rupture with the use of serial occurred on Peak +2 and Peak + 3 ( 18.5%) (F igure 61 -2).
ultraso und. In Figure 61-1, the results of 432 follicular
ultrasound studies done at the Pope Paul VI lnstitute A very interesting add itional observation has been made
show the corre lation ofthe timing of ovulation with the with regard to the occurrence ofthese pregnancies and
Peak Day in those cycles. While the rupture ofthe fo l- the mucus cycle score during the cycle of conception .
licle occurred most commonly on the Peak Day (31.9%), Th is data is shown in Figures 6 l-3 and 61-4. When the
in 94.5 percent ofthe cycles the rupture occurred from conception occurred in ad vanee of or around the timing
Peak -2 through Peak +2. Thi s is the most studied sign ofthe Peak Day, the mucus cycle score was much higher
in ali ofnatura l fertility regulation. than those pregnancies whi ch occurred on Peak +2 and
Peak +3. When this is studied by regression analysis,
During the course ofultraso und studies ofpatients with the correlation coefficient was 0.9871 (Figure 61 -4,
infertility, a unique opportunity has occurred to study p=.0002). Thi s is an extraordinary correlation and it sug-
pregnancy from the time of conception . In the cases gests that the main fertility oflimited mucus cycles is in
observed, it was found that ali of the pregnancies oc- the immediate post-Peak phase of the cycle (Peak +2
curred from Peak -2 through Peak + 3. In addition, a pre- and Peak + 3).
ponderance ofthese pregnancies (8 1.6%) occurred from
Peak -2 through Peak + 1 while a much smaller number When a wo man begins to track her fertility cyc le there
Correlation of Peak Day To 138 Day of Conception

Observation of Day of Follicle Relative to Peak Day
Rupture As Observed By 12 2 Mean Mucus Cycle Score (CrMS)
Patients With lnfertility By (lnfertility Patients, N=40)
Serial Ultrasound (N=432)
100·
!o
i 50
2. 1 6.7 17.4 31.9 26.6 10 5.3 P-2 P-1 Peak Oay P+ 1 P+2 P+3
P-3 P-2 P-1 PEAK P+l P+2 P+3
DAY O.y ol Concep11on (Uhrasoond day ol FA)
Relativa to Peak Day
Days t Peak Day
Figure 61-1: The correlation of the Peak Day to observation Figure 61-3: The mean mucus cycle score in patients using
of the day of follicle rupture as observed in patients with !he CrMS when !he day of conception is known relative to !he
infertility with the use of serial follicular ultrasound (N = 432) Peak Day (in patients undergoing serial follicular ultrasound).
(From : Pope Paul VI lnstitute research, 2004). Patients studied were infertility patients (N = 40) (From: Pope
Paul VI lnstitute research , 2004) .
40·r .,.;;_=-=-==-=-=-=-=-=--;;;
.1-;;.6.,.,;;:-:========:::;;--;;::::::=-;;1•;-;.5::;:.,.,-_...,:=
: ;;-, Day of Conceptlon Relativa to Peak Oay
35.• 15 Mucus Cycle Seores (CrM S) R = .9871
Day of Conception Relativa to All Pregnancies In Cycle of Ultrasound Serles p = .0002
Peak Oay Pregnancies (N=401
30 Observad in CrMS Users
Cycle of U11rasound Series
lnfertüity Patients
10
P- 1 Peak Oay P+l P+2 P+3 P-2 P-1 Peak P+1 P+2 P+3
Day of Concepbon (Ullrasound day ot FA)
Relatrve to Peak Oay By Ultrasound in Cycle or Conception
Figure 61-2: Pregnancies observed in CrMS users during Figure 61-4: A regression line drawn using the mean mucus
!he course of a cycle in which ovulation was observed by cycle score (CrMS) when the day of conception is know in
serial follicular ultrasound . The graph presents the day of pregnancies occurring during cycle of follicular ultrasound
conception relative to !he occurrence of !he Peak Day in a series and correlated to the Peak Day, R=.9871 (p= .0002)
group of infertility patients (From: Pope Paul VI lnstitute re- (From: Pope Paul VI lnstitute research , 2004).
search , 2004).
30 JI 32 33 34 35
Figure 61-5: This chart is representative of several situations that may be seen in women
experiencing infertility, miscarriage , ectopic pregnancy and other related reproductive
abnormalities. A brief description of the various cycles below:
Cycle A: This 28-day cycle reveals a limited mucus cycle. The mucus cycle score
(MCS) is 1.3 (a regular mucus cycle should score 9.1 or greater) . These types of
cycles have now been shown to be associated with significan! ovarian hormone
dysfunction and a high frequency of ovulatory defects .
Cycle B: In this cycle the mucus is observed far the normal number of days but the
amount of mucus discharged is significantly reduced . The MCS is 7.0 and is classified
as intermediate limited . The same associations as in cycle A are seen in patients with
this example.
Cycle C: In this cycle there is no mucus discharge at all. The MCS is O.O. These cycles
are also associated with the same problems as cycle A but also may occur with a
target organ failu re such as surgery on the cervix. In patients with endometriosis, 77.0
percent of cycles exhibit the signs seen in cycles A-C.
Cycle D: In th is cycle , the post-Peak phase is only five days in duration . Cycles such
as this are associated with spontaneous abortion because of an inadequate proges-
teron e support of the early pregnancy.
Cycle E: This cycle shows a normal mucus cycle (MCS = 12.3) anda normal length
post-Peak phase (13 days) . These cycles can be seen in cases of oligospermia or
azoospermia .
Chapter 61 : Preconceptiona l Ca re and t he CrMS 829
100
Parcant Limitad Mucus Cycles
Th e exact percentage ofincrease is not yet known since
90 87.5
Normal Fartlllty Controls vs . lnfertllity prospecti ve studies of a large group of women with
80 by Laparoscopic Diagnosis and SAB
71.9 limited mucus cycles have not yet been undertaken.
70 64.6 65.8 The studies showing the connection between limited
;: 60 55.6 rnucus cycles, mi scatTiage and ectopic pregnancies are
so.o
~ 50 seen in those patients who actually experience those
"'
D.
40 conditions. Thus, there is need for further research in
30 this area but it is almost certain that the risk is h igher.
21.7
20 The data, to date, is strongly in that direction.
10
Another biomarker of the CrMS is prernenstrua l spot-
Controls Nonna l Pel vic Endome1riosis Ali SAB
Nonnal Pclvic Adliesion lnfcrtility lnfertil ity Laparoscopy
ting. Again, in wo men who experience infe1iility, pre-
Fertilily Jnfcrtility lnfenility Group lnfcrtility menstrual spotting is observed in about 15 percent of
N=23 Nz lO =9 Nz 79 = 114 N=32 • 16
p-.2148 p=.0960 pz.0003 p=.0001 pz.0007 p <.000 1 pati ents (Table 61-1 ). T his is significantly more corn-
% Limitad Mucus Cycles Fishcr ex.et lest
rnon than in norma l fe1ii lity controls (p=.0028). The cause
ofpremenstrual spotting is generally thought to be sub-
Figure 61 -6: Th e percent of limited mucus cycle in women of
normal ferti lity (controls) versus women experiencing infer- optimal luteal phase hormone production , espec ia lly
til ity. Th e data is outlined by the laparoscopic diagnosis and in progesterone (Figure 61- 7). However, recent evidence
those women who have had spontaneous abortions (SAB ) also suggests that, in sorne cases where hormo ne pro-
(From: Pope Paul VI lnstitute research, 2004) .
duction is normal , this might be related to low-grade
infection.
are a variety of different patterns associated with repro-
ductive abnorrna lities. These are shown in F igure 61-5 Women who ha ve limited mucus cyc les also have what
and they include such conditions as lirnited rnucu s a ppears to be an increased risk of miscarriage (F igure
cycles, dry cyc les and short post-Peak phases . If the 61-8). ln this particular exarnple, the limited mucus cycle
wornan presents with limited rnucus cycles and infertil- is associated with an immature follicle (as identified by
ity, then there is also a strong correlation with sorne follicular ultrasound) and with suboptimal estradio l pro-
underl ying organic abnom1ality (Figure 61-6). While the ducti on preovulatory and postovulatory and subopti-
exact abnorrnal ity cannot be identified from the ma l progesterone production postovulatory. The LH
CREIGHTON MODEL chart, the suspicion that such an surge, interestingly eno ugh, is completely normal. Of
abnorrnality exists is strong. For example, 64.6 percent a li hormones, the LH surge is the least sensitive to
ofpatients with endometriosis will have limited mucus preconcepti onal eva luation . The data on the mucus
cyc les and 71.9 percent of women who ha ve a miscar- cycle seores in women that achieved pregnancy when
ri age wil l have lirnited mucus cycles. the pregnancy ended in miscarriage is shown in Table
6 1-2. The MCS was significantl y decreased in the mis-
We do know that in sorne women the limited rnucus carriage gro up.
cyc les are not prob lematic. These women can achieve a
nonnal pregnancy and have a normal outcome. How- Further eva luati on of th is has been conducted by cor-
ever, this is a question of dealing with " ri sk fac tors" and re lati ng the rnucus cycle sco re with the various events
with the presence of a lirnited rnucus cycle, the risk of
one of one these reproductive abnormalities increases .
Table 61-2: Mucus Cycle Seores' in Patients of
Normal Fertility vs. Those Women who Have
Table 61-1: lncidence of Experienced a Spontaneous Abortion
Premenstrual Spotting
Normal Controls vs. All lnfertility ' Mean Mucus
Patient Populátlon n Cycle Score
Prernensfrual Spott!ng
Total · Yes " ·· ' No
Normal fertility 22 10. 35
Study Grou p · N n % n %
Spontaneous abortion 31 1 5.43' 1
Normal fertility controls 54 O O.O 54 100.0
All infertility 114 17 ~ 97 85.1
1. The mucus cycles were objectively classified using the color, consistency,
change and sensation mucus cycle scoring system (3C's MCSS).
1. From: Pope Paul VI lnstitute research, 2004. 2. p=.0028 , chi-square analysis
From: Pope Paul VI lnstitute research. 2004.
o u 12 13 14 15 16
MCS=5.7
40.0 ng/dl-+~l-+--+-+-+-+~l-+--+-~~..........,......,-.,....-.-.....-.¡..-f.....¡-._-f.--1-+--1---1-..,_ 20.0 ng/mL
30.0ng/dl....¡.--1-+--+--+-t--+--+--+-t---+--+-+-t---+--+--+-._-+--+-+-+--+--+-+l--+--+-15.0ng/ml
20.0 ng/dl+-+~l-+-+-+-+--<1-+-...H~-+-+--+--+-+- +-.i•l-+-+~l-+-+-1-10 . 0 ng/ml
5.0 ng/ml
Figure 61-7 : A woman with premenstrual spotting , a history of fou r consecutive miscarriages and a clea rl y suboptimal luteal
phase hormone profile (From : Pope Paul VI lnstitute research , 2004).
32 33 34 35
Follicle <1.0 1.18 l .~7 l. F CLC
diameter Spontaneous
(cm) Abortion
U/S
LH
Progesterone
Estradiol-17
Figure 61-8: Conception in a limited mucus cycle leading to spontaneous abortion. The ultrasound study of the follicle and LH ,
progesterone, and estradiol levels are identified . All parameters measured were abnormal including the mucus cycle with the
singular exception of the LH surge {which is normal) (From : Pope Paul VI lnstitute research , 2004) .
Chapter 61 : Precon ceptional Care and the CrMS 831
ofthe CrMS chart and fo llicular ultraso und studies. In incidence ofregular mucus cycles in Figure 6 1- 1O.
Figure 61-9, the incidence oflim ited mucus cycle is seen
by comparing the timing of the pregnancy to the Peak In Figure 61 -11 , pregnancy outcome is shown relative
Day, the size ofthe ovarian follicle just prior to rupture to both the size of the ovarian foil icle and the type of
and the type of fo lli cular rupture pattern observed at rupture pattern. lfthe fo llicle is less than 1.9 cm MFD,
the time ofthe ultrasound series is shown . Limited mu- abnormal pregnancy outcome is significantly higher.
cus cycles are much more common, as indicated earlier, The types of abnormal pregnancies include miscarriage,
in pregnancies that occur on Peak + 2 and Peak + 3. But it ectopic pregnancy and preterm delivery. Thi s is also
also associated with a follicle size which is small (less true in partial rupture cycles.
than 1.9 cm MFD) and with ovulation patterns which
are consistent with immature follicles and partial rup- This is extended further in Figure 61 -1 2 in looking at the
tures. This data is shown in an opposite form with the mucus cycle score and other parameters as they relate
to the timing of conception around the Peak Day. The
Limited Mucus Cycles by Occurrence of FR, mucus cycle score is sign ificantly reduced in pregnan-
Size of Follicle and Type of Rupture (lnfertility Patients) cies that occur on Peak + 2 and Peak + 3 even though the
Actual Pregnancies in Cycle of U/S
% Limitad Mucus Cycle % Limitad Mucus Cycle % Umiled Mucus Cycie
size ofthe ovarian fo lli cle in those cyc les is not signifi-
Occurrence ol FA Slze of Folticle T ype of Rupture
cantly different. Pregnancy outcome, overall, is also not
100
different when pregnancy occurs on Peak +2 or Peak
+3.
75.0 75.0
This is more extensively elaborated on, however, in Fig-

ure 61-13 and 61-14. In Figure 61-13 , the mucus cycle
score is associated with severa! parameters. It is shown,
for example, that not only is the mucus cycle score re-
duced in pregnancies that occur on Peak +2 and Peak
P·2 P+2 2: 1.90 <1.90 MF IFS + 3 but it is also significantly decreased in those cyc les
To P+3 CA CA
P+ l PA which revea! an immature fo lli cle or partial rupture at the
p>".0066 pc.0319 ps.0239
FR-.Follicular Rup¡ure MF..MAtur• Follicle
IFS..lnvn.ture Follide Syndtome PA.aPattillRuptUre
CRsComplete Rupl\Ke
time of ovulation. lt is significantly reduced when the
Figure 61 -9: The incidence of limited mucus cycles in preg- follicle is small and even when the cumulus oophorus is
nancies observed during the course of follicular ultrasound absent, the mucus cycle score is significantly decreased .
studies. These are identified by occurrence of follicular rup- When one looks at the outcome of pregnancies, one
ture (FR), size of ovarian follicle (mean follicular diameter) observes that while the mucus cycle score is decreased
and type of rupture. These studies were done in infertility
patients (From: Pope Paul VI lnstitute research , 2004). in the group with abnormal outcomes, it is not signifi-
cantly different from the "normal" group (a lthough the
p-va lue is very close at .0608).
Regular Mucus Cycle by Occurrence of FR,
Size of Follicle, and Type of Ruptura (lnfertility Patients)
Actual Pregnancies in Cycle of U/S
% Regular Mucus Cycle % Regular Mucus Cycle °to Regular Mucus Cycie
Occurrence al F A Sil.e of Follide Type ol Rupture Pregnancy Outcomes by Size of Follicle and Type of Rupture
100 - Pregnancies in Cycle of U/S Series
90 lnfertility Patients
Noonal Pregnancy Abnormal Pregnancy Abnormal Pregnancy
80 Outoome Outoome Oulccme
69.7 Sizeol Follicle Size of Fonide Type ol Ruplure
70 100.0
!
!f.
60
50
40
3lJ
20
P-2 P+2 2: 1.90 <1.90 MF IFS

To P+3 CA CA
P+ PA
p:.0066 p- .0319 p=.0239
FA:tFolllCUar Rup!Uftl MF• Matute Follicll CRaCompiete Rupture
IFSalmmalure Folicle Syndrome PR..Partlal Ruptura
Figure 61 -10: The incidence of regular mucus cycles in preg- 2 1.9 < 1.90 ~ 1.90 <1.90 CA PA
ps0.0023 . . ..0023 .o-0.0115
nancies observed during the course of follicu lar ultrasound AIMr euct f }&hef elCIK:t Flshet'e.ir:act
studies. These are identified by occurrence of follicular rup- Figure 61-11 : The outcome of pregnancies by !he size of the
ture (FR), size of ova rian follicle (mean follicular diameter) ovarian fol licle and !he type of rupture in pregnancies occur-
and type of rupture . These studies were done in infertility ring in women undergoing follicular ultrasound studies (infer-
patients (From: Pope Paul VI lnstitute research , 2004) . tility patients) (From: Pope Paul VI lnstitute research , 2004) .
Conception on P-2 to P+1 vs. P+2, P+3:

Occurrence of Follicular Rupture, Mucus Cycle Score,
Size of Follicle and Pregnancy Outcome
lnfertility Patients in Cycle of U/S Series
Mucus Cycle Score % Limited Mucus Cycle Size of Follicle % Normal
Pregnancy Outcome -
10 100 - 100
9 - 90
8 77.3 - 80
7
e:
Q)
~
Q)
6
a..
5
o
P-2 P+2 P-2 P+2 P-2 P+2 P-2 P+2
To P+3 To P+3 To P+3 To To
P+1 P+1 P+1 P+1 P+3
p=.0030 p= .0066 p= .6696 p=.3219
1-test Fisher exact 1-test Fisher exact
Figure 61 -12: The mucus cycle score, size of the ovarian fol licle , the timing of the
occurrence of follicular rupture and the pregnancy outcome in patients who achieved
pregnancy from Peak -2 through Peak +1 and Peak +2 throug h Peak +3 (infertility pa-
tients) (From: Pope Paul VI lnstitute research , 2004).
Mean Mucus Cycle Score:

By Occurrence of Follicular Rupture, Type of Rupture, Size of Follicle,
Presence/absence of Cumulus Oophorus, Outcome of Pregnancies
lnfertility Patients Pregnant during Ultrasound Series
Occurence of FA Size of Follicle Type of Rupture Presence/Absence Outcome of
e.o . Pregnancy
10
9 .1 8.9
9
en
~ 8
7 .2
~ 7
o 62
en
Q)6
o
() 5
"'g
::J
4
:::<
3
P-2 P+2 2:1.90 <1.90 MF IFS + Normal Abnormal

To P+3 Centimeters CA CA co co SAB
P+1 PA ECT
Prem
p=.0030 p=.0023 p=.0048 p= .0236 p=.0608
FA=Foilicular Rupture; MF=Mature Folicie; CR=Complete Aupture; IFS=lmmature Follicle Syndrome; PR=Partial Rupture;
C.O.=CumWus Oophorus; SAB=Spontaneous Aboruon; ECT=Ectopic Pregnancy; Prem=Premature Oelivery
Figure 61 -13: The mean mucus cycle score (CrMS) correlated with the occurrence of
follicular rupture, the type of rupture pattern , the size of the ovarian follicle , the pres-
ence or absence of the cumulus oophorus (CO) and the outcome of the pregnancy
(infertility patients) (From : Pope Paul VI lnstitute research , 2004).
Chapter 61: Preconceptional Care and the CrMS 833
This is furt her examined in Figure 61-14. The mucus became pregnant in cycles which eventua lly had an
cyc le score used in the comparison in Figure 6 1-13 and abnormal pregnancy outcome such as miscarriage, ec-
considered "norma l" was 8.9. However, this was a group topic pregnancy or preterm delivery to a group of com-
ofwomen with prior inferti lity who hada norma l preg- pletely norma l ferti li ty controls (patients without preex-
nancy outcome. If one compares those patients who isting inferti lity) the mucus cycle score is signi fica ntly
decreased ( 10.1 to 6.4, p=.O 133). Thus, it is reasonab le
Mean Mucus Cycle Score to conclude that a decreased mucus cycle score is as-
Normal Fertllity Controls vs. Normal and Abnorma l
Pregnancy Outcomes, Patients w ith lnfertility
sociated with an increase incidence of abnormal preg-
12 ·~------------------~
nancy outcomes.
11 Mucus Cycle Seores
10. 1
10
In Figure 6 1-15, a CrMS chart with a short post-Peak
phase (five days) is shown in association with daily
hormone levels. The short post-Peak phase is associ-
ated with an inadequate ly short luteal phase and clea rl y
short and suboptimal progesterone product ion. Thi s
situation is the classic Type 1 luteal phase deficiency
which is assoc iated clin ica ll y with a very high rate of
1·
miscarriage. With a women charting her menstrual cycles
Nonnal Fert1lity
Conlrols
Normal Pregnancy
Ou1come lnlert1hty
Abnot'mal Pregnancy 1SAB
Ou1come lnlen11lty ECT using the CrMS , one can identify in advance th is ab-
PAEM
p=Values
ps.7642
p-.0703 normality and , with appropriate therapy (HCG supp le-
mentation during the post-Peak phase ofthe cycle), the
luteal phase can be corrected anda nom1al pregnancy
Figure 61 -1 4: The mean mucus cycle score (CrMS) in nor-
mal fertili ty contro ls versus normal and abnormal pregnancy can be anti cipated (w ith progesterone supplementation
outcome in patients with infertility. The mucus cycle score in during the course of the pregnancy) .
abnorm al pregnancy outcomes (spontaneous abortion , ec-
topic preg nancy and premature birth) are significantly de-
creased fro m the normal fertility controls (p=.0133) (From :
Additional features of the CrMS charting can also be
Pope Paul VI lnstitute research , 2004). identified in advance ofpregnancy. ln Figu re 61 -1 6, a
2 3 4 s 6 7 8 1 9 l 10 l 1 12 3 14 IS 16 17 18 19 20 1 23 2 125 26 7 2 29 30 31 32 33 34 s
~ ~~~~~!, ~~ª
f f f f f f ef t
lOCL IOKL 10Kl. IOKL IOIU. IOKL \OKL >AD
""º RU; ~
Estradiol-17 ~
1 Short Post-Peak Phase 1 Progesterone
Regular Mucus Cycle
•lll
-
1 1 1
40.0 ng/dl
1
... 5 Days
20.0 ng/ml_
-
- 30.0 ng/d L
... 15.0 ng/m l_
-
...
- 20.0 ng/dl 10.0 ng/ml_
-
>- 10.0 ng/d L
... 5.0 ng/m l -
-
EM NDI R: <)RO ºR t EW K;Ht RT, >TAi iilPS ANI
-
-
r1AK 'A~ POI liTM NT FOI . "
1
... lli
• .
Figu re 61-1 5: This CrMS chart shows a very short post-Peak phase (five days) . A hormone profile was being conducted
~
during the cou rse of th is cycle and revealed a very short and suboptimal luteal phase (seven days) . Such a cycle is associated
with a very high risk of miscarriage (From: Pope Paul VI lnstitute research , 2004) .
woman w ith " frequent 2W" observations is shown. In cl inical endometritis. How thi s affects pregnancy has
this particu lar examp le, cervical cu lture revealed an E. not yet been fu lly studied but one wo uld anticipate sorne
coli infection. In Figure 6 1-17 , a similar charting pattem deleterious effect in subsequent pregnancy.
is observed but in a woman who is now pregnant. This
" frequent 2W" observation pattem was associated with
group B beta strep. Such infection is known to be harm- Final Comment ---------~
fu l to the baby at the time of delivery and with monitor-
ing of the biomarkers of the CrMS, one can identify The CrMS, with its standardized and prospecti ve data
what wou ld otherwise be considered an asymptomatic collection on the va rious pararneters of the menstrual
cond ition. With proper cu lturing and the implementa- and ferti lity cycles, offers an extraordinary look at the
tion of antibiotics, the condition can be completely pre- conditions of reproductive health prior to conception.
vented. With know ledge ofthe biornarkers of the CrMS , treat-
rnent strategies for primmy prevention can be irn pl e-
Such a condition is also observed in Figure 61 - 18 where mented with sign ificant hope for the improvement of
tail -end brown bleeding is observed. More and more outcomes. Wh il e continued research is clearly needed
evidence is suggesting that this pararneter, while on to improve our overall unde rstanding ofthese relation-
occasion being assoc iated with decreased progester- ships, the fou ndation has been la id for the impl ementa-
one production , can also be associated with a low-grade tion of this new strategy.
4 IS 16 17 18 33 34 35
"' º º º º "' º º º º º º
Frequent 2W's
®Cervical culture = E-coli
Successfully trea ted with Kefiex
Figure 61 -16: In this patient "frequent 2W" observations during the pre- and post-Peak phase of the first and Y, of the second
cycle are observed. Cervical culture revealed E. coli. lt was successfully treated with Kefl ex and the 2W observations
disappeared (From : Pope Paul VI lnstitute research , 2004) .
Chapter 61 : Preconceptional Ca re and the CrMS 835
Figure 61-17: A patient who is a 36-year-old gravida 2 para 1 with "frequent 2W" observations. She is 19.1 weeks pregnant
and cu lture revealed yeast (candida albicans) and group B beta strep. Treatment with yeast medication and penicillin reverted
her observations back to dry (From : Pope Paul VI lnstitute research , 2004) .
u 13 14 15 16 17
'1PY ~py 8P'( 8 PV 9P'( IOK IOkL -c>.D

AD AO AD AD AD AD AD
Figure 61-18: These three cycles reveal tail-end brown bleeding (TEB) or black bleeding in a woman with infertility and
endometriosis. Al D&C , the endometrium revealed retained fragments of necrotic endometrial tissue. This is thought to be, at
leas! in part, dueto suboptimal production during the previous luteal phase . More recen! study also indicates that this may be a
sign of chronic endometritis which might be amenable to anlibiotic therapy. lf such a condition occurs in advance of pregnancy
it could potentially result in adverse outcomes (From: Pope Paul VI lnstitute research , 2004) .
1. Cunningham FG, Gant N F, Leveno KJ , Gil srrap LC, Hauth 2. Bayer SR, Alper MM , Penzias AS: Th e Boston IVF Hand-
JC, Wenstrom KD : Willi ams Obstetr ics 2 1" Edi ti on. book of ln ferti lity. Parthenon Publi shing Group Boca Raton
McGraw-Hill. New York, 200 1. 2002.
Part VI:
8ut~ NaProTECHNOLOGY
Thomas Hilgers, M.O. ".. .this is a surgical technique which requires patience on
Chapter 62
the part of the surgeon and meticu/ous attention to detail.
These surgical procedures will general/y be somewhat
/onger than the procedures to which the gyneco/ogist is
accustomed. "
837
838
What is Surgical NaProTECHNOLOGY?
is in this area that surgica l NaProTECHNOLOGY has its

A bout 30 years ago, the American Board ofübstet-
rics and Gynecology approved three new
subspecia lties in the field of obstetrics and gynecol-
major focus.
ogy. These subspeci alties were gynecolog ic oncology, Surgical NaProTECHNOLOGY is a specialized form of
peri nato logy and reproductive endocrinology. lt was gyneco logic surgery whose primary aim is to recon-
the hope when these subspecialties were developed that struct the uterus, fa llopi an tubes and ovaries in such a
they would advance those three areas ofwomen 's health. way that pelvic adhesive di ease can be eliminated and
not caused by the surgical procedure itself. lt is, in a
As one looks back on the development ofthe reproduc- sense, a "near adhesion free" form of surgery.
tive endocrinology tra ining programs, they ori ginally
started with an emphasis on pelvic surgery. However, in One ofthe best examp les of a surgical procedure which
1978 when the first baby was bom by in vitro fertiliza- has been lost in the transition to in vitro fertilizat ion, is
tion (IVF), the spec ia lty changed dramatically. Its focu s ovarian wedge resection. This is a procedure, which
over the last 25 years ha been on the development of many years ago, carried with it 70 percent pregnancy
the ski ll s needed for IVF. As a result, many younger rates . However, it was well known to be assoc iated with
reproductive endocrinologists do not, at this time, ha ve a high incidence of the formation of pelvic adhes ions .
the surgical skilis necessary to do sorne basic and most As a result, when clomiphene citrate became avai lable
advanced reconstructive pelvic surgeries. in the middle l 960s, this procedure was ali but aban-
doned becau e of the stated reason that it was signifi-
Over a decade ago, the Society of Reproductive Sur- cantly adhesiogenic. And yet, the pregnancy rate fol-
geons, a gro up within the American Society for Repro- lowing clomiphene therapy was significantly less than
ductive Medicine, began to recognize this deficiency that associated with ovarian wedge resection. Further-
and foster the development of postgraduate fellowship more, ovarian wedge resection made a major contribu-
programs which would ha ve as one of their major em- tion to the long-term treatment ofsome ofthe endocrine
phases, training in pelvic surgery, microsurgery, laser and menstrual cyc le abnormalities associated with
surgica l appl ications, and so forth. The e training pro- women who have polycystic ovaries. The use ofc lomi-
grams ha ve grown slowly over the past 1Oyears, but it phene citrate has no such long-lasting effect. More re-
839
cently, in vitro ferti li zation has been utilized for this surg ica l requirements , a specia l interest and dedi cation
purpose, and yet, the pregnancy ra tes are even lower to these surgica l princ ipi es is stro ng ly recommended.
and the health benefits absent.
In the meantime, a good dea l ofprogress has been made Selection of Patients - - -- ------,
in the preventi on of pe lvic adhes ions. Work done at the
Pope Paul VI lnstitute and by others has now shown In reviewing the surg ica l procedures of the Pope Paul
that ovarian wedge resection can be done in such a way V I lnstitute, approximately 60 percent of those patien ts
that it not only carries with it hi gh pregnancy rates, but who have endometri osis will be a bl e to have a correc-
also is associated with a ve ry low incidence ofthe for- tive surg ical procedure w ith lase r at the time of their
mation ofpelvic adhes ions. In add iti on, it ca n be done diagnostic laparoscopy (F igure 62- 1). What type of sur-
thro ugh a fairly small surg ica l incision w ith a low in ci- g ica l procedure is used wi ll de pend upon the ex tent to
dence of surgica l compli cation s anda good deal to be whi ch the pe lvis is in vo lved with endometrios is and
ga ined from its positi ve endocrine effects . Thus, surgi- adhes ive disease. In stage I endometriosis, 85.6 percent
ca l NaProTECHNOLOGY is an important deve lopment were treated by lase r laparoscopy whi le ali ofthose with
in the field ofreconstructive pelvic surgery with its major stage IV endometriosis were treated with laser laparo-
emphas is on adhes ion preventi on. lt is an extraordin ar- tomy.
ily satisfying surgica l invo lvement although it does re-
quire a commitment to excellence, patience, anda desire In prepari ng patients for di agnosti c laparoscopy, it is
to prov ide reconstru ctive pe lvic procedures that are important to di scuss with them the goa ls and obj ec-
accom pli shed without major adhes ion format ion . tives ofthat proced ure. In surgical NaProTECHNOLOGY,
the main goa l is to make a good di agnos is. The second-
Ln many ways, this portion ofNaProTECHNOLOGY has ary goa l is to treat it effect ive ly at the tim e of the
been deve loped within the standard practice of gyne- laparoscopy. Wh en it is treated effective ly, the goal is
co logic pelvic surgery. However, there are very few pro- to do it in such a way so that there is the greatest oppor-
gra ms around the United States that actua lly impl ement tunity fo r the di sease to be rem oved, with a limited ex -
the strategies in vo lved in thi s surgica l subspecialty. lt posure to the fo rmatio n of adhes ions. Thus, it is un-
is not that so me brand new way of perfom1ing a urgical u ual to combin e the di agnosti c lapa roscopy wi th a
procedure has now been invented . Rathe r, it is a urgi- major surg ica l procedure. The one exception to thi s is
cal subspecia lty which has been refi ned by incorporat- the pati ent who requires an ovarian wedge resecti on in
ing a number of different but current ly available appli - a situati on where this is the only di sease process present
cations, w hi ch have as the ir end result, the prevention or there is j usta limited amount of endometrios is that
of pel vic adhesive di sease. can be laser va pori zed at the time of the laparoscopy.
Combining those two surgica l procedures is not too
This section of thi s textboo k is devoted to bring ing to comp lex or d ifficu lt from a schedu li ng po int ofv iew.
the fo refront th e techniques in vo lved in s urg ica l
NaProTECHNOLOGY so that gyneco logic and genera l There are severa! difficulties in conn ecting a di agnosti c
surgeons can be trained to pro perly perform them. laparoscopy with a major surgica l procedure in surg ica l
NaProTECHNOLOGY. The first ofthese is the length of
time it takes to do the major surgica l procedure. These
Qualifications of the Physican ---~ procedures can often take three or four hours (some-
times longer) and when comb in ed with a di agnos ti c
A ph ys ic ia n w ho e n gages 1n su rg ica l lapa roscopy, can make the entire surgical procedure too
NaProTECHNOLOGY shou ld be, at the very least, be a long. One of the major prob lems is the p lann ing that
board-certified obstetrician-gyneco logist with a very goes into most of these surgica l procedures, inc lud ing
spec ial interest in these surg ica l applications. A board- such th ings as bowe l prep and advanced di scuss ion
certified general surgeon with these interests wo uld also abo ut the nature of th e surg ical procedure and the com-
be basicall y qualified . In both cases , additi onal exper- pli cations with w hi ch it might be associated. Thus, it is
tise in the use of laser (KTP, d:YAG, and C0 2 laser) and the practice at the Pope Paul VI 1nstitute to do the di-
in microsurg ica l appl ications is a lso necessary. Com- agnostic laparoscopy and if laser laparoscopy cannot be
pleting continuing medi ca! educati on instruct ion is im- perfom1ed at the same time, then the procedure is video-
portant and , in th e future, obta ining added experi ence ta ped and the patient is scheduled fo r a laparoscopy re-
through a surgical NaProTECHNOLOGY fe llowship will view (comprehensive management review) (Figure 62-2).
be very he lpful. In addition to these basic medi ca! and
Cha pter 62 : What is Surgical Na ProTec hnology? 841
Type of Surgical Treatment for Endometriosis - Laser laparoscopy

by Stage of Endometriosis (N=457) c=::J Laser laparotomy
100.0
100
90 85.6
82.4
80
70
60 58.3
e:
Q)
....
()
50
Q)
o.. 41. 7
40
30
20 17.6
14 .4
10
O.O
o Stage 1 Stage 11 Stage 111 Stage IV
Endometri osis Endometri osis Endometri os is Endometri os is
Figure 62-1 : This bar graph shows the type of surgical procedure selected for the treatment of endometriosis according to the
stage of endometriosis .
At thi s vis it, usually lasting 45 to 60 minutes in dura- ment can be developed and exp lained to the patient.
tion, the entire nature ofthe patient's case is presented From this review, the recommendation of the physician
to them from the point of view ofNaProTECHNOLOGY is made, discussion with the patient is undertaken and
and what it can offer the patient in terms oftreatment. lf questions are answered.
further surgery is contemplated, then a comp lete dis-
cussion of those surgical procedures and the poss ibl e
comp lications are also presented. Planning the Surgical Approach _ _-----.
At this laparosco py review, the videotape of the Whi le the major emph asis over the last 10 to 15
laparoscopy is viewed with the patient (even if major years in gyneco log ic su rgery has been placed on
surgery is not contemp lated, the laser laparoscopy is operative laparoscopy, the emphas is in surgica l
shown to them). The results ofthe selective hysterosa l- NaProTECHNOLOGY is on adhesion preventi on. lt has
pingogram are also rev iewed. The CREIGHTON MODEL been shown that one can prevent ad hes ions better when
chart is rev iewed for vari ous biomarkers which are im- undertaking major operative efforts with the abdomen
portant to be resolved relative to their infertility or mis- open and there is an ab ility to work directly with the
carriage hi story and a review of the entire endocrine tissues, particularly to reapproximate and repair the tis-
eva luati on is undertaken. sues once the pathology has been removed. In plan-
ning for the surgica l procedures, thi s is one of the most
The ultraso und evaluation of ov ul at ion is then dis- important aspects in vo lved in considerations with sur-
cussed and presented to them and if there are abnor- gical NaProTECHNOLOGY.
maliti es, that is presented in the context of the entire
probl em. Additional factors such as the results of en- There are a number of surgica l procedures whi ch can be
dometri al or endocerv ica l biopsies, the results of the done as a combined approach. For example, many women
semin al fluid analysis and other factors are also then with po lycystic ovarian disease also ha ve endometrio-
presented. By placi ng this into its tota l context at one sis. In those cases, th e endometriosis can be laser va-
visit, a comprehensive approach or strategy for treat- porized at the ti me of the laparoscopy and the ovarian
LAPAROSCOPIC REVIEW
Comprehensive Management Review
6901 Merey Road • Omaha, NE 68106 • Ph# 402-390-SSOO • Fax # 402-390-9851
Patientname: _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ Date: _ _ _ _ _ _ _ _ _ _ __
l. Laparoscopy
Date: _ _ _ _ _ _ _ _ _ _ __
Findings: _ _ _ _ _ _ _ _ _ _ _ _ _ __ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
Tubal patency: bilateral Y N; right Y N; left Y N
11. Gynecological Charting Record (CrMS)
111. Endocrine Evaluation
IV. Ovarian Cyst Evaluation (OCE)
V. EndometriaVendocervical Biopsy
VI. SFA Summary
Vll.Other (SHSG, HSG, PCT, etc.)
VIII. lmpressions IX. Treatment Recommendations

1. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ 1. _ _ _ _ _ _ _ _ _ _ _ __ _ __
2. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ 2. _ _ _ _ _ _ __ _ _ _ _ _ _ __
3. _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ 3. _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
4. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ 4. _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
5. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ 5. _ _ _ _ _ __ __ _ _ _ _ _ __
D1scussed 1n deta1ls. Yes No Physician's signature: _ _ _ _ _ _ _ _ _ _ _ _ _ _ __

Date: _ _ _ _ _ __
Figure 62-2: This is the form used during the course of the laparoscopy review (Comprehensive Management Review) at the
Pope Pau l VI lnstitute.
Chapter 62 : What is Surgical NaProTechnology? 843
wedge resection can subsequently be performed undergo a bowel preparation. There are a variety of dif-
through a small transverse incision. Whenever the dis- ferent bowel preps that are available and one should be
ease is located more anteriorly, it can usually be done chosen that is good at preparing the large bowel and
through a fair ly small incision. An ovarian wedge resec- the terminal ileum .
tion is an excellent example ofthis because the ovaries
are very accessible through such an incision . After this discussion has occurred with the patient, the
surgery is then scheduled and any incidentals with re-
Another example might be a patient who has peritoneal gard to the surgical procedure, idiosyncrasies that might
implants of endometriosis deep in the posterior cul-de- be important to this particular surgery, need to be re-
sac which lend themselves very nicely to laser vapor- viewed with the operating room staff so they are ad-
ization, but also has an ovarian endometrioma on one or equately prepared. Being organized in advance of the
both ovaries. In this case, laser vaporization can be surgical procedure is critica! to its successfu l comple-
undertaken by laparoscopy and the subsequent proce- tion. This involves not only the surgeon, but the
dure on the ovary can be performed through a small surgeon 's assistants, scrub tech , circulating nurse, and
incision. Because the ovaries are very accessible, the anesthes iologist if necessary.
endometriosis can be removed and the ovaries repaired.
In such a fashion, the procedure carries with ita similar By attending to the various details of the surgical pro-
postoperative recovery to that of an operative cedure, a procedure can be planned which will accorn-
laparoscopy. Such a procedure is not much different plish the two goals of removing the diseased or patho-
from having an appendectomy through a small incision. logic abnorma liti es and doing it in such a way so that
These patients do extremely well , recuperate their bowel adhesions are not fom1ed. If a second-look laparoscopy
function quickly, are moving in a short time, and usually is necessary to remove a Gore-Tex surgica l membrane,
return to work within two to four weeks. that also needs to be scheduled and discussed w ith the
patient.
On the other hand, ifa patient has extensive endometrio-
sis which requires excision from deep in the posterior In surgical NaProTECHNOLOGY, once again , the goal
cul-de-sac, then a larger Pfannenstiel incision is clearly is " near adhesion-free" surgery while at the same time
necessary. These two types of incisions are demon- removing the disease that is present. lt is a form ofsur-
strated in Figures 62-3 and 62-4. In these patients, it is gery which is in sorne ways similar to plastic surgery
absolutely essential that one gets good exposure in or- because of its goal to reconstruct the pe lvic tissues in
der to work effectively deep in the posterior cul-de-sac, such a way that they resemble tissues that have never
which is one ofthe deepest cavities in the body. lnstru- been adverse ly affected . While we are not entire ly ca-
ments need to be selected that are fine-tipped and long pable of doing this in a li cases, in nearly ali cases we are
so that they reach the curvature ofthe posterior pelvis. able to approach it. And in those cases, the overall sih1-
ation will be greatly improved. The surgical challenges
Ifthe patient has any involvement ofthe rectum or sus- are exciting and what can be accomplished to assist the
pected involvement of bowel , then the patient should patient is extremely satisfying.
Figure 62-3 : This is a small Pfannenstiel incision made far Figure 62-4: This is a larger Pfannenstiel incision used far
surgical procedures that are in the anterior portian of the pelvis. more extensive surgical NaProTECHNOLOGY procedures and
especially !hose procedures where one is working deep in the
pelvis.
Diagnostic Laparoscopy:
"Near Contact" Approach
D iagnostic laparosco py is an important tool in the

armamentarium of one who is interested in estab-
lishing so und diagnoses and constructing treatment
laparoscopy. The two ski li s are quite different.
lt has been shown that using th e magnification of the

plan s for va ri ous women 's hea lth problems. However, laparoscope for a close-up view can improve one's abil-
to become a good diagnostic laparosco pi st requires ity to detect va rious conditi ons . 1 Redwi ne introduced
good didacti c training, experience with repetition , and the term " near-contact" laparoscopy (NCL) .2 The au-
an interest in using laparoscopy for diagnostic pur- thor has used this approach for over 20 years and the
po ses. purpose of thi s chapter is to describe that technique in
greater detail so that the young surgeon can advance
Over the last 20 year , the skill in diagnostic laparoscopy the ir skili s in this area . This chapter will be di vided into
has improved significantly beca use ofthe work of indi - two areas of consideration. The first wi ll be a few tech-
vidual s such as Gold tein , 1 Redwine 2 and Marti n.3 How- nical considerations that the author fee ls to be extremely
ever, there continues to be performed laparoscop ies helpfu l in conducting NCL and the second part is a
where the potential for the di agnostic tool is not being description ofthe technique ofNCL.
fulfilled. The author has observed on a number ofocca-
sions a diagnostic laparoscopy that had been consid-
ered norma l but, when it was repeated, a high incidence
Table 63-1: Repeat Laparoscopies when
of abnormaliti es was identified. Table 63-1 presents 46
Previous Laparoscopy Considered Normal1
such cases. ln 41 of them (89 . 1%), endometriosis was
( =46)
fo und on the repeat laparoscopy. In 2 cases, ad hesive
disease was identifi ed (4.4%) and , in 3 cases (6.5 %),
normal pelvic anatomy was identified .
With endometriosis 41 89 .1
With adhesive disease 2 4.4

lmproved training in diagnostic laparosco py for indi -
Normal pelvis 3 6.5
v idu a l pra ct ition ers is n ecessary. Experience in
laparoscopi c sterili zations from a res idency program is 1. First laparoscopywas performed elsewhere. The repeatlaparoscopy
in adequ ate fo r s ubseq uen tl y perfo rmin g diagnostic was performed by the author.
845
Technical Considerations _ _ _ _ _~
This chapter will not thoroughly describe how to con-

duct a laparoscopic procedure. lt is presumed that the
reader airead y has those ski lis or is in a position to be
learning those ski lis. However, the following technical
considerations have been found to be extremely helpful
in conducting this diagnostic procedure and it is hoped
that the young surgeon may benetit from this input.
First of ali , a uterine manipulator should always be

used when conducting a diagnostic !aparo copy. This
manipulator must be one wh ich provides the abi li ty to
significantly mobilize the uterus so that the various crev-
ices ofthe pe lvic cavity can be eva luated. In fact, uter-
ine manipulators are often not very well chosen . The
manipulator recommended in this textbook is the one
shown in Figure 63- 1 (The 1 Endopath uterine manipu-
lator with sound dilator - 7-cm tip length ; Ethicon Endo-
Surge1)', !ne.). This manipulator allows for excellent
mobility ofthe uterus and the ability to place the utero-
sacral Iigaments on stretch i f doing laser laparoscopy.
The second technical consideration , which has been

found to be extreme ly helpful , is one used to elevate the
abdominal wall far trocar entry . This technique has
been previously described 4 but has been modified some-
what with experience and it will be described further
he re.
Laparoscopy is a blind surgical procedure in which a

sharp trocar is inserted into the abdominal cavity. One
of the complications which one should work towards
preventing, ifat ali possible, is injury to bowel or major
blood vessels as the result of entering the abdomen
with the trocar. A number of techniques ha ve been de-
scribed for this purpose. The first technique involves
Figures 63-2 through 63-4 : Techniques for elevating the

anterior abdominal wall for insertion of the Veress needle or
the trocar. In 63-2 , the lower abdominal skin is elevated with
the surgeon 's hand . In Figure 63-3 , towel clamps or Allis
clamps are placed periumbilically for elevation of the anterior
abdominal wall . In Figure 63-4, two medium Kocher clamps
are placed on the anterior rectus sheath for elevation of the
anterior abdominal wall .
Figure 63-1 : A uterine manipulator which is accompanied by
a sound dilator, 7-cm tip length (1 Endopath , Ethicon Endo-
Surgery, lnc.).
Chapter 63 : Diagnostic Laparoscopy: "Near Contact" Approach 847
graspin g the lower abdomina l wall with an operating

hand and physically lifting it as the trocar is inserted
(F igure 63 -2). Another is to grasp the periumbilical re-
gion with towel clamps or Ali is clamps and lift on the
abdominal wall as the trocar entry is occurring oras the
Veress need le is inserted (Figure 63-3). The technique
used by the author is illustrated in Figures 63-4 and 63-
5. After a smal l horizontal or vertical infraumbilical inci-
sion is made, a medium Kocher clamp is used to bluntly
di ssect free the subcutaneous tissue and make access
to the anterior rectu s fasc ia. Verification ofthe position
on the anterior rectu s fascia is obtained by manual pal-
pation through the incision with the index finger. The
Kocher clamp is then placed on the anterior rectus fas -
cia and the anterior abdominal wall is elevated. A sec-
ond Kocher clamp is then more securely placed just
caudal to the first clamp whi le the first clamp elevates
the abdominal wa ll. Once the second clamp is placed in
this fashion, the first clamp is then repositioned to ob-
tain a secure hold on the anterior rectus fasc ia. With
both Kocher clamps securely in position in th is fash-
ion , the abdominal wa ll can then be placed on strong
traction and a 12-mm disposable, protective trocar is
then in erted easil y without difficulty. Whi le the origi-
nal description of thi s technique continued to use the
Veress needle and sa line technique, in the overwhe lm-
ing majority of cases, that technique is not necessary
when elevating the abdominal wa ll in this fashion and
direct entry with the trocar can be safe ly accomp li shed .
The abdomina l wall can be elevated much hi gher with

the use of th is latter technique. Keeping in mind that
the parietal peritoneum is attached underneath the rec-
tus musc le and fascia, by placing the clamps directly on
the fascia and elevating the abdominal wa ll , the perito-
neum comes with it. This is demonstrated in Figures 63-
Figures 63-6 through 63-8: Visualization of !he bowel af-

ter a 12-mm infraumbilical trocar has been placed . In 63-6, no
elevation of !he anterior abdominal wall is being undertaken
and !he bowel is observed al !he tip of !he trocar. In 63-7 , !he
bowel continues to be observed even with elevation of !he
anterior abdominal wall with !he surgeon's hand . In 63-8 , a
space opens up with !he elevation of !he anterior abdominal
wall using Kocher clamps on !he anterior rectus sheath.
Figure 63-5: A demonstration of !he placement of the Kocher
cla mps on !he anterior rectus sheath after a small infraumbilical
incision has been made in preparation for placement of !he
tro car.
6 thro ugh 63-8. In Figure 63 -6, the bowel is immedi ately avo ided . T hi s is demonstrated in Figures 63 -9 and 63 -
underneath the trocar. Th is view is with no elevation at 1O. Whi le it is not common to deve lop difficulties or
ali. [n Figure 63-7, the elevation is prov ided by grasping problems when plac ing the trocar supra pubica lly, it can
the lower skin ofthe abdominal wa ll in the m idlin e and happen and occasiona lly can cause signifi cant hemato-
apply ing up wa rd tracti on. Aga in , the peri to neum has mas. Thi s techniq ue of transillu minati on is even more
not been ra ised very much and the bowe l is present importa nt w hen pl ac ing larger trocars in the left and
immediately under the troca r. However, in Figure 63 -8, right lower quadra nts w here blindly striking a b lood
usi ng the Koc her's on the anterior abdomi na l wa ll, a vessel is a more common pro bl em and is often more
space is developed between the pari etal peritone um and significan t.
the bowel a ll owing fo r the troca r to enter w ithout caus-
ing damage. F in a ll y, a probe mu st be used w ith a li di agno tic
laparosco pi es thro ugh the 5-mm sup ra pubi c trocar. In
A suprapubi c probe sho uld be used in ali cases of d i- addition, the ab ili ty to irrigate and sucti on must be ava il-
agnostic laparoscopy. Thi s is acco mplished by mak ing ab le. T hese two capabi liti es can be acco mp lished with
a small tran sverse inci sion just above the symph ys is the same instrument. Us ing a curved, blunted suction
pubis and pl ac ing a 5-m m retracti ble trocar thro ugh that irri gator (s uch as that demonstrated in Figure 63 -1 1)
incision and into the abdom inal cav ity under di rect vi- attached to a sucti on irrigati on tubing set (accompa-
sua li zation. However, prior to inserti ng that troca r, the nied by a battery pump), one can acco mpli sh exce ll ent
lower abdomina l wall should be transilluminated so irri gati on with lactated Ringer so lution and exce ll ent
that b lood vesse ls ca n be identi fted an d hopefu lly suction (Figure 63- 12). Whi le one wo uld th ink that a
pro be wo uld a lways be used in di agnostic la parosco py,
it has been observed that d iagnosti c lap aroscopy is
occas ionally perfo rm ed without such a probe. Such an
ap proac h is not appropriate laparosco pi c technique fo r
the purpose of di agnos is.
Near Contact Laparoscopy (NCL) _ _~
In co nducting good di agnostic la paroscopy, it is ve ry

important to be organi zed in th e approach by w hich
yo u v iew the pe lv ic ti ssues. 1t is best fo r the surgeo n to
develop a technique which is rou tine so th at each
la paroscopy is performed in the same sequence. A se-
quence shou ld be chosen that allows fo r observation
Figures 63 -9 and 63-1 O: Tran si llumination of the lower an-

teri or abdominal wa ll , suprapubically (Figure 63-9). In thi s Figure 63-11 : This demonstrates two different types of suc-
way, blood vessels can be identified and , when the suprapu- tion irrigators. The one on the left has a sharp circular tip. lt
bic trocar is inserted (Figure 63-1 O), !hose blood vesse ls can should be avoided. The one on the right has a blunt, ro unded
be avoi ded . Th is technique is also importa n! when placing tip and ca n be used safely as both a probe an d a suction
troca rs in the left and right lower quadrants. irrigator. These are manufactured by Circon Cabo!.
Chapter 63 : Diagnostic Laparoscopy: "Near Contact" Approach 849
ofall tissues within the pelvis along with the appendix ,

cecum , tern1inal ileum and rectosigmoid co lon . Such an
approach is illustrated in Figure 63-12. In this way, the
entire uterus, both t1.1bes and ovaries, the broad ligaments,
lateral pelvic walls, uterosacral ligaments, posterior cu l-
de-sac, anterior cul-de-sac, posterior bladder, appendix,
cecum, terminal ileum and rectosigmoid colon can be
evaluated. If one learns and adapts a routine sequence,
importan! findings will not be missed (Figure 63- 13).
In the " near-contact" approach, a general visualization

of the pelvis is undertaken upon initial entry into the
abdominal cav ity and after the bowel has been maneu-
vered cephalad (while the patient is in the moderately
Figure 63-12:This is a suction irrigation set with a battery steep Trendelenburg position). This is illustrated in Fig-
pump (Surgiflex WAVE XP-ACMI Corp., Southborough , MA) . ure 63-14. Jf the laparoscope continues to be at that
distance from the pelvic tissues, then significant pa-
thology will be routinely missed. In the "near-contact"
approach , the scope is brought closer to the tissues so
that magnification of the tissues can be obtained. lt is
suggested that this be accomplished both visuall y and
then subsequently with a video camera to magnify it
even further on a video monitor.
Using this technique, the surfaces of the peritoneum,

the various ligaments within the pelvis, both ovaries,
fallopian tu bes, both proximally and distally, the latera l
pelvic wall s and posterior broad ligaments, both utero-
sacral ligaments, the anterior rectum and posterior cu l-
de-sac, the areas latera l to each fallopian tube on the
antero lateral abdom inal wa ll and the area anterior to the
uterus and posterior to the bladder can ali be evaluated
closely. The appendix, cecum, terminal ileum and rec-
tosigmoid colon must also be evaluated. These steps
are ali illustrated in Figures 63-15 through 63-38.
Figures 63-13: In this diagram , an orderly sequence for evalu-

ation of the pelvis tissues, which is essential to doing good
diagnostic laparoscopy, is illustrated . The technique used in
this text, which is illustrated further in Figures 63-14 through
Figure 63-43 begins at the left posterior fundus and proceeds
in a clockwise, somewhat spiral fashion around to the right
and circulating in the way illustrated. In this way, if this be-
comes routine, the abi lity to miss importan! diagnostic fea-
tures of the pelvis, is significantly reduced . The surgeon should
choose sorne means of proceeding in every diagnostic
laparoscopy with a systematic, routine approach that care-
fu ll y evaluates all of the tissues within the pelvis, including
the appendix , cecum , terminal ileum and rectosigmoid colon .
Figure 63-14: After the bowel has been teased cephalad

and the patient is in the moderate Trendelenburg position , a
distan! view of the uterus, tu bes and ovaries can be ob-
tained . This is the beginning of the diagnostic laparoscopic
procedure .
Once the diagnostic procedure has been completed ,

then indigo carmine dye can be injected through the
uterine manipulator to see if one can demonstrate tuba]
patency (Figure 63-39 and 63-40). As the di agnostic
procedure is conc luding, the posterior cu l-de-sac can
be filled w ith Ringer 's lactate from the irrigation system
and th e distal fa llopian tubes can be immersed in the
Ringer's lactate and a good evaluation of the fimbria
can be undertaken (Figure 63-41 ). Finally, the upper ab-
domen looking at the liver, ga llbladder, the ligament of
Treitz and upper po1tion of the bowel can be viewed
(Figures 63-42 and 63-43). However, the young urgeon
should be reminded that diagno tic laparoscopy from a
gyneco log ic perspective must focus on the pelvic or-
gans and tiss ues . Too ofte n, the upper abdomen has
been the focus of a diagnostic laparoscopy and abnor-
malities ofthe pelvis have gone unnoticed.
Using the NCL technique can ignificantly improve the

ab ili ty of the diagnostic surgeon to evaluate and ob-
serve pelvic changes , which relate to the patient's pel-
vic pain, dysmenorrhea, or fe1tility-related problems
Figures 63-17 through 63-19 : In this closer view of the

distal end of the right fallopian tube (Figure 63-17), peritubal
cysts can be identified. The lateral portien of the right ovary is
closely viewed in Figure 63-18 and the medial surface is
viewed in Figure 63-19 after it has been elevated with the
use of the suction irrigator probe. In this fashion , a close
evaluation of the ovary can be obtained .
Figures 63-15 and 63-16 : The scope is placed closer to the
tissues and magnifies the left tube , the left ovarian ligamen!
and the left posterior fundus in Figure 63-15 and the same
stru ctures on the right side in Figure 63-16 .
Chapter 63: Dia gnostic Laparoscopy: "Nea r Contact" Approach 851
(s uch as infertility, recurrent mi scarria ge, and irregular

cycles).
This chapter has reviewed the " near-contact" approach

to diag nostic laparoscopy. The techni que has been de-
scribed , but in orderto comp letely fulfill the potential of
this approach to diagnostic laparoscopy, the reader is
referred to Chapter 64, Visual Appearance of En-
dom etriosis, and Chapter 65 , Atlas ofFindings in Diag-
nostic laparoscopy.
Figures 63-23 and 63-24: In Figure 63-23 , a series of small ,

darkened , pin-point lesions can be observed jusi medial to
the left uterosacral ligamen! as that ligamen! is retracted with
the probe. Upon closer evaluation in Figure 63-24 (NCL), these
are identified definitive ly as areas of endometrios is which
would be easily missed if the "near contact'' approach was
Figures 63-20 through 63-22: In this series, the right lateral not used .
pelvic wall and posterior broad ligamen! are observed (Fig-
ure 63-20) and deeper in the posterior cul-de-sac on the right
side Figure 63-21 . A closer view in Figure 63-22 reveals two
small vesicular lesions deep in the posterior cul-de-sac on
the right side .
Figures 63-29 through 63-31: In this sequenee, the distal

end of the left fallopian tube is observed with a peritubal eyst
attaehed to it (Figu re 63-29). Th e lateral aspee! of the left
Figures 63-25 through 63-28 : In this series, the left utero- ovary (Figure 63-30) and the medial aspee! of it (Figure 63-
saeral ligamen! is observed and a small peritoneal defeet is 31) are observed.
identified (Figure 63-25). As one brings the seope eloser in
Figure 63-26 and then 63-27 , a small peritoneal defeet is
observed within that original defeet. Later, as this lesion was
opened with laser, a lesion of endometriosis was observed
within that peritoneal poeket. In Figure 63-28 , a small blaek
lesion of endometriosis is observed jusi above the left ureter.
Chapter 63 : Diagnostic Laparoscopy : "Near Contact" Approach 853
Figures 63-32 through 63 -34: In this series , a most distan!

view of the anterior uterus and posterior bladder is observed
(Figure 63-32). As the scope is brought closer to the left
posterior bladder and anterior uterus (Figu re 63-33) and the
right posterior bladder and anterior uterus (Figure 63-34 ), a
closer evaluation of these tissues can be obtained . At times,
the scope can be brought even closer !han these photo- Figures 63-35 through 63-38 : In this sequence, the scope
graphs show and lesions can be identified . is now brought up to the area of the appendix and the appen-
dix is viewed (Figure 63-35). The cecum is then evaluated
(Fig ure 63-36) and various aspects of the terminal ileum are
also evaluated (Figure 63-37 and Figure 63-38). In this se-
quence, the tissues are normal.
Figure 63-41 : In this figure , the posterior cul-de -sa c has

been filled with Ringer's lactate . The distal tube is immersed
and the scope is placed under water. With this technique, the
fimbria float apart from each other and it is the only way that
a good view of the fimbria in this fashion can be obtained .
The fimbria in this photograph look quite normal.
Figures 63-39 and 63-40: Thi s is a close-up view of the

indigo carmine dye seen spilling from the distal end of the
right (Figure 63-39) and left fallopian tubes (Figure 63-40).
Figures 63-42 and 63-43 : In this view, the upper abdomen is

being evaluated . Here the liver and the falsiform ligamen! can
be observed to be completely normal.
1. Go ld ste in DP, C ho ln o ky C D, Emans SJ : Ado lesce nt En- 4. Hilgers T W: A S impl e, Safe Techn ique for Pl acement o f the
do metrios is. J Adol Hea lth Ca re 1:37-41 , 1980 . Ve ress Need le an d Troca r in Laparoscopy. J La paro Endo
Surg 4: 189-192, 1992.
2. Red win e DB: Th e Di stribution o f Endometri os is in th e Pe l-
v is by Age Gro ups and Fertility. Fen il Steril 4 7: 173 -1 75, 5. Batt RE, Wh ee ler JM : Endometri os is: Adva nced Di agnost ic
1987 . Laparoscopy. In: Atl as of Fema le Fertility Surgery. Hunt RB
(Ed) Second Ed iti on. Mosby-Yea r Boo k ln c., St. Lou is, MO,
3. Man in DC, Redwine DB , Reic h H, Kresch AJ: Laparoscopic
1992.
Appea ran ce of End ometri os is: Co lor Atl as . Second Editi on.
Resu rge Press, Mem phi s, TN, 1990 .
Visual Appearance of
Endometriosis*
ndometriosis has often been de scribed as a tal , Kingston, Pennsylvania; and Dr. Arnold Kresch (de-
E "powder burn" appearing lesion on the surface of
the peritoneum. However, this disease has multiple dif-
ceased), Stanford Uni versity Medica! Center have made
major contributions to our better understanding of the
ferent appearances to it. The individual who is inter- visual appearance of endometriosis.
ested in treating endometriosis must be thoroughly fa-
miliar with a li of its different appearances. A number of years ago, they published a classic co lor
atlas comparing the laparoscopic appearance of en-
Over the last 20 years, a great deal of progress has been dometriosis to its histopathology. With permission of
made in confirmin g the various appearances of en- the lead author, a number of these photographs and
dometriosis w ith histologic confirmation. Reproductive histopathologic sl ides are reprinted at this time for the
su rgeons such as Dr. Dan Martin , University of Ten- educational purposes of helping physicians gain confi-
nessee; Dr. David Redwine, St. Charles Medica! Center, dence in their ability to identify endometriosis.
Bend, Oregon; Dr. Harry Reich, Nesbit Memorial Hospi-
* Reprinted with permission of Dr. Dan Martin, Memphis, Tennessee.
* From: Martin D, Redwine D, Reich H, Kresch A: Laparoscopic Appearance of Endometriosis. Second edition . Th e Resurge
Press , Memphis , Tenessee, 1991 .
855
Figure 64-1 : Puckered black lesions have

been described as "classical" and "typical. "
These areas of endometriosis are !he easi-
est to see and !he most common to docu-
ment by a biopsy or excision of !he dark
area . This lesion is a diffuse mixture of fi.
brosis, stroma , hemorrhage and hemosid-
erin laden macrophages separating glands
and intraluminal debris (From: Laparoscopic
Appearance of Endometriosis, Second Edi-
tion , Martín OC , The Resurge Press , Mem-
phis, 1991 ).
Figure 64-2 : White scarred areas are easier

to see when the intraluminal areas of !he
glands contain debris from bleeding . These
areas are brown or black. The glands are
deep in !he fibrotic scar. When hemosiderin
and debris are contained within them, this
may be seen on !he s urfa ce (From :
Laparoscopic Appea rance of Endometrio-
sis, Second Edition , Martin OC, The Resurge
Press , Memphis, 1991 ).
Chapter 64: Visual Appearance of Endometriosis 857
Figure 64-3 : This white lesion involves

the left uterosacral ligamen!. The black par-
ticles on !he surface are carbon from pre-
vious C0 2 laser vaporizalion . In this area ,
sparse stroma and glands surrounded by
fibrous tissue and muscle is the predomi-
nan! picture. Trichrome stain was used to
demonstrate the fibrous components of the
fibra-muscular matrix (From : Laparoscopic
Appearance of Endometriosis, Second Edi-
tion , Martin OC , The Resurge Press , Mem-
phis, 1991 ).
Figure 64-4: When white scarred areas

are associated with red polyps , the red
polyps are most commonly endometriosis.
Red polypoid endometriomas can be as-
sociated with deeper glands and stroma
in the white fibrotic scar. The red polyps
are endometrial glands and stroma (From :
Laparoscopic Appearance of Endometrio-
sis, Second Edition, Martin OC, The Resurge
Press, Memphis , 1991 ).
Figure 64-5 : Clear polyps and vesicles may

be endometriosis or other pathology. These
lesions are noted lateral to the right fallo-
pian tube . Endometriosis can be seen as a
dilated vesicle with sean! stroma and little
vascula rization . Ot her patients have
edematous endometriosis presenting as
clear polypoid lesions (From : Laparoscopic
Appearance of Endometriosis , Second Edi-
tion , Martin DC , The Resurge Press , Mem-
phis, 1991 ).
Figure 64-6 : The angle of light reflection

was importan! in noti ng these clear and
wh ite les ions. All the lesions are initially seen
only at three or four locations . When the
angle of th e view cha nged , more lesions
we re seen. Sorne clear vesicles were di-
lated glands within fibrosis while other sec-
tions of the same pa tie nt showed both
glands and stroma (From : Laparoscopic Ap-
pearance of Endometriosis, Second Edition,
Martin DC, The Resu rge Press , Memph is,
1991 ).
Chapter 64: Vis ual Appearance of End ometri osis 859
Figu re 64-7 : Red polypoid areas have

been as small as 0.4 mm andas large as 7
mm . These are large lesions lateral to the
right fal lopian tube. Red polypoid lesions
can contain glands and stroma with vari-
able degrees of vascularity and hemor-
rhage . Scarring is seen at the base (From :
sis, Second Edition, Martin OC, The Resurge
Press, Memphis, 1991 ).
Figure 64-8 : The cluster of red endome-

triotic lesions at the right tubal cornua dem-
onstrates several histologic types . The
most distal lesion is highly vascular glands
and stroma . The most proximal lesion is
"an early mini-endometrioma " with red
blood cells dilating the glandular structures.
The collapsed vesicle has stroma (From :
sis, Second Edition , Martin OC , The Resurge
Figure 64-9: Teenagers co mmonly have

small red or pink polyps and white blebs as
isolated findings . In this 19-year-old , the
largest lesion was 400 microns in diameter
and is the small red polyp near the center
of the slide. The white light reflections on
the left of the slide are 200µ epithelial le-
sions . The 400µ polyp was comprised of
endometrial glands and stroma . The small
clear areas were epithelial lesions . The
epithelial lining of these was compatible with
endometriosis (From : Laparoscopi c Ap-
pearance of Endometriosis, Second Edition ,
Martin OC , The Resurge Press , Memphis,
1991 ).
Figure 64-10 : What appears to be a small

lesion on the sigmoid colon often represents
the "tip of the iceberg ." These can be easy
to palpate but hard to see. The red area at
the top of the bowel is an edematous vas-
cular area of glands and stroma . The mus-
cu lar infiltration can be seen beneath this .
The infiltration extends through 80 percent
of muscle wall (From : Laparosco pic Ap-
pearance of Endometriosis, Second Edition ,
Martin OC , The Resurge Press, Memphis,
1991 ).
Chapter 64: Visual Appearance of Endometriosis 861
Figure 64-11: Low power density C0 2 la-

ser vaporization can leave carbon on top
of residual endometriosis. This is particu-
larly true in the areas such as the broad
ligamen! immediately overlying the ureter.
When the area is resected , carbon and
granulation tissue is directly above the en-
dometriosis seen in the scarred right lower
area of the specimen (From: Laparoscopic
Appearance of Endometriosis , Seco nd Edi-
tion , Martin OC , The Resurge Press , Mem-
phis, 1991 ).
Figure 64-12: This area was resected at

second-look laparoscopy for persisten!
pain following CO, laser vaporization . The
surface has granulation tissue lying over
the residual endometriosis . High power
density C0 2 laser vaporization can avoid
carbonization. However, a resection is a
most predictable technique (From :
Press , Memphis, 1991 ).
Figure 64-13: Scarred black areas are not

always endometriosis. The right uterosac-
ral lesion is a foreign body and the black
lesion in the left uterosacral ligamen! is en-
dometriosís. Old suture material was seen
in the right uterosacral ligamen! lesion. This
was associated wíth scarring (From :
Laparoscopíc Appearance of Endometrio-
sís, Second Edition, Martín OC , The Resurge
Press , Memphis , 1991 ).
Figure 64-14: Clear and whíte ves icles on

the tube are ra rely endometríosis. However,
when the lesíons are lateral to the tube, the
diagnosis may be endometriosís . These
clear and white inclusions of the tube are
almos! uniform ly Walthard Rests (From:
Laparoscopíc Appearance of Endometrio-
Atlas of Findings in
Diagnostic Laparoscopy
I n order to develop one's skill as a diagnostic

laparoscopist, it is important to have multiple repeti-
tions in the operating room. It is the purpose of this
sentations ofperitonea l endometriosis ; peritoneal pock-
ets (müllerianosis) ; ovarian and tuba! endometriosis;
salpingitis isthmica nodosa ; endometriosis ofthe bowel;
chapter to enhance the yo ung surgeon 's ski l Is by pro- pelvic adhesions ; tuba! obstruction; polycystic ova-
viding an atlas of observations made at the time of ries; uterine leiomyomata; tuba! anomalies ; peritubal
laparoscopy. Through the repetition found in this atlas, cysts ; congenita l anomalies of the uterus, tubes, and
surgeons should be able to become more astute in their ovaries; and some miscellaneous findings.
di agnos t ic ac umen. At the heart of Surgical
NaProTECHNOLOGY is the ability to make a correct di- In reviewing this atlas, some of the findings are obvi-
agnosis. ous upon first observation while other findings are ob-
served only with the previously described technique of
This atlas reflects the author 's experience in over 2,500 "near contact" laparoscopy (NCL) (see Chapter 63).
diagnostic laparoscop ies. lt covers the myriad of pre-
863
864 The Med ica l and Surg ical Practice of NaProTECHNOLOGY
Peritoneal Endometriosis _______________________~
Figures 65-1 and 65-2 : A white starburst-appea ring lesion Figures 65-3 and 65-4 : A small well-circu mscribed lesion of
in Figure 65-2 is on the right lateral pelvic wall of Figure 65-1 . endometriosis is seen just above th e ureter on the right (65-3)
This is endometriosis and left (65-4) lateral pelvic wa ll.
Figures 65-5 and 65-6: Dark punctate lesions of endometriosis in the posterior cul-de-sac (65-6) from pelvis in 65-5.
Chapter 65: Atlas of Findings in Diagnostic Laparoscopy 865
Peritoneal Endometriosis, cont'd
Figures 65-7 and 65-8 : The red , angry-appearing lesion Figures 65-9 and 65-10 : The dark powder burn lesions and
deep in the right posterior cul-de-sac (65-8) is endometriosis whitish starburst les ion in 65-1 O is in the deep posterior cul-
from the pelvis in 65-7 . de-sac of the pelvis in 65-9. This is endometriosis. Note the
nodule in the right proximal fallopian tube (65-9) which is a
classic lesion of salpingitis isthmica nodosa .
Figures 65-11 and 65 -12: The dark powder burn lesions of endometriosis in the right posterior cul-de-sac (65-12) was only
observed after the cul-de-sac fluid from 65-11 was aspirated and the uterosacral ligamen! was retracted laterally.
Figures 65-13 and 65-14: A red "flame" lesion of endometriosis Figures 65-15 and 65-16: A powder burn lesion associated
at the apex of the left uterosacral ligamen! is shown . with scarring and an inflammatory cyst is seen on the left
posterior broad ligamen! (65-15) and in 65-16 a closer view
of the adhesion associated with endometriosis deep on the
right posterior uterus is shown. This can also be seen in 65-
15 but the degree of involvement is not apparent in that view.
Figures 65-17 and 65-18 : A classic powder burn lesion of endometriosis overlying the ureter on the left lateral pelvic wall is
seen in 65-17 and in the same patient, black and gray lesions high on the pelvic crest jusi lateral to the sigmoid colon are
observed (65-18) .
Chapter 65 : Atlas of Findings in Diagnostic Laparoscopy 867
Figures 65-19 : A classic powder bum strip of endometriosis

jusi medial to the proximal left fallopian tube and lateral to the
left ovarian ligamen!.
Figures 65-22 through 65-24 : This posterior cul-de-sac

looks normal at first glance (65-22) but by retracting the left
uterosacral ligamen! laterally (65-23) or by retracting the peri-
toneum medially (65-24), the peritoneal endometriosis is re-
vealed.
Figures 65-20 and 65-21 : Small gray lesions with a punc-

tate center are also an appearance of peritoneal endometrio-
sis .
Endometriosis: Peritoneal Pockets --------------------~
Figures 65-25 through 65-27 : Two peritoneal pockets can Figures 65-28 through 65-30: The peritoneal pocket in 65-
be observed in 65-25. Upon closer evaluation in 65-26 and 29 is from the pelvis in 65-2 8. When the peritoneum is re-
65-27, the endometriosis deep in the pocket can be observed . tracted to the left (65-30), the red lesion of endometriosis can
The findings of endometriosis in peritoneal pockets of this be seen .
kind is so common that it is to be expected .
Ch apter 65: Atlas of Findings in Diagnostic Laparoscopy 869
Endometriosis: Peritoneal Pockets , cont'd
Figures 65-31 through 65-33 : Another peritoneal pocket jusi

lateral to the right uterosacral ligamen! has a cobweb appearance
(65-31 ). Upon closer view with NCL, the red endometriotic lesion
can be seen (65-32 and 65-33) within the pocket.
Endometriosis: Posterior Bladder --------------------~
Figures 65-37 and 65-38: An area of endometriosis ap-

pears as a dark circumscribed area on the left posterior blad-
der. In 65-38, black pepper spots are seen on the righ t and
are co nsisten! with carbonization secondary to previous la-
ser vaporization .
Figures 65-34 through 65-36 : In the distan! view of the

anterior cul-de-sac and posterior bladder in 65-34 , the small
dark lesions of endometriosis in 65-35 and 65-36 can hardly
be seen . They are observed with NCL and in 65-35 there is
also a larger hemosiderin deposit (the golden brown tissue )
which is the result of endometriosis .
Chapter 65: Atl as of Findings in Diagnostic Laparoscopy 871
Posterior Bladder Endometri osis, co nt'd
Figures 65-39 and 65-40 : Endometriosis on the left poste- Figures 65-41 and 65-42 : Endometriosis throughout the pos-
rior bladder (65-39 and 65-40) and endometriosis with dense terior bladder (65-41) associated with adhesions of the pos-
scarring involving the right posterior bladder and anterior terior bladder to the anterior uterus (65-42).
uterus .
Ovarian Endometriosis --------------------------~
Figures 65-43 through 65-45 : This sequence shows the Figures 65-46 through 65-48: A similar sequence showing
pelvis (65-43), the right tube and ovary (65-44) and the en- an area of endometriosis on the inferior pole of the right ovary
dometriosis on the medial surface of the right ovary (65-45) (65-47) and on its medial surface (65-48).
which is only seen with NCL and exposing the medial sur-
face .
Ovarian Endometriosis , cont'd
Figures 65-49 and 65-50: Th e medial surface of the righ t

ovary in 65-49 is shown in 65-50 . This is endometriosis fol-
lowing a previous cauterization of the same.
Figures 65-51 through 65-53 : Three separate examples of

ovarian endometriosis . In 65-51 , the lesion is superficial and
associated with one or more developing follicles . In 65-52 , it
is a brown lesion associated with the medial surface of the
left ovary. And in 65-53 , the left ovary shows a dark brown
lesion densely adhered to the left lateral pelvic wa ll. With this
type of lesion , the ovary invariably contains an endometrioma .
Ovarian Endometriosis, cont'd
Figures 65-54 through 65-56 : In this sequence, !he ovarian en-

dometrioma on the left ovary is seen only when the medial surface is
exposed (65-55 , 65-56) . This also reveals the reactive tissue that is
often seen with endometriomas like this .
Tubal Endometriosis - - - - - - - -- - - - - - -- -- - - - - - -- ----,
Figures 65-57 and 65-58 : The constriction in the right tube Figures 65 -59 and 65-60 : A small area of superficial en-
(65-57) is caused by endometriosis (golden brown discol- dometriosis jusi medial to the left cornua (65-59) and a clas-
oration). In 65-58, the endometriosis is seen at the junction of sic linear powder burn streak near the left tubal mesentery
the right tube with the peritoneum overlying the (65-60) .
infundibulopelvic vein .
Figures 65-61 and 65-62: A lesion of endometriosis on the peritoneal surface of the left fallopian tu be (65-61) and another
lineal powder burn lesion causing an adhesion of the tube to the tubal mesentery (65-62).
Tubal Endometriosis , cont'd
Figures 65-63 : A puckered , deep blue

lesion of endometriosis seen at the distal
end of the right tube. This type of lesion
wil l ca use partial and at ti mes complete
obstruction of the distal tube.
Salpingitis lsthmica Nodosa (SIN) -------------------~
Figures 65-64 and 65-65: This shows the nodularity present Figures 65-66 and 65-67 : Figure 65-66 shows the nodularity
in a patient with bilateral SIN . of SIN associated with a powder bum appea rance on the
surface. In 65-67 , índigo carmine dye is seen to extravasate
into the large bilateral nodules of this patient with SIN . In spite
of these classic examples, SIN may also be present in tubes
that laparoscopically appear to be perfectly normal.
Chapter 65 : Atlas of Findings in Diagnostic Laparoscopy 877
Endometriosis: Rectosigmoid Colon - - - - - - - -- - - - - - - - - - - - - - ,
Figures 65-71 and 65-72 : A red lesion on an epiploic fat pad

(65-71) anda white scarified lesion in 65-72 are endometriotic
lesions of the rectosigmoid .
Figures 65-68 through 65-70 : A small dark lesion with a

white halo is seen on the rectosigmoid colon with NCL (65-
68) . In 65-69 , the lesions are white and on the lateral mesen-
tery of the sigmoid and in 65-70 , the same type lesionas seen
in 65-68 is observed along with a red blister-type lesion .
Endometriosis: Rectosigmoid Colon , cont'd
Figures 65-73 through 65-75: Red and scarified lesions on epi-

ploic fa! tags (65-73 and 65-74) are contrasted with the puckered
lesion on a fat tag in 65-75 .
Endometriosis: Anterior Rectum - -- - - -- - - - - -- - - - - - - - - --.
Figures 65-76 through 65-80 : In this sequence a small red

lesion is seen from a distance in the posterior cul-de-sac in
65-76. Upan closer observation and palpation with the irrig a-
tion probe, the lesion is identified as a nodule on the anterior
rectum (65-77 , 65-78 and 65-79). In 65-80 the lesion is more
erythematous because of the manipulation .
880 The Medical an d Surgical Practice of NaProTECHNOLOG Y
Endometriosis: Anterior Rectum , cont'd
Figures 65-81 through 65-83 : Only upon careful inspection Figures 65-84 through 65-86 : Several classic puckered
of the cul-de-sac in 65-81 can a red flame lesion be identified lesions associated with irritated (erythematous) peritoneum
(65-82) . Then , with an upward lifting motion of the uterine are shown for endometriosis of the anterior rectum .
manipulator by the surgical assistant, the nodule of endometrio-
sis on the anterior rectum is identified (65-8 3) .
Endometriosis: Anterior Rectum , cont'd
Figures 65-87 through 65-90 : In this sequence a patient whose cul-de-sac is obliterated is seen (65-87). This is caused in
part by an ovarian endometrioma under the left ovary (65-88) and endometriosis of the anterior rectum and/or the uterosacral
ligaments.
882 Th e Med ica l and Surgical Practice of NaProTECHNOLOGY
Endometriosis : Appendix ------------------------~
Figures 65-91 and 65-92: Endometriosis of the vermiform Figures 65-93 and 65-94: Endometriosis of the append ix
appendix . associated with stricture and edema.
Figures 65-95 and 65-96: An adhesion of the tip of the appendix toan area of peritoneal endometriosis on the right lateral pelvic
wall , near the pelvic eres! and just above the ureter.
Endometriosis: Terminal lleum ______________________-----.
Figures 65-97 and 65-98 : Two different examples of en- Figures 65-99 and 65-100 : Endometriosis on the terminal
dometriosis on the serosa of the terminal ileum . ileum (65-99) and its mesentery (65-100). In 65-99 sorne nar-
rowing of the lumen is present secondary to the scarring that
is present.
Pelvic Adhesions --------------------------~
Figures 65-101 and 65-102: An adhesion from the medial Figures 65-103 and 65-104: Adhesions in the left ad nexa
surface of the right ovary to the lateral pelvic wall (65-101 ). (65-103) are shown to be a complex of ovarian, rectosigmoid
On closer inspection (65-1 02) a dark lesion of endometriosis and lateral pelvic wall adhesions (65-1 04 ).
is seen at its base.
Pelvic Adhesions, cont'd
Figures 65-105 through 65-110: In 65- 105 , an omental ad-

hesion to th e right posteri or fu ndus is seen. Once that is
taken down , the complex mass of filmy adhesions involving
the right tu be and ovary can be seen (65-106). In 65-107
throug h 65-11 O the fil my adhesions involving the left tube and
ova ry are shown. When this type of ad hesion covers the
ovary, it is ca lled an ovarian investment adhesion.
Pelvic Adhesions, cont'd
Figures 65-111 through 65-113 : A dense adhesion from a left

ovarian endometrioma to the left posterior broad ligamen! and ute-
rosacral ligamen! is shown in 65-111 and 65-112 in a palien! pre-
viously treated with operative laparoscopy. In 65-113, this is an-
other palien! with large bilateral endometriomas adhered to each
other and the lower portian of the posterior uterus.
Pelvi e Adhesions, cont'd
Figures 65-114 through 65-118 : This sequence shows ex-

tensive periovarian and peritubal adhesions associated with
adhesions to the anterior rectosigmoid obliterating the cul-de-
sac. On close inspection (NCL) the right (65-117) and left (65-
118) distal tube and fimbria appear normal , suggesting repair
of this condition would hold definite hope for pregnancy.
Pelvic Adhesions , cont'd
Figures 65-119 through 65-121: In this sequence, the left tube

and ovary are densely adhered to the anterior uterus. This adhe-
sion is identified in 65-120 and it is also adhered to the right round
ligamen! and fallopian tube (65-121 ).
Fig ures 65-122 through 65-124 : Three different appearances

of a hydrosalpinx . The tube in 65-124 is very co nvo luted and
associated with a comp lex mass of adhesions involving the tube,
ovary, posterior uterus, broad ligamen! and lateral pelvic wa ll.
890 The Medical and Surg ical Practice of NaProTECHNO LOG Y
Polycystic Ovaries, ___________ _ _ _ _ _ _ _ _ _ _ __ _ __ _~
Figures 65-128 and 65-129: The dilated , surface blood ves-

sel pattern observed on sorne , but not ali , patients with PCO.
Figures 65-125 through 65-127 : This sequence shows

classic polycystic ova ries . The ovaries are enlarged , very
smooth , and white with surface blood vessels.
Polycystic Ovaries, cont'd
Figures 65-130 through 65-134: In this sequence , the poly-

cysti c ovaries are at first glance not readily identifiable (65-
130). However, once maneuvered with the probe, the lateral
and medial surface of the right (65-131 and 65-132) and left
(6 5-133 and 65- 134) ovary can be observed and the physi-
cal characteristi cs of the PCO made evident.
892 The Medical and Surgical Pract ic e of NaProTECHNOLOGY
Figures 65-135 through 65-137 : A uterine fibroid off the Figures 65-138 through 65-140: Two or three large intra-
right posterior fundus (65-135) and two similar fibroids off mural fibroids coming off the posterior uterus is shown (65-
the left posterior fundus are shown . Then a large peduncu- 138) along with a subserous fibroid on the right anterior uterus
lated fibroid off the left posterior fundus is shown (65-137 ). (65-139). In 65-140 , a smaller subserous fib roid is seen off
the left posterior uterus .
Figures 65-141 and 65-142: Classic Walthard rests (mul-

tiple small blister-like vesicles) on the medial surface of the
fallopian tube.
Figures 65-145 through 65-147 : This sequence shows

three types of peritubal cysts . The first is subserosal (65-
145); the second is pedunculated (65-146) ; and the third is
also pedunculated but also has endometriosis on its surface
(65-147).
Figures 65-143 and 65-144: Elongated fimbria ovarica of

the right (65- 143) and left (65-144) tube in the same patient.
Each measures > 5 cm.
894 Th e Medical and Surgical Practice of NaProTECHNOLOGY
Fallopian Tube Anomalies, cont'd
Figures 65-151: Two accessory fa llopian tubes coming off

the lateral aspect of the right tubal ampulla .
Figures 65-148 through 65-150: A cystic mass in the left

adnexa (65-148) is a large 5 cm peritubal cyst (65-149 and
65-150).
Chapter 65: Atlas of Findings in Diagnostic Laparosco py 895
Fimbria Under Water _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _~
Figures 65-152 through 65-154: By immersing the fimbria under

plain Ringer 's lactate at the time of laparoscopy, one can study
them. In sorne women with endometriosis, the fimbria are blunted as
in 65-152. More normal-appearing fimbria are seen in 65-153 and
65-154. This technique needs further study to elucidate its role in
diagnosis and evaluating prognosis.
Miscellaneous Observations _____________________ _~
Figures 65-155 and 65-156: Two normally developing , ma-

ture follicles .
Figures 65-157 through 65-159 : Three examples of superfi-

cial adenomyosis.
Miscellaneous Observations , cont'd
Figures 65-160 through 65-1 62 : A uterus with a broad fun- Figures 65-163 through 65-165: Two small ovarian fibromas
dus (increased distance between the insertion of the fallopian are observed in 65-163 and 65-164. In 65-165, the ovary is
tu bes) and an indentation in the top diagnostic of a large uterine very yellow, presumably due to a high intake of beta-carotene
septum (65-160 and 65-161 ). In 65-162 an accessory left ovary (from carrots). The palms of this patient's hands also showed
is observed. a yellow discoloration .
Selectiva Hysterosalpingography and
Transcervical Catheterization of the
Fallopian Tubes
I n evaluating infertility, it is common to perform hyste-

rosalpingography (HSG). The HSG has become a nor-
mal part ofthe routine infertility evaluation 1 (Figures 66-
known as selective hysterosalpingography (S HSG) and
has been popularized more recently by Lang, et al, 3
Capitanio et al ,4 Thurmond,5 and Gleicher, et al. 6 A num-
1 and 66-2). While this test oftubal integrity and study ber of other investigators have also added to the proce-
of the intrauterine cavity represented a significant im- dure various aspects oftranscervical catheterization of
provement over the previous Rubin test, it has contin- the fallopian tubes (TCFT). 1- 10 Gleicher et al 6 first re-
ued to have shortcomings. Perhaps one of the most ported on a standard ized tubal perfusion technique. lt
difficult aspects ofthe infertility eva luation is to study was suggested that the evaluation of tubal perfusion
the anatomic and functional integrity of the fallopian pressures could provide important diagnostic informa-
tu bes. tion and further investigation of this area was encour-
aged. In 1999, Hilgers and Yeung 11 described a group
The first effo11 to evaluate the fa ll opian tubes selec- of patients for whom the intratuba l pressure (ITP), at
tively using contrast material was by Corfman and Tay- the time of the SHSG, was obtained befare and after
lor in 1966. 2 This procedure subsequently became TCFT.
Figure 66-1 : Standard hysterosalpingogram showing the Figure 66-2: Standard hysterosalpingography revealing
oo•tomy of the iotmote1ioe ' " ' " ~ '""9e of dye dowo the f•llopioo t"be.
899
Watertown, MA). This device is a pressure-monitoring

syringe with a manometer attached for direct pressure
Selective hysterosalpingography and TCFT should be measurements.
scheduled in the early proliferative phase of the men-
strual cycle (genera ll y between days 4 and 8 of the The LeVeen syrin ge has a gri p that can be rotated eas-
cycle). After general anesthesia (in the case of proce- ily to inject the Sinografin in a steady stream. As the
dures done at the time of laparoscopy) or IV sedation grip is rotated steadil y and dye is observed either pass-
(in the case of procedures done separately), the pa- ing or not passing down the fallopian tube, the ITP is
tients are placed in the dorsal lithotomy position and measured directly at the point where it stabi li zes at the
prepared and draped to expose the perineum. A pelvic maximum leve!. Generally, 7 to 15 ce of dye is injected
examination is carried out with special reference to (for both tubes) to reach thi s point and comp lete the
whether the uterus is anteverted, mid-position or retro- procedure. The dial on the manometer is easy to read.
verted. A C-arm portable fluoroscopy unit is then put The ITPs are measured in atmospheres (Figures 66-4,
into position, the cervix is exposed and either a single- 66-5, 66-6).
tooth tenaculum ora long Ali is clamp is placed on the
anterior lip ofthe cervix. The uterus is sounded with a
uterine sound and a tuba! injection catheter is placed
within the uterus (Figure 66-3) Water-soluble, radio-
opaque dye (Diatrizoate Meglumine and lodipamide,
Meglumine-Sinografin; Braceo Diagnostic, Princeton,
J) is injected into the uterus under direct fluoroscopic
contro l to identify the uterine cavity.
Figure 66-4 : The LeVeen pressure monitoring syringe used

for SHSG and the measurement of the intratubal pressures.
Figure 66-3: This is the set-up in the operating room, with a

C-arm fluoroscopy unit for selective hysterosalpingography
and transcervical catheterization of the fallopian tube.
Figure 66-5: The tubal injection catheter that accompanies

The tuba! injection catheter is then advanced to the
the Jansen-Anderson catheter set-up.
interna! ostia of either the right or the left fallopian tu be,
whic hever is easier. There is an obturator that accompa-
nies the tuba! injection catheter which may be neces-
sary to utilize in more difficult cases in order to place the
tip ofthe tuba! injection catheter into the interna! ostia.
The dye is then injected directly into the fa llopian tu be
(se lectively) under direct fluoroscopic visua lization (ap-
proximately 7 kY 2.0 mA/s AutoSet) and the ITP is mea-
sured . For the purposes ofthis examination, a 5.7 F (29-
cm) Jansen-Anderson tuba! injection catheter (Cook Ob-
Gyn Spencer, 1 ) is used. Attached to the proximal end Figure 66-6 : The Jansen-Anderson 0.018-in ch , flexible-
tipped , stain less steel metal guidewire with its 3F delivery
ofthe tuba! injection catheter is a LeVeen 1Oce dispos- ca theter (Cook Ob-Gyn Spence r, IN ).
able inflati o n sy rin ge (Boston Scientific Corp,
Chapter 66: Selective Hysterosalpingography and TCFT 901
When the ITP becomes elevated to greater than or equal

to 0.7 ATM, a 3F (40-cm) delivery catheter is inserted
down the lumen ofthe tuba! injection catheter and placed
within the proximal po1tion ofthe fallopian tube (ifpos-
sib le). This tapered catheter naturally wedges itself
within the first 2 cm of the proximal fa ll opian tube. Un-
der fluoro scop ic control, a O.O 18-inch, rounded and
blunt, flex ible tip, stainless stee l guidewi re then is in-
serted through the deli very catheter and down the fa l-
lop ian tube (Jansen-Anderson catheter setup). At this
time, any additional obstructi ons or increased resistance
or "stiffness" ofthe fa llopi an tu be can be palpated. The
gui dewire is then advanced to the ampulla ofthe fallo-
pian tube (ifposs ibl e) and slow ly maneuvered back and Figure 66-8 : After catheterization , dye now passes the
forth to clear the fallopian tube. fallopian tube and the pressure has been normalized.
After TCFT with the flexible-tipped metal gu idewire,

the ITP and flow of dye down the fallopian tu be is re-
meas ured and assessed again. The flexible metal
guidewire is pl aced gently, at least two times and usu-
ally three times, in an attempt to clear the fa ll op ian tu be
befare the final ITP read ing is obtained. After one tu be
is assessed, the other tu be is eva luated in a similar fash-
ion (Figures 66-7 through 66-1 O). After TCFT, the tu bes
can be injected with a so lution con taining 25 ce of Ring-
ers lactate and 100 mg of Solu-Cortef (Upjohn Com-
pany, Kalamazoo, M 1) and l 000 units of heparin in an
attempt to cleanse them and keep them patent.
The proximal fallopian tu bes ca n be classi fied as eith er

freely patent, parti ally obstructed or comp lete ly ob-
structed. In free ly patent tu bes, the ITP ranges from 0. 1-
0.6 ATM and the dye tlows down the tubes with ease.
In partially obstructed tu bes, the ITP is greater than or Figure 66-9 : On the left side , the stainless steel metal
guidewire is inserted .
equal to 0.7 ATM and the dye tlows down the fallop ian
tubes. In comp letely obstructed tubes, neither the dye,
nor the flexible-tipped meta l guidewire proceeds down
the fa llopian tubes and the pressure wi ll be elevated .
Figure 66-7: Oye is injected into the uterine cavi ty and no dye
is observed to pass down th e fallopian tubes . A flexible- Figure 66-10: Oye is noted to freely spill down the left fallo-
tipped metal guidewire is inserted into the right fallopian tube pian tube and the tube is now patent.
(show n).
902 The Medica l an d Su rgic al Practice of NaProTECHNOLOGY
Intratubal Pressure (ITP) At Time of gitis (n=4), fibromuscular hyperplasia (n= 3), acute salp-
Selective Hysterosalpingography (SHSG ) (N=441 )
ingitis (n= 1), and intraluminal fibrous polyp with calcifi -
cation (n= 1). The total number of diagnoses exceeded
25 because there were multiple diagnoses in sorne cases .
~()
~) An organic cause for the obstruction was identified in
4\
4\
ali cases. 11
"''<1
11 "''~
~ ''l . .
~$ ~
~ 2$ The adequate evaluation of the fallopian tubes in pa-
~ 10 l{) i;:
]\
15
]]]
tients with infertility has been a problem for many years.
]]]
1
\ Because the fallopian tubes are not readily accessible,
direct access to them has generally not been possible.
However, with the advent of HSG, it is now possible to
assess the fallopian tubes more thoroughly and to get
more accurate information. In th is NaProTECHNOLOGY
practice, it has completely rep laced HSG as a d iagnostic
Figure 66-11 : The intratubal pressure (ITP) at the time of approach .
selective hysterosalpingography in the right and left fallopian
tube and for all of the tubes (N=441 ). The technique described in this chapter allows for the
measurement of the ITP in a relatively simple fashion
during the course of SHSG. These measurements ha ve
The mean intratubal pressure for the freely patent tubes revealed that sorne tubes previously considered to be
is 0 .53 ATM and for the partially obstructed tubes 1.25 patent because dye has been shown to flow down them,
ATM. The completely obstructed tubes have a mean actually are partially obstructed. This may be more com-
ATM of2 .79 (Table 66-1 ). Sorne degree of obstruction is mon in women w ith reproductive abnorma li ties than has
quite common in women w ith infertility problems. been previous ly thought.
With TCFT the pressure can be lowered to normal in On occasion , complete obstruction may exist when the
women with partially obstructed tubes, but in com- ITP is within the normal range . Sometimes, the tuba!
pletely obstructed tube , the pressure will remain un- injection catheter does not fit tightly into the interna!
changed (Table 66-2). This is graphically displayed in ostium and " leakage" occurs around the point of inser-
Figures 66-11 , 66- 12 and ++-13. tion which artificially lowers the lTP.
ln 25 patients with complete tubal obstruction who carne With the relatively easy technique of TCFT, usi ng a
for surgical excision and reanastomosis of the proxi- non-traumatic, rounded and blunt, tlexib le-tipped sta in-
mal fallopian tubes, a d iagnosis based upon the histo- less steel guidewire, many fallopian tubes can be opened
pathology of the observed tissue was made. The diag- completely and the ITP normalized. One can anticipate
noses were distributed in the following fashion: salpin- that with ITPs greater than or equal to O.7 ATM, o ver 75
gitis isthmica nodosa (n= 1O), endometriosis (n=8), lumi- percent can develop normal ITPs after TCFT. 11
nal stenosis (n= 5), tuba! fibrosis (n=4), chronic salpin-
In partially-obstructed fallopian tubes, it has been pre-
viously reported that an amorphous material of unknown
etiology often is present in the form of a caste within
Table 66- 1: Mean lntratubal Pressu re Measured at the proximal po11ion ofthe tube . 12 Such " plugs" may be
Selective Hysterosalpingography 11 the cause ofthe partial tuba! occ lusions that have been
Mean ±. SD
observed. This also cou ld expla in why the normaliza-
Tubal patency n pressure (atm ) tion of the ITP after TCFT occurs in such a high per-
centage of cases. It mayal o explain why, with standard
Freely patent 110 0.53 ±. 0.06·
hysterosalpingography, the observation that dye will
Partially obstructed 254 1.23 ±. o.s2t
not initially go down the fallopian tube, but with addi-
Completely obstructed 77 2.79 ±. 1.40
tional pressure, does go down the tu be, may occur. Be-
~.0001 (mean intratubal pressure of freely patent group versus mean fore this time, tuba! spasm was usually given as the
intratubal pressu re of partially obsrtucted and completely obstructed
groups). explanation for this observation. However, these cases
t ~.000 1 (mean intratubal pressure of partially obstruded versus complelely are a more likely explanation.
obstructed groups).
Chapter 66: Selective Hysterosalpingography and TCFT 903
Intratubal Pressure (ITP) Before and After

Transcervical Catheterization of the Fallopian Tu bes
Partially Obstructed Tubes (N=154)
80 Ro
l()
60 'º60
so 5()
40 4()
31) 3o
'ºIO 'ºIO
o o
In sorne cases of partial obstruction, the ITP <loes not than in oviducts considered to be diseased. The lTPs
normalize and/or there is a palpable obstruction. As in were 429 +/- 375 mmHg (0.56 +/- 0.49 ATM) in the fom1er
cases of compl ete obstruction there appears to be a group and 957 +/- 445 mmHg ( 1.24 +/- 0.58 ATM) in the
spec ifi c organi c cause. lt has been noted that in most of latter group. They also noted that in sorne cases, the
these cases, the externa! appearance ofthe proximal fal- ITP exceeded 1500 mmHg ( 1.95 ATM). This is cons is-
lopian tube at the time of laparoscopy is usually normal. tent with the findings of Hilgers and Yeung. 11 The ma-
The hi sto log ic findin gs reported with regard to com- no meter used in this technique is readily ava il able and
plete obstruction, 11 are similar to what ha ve been previ- easy to use.
ously reported . 13- 15
lt has also been reported that intrauterine pregnancy
Intratubal perfus ion pre sures have previously been rates after SHSG and TCFT range from 9 to 37 percent. 16•17
measured using trace paper recordings with a constant While pregnancy rates were not the focus ofthe Hilgers
rate infu sion pump and reported in millimeters ofmer- and Yeung study, SHSG and TCFT are now considered
cury. Gleicher6 reported that functionally normal ITPs to be important components of a basic eva luation for
during SHSG were in the range of 40-350 mmHg (0.05- wornen who have had difficulty achieving pregnancy. It
0.46 ATM). In ov iducts that were judged to be normal is a significant improvement over hysterosalpingogra-
by opacification pattern , ITPs were significantly lower phy without losing any of the component aspects of
Table 66-2: Mean lntratubal Pressure Before and After

Transcervical Catherization of the Fallopian Tube 11
Mean {±: SO)

lntratubal Pressure (aim)
Tubal patency n Before TCFT AfterTCFT
Partially obstructed 154 1.26 ±_ 0.49 0.64 ±_ 0.31"
Completely obstructed 77 2.46 ±_ 1.17 1.86 ±_ 1.35t
Note: TCFT = tra nscervical catherization of the fallopian tu be

p~ . 000 1 (versus before TCFT)
t Statistica lly significan! (p=.0225). The difference remained significan! for the left tube
(n=24) before (2.258 ± 1.12 atm) and after 1.83 ± 1.30 atm) TCFT (p=.0362). The diffence
did not remain significan! for the right tube (n=20) before (2.43 ! 1.29 atm) and after (1.93±
1.51 atm) TCFT (p=.2681).
Intratubal Pressure (ITP) Before and After

Transcervical Catheterization of the Fallopian Tu bes
Completely Obstructed Tubes (N=47)
Figure 66-13: The intratubal pressure (ITP) befare and after transcervical
ca th eterization of the fa\lopian tubes in completely obstructed tubes (N=47).
the tradi tiona l HSG (Figures 66-14, 66-15 , 66- 16).
The mea n ex posure to flu oroscopy in thi s proced ure

has been calcul ated to be 138 +/- 59.4 seco nd s. This is
well w ithin the ra nge ofradiation safety which has been
previously reported. 18 The safety margin is adequate
even if a secon d procedure i neces ary. De li very of
medications to th e fallopian tube has a lso been prev i-
ous ly described. 19
Figure 66-15 : Selective hysterosalpingography in a palien!

wi th bilateral hydrosalpinges cons isten! with the previous
use of HSG.
Figure 66-14: Selective hysterosalpingog raphy in a palien!

who has a co llection of dye at th e distal fallopian tubes Figure 66-16: SHSG in a palien! with a submucous uterine
cons isten! wi th previous HSG studies demonstrating peritubal fibroid . The fibroid is in the lower right portian of the intrauterine
adhesions. cavity. The upper radio-opacity is an air bubble .
Chapter 66: Selective Hysterosalp ingography and TCFT 905
1. Siegler AM: Hysterosalpingography. In: Wallach EE and Zacur HA 1O. Thompson KA , Liltz RJ , Coci T, Cabus ET, Kletzky OA .
(Eds). Reproductive Medicine and Surgery. Mo by, St. Louis, pp Transcervical fallopian tube catheterization and recanalization for
481-588, 1995. proximal tuba! obstruct ion . Ferti l Steril 61:243-247, 1994.
2. Corfman PA, Tay lor NC. An instrument for transcervica l treatment of 11 . Hil gers TW, Yeung P. lntratuba l pressure before and after transcervica l
the ov iducts and uterine cornua. Obstet Gyneco l 27:880-884, 1966. catheterization ofthe fal lopian tubes. Ferti l Steril 72: 174-178, 1999.
3. Lang EK, Dunaway HE, Roniger WE. Selective osteal salpingogra- 12. Sulak PJ , Lettlerie GS , Coddington ce, Hayslip ce, Woodward JE,
phy and transvaginal catheter dilation in the diagnosis and treatment Klein TA, Histology ofprox imal tuba! occlus ion. Ferti l Steri l 48:437-
of fa ll opian tube obstructi on. Am J Roentgenol 154:735-740, 1990. 440, 1987.
4. Capitanio GL , Ferraolo A, Croce S, Gazzo R, Anserini P, de Ceceo 13. Fortier KJ , Haney AF. The pathologic spectrum of uterotubal junc-
L. Transcervical se lective salpingography: a diagnostic and therapeu- tion obstruction. Obstet Gynecol 65:93-98, 1983.
tic approach to cases ofproxima l tubal injection failure. Ferti l Steril 14. Lettl erie GS , Sakas EL. Histology of prox imal tuba! occl usion in
55: 1045-1050, 1999. cases of unsuccessful tubal ca nalizat ion. Fertil Steril 56:83 1-835,
5. Thurmond AS. Selective salpingography and fallopian tu be recanali- 1991.
zation. Am J Roentgenol 156:33-38, 1991. 15. Thurmond AS, Burry KA , Novy MJ . Salpingitis isthmica nodosa:
6. Gleicher N, Parrilli M, Redd ing L, Pratt D, Karande V. Standardiza- Results of transcervical fluoroscopic catheter reca nali zation. Fertil
tion ofhysterosalpingography and select ive salpingography: A valu- Steril 63:715-722, 1995 .
able adjunct to simple opacification studies. Fertil Steril 58: 1136- 16. Thurmond AS. Pregnancie after selecti ve salpi ngography and tuba!
1141, 1992. recanalization. Radiology 190: 11-13, 1994.
7. Kumpe DA, Swerd linger SC, Roth barth LJ, Durham JD, Albrecht 17. Martensson O, Ni lsson B, Eke lund L. Selective salpingography and
BH. Proximal fa llopian tube occlusion: diagnosis and treatment with flu oroscopic transcervical salpingoplasty for diagnosis and treatment
transcervical fallopian tube catheterization. Radiology 177: 183- of proximal fa llopia n tube occ lusions. Acta Obstet Gynecol Scand
187, 1990. 72:458-464, 1993.
8. Deaton JL, Gibson M, Riddick DH , Brumsted JR. Diagnosis and 18. Karande VC, Pratt DE, Balin MS , Levrant SG, Morri s RS, Gleicher
treatmem of cornual obstruction using a flexible tip guidewire. Fertil . What is the radiarion exposure to pat ients during a gynecoradiologic
Steril 53:232-236, 1990. procedure? Fertil Steril 67:401-403, 1997.
9. Liss K, Sydow P. Fal lop ian tube catheterizat ion and recanalization 19. Risquez F, Confino E. Transcervical tuba! cannu lat ion , past, present
under ultrasonic observat ion: The simpl e tech niq ue to evaluate tuba! and future. Ferti l Steril 60:2 11 -226, 1993.
patency and open proximally obstructed tubes. Fertil Steril 56: 198-
201 , 1991.
Fundamental Anti-adhesion
Surgical Techniques
n surgical NaProTECHNOLOGY, the goa l is to per- whi ch also may contribute to the fo rmation of adhe-
I form adhesion-free surgery and to preserve and en-
hance procreati ve functi on. Whil e it cann ot be guaran-
sions. Whil e bl ood itse lf is thought not to ca use adhe-
sions, when raw and ex posed ti ssue surfaces are com-
teed that any surgical procedure on the pelvic anatomy bined with bl ood, thi s may predi spose to the develop-
can be performed in such a way as to elim inate ali adhe- ment of ad hes ion fo rm ati on.4
sion formation , 1-3 there is no questi on that surgica l pro-
cedures perfom1ed on this anatomy can be accomplished Genera ll y speaking, there is set in moti on a cascade of
in a way which signifi cantl y reduces not onl y ex isting events which starts with the di sruption of stromal mast
adh es ions, but al so the re-fo rmati on of adhes ions. In ce ll s. Thi s may then lead to the release of certain vaso-
order to accompli sh thi s, meticulous allention to detail active substances, such as hi stamines, leukotri enes and
is required and a pati ent approach to the overa ll con- prostag landin-estradioLThe permeabili ty of bl ood ves-
duct of the surgical procedure and a commitment to se is is in creased and th is produces an ex udate of fibrin .
perform the bes! anti-adhesion surg ical procedure This ex udare may then lead to a deve lopment ofserosal
possible is necessary. When these characteristics come adh e ions in as short a peri od of time as three hours. 5
together, the potential to reduce adh es ion fo m1ation is Thi s acti vity is modul ated by pl asmin ogen acti vator
significant. acti vity, whi ch is normall y present in the mesothelium
and sub-mesothelium ofth e bl ood vesse ls. Under more
normal conditi ons, the fo rmati on of pl asmin (fibrin ol-
Development of Adhesions _ _ _ __ ys in) fro m pl asminogen and subsequent fibrin olys is,
act to spontaneously lyse many of th e ea rl y fi brin ous
Operating within the pelvic anatomy, whi ch prod uces adhes ions over the first 72 hours. Wi th the presence of
surgical inju ry to vari ous tissues, is often ali by itse lf, ischemi a whi ch may be ca used by clamp , ligatures or
ve ry adh es iogenic. Any in sult to these tiss ues, the thermal inj ury, there may be a reduction oftissue plasma
ovary, uteru s, periton eum , bowe l, bl adder, etc. , will reacti vator whi ch would then impair the fibrin olytic sys-
sult in adhesion form ation ifleft to its own. Because the tem. The fibrin ous ex udate is infi ltrated by fibrobl asts
pelvic ti ss ues are located within the pelvic cav ity whi ch and adh es ions are fo rmed. Beca use of the nature of
is gravity-dependent, bl ood can also poo l in the pelvis pelvic surgery where bleedin g, raw surfaces and the
907
908 The Medical and Surgi cal Practice o f NaProTECHNOLOGY
need for sutures is present, adhesions are likely to form For the young surgeon beginning to use this type of
if cou nter measures are not taken. surgical approach ora more experienced surgeon w ho
wishes to become more invo lved with it, the biggest
hurdle to overcome is the actual bel iefthat one can do
Surgical Anti-adhesion Measures --~ major surgica l procedures in such a way as to reduce
adhesions. In actua l fact , there has been a considerable
In order to prevent or signi ficantly reduce the appear- amount ofprogress made in thi s field over the last 15 to
ance of pe lv ic adhesions following a reconstructive 20 years. However, much ofthi s has onl y reached cer-
pelvic su rgery, the surgeon mus/ alfend to the details tain major centers and university programs. Young ob-
of surgical anti-adhesion technique. Over the years , stetrician-gynecologists are, for the most part, not ad-
there has been a tendency to suggest that one or an- equately instructed in good adhe ion-prevention tech-
other ap proach to adhesion prevention will resu lt in an nique . Having said this, the details of this chapter are
an ti-adhesion postoperative environment. However, within the reach of every gynecologic surgeon and we
there is no one approach or one surgica l technique that owe it to our patients to see that we implement it. These
wi 11 accomp l ish this. In fact, an anti-adhesion oradhe- techniques, in the genera l order in w hich they are uti-
s ion-free environmenl can only be accomplished when li zed in the operati ng room, are now described.
a compehensive surgica/ approach to adhesion pre-
ven /ion is implemented.
Skin lncision
This comprehensive approach to surgical technique
begins with the sk in incision and progresses to the way Adhesion prevention begins with the skin incision (F ig-
the bowel is packed away, the type of retraction one ure 67-1 through 67- 11 ). The incision in the skin is made
uses, the use of constant irrigating solutions, the type with a scalpel and the subcutaneous tissue is taken
of suture th at is chosen , the use of microsurgical tech- down with electroca utery at the usual setting to get
niques, the technique for closi ng a li tissues and repair- good hemostasis. Prior to opening the fasc ia, the sub-
ing them , uterine suspension, the use of various anti- cutaneous tissue sho uld be met icu lo usly dry (F ig-
adhesion barriers, meticu lous hemostasis at the con- ure 67- 1).
clusion ofthe surgica l procedure, the use of intraperito-
neal adhes ion prevention instillates and even the way The author prefers to open the fascia with the C0 2 laser
the peritoneum is closed at the conclusion ofthe proce- at 50 watts of continuous energy power. The main rea-
dure, wi ll ali add up to a surgical procedure which can son for this is the decreased amount of discomfort that
significantly reduce the potential for formation or re- is seen following an abdominal laser incision versus
format ion of surg ical ad hesions (Table 67-1 ). standard incisions in the fasc ia with either scalpel or
cautery. However, it is important to be carefu l in how
the fasc ia is opened. 1f the surgeon is experienced, a
laser incision into the fasc ia, which is done fa irly qu ickly,
can be done without injuring the underlying rectus
Table 67-1: Fundamental Anti-adhesion
muscle (F igure 67-2 through 67-6). However, for the new
Techniques
surgeon, a st

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THE

MEDICAL & SURGICAL

Tho1nas W. Hilgers, M.D.

With the exception of short exerpts fo r critica! reviews, no pan of this

lntemational Standard Book Number: 0-9744147-0-0

Medi ca! photography: Th om as W . Hilgers, M.D .

First Edirion July 2004

~ Our patients, who have served th is work so ge nero usly

~ Po pe Paul VI and his encyclical letter Hu manae Vitae

Thomas W. Hilgers, MD, Dip. ABOG , ABLS , SRS

Philip c. Boyle, MICGP, MRCGP, Renée Mirkes, OSF, PhD

Tracey Parnell, MD, NFPMC

Dana Reed-Kane, Pharm. D, FCP,

Joseph B. Stanford, MD, MSPH ,

About the Author vii

List of Abbreviations xli

Special Note xliii

Renée Mirkes, OSF, PhD

41 PART 1: lntroduction to the CREIGHTON MODEL System

Basic C harting • Bas ic C hart Read ing

ldentification of Potential Situati ons/Problems • lnterpretation of ltems ldentified • lntegration of

249 PART 11: Laboratory Support for NaProTECHNOLOGY

Targeting the Cycle

PART 111: Medica! NaProTECHNOLOGY 291

Overview of Stero id Biochemistry • Progesterone and Estrogen Receptors • Effects of Progesterone

Types of Progesterone Support • Human Chorionic Gonadotropi n (HCG) • Cooperative Estrogen

Exercise and Nutrition: Non-Pharmacologic Approaches to Treatment • Phannacologic Therapy •

Endo metri al Ca ncer • Breas! Ca ncer • Ova ri an Ca ncer • Final ote

Theory • Di agnosis • Treatment • Resu lts of Treatment • Final ote

PART IV: lnfertility 475

Keeping Perspective • Clom iphene Citrate • Human Menopausa l Gonadotropins • Gonadotropin-re-

Measuring Effectiveness • Results of NaProTECHNOLOGY • Conclusions

PART V: Perinatal NaProTECHNOLOGY 695

Pope Paul VI lnstitute Eva luati ons • Final Note

837 PART VI : Surgical NaProTECHNOLOGY

Techni cal Consideration • Nea r-Contact Laparoscopy (NCL)

Appendectomy • Small Bowel • Rectos igmoid Colon • Anteri or Rectum

Surgical Techn ique

The LUNA Procedure: Technical Details • Results • Final Comment

Laparoscopy: Postoperative Ca re • Laparotomy: Postoperative Care • Laparo copy: Comp lication s •

PART VII : NaProTECHNOLOGY in Practice 1099

Chronic Di scharges • Targeted Hormone Profi le • CPRT/CE RT • Premenstrual Synd ro me • Ovarian

lnformed Consent • Researc h Strengths • Limitations of this Study • Evidence-Based Re producti ve

CREIGHTON MODEL System • Laboratory Suppon • Medica! NaProTECHNOLOGY • Reproductive

Progesterone Assessment in Pregnancy:

ln Humana.e Vitae, Pope Paul VI wrote:

Resp onsib/e Parenthood

Respect for the Nature and Purpose of the M arriage Act

To Doctors and Medica/ Personnel

... the thoug ht o/ St. Thomas A quinas

Aga in, in the encyc li ca l, Fides et Ratio Pope Jo hn Pa ul 11 continues :

[n the Pastoral Directives of Humanae Vitae , Pope Paul VI says :

Furthermore, he teaches in a very profound and understandable fashion that "contraception :

~1...e.i-e "'""·Jt !:e Pe..i-c:e

'J¡ 'J C-"l-I\. di,e.-"i,ll\.

We ' re lost in a cloud

And while [can think

Please let my dream

Thomas W. Hilgers, M .D.

the CREIGHTON MODEL FertilityCare™charts that are included in this book.

AAFCP American Academy ofFertilityCare Professiona ls

BBT basal body temperature

CERT cooperative estrogen replacement therapy

FCCA FertilityCare™ Centers of America

The Medical & Surgical Practice of NaProTechnology (2004, Hilgers)

The Medical & Surgical Practice of NaProTechnology (2004, Hilgers)

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