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Enyonam Yao Kwawukume

Bissallah Ahmed Ekele
Kwabena Antwi Danso
Eiiro Eddie Emuveyan
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COMPREHENSIVE
GYNAECOLOGY
IN THE TROPICS
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CHIEF EDITOR
Prof. E Y KWAWUKUME
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I President, Family Health Medical School, Family Health University College, Accra
Professor of Obstetrics and Gynaecology, University of Ghana Medical School
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lnaugural KK Bentsi-Enchill Professor and Chair, College of Health Sciences, University of Ghana
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Former Head, Department of OBGYN Korle Bu Teaching Hospital
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Examiner, West African College of Surgeons
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SUB . EDITORS
Prof BA Ekele Prof KA Danso Prof EE Emuveyan
BA Ekele
P;;f*;;; of obstetrics and Gynaecotost,
..-.i:.i.'.i.
Consultant Obstetrician.Gynaecologisu:Univq$ity,.of Abuja,iGaehrns,iosp.'i ; Abuja, Nigeria
Dean, Faculty of $linical Sciencesii8o[e$lof tHeelth,seiences, Universty of Abuja, Abuja, Nigeria
Former Head, Departrnent of Obstetrics'andiGynaecology, University,o'!Abuia, Abuja, Nigeria
Former Head of Department; UsmqtuD.dnfodiYo.Unittersis Sok$o,,!.t8elB',' ,
Visiting Professor: University rof,Gambia,.,$Iedical Schosl; Baniul,,fherGambia '
KA Danso
Professor of Obstetrics and Gynaecolqgy, KNUSI SMS
Consultant Obstetrician-Gynaecolggist;rKqmfo Anokye Teach,ing'Hospital, Kumasi, Ghana

Former Head, Department of OBGYN -I(NUST SMS and KATH,
i
Former Dean, School of Medical Sciences, Kwame Nkrumah Universi$ of Science and Technology,
Kumasi, Ghana
EEEmuveyan',:.''i'i].]i'l.'.]..:
Professor of Obstetn'cs and Gynaecgtqgf' . : :
Consultant Obstetrician-Gynaecologist, University of Lagos Teaching Hospital, Lagos, Nigeria

Former Head of Department, Univenity,of Lagos, Lagos, Nigeria
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CONTRIBUTING AUTHORS
Abiodun PeterAboyeji, MBBS, FWACS, FIGS.

Professor of Obstetrics and Gynaecology,
Consultant Obstetrician & Gynaecologist, University of llorin Teaching Hospital, llorin, Nigeria
Head, Department of Obstetrics and Gynaecology, University of llorin, llorin, Nigeria
Aisha Nana Adamu, MBBS, M Sc, FWACS.

Consultant Obstetrician & Gynaecologist, Federai Medical Center, Birnin Kebbi, Nigeria
Visiting Lecturer, Department of Obstetrics and Gynaecology, Usmanu Danfodiyo U niversity, Sokoto. Nigeria.
E Teddy Agida, MBBS, FWACS, FICS

Senior Lecturer and Consultant Obstetrician & Gynaecologist, University of Abuja Teaching Hospital, Abuja,
\ Examiner, West African College of Surgeons
Christopher Odianosen Aimakhu, MBBS , FWACS, FMCOG , FICS.

Senior lecturer and Consultant Obstetrician & Gynaecologist, College of Medicine, University of lbadan and
University College Hospital, lbadan, Nigeria
Godwin O. Akaba, MBBS, FWACS

Senior Lecturer and Consultant Obstetrician & Gynaecologist, University of Abuja Teaching Hospital, Abuja,
Oluwarotimi lretiAkinola, MBBS, FWACS, FICS

Consultant Obstetrician-Gynaecologist, Lagos State University Teaching Hospital, lkeja, Nigeria
Former Head, Department of Obstetrics and Gynaecology, Lagos State University, lkeja, Nigeria
F. K. Ankobea- Kokrde
\- Lecturer, School of Medical Sciences
Kwame Nkrumah University of Science and Technology
Kumasi Ghana
Hannah N.G. Ayettey Ani. MB.CHB ,MGCP

Special ist Radiation/Cl i nica I Oncologist
National CentreforRadiotherapy and Nuclear Medicine
Korle Bu Teaching Hospital
Accra
Eric I. Archibong, MBBS, FMCOG, FWACS, FRCOG.

Consultant Obstetrician-Gynaecologist, University of Calabar Teaching Hospital, Calabar, Nigeria
Former Provost, College of Medical Sciences, University of Calabar, Calabar, Nigeria
;- Ayodele O. Arowojolu, MBBS, FMCOG, FWACS, FRCOG.

, Professor of Obstetrics and Gynaecology, :
!' Consultant Obstetrician & Gynaecologist, College of Medicine, University of lbadan and University College
: Hospital, lbadan, Nigeria. Former Head of Department, University of lbadan, lbadan, Nigeria
Contributing Authors
Visiting Professor, University of Gambia Medical School, Banjul, The Gambia

xaminer, West Airican College of Surgeons
Edward Ejiro Emuveyan, MBBS, FMCOG, FWACS, FICS.

, t- Professor of Obstetrics and Gynaecology,
Former Head of Department, University of Lagos, and Consultant Obstetrician-Gynaecologist, University of Lagos
Teaching Hospital, Lagos, Nigeria
' Former UNFPA Reproductive Health Consultant & Consultant ln charge Princess Christian Maternity Hospital,
Fourabay Road, Freetown, Sierra Leone.
. Examiner, West African College of Surgeons
Saturday Job Etuk, MBBS, FMCOG, FWACS, FICS

' Professor of Obstetrics and Gynaecology,
Consultant Obstetrician-Gynaecologist, University of Calabar Teaching Hospital, Calabar, Nigeria
' Former Provost, College of Medical Sciences, University of Calabar, Calabar, Nigeria
' Oluwarotimi O. Fakeye, MBBS, FMCOG, FWACS, FACOG.

:-
- - Consultant Obstetrician & Gynaecologist and Former Chief Medical Director, University of llorin Teaching
Hospital, llorin, Nigeria
" Examiner, West African College of Surgeons
Osato F. Giwa-Osagie, MA, MBBChir, M Sc, FRCOG, FWACS, FICS.

' Emeritus Professor of Obstetrics and Gynaecology,
Former Consultant Obstetrician & Gynaecologist, Lagos University Teaching Hospital, Lagos, Former Head of
. Department, University of Lagos, Nigeria
Past President, West African College of Surgeons
.
Bismarck Hottor MB, ChB, PhD
. Lecturer, Dept of Anatomy
School of Medicine and Dentistry
Korle Bu Teaching Hospital; Accra, Ghana
Hadiza S. Galadanei, MBBS, MSc, FWACS, FRCOG

' \- Professor of Obstetrics and Gynaecology
Consultant 0bstetrician & Gynaecologist, Aminu Kano Teaching Hospital, Kano, N igeria
. Former Head, Departmeni of 0bstetrics and Gynaecology, Bayero University, Kano, Nigeria,
' Audu ldrisa, MBBS, FWACS, FICS

Professor of Obstetrics and Gynaecology
. Consultant Obstetrician and Gynaecology, University of Maiduguri Teaching Hospital, Maiduguri,
Former Head of Department, University of Maiduguri, Nigeria
xaminer, West African College of Surgeons.
. Joseph L lkechebelu, MBBS, FWACS, FICS

. Professor of Obstetrics and Gynaecology
Consultant Obstetrician and Gynaecologist, Nnamdi Azikiwe University and Teaching Hospital, Nnewi, Anambra
State, Nigeria.
' Former Dean, Faculty of Medicine, Nnamdi Azikiwe University, Awka, Nigeria.
\- Examiner, West African College of Surgeons.
. John E. lkimalo, MBBS, FWACS, FICS.

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Comprehensive Gynaecology in the Topics
Consultant Obstetrician & Gynaecologist, University of Port Harcourt Teaching Hospital, Port Harcourt,
Former Dean, Faculty of Medicine, University of Port Harcourt, Nigeria
Aliyu Yabagi lsah, MBBS, FMCOG

Associate Professor of Obstetrics and Gynaecology,
Consultant Obstetrician and Gynaecologist, University of Abuja Teaching Hospital, Abuja,
Head of Department of Obstetrics and Gynaecology, University of Abuja, Abuja, Nigeria
Examiner, National Postgraduate Medical College of Nigeria
Celestine Theophilus John, MBBS, FMCOG, FWACS, FRCOG, FICS, KSM.

Visiting Consultant Obstetrician & Gynaecologist, Federal Medical Center, Yenagoa, Nigeria
Former Head of Department of Obstetrics and Gynaecology, University of Port Harcourt, Nigeria
CecilAdjei Klufio, MBChB, FRCOG, FRCSE, FWACS, FGCS

Associate Professor of Obstetrics and Gynaecology
Former Head, Department of OBGYN, Papua New Guinea
Thomas O. Konney MD, FWACS, FCGS

Lecturer and Senior Specialist
School of Medical Sciences, Kwame Nkrumah University of Science and Technology.
Consultant Gynaecologic Oncologist, Department of Obstetrics and Gynaecology,
Consultant 0bstetrician-Gynaecologist, Komfo Anokye Teaching Hospital, Kumasi, Ghana
lsaac Koranteng, MB ChB, FWACS, FGCS

Senior Specialist,
Department of Obstetrics and Gynaecology, University of Ghana Medical School
Consultant Obstetrician and Gynaecologist, Korle Bu Teaching Hospital, Accra, Ghana
Robert A. Kwame-Aryee, MBChB, FWACS, FGCS

Senior Lecturer,
Department of Obstetrics and Gynaecology, University of Ghana Medical School
Consultant Obstetrician ahd Gynaecologist, Korle Bu Teaching Hospital, Accra, Ghana
Examiner, West African College of Physicians and Surgeons
Enyonam Yao Kwawukume, MBChB, FWACS, FGCS, FACOG. ADM. & MGT
President and Founder, Family Health Medical School, Family Health University Collge, Accra
Professor of Obstetrics and Gynaecology, University of Ghana Medical School
lnaugural KK Bentsi-Enchill Professor and Chair, College of Health Sciences, University of Ghana
Henry Laryea, MB CHB, FWACS, FGCS

Senior Specialist, Korle Bu Teaching Hospital, Accra
AnyeteiTornyeli Lassey, MBChB, FRCOG, FWACS, FGCS

Associate Professor of Obstetrics and Gynaecology, University of Ghana Medical School
vill
Kareem Mumuni, BSc. MB, CHB, FWACS, MPH, FGCS

Senior Specialist and Lecturer. School of Medicine and Dentistry, Korle Bu, Accra
o Josiah Turi Mutihir, MBBS, FWACS, FICS.
Consultant Obstetrician and Gynaecologist, Jos University Teaching Hospital, Jos, Nigeria
Former Head of Department, Faculty of Medical Sciences, University of Jos, Nigeria
Kobby Nkyekyer, MBChB, FRCOG, FWACS, FGCS

Associate Professor of Obstetrics and Gynaecolgy, University of Ghana Medical School
Micheal Ntumy, MB ChB, FWACS, FGCS

Senior Specialist and Lecturer, Department of OBGYN, University of Ghana Medical School
-.
Emmanuel lfeanyichukwu Nwobodo, MBBS, FWACS, FICS
Consultant Obstetrician & Gynaecologist, Usmanu Danfodiyo University Teaching Hospital,
Former Head of Department, Usmanu Danfodiyo University, Sokoto, Nigeria
SamuelA. Obed, MBCHB, FWACS, FGCS

Associate Professor of Obstetrics and Gynaecology, University of Ghana Medical School
Head, Department of Obstetrics and Gynaecology Korle Bu Teaching Hospital, Accra, Ghana
Alexander Tawiah Odoi, BSc, MBChB, FWACS, FGCS

Associate Professor of Obstetrics and Gynaecology, Kwame Nkrumah University of Science and Technology
School of Medical Sciences, Kumasi.
Consultant Obstetrician-Gynaecologist, Komfo Anokye Teaching Hospital, Kumasi.
Former Head, Department of OBGYN KNUST SMS and KATH
i ,_ Examiner, West African College of Surgeons
; Akintude A. Odukogbe, MBBS, M. Sc, FMCOG, FWACS

i nssociate Professofr and Consultant Obstetrician & Gynaecologist, College of Medicine, University of lbadan and
i University College Hospital, lbadan, Nigeria
r Examiner, West African College of Surgeons
Richard A. Offiong, BM BCh, FWACS, FICS

- Chief Consultant Obstetrician & Gynaecologist, University of Abuja Teaching Hospital, Abuja,
Coordinator, PMTCL University of Abuja Teaching Hospital, Abuja, Nigeria
- Examiner, West African College of Surgeons
. Anthony Amanfo Ofori; BSc, MB ChB, FGCS, MBA

Obstetrician a nd Gynaecologist,
t<umasi, Ghana
;--* Olasurubomi K. Ogedengbe, BMBCh, MA, FMCOG, FWACS, FRCOG.

r Professor of Obstetrics and Gynaecolory,
. Consultant Obstetrician & Gynaecologist, Lagos University Teaching Hospital, Lagos, Nigeria
Former Head of Department, University of Lagos, Nigeria

Past President, West African College of Surgeons
Olayinka O. Ogunbode, MBBS, FWACS, FMCOG, FICS.

Senlor lecturerand Consultant Obstetrician & Gynaecologist, College of Medicine, University of lbadan and
University College Hospital, lbadan, Nigeria
Temidayo O. Ogundiran, MBBS, FRCS, FWACS

Consultant General Surgeon, University College Hospital, lbadan Nigeria
Joseph A. Olamijulo, MBBS, FMCOG, FWACS, FRCOG

Associate professor, University of Lagos and Consultant Obstetrician-Gynaecologist, University of Lagos Teaching
Hospital, Lagos, Nigeria
Former Head of Department, University of Lagos, Nigeria
Examiner, National Postgraduate Medical College of Nigeria
Timothy O. A. Oluwasola, MBBS, M Sc, FWACS.

Lecturer in Obstetrics and Gynaecology,
Consultant Obstetrician & Gynaecologist, University of lbadan and University College Hospital, lbadan, Nigeria
Raymond Ugochukwu Okolo, MBBS, M Sc, Ph D

Senior Lecturer, Department of Anatomy, University of Abuja, Abuja, Nigeria
Former Head, Department of Anaiomy, Usmanu Danfodiyo University, Sokoto, Nigeria
Jude Okohue, MBBS, FWACS, FMCOG, FICS,

Senior Lecturer,
Department of Obstetrics and Gynaecology, Madonna University and Teaching Hospital, Elele, Rivers State,
Nigeria,
Anthony O.U. Okpani, MBBS, FWACS, FICS

Consultant Obstetrician & Gynaecologist, University of Port Harcourt Teaching Hospital,
Former Head of Department, University of Port Harcourt, Nigeria
Examiner, West African eollege of Surgeons
Akinyinka O. Omigbodun, MBBS, FMCOG, FWACS, FICS.

Consultant Obstetrician & Gynaecologist, University College Hospital, lbadan, Nigeria
Former Provost, College of Medicine, University of lbadan, Nigeria
Lawrence A. Omo-Aghoia, MBBS, FMCOG, FWACS

Consultant Obstetrician & Gynaecologiit, Delta State University Teaching Hospital, Oghara, Dean, Faculty of
Medicine, Delta State University, Abraka, Nigeria
Olatunde Onafowokan, MBBS, FMCOG, FWACS.

Consultant Obstetrician & Gynaecologist, University of Abuja Teaching Hospital, Abuja, Nigeria
Former Head of Department, University of Abuja Teaching Hospital, Abuja, Nigeria
Henry Sakyi Opare-Addo, BSc, MBChB, FWACS, FGCS

Assoiiate irofessor of Obstetrics and Gynaecology, Kwame Nkrumah University of Science and Technology
School of Medical Sciences, Kumasi. :
Consultant Obstetrician-Gynaecologist, Komfo Anokye Teaching Hospital, Kumasi.

Former Head, Department of OBGYN KNUST SMS and KATH
,\ Examiner, West African College of Surgeons
Baafuor KofiOpoku, BSc, MB Chts, FWACS, FGCS

Associate Professor, Department of Obstetrics & Gynaecology, Kwame Nkrumah University of Science &
Technology School of Medical Sciences, Kumasi
Consultant Obstetrician/Gynaecologist, Komfo Anokye Teaching Hospital, Kumasi.
Examiner, West African College of Surgeons.
Roderick Emil Larsen-Reindorf, BSc, MBChB, MSc BioMedED, FWACS

Senior Speciallist and Lecturer, Department of Obstetrics & Gynaecology, Kwame Nkrumah University of Science
& Technology, Kumasi
Co nsu lta nt Obstetri cia n/Gynaecol ogist, Komfo AnokVe Teach i ng Hospita I
AliSamba, MB, CHB, FWACS, FGCS

Senior Specialist and Lecturer, University of Ghana Medical School
, Director, Family Planning and Reproductive Health, Korle Bu Teaching Hospital, Accra, Ghana
PearlAba Anoa Scott, MB,ChB ,MGCPS

Specialist Radiation / Clinical Oncologist
National Centre for Radiotherapy and Nuclear Medicine
Korle Bu Teaching Hospital
Accra, Ghana
Joseph D. Seffah, MBBCh, FWACS, FGCS

Associate Professor of Obstetrics and Gynaecology, Ghana Medical School
Former Deputy Provost, College of Health Sciences, University of Ghana,
Daye Seleye-Fubara, MBBS, FWACB FMCPath

Professor of Pathology, Department of Anatomical Pathology,
\- University of Port Harcourt, Port Harcourt, Nigeria
Examiner, West African College of Physicians
Sunday Oladapo Shittu, MBBS, FWACS, FICS

Professor of Obstetrics and Gynaecology
Consultant Obstetrician & Gynaecologist, Ahmadu Bello University Teaching Hospital, Zaria, Former Head of
Department, Faculty of Medicine, Ahmadu Bello University, Zaria, Nigeria
E K Srofenyoh, MB ChB FWACS, FGCS

Consultant Obstetrician and Gynaecologist
Ridge Regional Hospital
Accra, Ghana
C N B Tagoe, MB. ChB, PhD

Professor of Anatomy, School of Medicine and Dentistry, Korle Bu
\- Former Vice-Chancellor, University of Ghana, Legon
Examiner in Anatomy, Faculty of Surgery, West African College of Surgeons
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Comprehensive Gynaecologlr in the Topics

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JamiluTukur, MBBS, FWACS, FICS

Professor of Obstetrics a nd Gynaecology,
Consultant Obstetrician & Gynaecologist, fotdm lGno Teaching Hospital, Kano, Nigeria
Former Head of Department, Bayero Unhe#,furo, Nigeria
Exa m iner, West Africa n Col lege of Surgeoqe'
Karima Tunau, MBBS, FWACS.

Senior Lecturer and Consultant Obstetrician & Qrnmologist, Usmanu Danfodiyo University Teaching Hospital,
and Usmanu Danfodiyo University, Sokoto, t$Cria
CornetiusArcherTurpin, BSc, MB Ch8, Rffffii, FGCS

O bstetri cs a nd Gynaesql@r
Associ ate Professor of
Head, Department of Obstetrics and Gynaecology, Kwame Nkrumah University of Science and Technology
School of Medical Sciences and KATH, Kumasi.
ConsultantObstetrician-Gynaecologist, KomfoAnokyeTeachingHospital, Kurnasi.
Examiner, West African Cotlege of Surgeons. i
Vena DNKVanderpuie,
MBCHB, FWACS, FGCPS
Consultant Radiation And Clinical Oncologist Dept Of Radiation Oncology I
Korle Bu Teaching HospitalAccra Ghana W-Africa I
lbrahimAdamuYakasai, MBBS, FMCOG, FWACS, FRCOG, FICS

Professor of Obstetrics and Gynaecolory,
Dean, Faculty of Medicine, Bayero University, Kano, Nigeria
Consultant Obstetrician & Gynaecologist, Aminu Kano Teaching Hospital, Kano, Nigeria
Former Head of Department, Bayero University, Kano, Nigeria
Examiner, West Af rican Col lege of Surgeons
x$
FOREWORD
I feel privileged to be asked to write a foreword for the second edition of the 'Comprehensive Gynaecology in
the Tropics'.
When Tim Johnson and I discussed the idea of training Residents fully in Ghana so that the number of
Obstetricians in the country would increase, the possibility seemed so remote that I felt we'were dreaming!
The start of the full Postgraduate training programme in Ghana sponsored by the Carnegie Corporation of New
York in 1989 was a "silver lining" in the cloud that had come over postgraduate training as residents could no
longerfurthertheirtrainingabroadforlackof financialsupport. The program brought in theAmerican Collegeof
Obstetrics & Gynaecology (represented by Professors Tim Johnson, Tom Elkins and J. Sciarra) and the Royal
College of Obstetrics & Gynaecology (represented by Professors J. B. Lawson and John Macvcan) to help in
training our residents. Today, nearly 150 specialists have qualified from both the West African and Ghana
Postgraduate Colleges. lt is worthy of note that all the lecturers in the Obstetrics & Gynaecology Departments of
the Medical Schools in Ghana are products of this program. The dream came true with the graduation of ourfirst
specialists - Drs. G. Addo Tagoe (of blessed memory), Yao Kwawukume and Kwabena Danso.
Prof. Yao Kwawukume, the Chief Editor of this book, with whom I have been associated for nearly four decades,
used to "think and dream big". His tenacity of purpose and dogged determination has led not only to the
production of the books, 'Comprehensive Obstetrics', 'Comprehensive Gynaecology', and 'Comprehensive
Reproductive Health and Family Planning', but also to the establishment of a private specialist Hospital, a
private Nursing and Midwifery School, and the first private Medical School in Ghana which is now a University
College. I doff my hat to him and say, 'Ayekoo".
Prof. Kwabena Danso and I have been associated since his residency days. His profound academic knowledge
and excellent clinica.l skills propelled him to become Head of the Obstetrics and Gynaecology Department and
then Dean of the Kwame Nkrumah University of Science and Technology Medical School.
Professors Emuveyan and Ekele are both distinguished academics in Lagos and Abuja respectively and have
both served as Heads of Departrnent in their Universities and Chairmen of the Faculty of Obstetrics and
Gynaecology (West African College of Surgeons). Prof. Ekele is currently Dean of the Medical School in Abuja.
I wish to congratulate all the Editors and Contributors for a job well done.
The text book'Comprehensive Gynaecology in the Tropics' came out in 2005 as a complement to the obstetric
volume and it offers a very detailed book for practice in the topics. ln only a few years a new edition has been
produced. The Editorship and Contributors have been extended to involve teachers from many more Universities
in the West African Sub-region who are also specialists involved in active clinical practice. They have brought
their vast academic knowledge and rich clinical experience to the production of this book. Most of the
contributors are also Examiners in their various Medical Schools and the West African College of Surgeons, the
Nigeria Postgraduate Medical College and the Ghana College of Physicians and Surgeons. The topics have been
reviewed in line with advancing knowledge of Gynaecology and two new chapters have been added.
xilt
The book is very easily readable, and B &
ortlutt read" for Residents in training and 6ll.!9.]orerpQcti!ln$
Gynaeeolory in the Sub-region.Und4 t students can also use this as a reference book. The book
is a must read beeause it is th€ written cxclusively by West African authors for
practitioners, teacherc a nd
I gladly recommend the second prehensive Gynaecology in the Tropics to all who
practice Gynaeeology in the
Bh John Baptist Wtlsun K$G" ',r,,.,,,,'...

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FormerHead,Departm6ntooffiUniversityofGhanaMedical&DentalSchool
Korte Bu Accra, Ghanr, rr:!r&::;+.$;*1ii-+,!:i;-ii:r l.
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Former Chainnan, Faculty of,.OU tl&st African College of Surgeons;
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Preface to the second edition
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PREFACE TO THE SECOND EDITION
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It is almost two years that the second edition of the eqmpanion volume to this book, , Comprehensive Obstetrics
in the Tropics 2nd Edition, was published. Just as was thq case for rpvising CompreJrensive Qbstetrics in the
Ttopics, the specialty of Gynaecology continues to develop and advance with new information each passing day.
Revising a textbook such as this with a view to keep abreast with these advances is.always a challenge. There is
already a plethora of textbooks on gynaecological practice in high income countries. But this is yet not the
situation in low income or developihg countries where very few textbooks are found , written by purely sub=
regionalteacherswith emphasison the practicalapproaeh to the trainingof both undergraduateand post'
graduate medical students in these areas. This edition of Comprehensive Gynaecology in the Tropics
has therefore also been done with these objectives in mind.
ln line with the need for a multidisciplinary approach to the challenges of clinical practice and the understanding
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of the discipline of Gynaecology, many new and young contributors have been added to the original ones to
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generate a hybrid of experts. Contributors are all fellows in the West African sub region currently involved in
i teaching, training, examining and shaping of Gynaecological care and to that extent have f irst-hand experience
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and are also conscious of evidence-based practice. The chapters have therefore been revised and updated based
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on current evidence and best clinical practice. Besides, new chapters have been included in this edition and the'
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editorial team has worked closely to maintain the template and format of the f irst ed ition.
The book is still focused mainly on problems and solutions to Gynaecological practice in the tropics.
Furthermore, the excitement of "controversies and discussions at the end of the chapters" has been retained
because these are the issues that the post graduate student faces at grand ward rounds and during fellowship
examinations. The different opinions expressed by faculty members are some of the 'ammunitions' needed to
r su rvive these sessions!
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As usual, we welcbme comments and constructive criticisms from our readers worldwide towards the
preparation and enrichment of future editions of the textbook. Happy reading!
EY Kwawukume, Accra, Ghana

BA Ekele, Abuja, Nigeria
KA Danso, Kumasi, Ghana
EE Emuveyan, Lagos, Nigeria.
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Acknowledgment
ACKNOWLEDGMENT
The editorial team is very gratbfulb of the University of Michigan, Ann Arbor, USA, for
his perpetual mentorship, suppOrtifr f towards the development of the first and now, the
second edition of this book. We fwffi thank the contributing authors and their affiliate
institutions, as well as all those u'+i"t;Fa$g but quietly with the authors behind the scenes,
retris* :
.':... #i
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towardsthe preparation of their
We give special thanks to our , , Agnes, and Eseovwe and our children for the
encouragementand the insplration*htf frmnthe beginningto completion of this book.
Finally, the Editorial team and Contributors wish to rccognlze and thank,Abigail , Family Health Medical School,
Family Health University College, Accratheseretariatsupport in the preparation of this second edition
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Table of contents
TABLE OF CONTENTS
\- 1:
" ,,1:
.
. SECTION I- BASIC SC]EMGES
CHAPTER I _ EMBRYOLOGY 01-16

Bismarck Hottor
CHAPTER 2 - FUNDAMENTALS OF HUMAN GENETICS t7-32

Bartholomew Dzudzor
CHAPTER 3 _ FEMALE REPRODUCTIVE ORGANS 33-50

C N B Tagoe and R lJ Okolo
\- CHAPTER 4 _ REPRODUCTIVE ENDOCRINOLOGY - BASIC CONCEPTS 51-66

EY Kwawukume and L A Omo-Aghoja
SECTION 2 . GENERAL GYNAECOLOGY
I cHAprER 5 - HrsroRy AND ExAMTNATIoN 67-82

CA Klufio and BA Ekele
CHAPTER 6 _ REPRODUCTIVE HEALTH 83-88

i S OShittu ASambaand EY Kwawukume
r
I CHAPTERT-MTSCARR|AGE 89-96
I n S. Galadanci
I
r \- CHAPTER 8 -
ECTOPIC GESTATION 97-LO6
II tY Kwawukume and BA Ekete
I
It- CHAPTER9-VULVOVAG|N|TTS 107-tL4

f
l. Koranteng, R Acquaah- Arhin, E Y Kwawukume
I ,
: CHAPTER 10 - HIV/ AIDS AND OTHER STDS 1 15-136

I RUOffiongandGOAkaba
:
r CHAPTER 1I - PELVIC INFLAMMATORY D]SEASE Lg7-146
', J D seffah
I
T CHAPTER t2 * ABNORMAL UTERINE BLEEDING 147-156
; BA Ekele
CHAPTER 13 _ BARTHOLINS GLAND CYST AND ABSCESS 157-160

2* Kareen Mumuni'and T Boafo, K A Danso,
F
r CHAPTER 14 - BENIGN LES]ONS OF THE VULVA L6L.T72
i P AKwame-AryeeandTBoafo
t"
rvt!
CHAPTER 15 - LEIOMYOMA OF THE UTERUS 173-186.

EY Kwawukume, M Ntumy
CHAPTER 16 _ PELVIC RELAXATION 187-196

S A Obed and M Ntumy
CHAPTER 17. URINARY INCONTINENCI 1,.972O6,

K A Danso, Ankobea- Kokroe and Ofori-Manfo
CHAPTIR 18 * ADNEXAL MASSES 207-2tO ,
K A Danso, C A Turpin and J.J.K Annan
CHAPTER 19 - ENDOMETRIOSIS 2tt-222

CTJohn,andJllkimalo
CHAPTER 20 _ DYSMENORRHEA AND PREMENSTRUAL SYNDROME (PMS) 223-232'

'.
C O Aimakhu and O Fakeye
CHAPTER 2I - GENITAL TRACT FISTULAS 233-2.42

KADansoandAfkssey
CHAPTER 22 _ SEXUAL DYSFUNCTION :::. i ,?:3:21?

B A Ekete and A N Adamu ' ' :'ii 1'
CHAPTER 23 _ THE FEMALE BREAST 253-260

l,
A:O Omigbodun And T O Ogundiran - i
CHAPTER 24 _ OPERATIVE ENDOSCOPY IN GYI{AECOLOGY 261-276

,: :'
J.l lkechebelu and J Okohue .l ..
CHAPTER 25 _ PREOPERATIVE MANAGEMENT 277-284

A Y lsah and O Onafowokan
CHAPTER 26 _ POSTOPERATIVE CARE AND COMPLICATIONS 285-304

j.l'r.'
R- E, Larsen-Rei ndorf and H S Opare-Addo :
,:
CHAPTER 27 - ADVANCES IN CONTRACEPTION 305-316
-i,
J T Mutihir and E E Emuveyan
CHAPTER 28 _ INFECTION PREVENTION 317-336

BRDTAnnanandASamba
CHAPTER 29 - ABNORMALITIES OF THE FEMALE GENITAL TRACT

AND ACQU IRED GYNAETRESIA ' 337-346
i ,.
APAboyejiandJDSeffah
CHAPTER 30- FEMALE GENITAL MUTILATION , ,, ' .: i 347-3,60

i^. .l.
AT Odoi and ET Dassah
CHAPTER 31* DIAGNOSTIC PROCEDURES

' :1 I
"361-390
P H Daru, ET Agida and EY Kwawukume
'xIilil
Table of esntents
SECTION 3 - REPRODUCTIVE ENDOCRINOLOGY AND INFERTILITY
E Y Kwawuhume and K. Adu-}onsafful,
CHAPTER 33 - PUBERTY 401-406

E t Nwobodo and K Tunau
CHAPTER 34 - AMENORRHOEA to +0'7-422

EE Emuveya,
CHAPTER 35 _ ANOVULATION AND INDUCTION OF OVULATION 423-434
O K Ogedengbe and J A Alamijulo
CHAPTER 36 _ POLYCYSTIC OVARY

'vARY SYNDROME SYNDR,ME 435-440
I A yakasai and J Tukur
I QHAPTER 37 _ INFERTILITY 44I-462
L A Omo-Aghoja and A ldrisa
CHAPTER 38. INFERTILITY SURGERY 463-472

O K Ogedengbe and A A Babah
CHAPTER 39 _ ASSISTED REPRODUCTIVE TECHNOLOGY 473.488

O F Giwa - Osagre and E R Efetie
CHAPTER 40_ THE CLIMACTERIC AND MENOPAUSE 489-502

O a Agunbode and A O Arowojolu
CHAPTER 41 _ HYPERPROLACTINAEMIA AND PROLACTINOMAS 503-520

C A Klufio and Jerry Coleman
\ SECTION + . CVTTNECOLOGY ONCOLOGY
CHAPTER 42- PRINCIPLES OF RADIATION THERAPY AND CHEMOTHERAPY 52T-542

I N GYNAECOLOGICAL CANCER
Verna DNK Vanderpuye, Pearl Aba Scott, Hannah Ayettey-Anie
CHAPTER 43- PREMALIGNANT LESIONS OF THE FEMALE GENTTAL TRACT 543-564

O. Konney, E K Srofenyoh and EY Kwawukume
T.
CHAPTER 4/$_ CERVICAL CANCER 565-582

R Kwame - Aryee
CHAPTER 45 - ENDOMETRIAL HYPERPLASIA 583-588

Baafuor K. Opoku and E.
Y Kwawukume
CHAPTER 45 _ ENDOMETRIAL CANCER 589-604

F.
I Henry Laryea, A A Odukogbe and B Audu, EY Kwawukume
xlx
,,
ComprehensftnsGyna i1n X6.'ffi-
CHAPIER 47 _ EPITHEL.{AI 6Q5-634

CA Ktufio and T. O. KonneY
CHAPTER 48 - OVARIAN 635-646

A A Adukagb and TAA
CHAPT,ER 49 . SEX - CORD. 647-654

A.O.U. Okpani and Daye
655-670
CHAPTER 50 - VULVAR
C A Klufio and Jerry Coleman
CHAPTER 51 _ GESTATIONAL 671-68,6

K Nkyekyu and O I Akinsla
CHAPTER 52 - REPRODUCflITE PREGNANCY 697-693

A A dmisbodun and A A Ayinde
;j
l
..a
!
i
sir.rliii;,ll*r, .:.r.-
cHAPTE-1
Embryology
Bismarck Hottor
GAMETOGENESIS
The hurnan male got it all wrong right from the Gametogenesis - formation of the male and female
beginning, so that from the days of yore, he arrogated gametes by processes that always involves Meiosis,
unto himself superiority and supremacy, even and this takes place only in the gonads. ln the male
lordship over his female qounterpart. Little did he gonad, gametogenesis is called spermatogenesis
reali2e that nature had already bequeathed the while in the fernale, gametogenesis is known as
accolade of greater-iespect, honour and dignity to oogenesis. The two processes are similaryet differ in
the human female, by entrusting her with the most many ways
important and delicate assignment of all humanity -
the nurturing of the developing baby and infant, in SPERMATOGENES!S
order to continue the existence of rnanl The male's
contribution to procreation is simply a brief period of Spermatogenesis begins after puberty and takes
placq in the seminiferous tubules of the testes. The
'care-abandon; some may ev€n say of irresponsibil-
ity'. But the onerous task of prenatal nurture,is left to cells in the seminiferous tubule epithelium that will
the respectful good sense and dignified responsibility
eventud]ly form spermatozoa are Diploid
of the female! Therefore,. [fr8 heaftfr of the'woman, spermatogonia' cells. The process involves differen-
ti ation (i pe i'in atocytoge n esi s ) of spe rm atogon a cel Is
r non-pregnant as Well as pregnant should be of i
paramount importance, and should be given the forming primary spermatocytes. Primary spermato-
I
cytes intend undergo first meiotic division resulting
r in formation of secondary spermatocytes which
Society has entrusted its Health to neatttr-carers, and subsequently complete the second meiotic division
I
r in order to understand the compielltjes of the human (Fig 1-1). The cells thus formed are spermatids with
r body and its reproductive probessOs,.students of. haploid number of chromosome number. They are
I
medicine need tostart right from the beginning with .,,-; tra nsfo rrned i nto spwm atozoa th ro u gh cytod ifferen-
i -' -'
i the study of the fu ndamental subject - Em bryology. iion'process that involves loss of most of its cyto-
t
p{asrh, reorganization'of the organelles and acquisi-
i PREZYGOTIC PROCESSES tion of flagellum. While spermatogonia are found in
I
I
!a
the basal.eompartment of the seminiferous tubule
I These are processes that must take place before epithelium, the rest of the cells migrate into the
I
fertilization can occur, namely: adluminbl compartment of,the seminiferous epithe-
t_ 1 Gametogenesis:-formation of sperms and ova ,: lium housed within plasmalemmal invaginations of
2 Uterine Cycle the cytoplasm of the !upporting (Sustentacular) cells
r 3 .Capacitation of sperms of Sertoli) (Fig. 12). The occluding junciions
L
I 4 Acrosomal reaction and fertilixation
between the plasmalemma of adjoining supporting
r
F
5 Zonal and cortical reactions
cells (Fig. L2) constitute the BLOOD-TESTIS
01
7V
BARRIER protecting the developing gamete from

immune attack.
The release of formed sperms from the cytoplasm 0f

the Sertoli cell is termed SPERMIATION.
Cffilhatanffiryulory
FPEEtfirOEEil#S* q,qqEilES16
filrttry RirctX
ryxnnfutila pouyts
t{+rff *{+}0(
dudo G attde C-e
fiEFTIGATIOH
Pffin*y Btmry
sFrrmsffil& Es!&
il*+)ff {d +)0(
dtruHECt dilfil* Gt
HEEr ilH{rmE Dtu&l{
Acmndnrf SmMerI
ffirtniloEAa mqre
aE+v g+N
dil*tu tuubh B
Il +x
Srrg& G nolrr bodhr
*t+N,trlghs
,r+x&dr Itr +Yrhgbe

$cnn rFerm
Fig 1.1 GAMETOGENESIS

EmbryologY
giving rise to secondary oocyte and one polar body.

Therefore, the first ovum to ovulate at puberty would
have been in diplotene for aboui 12years, and the last
to ovulate just before the menopause would be about
I
50 years old. Little wonder, therefore that the older the
woman, the more likely she is to have an abnormal
baby because of the possibility of 'damage' to the
chromosomes duringthe longwait in diplotene.
At the beginning of each ovarian cycle, 15 -20 follicles

begin to develop, usually only one secondary oocyte
Fie 1.2 Blood-testis barrier develops and starts the second meiosis but it gets
arrested, at the 2nd meiotic metaphase stage just
before ovulation. The second meiotic division is only
Formed spermatozoa are stored in the epididymis. lf completed when the secondary oocyte is fertilized. The
their services are not called upon, they are digested and rest undergo atresia. However occasionally 2 or 3 are
absorbed, as new ones are formed. About one hundred teleased, and when fertilized, form unidentical twins
L- million spermatozoa are found in one deciliter of ortriplets.
ejaculum i.e. 100,000,000/dl. Once started (at
puberty) spermatogenesis continues into old age except On the other hand, IDENTICAL TWINS are formed
that thenumber of spermatozoa produce tend to when ONLY ONE OVUM is fertilized, but after its first
decrease with age. mitotic division each daughter cell develops into a
SEPARATE baby. lncomplete splitting of the morula
OOGENISIS forms conjoined (Siamesa twins).
Starts BEFORE BIRTH

ln the 6'n week after fertilization, some oogonia, During the development of the ovarian follicle, the
primordial germ cells migrate from the yolk sac surrounding follicular cells and the oocyte secrete
endoderm into the developing ovaries in the genital glycoprotein material called the Zona pellucida. The
ridge, They undergo several mitotic proliferations up follicular cells which rest on basement membrane, at
until the 5'n month of gestation so that by this time there this stage are stratified and known as granulosa cells.
are about 5,000,000 to 7,000,000 oogonia in each The basement membrane separates the granulosa cells
ovary. Most of these oogonia degenerate leaving only from the surrounding stromal cells (theca folliculli).
one million, each of which is surrounded by epithelial The theca cells will soon differentiate in an inner
follicular cells of the ovary at the time of birth. The secretory layer, theca interna and an outer capsular
surviving oogonia begin meiotic division and they are layer, theca externa all of which exclude blood vessels
now called primary oocyte. The process, however, is from having direct contact with the developing ovum.
arrested at diplotene stage of meiotic prophase I and Thus, like the 'blood-testis' barrier, there is also a 'de
remains so until puberty. The the inhibition of meiosis is facto' BLOOD-OVARY BARRI ER.
caused by meiosis=preventing-substance believed to be
Once ovulation has occurred, the follicular cells are
elaborated by fol icular cel ls of the ovaries. At the ti me of
I
quickly transformed by the Pituitary gland hormone
the birth of the female, the total number of primary Luteinizing Hormone (L.H.), into very large
oocyte in their ovaries is about 600,000 to 800,000. progesterone secreting cells to form the Corpus
Many oocytes degenerate between childhood and Luteum, which will continue to secrete for 9-10 days
puberty so that at puberty a female will have between
postovulation. lts progesterone secretions are needed
300,000 and 400,000 follicles. Only about 450 will be for preparing the endometrium for implantation. lf the
ovulated in a woman's life time. At puberty, the ovarian
ovum is notfertilized:
follicles containing primary oocyle and follicular cells
begin to develop. Just preceding ovulation, there is a
(i) The 2"omeiotic division is not completed and the
surge in luteinizing hormone concentration, and
ovum dies
together with meiosis-inducing substance, the primary
, (ii) The Corpus Luteum, involutes, and overthe next
oocyte resume and completes the first meiotic division 4-5 days is replaced by a fibrous (scar) tissue
03
called Corpus Albicans. Thus the events from the granulosa cells and continued formation of f luid filled
development of the primordial follicle to the space within the granulosa cells. This results in the
corpus albicans constitute the OVARIAN CYCLE. formation of a graafian (mature) follicle. lt is large
(Fig. 13). When there is no fertilization with a diameterthat may be as large as2.5 cm atthe
menstruation occurs which has also been time of ovulation.
euphemistically described as the 'tears of a
disappointed uterus!!!' The cycle then starts Summary of Ovarian Follicular Growth
again. The growi ng fol I icles a re d ivided i nto five stages :
o Primordial,
OVARIAN CYCLE
o primary
. Secondary
At birth each primary oocyte is surrounded by a single o Tertiary
layer of flat cells, and together they form the . Graafian follicle
PRIMORDIAL FOLLICLE, the onty follicles in the young
ovary before puberty. Primodialfollicle
. This is the ovum in a female child at birth
. Surrounded by a single layer of granulosa
cells
.
sr Granulosa cells provide nourishment for the
mi*ldsl ovum
"fffda
. Granulosa cells secrete an Oocyte
Iilfisrf f.
maturation-inhibiting factor keeping the
ElouiluEfr,ttt
ovum in the primordialstate in the prophase
of meiotic division
m*tm{keryf o Then, after puberty, FSH and LH from
&aEilErf#a anterior pituitary work on the ovaries to grow
with follicles
n$ f{ nffiffil O,nydrilfu Cla hn qph

Primary Follicle
a This is the first stage of follicular growth
a Surrounded by one or two layers of flattened
At puberty, the first sign of resumption of oogenesis is granulosa cells.
that the flat cells surrounding the primary oocyte A group of primary follicles are recruited in
become cuboidal and, undergo mitosis soon the late luteal phase of the previous cycle.
increasing their numbers, and are called granulosa Development of these primaryfollicles starts
Cells (Fig. 1.3). with an increase in size of the ovum and its
nucleus.
Under the influence of a Follicular Stimulating The surrounding granulosa cells then
Hormone (FSH) produced by the Pituitary Gland, 15- become cuboidal and multiply to form a
20 follicles begin developing at a time, Once the multi-layer of cells.
follicular cells become cuboidal, that stage is called
Secondary follicle
PRIMARY Follicle stage. At this same stage the
follicular cells and the oocyte secrete a layer of
. The distinctive feature is the granulosa cell
layer.
glycoproteins, Zona Pellucida to surround and a It also has an outerrnost layer of theca cells.
protect the oocyte. The zona pellucida contains three
a The theca adjacent to the basal lamina is the
glycoprotein types, ZPt, ZP ,, and ZP ,. As
theca interna
development continuous, cavities develop within the
the thecal cells merging with the
granulosa cells. These spaces mer-geforming a larger
surrounding stroma is the theca externa.
space called antrum. The follicle therefore The secondary follicle has an independent
transforms into secondary follicle. The follicle blood supply made up of arterloles
develops further by continued proliferation of the
04
Embryology
. The secondary follicle develOps into the (b) to digest the zona pellucida. This is the acrosomal
: tertiary follicle reaction. Then fertilization can occur, usually at the
lateral end of the uterine tube.
The Tertiary follicle
. There is a fluid-filled space calhd the (c) ZONALAND CORTICAL REACTIONS
antrum. As soon as a sperm enters an oocyte, both the zona
. There is further hypertrophy of the theca pellucida and the cell wall of the ovum change their
. tertiary follicle is also bigger than 'the composition and structure so that no other sperm
secondary follicle. can penetrate thern, thus preventing polyspermy of
. The fluid in the antrum consists of a plasma one'ovum and certain death of the zygote. This is
transudate and secretory products of because unlike some ladies, the self-respecting
granulosa cells.
ovum would rather die than soil her impeccable
. The fluid contains high concentration of reputation byallowingtwo gentlemen in l!!
estrogen
TH E PREEMBRYONIC PERIOD
The Graafian follicle
. The tertiary follicle is stimulated further by 1"'Week
gonadotropi ns causing fu rther enlargement
Once fertilization has been completed the zygote
. The antrum enlarges and the follicular fluid
begins a series of rapid mitotic divisions to form the
increases in volume.
morula - a ball of cells. Thegg first cell divisions is
. The ovum is located eccentrically in the
known as cleavage
follicle
o lt is connected to the granulosa layer by the
MORULA
cumulus oophorus granulosa cells.
The morula is formed within 3-4 days as the zygote

FERTILIZATION
moves alongthe uterine tube. lt is formed as the cells
Fertilization is the central feature of reproduction. lt of the compacted embryo divide to form a solid ball
involves the fusion of the two gamete pronuclei to of 16- cells called the morula. Travel of the zygote
form the zygote. Fertilization ours normally in the along the uterine tube is aided by (a) action of
ampullary region of the Fallopian tube but can occyr ciliated cells in the uterine tube epithelium, and (b)
at some other sites. The following steps are involvedr rhythmic contractions of the muscular wall of the
capacitation, acrosomal reaction, and zonal and uterine tube.
cortical reaction.
BLASTOCYST
(a) CAPACITATION: Sperms stored in the epididymis
are incapable of fertilizing the female gamete until During the 32- to 64-cell cycles, the morula in the
they have undergone 'puberty rites', which then uterine cavity imbibes water in such a way that a
empower them to fertilize an ovum. These 'rites,, group of differentiated cells move to one end of the
capacitation, is not well understood but believed to fluid filled structure, to form the inner cell mass and
involve the removal of seminal proteins and polar cells that surround the cavity (trophectoderm).
glycoprotein overlying the acrosomal cap during the This converts the ball of cells, the morula, to a
6-8hrs journey of the sperms through the female sphere, the blastocyst (Fig. 1-4). The differentiated
genital tract. lt is only then that the acrosomal inner cells mass, called embryoblasts would then
reaction ca n occu r to effect fertil ization. form the tissues of the body of the baby, and the
surrounding trophoblastic cells will form the
(b) ACROSOMAL REACTION The ovulated ovum is placenta and other membranes of the embryo.
securely guarded by both, the zona pellucida, and the
Between days 6 to 7 afterfertilization, the blastocyst
f. corona radiata (follicular) cells. Before fertilization
hatches out of the zona pellucida which forms a
can occur, enzymes stored in the acrosomal cap are
shield of protection around the ovum and the zygote
released to (a) disperse the corona radiata cells, and
up until this stage. The free blastocyst is now ready
o5
for implantation. The hatching proce$s is aided by with each half capable of developing into a complete
an enzyme that functions similarly like trypsin. lf the individual (one means by which monoygotic twining
blastocyst does not hatch out within the ap,prqriate can occur).
time interval, the blastocyst can be divided into two
EJbfrophohh,f;t
gEhdErm
hlood rts$l
e*tlt}
{unru6ngld*llt
hE*mi
*SffiITfrfiYYilJ(8fi8
€rd€dfffi
andddsrm
tnffi*rbrXo HiE rylErd*ie rnoeodsr*
$*rf,'tfitb{p$ie *uaturn
sssfryl
ffiimbrffiie efirdi* I'dmdeflli
Fig. 1.4 Blastocyst
IMPLANTAT!ON Second week of development

The blastocyst usually implants on the posterior or ln the mammalian embryo, the earliest development
anterior uterine wall in between the openings of is extraembryonic structures that will support and
glands. lmplantation .(before villus development) nourish the embryo during development. The source
occurs within a period of 7-12 days postovulation. lt of the cells that form the extra-embryonic structures
is the trophoblastic cells, which lead the way with is now known to be from both trophoblast and the
their developed enzymes helping them to pdnetrate inner cell mass. The trophoblast over the inner cell
between the epithelial cells. Slowly but surely, by mass differentiates into an inner layer of cells with
about the 9th day after fertilization, the developing single nucleus and well defined cell outline called
blastocyst has buried itself completely in the cytotrophoblast. The cytotrophoblast layer divide to
endometrium give rise to outer cells, syncytiotrophoblast, that fuse
to form giant cells with undefined cell boundaries,
The endometrium surrounding the embedded and they have multiply nuclei.
Lacunae appear in
blastocyst becomes very oedematous with its cells the syncytiotrophoblast layer. The embryoblast (inner
accumulating large quantities of glycogen and lipids. cell mass) differentiates to form the epiblast and
This is called DECIDUAL REACTION, and soon hypoblast layers.
spreads throughout the whole endometrium, which
ishow known asthe DECIDUA. Epiblast will give rise later to the three germ layers.
Hypoblast on the other'hand is a transi'ent layer that
Pinching off the lower part of the original large is replaced by endoderm
PRIMITIVE yolk sac
Togelher these layers form the bilaminar embryo at
this early stage of embryo development. A cavity
06
Embryology
appears in the epiblast and enlarges to becorne the 2 cell layers. The superficial layer is called the
amniotic cavity. The epiblast cells adjacent to the EPIBLASL the deeper layer, the HYPOBLAST. Thus
cytotrophoblast are called amnioblasts. Cells a BILAMINAR GERM DISC isformed.
believed to derive from the hypoblast layer stream out
and line the inner surface of the cytotrophoblast (3) Cavities: ln addition to the original blastocyst
forming Heuser's membrane. The Heuse/s mern- cavity (chorionic), fluid is imbibed to form another
brane and the hypoblast cell layer constitute the cavitywithin the epiblast layer called the AMNIOTIC
lining of the exocoelomic cavity, now called cavity
exocoelomic cavity or primitive yolk sac. Cells from
the epiblast layer stream out to lie between the The Embryonic Period (3'o to 8'n Week
Heuser's membrane and the
cytotrophoblast thus forming the
' extraembryonic mesoderm. A cavity,
- extraembryonic coelom, develops in
' the extraemb-ryonic membrane lhbffi
- dividing it into somatopleuric Fnffi'"
#Sk
- mesoderm close to the cytotrophoblast
' and splanchnopleuric mesoderm close Ctuicd
. to the Heuser's membrane. The

iitfibEe
remaining unsplit mesoderm is the

BODY (CONNECTING) STALK, which
will become the umbilical cord.
' The original yolk sac, (the primitive

yolk sac) is lined by the flat cells of
' Heuser's membrane, lt is transformed
into a smaller SECONDARY or DEFINI-
s€&i0r$o
r JIVE yolk sac by PRIMITIVE yolk sac, A- M rigr{
The secondary yolk sac is thus smaller 8-Trmurtrscdon
C- tont'tdd rcdor
r drd is lined by cuboidal extra-
, embryonic endodermal cells.
Fig. 1.6 GERM DISC
I
(4) CIIORION The extra-embryonic somatic
I
mesoderm AND the trophoblast TOGETHER form the
F
chorion . At the beginning of the third week, the embryo is

I
I
bilaminar disc rnade up of, epiblast and hypoblast.
I The Znd Week usually termed week of twos (Fig The bilaminar disc has three cavities surrounding it.
1.5). This is because during the second week of These are amniotic, Yolk sac and Chorionic /
development, the cells of the early blastocyst under- extraembryonic cavities. The primitive streak is first
goes a series of differentiations that produce pairs of seen on the epiblastic surface of the embryonic disc
structures from one, and these can be summarised as in the caudal region of the embryonic disc. At this
follows: stage, it is a collection of pluripotent cells that lined
up along its long axis in the midline. The develop-
(1 ) Trophoblast: The superficia I ly- pl aced trophoblast ment of the streak is promoted by the underlying
cells soon begin to fuse thus forming a superficial visceral hypoblast. The cells of the epiblast then
layer of a mass of cytoplasrn with large numbers of produce extraembryonic mesenchyme from its
nuclei dotted in it. This layer is then termed the caudal margin. The epiblast cells on either sides of
SYNCYTIOTROPHOBLAST. The inner layer cells the primitive streak proliferate greatly causing the
tI
with cellwalls are then called CYTOTROPHOBLAST. formation of two ridges on each side of the streak.
I
The streak, as a result, appears to sink between the
(2) Embryoblastr The embryoblasts differentiate into
01
- ---:----!

I
T
ridges. The lower midline portion of the streak is ate at the time the hypoblast cells are being replaced
termed prjmitive groove whilst the ro,stral."r€,ien :is by endodermal cells, and subsequently detach from
the primitive node or Hensen's node. The grirr$tive pit it. The plate then forms a cord of cells, the definitive
is the most rostral part of the primitive gwtre; {f,.!8. to an area caudal to the
notochord that extends
1.6). :;.:: . buccopharyngeal membrane. This area is the
:
:
prechordal plate. Caudally, it reaches the primitive
The appearance of the primitive streak trigws a pit lt has 2 importantfunctions, namely:
process whereby cells of the epiblast either passi*eep 1. lt establishes the antero-posterior axis of the
to the epiblast layer to form the populations of cells embryo and
within the embryo, or remain on the dorsal aspect of 2. lt induces theformation of the neural tube
the embryo to become the embryonic ectoderm.
(3) NEURAL PLATE AND FOLDS
Cells of epiblast first enter the primitive streak and
then invaginate and migrate awayfrom the streak. ln
At the beginning of the 3rd week, and under the
the human embryo, this process of cellular rearrange-
induction of the notochord, the overlying ectoderm
ment, migration and,folding is referred to a gastrula-
undergoes rapid mitosis to form the neural plate
tion, although a' real 'gastrula is not formed. Cell
migration and' specification are
controlled by fibroblast growth
factor 8 (FGF 8) synthesized bY the
streak. Once the cells ingress, some
displace the hypoblast forming
embryonic endoderm.
(1) INTRAEMBRYONIC IJ .
MESODERM
New cells differentiate from the

deep cells of the primitive streak and
populate the space between the
newly laid down endoderm and
epiblast. This Iayer is called
M ESODERM. The. mesoderp utlhffi$qd
extends from just caudal to
buccopharyngeal membrane to
cloacal membrane. The remaining
epiblast cells differentiate into
ectoderm, Thus a, TRILAMINAR
GERM DISC is formed that will give
rise to the four basic tissues in the
body.
(2)NOTOCHORD
Fig. 1.7 Developing Villi
The cells that invaginated through the primitive pit

constitute prenotochordal cells. They subsequently marking the beginning of NEURULATION. The
move cranially after migrating through the pit until induction of the neural plate is cauied by presence
they come into contact with the prechordal plate of fibroblast grgwth factor (FGF) and inactivation of
extending from the buccopharyngeal membrane. bone morpfrorgenetic protein 4 (BMP4)". Thq
These cetls integrate themselves among the mechanism of FGF regulation neural pafhuiays is
hypoblast cells in the midline of the embryo forming unknown but it is known that it suppresses BMP
the notochordal plate. The cells of the plate prolifer- transcription and increases levels of ,c-ho1di4.'.3nd
08
Embryology
t' (. .'-J
f tt.lr
t
.t t
tli i-
t* * "
&&,
fifii
B* IIffi.E
&s ll&e
s{ t*mfr d*ffiYBhr
hffihrfrngftrr#nC #ftEd
milft n*fr rJp d{$ sffiErr|l&r df-siffi* }fCI6d
flryild {UlErd*moemUa*
Fig. 1.8 Tranverse sections of Stages of Placental Villi
noggin which are inhibitors of BMP activity. Three medulla and schwann cells, facial skeleton, cells of
proteins, chordin, noggin and follistatin,present in cranialganglia and glialcells. :
the primitive node, notochord and prechordal

membrane inhibits BMP4 which causes ectoderm (4)VILLIoFTHE PLACENTA(Fis. 1.7 & Fig. 1.8)
to form epidermis, and transforms mesoderm into
intermediate and lateral plate mesoderm. The three
As the syncytiotrophoblast grows, little spaces
proteins form neural tissue trom ectoderm. This termed LACUNAE appear within it and maternal
neutralization occuls in the forebrain and mldbrain
blood flows into them from the eroded maternal
spiral arterioles in the endometrium. As the lacunae
regions. lnduction of the part of the neural plate that
forms the hind and spinal cord is dependent on the
enlarge and orientate themselves radially, radial
columns of syncytiotrophoblast separate the lacunae
two proteins; WNT3a and FGF. By the end of the 3rd
and these columns are then called PRIMITIVE VlLLl,
week, the edges of the'pilate have.become eievated to
(Fig. 17 AA: Fig. 18 AA). When the.underlying
form the neural folds. The middle portion of the plate
cytotrophoblast invades their core, the columns
is depressed as a result and is called neural groove.
become PRIMARYVILLI. (Fig. 1-7 B-B: Fig 1-8 B-B)
The neural folds gradually approach each and fuse
Mesenchymal core invasion transforms,them ihto
formingthe neuraltube. Thefusion begins in the mid.
SECONDARY VILLI Gig.l-7 C.C : 1-8 C-C). When
section and advances both cranially and caudally.
The tube remains open at both cranial and caudal
finally, blood vessels are formed within the
mesenchymal core they become TERTIARY VlLLl.
ends through the neuropores. The branial neuropore
(Fig. 1-7 D-D: 1-8 D:D).
closes on day 25 while the caudal one closes tWo
days later. Their closure marks the end of neurulation.
Thus the basic structural pattern for the placenta is
The cells, lateral to the neural fold are called neural
laid down, although it would not start functioning
crest cells. They change morphology from ectodermal
until later (in 4th month), when a definitive placenta
I to mesenchymal phenotype. The following cell types
is formed and respiratory bfanche5 of the tertiary villi
F derive from neural crest cells: melanocytes, sqnsory
rr sproutout. (Fig. 7-7 e-e Fig. 1-8e-e).
I
ganglia, sympathetic and enteric neurons, adrenal
I
r,
f
I
t
09
(
i
(5) ALLANTOIS (c) Lateral plate mesoderm This plate of cells

thickens and is then split by a space called the
Forms in the third week as a diverticulum from the COELOM, into Splanchnic and Somatic
posterior part of the yolk sac, posterior to the cloacal mesoderms and their derivatives.
membrane and extends into the body stalk.'(Fig'1-
9). (i) Splanchnic - forms smooth muscular walls
' il-
of viscera
BODY FORM AN D ORGANOGENESIS (38WEET(S) (ii) Somatic - forms dermis and
subcutaneous tissue
During the early part of this period, the flat trilaminar (iii) Coelom -forms the pericardial, pleural and
embryonic disc is converted into a rounded bodyform peritoneal cavities
by the simple process of head, taiI and lateral FOLDS
(Fig. 1-9). lt is during this embryonic period that the Derivatives of Endoderm 3.1 Epithelial lining of the
three germ layers give rise to specific tissues and Gastrointestina! tract and its glandular derivatives,
organs, which form the major systems of the body. i nctuding liver, pancreas.
(Organogenesis)
3.2 Epithelial lining of the Respiratory tract and its
It is also the most vulnerable period of development glands
because as cells differentiate and move to new 3.3 Epithelial lining of tympanic cavity and the
pharyngotympanic tube
locations, the slightest external disturbance from
drugs, chemicals, infective agents' radiation etc.
3.4 Thyroid, thymus, parathyroids, and stroma of
palatine tonsil
causes congenital abnormalities.
3.5 Epithelial liningof urinary bladderand urethra
SUMMARY OF DERIVATIVES OF THE THREE
DEVELOPM ENT OF TH E PLACENTA
GERM LAYERS
By the beginning of the 2nd month, the whole
Derivatives of Ectoderm
surface of the embryo is full of secondary and tertiary
1.1 The Nervous system, adrenal medulla and
villi (Fig. 1-9), with maternal blood in the intervillous
neurohypophysis, through the formation of
spaces and foetal blood within capillaries of the villi.
the neural tube and neural crest.
1.2 Epidermis and its derivatives e.g. hair, nails, Next, the cytotrophoblast within the villi mushroom
mammary gland, teeth
out at the tips of the villi, spread out in all directions
1.3 Special sensory epithelium of eye (retina); ear
(membranous labyrinth) nose (olfactory and join with each other such that a complete shell,
with holes for blood vessels, is formed to enclose the
epithelium)
whole embryo (Fig. 1-9). This is known as the
Derivatives of Mesoderm CYTOTROPHOBLASTIC SHELL. The inner surface
lnitially the mesoderm divides into (a) paraxial (b) of the shell enclosing the intervillous space is then
intermediate and (c) lateral plate covered by the syncytiotrophoblast extending from
the outside of the villi.
(a) Paraxial mesoderm This subdivides into blocks
called somites. Each somite has the following The intervillous space is initially an open space' At
parts and derivatives: this stage the tertiary villi are relatively thick and are
called STEM VlLLl. Additionally there are 4 layers
(i) Dermatome - forms the dermis separatingfoetal blood from maternal blood namely:
(ii) Myotome - forms striated muscle (a) foetal endothelium (b) somatlc mesoderm (c)
(iii) Sclerotome - forms the body of vertebra cyotrophoblast a nd (d) syncytiotrophoblast.
and rib
(b) lntermediate mesoderm Differentiates into: villi bud off numerous smaller and
Soon, the stem
(i) KidneY smaller branches, which, by the 4th month
(ii) Ovary or Testis completelyfill the intervillous space (Fig' 1-9)' There
are two advantages of the branching:-(a) the total
10
Embryology
of gases and nutrients

surface area fo,' exchange As development continues, the villi on the embryonic
between foetal and maternal blood is greatly side grow luxuriously, and together form the
increased, and (b) the placental barrier is reduced to CHORION FRONDOSUM. However, the villi on the
2 layers namely (i) foetal endothelium and (ii) abembryonic side DEGENERATE until they all
syncytiotrophoblast, thus greatly facilitating rapid disappear. Thus a circular chorion frondosum
diffusion. derived essentiallyfrom the chorion is formed.
The part of the endometrium to which the chorionic

frondosum is attached is called the DECIDUA
BASALIS, and together they form the mature
placenta. The decidua surrounding the embryo is
.*&d
sdm termed CAPSULARIS, and that NOT invaded is the
PARIETALIS. (Fig. 1-1 1).
Thus a uterine cavity temporarily exists between the

filtrd
capsularis and parietalis. However as development
continues the uterine cavity is completely obliterated
Fig. 1-9
by the union of the capsularis and parietalis' The
r&rdHood*q$ds expanding amnion also completely obliterates the
extraembryoniccoelom (Fig 1-i i).
brdfi MATURE PLACENTA

c$otaplo!&il|ei 1 ls derived from the CHORION and therefore
classified as haemo-chorial
htcnJhls#ca
Bifi rnNhrrdHood 2 ls discoid with an average diameter of 15-
$eE 25cm
SEE}ll$n!a 3 Averagethickness:3cm
4 Averageweight:500-600gms.
pk!*
5 Cord and placenta are covered by amnion
6 The decidua basalis sends septa, which project
(
i
downwards but do not reach the chorionic
!.
Fig. 1-10 Placenta in 4th month
I
ktre
I
I
i_
p{dm
f
Siru
e&
4{6fi$
ryS
|ffifi!&frtd rxffie&r*r
ffipudcFnkaPlrn *RSmmn$f&ryryt*(
rr!d{{ee&,
Fig. 1-11
11
into
plate. These septa divide the.frondosum hernia would appear within the primitive
l5-20 portions, which are called umbilicalring.
COTYLEDONSoT LOBES.
NB: lnfectious agents and drugs may be transmitted

across the placental barrier from mother to foetus,
BUT THESE ARE NOT FUNCTIONS of the piacenta
and should NOT be placed under pJacental
Fu nctions! !! ! They are DISADVANTAGES!
fiddb{heMt
UMBILICALCORD
1 . As the amnion expands it crowds together:
(a) The body stalk and umbilical vessels
ut*Iicdtlt$ds
(b) The allantois
( c) The diminishing secondary yolk sac,
surrounded by
(d) Part of the extra embryonic coelom
Alt these together form the PRIMITIVE UMBILICAL

CORD (Fig. 1-12)
2. TEMPORARILY the physiological intestinal

Fis. {-ti
ydkiHilk *,d
mffi0oq$rffi
rulkser
Fig. 1.13 Primordial Germ Cells
L2
Embryology
3. Further expansion of the amnion and retraction (4) END OF 9" MONTH
of the hernial loop narrows the primitive cord 4.1 Weight about 3000 grams (3kg)
which is then converted into the DEFINITIVE 4.2 Spinal cord ends at L3 vertebra
UMBILICAL CORD which thus contains: 4.3 Time for Birth
(a) One umbilical vein and two umbilical
(5) POST TERM BABIES
arteries
(b) Wharton's jelly, derived from extra
embryonic mesoderm
@l + wks) are more prone to pneumonia due
(c) Remnants of yolk sac and urachus
to meconium aspiration. They have no vernix,
and the skin cracks and desquamates.
THE FEMALE GENITAL SYSTEM

N.B: The yolk sac and urachus usually disappear
altogether by the time of birth
FOETAL PERIOD (39 MONTHS)

Since by the end of the month (Embryonic period)
2"0
all major structures and organs would already have
been formed, the foetal period is essentially for
maturation and growth of these structures as well as
the foetus as a whole. The following landmarks are
worthy of note:
(1) 3*oMONTH
1.1 Weight averages 30 grams
7.2 Face looks human
1.3 The sex of the baby can be determined by
the external genitalia
7.4 Head is the length of the baby
Fig. 1-14 Developing female internal genitalia
(2) 5" MONTH
2.7 Weight about 350 grams
2.2 Head is about 1/3rd of the length of the
body
2.3 Body is covered by fine LANUGO HAIR,
and coarse hair on head and eyebrows
present
2.4 SPINAL CORD occupies whole length of
spinal canal
2.5 Mother is able to feel movements of
foetus
(3) 7" MONTH

3.1 At 28 weeks weight is about 1000 grams
3.2 Secretory products of sebaceous glands
form a protective whitish layer on ihe
skin called VERNIX CASEOSA.
3.3 Subcutaneous fat begins to appear so Fig. 1-15 Development of Vagina
that the wrinkled skin of the premature
baby disappears
I
3.4 Foetus can survive if born, since
respiratory and nervous systems are
sufficiently matured
13
t-
PR!MORDlALGERM CELLS would naturally be absent. WNT4 is the ovary

determining gene. lt stimulates increase levels of
These are very special cells differentiated from the DAX1 that inhibits SOX9. Estrogen stimulates
endodermal cells on the posterior wall of the yolk sac, paramesonephric ducts to form uterine tube, uterus,
and are destined to form the'ova and sper{rts. (Fig. 1- cervix and upper vagina.ln the absence of both the
13). SRY gene and MIS the para-mesonephric ducts
develop strongly, and the mesonephric ducts regress.
OVARIES The para-mesonephric ducts unite at their lower
ends and abut on the posterior wall of the pelvic
These start as short longitudinal GONADAL RIDGES urogenital sinus. Thus would form the uterus and
by the proliferation of underlying intermediate tubes, as well as the upper 1/3rd of the vagina. (Fig.
mesoderm on the medial side of the mesonephros. 1-15).
Primordial Germ cells then migrate by amoeboid
movements along the yolk stalk and dorsal LowerVagina
mesentery of the hindgut into the gonadal ridges, by As the united tip of the paramesonephric ducts
the 6th week. (Fig. 1-13). The proliferating coelomic reaches the pelvic urogenital sinus, they engen
epithelial cells then form irregulhr cords which the growth of two solid bulbs, the SINOVAGII\'.-
immediately surround the primordial germ cells. BULBS which soon unite to form a thick VAGINAL
These are the PRIM ITIVE SEX CORDS. There is a sex- PLATE that pushes the united tip farther away. (Fig.
determining-region-Y gene (SRY gene) on the short 1-15), The plate as well as the distal end of the
arm of Y chromosome (Yp11) which encodes the united paramesonephric ducts becomes canalised to
testis determining factor (TDF). lf the embryo is form the lower 2l3rd part of the vagina except at the
female, and in the absence of a Y chromosome and very end where a plate of tissue remains, called the
therefore of the SRY gene, the sex cords form in the HYMEN. A pinhole opens in the hymen. Thevagina is
medullary region, each group of cells surrounding a then orientated downwards by the expansion of the
primordial germ cell. They later disappear and lower end of the pelvic urogenital sinus which
replaced by vascular stroma. ln the 7th week, contributes to the formation of the VESTIBULE. (Fig.
proliferating epithelial cells give rise to second 1-15).
generation of cords, cortical cords. Later the cortical
cords break into cluster with the cells surrounding 1 The vagina therefore develops partly from
or 2 primitive germ cells. Germ cells form oogonia paramesonephric ducts and partly from the
and surrounding cells fbrm follicular cells. urogenital sinus.
DESCENT OF THE OVARY Duplication, atresia and other malformations of the

birth canal are thus easily explainable.
The ovary descends, guided by the gubernaculums'
However, as it stops in the pelvic cavity, the laterally
expanding uterus bisects the gubernaculurns to form gffilH
(a) the round ligament of the ovary, and (b) the round irbsrde latfum
ligamentof the uterus (Fig. 1-16). diUrfre r{nua
Development of Uterine Tubes, Uterus and Upper

Vagina
These structures form part of the genital duct in
females. They develop from two duct systems.
These are paramesonephric (Mullerian) and
mesoneph ric (Wolffian) ducts.
ilHr5r*l&
ln a female embryo a Mullerian lnhibiting Substance
(MlS) also known as Antimullerian hormone Development of the External genitalia
producecd by the sustentalular cells of the testis
t4
l'-'
I
Embryology
t
EXTERNAL GENITALIA Estrogens stimulate development of the female
r external genitalia. ln the presence of the hormone,
t The primordia are indistinguishable ahut the genital tubercles elongate only slightly to form
week 12.
|._ the clitoris. The urethral folds do not fuse and form
labia minora.
Mesenchyme around the c
t proliferates to form two pairs of The genital swellings enlarge and form the labia
l membrane (Fig. 1-16). These are: majora and then urogenital groove forms the
t. gen ita I swel i ngs. The cloaca I swdli+E$,@tra+1ia I
I
vestibule
to the cloaca I mem bra ne form i ng the geniHl B*scle.
r
r Caudal part of the swelling remain unfusd anteniorly 5. The point of union of the uro-rectal septum
i
as the urethral fold but fuse posteriorly as'anallold . A and the cloacal membrane forms the
t-
pair of genital swellings forms on either sidrx of the PERINEAL BODY.
urethralfolds.
i
tr
r-
L
r References
I
r' 1 Human Embrology by Hamilton, Boyd and Mossman

I 2 Langman's Medical EmbryologrT by TW Sadler. Williams and Wilkins. Publication
i 3
4.
Concise Human Embryoogy by E Nii-Lomote Engmann. Vieso Universal Publication
Standring, S. (2008). Grays Anatomy: The Anatomical Basis of Clinical Practice.
F
a
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{
I
15
CI{APTE
i
",H
Fundamentals of Human Genetics
Bartholomew Dzudzor
That plants and animals as well as we 'exalted' Q-Bands: respectively. The banding patterns are
human beings inherit traits and characteristics from unique for each chromosome. Chromosomes at the
progenitors and parents has been appreciated since metaphase can be arranged from the longest to the
the days of antiquity, However, humanity had to wait shortest, the longest being chromosome 1 and the
till 1865 when the methodical and brilliant shortest autosome being chromosome 22. However
experiments performed by the father of genetics, latest evidence indicated that chromosome 22 might
Gregor Mendel revolutionized the genetic basis of be slightly longer than chromosome 21 yet still,
understanding hereditary not only in plants but more cytogenetics stack to the older form of the
importantly in humans. His excellent works now arrangement. Chromosomes can also be classified
make it possible for mostly accurate prediction of how based on the location of the centromere as
certain disorders are inherited through autosomal metacentric, submetacentric and acrocentric.
dominant and autosomal recessive means. Metacentric chromosomes are virtually divided into
equal arms by the centromere, submetacentrics
Now it is common knowledge that the chromosomes have the slightly shorter and longer arms described
that carry the heritable units called genes are located as petit (p) and q respectively. This is the form which
in the nucleus of eukaryotic cells and their is more familiar to students of biology. However, it is
mitochondria, The chromosomally located genes in important to point out right from the outset that the
eukaryotes are currently predicted to be about familiar X-shaped chromosomes are only temporary
25,000. However due to the phenomenon of structures found solely during cell division, and that
alternative splicing, the number of protein products the normal-functioning chromosomes are long single
from these genes are yet to be determined. threads.
THE NATURE OF MAMMALIAN CHROMOSOMES These long threads are'matted'together and are seen
under the microscope as a network, and where they
ln the nuclei of normal non-dividing cells, the cross, as granules. This network is normally
chromosomes are in the form of extremely thin and
stainable in normal histological procedures and is
long single threads of differing lengths, not called Chromatin, whereas the parts of the nucleus
I discernible under the light microscope, nor even in between the strands and granules are described as
under the electron microscope. However, during cell
Achromatin. Chromosomes (chromatin) are now
division the chromosomes replicate and shorten to known to be composed of Deoxyribonucleic acid
form double-stranded X-shaped structures which can (DNA) together with histone and non-histone
be visualized under the microscope after staining proteins. lt is worthy to note that the nucleosome
with Giemsa or Quinacrine. When either Giemsa structure is the basic level of folding of the one-meter
staining technique or Quinacrine procedure is used, long DNA material which needed to be
the banding patterns are described as G-Bands and
i L7
:
(
accommodated in 6 micrometers (6pm) diameter of

the nucleus. Compacting of DNA is greatly facilitated ft**n sr
by electrostatic attraction between the negatively mdmldx*
charged DNA backbone (due to phosphates) and the be**
partial positively charged histones because of their
rich composition of basic amino acids lysine, arginine
and histidine
FElrtffi
Fig.2-2. Nucleotide Structure. lf the hydroxyl group at the 2'

{ position is replaced by hydrogen, then it is deoxyribose sugar
(DNA) nucleotide. dNTPs have three phosphates esterified to
the 5'hydroxyl group.
DNA
The double-helix structure of DNA as elucidated by
Fig. 2-1. The X-shaped structure of chromosome at
metaphase. The centromere (the largest constriction) the Watson and Crick through their brilliant experiments
telomeres (the ends) of chromosomes, lighter-staining in 1953 is shown in Fig. 2-3.was preceded by
euchromatin includes many protein encoding genes. The equally brilliant experiments by Erwin Chargaff and
centromere divides this chromosome into a short arm (p) and Rosalind Franklin in i950 and 1951 on the base
a long arm (g). This chromosome is in the replicated form.
pairing and X-ray diffraction to determine the
Courtesyfrom Lewis Human Genetlcs Concepts application.
molecular dimensions respectively of the DNA. The
spiral polynucleotide chains are bonded together by
the bases Adenine (A), Thymine (T), Guanine (G) and
BIOCHEMICAL STRUCTURE OF NUCLEIC ACIDS Cytosine (C) which constitute nucleotides found in
(DNAAND RNA) DNA. Moreover, Watson and Crick's DNA which is
later described as B DNA (the predominant form of
The monomeric units of nucleic acids are DNA found in the cell) is right-handed helix. Other
nucleotides. Nucleotides are made up of the three forms of DNA such as the A-form (stabilized by
components; nitrogenous base, pentose sugar and
dehydration) and the Z-form (zigzag backbone and
phosphate(s). The base can either be a purine or
left-handed) also exist depending on the sugar
pyrimidine, a pentose sugar can be ribose or puckering which further determines how compact a
deoxyribose depending on whether you are particular form of DNA will be. The B- and A-forms
describing RNA of DNA respectively and the have the 2' and 3'-endo respectively whereas the Z-
phosphate which is esterified to the 5' hydroxyl group
form has both 2' and 3'-endo puckering of the sugar.
of the sugar can be one, two or three. The nitrogen The pentose sugar and phosphate make up the
atoms at position 1 and 9 of the pyrimidine and backbone of the DNA. Furthermore, the phosphate at
purine bases respectively are linked to the anomeric
the 5' position of the deoxyribose and the hydroxyl
carbon atom 1' of the pentose sugar through B-N- group at the 3' position gives the polarity (5'3') to the
glycosidic linkages. The sugar and phosphate
nucleic acid. Strands in DNA are anti-parallel.
backbone makes the nucleic acid soluble in aqueous
environmenL Fig.2-2 Adenine forms two hydrogen bonds only with and I
G three hydrogen bonds only with C. Thus on any one
chain, wherever A and G appear they will need T and
C on the other chain to base pair with. Therefore, the
sequence of bases along one chain automatically
determines the sequence of bases on the other chain.
18
Thus the two ch;ins are exact mirror-images of each THE REPRODUCTIVE AND DIRECTORATE
other! The compl:mentarity of the. bases, together POWERS OF DNA (DNA REPLICATION)
with the stable features of DNA because of the
deoxyribose sugar contributes to making.DNA the The DNA molecule has the amazing power of
genetic material for storage and transrnission of reproducing an exact copy of itself by the process of
biological i nformation. Replication. lt can also, through the method of
Transcription, produce an unidentical offspring in
the form of an RNA molecule, which in turn is able to
The basic structure and function of RNA are similarto direct the formation of proteins by the process of
that of DNA except for the following differences, Translation. Replication simply involves the
1 The nucleotide in RNA has ribose sugar instead of separation of the 2 strands of the helix and building a
deoxyribose new mirror-image strand on each original one (Fig.
2 RNA has the base Uracil (U) instead of Thymine 2-4).
(T)
Replication is semi-conservative as proven by
1 RNA is usually single stranded as opposed to the ingenious experiment carried out by Meselson and
double-stranded chain of DNA Stahl in 1956, lt starts from a single origin in
2 DNA is mostly located and replicates in the bacteria but multiple origins in eukaryotes. ln
nucleus whereas RNA is synthesized in the humans, replication process begins by recruitment
7
nucleus and exported to the cytoplasm where it of helicases to unwind the double helix at origin
serves as template for protein synthesis or recognized by origin recognition complex (ORC),
involved in the mechanism of protein synthesis. replication protein A (RPA) binds to the single
3. DNA stores the genetic information whereas RNA strands to keep them apart and prevent re-
is the medium of genetic information, which annealing, RNA primers are then laid by DNA
translates i nto protei n synthesis. polymerase o. DNA polymerase 6 then comes in to
4. Purine and pyrimidine nucleotides are not equal in
extend the primer from the 5' to 3' direction. Since
RNA unlike DNA where they are almost equal.
polymerases in general synthesizes DNA from the 5'
5. Presence of 2' hydroxyl in RNA makes it more
susceptible to alkali hydrolysis compared to
to 3'directions, one strand is synthesized
continuously because the template end is 3' and the
DNA
other strands are synthesized discontinuously like
back-stitching into fragments known as the Okazaki
fragments. The RNA primers are later removed by
RNase H, the gaps filled with DNA nucleotides by
DNA polymerase B followed by ligation of the
Okazaki fragments together by DNA ligase. The 3'
hydroxyl group of RNA primer serves as the
nucleophile to attack the alpha phosphate of the
Deoxyribonucleoside triphosphates (dNTP)
catalyzed by DNA polymerases and the process
contii,re by incorporating the various dNTPs based
on complementary base pairing with the template
nucleotide. The binding pocket of the polymerase,
clamps tightly around the correct base before
catalysis can occur.
Fig. 2-3. DNA double helical structure. Guanine nucleotides

forms three (3) hydrogen bonds with Cytosine Nucleotides
and Adenine, two (2) with Thymine
19
opening of the double helix known the transcription

bubble by helicases) is also described as the
antisense strand and the non-coding strand.
Tianscription is the gatekeeper of gene expression
because it eventually determines the amount of
protein synthesized from a particular gene. The
amount of the protein determines the functions of
individual cells in the human body. Too much or too
little of the protein in the cell results in diseases, The
timely expression of the proteins is also very critical
in determining the normal function of the cell.
Transcription is gene-specific unlike replication
which requires the entire genome to be copied.
Therefore, the RNA polymerase does not need to be
as processive as DNA polymerase which has the
Fig.24. Eukaryotic replication fork. DNA synthesis
processivity factor. Transcription begins at the
occurs bidirectionally in the 5'to 3' direction. DNA
promoter region usually located at the 5' region of
polymerase 6 is the main enzyme that copies the
genes they regulate. The promoter region of Class ll
eukaryotic genome, DNA polymerase q has primase
genes (genes transcribed into mRNAs) usually have
activity that lays down the primer, extend with dNTPs
before falling off. Proliferating cell nuclear antigen
two of the following consensus elements or
(PCNA) is the trimeric clamp is the processivity for sequences present in their promoter region: TATA box
found at negative 30 region (-30); the lnitiator
DNA polymerase 6, minichromosome maintenance
Region (lNR) located at +1 region (first nucleotide
protein complex (MCM) is the helicase, replication
incorporated into mRNA); and the Downstream
factor C (RFC) loads the PCNA to the template,
Promoter Element (DPE) found at +30 region (thirty
replication protein A (RPA) keeps the single strands
nucleotides downstream of where transcription
apart to prevent re-anneali ng.
begins). Variation in these promoter is the first level
Wobble pairs do not fit and therefore catalysis cannot of regulation of transcription. The more identical the
occur since the polymerases are able to read the sequence found at the promoter region of a particular
template strand to know which base should form the gene is to the consensus sequences, the stronger the
appropriate hydrogen bgnd with the template base. promoter and therefore the more often that particular
Furthermore, the polymerases prefer the keto- gene will be transcribed and vice versa. RNA
tautomers of the nucleotides since the enol synthesisin human cells is catalyzed by complex
tautomers are unstable and cannot form the correct enzymes generally referred to as RNA polymerases.
Watson and Crick base pairs. The polymerases are The polymerases are classified into three, based on
able to edit their own synthesis using the 3'5' their sensitivity to a toxic substance, q-amanitin
exonuclease activity. Again immediately after produced by the world's most dangerous toxic
synthesis is done, there are enzymes that carry out mushroom Amanita phalloides. RNA polymerase l,
methyl-directed mismatch repair. Together, these which mainly transcribes ribosomal RNA is not
contribute to the very high fidelity of DNA synthesis sensitive to the toxin, RNA polymerase lt which
whereby only one possible mistake can be made in transcribes messenger RNA, small nuclear RNAs
incorporating about one billion nucleotides in DNA Ul, U2, U4 and U5 is extremely sensitive whereas
synthesis. This makes DNA polymerases one of the RNA polymerase lll which transcribes transfer RNA,
most efficlent enzymes known. 55 ribosomal RNA and U6 is moderately sensitive to
o-amanitin. RNA synthesis occurs de novo, unlike
TRANSCRI PTION (RNA SYNTH ESIS) DNA synthesis that requires RNA primer. However,
RNA synthesis requires a template and the synthesis
RNA synthesis (transcription) uses DNA template to occurs in 5' to 3' direction similar to replication but
make RNA which is complementary to the template. with a low fidelity compared to replication.
The template strand of the DNA (created from local
20
Transcriptionis initiated by general transcription differential gene expression driven by these gene-
factors recruiting the RNA polyrnerase to the specific transcription factors are critical in
promoter region followed by unwinding of the double differentiation, time-specific gene expression and
helix to create the transcription bUb8tfl, Tho first cellular specialization. Specific transcription factors
general transcription factor to recognize th* Somoter do not bind to promoter regions but rather to
is usually transcription factor llD (TFllD) because it enhancer sequences which can be located in
has TATA binding domain (TBP) that recognizes and variable positions with respect to the gene they
binds to TATA box as well as TATA associated factors regulate. Some of these specific transcription factors
(TAF) that recognizes and binds to INR and DPE are folded into domains such as helix-turn-helix
sequences. Transcription factor llH ffFllH) is the last (HTH), Zinc Finger motifs (Zn Finger), basic leucine
general transcriptioh factor to bind. TFIIH has zippers (bZip) and helix-loop-helix (HLH) motifs.
helicase activity that unwinds the double helix Jun, Fos, Myc are common specific transcription
thereby creating the transcription bubble as well as a factors. All specific transcription factors have DNA
kinase activity. Phosphorylation of the carboxyl binding domain and activator or repressor binding
terminal domain (CTD) of RNA polymerase ll is very domain. Mutations in these factors are reported in
critical for promoter clearance, hence proeessivity of many disorders including cancer. Transcription is
the RNA polymerase as well as serving as a docking also regulated at the level of the chromatin structure.
site for the primary RNA processing enzymes and Regions of the chromatin that tends to be highly
proteins. The proteins docking at the phosphorylated acetylated generally recruits activators to enhance
CTD include the 5'capping, polyadenylation, splicing gene expression whereas methylated regions seem
and alternative splicing enzymes. The important to bind to repressors that reduce the rate of gene
functions of TFIIH in nucleotide excision repair and expression. Since DNA and RNA speak and write the
transcription cannot be overemphasized not same nucleotide language that is why RNA synthesis
surprisingly, mutation in TFIIH leads to the is termed transcri ption.
xeroderma pigmentosum and Cockayne's syndrome
characterized by arrested growth, neurological
disorders and photosensitivity. The role of TFIIH in
/ both repair and transcription may help explain
r
transcri ption coupled repai r.
i
I
k-
It
Mechanism of transcription is similar to replication
whereby the 3' hydroxyl group of the ribose sugar
serves as the nucleophile to attack the alpha
phosphate of the next nucleotide based on the DNA
template nucleotide, releasing pyrophosphate which
is further hydrolyzed into inorganic phosphate,
releasing Gibbs free energy that d.rives the
polymerization reaction forward. Transcription is
terminated when a termination signal sequence
which could be two inverted GC rich regions
separated by intervening region followed by AT rich
i
i
I'
sequences. Once this sequence is transcribed, it Fig. 2-5. Overview of gene expression in eukaryotes.
a forms a hairpin structure which cannot be held at the Transcription and translation in eukaryotic cells are separated
t polymerase active site therefore the nascent RNA is in space and time. Extensive processing of primary RNA
t
transcripts in eukaryotic cells.
released and transcription is terminated. RNA
synthesis is also regulated by specialized
transcription factors in a cell-specific manner. These PROCESSING OF PRIMARY MESSENGER RNA
/ specialized transcription factors act as activators, co-
activators, repressors and co-repressors to determine There are three main processing that pre-mRNAs
i, cell-specific expression of particular genes. The undergo before they become mature to be used as a
:
2L
a
.
template for protein synthesis. Once transcription These self-splicing RNA particles are ribozymes'
begins in the nucleus and the nascent RNA is about Group I uses exogenous guanosine as a nucleophile
20 nucleotides long, a cap structu,re (7- and no lariat structure is formed whereas group ll is
methylguanosine) is added to the 5' end this similar to the spliceosome type of splicing but just
precedes splicing and polyadenylation. This requires that no spliceosomes are required.
the addition of the 7-methyl guanosine in an unusual
Shortly after RNA polymerase ll passes an AAUAAA
5',5'- triphosphate linkage. A reaction. catalyzed
hexamer "polyadenylation signal" sequence, the 3'
sequentially by phosphorylase, guanylyl transferase,
guanine 7-methyl transferase and o'2' methyl end of the transcript is generated by cleavage and
polyadenylation. Cleavage and polyadenylation
transferase enzymes. The cap structure renders the 5'
end of the messenger RNA resistant to exonucleolytic
specificity factor (CPSF) recognizes the hexamer,
cleavage stimulatory factors (CStn recognizes and
degradation and is also required forthe recognition of
bind to the G/U rich element 50 to 100 nucleotides
the mRNA by the ribosome during protein synthesis.
downstream of the hexamer followed by additional
Spliceosomes (proteins that excise the introns and cleavage factors binding. Template Independent
join together the exons) assemble onto the introns of nucleic acid polymerase Polyadenylation Polymerase
the nascent RNA as transcription continues. Splicing (PAP binds to the complex and adds about 7O lo 2Ott
then continues until after the nascent RNA is adenosine nucleotides to the trimmed 3'end of the
released by the RNA polymerase. The spliceosomes RNA using Poly (A) Binding Protein I (PAB l) for
are ribonucleoprotein particles made up of protein processivity. The poly (A) tail protects the mRNA
component and small RNA which is rich in the uracil against 3'to 5' exonucleolytic degradation, helps in
nucleotides and as such they are simply named as the export of the mature mRNA from the nucleus to
U1, U2, U4, U5 and U6. Splicing sites are precisely the cytoplasm and also facilitates ribosome binding
identified by the spliceosomes using complementary and protein synthesis.
base-pairing of their RNA component with the 5' and
TRANSLATION
the branchpoint splice sites. U1 recognizes the 5'
splice site and U2 the branchpoint which has a
Protein synthesis occurs in the cytoplasm where the
conserved Adenosine residue that does not vary
ribosomes, serving as platform for protein synthesis
because it is the one that serves as the first
are located. Translation requires mature mRNA (that
nucleophile in the transesterification reaction'
serves as template directing the order of amino acid
Precision of splicing is.very critical otherwise, exon growing peptide),
to be incorporated into the
sequences can be added to intron sequences and
aminoacyl-tRNA (which acts as the adaptors to bring
\/l
introns to exon sequences creating a frame-shifted
amino acids to the ribosome in a high energy state),
mature mRNA, truncated mRNA with loss of exons or
ribosomes (which acts as the engines for protein
longer than normal RNAs. lndeed, there are many
synthesis) and soluble protein factors to occur. Some
disorders including Thalassemia, Systemic Lupus
of the soluble protein factors have GTPase activity
Erythematosus etc. which are due to mis-splicing of
which is usually needed during the processes in
primary RNAs. Splicing also generates diversity
translation that require absolute precision. GTP
whereby one nascent pre-mRNA can be alternatively
hydrolysis is not associated with covalent bond
spliced into many mature RNA in different cell types
formation; rather, it is coupled to conformational
providing differential functions of these cells' This is
changes of translational machinery which is
one reason why proteomics cannot as yet predict the
important for making reactions fast and irreversible
number of proteins that can be synthesized from
as well as fidelity of protein synthesis. Translation of
about 25,000 genes in the human genome.
nucleotide language into amino acid language in
Alternative splicing allows neurons to distinguish self
proteins is made possible by the Genetic Code (Table
from non-self, which is critical for properwiring of the
2-r).
brain in the fruit fly. Group I and ll setf-splicing
systems (no requirement of spliceosomes) has been The Genetic Code
reported in some protozoa, bacteria, archaea, fungal The chromosomes contain the genetic information as
and plant mitochondria as well as plant chloroplast. genes which is composed of the DNA nucleotides'
22
Fundamentals of Human Genetrcs
The Genetic Code is a triplet code (specified by DNA Table 2-1. The Genetic Code
but read from RNA) Each triplet is called a "codon".
Since there are four bases in RNA (A, G,-C, U) and
also the code is triplet implies 4' = 64 p@tibte triplet
combination of 4 bases. However, 61 d #ies are
coding (or sense) codons (coding triplek spae*fy one
of the 20 common amino acids). Three (3) are non-
coding (or "nonsense") codons (these specify "stop").
The stop codons are combination of'U andthe purine
bases A and G (UAA, UAG and UGA) except UGG
which codes for Tryptophan. The code is degenerate
(more than one codon codes for each amino acid,)
except Methionine and Tryptophan which are each
coded for by one codon (AUG and UGG respectively).
The Genetic Code is "universal". Meaning that
"basically", one nucleotide sequence will produce the
same protein product in a human cell or bacterium
(yeast, mouse, etc). This feature speeds up
cha'raclerization of gene products and the
development of genetic therapies and drugs. There
are few exceptions where mitochondria have a few
differences in codon meaning, and different species '!r@ x*m xh ne*tb m* m, br*ir' &x xe ifucc rdfi*
rddax rc rE{" *a{ ffi xr*q**d rs#m n* fry,rle,
have distinct preferences in codon usage. Also, the i*Xl,S !M frur $f &$ ieekexdil*l! x rd r & er t**rxd
Genetic Code provides "Start" and "Stop" signals !*xre$&.
which define an "open readingframe" (ORF). Within
an ORE mRNA sequence direcily equates with
Once positioned at the A site, the amino group of the
protein sequence. ln any codon, changes in the first
charged amino acid linked to the tRNA uses the lone
and second base usually result in an altered amino
pair of electrons on the nitrogen of the amino group
acid whereas changes in the third base have much
as a nucleophile to attack the carboxyl functional
less effect e.g. CAU and CAC both encodes Histidine.
group of methionine thereby transferring the
The third position is called the "Wobble" base which
is a feature permitted by tRNAs that allows one IRNA
methionine onto the amino acid lin ked to the tRNA at
to read more than one codon. lt is also a feature that the A site. The formation of the peptide bond called
protects against mutation. peptidyl transferase reaction (transpeptidation) is
catalyzed by the 28S rRNA of the large ribosomal
Briefly, mechanism of protein synthesis requires the subunit. The ribosome then moves a codon at a time
binding of the small ribosomal subunit (40S) to the on the mRNA (facilitated by soluble factors referred
mature mRNA followed by the hunt for the first to as the translocase) forming the peptide bond from
START codon (AUG) which is usually present in the the 5' end of the mRNA towards the 3' end until a
preferred Kozak consensus (RCCAUGG). Once the stop codon is encountered. At this point ribosome
AUG is located, the met-tRNA, binds to the peptidyl releasing factor recognizes the stop codon, bind to it
binding site (P site) of the ribosome followed by the and block the movement of the ribosome and
binding of the 605 large ribosomal subunit to the .
everything dismantles with the protein hydrolyzed
t
I small subunit forming the 80S ribosome. The from the IRNA. Since different proteins are formed
i
aminoacyl-tRNA binding site (A site) is then bound by from different sequences of amino acids, the varying
the next aminoacyl-tRNA charged with its cognate sequential arrangements of codons form the different
amino acid based on the codon as read by the proteins. Now then, a sequence of chromosomal
aminoacyl tRNA synthetases that has editing DNA codons that forms one functional protein or trait
function and links the correct amino acid to the or characteristic is called"a gene. For example,
5
( correct tRNA at the 3'-terminal Adenosine residue of formation of normal haemoglobin is controlled by a
?
the tRNA gene. The nucleotide language in mRNA must be
(
a
23
'translated'into amino acid language in protein hence chromosome. Deletions of parts of chromosomes as
the use of the term translation to describe protein well as monosomies example in Turner's syndrome,
synthesis. would cause reduction in gene dosage and hence
loss of function. Similarly, intra-chromosomal
MUTATION duplications and trisomies example Down syndrome,
can also cause disease by increasing synthesis of
A permanent change or modification in the gene DNA normal proteins as a result of increased gene dosage.
sequence that may affect structure or amount of
genetic material is known as mutation. Germ cell For example, the normal globin gene for normal
mutations are usually transmitted to progeny as haemoglobin is A. However, in Sickling haemoglobin
inherited disease of defect whereas somatic the adenine in the codon GAG has been replaced by
mutations may lead to cancers, some congenital thymine to form a GTG codon, which then produces
malformations and other diseases but not the amino-acid Valine instead of glutamic acid.
transmitted to offspring. There could be mutatiotts in Although the oxygen carrying power of the sickling
a gene or chromosomes. Gene mutations result in Haemoglobin so formed is not affected,
partial or complete deletion of a gene or more often in deoxygenation causes it to sickle, forming molecul
alteration in single base or base sequence. Example rods that deform red blood cells which m" ,
substitution of a single nucleotide base by another as eventually rupture.

well as inversion of two or more nucleotides may
result in point mutation. Deletion or insertion of ACTION AND INHERITANCE OF GENES
nucleotides which are not integral multiples of three
(3) will lead to alteration in reading frame known as Mode of Action
frame-shift mutations. lf the mutation is severe, the Each gene occupies a particular position, called a
resulting modified gene would either produce a locus on a particular chromosome from a father. A
totally different protein altogether both in structure sister gene which is identical or slightly different
and function, or produce a non-functional protein. lf would also occupy a similar locus on the sister
the mutation is minor example, involving only a chromosome from the mother. These 2 genes are
single replacement of one base, the protein may be known as alleles and work in concert to produce a
identical or similar to that of the normal gene normal protein product. For many genes, there is a
depending on whether the change occurred at the common type that occurs in many individuals called
wobble position of a codon or not. A point mutation the normal or wild allele. 0n the other hand, there
can be conservative which exhibit little change in can be variants of these, called mutant alleles, which
function or non-conservative which produces change would produce variants of the protein product.
in function. There are many types of point mutation in
Example, apart from the HbA gene, there are HbS,
a gene including those that occur in coding HbC, HbE etc. Any two of these alleles can occur
sequences, non-coding regions, deletions and together as in AA, AC, AS, SS, SC etc. and the
insertions (lndel), trinucleotide repeat mutations and manifestations of each would be different.
many more. Mutations occurring in non-coding
Mode of inheritance
regions may affect promoter and enhancer sequences
As a result of meiosis, only one sister chromosome of
and therefore poor or enhanced binding of a pair appears in either the sperm or the ovum. Thus
transcrlption factors which can lead to altered gene
on fertilization each sister chromosome brings its
expression at the transcription level. Within introns,
all6le. The child therefore inherits one allele from
mutations at the splice sites could lead to defective
each parent (fig 4. ln the child, the end productof the
splicing and processing of primary mRNA which can
2 alleles may thus be the same as, or different from
lead to truncated, elongated or no protein being
those of the parents.
expressed or produced.
Results of inheritance
Chromosomal mutations can be numerical or When two human beings arg given a job to do,
structural. These mutations involve addition, deletion uSually the ebullient character usurps the leadership
translocation, non-disjunction of a piece or a whole role, or the softer person allows the other to lead. lf
24
X-linked inheritance
a) Dominant
This is more complicated since there are two )G in the
female and only one in the male. lf the allelefora trait
on the X chromosome is dominant in a father then
the trait will appear in all daughters but not in any
son, since the sperms forming the daughters will
carry the dominant allele on the X chromosome. X-
linked dominant disorders are due to dominant
mutant genes on X chromosome and it's transmitted
by heterozygous females to half her daughters and
half her sons. Affected male transmits to all his
daughters and none of his sons if the female parent is
unaffected
b) Recessive
On the other hand, if recessive, the female
heterozygote, Xx, will not show the trait but the
;
homozygote xx will show the trait. In X-link recessive,
genes on X have no corresponding genes on Y hence
males are hemizygous for X-linked mutant genes and
express the disease even though the X-linked trait is
recessive. Affected male does not transmit the
disease to his sons and all daughters are carriers. Fig. 2-6. Giemsa stain of Human Male Chromosomes. The
banding pattern is unique for each chromosome allowing
each chromosome to identified and numbered. The knobs on
THE HUMAN CHROMOSOMES
acrocentric chromosomes 13, 14, 15,21, and 22 indicate
the positionsof genesthatcodeforthe large ribosomal RNAs
As indicated earlier the double helix of DNA with its
genetic code, forms the essential part of CHROMOSOMAL ABNORMALITI ES
chromosomes which therefore forms the basis of
Hereditary. ln the human, there are 44 (22 pais) of As indicated earlier, abnormalities of the
autosomes, and X and Y sex-chromosomes. The chromosome complement can be numerical or
female has 44 +XX and the male 44 +XY structu ral.
chromosomes. Using the size of chromosomes and
the position of the centromere, chromosomes can be N umerical Abnormalities
arranged in a logical order and given numerical The usual causative mechanisms are:
names I - 22 for each pairof autosomes. Banding a) Non-disjunction during meiosis. This is when
techniques which produce different patterns of paired chromosomes fail to separate either during
banding on different chromosomes can be used to the 1st or 2nd meiotic division resulting in gametes
identify each autosorne or sex chromosome. A wilh 24 or 22 chromosomes. When these are united
logically arranged set of chromosomes from one cell with a normal gamete with 23 chromosomes, then a
is described as Karyotype, which enables the study of 47 or 45 chromosome zygote is produced. Thus
chromosome numbers and morphology (fig.2-6). instead of a pair, there would be either 3 (trisomy) or
This method of study of chromosomes is called one (monosomy) of the affected pair. The non-
Cytogenetics. By this means it is possible, not only to disjunction can affect either an autosome or sex
identify each pair of the 23 chromosomes but also to chromosome, thus producing example a 47 (+27) or
discover any numerical or structural abnormalities 45G27) or44 +XXX,or 44 + X individualsFig.2-7 .
such as breakages, or trarslocation.
b) Chromosomes lag and loss. lf there is difficulty
and late separation, then one of a pair might lag
behind during telophase and be excluded from the
26
I
i
, Fundamentals of Human Genefics

i
{
i nucleus so that a normal 23 but an abnormal 22 ln Robertsonian translocation the breakpoints are
II located at, or close to, the centromeres of two
chromosome gan ete is produced.
r acrocentric chromosomes (chromosomes 13,
ir* c) Non-disjunction during mitosis. Non-disjunction I4,I5, 2l and 22). Centric fusion of acrocentric
: can also occur during mitosis after the first few chromosomes results in the loss of short arms of
I
t normal divisions of the zygote during cleavage. The each chromosome thereby reducing the total
t
chromosome number to 45. As there is no loss or
first few divisions would produce normal46 gain of important genetic material, this is a
i
chromosome cells. However, when non:disjunction
l functionally balanced rearrangement
r occurs in a subsequent mitosis as a single event, 45
i and 47 chromosomes cells are added, and 46, 45
: and 47 cell lines are established. lf normal mitosis
now occurs throughout the rest of the development of
r
the baby, then theoretically the baby will be made up
of the 3 different cell lines. This is the condition
known as Mosaicism. Sometimes, depending on -+ t
I
i
f!
I
I
which chromosome is involved in the abnormal cells,
either the 45 or 47 cell line will be eliminated by
death of those cells, but once there is more than one
llrr
l4
2t
I
2l
14p2lp
(gets loet)
cell line, then mosaicism still exists. ln mosaicism the L4qZlq

r
I stigmata associated with the abnormal cell line will
I
I
i
be variable and certainly less severe than in the non-
!
mosaic individual whose cells all have that
Fig. 2-8. Fusion of two acrocentric chromosomes reducing
I
chromosomal abnormal ity. the chromosome numberto 45.
I
7
I d) Translocation: This simply means one Structura! Abnormalities
t
to another thereby
chromosome getting stuck on The common causes of structural abnormalities are:
I
i
transferring the genetic material between a) Deletions - when part of a chromosome breaks off
1
chromosomes. ln reciprocal translocation, there is no and is lost b) Duplication - may involve part or the
i chromosomal material lost, a break occurs in each of whole chromosome
4
two chromosomes with the segments being
r c) lsochromosome - is a chromosome in which the
r exchanged to form two new derivative chromosomes.
short or long arm breaks off and is replaced by a
I Usually, the indlvidual will be normal. However,
mirror image duplicate of the remaining arm. A
!w
!
during meiosis, the abnormal chromosome may person with an isochromosome therefore would have
produce an abnormal gamete and an abnormal baby
+
only one copy of the genetic material of one arm but
(
t three of the other arm, with dire consequences.
I
t fr
I{
ta
'T fi
3
}{ t$f;r
td*
d) Translocation - A whole chromosome, usually an
acrocentric, can be translocated onto another,
resulting in a 45 complement, but also producing an
abncrmal (structural) chromosome. On the other
I{* r*il, p tt q$ hand, two chromosomes could exchange parts of
b" t$
their arms. Since no genetic material is lost, this is
called a Balanced Translocation and the person will
*Itl t*
td
}Ilf *r l*
'r* I {tlt
be normal. However, the offspringwho inherits either
of the translocated chromosome will have excess
\v r*x
and/or less set of genes on the translocated arm.
{{It IT
3S
/rr: IIx?
Fic. 2-7. Down Syndrome. This is indicated by trisomy 21

an acrocentric chromosome.
27
lhrmal 1. Autosomal Dominant Diseases

Once a mutant dominant gene has appeared in a
family alI subsequent generations will usually have
an affected person(s) until the offending gene is
firommmrl*i+ removed from thatfamily by a selection bias.
It is unusual to have both parents carrying the

mutant dominant gene, since marriage between two
affected persons is not common. Nevertheless, from
time to time two affected people do marry to produce
Wd
homozygotes (Fig. 2-lOa) who usually have more
severe disabilities than the heterozygotes. Criteria for
autosomal dominant trait includes: both sexes can
be affected; male to male transmission can occur;
both sexes can transmit the trait with equal
Fig.2-9. Reciprocal translocation between chromosomes 8 frequency; successive generations are affected and
and 14.
transmission stops if a generation arises in which no
one is affected.
lndications for Chromosomal Study
The following are some of the important indications
for cytogenetic investigation in Obstetrics and ffid haerqeffilur psrert {A*l
Gynaecology.
A *
1 Repeated abortions
2 Repeated still-birth or neonatal death. This is A AA *a
either to discover or rule-out a chromosomal jftrf*e*dMrnryur Idfia€tad Altafted
pnrent{Arl lrsmcrrottl helefimlr[Er-tg
cause.
3 lnfertility in couples T a* x
arft(ri{l Uruf!*rtGd
4 Previous child with a chromosomal lumrscvaou* honffilrilrr
abnormality
5 Pregnancy in the older woman Fig. 2-10a. Autosomal dominance. lnheritance pattern
6 Amenorhoea between two heterozygous parents.
7 Premature menopause
8 lntersex
hptrmqnpsE w*ld {Arl
GENETIC DISORDERS (DISEASES)
Genetic disorders can broadly be classified into three, A a
namely:
L tt
l
a
iuuom**nx hsmsrypl* Un*frlctcd
1 Single-genedisorders Firefit {6t} lwmawgour
2 t
I=
Chromosomaldisorders tt,
i.lnsk*ed
3 Multifactorial disorders - ie multiple genes homul
causing diseases in collusion with
environmental factors. Fig. 2-10b. Autosomal dominance. lnheritance pattern
between an affected heterozygous and unaffected
SINGLEGENE D!SORDERS homozygous parents.
These can be dominant, recessive or sex-linked.

Fortunatety, mutant single genes that cause diseases There is a 25% chance of a severely affected
are much fewer in the general population than homozygote AA, a 50% chance of affected
normal alleles, presumably because there is a heterozygote Aa, and a 25%.chance of a normal
selective bias against those individual carrying those offspring aa. The usual mating pattern however is
mutant genes. between an affected and a normal parent. Thus there
28
{I
I
i Fundamentals of Human Genetics

i
I is a 50% chance of each child being affected or being family members, has always been firmly discour-
I
normal (fig.10). Examples of dominant trait inheri- aged by Societyl

i tance are Hereditary Nonpolyposis Colon Cancer,
l\- Ma rfa n's Synd rome, Polycystic Disease; Retinoblas- X-LINKED DOM I NANT I NH ERITANCE
r toma, Achondroplasia, Familial Hyper"cholestero-
laemia, Familial Hypercholestero-laernia, Familial This mode of inheritance is rare. The dominant gene
I
Adenomatous Polyposis, Huntington Disease and is usually on only one X chromosome. Therefore,
Hereditary Breast and Ovarian Cancer. Alzheimer each child, male orfemale of an affected mother and
f
disease may also be autosomal dominant. a normal father has a 50% chance of being affect.
Gie.2-72)
2. Autosomal Recessive Diseases
As indicated earlier, one mutant recessive allele is
{ilornld f#prtltrY}
unable to cause disease unless there are two of them I
I
present. ln such cases both parents must carry the

l
lAfl*ct*d $od*r $hfi*,

H Y
h sfid x$Y IJIBd
mutant gene in order to produce an affected
I
: Xri xfid xdY o*&ffi

homozygote. The heterozygote therefore is an
unaffected carrier. The usual mating patterns are
fv Fig. 2-12. X-linked dominance inheritance between normal
\
shown in fig. 2-11 in which 'D' is normal dominant father and affected mother
l
and 'd' is recessive mutation gene. Criteria for an

autosomal recessive trait includes: males and On the other hand, an affected father, married to a
normal mother will produce all affected daughters,
1
females are affected; affected males and females can

transmit the gene, unless it causes death before but NO affected sons. (fig.2-13)
I
reproductive age; the recessive trait can skip genera-

tions and parents of an affected individual are I rilhcbdreffqY
heterozygous or have the trait.
xn Y
xd ,ffixd ffi
Normal x Carrier DDx Dd :
DD Dd Dd DD )U mxd &Y
Carrier x Carrier Dd x Dd = DD Dd Dd dd l*rgfundxd *M It*dhtrd
Carrier x Affected Dd x dd :
Dd Dd dd dd ffi rdrr
Fig.2-77
Fig. 2-13. X-linked dominance inheritance between affected
:
Examples of autosomal recessive diseases are father and normal mother.

I
; \-, Cystic Fibrosis, Tay-Sach's disease, Xeroderma
Pigmentosum, and Thalassemia. An example of an X-linked dominant disorder is X-
linked Hypophosphatemic rickets (vitamin D
Consanguinity resistant rickets) in which the kidney tubules are
Because alleles are inherited from parents, the unable to re-absorb filtered phosphate. Serum
incidence of mutants in an affected family will be phosphate levels are therefore low.
much greater than in the general population. With a
dominant allele, all those in a family who inherit it will
4. X.LINKED RECESSIVE !NHERITANCE
be affected by its particular disease. Not so with
Haemophilia, Duchene Muscular Dystrophy, Fragile
recessive alleles. Because they are recessive, all
X Syndrome, G6PD Deficiency are the well-known
those in the family who possess it would be carriers
examples of this type of inheritance.
but clinically normal. However, since that mutant
allele is in the family, marriage between blood-related
family members is more likely to produce affected
I
i
rilh#firrud+Srr{itY}
homozygous offspring than marriage between non-
I
I tr Y
blood related persons.
,
! x Irx n,
lllua$grm.Lethll x x{ XY
1
I gilk f*!rr.a
This is one very good reason why since antiquity,
!
I
Fra*r rrdr
,,
marriage between firstdegree, or even second degree
Fig.2-14a
29
fforil*fdttrSffl 2 Cri-du-chat' Syndrome (partial deletion of the

short arms of chromosome 5) is an example of a
x T structural abnormalitiy. As the name suggests,
x Ix( xf-., these babies have a high pitch cry, like that of a
,
Cnrhrt!ffixXrX I cat. They have microcephaly, hypertelorism etc.
G
h?.
X! ;8X
e*k: with severe mental retardation.
fgnb.
Fig25. Down Syndrome
Sex chromosome abnormalities

Figs.2-74b 1 Turner Syndrome (45,X0) - They usually have a
This is more common than its dominant counterpart.
short stature, ovarian dysgenesis and no menses
Since females have two Xs, only those who have the
and therefore are sterile.
mutant gene on both Xs (that is XaXa homozygous) 2 Klinefelter Syndrome (47,XXY) -
(Fig.2- 15).
would be affected, the heterozygous XXa remaining Thin and tall, underdeveloped secondary sexual
unaffected, but being a carrier. characteristics, reduced facial and body h ;r.
hypogonadism, and therefore steri le,

The male on the other hand, if hemizygous for the
3 Double Y Syndrome (47,XYY) - Usually tall,
mutant X-linked recessive gene, will be affected. aggressive and may be mentallysub-normal,
However, he can only transmit the mutant gene Xa to 4. XX Males (46, /rX) - The SRY region on the short
his daughters, to be carriers, but all his sons will be arm, determining the TDF, (testicular
unaffected. Gig. 2-74 a) determining factor) is presumably translocated
on to one of the X's.
An affected mother (homozygotes) would transmit 5. Translocated Down Syndrome -Down Syndrome
the mutant gene to all her offspring, the females with 46 chromosomes is an example of
becoming carriers, but the males being affected. translocation in which the extra chromosome 21
Thus a grand-father transmits the mutant gene is translocated onto another acrocentric
through a daughter as a carrier (Fig.2-14a) to a chromosome, usually 74 or 21. (Fig. 2-8) The
grandson who will be affected. Gie.2-I4b)
stigmata are the same as for the Trisomy - 21
Down syndrome.
Haemophilia is the well-known example of X-linked
recessive inheritance which apparently was
transmitted by Queen Victoria of Britain to her
lilBuftfter Spdtusne
descendants.
5, YLINKED INHERITANCE - Rare, and medically

insignificant
6. ATYPICAL MODESOF !NHERITANCE iltililfiilfr*ililttililnn

I?${50?&
There are several unusual modes of inheritance for
:Medical .Genetics
which textbooks of should be
consu lted.
CHROMOSOMAL DISORDERS
nilfrffr|*ililtnililtrr
9IOItt3t3?{15}6
Autosomal abnormalities
1. Down Syndrome (trisomy 27) Gie.2-7) is the
commonest numerical abnormality with short
stature, short neck, loose skin on the nape,'flat
ilx rr
r? t&
ttismm
ilil *tr
occiput and flat nasal bridge, low-set ears, mental
retardation etc.
Fig. 2-I5. Klinefelter Syndrome (47 , y,XY)
30
MULT!FACTORIAL DISORDERS REFERENCES

This presentation so far has
specific traits or abnormalities
specific identifiable SINGLE seffi lntroduction to MedicalGenetics by JA Frazer
Some anomalies however Roberts. Marcus E Pembrey. Oxford Medical
combination of more than one Publication
Thompson and Thompson. Genetics in
some environmental factors.
Medicine by RL Nussbaum, RR Mclnnes and
(r inheritance is called HF Willard. WB Saunders Co. Publication
lnsulin-Dependent Diabetes Elements of Medical Genefrcs by Alan EH
t destruction of islet Beta cells) as well i Emery and Robert F. Muller. Churchill
5
Dependent Diabetes Mellitus (l Liv i ngston Publ ication
t
{ resistance).
{
r,
r
rr
f
I
r
f
t
F
t
a
rI
?
it
g
t
r
t
3
t
l
F
I
f
i(
I
?
I
fi
(
t
II
f a
r
t)
t
I
/.
II
,lv
31
{
I
I
t
32
The Female Reproductive Organs
CNBTagoeandRUOkolo
of lesser (true) pelvis. The external components

The female reproductive organs (genitalia) consist
internal and external components. The internal (external genitalia) include the lower part of the
components (internal genitalia) are the two ovaries, vagina, the vaginal vestibule, the mons pubis, the
\> the
labia majora and minora and the clitoris. They are
the two fallopian tubes, a midline uterus and
upper part of the vagina. They are located within the located in the perineum.
THE INTERNAL GENITALIA
tf*r Li*ir binxt ,ffitii m*ftrti*

enm hi D*
YIEffi,
Wtu
UErmI
Mti- I- d-sry n* 6xt{* grr*fr t&ffi
s*md
fraa{dfr*m {nrd* *- # -*llrlrLc
Iofiro.t
{**r3* {s!r!mr sn tErf C
drn*r*
S'E|*
M
te&6*rX
dffi
Fig. 1a Female lnternal Genitalia.

Adapted from Atlas of Human Anatomy by Frank H. Netter.
4'n Edition, Saunders Elsevier, 2006.
33
ryilqtsrtrl
l*
{{*r
{f f,fir
*mr
lmfi
E{!*llt{iln*:-
l*^tmr,
uns*ils*
Fig. 1b. Mid-sagittal section of female pelvis.

Adapted from Atlas of Human Anatomy by Frank . H. Netter.
THE OVARIES peritoneum of the ovarian fossa, which separates it

from the obturator nerve and vessels. The medial
The ovaries are the female gonads (homologue of surface is related to the uterine tube, the two being
testis in the male). They produce the fernale germ separated by a peritoneal recess, the ovarian bursa.
cells (oogonia) and perform endocrine functions
(production of female hormones, estrogen and The ovarian surface is smooth before regular
progesterone). They are small oval structures ovulation begins but becomes distorted thereafter by
measuring 3 x2x1cm in size and are located, one on scarring resulting from degeneration of successive
each side, in the ovarian fossa, in the lateral wall of corpora lutea. The ovary has no peritoneal covering
the of the lesser pelvis. The ovarian fossa is located and hence during ovulation the oocyte is expelled
on the posterior aspect of the broad ligament, just into the peritoneal cavity where it is trapped by the
below the pelvic brim. The fossa is bounded fimbriae of the uterinetube,
anteriorly by the superior vesical artery and
posteriorly by the ureter and the internal iliac The surface of the ovary in young females is covered
vessels.The arterior border of the ovary is attached to by a single layer of cuboidal epithelium giving it a dull
the posterior leaf of the broad ligament by a grey appearance, which contrasts with the glistening
peritonealfold, the mesovarium. lts posterior border peritoneum of the mesovarium. The tissue deep to
is free, lts superior or tubal extremity is attached to the epithelium is a collagenous coat whie h surrounds
the ovarian fimbria of the uterine tube and the an outer cortex and an inner medulla. The cortex
suspensory ligament of the ovary (infundibulopelvic forms the major part of the ovary after puberty and
ligament). The latter is a peritoneal fold, which contains ovarian follicles of various sizes and corpora
contains the ovarian vessels and nerves, which pass lutea (and their degenerative remnants), depending
u pwa rds over the external iliac vessels. The inferior or on the menstrual cycle or age (see fig 2). The medulla
uterine extremity is attached to the uterus by a band is highly vascular, more so than the cortex. The
of fibrous tissue called the ovarian ligament, a vessels enter and leave thb organ from the
remnant of the gubernaculum (see embryology mesovarium through a slit in the cortex called the
section). The lateral surface of the ovary contacts the hilum.
34
fttirffi*{il
Hnca6s
I ArBile
r ar$trgk
I
a
I
I
*Htrlsy
r€dfii
i
t
I
a
I
I
Prs.'vuMry
I
I hlliel6
I
I eurfryk*k
I
t
t'
I
Flg. 2. Schematic Representation sf the lnternal Structure of the Ovary.
; Basic Histology; Text and Atlas. L. C. Junqueira and J. Carneiro. McGraw-Hills Companies, 2OO7.
of
I
Vuscular supply *The ovarian arteries are branches ovaries are drained by a panpiniform plexus of veins
I
I They
the abdominal aorta at the level of L2 vertebrae. in the suspensory ligaments. This plexus drains into
I descend on the posterior abdominal wall, a pair0f veinswhich accompanyeach ovarian artery.
I retroperitoneally, cross over the pelvic brim on the They eventually join before termination. The left
. external iliac vessels to enter the suspensory ovarian vein drains into the left renal vein while the
i ligaments. Each ovarian arlery givesa branchtothe righijoinstheinferiorvenacava.(Seefig.3)
! uterine tube and ends by supplying the ovary. The
r
I
I
t
I
i
?/
t
f
rrqrilqmf drtfrrair
I
i
Fig. 3. Blood supply to Uterus, Ovary, Uterine Tubes and Vagina.

i( Adapted from Atlas of Human Anatomy by Frank H. Netter
: 4'n Edition, Saunders Elsevier, 2005.
;
35
Lymphatic drainage is by vessels which ascend along on each side of the uterus in the upper border of the
the ovarian artery to the lateral aortic and pre-aortic broad ligaments (Fig. 1a). The part of the broad
:f,1T,.T:,?"ly::?,.:hi',l'J::,1[ Hil'iJr.
uterine
v
l
Nerves to the ovary consist of postganglionic opens into the uterine cavity medially by the
sympathetic, preganglionic parasympathetic and ostium and laterally into the peritoneal cavity by an
autonomic afferents and run along the ovarian abdominal ostium, near the ovary. For descriptive
vessels. purposes the uterine tube is divided into four parts
from lateral to medial: infundibulum, ampulla,
THE UTERINETUBES isthmus and intrauterine part (Fig. 4a).
The uterine tubes, more commonly referred to as the

fallopian tubes or oviduct, are 10-12cm long and lie
firtfirrdutail.E
ssdu
dulrrlri
Ms
&ftrrt
tf,aml
dor*y Srfipc4dorYt0rrsr{'
dd41licot*rt
trrrrLfivarilbl
Mqc!&i**t
*qeee*Ftl
mr*CI,n'ra*mld
bmdMl
edn&
ol
{dm!t ffitdtw:a,smt
a#,isd$.
[Mrt
fo,s"N
drrd
ne&o&raxlhl*k
h,* fffirlxrtrnr
Ftg.4a. Parts of the Uterus, Fallopian tube, Vagina and Ovary in coronalsection.
Adapted from Atlas of Human Anatomy by Frank H. Netter
Thelnfundibulum-alSoknownasthefimbriatedthelargerfimbriaethemucosahaslongitudinalfolds
end, is formed by a funnel-shaped expansion of the which are continuous with those in the
uterine tube. lts margin is prolonged into a variable infundibulum. The fimbriae spread over the ovary
number (20-30) of finger-like processes called and help to capture the released unfertilized ovum, ' -'
fimbriae. The ovarian fimbria is the largest fimbria passing it into the lumen of the. uterine tube through
and is applied to the tubal pole of the ovary. The the abdominal ostium. The ostium is 2-3mm wide
fimbriae are lined by ciliated columnar mucosa; in andissituateddeepwithintheinfundibulum.
35
The ampulla - begins at the medial end of the The ampulla - begins at the medial end of the
infundibulum and is tortuous and thin-walled. lt is infundibulum and is tortuous and thin-walled. lt is
the longest and widest (up to 1cm) part, making up the longest and widest (up to 1cm) part, making up
over half of the tube's length. lt is here that over half of the tube's length. lt is here that
fertilization takes place. The lum-en is,fii@ by a fertilization takes place. The lumen is filled by a
complex plication of the mucosa (Fie. 4b). complex plication of the mucosa (Fig. 4b).
O{rrhllglirdlnal
rmoo0rdultll
kuscrluk
nuao&nnurda
ryilt*,m
Lrrrrffiott E!h.
ller,
Xlffi.LlF{f,rL
Lxdn*ftuprlr
Fig. 4b. Transverse Section of Fallopian Tube.

Adapted from diFiore's Atlas of Histology with Functional Cotrelations. 1lth Edition.
V. P. Eroschenko. Lippincott Williams & Wilkins 2008.
The isthmus is short (about 2.5cm), rounded and peritoneum and is continuous with the broad
muscularwith a narrow lumen (0.1-0.5mm). ligament.
The intrauterine (intramural or interstitial) part lies Vascular supply - the uterine tube receives arterial
within the wall of the uterus, is about 1cm long, and blood supply from both the uterine and ovarian
opens into the main uterine cavity near its upper end, arteries. Venous plexuses in the tubal wall eventually
atthe cornu, through a minute uterine os. join the uterine and ovarian veins.
Histologically, the tube has three layers: an internal Lymph vessels from the uterine tube follow the
mucosa, an outerserosa and an intervening muscular ovarian veins to the lateral aortic and pre-aortic
layer. The mucosa has ciliated columnar cells nodes.
interspersed with secretory cells which secrete a
thick mucus and peg cells. The cilia beat towards the Nerves to the uterine tubes are partly from the
uterine cavity. ovarian plexus and partly from the uterine plexus,
both of which are sympathetic (T11 L1). -
The muscular layer is composed of an outer Parasympathetic innervation comes from the vagus
longitudinal and inner circular layers of smooth nerve to the lateral half and lhe pelvic splanchnics to
I muscle; some parts of the tube may have an the medial half of thetube.
additional inner longitudinal layer. The serosa is the
37
THE UTERUS uterus weighs 30-409 and measures about 7.5cm

long, 5cm in its widest breadth, and 2.Scm thick,
The uterus is the organ of gestation. lt is a hollow
pear-shaped thick walled muscular organ, normally lts position in the pelvis may vary with the distention
v
situated in the lesserpelvis between the rectum andof the bladder and rectum, lts long axis is tilted
urinary bladder (Figs. 1 and 4a). lt receives thesuperiorly forwards and is nearly at right angles to
uterine tubes in its upper part and is continuous that of the vagina. lt is bent forward above the
below with the vagina. The adult non-pregnant bladderinanteversion(Figs7b,4aand5).
&tqlprCm
€\
Antdsadd r
idundG
- i6ari,#i-
llinsy ta(r*d61fo
txdvqirs
Fig. 5. Positions of the Uterus telative to the Vagina
The uterus is divisible into two parts, the corpus or body forming its upper two-thirds and a narrower lower one-
third called the cervix, a slight constriction marking the junction of the two.(see figs 4a and 6)
I
l-C Conff
a
I
Fie. 6. Parts of the Uterus and Fallopian tube.
38
lnternally the cavities of the two parts are continuous The cervix projects into the vaginal vault through the
through the internal os: the lower end of the cervix anterior wall, for about half of its len$h, and is
opens into the vagina by art external os. (figs 4a and therefore, divided into supravaginal and vaginal
6). parts (Figs. 1, 4a and 6). The supravaginal part is
surrounded by cellular connective tissue (part of the
The body of the uterus (corpus uteri) is somewhat parametrium) which separates it from the bladder
flattened anteroposteriorly. lts rounded upper end and which contains the uterine arteries and the
above the attachment of the uterine tubes ls called ureters laterally. The peritoneum covers it posteriorly.
the fundus. lts surfaces are anterior (vesical) and The vaginal part is surrounded by grooves formed by
posterior (intestinal). The anterior surface, related to the upper part of the vagina called fornices - anterior,
the bladder is covered with peritoneum, which is posterior and right and left lateralfornices. lts lower
reflected at the level of the internal os onto the end bears the external os, the communication
bladder, the so called utero-vesical fotd. The space between the cervical canal and the cavity of the
within this fold is called the vesico-uterine pouch. (fig vagina. ln the nulliparous woman the external os is
1b), which may be occupied by part of the small circular but after child birth it becomes transverse
intestine. The posterior surface of the uterine body, with anterior and posterior lips. The anterior lip is
also covered with peritoneum which continues down shorter but projects further inferiorly; both Iips are
to the cervix and upper vagina and is then reflected usually in contact with the posterior vaginal wall.
back to the rectum, forming a recto-uterine pouch ( of The vaginal part is covered by squamous epithelium
Douglas) (Fig. 1b). continuous with that of the vagina.
The fundus, covered by peritoneum, is usually in The cervical canal is fusiform longitudinally (Figs 4a
contact with coils of small intestine. The lateral and 6) but flattened transversely. lt communicates
margins give attachment to the broad ligament, a above with the uterine cavity by the internal os, and
double layered fold of peritoneum which drapes over below, with the vaginal cavity through the external
each uterine tube towards the pelvic floor and os. The canal itself is thrown into folds which
stretching to the lateral pelvic walls. The point of interdigitate to close it.
attachment of each uterine tube is known as a cornu.
Antero-inferior to this is attached the round ligament The folds consist of two longitudinal ridges, one each
of the uterus, while postero-inferior to it the ligament on the anterior and posterior walls, and from which
of the ovary is attached; both ligaments run in the small oblique folds (palmate folds) extend laterally
broad ligament. like the branches of a tree (arbor vitae) (Figs 4a and
6). The upper third of the canal is gradually taken up
The cavity of the uterus is small compared to the thick into the body of the uterus from the 2nd month
wall. ln the body it is flattened anteroposteriorly, thus onwards, to form the'lower uterine segment'.
presenting as a slit in sagittal or transverse section,
the anterior and posterior walls being almost in ln gross histologic structure, the uterine walls consist
contact. of three major layers, an internal endometrium, a
middle myometrium (smooth muscle layer) and an
ln coronal section it is triangular, broad above and outermost perimetrium or serosa. The endometrium
narrow below at the internal os. lt is 6cm deep when consists of a lining of simple columnar epithelium,
measured from the external os to the fundus. which is ciliated in part, and a large number of
tubular or coiled glands, embedded in connective
The cervix uteri or neck of the womb is a narrow
tissue stroma. The superficial stratum functionalis
hollow cylinder, about 2.5cm long in the non-
forms most of the thickness of the endometrium and
pregnant uterus. lt is less mobile than the body and
it's blood vessels are tortuous with fine branches
hence their long axes are seldom in line; therefore,
feeding capillary plexuses near the surface; this layer
the axis of the whole uterus is usually curved is shed during menstruation. The deeper part,
i forwards, concave below, a state described as
stratum basalis contains small straight arteries and
anteversion (the bend is at the level of the internal
arterioles and forms a reserve for regeneration of the
os).
39
functionalis. The cervical canal is lined in its upper The perimetrium is composed of peritoneum. Vessels
two-thirds by a simple columnar epithelium with and nerves of the uterus Arterial supply (Fig. 3) - the
tubular glands (glands of Naboth); its lower,thlrd has main artery of the uterus is the uterine branch of the
stratified squamous non-keratinizing internal iliac artery on each side. The uterine artery 4
continuous with that of the vaginal part of flre cervix. runs medially in the broad ligament to the cervix.
The glands secrete clear alkaline mucus a!4 are a About 2cm from this, it crosses above and in front of
frequent site of cyst formation (Nabothian cysts). the ureter and above the lateral vaginal fornix. At the
level of the internal os, it divides into a large
The myometrium is fibromuscular and forms the bulk ascending branch and a small descending branch'
of the wall of the uterus. lt usually presents as four The ascending branch is tortuous and ends by
layers of smooth muscle in the body, from within anastomosing with the ovarian artery. The paired
outwards - submucous, vascular, supravascular and uterine arteries anastomose extensively with each
subserous. The two outermost layers continue into other across the midline. Terminal branches in the
the uterine tubes, ovarian and round ligaments, uterine muscle are tortuous and called helicine
broad ligaments and uterosacral ligaments. Below, arteries (see Fig.7). The descending branch supplies
they merge with the dense irregular connective tissue the cervix and vagina.
of the cervical wall.
Frs$io|r*l
hfer
Endam*ium
BeBsl
hysr
lirllE{neflL&r
SrahFttarbry l'tslkdafisry *rat*ba$Bry

and veln
Ftg.7 . Schematic representation of the Spiral arteries of the Uterus.

Adapted from Elsevier. Gartner and Hiatt: Colour Textbook of Histology 3E- www.studentconsult.com
Venous drainage (FiS. 3) - veins from the uterine wall Iateral aortic and pre-aortic nodes, while others go to
for.m a uterine venous plexus in the broad ligament, the external iliac nodes or run along the round
near the cervix. The plexus is drained by the uterine ligaments to the superficial inguinal nodes' From the
vein into the internal iliac vein. body, lymphatics pass through the broad ligament to
the external iliac nodes. Vessels from the cervix pass
-
Lymphatic drainage (Fig. 6) most lyrnph vessels to the external iliac, internal iliac, sacral, rectal and
from the fundus run with the ovarian vessels to the obturator nodes,
40
Nerve supply - the sympathetic supply to the uterus down they are in contact with the levator ani
(originating from l'10 - L1 spinal segments) is from sphincter urethrae; the greater vestibular glands and
the uterovaginal plexus (in the broad ligament) which the bulbs of the vestibule.
t---- in turn arises from the inferior hypogastric,plexus.
Parasympathetic supply is fronr the pelvic The pubovaginalis part of the levator ani, the
splanchnics (nervi erigentes) containing 32-S4 urogenital diaphragm and the bulbospongiosus
fibres. Nerves to the cervix form a plexus in which are muscle act like sphincters for the vagina on
Iocated small paracervical ganglia, of which one is contraction.
normally large and called the uterine cervical
ganglion. Vessels and nerves of the vagina
Arterial supply (Fig. 3) - the vagina receives blood
THEVAGINA from a number of sources. The two vaginal arteries
may arise directly from the internal iliac or from the
The vagina is the female organ of corpulation and uterine artery. They anastomose with each other and
forms the lower portion of the genital tract or birth with the cervical branch of the uterine artery.
canal. lt is a 7-9 cm long tube or sheath and extends Branches from the internal pudendal and middle
anteroinferiorly from the uterine cervix to the rectal arteries also supply the vagina.
vestlbule (Fig. 1). Except at the fornices its anterior
and posterior walls are in opposition, the cavity being Venous drainage (Fig. 3) -vaginal venous plexuses in
a transverse slit. the walls drain into the internal iliac veins; they
communicate with the vesical, uterine and rectal
The cervix uteri projects into the upper part of the venous plexuses.
vagina through the anterior wall resulting in the
anterior wall being about 1cm shorter than the Lymphatic drainage (FiC.6) - three sets of lymphatic
posterior wall. Also, the long axis of the vagina is vessels drain the vagina. From the upper part the
almost at right angles to that of the uterus. The vessels accompany the uterine artery and end in the
grooves or recesses formed by the vagina around the internal and external iliac lymph nodes. The middle
cervix are the fornices, the posterior fornix being the part of the vagina is drained by vessels which run
deepest (the others are anterior and right and left with the vaginal artery to the internal iliac nodes.
lateral). Vessels from the vestibule end in the superficial
inguinal nodes.
The vagina communjcates above with cervical canal
through the external os and opens to the exterior (into Nerve supply - the vagina receives innervation from
the vestibule) via the introitus. The vagina pierces the the uterovaginal plexus which lies in the base of the
levator ani and the urogenital diaphragm. broad ligament; the fibres are from the inferior
hypogastric plexus and the pelvic splanchnic nerves.
Relations of the vagina (Fig. 1) The vagina is lined by stratified squamous non-
Anteriorly, the vagina is in contact with the fundus of keratinlzed epithelium supported by a lamina propria
the urinary bladder below where the uterine cervix containing thin-walled veins. This mucosa has two
pierces the anterior wall. One or other of the ureters median longitudinal ridges, anterior and posterior
also lies here on the way to the bladder. Below this columns. From these numerous transverse folds or
level, the urethra is embedded in the anterior wall of rugae extend; the rugae are especially well developed
the vagina. The posterior wall is covered in its upper before parturition. The epithelium thickens after
part by peritoneum and a penetrating wound in the puberty and becomes rich in glycogen. The human
posterior fornix may involve the peritoneal cavity vaginal epithelium does not undergo marked
(pouch of Douglas), which contains instestines here. changes during the menstrual cycle but the glycogen
Below the perintoneal reflection loose connective content increases after ovulation and diminishes
tissue separates the vaginal wall from the rectum. towards the end of the cycle. Action of the
a Most inferiorly is the perineal body. Laterally, the Doderlein's bacillus (Lactob'acilus) on the glycogen
vagina is related to the ureters and uterine arteries as rich desquamated cells renders vaginal fluid acidic,
they lie in the broad ligaments at the fornices. Lower which discourages the growth of micro-organisms.
4L
There are no mucosal glands; the vagina is normally THE EXTERNAL GENITALIA (Fig. 8)
lubricated by mucus from the cervical glands. The
These lie in the urogenital triangle of the perineum
outer, muscular coat of the vagina consists of'two
layers of smooth muscle. The lower vagina is and are collectively known as the vulva or
pudendum. They include the mons pubis, labia
surrounded by the skeletal musc[e fi'bres'of
majora and minora, clitoris, vestibule, vestibular bulb
bulbospongiosus. External to the muscle is loose
and greater vesti bular glands.
connective tissue containing extensive'vascular
plexuses.
Mons pub$s FreBuec af dieris
Frenulurn of
Clihris Clilcris
L*iummai .*.- Exbfinalurelhral

a*fice
Labium minilc
orifice
,{introit*s}
Hymen'-*
' Gyn*ecolagicd perinaum

{orrerlie* perinwl boelyJ
Fig. 8. Female external genitalia.
THE MONS PUBIS (MONSVENERIS) intermingled with smooth muscle fibres. Anteriorly
This is the rounded eminence overlying the pubic the labia join to form a commissure. However, their
symphysis and is formed by a mass of subcutaneous thinner posterior parts form a low ridge with the
fat. At puberty it becomes covered by coarse hairs connecting skin between them, the posterior
over an area usually with a horizontal upper border. commissure. The area between this and the anus is
THE LABIA MAJORA the'gynaecologica l' peri neu m ( peri nea I body, covered
with skin). The round ligament of the uterus and a
These are two prominent skin folds extending
persistent processus vaginalis may reach the labia
backwards from the mons pubis towards the anus
majora
and forming the pudendal cleft into which open the
THE LABIA MINORA
vagina and urethra- Each labium has a smooth
internal surface with numerous large sebaceous These two folds of skin lie within the labia maiora, are
glands and an outer surface bearing hairs. The labia devoid of fat and pass downwards and backwards
contain loose connective and adipose tissues where their posterior ends may be joined by a skin
42
fold, the frenulu ,r of the labia minora or fourchette. shape varies from a round aperture to a slit, crescent
Anteriorly, each la'rium splits into two, its upper layer or stellate, with raised margins. lt is very distensible.
passing above the :litoris to form with itscounterpart On each side of the orifice are the openings of the
a fold, prepuce or foreskin, which:svgrh?.r.tgs the ducts of the paraurethral glands (Skene's glands);
glans clitoridis. The lol".:r layer paSseg:'under the these are homologous to the prostate gland in the
clitoris to form with its fellow the frenulum clitoridis. male.
The inner surfaces are provided..,urffi.,,hgrl€rous THE HYMEN (Fig.8)
sebaceous glands. ln sexual excitement.'the, fabia
minora become engorged with blood and,areturgid. This is a perforated diaphragm or thin fold of tissue
situated just inside the vaginal orifice. lts internal
THE CLITORIS surface is mucous membrane while the external
surface is skin. lt varies greatly in form-annular,
This is a small erectile organ homologous wrin the semilunar, cribriform or fringed. lt may be absent or
penis, and situated just postero-inferior to the completely closed (imperforate hymen). When torn,
symphysis pubis. lt is partially enclosed by the its remnants of small tags of skin are seen at the
bifurcated ends of the labia minora (prepuce and vaginal orifice - carunculae hymenales or
frenulum). It consists of a root, body and glans (Fig, myrtiformes.
8). The root is composed of two crura attached to the
ischiopubic rami. Each crus continues forwards as THE BULBS OF THE VESTIBULE (FIG. 8)
corpus cavernosum, the two being bound by dense
fibrous tissue to form the body. These are two elongated erectile masses
homologous with the single penile bulb and corpus
The glans clitoridis is a small round mass of spongy spongiosum, they flank the vaginal orifice. Each is
tissue; its covering skin has rich sensory innervation, about 3cm long with an expanded posterior end
important in sexual responses. Like the penis, the which is in contact with the greater vestibular gland.
clitoris has a suspensory ligament and Their anterior ends are tapered and are joined to one
lschiocavernosus muscles covering the crura. another by a commissure and also to the glans
clitoridis by two slender bands of erectile tissue.
THE VESTIBULE Superficially, each is covered by a bulbospongisus
muscle but their deep surfaces are attached to the
This is the space enclosed by the two labia minora perineal membrane.
(Fig. 8). Opening into it are the vaginal and external
urethral orifices as well as those of the greater THE GREATER VESTIBULAR GLANDS [Bartholin's
vestibular glands. and numerous other lesser Glandl (FIG.9)
vestibular glands.
I Also known as Bartholin's glands and measuring
I TH E VAGI NAL ORIFICE (I NTROITUS) about 0.5cm in diameter, these glands are located
I
on *ither side of the vestibule in the fatty tissue of the
i labia majora posterolateral to the vaginal orifice.
I This presents as a sagittal slit postero-inferiody to the
t urethral opening. The size varies inversely with that of They have an oval or round shape and in contact with
I the hymen but is capable of great distention oroften overlapped bythe posteriorend of the bulbof
,* the vestibule. From their anterior ends issue 2cm
I particularly during child birth.
i long ,Jucts which open into the vestibule in the
I
groove between the hymen and the labium minus.
I THE EXTERNAL URETHRAL ORIFICE (Fig. 8)
I
t
/- This lies about 2.5cm postero-inferior to the glands
I
F
clitoridis, between it and the vaginal opening. lts
I
i
i
,y
43
l
furuphydeptli*
t%, -"o
Itrdii{e&gmals
m.6dg
l.Htrdrm'ft6
Blbdfiav:&,&
Mradmgn*t*x
{nkrhsdeof
'ry{ffi|{#figm}
Ssme&&u(ts
ligrowd
&aaryut4flx&
{8f,Mif5}@
Eubu*meimu* *
firrBd*
a*d@a'!dEr I
Fig. 9. Diagram of dissected Female Perineum.

and of the labia receive blood from the superficial and

The glands are composed of tubulo-acinar units
secrete clear or whitish mucus under sexual deep external pudendal branches of the femoral ,
stimulation which provides lubrication for coitus. artery of each side. The arterial blood supply is
lmmuno-histochemical studies have shown the massiveandhencehaemorrhagefromvulval injuriet
secretion to contain serotonin, calcitonin, bombesin, may besevere.
--
hCG a nd kataca lci n. The greater vesti bu lar gla nds a re
homologues of the bulbourethral glands in the male.
Venous drainage - this is via veins accompanying the
Lesser vestibular glands are present in the vestibule above arteries and ending in the internal iliac and
and open into it between the urethral and vaginal greatsaphenousveins'
orifices. They also secrete mucus which moistens the
Nerve supply (Flg. i0) - motor innervation is
labiaandvestibule.
supplied by the pudendal nerve. Sensory nerve
BLOOD SUppLy, NERVE SUppLy AND supply to the anterior third is from L1 spinal nerve I
LyMpHATIC DRAINAGE OFTHEVULVA through the ilio-inguinal nerve and genital branch of
thegenitofemoralnerve. l
Arterial supply - this comes mainly from the internal
pudendal artery, a branch of the anterior division of
the internal iliac. The mons pubis and anterior parts
M
Fig 10. Nerve Supply of the Female Perineum

The posterior two-thirds of the vulva receive sensory levator ani and coccygeus (fig.8) with the
innervation from 53 spinal segment by way of the corresponding ones of ihe opposite side, These
pudendal nerve and the perineal branch of the muscles, variable in thickness, are attached to the
posterior femoral cutaneous nerve. A spinal back of the pubis infront, to a thickening in the
anaesthestic, therefore, must be injected higher in obturator fascia (tendinous arch) laterally and
order to anaesthetize the anterior region. posteriorly to the coccyx. Medially, the muscle fibres
blend with the walls of the viscera; between the
Lymphatic drainage - lymphatic vessels originating lower vagina and the anal canal they insert into the
in a rich plexus pass to the superficial inguinal nodes. perineal body. The pelvic diaphragm is traversed
Those from the clitoris and labia minora drain to the from before backwards by the urethra, vagina and
deep inguinal nodes and direct clitoridial efferents rectum.
may pass to the internal iliac nodes.
The fascia covering the upper surface of the muscles
SUPPORTS OF PELVIC VISCERA . THE PELVIC is known as the superior fascia of the pelvic
FLOOR diaphragm. Condensations of this fascia form
important mechanical supports of the uterus -
transverse cervical, pubocervical and uterosacral
i
I This is formed by the pelvic diaphragm, a funnel-

shaped musculofascial shelf which closes the pelvic ligaments (Fig. 11).
outlet. The muscles of the pelvic diaphragm are the
45
{i{ru}bffitr
H.tocxrial
rusrnd
TramusrEs{snld
{eilk$srtttr*
Fig. 11. The Pelvic Fascia and Ligaments.
The transverse cervical ligaments (of Mackenrodt) or Broad ligaments (Fig. 1a) - these are a double layers
cardinal ligaments are the largest and most of peritoneum which drape over the uterine tubes and
important clinically. They extend from the side of the extend from either side of the uterus to the lateral
cervix at the level of the internal os, and vault and pelvic walls and floor. Laterally, they extend over the
lateral fornix of the vagina to the lateral walls of the ovarian vessels as the infundibulopelvic ligaments or
pelvis. the suspensory ligaments of the ovary. The broad
ligament contains extraperitoneal connective tissue
The pubocervical ligaments extend forwards from the and smooth muscle, termed the parametrium.
cervix and uppervagina, diverging around the urethra
to attach to the back of the pubis. The posterior layer projects backwards as the
mesovarium which gives attachment to the anterior
The uterosacral ligaments pass backwards from the border of the ovary. Blood vessels to and from the
cervix on either side of the rectum and attach to the ovaries are carried in the suspensory ligaments of the
lower part of the sacrum. These contain smooth ovary attached to the lateral wall of the pelvis, not in
muscle fibres and are palpable through the rectum. the mesovarium. This statement should be deleted..
The part of the broad ligament between the uterine
The lower, inferior fascia of the pelvic diaphragm is
tube and the mesovarium is the mesosalpinx while
thin and is continuous with the obturaior fascia and the remainder alongside the uterine body is the
the fasciae over the external anal and urethral
mesomeirium.
sphincters.
The uterovesical fold of peritoneum (anterior
Other ligaments of the uterus ligament) and the rectouterine fold (posterior
These include the folds of peritoneum connecting the
I igament) have been descri bed above.
uterus to the bladder, rectum and the lateral pelvic
wall, and the round ligaments of the uterUs. Round ligaments (Fig. 1a) - these are fibrous cords
containing smooth muscle running from the anterior
46
parts of the uterine cornua and passing through the reach the level of the umbilicus when full. lt has
inguinal canals to insert into the fatty tissue of the normal capacity of up to about 500m1. The empty
mons pubis or labia majora. Blood vessels, nerves bladder is somewhat tetrahedral in shape and has an
and lymphatics run along the round ligaments; the apex, fundus (base or posterior surface), a superior
lymphatics end in the superficial inguinal nodes. and two inferolateral surfaces. The apex is anterior
These ligaments are considered to be respons'tble for and points toward the upper edge of the symphysis
holding the uterus in anteversion and theirstrdching pubis. The fundus is triangular, lies posteroinferiorly
or laxity results in the uterusflopping backwards. and is closely related to the anterior wall of the
vagina. The superior surface is triangular and is
The Perineal Body in the Female (Fig. 9) covered by peritoneum except its most posterlor part
The perineal body, or central tendon of the perineum, which is separated by connective tissue from the
is a wedge-shaped fibromuscular mass lying in the supravaginal cervix. The peritoneum is reflected on
midline between the lower end of the vagina and the to the uterus at the level of the internal os. The
anal canal. lt forms the landmark of the perineum in inferolateral surfaces rest on the pubis (separated by
which several muscles and fasciae converge and retropubic fat) and the fasciae covering the levator
interlace. The muscles include the levator ani, the ani and the obturator internus muscles. The inferior
transverse perineal, the bulbospongiosus and parts of angles of the inferolateral surfaces and the fundus
the external anal sphincter. meet inferiorly at the neck of the bladder' This is the
most inferior and fixed part of the viscus and is
THE PELVIC PART OF THE URINARY TRACT pierced by the internal urethral orifice. The wall of
(Figs.1b, 8 and 9)
the bladder consists of a mucosa, muscle and
adventitia (or serosa on the superior surface).
This part of the urinary tract includes the pelvic
ureters, the bladder and the urethra. The mucosa consists of transitional epithelium
(urothelium) supported by loose connective tissue.
The pelvic ureters - are narrow, thick-walled
The muscle coat (detrusor muscle) consists of
muscular tubes, 25cm in length and continuous
interlacing bundles of smooth muscle fibres arranged
above with the abdominal parts of the ureters. Each
in three indistinct layers. The fibres in the neck
enters the pelvis by crossing the end of the common
region are continuous with those in the urethra. ln
iliac artery or the beginning of the external iliac artery
the empty bladder the muscosa is thrown into folds
at the pelvic brim. ln the pelvis the ureter courses
except at the fundus where it is smooth and adherent
posteroinferiorly along the anterior border of the
to the underlying muscle layer; this is the trigone and
I
greater sciatic notch'and anterior to the internal iliac

has the ureteric openings at its superolateral angles.
artery, forming the posterior boundary of the ovarian
I
fossa, At the level of the ischial spine, it turns

anteromedially in the fascia above the pelvic floor to
-
The urethra is approximately 4cm long and runs
antero-inferiorly behind the symphysis pubis. lt is
enter the base of the bladder at the posterosuperior embedded in the anterior wall of the vagina and
t
angle. ln this latter part of its course, it lies in the opens at the external urethral orifice into the vaginal
I
parametrium in the inferomedial part of the broad
I
vestibule. (tie. 7 & 8). The urethra is lined by
ligament where it is crossed anterosuperiody by the urothelium continuous with that of the bladder'
uterine artery (Fig. 3), to which it is related for a External to this are smooth muscle fibres arranged
distance of about 2.5cm. lt then comgg.to lie above mostly longitudinally. Skeletal muscle, thickest in the
the lateral vaginal fornix, lateral to the cervix; at the middle third surrounds the urethra and forms the
base of the bladder it is related to the anterior wall of
,.
external urethra I sphi ncter.
the vagina.
APPL!EDANATOMY
The bladder - is a hollow muscular organ for storing
urine. The empty bladder lies in the lesser pelvis This section correlates anatomical structures with
I behind the pubic bones and pubic symphysis but on function in health, disease cbnditions and diagnostic
distension it rises into the abdominal cavity and may procedures.
47
l. Variations in position mediolateral i ncision is advocated.

The normal anatomical position of the uterus is
anteversion and antiflexion. Under some conditions V. Vaginalfistulae
e.g. after delivery and increased intra-abdominal The anatomical relationship between the vagina and
pressure, the uterus may be displaced from this the Urinary bladder and urethra anteriorly and
normal position, to positions of retrofleetion, rectum posterioly disposes it to developmental of
f istu las (vesicovagi na, u reth rovagi na I or rectovagi na I
retroversion or prolapse. Prolapse usually follouvs a
disruption of the supports of the uterus especially the fislulae). These usually are associated with
pelvic floor and its I igaments. instrumental or prolonged difficult deliveries.
V. Anesthesia of thebirth canal

Il. Embryonic Anomalies
Various developmental anomalies can present in The uterus and upper parts of the vagina above the
deep perineal space are located within the pelvis and
relation to the female genitalia. They range from
anomalous fusion of the paramesonephric ducts and are supplied by the autonomic nerves and visceral
its derivatives. They range from double uterus afferents. The inferior part of the vaginal receives
(didelphis) to unicornate or bicornate uterii. They somatic innervation from the pudendal never (S2
may also give rise septation or duplication of the -S4). Pain from the cervix and vaginal trav
vagina or failure of canalization of the vagina. The retrogradely along parasympathetic pathways to 52-
ductal system may be entirely absent or poorly 54, whereas pain from the body and fundus of the
developed (hypo plastic). uterus travels retrogradely along the sympathetic
pathway to the superior lumbar and lower most
The hymen may fail to perforate (lmperforate hymen) thoracic spinal ganglia. Therefore pudendal blocks
or present with various forms of perforation' The anaesthetize the perineum and lower part of the
imperforate hymen usually present at puberty with vaginal whereas sacral (caudal epidural) blocks
haematcolpos. anaesthetize the birth canal reduces pain of labor'
Uterine contractions will be felt but spinal blocks via
Embryonic remains related to the female genitalia lumbar puncture al L3lL4, anaesthetizes from the
maybe encountered and include the epoophoron - waist region downwards.
remnants of the mesonepheric tubules in the
mesovarium, between the ovary and the fallopian Vl. Pathological conditions
tube. These blind tubules may persist close to the lnfection: The peritoneal cavity is open to the outside
uterus as paroophoron. Remnants of the through the fallopian tubes, uterus and vagina
mesonephric duct may persist in the broad constitute a potential pathway for infections leading
ligaments, adjacent to the uterus. This remnant may to peritonitis, salplngitis, and consequent tubal
become cystic and form the Gartner's duct cyst. The blockage - a leading cause of infertility.
cranial end of the paramesonephric duct, not
Vll. Diagnostic Procedures
incorporated in the fallopian tube may remain
Application of the anatomy of female genitalia,
attached to the fimbral end of the tube, forming the
relevant to laboratory procedures include tubal
appendix vesiculosa .
patency test (hysterosalpingogram), visualization of
I ll. Trauma associated with the female genitalia. uterus and fallopian tubes (laparoscopy,
Surgical operations on the uterus (hysterectomy) may hysteroscopy) vagi na (cu ldoscopy) and
lead to injury to the ureters which run just superior to culdocentesis (drainage of fluid from the peritoneal
the lateral fornices of the vagina and inferior to the cavity from the posterior vaginal wall), and
u ltrasonography and i magi ng techn iques.
uterine vessels. As a result of this relationship,
urdteric stones could be felt in the lateral fornix of the
The vagina is capable of enormous distension which
vagina. Episiotomy- a surgical producer to enlarge
facilitates clinical pelvimetry and palpation of other
the birth canal is done beginning at ihe vaginal
pelvic organs e.g. ovaries during pelvic assessment.
fouchete into perineal body (median)' The anal
And in deed, vaginaldeliverY!
sphincter and canal are prone to injury' Therefore a
48
]-sFT
I
The Female Reproductive Organs I
il
REFERENCES 1
,
Y
;
,j
l
1. Panici PB, Scambia G, functional anatomy of the pelvic floor, Obstet i
3
Anatomical study of Gynecol 1980;55; J35 :.]l
> lymph nodes in 7. Harold Ellis: Clinical Anatomy, 11th ed. 1
B I ackwel I Pu bl i sh i ng, 2006.

Obstet Gynecol 1992; 79: t
F 2. Clement CD. Gray's a 8. Moore KL, Dalley AF, Agur AFR. Clinically
Philadelphia, Lea &Febiger, 1985 Oriented Anatomy, 7th ed. Lippincott Williams
1
a 3. Grant JCB. An atlas of 9, . &Wilkins,2014 ti
Balti more, Wi I I ia m & Wi I ki ns, 9. Netter FH, Atlas of hum::n anatomy. 4th ed,
4. Plentl A and Friedman EA. of Saunders El sev ier, 2006. d
the female genitalia: The of 10. Junqueira LC, Carneiro. Basic Histology; Text I
"1
on co I ogi c d i a gnosi s an d th e rap$' F$iffitph i a, and Atlas. 1lth ed, McGraw-Hills Companies,.
WB Saunders Co. 1971 2005
5. flw Clin
Wall LL. The muscles of the pelvic 11. Eroschenko VP diFiore's Atlas of Histology with
r
I
I
Obstet Gynecol 1993; 36: 9 1 0
6. Zacharin RF. Pulsion enterocele: review of
Functional Correlations. 1lth ed. Lippincott
Williams &Wilkins
:
I
1
:l
j
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l
I
t
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r
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fr
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cHAPTE
"4
Reprod uctive Endocri nology;
Basic Concepts
Kwawukume EY and Omo-Aghaja LA
Background The field of medicine that identifies and treats

The normal human reproductive system - both infertility and other reproductive challenges in
anatomically and physiologically is designed and general, with a composite understanding of human
programmed for procreation, The differentiation and reproductive hormonal functions is referred to as
development of the normal anatomy right from in reproductive endocrinology. This field of medicine is
utero through pubertal developmental to attainment absolutely important as infertility and challenges of
of adult status (by which time the individual becomes reproduction is an issue of global public health
functionally able to reproduce) is hormonally driven concerns with an average of about 75% of couples in
r and modulated'''. When eventually the adult status is general and reports indicating up to 45% or more
tt attained, the normal physiological function of the from Africa and low resource settings having or
r anatomic reproductive system is hormonally driven experiencing fertility issues, and many will be
through the hypothalamo-pituitary-ovarian axis diagnosed with a reproductive disorder that is
t including the uterus and the outflow tract. With a
r hormonally driven.
normal menstrual cycle which determines the fertility
r potential of an individual being hormonally regulated Therefore, for a clear and precise identification of
and driven. lf eventually the individual becomes factors involved in infertility and reproductive
I pregnant, a successful pregnancy course is again challenges, and deciding on the appropriate
( methods to treat these factors require a proper
dependent on a proper functioning endocrine system
r of the normal functioning of
I as cascaded through the hypothalamo-pituitary- understanding the
(.
ovarian axis, corpus luteum and placental. cascade of the reproductive hormones.
l
.t
It- It is trite therefore, that the hormones from these Relays and Triggers: Hormonal lnteractions'-'
cascades that impinges on the reproductive system The female reproductive process involves the central
I
t
developmentally and functionally constitute the nervous system (primarily the hypothalamus), the
t:
I
reproductive hormones; though other endocrine pituitary gland, the ovary, and the uterus
r
systems such as the thyroid and adrenal system may (endometrium). All these must function appropri-
also have modulating effects, ately for normal reproduction to occur.
t
An abnormality in any point or points of the normal Hypothalamic gonadotropin-releasing hormone

reproductive hormonal chains may result in an (GnRH) simultaneously regulates both luteinizing
anatomical and or physiological clinical entity that hormone (LH) and follicle stimulating hormone
I
I will lead to deranged fertility in an individual resulting (FSH) in the pituitary, and does so by being secreted
l. in infertility and reproductive challenges. in a pulsatile manner. The pulse frequency deter-
i
I
i
i 51
mines the relative amounts of LH and Summary recap

FSH secretion.
The ovary responds to FSH and LH in

a defined, sequential manner to
produce follicular growth, ovulation,
and corpus luteum formation. The
cycle is designed to produce an
optimal environment for pregnancy;
should this not occur; the cycle
:
begins again.
The ovary produces estrogen in the

early menstrual cycle, which is
responsible for endometrial growth. l
Following ovulation, progesterone is

also produced in significant quanti-
ties, which transforms the
endometrium to a form ideal for
implantation of the embryo. lf no
pregnancy occurs, the ovary ceases
to produce estrogen and progester-
one, the endometrium is sloughed,
and the cycle begins again.
The reproductive process in women

therefore is a complex and highly Luteolysis (PGF2u, Endothelin-1)
Figure 1: Relays and Triggers: Hormonal lnteractions
evolved interaction of many compo-
nents. The carefully orchestrated
series of events that contributes to a
normal ovulatory menstrual cycle Anatomy of neuroendocrine aspects of reproductive hormones
This is relevant because the menstrual cycle cascade at one end has
requires precise timing and regula-
neuro-secretions that functions as hormones in the pathway and the
tion of hormonal input from the
cycle in turn is regulated through the feedback of hormones on the
central nervous system, the pituitary
neuraltissue of the central nervous system (CNS).
gland, and the ovary. This delicately
balanced process can be easily
1. Hypothalamus
disrupted and result in reproductive The hypothalamus is a small neural structure situated at the ^
failure, which is a major clinical issue base of the brain above the optic chiasm and below the third
confronting gynaecologists. To ventricle. lt is connected directly to the pituitary gland and is the 'l
effectively manage such conditions, part of the brain that is the source of many pituitary secretions.
it is critical that gynaecologists
understand normal reproductive :
The hypothalamus also has multiple interconnections to other
endocrine physiology of the men- parts of the brain, and these pathways form feedback loops to
strual cycle. The anatomic struc- areas supplying neural input to the hypothalamus.o,u'u
tures, hormonal components, and
interactions between the two play a There are several levels of feedback to the hypothalamus and
vital role in the function of the are known as the long, short, and ultrashort feedback loops.
reproductive system.' .^
The long feedback loop is composed of endocrine input from

circulating hormones, just as feedback of androgens and
52
Reprod uctive Endocri nology; Basic Concepts
estrogens onto steroid receptors is present in the primarily from the hypothalamus to the pitu-
hypothalamus.''' Similarly, pituitary hormones itary. Blood is supplied to the posterior pituitary
I
may feed back to the hypothalarnus and serve via the superior, middle, and inferior
important regulatory functions in short-toop
I
hypophyseal arteries. ln contrast, the anterior

feedback. Finally, hypothalamic secret'ions may pituitary has no direct arterial blood supply.
directly feed back to the hypothalanrus itself in lnstead, it receives blood via a rich capillary
an ultrashort feedback loop. plexus of the portal vessels that originate in the
median eminence of the hypothalamus and
The hypothalamus functions by way of releasing descend alongthe pltuitarystalk. This pattern is
factors that impinges on the piiuitary and cause it to not absolute, however, and retrograde blood
secrete hormones that have reproductive functions'o. flow has occurred. This blood flow, combined
The major secretory products of the hypothalamus with the locaiion of the median eminence
a re the pitu ita ry-releasi ng factors: outside the blood-brain barrier, permits
. Gonadotropin-releasing hormone (GnRH) - this bidirectional feedback control between the two
is involved with the control of the secretion of LH structu res.t-u
& FSH
. Growth hormone-releasing hormone (GHRH) - The anterior pituitary acts by way of substances
this is involved with the control of the release secreted for specific cells."These specific secretory
of growth hormone (GH) cells of the anterior pituitary is usually classified
. Thyrotropin-releasing hormone (TRH) - this is based on their hematoxylin- and eosin-staining
involved in the regulation of the secretion of patterns.
thyroid stimulating hormone (TSH) . Basophilic cells secrete gonadotropins
o Corticotropin-releasing hormone (CRH) - this is . Acidophilic-staining cells primarily secrete GH
involved with the control of the secretion or and prolactin and, to a variable degree, ACTH
release of ACTH o Neutral staining ch romophobes secrete TSH
All neurohypophyseal hormones are produced in
the hypothalamus. The posterior pituitary is The Reproductive Hormones
neural in nature and usually considered as a Gonadotropin-releasi ng hormone (Gn RH)
direct extension of the hypothalamus connected This is otherwise called luteinizing hormone
by fingerlike infu nd ibu lar stalk.' releasing hormone (LHRH), and it controls the
release of gonadotropins - FSH and LH". lt is a
2. Pituitarygland. decapeptide produced by neurons with cell bodies
The pituitary is divided into 3 regions or lobes: primarily in the arcuate nucleus of the hypothala-
anterior, intermediate and posterior. The anterior mus. These neurons originate in the olfactory pit
pituitary (adenohypophysis) is quite different during embryological development and then migrate
structurally from the posterior neural pituitary to their adult locations. These GnRH neurons project
(neurohypophysis), which is a direct physical axons that terminate on the portal vessels at the
extension of the hypothalamus.' The median eminence where GnRH is secreted for
adenohypophysis is derived embryologically delivery to the anterior pituitary.
from the epidermal ectoderm from infolding of
Rathke's pouch. Therefore, it is not composed of It is secreted in pulsatile fashion to be effective,
neural tissue, as is the posterior pituitary, and Hence continual exposure of the pituitary
does not have direct neural connections to the gonadotroph to GnRH results in a phenomenon
hypothalamus. Instead a unique anatomic referred to as down regulation, through which
gonadotroph cell surface GnRH receptors is
. relationship exists that combines elements of
neural production and endocrine secretion. The decreased. Similarly, intermittent exposure to GnRH
adenohypophysis itself has no direct arterial will "upregulate" or "autoprime" the gonadotroph to
blood supply. lts major source of blood flow is increase its number of GnRH receptors. This allows
I
also its source of hypothalamic input-the portal the cell to have a greater response to subsequent
vessels. Blood flow in these portal vessels is GnRH exposure."'"
53
The pulsatile release of GnRH is continuous because although helping to regulate gonadotropin levels,
of its short half-life of 2-4 minutes due to rapid may contribute to cycle-specific symptoms experi-
proteolytic cleavage. The pulsatile secretion of GnRH enced by ovulatory women. For example the
varies in both frequency and amplitude throughout dysphoria experienced by women in the
the menstrual cycle and it is tightly regulated. The premenstrual phase of the cycle may be related to a
follicular phase is characterized by small frequent, withd rawal of endogenous opiates."

small-amplitude pulses of GnRH secretion. ln the late
follicular phase, there is an increase in both fre- Anterior pituitary hormones
quency and amplitude of pulses. The amplitude in The anterior pituitary is responsible for the secretion
the luteal phase is higher than that in the follicular of the major hormone-releasing factors -FSH, LH,
phase, but it declines progressively over the two TSH AND ACTH. Each hormone is released by a
weeks. This variation in pulse frequency allows for specific pituitary cell type.
variation in both LH and FSH throughout the men-
Gonadotropins
strual cycle. For example, decreasing the pulse
The gonadotropins FSH and LH are responsible for
frequency of GnRH decreases LH secretion but
ovarian stimulation and they are produced by the
increases FSH, an important aspect of enhancing
basophilic gonadotroph cells of the anterior pituitar-
FSH availability in the luteal phase. The pulse gland.u FSH and LH are very closely similar in terms
frequency is not the sole determinant of pituitary
of their structure. They are both glycoproteins that
response, however; additional hormonal influences,
share identical a subunits and differ only in the
such as those exerted by ovarian peptides and sex
structure of B subunits, which confer receptor
steroids, can modulate the GnRH effect."''o
specificity.3 The synthesis of the B subunits is the
rate-regu lati ng step i n gonadotropi n biosynthesis. "'"
The gene that encodes GnRH produces 92 amino
Other hormones that share identical u subunits with
acid precursor protein, which contains not only the
the gonadotropins are thyroid-stimulating hormone
GnRH decapeptide but also a 56 amino acid peptide
and placental human chorionic gonadotropin (hCG).
known as GnRH-associated peptide, or GAP The
There are several forms of each gonadotropins,
GAP is a potent inhibitor of prolactin secretion as well
which differ in carbohydrate content as a result of
as a stimulator of gonadotropin release.
post-translation modification. The degree of modifi-
Endogenous Opioids and effects on GnRH cation varies with steroid levels and is an important
The endogenous opioids are three related families of regu lator of gonadotropin bioactivity.
naturally occurring substances produced in the CNS
that represent the natural ligands for opioids recep- Follicle stimulating hormone (FSH)
The FSH release is stimulated by GnRH from the
tors.''" There are three major classes of endogenous
anterior pituitary. lt in turn stimulates folliculoge-
opioids, each derived from precursor molecules:
r nesis - the development and growth of follicles in the
Endorphins
. Enkephalins ovaries, indeed it is responsible for early follicular
o Dynorphins maturation, and together with LH are responsible for
final follicular maturation. The half-life is about 170
The endogenous opioids play a significant role in the minutes.
regulation of hypothalamic-pituitary function.
Endorphins appear to inhibit GnRH release within FSH Tests are designed to detect elevated amounts
the hypothalamus, resulting in inhibition of gonado- of follicle stimulating hormone and indicates
tropin secretion. Ovarian sex steroids can increase impending ovarian failure or menopause, or if there
the secretion of central endorphins, further depress- may be an issue with the egg supply f rom the ovaries.
i ng gonadotropin levels.
Luteinizing hormone (LH)
Endorphins levels vary significantly throughout the
As the follicles (or eggs) become matllre, FSH
production is decreased and,' as the mid-cycle
menstrual cycle, with peak levels in the luteal phase
approaches, LH is released in a large and sudden
and a nadir during menses. This inherent variability,
burst. This is called the LH surge and marks the end
54
Reproductive Endocri nology; Basic Concepts
of the follicular phase of the menstrual cycle. The LH Thyroid-stimulating Hormone (TSH), Adrenocor-
surge, is responsible for triggering ovulation, or the ticotropic Hormone (ACTH), and Growth Hormone
release of the egg from the ovary and the initial
formation of the corpus luteum. The half-fife is about TSH is secreted by the pituitary thyrotrophs (neutral
60 minutes staining chromophobes) in response to TRH.
Synthesized primarily in the arcuate nucleus of the
LH Tests: Urine Ovulation Tests detect the LH surge hypothalamus and is then secreted into the portal
and indicates that ovulation is about to take place. circulation for transport to the pituitary.3 TSH
This is the best time of the month to have timed coitus stimulates release of T. and Trf rom the thyroid gland,
for cou ples trying to become pregnant. which in turn has a negative feedback effect on
pituitary TSH secretion. Abnormalities of the thyroid
Prolactin secretion (both hyper- and hypothyroidism) are
This is a 198-amino acid polypeptide secreted by the frequently associated with ovulatory dysfunction as a
anterior pituitary lactotroph (acidophilic staining result of diverse actions on the hypothalamic-
cells) and it is primarily responsible for synthesis of pitu itary-ovarian axis.'
milk bythe breast.'''o
ACTH is secreted in response to CRH and stimulates
Prolactin secretion is under tonic inhibitory control by the release of adrenal glucocorticoids. lt has diurnal
the hypothalamic secretion of dopamine. Therefore, variation with an early morning peak and a late
disease states characterized by decreased dopamine evening nadir. lts secretion is negatively regulated by
secretion or any condition that interrupts transport of feed back f rom its pri ma ry end prod uct, cortisol.
dopamine down the infundibular stalk to the pituitary
gland will result in increased synthesis of prolactin. ln GH is the anterior pituitary hormone secreted in the
this respect, prolactin is unique in comparison with greatest absolute amount in response to GHRH,
all other pituitary hormones: it is predominantly thyroid hormone and glucocorticoids. lt appears to
under tonic inhibition, and release of control pro- have a role in breast development and regulation of
duces an increase in secretion. Clinically, increased ovarian function. The degree of the ovarian regula-
prolactin levels are associated with amenorrhea and tion is unclear.'
galactorrhea, and hyperprolactinemia should be
suspected in any individual with symptoms of either Ovarian steroids
of these conditions.'''u Estrogens
Estrogen is the primary female sex hormone. lt is
Many stimuli that are known to stimulate the release responsible for the development and regulation of
of prolactin despite being thought to be primarily the female reproductive svstem and secondory sex
u nder in hi bitory control, includes: characteristics.'u'" Ihe estrogens, in particular
. Breast stimulation, estradiol, is a key reproductive hormone that plays
. Drugs, its most active role during the first half of the men-
. Stress, strual cycle - the follicular phase. During the
. Exercise, and
follicular phase, the developing follicles produce
r Certain foods.
estrogen via the process of steroidogenesis, which is
o Hormonesr those that may stimulate prolactin
critical for the build-up of the uterus, in particular the
release include:
uterine lining. This ensures that the uterine lining will
. TRH,
. Vasopressin, allow a fertilized egg to "implant" in the uterus.
. y-aminobutyric Estrogens may be steroidal or non-steroidal.
acid (GABA),
. Dopamine,
o B-endorphin,
The steroidal variants include endogenous and
o Vasoactive intestinal peptide (VlP), synthetic entities. The three major endogenous or
. Epidermal growth factor, naturally occurring estrogens in women are
t . Angiotensin ll, and possibly
. GnRH. . Estrone (E1),
o Estradiol (E2), and
55
t
{
:
. Estriol (E3). estrone). A related and very similar product to CEEs

is esterified estrosens (EEs). The common non-
Estradiol is the predominant estrogen during repro- steroidal estrogen is Diethvlstilboestrol that is no
ductive years both in terms of absolute sefurn'{s/els longer used medically.
as well as in terms of estrogenic activity. Dtr'ing i ,l
Estrogens, in females, are produced primarily by the
I
menooause, estrone is the predominant circr'rlating
estrogen and during pregnancy estriol is the prcdomi- ovaries, and during pregnancy, by the pla-
nant circulating estrogen in terms of serum levels. centa."Follicle-stimulating hormone (FSH)
Though estriol is the most plentiful of the three stimulates the ovarian production of estrogens by the
estrogens it is also the weakest, whereas estradiol is granulosa cells of the ovarian follicles and corpora
the strongest with a potency of approximately 80 lutea. Some estrogens are also produced in smaller
times that of estriol."Thus, estradiol is the most amounts by other tissues such as the liver, adrenal
important estrogen in non-pregnant females who are glands, and the breasts. These secondary sources of
between the menarche and menopause stages of life. estrogens are especially important in
However, during presnancv this role shifts to estriol, postmenopausal women. Fat cells produce estrog
and in postmenopausal women estrone becomes the as well.'u
primary form of estrogen in the body. Another type of
estrogen called estetrol (E4) is produced only during ln females, synthesis of estrogens starts in theca
pregnancy. All of the different forms of estrogen are interna cells in the ovary, by the synthesis of i
synthesized from androgens, specifically testoster- a nd rostened ione f rom choleste rol. And rostened ione
one and androstenedione, by the enzyme is a substance of weak androgenic activity which
aromatase. Estradiol, estrone, and estriol have all serves predominantly as a precursor for more potent
been approved as gharmaceutical drugs and are androgens such as testosterone as well as estrogen.
used medically. This compound crosses the basal membrane into the
surrounding granulosa cells, where it is converted
A variety of synthetic estrogens such as: either immediately into estrone, or into testosterone
. estradiol cypionate,
and then estradiol in an additional step. The conver-
. estradiolvalerate,
sion of androstenedione to testosterone is catalyzed
. estradiol acetate, and (17B-
. estradiol benzoate,
by 178-hvdroxvsteroid dehvdroeev6nase
are available as estrogen esters and are used HSD), whereas the conversion of androstene-dione
clinically. and testosterone into estrone and estradiol, respec-
tively is catalyzed by aromaiase, enzymes which are
The aforementioned compounds behave as prodruss both expressed in granulosa cells. ln contrast,
to estradiol, and are longer-lasting in comparison. granulosa cells lack L7o-hvdroxvlase and 17,20'
Esters of estrone and estriol also exist and are lyase, whereas theca cells express these enzymes
employed in clinical medicine. and 178-HSD but lack aromatase. Hence, both
granulosa and theca cells are essential for the
Ethinvl estradiol (EE) is a more potent synthetic production of estrogen in the ovaries [the 2-cell
analosue of estradiol that is used widely in hormonal theory of estrogen productionl.'u
contraceptives. Mestranol, moxestrol, and
quinestrol are derivatives of EE used clinically. A Estrogen levels vary through the menstrual cvcle,
related drug is methvlestradiol, which is also used with levels highest near the end of the follicular
clinically. Coniusated equine estrosens (CEEs), such phase just before ovulation. The functions of
as Premarin, a commonly prescribed estrogenic drug estrogen includes:'u
produced from the urine of pregnant mares, include

. Promotion of the development of female
secondary sexual characteristics, such as
the natural steroidal estrogens equilin and equilenin,
breasts,
as well as, especially, estrone sulfate (which itself is
o Thickening of the endometrium
inactive and becomes active upon conversion into
Regulati ng the menstrual cYcle.
55
Reproductive Endocrinology; Basic Concepts
. ln males, estrogen regulates certain functions The functions of progesterone includes:

of the reproductive svstem impodant to the n Progesterone has a
number of physiological
effects that are amplified in the presence of
maturation of sperm and may be necessary for
estrosens. Estrogens through estrogen recep-
a healthy libido.'0"
. Furthermore, there are several otherstructural tors (ERs) induce or upregulate the expression
I
changes induced by estrogen in addition to of the progesterone receptors (PR). One
otherfunctions. example of this is in breast tissue, where
. Medicalapplications estrogens allow progesterone to mediate
. OralContraceptivePills lobulo-alveolar development. Though recent
. HormoneReplacementTherapy evidence suggest that progesterone is also
. Antiestrogens for breast cancer involved in modulation of ductal development
. For treatment of men with prostatic cancer of the breast.3'11'35-37
. Promotion of wound healing
. Growth attenuation in tallgirls" * Progesterone has key effects via non-genomic
. Most recently, estrogen has been used in signalling on human sperm as they migrate
experimental research as a way to treat through the female tract before fertilization
women suffering from bulimia nervosa, in occurs, though the receptor(s) as yet remain
addition to cosnitive behavioral therapy, unidentified.3s
which is the established standard for treat-
ment in bulimia cases. The estrogen research t Progesterone is sometimes called the "hormone
hypothesizes that the disease may be linked to of pregnancy", and it has many roles relating to
a hormonal imbalance in the brain. the development of the fetus:'e
. Estrogen has also been used in studies which . Progesterone converts the endometrium to its
indicate that it may be an effective drugfor use secretory stage to prepare the uterus for
i
in the treatment of traumatic liver injury implantation. At the same time progesterone
i
affects the vaginal epithelium and cervical
I Progestero n e26'27'33'34 mucus, making it thick and impenetrable to
a
I
Progesterone (abbreviated as P4), also known as sperm. Progesterone is anti-mitosenic in
I
pregn-4-ene-3,20-dione, is an endogenous steroid
I
endometrial epithelial cells, and as such,
t that is produced by the corpus luteum (a part of the
I mitigates the tropic effects of estrosen. lf
I
ovary from which.the mature egg bursts during pregnancy does not occur, progesterone levels
ovulation) and a progestogen sex hormone will decrease, leading, in the human, to
involved in the menstrual cycle, Plegrl3llcY, dfld
I
I menstruation, Normal menstrual bleeding is
r embryogenesis of humans and other species. lt
r progesterone-withd rawa I bleed i n g. lf ovu lation
belongs to a group of steroid hormones called the
I
does not occur and the corpus luteum does not
I
I
f progestogens, and is the major progestogen in the develop, levels of progesterone may be low,
I
;
body. Progesterone is also a crucial metabolic leading to anovulatorv dvsfunctional uterine
lr' intermediate in the production of other endogenous bleeding.oo
steroids, including the sex hormones and the
I
corticosteroids, and plays an important role in brain . DLlring implantation and sestation,
function as a neurosteroid. Progesterone, like all progesterone appears to decrease the
other steroid hormones, is synthesized from maternal immune response to allow for the
I
pregnenolone, which in turn is derived from choles- acceptance of the PregnancY.
i
i terol. lt is on the WHO Model List of Essential . Progesterone decreases contractility of the
Medicines, the most important medications needed uterine smooth muscle.'e
in a basic health system.
. ln addition progesterone inhibits lactation
)I during pregnancy.'The fall in progesterone
levels following delivery is one of the triggers
:
for milk production.
57
. A drop in progesterone levels is possibly one Vaginally dosed progesterone is being

step that faci I itates the onset of labor. investigated as potentially beneficial in
. The fetus metabolizes placental progester- preventing preterm birth in women at risk
one in the production of adrenalstergid8. for preterm birth with promising results.
Progesterone is used for luteal support in
{. Progesterone and its neurosteroid at * Assisted Reproductive Technology (ART)
metabolite allopresnanolone appear to be cycles such as ln-vitro Fertilization (lVF).
importantly involved in sex drive in females.o' Progesterone is used to control persistent
anovulatorv bleeding.
Evidence also suggest that it drives homosexual- It is also used to prepare uterine lining in
ity in both male and females infertility therapy and to support early
pregnancy.
, Useful in traumatic brain injury and combined Patients with recurrent pregnancy loss
with vitamin D synergizes this effect.o' due to inadequate progesterone production
.:. may receive progesterone.
Other effects
. Progesterone is also used in nonpregnant
During pregnancy, progesterone is said to
women with a delayed menstruation of one
decrease i rrita bi I ity.a3
. During pregnancy, progesterone helps to or more weeks, in order to allow the thick-
ened endometrial lining to slough off. This
suppress immune responses of the motherto
process is termed a progesterone with-
fetal antigens, which prevents rejection of
drawal bleed. The progesterone is taken
the fetus.o'
. Progesterone raises epidermal growth orally for a short time (usually one week),
after which the progesterone is discontinued
factor-L (EGF-1) levels, a factor often used
and bleeding should occur.
to induce proliferation, and used to sustain
Progesterone can be used to treat
cultures, of stem cells.
catamenial epilepsy by supplementation
Progesterone increases core temperature
(thermogenic function) during ovulation. The during the menstrual cycle.
Progesterone is being investigated as
function of the temperature increase is to
potentially beneficial in treating multiple
create a warm, friendly, and cozy zone for the
sclerosis, si nce the cha racteristic deteriora-
developing fetus fol lowi ng conception.'u
Progesterone normalizes blood clotting and tion of nerve myelin insulation halts during
pregnancy, when progesterone levels are
vascular tone, zirlc and copper levels, cell
raised; deterioration commences again
oxvsen levels, and use of fat stores for
when the levels drop.
energy. . Progesterone also has a role in skin elasticity
Progesterone appears to prevent
and bone strength, in respiration, in nerve
endometrial cancer (involving the uterine
tissue and in female sexuality, and the
lining) by regulating the effects of estrogen.
presence of progesterone receptors in
Progesterone plays an important role in the
signaling of insulin release and pancreatic certain muscle and fat tissue may hint at a
function, and may affect the susceptibility to role in sexually dimorphic proportions of
d iabetes or gestational d iabetes.oo,ou
those.
Progesterone may play a role in male Antiprogestins
behavior, such as in male aggression
. and selective progesterone receptor
towards infants.ou modulators (SPRM)s, such as
mifepristone, can be used to prevent
{. The use of progesterone and its analogues have conception or induce medical abortions
many medical applications, both to address (note that methods of hormonal contra-
acute situations and to address the long-term ception do not contain plogesterone but a
decline of natural progesterone levels.*' progestin).
58
Reproductive Endocri nology; Basic Concepts
Progesterone is starting to be used in the ln females

treatment of the skin condition hidradenitis lnhibin is produced in the gonads, pituitarv gland,
suppurativa. placenta, corpus luteum and otherorgans.
I
Progesterone is FSH stimulates the secretion of inhibin from the

component of sranulosa cells of the ovarian follicles in the ovaries'
therapy for trans womerl; ln turn, inhibin suppresses FSH.
:^
. ..':::i: : . lnhibin B reaches a peak in the early- to
. Basal BodyTemperatureChart: mid-follicular phase, and a second peak at
The most important piece of ir#ormation on a ovulation.uo
fertility chart is when the basal temperature . lnhibin A reaches its peak in the mid-luteal
increases. This sudden incrsmre.,:in body phase.uo
temperature is due to progesterone effect. lnhibin secretion is diminished by GnRH, and
Once the body temp spikes, it is indicative of en hanced by insu lin-like growth factor- 1 (lG F- 1 ).
ovulation. ln the image below, note how the
black line suddenly rises and, for the most Much less is known about the mechanism of action
part, stays elevated forthe rest ofthe cycle. of inhibin, but may involve competing with activin for
bindingto activin receptors andlor bindingto inhibin-
specific receptor
;
ln males
It is secreted from the Sertoli cells, located in the
: seminiferous tubules inside the testes. Androgens
stimulate inhibin production; this protein may also
help to locally regulate spermatosenesis.o'
Clinical significance
1. Quantification of inhibin A is part of the
prenatal quad screen that can be
administered during pregnancy at a
gestational age of 16-18 weeks. An
I
elevated inhibin A (along with an increased
beta-hCG, decreased AFP, and a decreased
nryef}'Mils}* estriol) is suggestive of the presence of a
I
frwW&kMdxkxry&&ffir fetus with Down svndrome.u'As a screening
a
ffgrwc$mdffirffimqd# test, abnormal quad screen test results need
I
I' Figure 2: Basal body temperature chart to be followed up with more definitive tests.
fr
I
r
2. lt also has been used as a marker for ovarian
ut'uo
I lnhibin ca nce r.
t
I
lnhibin is a protein secreted by granulosa (female) 3. lnhibin B may be used as a marker of
r
a and Sertoli (male) cells in response to FSH, and its spermatogenesis function and male
major action is the negative feedback control of infertilitv.
I
r
pituitary FSH secretion. lt is found in blgod plasma, The mean serum inhibin B level is
( although difficult to detect until recently. lt is found in significantly higher among fertile men
?
great quantities in seminal plasma and follicular (approximately 140 pg/mL) than in infertile
fluid. ln both females and males, inhibin inhibits FSH men (approximately 80 pg/mL).uu ln men
production. lnhibin does not inhibit the secretion of with azoospermia, a positive test for inhibin
! GnRH from the hypothalamus.o'''^n B slightly raises the chances for successfully
\
?
achieving pregnancy through testicular
( However, the overall mechanism differs between the
sperm extraction (TESE), although the
SEXCS:
t
i
I
59
i
t
f
------.-----'!
association is not very substantial, having a n Like other eonadotropins, it can be

sensitivity of 0.65 (95% confidence interval extracted from the urine of pregnant women
lCll: 0.56-0.74) and a specificity of 0.83 or produced from cultures of genetically
(Cl: 0.64-0.93) for prediction the presence modified cells using recombinant DNA
of sperm in the testes in non-obstructive technology.
azoospermia.uu n ln Presnyl, Follutein, Profasi, Choragon and
Novarel, it is extracted from the urine of
hCG - or human chorionic gonadotropin pregnant women. ln Ovidrel, it is produced
Human chorionic gonadotropin (hCG) is a hormone
with recombinant DNA technologY.
produced by the embrvo after !mp.la-0laEgo.u''u'
Naturally, it is produced in the human placenta by The function of hCG includes:
the svncvtiotrophoblast. The presence of hCG is * Human chorionic gonadotropin interacts
detected in some presnancy tests (HCG oresnancv with the LHCG receptor of the ovary and
strip tests). Some cancerous tumors produce this promotes the maintenance of the corpus
hormone; therefore, elevated levels measured when luteum during the beginning of pregnancy.
the patient is not pregnant can lead to a cancer This allows the corpus luteum to secrete the
diagnosis and, if high enough, paraneoplastic hormone prosesterone during the first
svndromes. However, it is not known whether this trimester. Progesterone enriches the uterus
production is a contributing cause or an effect of with a thick lining of blood vessels and
carcinosenesis. The pituitary analog of hCG, known capillaries so that it can sustain the growing
as luteinizing hormone (LH), is produced in the fetus
pituitary gland of males and females of all ages.u''u'
hCG also feedback to the corpus luteum to keep * Due to its highly negative charge, hCG may
ma ki ng progesterone a nd prevent menstruation. repel the immune cells of the mother,
protecting the fetus during the first trimester.
Human chorionic gonadotropin is a glvcoprotein
composed of 237 amino acids with a molecular mass n lt has also been hypothesized that hCG may
of 25.7 kDa. lt is heterodimeric, with an n (alpha) be a placental link for the development of
subunit identical to that of luteinizine hormone (LH), local maternal immunotolerance. For
follicle-stimulatins hormone (FSH), thvroid- example, hCG-treated endometrial cells

stimulatins hormone (TSH), and p (beta) subunit induce an increase in T cell apoptosis
(dissolution of T cells). These results suggest
that is uniqueto hCG.
n The a (alpha) subunit is 92 amino acids that hCG may be a link in the development of
long.uo peritrophoblastic immune tolerance, and
may facilitate the trophoblast invasion,
* The B-subunit of hCG gonadotropin (beta- which is known to exPedite fetal
hCG) contains 145 amino acids, encoded by development in the endometrium.u'
six highly homologous genes that are
arranged in tandem and inverted pairs on * lt has also been suggested that hCG levels
chromosome 19q13.3 - CGB (L, 2, 3, 5,7, are linked to the severity of morning sickness
8).u, or Hvperemesis sravidarum in pregnant

women.63
* Regarding endogenous forms of hCG, there
are various ways to categorize and measure , Because of its similarity to LH, hCG can also
them, including total hCG, C-terminal be used clinically to induce ovulation in the
peptide total hCG, intact hCG, free B-subunit ovaries as well as testosterone production
hCG, p-core fragment hCG, in the testes
hyperglycosylated hCG, nicked hCG, alpha
hCG, and pituitary hCG. * As the most abundant biological source is
50
Reproductive Endocri nalogy; Basic Concepts
women who are presently pregnant, some treatment of ectoPic PregnancY'

organizations collect urine from pregnant . The lack of a visible fetus on vaginal
women to extract hCG for use in fertilitv ultrasound after the BhCG levels have
treatment. reached 1500 mlU/ml is stronglY
indicative of an ectopic pregnancy'"
* Human chorionic gonadotropin also plays a . Still, even an hCG over 2000 lU/l does
role in cellular differentiation/proliferation not necessarily exclude the presence of
and may activate aooptosis.uo a viable intrauterine pregnancy in such
{. hCG levels are also a component of the triple cases.67
test, a screening test for certain fetal

ch romosoma Ia bnorma I ities/bi rth defects.
* As pregnancy tests, quantitative blood tests
and the most sensitive urine tests usually
Series of tests which may detect hCG includes: detect hCG between 6 and 12 days after
Blood or urine tests measure hCG. Concentrations ovulation.ut However, it must be taken into
are commonly reported in thousandth international account that total hCG levels may vary in a
units per milliliter (mlU/ml). very wide range within the first 4 weeks of
, These can be presnancv tests. hCG-positive gestation, leading to false results during this
indicates an implanted blasto-cvst and period.u' A rise of 35% over 48 hours is
proposed as the minimal rise consistent with
ma mma lia n embrvoqenesis.
* These can be done to diagnose and monitor a viable i ntrauteri ne pregnancy.u'
serm cell tumors and gestational

trophoblastic diseases.
n Gestational trophoblastic disease like
hydatidiform moles ("molar pregnancy") or
Most tests employ a monoclonal antibody, which is choriocarcinoma may produce high levels of
specific to the B-subunit of hCG (F-hCG). This BhCG (d ue to the Presence of
procedure is employed to ensure that tests do not syncytialtrophoblasts- part of the villi that
make false positives by confusing hCG with LH and make up the placenta) despite the absence
of an embryo. This, as well as several other
FSH. (The latter two are always present at varying
levels in the body, whereas the presence of hCG
conditions, can lead to elevated hCG
readings in the absence of pregnancy.
al most always i ndicates pregnancy.
* Early in pregnancy, more accurate results
* A study of 32 normal pregnancies came to
may be obtained by usingthefirst urine of the
the result that a sestational sac of 1-3 mm
morning (when hCG levels are highest).
was detected at a mean hCG level of 1150
When the urine is dilute (specific eravitv less
than 1.015), the hCG concentration may not
Ulil (range 800-1500), a volk sac was
,
detected at a mean level of 6000 Ul/l (range
: be representative of the blood concentration,
and the test may be falsely negative.uu
4500-7500) and fetal heartbeat was
* The serum test, using 2-4 mL of venous visible at a mean hCG level of 10,000 Ul/l
(range 8650-72,200)'o
blood, is typically a chemiluminescent or
fluorimetric immunoassay'u that can detect
The common clinical use of hCG includes:
BhCG levels as low as 5 mlU/ml and allows * As a tumor marker"
quantification of the BhCG concentration.
Human chorionic gonadotropin can be used
as a tumor marker, as its B subunit is
The values obtained may be interpreted variously:
. *The ability to quantitate the BhCG level is secreted by some cancers including:
.
useful in Seminoma,
. The monitoring serm cell and . Choriocarcinoma,
. Germ CellTumors,
l .
trophoblastic tumors, . Hydatidifoim Mole,
.
Follow-up care after miscarriase, and . Teratoma with elements of
ln diagnosis of and follow-up care after
choriocarcinoma, and
61
-
--T-:-----'!
. lslet Cell Tumor. retrieval performed at about 34 to 36 hours

after injection by, a few hours before the eggs
For this reason a positive result inruek can actually would be released from the ovary.
be a test for testicular cancer.. lt$,,@tnat * As HCG supports the corpus luteum,
range for men is between 0:5'ffirrl. administration of HCG is used in certain
Combined with alpha-fetoprotein; FI{CG is circumstances to enhance the production of
an excellent tumor marker forthe monibring Progesterone.
of germ celltumors n ln the male, HCG injections are used to
stimulate the Leydie cells to synthesize
* ln infertility management testosterone. The intratesticular
Human chorionic gonadotropin is testosterone is necessarY for
extensively used parenteraJly for final soermatosenesis from the sertoli cells.
maturation induction in lieu of luteinizing Typical uses for HCG in men include
hormone. ln the presence of one or more hvposonadism and ferti ity treatment.
I
mature ovarian follicles, ovulation can be i. Several vaccines against human chorionic
triggered by the administration of HCG. As gonadotropin (hCG) for the prevention 'f
ovulation will happen between 38 and 40 pregnancy currently in clinical trials"
hours after a single HCG injection,"
procedures can be scheduled to take Hormonal variation in the menstrual cycle and
advantage of this time sequence, such as /control of ovulation
intrauterine insemination or sexual The relative pattern of hormonal variation along the
intercourse. AIso, patients that undergo lVF,
normal menstrual cycle is depicted in the chart
below:
in general, receive HCG to trigger the
ovulation process, but have an oocvte
12'34,5 G 7.&g3t&{$ !t'@. 1,fi tfif 1S 19?0 :?{.22 23 24 25.?S?TtB

Bq&, 0f I
rd*iiiitriral Qrul*
Figure 3: Hormonal variation in the menstrual cycle
At the beginning of each monthly menstrual levels begin to rise, and a cohort of growing
cycle, levels of gonadal steroids are low and follicles is recruited. These follicles each
have been decreasing since the end of the secrete increasing levels of estrogen as they :
luteal phase of the menstrual cycle. grow in the follicular phase. The increase in
estrogen, in turn, is the stimulus for uterine
With the demise of the corpus luteum, FSH endometrial prol iferation.
62
Reprod uctive Endocri nology; Basic Concepts
Rising estrogen levels provide negative until the midluteal phase, when it begins to
feedback on pituitary FSH secretion, which rise again as a result of corpus luteum
begins to wane by the midpoint of the secretion. Similarly, inhibin-A is secreted by
follicular phase. ln addition, the growing corpus luteum.
follicles produce inhibin-8, wF+ich also
suppress FSH secretion by the'rffiuitary. Progesterone levels rise precipitously after
Conversely, LH initially decrsases in ovulation and can be used as a presumptive
response to rising estradiol levels, but late in sign that ovu lation has occu rred .
the follicular phase the LH level is increased
Progesterone, estrogen, and inhibin-A from
d ramatica I ly (bi phasic response).
the ovary/corpus luteum (and this is
At the end of the follicular phase (just before sustained by the placenta as from the 12th
ovulation), FSH-|nduced LH receptors are week if pregnancy occurs), act centrally to
present on granulosa cells and, with LH suppress gonadotropin secretion and new
stimulation, modulate the secretion of follicular growth. These hormones remain
progesterone. elevated through the life span of the corpus
luteum, however, in the absence of
After a sufficient degree of estrogenic pregnancy, this remnant of the released
stimulation, the pituitary LH surge is ovum (corpus luteum) under goes self-
triggered, which is the proximate cause of degeneration (luteolysis) as from the 24lh
ovulation that occurs 24 to 36 hours later. day of the cycle (3-4 days before
Ovulation heralds the transition to the luteal- menstruation) under the influence of PGF2u
secretory phase. and possibly endothelin-i thereby setting
The estrogen level decreases through the the stage for the next cycle.
early luteal phase from just before ovulation
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66
CuaDrE"
5
History and Exarnination
CAKlufioandBAEkele
!ntroduction empathy, patience, and understanding without being

Gynaecology (from the Greek gune gunaik - woman, condescending. He/she must have respect for the
and logo - discourse) is the branch of medicine that patient's personality, dignity and intelligence. lt is a
deals with diseases and conditions of the female fallacy and a great mistake to assume that because
reproductive tract and female reproduction. somebody is not educated that person would not be
able to understand what we try to explain to her. lf
History-taking and physical examination in the patient failed to grasp what we were trying to
gynaecology starts with confidence-building. First explain, the fault is unlikely to be the woman's' More
impressions matter a great deal. Remember that as likely we were inadequate in our efforts: we did not
the patient enters your consulting room, or as you spend enough time or we did not have the patience
approach her bed, she is assessing you through your or aptitude.
smile or grimace, and body language, generally. You
must do the same and react appropriately. Show her Experience at the gynaecology clinic teaches us that
that you are interested, not only in her problem, but in the patient's primary complaint may not be the chief
her as a whole person. Do so without being unduly concern for which she is in the clinic. No matter how
familiar. open-minded the gynaecologist may be, some
patients will feel embarrassed about talking about
ln the developing world, many women may not their worries. Patience and tact are needed in such a
attend another doctor apart from an obstetrician- case. The empathic gynaecologist will sense this
4 gynaecologist. Therefore, in these countries, the reticence and he/she will encourage the patient to
/
obstetrician-gynaecologist may be the only physician talk freely. Direct questioning may be necessary, but
I who is in a position to provide regular primary health chastising the patient for wasting one's time is not
care for the majority of women. The obstetrician- helpfuland is unkind!
gynaecologist must recognise and accept this
responsibility. The specialist must regard It may seem trite to say it, but the primary purpose of
himself/herself, not only as a "women's physician", history-taking and physical examination is to make a
but must also act as a committed and active advocate diagnosis. The common symptoms the
forwomen's health. gynaecological patient may complain of are quite few
and include: abdominal pain, abdominal mass,
Further, the ob-gyn specialist must realise that pelvic pain, menstrual problems, non-menstrual
gynaecology deals with the most personal and vaginal bleeding, infertility, miscarriage, vaginitis
intimate matters in medicine; problems and and vaginal discharge, pruritus vulvae, vulvar pain,
questions which the woman may find difficult to talk vulvar swellings, coital problems, menopausal
r' about, and which she would not think of telling or symptoms, symptoms of pelvic floor dysfunction and
F
asking anyone else. The ob-gyn specialist is therefore urinary incontinence.
l.
I
in a privileged position. He/she must have tact,
I
i
)
I
67
a Its intermittency or constancY

The gynaecologist must treat whatever a The time relationship with the menstrual
he/she is told or finds with the utmost cycle
confidence. He/she must not be judgmeilal. . lts severity:
}f it is pain, does it increase in severity before, during

or after the periods? Or is there no consistent rela-
The History tionship?
Taking the history affords the opportunity to:gain the
patient's confidence and build a rapport. Try to listen How does the symptom affect the patient's quality of
to the patient without unnecessarily interrupting her life? ls it incapacitating? Does it interfere with sleep?
story or looking bored. Her confidence will grow as
she notices that you are intently listening, and you lf the patient complains of pain, its site and radiation,
may find that her most pressing anxieties come out at and relieving and exacerbating factors must be
the end of her story. Unless the patient broaches the established.
subject herself, leave the sexual history and any other
The patient's complaint should be written in the
questionsthat may embarrass hertothe last. Bythen
hospital notes in the patient's own words.
you would have gained herconfidence and shewould
be more at ease. As in most branches of medicine,
Age
the history will provide the most useful lead to the Knowing the patient's age is important. Certain
cause of the patient's dis-ease. By the time we finish conditions occur more commonly at certain ages,
taking the history, we should have a fair idea of the and the management of the same condition may vary
patient's problem, a provisional diagnosis; however, according to age. lf she cannot give her age, use
we must not close our minds to other possibilities. calendar events to make an educated guess.
This is why we need a differential diagnosis at the end
of the history. We may revise this as we examine the Gy naecoI ogi ca I H i sto ry
patient. Patient ldentification Particulars The Menstrual History
patient's name and residential address, and if A carefully taken menstrual history can prevent
applicable, her occupational address should be noted mistakes in diagnosis.
in the hospital records. She should be asked to give a . Menarche: The age at the menarche must
contact name and address. This could be her be ascertained. Delayed menarche may be
husband's/partner's or a relation's. Occasionally, a a familial condition. The patient's mother
laboratory report or'other information which or elder sisters may have a similar history'
demands prompt investigation and/or treatment may . Menstrual cycle: The length and regularity of
come to the attention of the clinician. Should the the cycle, the duration of flow, and the
patient fail to keep her follow up appointment, she patient's assessment of the loss must be
ca n be traced if the above particu la rs a re ava i la ble, established.
. Last menstrual period (LMP): Was the LMP
The Patient's Com pl a i nt a normal period? Was the date of onset at
The patient should be asked to describe her problem the expected time? Were the duration of flow
by an encouraging question, such as, "Would you (in number of days) and amount and
mind telling me what your problem is?" or "What is character of flow normal for the individual?
the problem which you have come to see me about?" Do the menses contain any clots? Does the
Having asked the question, it is important to listen to patient understand ourdefinition of the LMP
the patient carefully. Maintain eye contact with the or is she giving the date of the first missed
patient; note her body language and her choice of period? Any woman in the child-bearing age
words. Establish the following about each of the may be pregnant. Failure to ascertain the
patient's complaints: LMP and failureto establish whetherthe last
. lts duration bleed was or was not a normal period can
. The circumstances surrounding its onset lead to mistakes in diagnosis: a pregnanc!
58
H istory and Exami nation
may be missed; an ectopic pregnancy may difficulty initiating urination, or does she have to use
be misdiagnosed. a manoeuvre to start the stream to void? For exam-
. Dysmenorrhoea: Does the patient suffer ple, does she have to put a finger in the vagina to
menstrual pain? ls it spasrnodic (primary) or push something up? ls she able to empty the bladder
congestive (secondary) dysmenorrhoea? completely without having to put her finger in the
How does it affect the patientts quality of life? vagina? Does she have satisfactory bowel control or
. lntermenstrual bleeding: Does the patient does she soil her underwear? ls she able to evacuate
have any vaginal bleeding apart from the her bowel satisfactorily or does she get the feeling
normal period? lf so, is it provoked (e.g. by that there is something still there? Does she have to
coitus or washing the vagina) or spontane- use any manoeuvre, for example, pressing on the
ous? perineum, to achieve complete bowel evacuation?
. Postmenopausal bleeding: lf the patient is For how long has she had any of the above symp-
menopausal, it is important to find out the toms? Have the symptoms remained the same in
age at menopause and whether she has had severity or are they getting worse? Does she have a
any bleeding since her periods ceased? chronic cough or chronic constipation? Has she had
Vaginal Discharge treatment in the pastfor any of these symptoms?
Does the patient have a vaginal discharge? How long Past I nvestigations and Admissions
has the patient had it? What is its time relationship to Gynaecological investigations, including infertility
the menses? What is the amount and colour of the investigations and Pap smear tests, when and where
discharge? Does it have a disagreeable smell? ls the they were performed, and their results should be
smell particularly disagreeable after sexual inter- recorded. Has the patient ever been admitted to
course? Does the discharge stain her underwear? hospital with salpingitis (lower abdominal pains)?
What is the colour of the stain? ls the discharge We must note any gynaecologicalsurgical operations
associated with vulvar itch or irritation? Was it she has had, including vaginal operations.
precipitated by any medication the patient was
taking? Had the patient had similar episodes in the Obstetric History
past? lf so, how were the past infections treated? The obstetric history is very important, and this
inquiry must be made methodically if significant
Prolapse and urinary incontinence points are not to be missed. Some complications of
Does she get the feeling that something is coming pregnancy, labour and the puerperium can have
down the vagina? When she inserts her fingers in the gynaecological sequelae. As examples, severe
vagina, does she feeit something, which she had not antepartum and postpartum haemorrhage can lead
previously felt, low in the vagina? Has she seen to Sheehan's syndrome (anterior pituitary infarction,
anything protruding from the vagina? lf the answer to secondary amenorrhoea and infertility); post-abortal
any of these questions is "yes", when does she get and puerperal sepsis can cause pelvic inflammatory
these symptoms? Does she get them when she is disease and tubal infertility; a uterine perforation
lying in bed or when she has been up and about. Do produced in inducing abortion can predispose to
they occur in the morning or at the end of the day? endometriosis.
What gives her relief? Has there been a change in her
urinary habits? On average, how many times does ln taking the obstetric history, the gravidity and parity
she urinate during the day and during the night? of the patient isfirstgiven. Then, allthe patient's past
When she feels like urinating, does she have to run to pregnancies are listed in chronological order, noting
avoid leaking? Does she have satisfactory control of the following information about each pr€gnanc!:
urination or does she involuntary leak involuntarily? lf
so, is the incontinence constant or episodic? lf Pregnancy
. Antenatal care facility: Where did she
episodic, what precipitates the leak? Does a sudden
attend for antenatal care? The date and
{ rise in intra-abdominal pressure cause it? As exam-
place where the pregnancy ended.
h ples, does coughing/sneezing or lifting a weight or
bending down cause herto leak urine? Does she have
59
'----!
. The duration of the pregnancy: lt the stillbirth. Did she stop feeling fetal move-
patient is illiterate she may be able to say ments before labour started? What did the
if she delivered at the expected time, or baby look like?
earlier or later. Any complications du,rin8, a Were there any complications?
the pregna ncy a nd antenata I admrssions a How many days did she stay in the delivery
facility before she was discharged home?
Labour Did she have puerperal sepsis? Did she have
Was the onset of labour spontaneous or induced? lf fever?
induced, what was the indication forthe induction? Did she have secondary post-partum
Was the labour preterm, term, or post-term? How haemorrhage?
long did the labour last? lf she is not able to give the Did she have any problem with the breasts or
answer in hours, she is asked when the labourstarted with breast-feeding?
and when the baby was delivered and the duration Did she breast-feed successfully? Was the
then calculated. Did the labour last less or longer baby exclusively breastfed? lf so, for how
than one day? Was the labour augmented? Was she many months was it exclusively breastfed? lt
given an intravenous infusion because the contrac- is our duty to educate all women about the
r tr'
tions were weak? i m po rta nce of excl usive breastf eed i nB fo
"
first 6 months.
Delivery Miscarriages
o What was the mode (method) of o lf she has had any miscarriages, were these
delivery? lf it was not sPontane- spontaneous or i nduced?
ous vertex or assisted breech, she o What was the gestational age at which each
is asked the indication for the pregnancy was term i nated?
mode of deliverY, using leading o lf induced, what was the method used? Was
questions as necessarY. she aware of what was done, or was it done
o What was the duration of the 3rd when she was unconscious? What was the
stage? How soon after deliverY of indication for the i nduced abortion?
the baby was the Placenta . Did she have any problems after the abor-
delivered? tion? lf her answer is yes, she is directly
. Did she have any tears or an questioned about bleeding, offensive
episiotomy? Was she stitched? discharge, lower abdominal pains and fever'
. Did she bleed alter delivery of the Was she put on antibiotics at the time of the
baby or the Placenta? After the procedure or later? Did she have to go back
delivery, did she have an intrave- to the one who performed the procedure?
nous drip? Did she have a blood . Was there a repeat evacuation? How many
transfusion? times was the evacuation rePeated?
Repeated evacuations for a supposedly
The Baby and PuerPerium incomplete miscarriage or an incompletely
o What was the condition of the baby at induced abortion should make one suspect a
birth? Did it crY immediatelY? chronic ectoPic or a gestational
o What was the baby's sex? trophoblastic neoPlasm.
. What was the birth weight? lf she cannot tell
the birth weight, she can be asked if the baby Family History
was of average size or was small or bigger The family history must include the health of all first
than usual? degree relatives and the patient's grandparents. The
. Was the baby with her all the time or was it objective is to find out if there is any heritable
admitted to Special Care Nursery or NICU? disease, or if there is any disease, the aetiology of
o How is the baby now? which is influenced by close contact and by environ-
o lf the baby was stillborn, it is important to mental factors, The patient may have the disease
find out if it was a macerated or fresh without being aware of it. She may pass on the
70
History and Examination
disease to her children, or the children may be methods? lf the answer is yes, what were the
affected because they share the same environment methods used? When did they start using each
with the family. Diseases that may run in families method, and when and why did they stop using
include sickle cell disease and other haematological them? Were they satisfied with the method? lf it was
diseases, hypertension, familial heart disease, a female method, were there any side effects? Is
diabetes mellitus, asthma, r€nal disease, there a past history of involuntary infertility? How
cerebrovascular accidents, bleeding diasthesis, long ago was it? For how long did the couple try
ovarian, breast and colon cancers; tuberculosis, before they achieved a pregnancy? ls there a present
delayed menarche, early menopause, hirsutism and history of involuntary infertility? For how long have
other endocri nopathies. the couple being been trying to achieve a pregnancy?
Have they undergone any investigations for infertil-
Social History ity? lf so, what were the results? Have they had any
The patient's complaints and her reactions to them treatment?
must be put in the context of her social background:
her ethnic origin; her parents' social status, her The Breasts
marital status and if married, number of years The patient should be asked if she has any symp-
married; education (number school years com- toms. lf she replies in the negative, she should be
pleted); occupation and current employment status; asked if she has noticed any change in either breast:
religious denomination and cultural beliefs; hus- pain, a lump, change in skin colour or skin texture,
band's/partner's name, age and occupation; hus- dimplingorwrinkling, distortion of the nipple; nipple
band's school years completed; area of residence - discharge, and if so, the colour of the discharge and
urban, urban slum, village; dietary history. Does she in particular if it is blood-stained.
live in the same house with her partner/husband? All
these may have an influence on her symptoms and SexualHistory
treatment. Some treatments may be taboo in some Over 207" of the drsease burden among women of
religious denominations and cultures. reproductive age rs connected with sex and repro-
duction tREF 1l lt is a serious and common problem.
Med ica I/ Surgica I H istory Unless a sexual problem is one of the patient's
Medical history: Details of any serious illnesses, complaints, the sexual history should be taken
including psychiatric illnesses and hospital admis- towards the end of the session. By that time the
sions; blood transfusions, excesslve weight gain or patient's confidence would have been earned, and
loss. Systemic inquiry: Direct questions about the patient would be more at ease. She should be
function of the various systems: gastrointestinal, asked if she is sexually active. Direct questions
I urinary, respiratory, cardiovascular, haematology should be asked about symptoms which the patient
(including bleeding diatheses). may not mention. As examples: Does she have pain
r during or after intercourse? Does she get an offensive
t
Surgical operations: Details of any abdominal and vaginal discharge immediately after coitus? Has she
pelvic operations. experienced post-coital bleeding? ls there a loss of
i
libido? Has the frequency of coitus decreased? lf so,
Drug history what is the reason? Has her partner complained
Alcohol, tobacco, narcotic and hard drugs: lf the
about their sexual relationship? Has their sexual
answer is in the affirmative, estimate the quantity.
relationship become unsatisfactory in any way? Has
Does the husband/partner smoke? Remember the
she been trying to conceive? lf so, for how long has
health risks of passive smoking. ls patient on any
she been trying? Whether the history is difficult to
medications now? Has the patient any drug allergies?
obtain or not will largely depend on the gynaecolo-
gist. Gynaecologists must feel comfortable about
Contraceptive Practice and History of lnvoluntary
asking these questions. lt must be remembered that
lnfertitity
ls the patient married or is she in a stable relation- there is no upper age limit to.sexual activity, alihough
performance wanes after middle age. However, the
ship? Have the patient and her husband/partner ever
used any family planning methods, including natural
social background of the patient should be taken into
71
-------i
account when broaching the subject. For example, it specialist is usually the woman's primary health care
would not be appropriate to raise the subiect when giver. Therefore, at the patient's initial visit, a full
dealing with a 7S-year old who had been recently general examination must be performed.
widowed and had come with symptoms'of pelvic "-:
floor dysfunction, unless, of course, she brought it lnformed Consent

up. On the other hand, one must not presume that It is very important to take a couple of minutes to )
I
because a woman is etderly she or her partner is no

explain to the patient what you will do during the
examination and to obtain her consent.
longer interested in sex. Although compared with
the developed world, the age pyramid of the devel-
!nspection General impression and general
oping countries rs relatively young, it is important to
physique: Before you start speaking to the patient,
remember that over 50"/" of women aged more that observe her appearance and demeanour so that you
60yrs live in developing countries IREF 21. Does the may be able to interact with her appropriately' Does
patient have a past history of a sexually transmitted she look nervous, frightened or unsure of herself?
infection? How many episodes has the she had? Does she look hurt, annoyed or aggressive? Does she
Where and how was she treated? How about her look reserved or confident and open? Does she look
partner/husband? happy orsad? Does the patient look well or unwell? ls
she of average build or is she thin or obese? Whai
her nutritional status? Note the presence of
Summarize the history with one to two hirsutism, acne and the hyperpigmentation of
acanthosis nigricans which may be present in
sentences before proceeding to examine the polycystic ovary syndrome.
patient
Height and weight: Measure her height -and weight
andlalculatethe body mass index (k{m"). Height is
The Physical Examination an important clinical sign in chromosomal
Forthe gynaecological examination, the presence of a abnormalities, especially Turner's. A low or a high
female nurse is mandatory. Medico-legal and ethical
BMI is associated with hormonal and menstrual
abnormalities and anovulation.
considerations require it, and it is appropriate and
correct that we insist on it. lf the patient wishes that
Eyes: Pallor and jaundice
her husband/partner be present during the Mouth: Oral hygiene and dental caries
examination, we must agree, but it is important to
Neck:
note that his presence cannot substitute for the
6 Stand in front of the patient and inspect for
presence of the female nurse. The physical
thyroid enlargement. Let the
-patient swallow'
examination is conducted in thefollowing sequence:
Stand to the side of the patient, your eyes level
. General
with her Adam's apple, and ask her to swallow
. Breasts
again. Stand to the side and a little behind
. Systemic patient and palpate thyroid; let patient swallow
while palpating.
Abdominal : visual i nspection, palpation, percussion 6 Palpate for cervical lymphadenopathy.
Pelvic:
. Visual inspection
. Speculum Hands:
. Pap smear, visual inspection with acetic acid lnspect palms and nail bedsfor pallor
(VlA), or HPV-testing lnspect fingers for oedema
. SuperficialPalPation
. Bimanualvaginal Lower limbs:
. Rectal-vaginal lnspect for varicose veins with patient
. Rectal standing. lnspect dorsum of feet, ankle,
and legs for oedema; Pa'lPate for
General Examination oedema.
As already stated, in the developing world, the ob-gyn
72
Breasts Next, the examiner takes the patient's left hand with
The gynaecologist, as the primary health physician, is his/her left hand, flexes the patient's elbow at 90o,
obliged to examine the breasts of evtlrY'Fatient she and draws the patient's forearm across her chest,
sees; with the patient's consent, of cg.ir$:'U ess the and supports the patient's forearm. This manoeuvre
gynaecologist has had special-tru'ffi:.in the relaxes the patient's pectoralis muscles. Using the
diagnosis and management of diseasesdffi breast, pads of the index, middle and ring fingers of his/her
tre/ihe should refer any patient vuho l#iins of a right hand, the examiner palpates for the axillary
lump in the breast or a blood.st*i@ nipple nodes. Standing behind the patient, the
discharge for a surgical opinion. The:gynaearlogist gynaecologist now palpates the supraclavicular
should follow this advice even if he/she dm not find nodes.
any abnormality in the breast. There is nothing more
devastating and depressing than to reassure a patient Finally, the patient is made to lie supine with a small
who has a breast complaint that there is nothing pillow beneath the shoulder of the breast to be
wrong with her only for the patient to turn up a.few examined. The arm of that side is raised and tucked
months laterwith advanced breast cancerl' behind the head in order to flatten the breast.
Starting from the outermost section of each quadrant
Examination of the breast must be performed and moving towards the nipple, the breast is
methodically, according to a strict routine to make carefully and gently palpated by pressing the tissues
sure that no part is omitted from the examination. against the underlying chest wall. The pressure
exerted by the pads of the middle three fingers is
Visual inspection varied. The whole breast must be covered, including
The patient sits, undressed to the waist and facing the axillary tail. The breast is now examined with the
the gynaecologist. From the front, the gynaecologist patient's arm by her side. The entire procedure is
I
inspects both breasts, with the patient's arms in 3 repeated on the other side.
; different positions in turn: first by her side, second
with the hands clasped behind her head and her lf a lump is palpated, its size, consistency,
shoulders retracted back, and lastly, with her hands smoothness, discreteness and mobility must be
pressed on her hips so as to tense up the pectoralis
determined and noted. The skin overlyingthe mass is
muscles. The gynaecologist looks at the breasts for
pinched to determine if the skin isfixed to the mass.
asymmetry, visible lumps, dimpling or wrinkling,
fixation or retraction, vascular pattern, oedema, peau
d'orange (a goose-pimple appearance), distortion of To find out if the mass is fixed to pectoralis major
the nipples, unilateral nipple inversion, and other muscle, its mobility when the muscle is relaxed
skin lesions. lf the breasts are pendulous, they are (patient's arm by her side) is compared with its
lifted up to inspeCt their under-surface and the mobility when the muscle is contracted (hands
underlying chest wall for chafing, infections or pressed firmly on hips). lf the patient complains of
rt nipple discharge, it is important to determine if it is
intertrigo.
(.
localised to one duct or if it is arising from several
f Palpation ducts. The former would suggest a local cause,
r
Palpation must be performed according to a strict whilst the latter would indicate a systemic cause.
The distinction is established by gently pressing on
T
geometric routine, carefully assessing each qtradrant
in turn to make sure that no portion of the breast is the areolar margin with the palmar aspect of one
omitted in the examination. ln each quadrant, the finger, starting at 12 o'clock and going round the
t pressure exerted by the fingers must be varibd, First, perimeter of the areola , back to 1 2 o'clock. Next, the
,' the patient sits in front of the gynaecologist, leaning tissue under the nipple is picked up with the thumb
I
forward, and with her hands on his/her shoulders. and forefinger and gently compressed to see if any
After inspecting the breasts, the gynaecologist places discharge can be produced. lf any discharge is
: the fingers of one hand beneath the breast and the produced, its consistency and colour are noted, in
I
fingers of the other hand above the breast, so that the particular, if it is bloody. lf it appears tinged with
finlers are perpendicular to the chest wall. The blood, a clean frosted or albumin-coated glass slide
finEers of the two hands gently squeeze the breast. As is pressed against the discharge to prepare a slide for
they do so, the two hands gently pull the breast microscopic examination fol red cells and pus cells'
I towards the examiner so that th6 tissues close to the
chest wall can also be bimanually palpated' The patient should be taught how to perform
monthly breast self-examination' This should be
73
done on the same cycle day each month, preferably her attire downwards to exPose the
during menses, when the ovarian follicles are abdomen down to the symphysis pubis or
smallest in size. ask her permission for the female nurse to do
Systemic Exa mination it. Do this and inspect the abdomen carefully
Cardiovascular System before you say there is no surgicalscar!
. ls patient comfortable whilst tyirl$ ai r Presence of scarifications
is she breathless or distressed? : , l o Presence of prominent vessels that may
o Position her correctly and obgeru€ iusdsr indicate obstruction in the main abdominal
venous pressure. vessels and compensatory enlargement of
r Measure the pulse rate and note tfie collaterals
characterof the pulse.
. Measure the BP General light (superficial) palpation
o Palpate for position and character of the apex It is for tenderness and presence of a mass other than
the uterus.
beat.
r Palpatefor parasternal heave. Traditionally, for the purposes of examination, the
. Listen to the heart sounds and fsr muFmurs. abdomen has been split into four quadrants or nine
ln the presence of severe anaemia, corilrnent
regions as shown in Fig i below.
on the presence or absence of haernic

murmurs and heart failure.
Respiratory System
o lnspect the chest for symmetry and for
respiratory movements
. Measure the respiratory rate.
. Auscultate the lungs for breath sounds and
note any adventitious sounds.
Abdominal examination
The bladder must be empty before the examination.
lnspection Deeper palpation

For enlargement of liver, spleen and kidneys: lf the
I nspect the abdomen for:.
. liver or spleen is palpable, the enlargement must be
Hair distribution
measured in cm from the costal margin. lf the liver
o Enlargement or distension: Usually, an
and spleen are not palpated as you approach the
enlargement is readily seen. lf enlargement is
costal margin, ask the patient to take in a deep
present, note its position and symmetry. lf
breath, and as she does so palpate to determine if
you are not sure that enlargement is present,
you can feel the liver or spleen which can just be
kneel by the side of the bed or examination
"tipped" because it is only slightly enlarged.
couch with your eyes level with the top of the
patient's abdornen. A not so obvious mass For any abdominal mass: Carefully palpate all areas
will become obvious. of the abdomen. lf you are unable to feel any mass,
o Movement of the abdomen with respiration before you say there is no palpable mass, proceed as
o Presence or absence of scars: Remember follows. With the palmar surface of your left hand
that a transverse supra-pubic scar (from a facing the pelvis, put the ulnar aspect of the hand on
' Pfannenstiel's incision) may be so fine as to the patient's abdomen just below the umbilicus.
be ditficult to see and may also escape Gently press the hand into the abdomen and see if
detection unless the abdomen is carefully you can feel a mass. lf not, move the hand a little
inspected right down to the top of the lower and palpate again. Repeat the manoeuvre at
symphysis pubis. Ask the patient to move short intervals until you reach the symphysis pubis.
74
An Abdominal Mass ovarian tumour from an ovarian malignancy. But

lf a mass is present in the abdomen, a full bladder rememberthat even when no mass is palpated, there
must be excluded, and if the patient isqf'r*fftductive may be ascites when abdomino-pelvic tuberculosis
age, pregnancy must also be exctuffijffi mass is present.
must then be described, according,.&,$ryg,ffiySicat
findings: The features of the ma$$ $ffi.,sftust be Pelvic Examination
are: This must follow the abdominal examination. Unless
noted ,; ,
r lts size in centimetres verticatly and the abdominal examination is performed before the
transversely at its widest part, qnd1or by vaginal examination, the latter may not be as
comparison with what a normal Bregnansy informative as it can be. As already stated; it is
of that size would be in weeks' gestational necessary to explain the purpose and the procedural
age. steps of the examination to the patient and to obtain
. lts consistency her informed consent. The gynaecologist must be
. The regularitybf its surface ls ittender? patient and gentle in his/her approach (in his/her
ls it mobile? From side to side (left to right): words and actions) and the patient must be given a
Unless fixed by adhesions, both ovarian and running commentary of what the examiner is doing
uterine masses can be moved from side to and of the findings. This will help the patient to relax.
side It must be remembered that a rough and painful
examination in a patient who is tense, rarely
Vertically, up and down: Unless fixed by adhesions, produces any useful information. What is more, the
an ovarian mass can be moved a tair distance experience can prejudice attempts at examination at
E
upwards (cranially) and-dovflt, but because of its subsequent visits. A female nurse or chaperone must
attachment to the vagina the uterus cannot be so be present. Other prerequisites are:
moved.
lnfection prevention measures are absolutely
ls the mass arising from the pelvis? Can the examiner essential to protect the patient and health workers.
get below the mass? Standing facing the legs of the Disposable gloves and vaginal specula should be
patient, and with the left palm on the left side of the used. Non-disposable instruments e.g metal vaginal
mass and the right palm on the right side of the mass, specula, vulsella and sponge-holding forceps,
the two hands are moved lower and lower on the should be treated according to a strict protocol after
mass towards the pelvic brim. At the pelvic brim, can each use: immediate decontamination in a bleach
the fingers of the two hands be made to meet below solution followed by cleaning, and then sterilisation
the mass? ln a reproductive age woman, a mass in an autoclave.
t
r arising from the pelvis must be presumed to be a
(( pregnant uterus, until otherwise proven by an The patient's bladder must be empty. However, if
!
I ultrasound scan. Can the right hand, with its ulnar urinary incontinence was one of the patient's
edge pressing into the abdomen, be interposed complaints, then tests for incontinence must be
I
t between the mass and the pelvic brim? The foregoing performed before the patient empties her bladder,
manoeuvre should be used before this one.ls the otherwise the tests may give negative results. The
;
i mass intraperitoneal or retroperitoneal? A rectosigmoid must not be loaded. The patient's
retroperitoneal tumour is almost always tympanitic to bowel habit and when she last went to stool should
: percussion because of loops of bowel that are be one of the questions asked in the history-taking.
i
necessarily anterior to it. On the other hand, an
intraperitoneal mass is commonly dullto percussion. Visual inspection of vulva
/
This is performed with the patient in the dorsal
Testing for ascites position with the knees drawn up and separated or in
Always test for ascites by testing for shifting dullness the lithotomy position with the legs in stirrups. lf the
and a fluid thrill, particularly when an abdominal or patient is in the dorsal position and the patient
t
i pelvic mass is present. The absence or presence of cannot relax, she should be asked to appose the
: ascites helps to differentiate a fibroid or simple soles of the feet, so that the weight of the legs can be
,
!
75
supported by the apposition of the soles with-out any obvious genital prolapse can be demonstrated'
muscular effort on her part, and the knees shqu{d be Examination of the patient who complains of
allowed to fall as close to the couch gr,,p$..as symptoms suggestive of genital prolapse or urinary
naturally possible. incontinence is described below.
The mons pubis is inspected to note tE' Speculum examination

(texture) of the hair and whether the haii disfifbu$on Before the speculum examination, the materials for a
is of a mal'e or female pattern, and whethel the Pap smear (Ayre spatula, clean glass slides,
patient has recently shaved. Pubic lice and their nits endocervical cytobrush, fixative) must be ready'
Extended tip spatulas are more effective in collecting
are closely looked for. The skin of the vulva and
perineum is inspected for redness, hyper-or hypo- endocervical cells than the commonly used Ayre
pigmentation, ulceration, scratch marks, excoriation spatula. The most effective combination appears to
be the cytobrush with an extended tip spatula [REF
or chaffing or any sign of infection, and for masses
and warty growths, naevi, scars, and varicose veins'
3l The speculum examination is usually performed
before the bimanual examination for the following
The presence of any vaginal discharge and its colour
Ie?soIlS: The bimanual :
or blood at the introitus or on the vulva should be
noted. Evidence of female genital mutilation should
. May require lubrication, and the lubricant
may contaminate any discharge present in
be looked for, and if present, the type Oypes 1-4)
should be recorded, and the patient asked how she
the vagina, frustrating bacteriological
examination of the discharge
acquired the iniury. The presence of haemorroids and
anal tags is noted. Remember that bleeding
. May provoke bleeding if a friable lesion is
:
Present
haemorrhoids ca n be an i m porta nt cause of a naemia'
Now, the examiner takes up a position on the right
The bleeding:
side of the patient. With the joints of the middle, ring o May make adequate visualisation difficult or
and little fingers of the left hand fully flexed so that impossible.
the tips of the fingers are touching the palm, the o May make it impossible to take the Pap
thumb and index finger are used to separate the labia smear, or if it is taken, it may be reported as
minora to expose the vestibule, clitoris, external "u nsatisfactorY".
urethral meatus and introitus.
Having taken note of the capacity of the introitus, a
The following should be noted: evidence of female speculum of the appropriate size is selected' To
genital mutilation, size of the clitoris and prepuce,
visualise a child's vagina, or the vagina of an adult
external urethral meatus (any discharge, redness, with an intact hymen, a nasal speculum, a large
prolapse of mucosa, caruncle or other mass),
aurioscope (otoscope), or a Kelly air cystoscope, may
symmetry of the labia minora and majora, the be used. ln the usual case, foradequate inspection of
fourchette; state of the hymen - whether ruptured the cervix and vaginal walls, a bivalve speculum, e'g'
with hymenal tags (carunculae myrtiformes), a Cusco's, a Graves or a Pederson's speculum, serves
denoting past sexual experience, or whether intact the purpose better than the Sim's. The blades of the
normal, com pletely i mperforate, cri briform, an n u la r,
Graves speculum are broader those of Pederson's
(
septate); deficiency and distortion or scarring of the speculum. The two blades of a Cusco's speculum are
perineum. lf a purulent urethral discharge is present,
of the same len$h. lt must be remembered that if
a specimen should be taken with a white cotton- one blade of a bivalve speculum is longer than the
tipped swab for bacteriology' lf the discharge stains other (e.g. Pederson's or Graves), then the longer
the white swab yellow ("muco-pus" test), it can be blade is the posterior blade. Because of the deeper
presumed that infection with C' trachomatis or N'
posterior fornix, the posterior vaginal wall (8-12cm)
gonorrhoeae is present. The capacity of the introitus
is longer than the anterior wall (6-9cm).
is carefully evaluated and noted.
Usually, there is no need to lubricate the speculum

The patient is now asked to strain (bear down) and before inserting it. However, lf inspection revealed a
then cough to determine if stress incontinence or an dry introitus and vagina, as may be the case in a
76
woman who has been menopausalforyears, then the the external os and rotated through 360" so as to
tip of the speculum can be dipped in sterile water or scrape cells from the lower endocervix, the
saline before insertion. lf a lubricant is t"lsed, it must transformation zone and the portio vaginalis. The
be one that is not an antiseptic, in case-a .s,iryab for collected material is thinly smeared on a second
t' culture has to be taken. ,l
glass slide, immediately fixed, and labelled
"ectocervix". Lastly, the opposite end of the spatula is
lnserting the speculum: With the:iffir'harrd still used to scrape the posterior fornix to prepare the
exposing the introitus, and with the blAdes of the vaginal pool smear. This is also immediately fixed on
bivalve closed, the speculum is ge_ntly 'inserted a third slide and labelled "vagina". The cervix is again
directly in the transverse diameter of the vaiina, i.e. observed to see if the procedure has provoked any
with the edges of the speculum in the transverse bleeding.
plane, or in the oblique diameter and rotated to the
transverse. lt is inserted to its full length in the axis of Vagina: ln the reproductive age woman, who has not
the vagina, the direction of which is cranial and indulged in regular coitus, the vaginal walls are thick
posterior, (i.e. at 45" to the horizontal); then the and have numerous transverse folds of epithelium
blades are slowly opened. lf the patient is relaxed and (rugae), most prominently in the lower third. With
the instrument is being correctly inserted, the regular coitus andlor frequent childbirth, the rugae
speculum virtually "falls in". The speculum must not disappear. After the menopause, with oestrogen
be inserted in the antero-posterior diameter and then withdrawal, the vaginal walls become thin and
rotated because this is the smallest diameter of the smooth and dry and tend to break down easily; the
vagina and the lpeculum may impinge on the vagina becomes less distensible and shortens in
sensitive urethral area. length (atrophic vagina). Aftertaking the Pap smear,
as the speculum is slowly withdrawn, the vaginal
Cervix: The cervix is visually assessed: the portio walls are inspected for erythema, vaginal discharge
vaginalis (normally pink, smooth and shiny; ulcers, and any lesions. The blades must not be opened too
vesicles of herpes genitalis infection, growths, polyps widely as the speculum is withdrawn; and, as it exits
or other lesions are noted); the position of the the introitus, the blades must be closed to avoid
squamocolumnar junction is noted; this is usually causing the patient undue discomfort or even pain.
just within the external os, but it may be outside the lf vaginal discharge is present, a wet mount should
r
I os, so that endocervical columnar epithelium can be be prepared by placing a drop on a glass slide, cover-
(
r seen on the portio (ectopy); the external os is slipping the drop, and examining the preparation
inspected for any discharge or bleeding; the under the microscope with low-power magnification
nulliparous os is round and the parous os transverse; for motile flagellate protozoan organisms
if lacerations occurred during childbirth, the scars are (Trichomonas vaginalis). Epithelial squames in the
t
I commonly at 3 and 9'oclock and these may cause wet preparation are also closely examined under
I eversion of the anterior and posterior lips of the high power magnification to determine if their
f
( cervix, thus producing an ectropion, in which the surfaces and edges are sharp and distinct or whether
reddish endocervical columnar epithelium can they are obscured by dense clusters of adherent
readily be seen. bacteria, i.e. to determine whether clue cells that
would suggest Bacterial vaginosis are present. A
Papanicolaou smear.' A Pap smear is now taken. Any second drop of discharge is placed on another glass
excess mucus is gently wiped off the cervix with a slide and mixed with a drop of 7O% potassium
cotton-tipped swab. First, an endocervix specimen is hydroxide. With T. vaginalis and B. vaginosis
taken with a cytobrush. The cytobrush is inserted into discharge, this will produce an offensive amine-like
the cervical canal and rotated through 360o. lt is odour (whiff test or amine odour test). The KOH wet
withdrawn and the brush rolled (rotated) through preparation is cover-slipped and examined underthe
360o on the slide to prepare a thin smear. A fixative microscope for Candida albicans infection. The KOH
(95% alcohol) is immediately applied to fix the lyses epithelial squames, pgs cells, red cells and T.
I preparation and it is labelled "endocervix". Next, the vaginalis, but not the blastospores and
extended tip of the Ayre spatula is inserted through pseudohyphae (mycelia) of C. albicans. Therefore, if
.|.
I
77
candida infection is present, the mycelia and urethra, and descent of the cervix, ln the normal
blastopores will be clearly seen. patient, the bladder neck (urethro-vesical angle) and
urethra are well supported by the post-urethral
Palpation ' ,..--, ligament. The vaginal skin overlying a normal post-
As previously described, the thumb andtiffiffi*tr urethral ligament is seen on the anterior vaginal wall
of the left hand are used to separatethe'lebiE ffrfuorA. as a 3cm-wide strip just below the external urethral
The last two fingers of the right hand arc fl€xs$ so meatus, and with many irregular rugae. The lower
that their tips are touching the palm. The riEfrtfit*rrrb border of the strip is a groove (sub-meatal sulcus)
is flexed on top of the last two fingers. lf neCegsary, just below the external urethral meatus and the
the right middle finger is lubricated. lt is gently upper border is a second groove, the transverse
inserted into the vagina and used to press on the vaginal sulcus. On the sides of the portio vaginalis,
posterior introitus. This tests the thickness of the just above the external os, the attachments of the
perineal body and creates space anteriorly for the cardinal-uterosacral ligaments to the cervix are seen
right index finger, which is now inserted above the as dimples at the 3 o'clock and 9 o'clock positions.
middle f inger. Any bulge anterior to the line joining these points is a
bulge of the bladder andlor urethra; a bulge which is
Palpating for Bartholin's gland and duct= With the
posterior to this line is an enterocele.
two fingers in the vagina and the thumb outside, the
lower third of the right labium majus is gently Posterior wal/ prolapse.'The fingers are now used to
palpated for enlargement, a cyst or tenderness in the
lift the anterior vaginal wall to expose the posterior
right greater vestibular (Bartholin's) gland and its wall. Again, the patient is asked to bear down and
duct. Keeping the two fingers in the vagina, the cough to test for bulging of the posterior vaginal wall
forearm is pronated anticlockwise to palpate for the (rectocele). An enterocele, is herniation of the pouch
gland on the left side. The glands are situated at
of Douglas which contains small bowel. Unless very
about 4 and 8 o'clock, embedded in the posterior end severe, an enterocele is usually too high up to be
of ihe vestibular bulb. Both gland and vestibular bulb revealed by this manoeuvre (see below under
lie on, (i.e. are superficial to) the inferior layer of the "Speculum examination for prolapse or urinary
urogenital diaphragm (triangular ligament), but are incontinence"). With the labia minora stillseparated
covered, (i.e. are deep to) the bulbospongiosus by the left hand, the tip of the right middle finger is
(bulbocavernosus) muscle. Each gland is the size of a
used to exert gentle pressure on the urethra at the
pea, and normally, cannot be seen or palpated. lf an
urethro-vesicle junction. The finger is moved down to
abnormality is detected in the gland or duct, the the external urethral meatlts, while maintaining the
examiner should look for the orifice of the duct. The compression, to "milk" the urethra. This manoeuvre
duct is approximately Zcm long and runs anteriorly will express any discharge out of the urethra, a
and medially to open at the introitus at the junction of urethral diverticulum, or the paraurethral tubules
the lower third and anterior two-thirds of the labium (Skene's glands), or urine in a urethral diverticulum.
minus, in a groove between the labium minus It will also reveal any irregularities and masses in
superficially, and the hymenal ring posteriorly. ln the Skene's glands. Skene's glands are rudimentary
normal gland and duct, the orifice of the duct is not structures which are analogous to the prostate. They
visible, but when infection is present in the gland or lie posterior to the urethra and their two ducts open
duct, the orifice may appear as a reddened dot. into the floor of the urethra, just within the external
urethral meatus. Any purulent discharge expressed
Anterior vaginal wall and uterine descent.' The
should be subjected to microbiological examination
palmar surfaces of the two fingers are now used to
for N. gonorrhoeae.
press the posterior vaginal wall, including the
posterior commissure (fourchette). The patient is Speculum examination for prolapse or urinary
asked to bear down and cough to test for stress incontinence
incontinence, anterior vaginal wall prolapse lf the patient's complalnt indicates genital
(cystocele, urethrocele, cystourethrocele), abnormal prolapse or urinary incontinence, then the
descent (hypermotility) of the bladder neck and speculum, not the fingers, must be used to
78
82
95
History and Exami nation
demonstrate the prolapse or incontinence. kfienf's fornix); whether the os is closed or op€r; regularity of
position: The examination can be canied out in the the os; consistency; regularity (smoothness);
lithotomy position with the patient's buttocks at the whether there is a mass. Second, the cervix is
edge of the examination couch, so tfi€I the Sim's stabilised by placing the index finger on the left side
speculum can be used to retract the peterig yeginal of the cervix and the middle finger on the right. The
I
I wall without the bed/couch being in the ui*y of the cervix is gently lifted from the pelvis towards the
I
I
handle of the speculum. This posltiofl r&uiras the anterior abdominal wall. The normal-sized uterus is
{
I
examiner to sit on a high stool directly ifl frOnt of the thus made an abdominal organ. ln a thin woman
f vulva and perineum. Some preferthe modified Sim's who is relaxed, the abdominal wall may be seen to
semi prone position (lateral position). This is a very bulge as the fundus of the uterus hits it. The vaginal
useful position for demonstrating all types of hand holds the cervix steady, whilst the abdominal
a
I prolapse. lts only disadvantage is that h'satiffictOry hand is made to move down towards the symphysis
bimanual examination is difficult in'this position. pubis in steps. At each step an attempt is made to
f Therefore, for the bimanual examiriation,.the patient palpate the uterus between the two hands, the
I
will have to be repositioned in the dorsal or lithotomy fingers of the abdominal hand doing all the work. The
(
position. abdominal hand palpates the fundus and posterior
1
I
surface of the uterus. lf the uterus is normal in size, it
The speculum; The only satisfactory speculum for will be felt when the abdominal hand is close to the
I
prolapse and urinary incontinence is the Sim's symphysis pubis. lf it is enlarged, itwill befelt earlier,
vaginal retractor. A bivalve speculum cannot be used i.e. higher up in the abdomen. Assuming the patient
I
1 for genital prolapse for two r€ilsonS: is relaxed and the technique is correct but the uterus
I
t
1. Because the blades cover the anterior and cannot be felt between the two hands, then it is most
I posterior walls, a fistula or a bulge of either
i
likely retroverted. Provided the uterus is mobile, an
vaginal wall cannot be seen. attempt should be made to anteflex it by pushing the
I 2. The tips of the speculum in the anterior and
cervix backwards as it is lifted towards the anterior
posterior fornices support the cervix and
abdominal wall in an arc. The following are noted
uterus and prevent them from descending. A
about the uterus: size; position (normally it is
uterine descent cannot therefore be
anteverted, but it may be retroverted, or in the
demonstrated even if it is present.
midposition or axial, i.e. in the axis of vagina), shape
I
(normally pear-shaped); regularity or irregular with
/ Other instruments; A second Sim's speculum of a
smaller size; curved sponge-holding ring forceps; a
fibroids: consistency (normally firm); mobility
(normally can be moved from side to side and a little
tenaculum. The steps in the examination and the
grading of prolapse are described in the respective up and down, but may be fixed by adhesions from
inflammation or endometriosis); tenderness from an
chapters.
inflammatory process or endometriosis. Ihird, the
Bimanual palpation adnexa and the pouch of Douglas are examined. To
a The bimanual examination is performed to assess the examine the left adnexum, the middle finger is
uterus, appendages and the pouch of Douglas. The moved across from the right side to join the index
a introitus is exposed with the left hand as already finger on the left side of the cervix, while stabilising
:
described. The middle and index fingers of the right the uterine fundus with the right hand. The two
hand are gently inserted into the vagina as already fingers are moved into the left fornix whilst the
described. The left hand is now placed flat on the abdominal hand is made to slide down from the
abdomen with the fingers close together, just below fundus to the left side of the uterus. The tissues
the umbilicus. First, the vaginal hand locates the between the abdominal hand and the vaginalfingers
cervix by palpation. The following are noted about the are gently palpated for masses, thickening, and
cervix: size; position (external os poirrting posteriorly, tenderness, starting from the side of the uterus
anteriorly or in theaxis of the vagina -this is a pointer towards the pelvic wall.
l
t to the position of the uterus; in the normally
To examine the right adnexum, the abdominal hand
anteverted uteruE, the cervix points into the posterior
is moved back to the uterine fundus, whilst the
79
--l
middle finger, followed by the index finger, is moved withdrawing the finger from the rectum, it is
to the right side of the cervix. The two fingers qre now inspected for blood.
pushed into the right fornix, whilst the,a-W=o...Ei.flal
fingers slip down to that side of ther! ,.,,,,,1,. A rectal examination can be used as an alternative to
a vaginal examination in children and in adults who
:'
palpation is performed as was Oone on
When there is no abnormality in the, €$erurm, have never had sex (virgo intacta). lt is less sensitive
nothing is palpated and tenderness is .q, $.,9f than a vaginal examination and can be quite
minimal. Fourth, the pouch of Douglas is pajpatedfor uncomfortable but it will help pick up a pelvic mass'. t
l
any masses (loaded rectum, retroverted uterus,
ovarian tumour, fibroid, pelvic haematocele, or
rectosigmoid malignancy) and nodules on the At the end of history taking and
uterosacral ligaments which may indlcate the examination, meticu lous
presence oJ endometriosis. Fifth: the cervix is moved
documentation is centralto good
from side to side to determine if cervical motion
(excitation) pain can be elicited. practice!
Moving the cervix to one side pushes the uterine

fundus to the opposite side and thus puts the adnexal
Discussion and Controversies
structures on the side to which the cervix is being
moved on the stretch. lf inflammation or an ectopic l. Should miscarriages or abortions be discussed
pregnancy is present on that side, the manoeuvre under Gynaecological History or in Obstetric History?
produces ipsilateral pain, called cervical (excitation) Miscarriages are gynaecological conditions and so
motion pain. Finally, on withdrawal of the vaginal there is the temptation to discuss or analyze them
fingers they are inspected to see if they are coated under Gynaecological history but it is neater and
with blood or discharge. more logical for them to come under Obstetric history
since Obstetric History covers all past pregnancies
Rectovaginal examination
and theiroutcome in a chronologicalorder.
This examination allows assessment: of the
rectovaginal septum for endometriosis; for the ll. Lifetime Sexual Partners. ln the professional
intestinal loops in an enterocele, and palpation of a clinical examination of the WACS, some candidates
retroverted uterus. lt also helps to discriminate routinely ask patients the number of lifetime sexual
between genital and bowel lesions. A new glove is partners they have had and announce same to the
placed on the right hand. The middle finger is team of examiners. lt can be very embarrassing!
lubricated and inserted into the rectum and the index What is the relevance of the number of Lifetime
finger into the vagina. The rectovaginal septum is Sexual Partners in an Obstetric patient who has just
palpated between the two fingers. The uterosacral come to book for antenatal care with no complaints
ligaments are palpated for thickening, nodules and or to honour a follow-up appointment or of a Gynae
tenderness. patient with complaints not suggestive of STDs, PID
or Genital malignancies? The history is expected to
Rectal examination
be customized or tailored to the patient's presenting
This allows assessment of: the anal sphincter;
complaint. Truly, some questions may not only be
haemorrhoids and anal fissures; masses, including
unnecessary but in ourview, unkind to the patient!
malignant tumours of the rectum; the parametrium
and paracolpos from the midline to the pelvic lll. How much of the examination of the patient
sidewalls for lesions, including malignant should be done by the candidate before the arrival of
secondaries. ln a case of cervical malignancy, this is
the Examiners? Prwided there is a chaperone, a
how parametrial spread (Stage llB or lllB) is
candidate can undertake all aspects of the
determined. However a satisfactory examination to
examination of the patient excdpt pelvic examination
stage the disease requires that the examination be
before the arrival of the examine(s). llowever, in
done under general anaesthesia. Again, after practice, the time allotted for the clerking of the
80
patient is not enough to take history and do a References

t
complete physical examination before the examiners
, are ushered in; hence most candida@ re able to
take history and perform gener*l..ffi
E
h- ction
1/ 1. United Nations Population Fund. The state of
including vital signs of the patient wlof the world population 2002. New York: UNFPA,
the examiners.
2002
2. Bonita R. Women, ageing, and health:
I lV. The precision and accuracyof trans$&n#al and
achieving health across the life span. 2nd ed.
transvaginal ultrasound scans will
undoubtedly
Geneva: World Health Organization, 1998.
continue to improve; the costs of these investfiations
3. Martin-Hirsch E Jarvis G, Kitchener H, Lilford
will continue to decrease, and they will become R. Collection devices for obtaining cervical
universally and more readily accessible. As these
cytology samples (Cochrane Review). ln: The
improvements continue, will bimanual (pelvic)
Cochrane Library, lssue 4, 2002. Oxford:
palpation for the detection of pelvic masses continue
Update Software.
to have a role in the examination of the 4. Monga A. and Dobbs S @ds). Gynaecology by
gynaecological patient or will it, at some point in Ten Teachers. 19'n Edition. London: Hodder
time, become obsolete? We are almost getting to that Arnold, 2011
point at least from the perspective of the Fellowship
examinations, for it is now rare to ask a candidate to
perform a pelvic examination on a patient at the
clinicals!
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82
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ti
CHAPTER
V
F
SO Shittu, Samba A, EY Kw *ume
INTRODUCTION: including nutrition, with early detection and referral

of those at high risk; the assistance of a trained
L.: ln the early 1960ies, reports on maternal newborn person at all births; and access to the essential
and child health in Europe and USA had made it elements of obstetric care for women at higher risk.
I obvious to the global community that the physiology Although maternal mortality declined in a number of
of pregnancy and childbirth must not be taken for countries, the SMI fell short of its targets and the
Y
granted, interventions such as antenatal care, reasons ascribed were faltering political
emergency preparedness and skilled attendance at commitment, inadequate funding, and a lack of clear
delivery, among others must be instituted to technical priorities. Another major flaw in the SMI
safeguard the safety and wellbeing of mothers and was its approach to maternal mortality reduction as
their newbornst. a purely health issue. lmprovement on the SMI
strategies came at the 7994 lnternational
By the 1980ies, it was obvious that whereas global
Conference and Development (ICPD), when the
neonatal outcomes were improving, the maternal
concept of Reproductive Health (RH), as a human
ones were not. The reasons for the latter were soon to right, was introduced. This placed maternal and
be revealed by a landmark publication in 1985, titled newborn health on a new pedestal: it was to be
"Child-bearing, health and social priorities: a survey guaranteed by all governments; it was to be pursued
of 22,774 consecutive births in Zaria, Northern by inter-sectorial collaboration; and it was linked
Nigeria"', which revealed existence of considerable with development.
maternal mortality in tertiary healih facility and
clearly showed the major contributors to be non- DEF!NITIONS:
medical factors of social, cultural, infrastructural and
economic ones and highlighted their preventability. Reproductive health:'A state of complete physical,
These factors were soon categorized into three levels mental, and social wellbeing and not merely the
of delays: Type l, in decision-making; Type ll with absence of disease or infirmity, in all matters related
transportation to health facility; and Type ll, in to the reproductive system and to its functions and
obtaining appropriate intervention whilst in the process"t. Reproductive health addresses the human
health facility. The initial global response was the sexuality and reproductive processes, functions and
enunciation of the Safe Motherhood /nitrafive(SMl) system at all stages of life (from the womb to the
in February 7987, that sought to reduce maternal tomb) and implies that people are able to have "a
mortality by half within a decade through the 4- responsible, satisfying and safe sex life and that they
pronged strategies of: adequate primary health care have the capability to reproduce and the freedom to
and an adequate share of available food for females decide if, when and how often to do so." This implies
from infancy to adolescence, and universally that every man and woman has the right to be
available family planning; good prenatal care, informed and have access to services that guarantee
83
their: ability to reproduce; freedom to control tract infections (RTl), including Sexually
reproduction; ability to go through pregnancy and Tra nsmitted Diseases (STD), H lV/Al DS;
childbirth safely, with successful rnaternaland infant . Prevention and treatment of infertility;
survival and outcomes; ability to obtain infomldion o Management of cancers of the reproductive
about and access to safe, effective and affordaHe system, including breast, testicular and
methods of family planning; ability to have a prostatic cancers; Prevention and
satisfying, safe sex life, free from fear of pregrrarrcy management of cervical cancer;
and disease; and ability to minimize reproductive
. Respondingto concerns of menopause;
tract disease and risk throughout all stages of life'
o Elimination of harmful traditional practices
Reproductive health is life-long, beginning even
that affect the reproductive health of men
before women and men attain sexual maturity and
and women such as female genital
mutilation, sexual trafficking and violence
conti nu i ng beyond a woman's child-beari ng years.
againstwomen;and
Reproductive Rrihts: The 1994 ICPD did not o lnformation and counselling on human
introduce new human right, but it acknowledged the sexuality, responsible sexual behavior,
affirmation of reproductive health in existing adolescent health, responsible parenthood,
declarations, including: the Universal Declaration of preconception care and sexual health.
Human Rights, 1948; the Convention on the
lf the objectives of offering these reproductive health
Elimination of All Forms of Discrimination Against
care services are to be achieved, they must exhibit
Women, 1979; the Programme of Action, from the
the following attributes:
lnternational Conference on Population and
Development, Cairo L994; and the Platform for o Avaitability: Sexual and reproductive health
Action at the Fourth World Conference on Women,
and health care facilities, goods and
Beijing 1995. These rights include: the right to
services, as well as programmes, should be
health in general; the right to reproductive choice;
available in sufficient quantity within the
the right to receive reproductive health services; the
country. These goods and services include
right of men and women to marry and found a family;
safe and potable drinking water and
the right of individuals to make reproductive adequate sanitation facilities, hospitals,
decisions free of discrimination, coercion and
clinics and other health-related buildings,
violence; the right of the family to special protection;
trained medical and professional personnel
and special rights in relation to motherhood and
receiving domestically competitive salaries,
childhood (pre- and postnatal care). Other essential
and essential drugs.
human rights permit women to reatize their dignity e Accessibility: Sexual and reproductive
economical ly, socially, and culturally.
health facilities, goods and services have to
Reprductive Heatth Care (RHC): The 1994 ICPD

be accessible to everyone without
discrimination. Accessibility has four
also defined RHC as "the constellation of methods,
techniques and services that contribute to
overlapping dimensions: non-
discrimination; physical accessibility;
reproductive health and well-being through
affordabi I ity; a nd i nformation accessi bil ity'
preventing and solving reproductive health
problems". These services should be integral of
. Acceptability; All sexual and reproductive
health facilities, goods and services must be
primary health care and includer
respectful of medical ethics and culturally
. Safe Motherhood including antenatal, safe appropriate; respectful of the culture of
delivery and postnatal care especially breast
individuals, minorities, peoples and
. communities, sensitive to gender and life
feeding, infant health and women's health;
cycle requirements, as well as designed to
Family planning;
o Prevention and management of unsafe respect confidentiality. and improve the
abortion and post abortion care health status ofthose concerned'
o Prevention and treatment of Reproductive
o Quatity; As well as being culturally
84
acceptable, sexual and reproductive health childhood deaths occur in the developing regions of
facilities, goods and services must also be the world. Associated with perinatal mortality are:
scientifically and medically appropriate and poor maternal health or nutrition, inadequate care
of good quality. This requireS, @,€x!ynpls, during pregnancy, poor complications management
skilled medical personnel, sffiffieally during pregnancy and delivery, and preterm birth.
approved and unexpired drugs ard hospital Others are unsanitary delivery, maternal infections
equipment, safe and potable water, and and neonatal tetanus.
adequate sanitation.
Low-birth weight refers to babies born with weight of
Reproductive Health lndicatorst Global indicators less than 2.5Kg. Annually, 15 million babies are
have been selected for appraising and comparing born prematurely and 32.4 million are born with a
reproductive health across countries, geographic weight below the tenth percentile for their
locations and timelines, these are: Fertility; Life- gestational age, 957" of which occur in developing
expectancy; Perinatal Mortality; Low birth weight; countries. The prevalent causes of these births are: .
and Maternal Mortality. preterm delivery, restricted fetal growth, poor

socioeconomic condition, maternal malnutrition and
Fertility is a measure of the average number of toxic exposures, and maternal infections such as
children women in a society have; it influences the malaria, HIV and syphilis.
rate of naturalgrowth of the society, and is dependent
on couples'ability to control reproduction and infant Maternal Mortality refers "the death of a woman
survival. A fertility rate of 2.L is considered while pregnant or within 42 days of termination of
replacement rate for a population, the average pregna ncy, i rrespective of the d u ration a nd site of the
number of births per women required for a population pregnancy, from any cause related to or aggravated
to replace itself in the next generation. Fertility along by the pregnancy or its management but not from
with mortality, are the two major determinants of accidental or incidental causes". lt is measured
natural increase in a population. usi ng any of the fol lowing criteria :
Life expectancy is a measure, in years, of the o A maternal mortality ratio (MMR), which is
expectation of the length of [ife, calculated most the number of maternal deaths per
typically from the time of birth. lt is commonly used, 100,000 live births during a given time
in a summary way, to reflect the overall health of a period;
society. Life expectancy has lengthened markedly
since the 20th century as a result of improvements in o A maternal mortality rate, the number of
health care, preventive measures, sanitation and maternal deaths per 100,000 women of
nutrition. However, considerable variations in life reproductive age in a given time period.
expectancy exist between the sexes, being shorter for This measure reflects the frequency with
males than females, and between countries of the which women are exposed to risk through
world, with lower expectancy in developing countries pre$nanc!; and
being influenced by poverty, environmental and
occupational exposures, individual risk factors such o The lifetime risk of maternal death,
as smoking, obesity, access to health care, and expressed as a risk of 'one in into
diseases such as HIV/AlDS. account both the probability of becoming
pregnant and the probability-'takes
of dying as a
Perinatal mortality refers to stillbirths after result of that pregnancy cumulated across a
attainment of age of viability and deaths of newborns woman's reproductive years.
within the first seven days of life. Of the 2.9 million
babies that die each year duringthe first month of life, It is estimated that 287 ,OOO maternal deaths occur
2.6 million of them will die in the last trimester of world-wide each year, 997o of them occurring in the
I pregnancy or during the first week of life, considered developing countries, from^ causes that include:
the perinatal period'. Ninety-eight percent of early Haemorrhage, infections, unsafe abortions,
85
eclampsia, obstructed labour, other direct causes, Four other goals were also promotive of reproductive
and indirect causesu. health and health overall:
FURTHER GLOBAL EFFORTS ON ! :::::+- +!:.a: ' Goal 1 Eradicate extreme poverty and
REPRODUCTIVE HEALTH: hunger
ln other to build on the gains made since
of reproductive health was introduced, ,ggccry@
' Goal 2 Achieve universal primary education,
and
global conferences and programs have given it
priority. At the Fourth Wortd Confereneeon.t@8?err,
' Goal 7 Ensure environmentalsustainability.
held in Beijing in 1995, governments.reognid'that' The most recent of the global commitments, the
entrenched patterns of social and cultu:ral Sustainable Development Goals (SDGs), dedicates
discrimination are major contributors to sexual and SDG Goal-3 to "Ensure healthy lives and promote
reproductive ill-health, along with the.'lamk,:of well-being for all at all ages", and seeks to achieve
information and services. Consequently, sexual.and among other objectives:
reproductive health efforts must be coordinated with
interventions that address the patterns of social . "By 2030, ensure universal access to sexual
discrimination, gender inequalities and exclusion and reproductive health-care services,
that hinder women, men and adolescents from their including for family planning, information
exercising their reproductive rights. Reaffirmation of and education, and the integration of
these commitments were made at the ICPD+5, reproductive health into national strategies
ICPD+ 10 and the United Nations GeneralAssembly and programmes:
Special Session (UNGASS) on HIV/AIDS and the . End preventable maternal mortality by
political Declaration in 2006. At the 2005 World 2030u; and
Summit, world leaders committed themselves to . End preventable stillbirths and newborn
"achieve universal access to reproductive health by deaths by 2035'.
2075, as set out at the lnternational Conference on
Population and Development, integratingthis goal in With these new global targets, strategies
strategies to attain the internationally agreed recommended for their successful pursuit include:
development goals, including those contained in the strengthening care around time of birth;
Millennium Declaration, aimed at reducing maternal strengthening the healthcare system; reaching every
mortality, improving maternal health, reducing child woman and newborn; harnessing the power of
mortality, promoting gender equality, combating parents, families and communities; and improving
HIV/AIDS and eradicating povefi." data fordecision making and accountability.
The United Nations Millennium Development Goals CURRENT STATE OF GLOBAL REPRODUCTIVE
(MDG's), which emanated from the United Nations HEALTH:
Millennium Declaraiion adopted by 189 member The scorecard at the recent close of the MDGs in
states in 2000, provide an international framework 2015' give a glimpse of the current state of global
for measuring progress towards sustaining reproductive health, as well as for individual
development and eliminating poverty. Of the eight countries. For the MDGs directly related to
Goals, four are directly related to reproductive health:
reproductive health, MDGs 3,4,5 and 6:
MDG-3: Promote Gender equality and empower

r Goal 3 Promote gender equality and
women - Women have gained ground in
empowerwomen parliamentary representation in nearly 90 per cent of
. Goal 4 Reduce child mortality the 174 countries with data over the past 20 years'
. Goal 5 lmprove maternal health, and The average proportion of women in parliament has
. nearly doubled during the same period' Yet still only
Goal 6 Combat HIV/AIDS, malaria & other
one in five members are women
disease
86
MDG-4: Reduce Child Mortality - The global under- century. ln 2015, 91 per cent of the global
five mortality rate has declined by more than half, population is using an improved drinking water
dropping from 90 to 43 deaths per 1,0O0 live births source, compared to 76 per cent in 1990.
t, .'
I
between 1990 and 20L5. Despite popula ,gprrrrth Worldwide, 2.1 billion people have gained access to
in the developing regions, the nurnhgr,#.&Srs of improved sanitation. The proportion of people
children under five has declined frqm trZ-T.mitlion in practicing open defecation has fallen almost by half
1990toalmost6millionin2015gl := since 1990.
MDG-S: lmprove Maternal Health -sinE61@, the
global Maternal Mortality Ratio has deelined by 45% CONCLUSION:
and most of the decline occurred after 200O.
STRATEGIES FOR ACHIEVING UNIVERSAL
MDG-6: Combat HIV Malaria and other diseases - ACCESS TO REPRODUCTIVE HEATTH SERVICES
New HIV infections fell by approximately 40 per cent Countries need to review existing policies and
between 2000 and 2013, from an estimated 3.5 interventions in the area of maternal health care;
million cases to 2.1 million. Over 6.2 million malaria ldentify the key bottlenecks to the implementation.
deaths have been averted between 2000 and 20L5, and attainment universal access ldentify gaps in
primarily of children under five years of age in sub- existing policies and interventions;
I
t-. Saharan Africa. The global malaria incidence rate has
f fallen by an estimated 37 per cent and the mortality
Develop cost-effective solutions that can accelerate
progress towards the attainment of universal access
rate by 58 per cent. Between 2000 and 2013,
tuberculosis prevention, diagnosis and treatment Design an action plan for implementing the
interventions saved an estimated 37 million lives. i nd icative i nterventions a nd mon itor progress.
The tuberculosis mortality rate fell by 45 per cent and
the prevalence rate by 41 per cent between 1990 Countries and governments should budget for and
and 2013. commit resources to implementation of reproductive
hea lth service programs.
For the MDGs that were indirectly related to
reproductive health, MDGs 7, 2 and 3, similar There is the need to mobilise these resources in
progress were recorded :
country and reduce the over reliance of governments
on donor support for the running of reproductive
MDG-I: Eradicate Extreme Povefi and Hunger -
health programs
Extreme poverty has declined significantly over the
last two decades.
'ln 1990, nearly half of the
The advent of the reproductive health concept in
r population in the developing world lived on less than 1994 introduced a paradigm shift that has
$1.25 a day; that proportion dropped to 14 per cent presenteda broad-based platform for keeping it
in 2015. Globally, the number of people living in relevant and in the front burner of global
extreme poverty has declined by more than half, programming and healthcare service provision to
falling from 1.9 billion in 1990 to 836 million in date. This has also given it the consistent attention of
2015. global partners, national and sub-national policy
makers, whose responsibility it is to prioritize
MDG-2: Achieve Universal Primary School Education
healthcare and make budgetary allocations. The
- The global out-of-school children of primary school considerable improvements recorded in global
age reduced from 100 million in 2000 to 57 million
reproductive health indices are by all means
in 2015.
attri buta ble to these developments.
MDG-7: Ensure Environmental Sustainability - 1.9

billion people have gained access to piped drinking
water since 199O. Ozone-depleting substances have
t been virtually eliminated since 1990, and the ozone
layer is expected to recover by the middle of this
87
'fr€
I
- .t,l
:I
rl
-r,1\-i
4
REFERENCES
.t)
j
!
rl
,j d
t
1. Antenatal care in a d o Ie sce nt/to pi c s/n ew b o rn/e n a p_co n
promises, achievements ,1
sultation/en/. I
!
opportunities: an analysis of r
J
and differentials, 1990-2AAL WHO, Unicef, IJNFPA, The Wortd Bank, i I
UNICEE 2003 ".r.;i,.+:,q{"&&Y l United Nations Population Division. Trends {

I: ti:*,.i!{it**ffi&*S in maternal mortality: 1990-2013. May ,1
2. Harrison KA et al. (198il 2014. www.who.int/

health and social priorities: a ffiS,, re p rod u ctive h e a lth /p u b I i cati o n s/m on it ,
22,774 consecutive birtlq S:fffi, oring/ maternal-moftal ity-20 I 3/en/.

..r
Northern Nigeria. Br J Obs@l4€1re@, i

(SupplS): 1-119. 6. WHO. Strategies toward ending preventable
maternal mortality (EPMM). 2015.
lnternational Conference on Poputatior* aN
h ttp : //w h o. i nt/ re p ro d u ctiv e h e a lth /
3.
Development Programme of Action. Mry 13t
top ics/m ate rn al pe rt n atal/e pm m/e n/.
1 9 9 4 : http ://www. u nfoa. o rglicpd L
7. United Nations, New York. The Millennium

4. Unicef, WHO. Every newborn: an action plan
Develop ment Goa I s Report. 20 1 5
to end preventable deaths.2014. (
i
www.who.int/materndl child
88
c,APrE
"7
Miscarriage
H S Galandanci
SPONTANEOUS M ISCARRIAGE As well as facilities for providing both medical and

a
surgical treatment of miscarriages. Adequate pre-
Introduction treatment and post-treatment counseling should
I
The term miscarriage simply means spontaneous loss also be available. lt is essential that staff in such
aslS-20%of
of pregnancy beforeviability. As much units should be well trained to provide adequate
all pregnancies end up with spontaneous information for women to make informed choices on
t miscarriage.' lnitially all pregnancy loss before their method of treatment.
viability is termed abortion, but in modern obstetrics
miscarriages are now classified as early pregnancy Diagnosis
loss which is defined as loss of pregnancy before 12 Adequate history and physical examination lre
weeks of gestation, delayed pregnancy losS formally essential in making a diagnosis of miscarriaF ln
termed missed abortion and late pregnancy loss, view of the variability of the menstrual cycle, the r-.:st
which is loss of pregnancy between 72 and 24 weeks Menstrual Period should be used with caution in
gestation. Whilst recurrent miscarriage is defined as ascertaining the gestational age. Ultrasound is an
3 early consecutive pregnancy losses or 2 lale essential tool used to confirm intrauterine pregnancy
pregnancy losses. lt is essential that all patients with and its viability. However, it is important to state here
early pregnancy complications are treated with care that a transvaginal ultrasound is usually preferable.
and support and given evidence based information. It is used to identify the location of the pregnancy as
This is because it is usually an emotional period for well as visualize the fetal pole and the fetal
the woman, her partner and her relatives. lt is heartbeat. An abdominal ultrasound can be done if
sometimes associated with significant distress for transvaginal ultrasound is unavailable, or
both the women and her partners. Early pregnancy unacceptable or in the presence of pelvic pathology
loss can also be associated with morbidity and such as uterine fibroids and ovarian cyst.' ln using
unnecessary mortality. lt can also have adverse ultrasound for assessment of early pregnancy the
effects on the quality of life of many women. viability of the foetus is determined by identifying the
heartbeat and the fetal pole should be identified and
Early pregnancy bleeding [s one of the commonest crow-rump length measured. ln the absence of a
presentation at gynaecological emergencies. As such fetal pole, the mean gestational sac diameter should
hospitals now have early pregnancy assessment be measured.'A repeat ultrasound is usually
units, which are units dedicated to managing all necessary before a final diagnosis can be made. lt is
women with early pregnancy complications pertinent to mention here that the ultrasound should
especially bleeding in early pregnancy. Early be performed by trained personnel who have
pregnancy assessment units should have facilitiEs for adequate skills and experieRce. ln the presence of a
t making early pregnancy diagnosis such as fetal heart beat in ultrasound and a confirmed
transvaginal ultrasound and serial HCG estimation. intrauterine pregnancy, a diagnosis of threatened
89
rniscarriage can be made. On the other hand, in the report is suggestive of retained products of 15m or
presence of a gestational sac with an absent fetal less, an expectant management can also be offered.'
pote, the measurement of the sac is done and a Women who opt for expectant management must be
repeat ultrasound is performed 7 tO 14 d@&.qe given adequate information on the following:
making a diagnosis of incomplete or e@#ffi-€te
m sca rri a ge. A lth o u gh co m p ete m isca rri age ean'cmly
. Whatto exPect
i I
. What to do if symptom persists or new

be diagnosed in the presence of a previous ultrasound
symptoms present for example more bleeding
confirming an intrauterine pregnancy. The use of
occurs or worseni ng of lower abdomi nal pain'
serum Beta Human Chorionic Gonadott'ophin . lnformation on the various option of
(BHCG) in early pregnancy assessment is rna'inly to
management
predict the outcome of the pregnancy especially in . Procedure of manual vacuum aspiration and
cases of suspected ectopic pregnancy, where its post evacuation care
monitoring the serum BHCG 48 hours apart can aid . The effect of the evacuation on her future
in diagnosis .
fertility and the possibility of a repeat
m iscarriage i n subseq uent pregna ncies.
Expectant Management . Clear any misconception about miscarriages
ln deciding the treatment option to offer a woman . Providefollow uP aPPointment
with early pregnancy bleeding, the following should . Provide leaflets and other counseling services
be considered: if available
1. Type of miscarriage
2. Clinical presentation of the patient After 2 weeks of expectant management, the woman
3. Amount of refined products obtained from
is reviewed, if bleeding and pain have resolved, she is
an ultrasound lf the bleeding and pain has persisted
reassured.
4. Patient's choice
then a repeat ultrasound is performed and if
suggestive of incomplete miscarriage, she is offered
lf a woman presents with vaginal bleeding in early
pregnancy and no cervical changes with a confirmed the treatment options of medical management,
viable intrauterine pregnancy, which means with a surgical evacuation or a continued expectant
management.'
fetal heartbeat on ultrasound, a diagnosis of
threatened miscarriage is made in such a case. The
Medical Management
treatment of choice is to advice on bed rest and Medical management is now an option of
hematinic. lf bleeding.persists up to 2 weeks, or management of incomplete or missed miscarriage. A
become worst, or if lower abdominal pain increases
randomized clinical trial on the use of medical
she should be reassessed and appropriate treatment
management in the management of missed abortion
instituted. lf, however bleeding stops, she repeats an showed 80% success with vaginal misoprostol and
ultrasound and the care of the pregnancy continues' 76% in the control arm.o Misoprostol is a
Women who present with incomplete miscarriage,
prostaglandin analogue and is the drug of choice in
inevitable or delayed miscarriage have usually been
incomplete or delayed miscarriage especially as it is
offered surgical evacuation, but studies have now
cheaper than gameprost and has different routes of
reported similar success rates and complications
administration and does not require refrigerator.' lt
between expectant management and surgical
can be given sublingual, oral or the vaginal route and
evacuation in women with inevitable or incomplete
a dose of 600microgram can be given for incomplete
miscarriage.t Once a woman is confirmed to have
or missed abortion.'The supportive management of
spontaneous miscarriage she is offered expectant
pain relief and antiemetics may be indicated in view
management except she is bleeding excessively, has
of the possible side effects, mainly of vomiting and
increased risk of hemorrhage, has previous
diarrhoea. Women being offered medical
complicated pregnancy such as stillbirth or
management should be given adequate information
miscarriage, has increased risk of coagulopathies or
including what to expeci during the process of the
has evidence of infection, in which case other options
miscarriage and possible side effects of the drug- lf at
of management should be considered.' lf ultrasound
any time, there is worsening of symptom a
90
Miscarriage
reassessment of the woman is done and appropriated required specialists, in addition to a gynaecologist.
treatment is instituted. lf after 3 weeks'a repeat
Risk factors for Recurrent Miscarriage
pregnancy test is positive, the possibilities. , laror
't''* ectopic pregnancy should be :eet*;*$sed.'
Epidemiological Factors
Mifepristone is only used to induce q€i@S*atres
Advancing maternal age has been associated with
and therefore not indicated in rnlssed rlr
recurrent miscarriage. Women that are older are
miscarriage
more likely to have recurrent miscarriage as
Surgical Management compared to younger women. One of the identified

Surgical management may be indicated in the r:isk factor of advancing maternal age that
following: :' ' .
predisposes a woman to recurrent miscarriage is the
1. Women with excessive hemorrhage decline in the number and quality of oocytes within
2. Women with persistent bleeding after 2 the ovary.' Advancing maternal age is also
weeks of expectant management.. associated with increased risk of fetal chromosomal
3. Women who opt for surgical management abnormalities such as fetal trisomy. Women with
. after considering all other options. previous history of a pregnancy loss are also at a
4. Women with unstablevitalsigns. higher risk of repeat miscarriage. lt has been shown
5. Women with retained tissue that is infected. that the risk of repeat miscarriage is approximately
40% after 3 consecutive pregnancy losses.' Other
Suction evacuation is associated with fewer
associated risk factors are maternal cigarette
complications therefore is the method of choice in
1 smoking, coffee consumption, and alcohol
surgical management. Suction evacuation using
a
consumption,e as well as obesity.'oThese have all
manual vacuum aspiration (MVA) is associated with
been associated with increased risk of sporadic
less risk of uterine perforation and hemorrhage, less
> miscarriage.
risk of intrauterine adhesions and cervical tears.
Another advantage is its use with local anesthesia Genetic Factors
and as an outpatient procedure. Therefore, reducing Parental chromosomal abnormality has been found
the cost of admission and theatre use. in 3-5% of couples with recurrent miscarriage.u
Balanced structural chromosomal anomaly is one of
Use of cervical priming agent may be considered the common anomaly associated with increased risk
before suction evacuation in certain cases.' Women
,,, of miscarriage. The balanced reciprocal
,must be given adequate information about the translocation is seen more in females, and even
procedure including possible complications before an
though carriers are usually phenotypically normal
informed consent is obtained. Sending the sample
:
they can have unbalanced gametes and embryo.u
obtained from evacuation for histology is an essential
With regards to the foetus, fetal aneuploidy is the
part of the management and should not be omitted.
commonest chromosomal abnormality and is the
single most common cause of miscarriage. Fetal
RECURRENT MISCARRIAGE
trisomy can be found in up to 30% of miscarriages
I
Recurrent miscarriage is defined as three or more and has been shown to be associated with advanced
consecutive miscarriages. lt affects about 1% to:2"/o maternalage.
of women that conceive.u There aie a,nurnber of risk
Endocrine Disorders
factors associated with recurrent miscarriage,
Different endocrine disorders have been associated
although as much as 50% of women with recurrent
with recurrent miscarriage. For a long time,
miscarriage will have no identified risk factor even
deficiency of progesterone secretion by the corpus
after extensive investigations.s ln view of the barrage
luteum, also known as luteal phase defect has been
of tests required to investigate a 'woman with linked with early trimester miscarriage. This has
reiurrent miscarriage, she should be managed in
necessitated some doctors to be giving progesterone
I centers with adequate facilities and specialists in that
L to women with recurrent firdt trlmester miscarriage.
area. Genetic counsellors, endocrinologist, However, Cochrane review did not show any benefit
i
embryologist and immunologist arb some of the
! of giving progesterone in reducing the rate of
\:
I
91
I
l Comprehensive Gynaecology in the Topics
,---_-.t
miscarriage in women with sporadic miscarriage.T prevalence in the literatui'e of 1.8% to 377" af uterine
malformations among women with recurrent
Other endocrine disorders such as dia$ts$,Mf'$tus' miscarriage."
and thyroid diseases have also been associ# with Cervical incompetence is known to cause second
recurrent miscarriage. lt is irhportam to:tiffffiffi:a trimester miscarriage. Women with history
well-controlled diabetic is not at risk'of:miiicairt@, suggestive of cervical weakness associated with
but a diabetic woman with high haemoglobin A 1c second trimester miscarriage should be assessed
level in the first trimester is at risk of miscarrirye and adequately for possible benefit of cervical cerclage
fetal malformation.' The presence of anti-thyroid insertion.
antibodies has been linked with recurrent
miscarriage, although the literature is not supportive lnfections
of that.u Likewise, studies have shown that women The exact relationship between recurrent
with recurrent miscarriage have similar prevalence of miscarriage and infection is not clear, even though
diabetes and thyroid dysfunction as compared to severe bacterial or viral infection is known to be
women without recurrent miscarriage." associated with sporadic miscarriage. lntrauterine
infections that can cause misca rriage are
Polycystic ovarian syndrome (PCOS) had been toxoplasmosis, rubel la, cytomega lovirus, herpos a nd
associated with various endocrine pathologles and syphilis infections (TORCHS). lnfection v' Lh
recurrent rniscarriage. Hypersecretion of luteinizing bacterial vaginosis can also lead to second trimester
hormone which was thought to lead to the rnlscarriage and preterm delivery. This is supported
miscarriage has been disputed by the literature.6 The by evidence of reduction of risk of second trimester
insulin resistance, and hyperinsulinemia and miscarriage and preterm delivery in women treated
hyperandrogenemia in women with PCOS is now with clindamycin."
believed to be responsible for the increased risk of
miscarriage fou nd i n them.' lmmune riskfactors
It is known generally that the maternal immune
Auto-immune Diseases system is not suppressed in pregnancy but rather
Another major risk factor for recurrent miscarriage is reproductive immunology suggests an interaction
antiphospholipid syndrome (APS). Once diagnosed, between individual cells and molecules of the
treatment with heparin and aspirin can be offered. ln maternal lmmune system and the foetus for optimal
about 15% of women with recurrent miscarriage, the fetal survival.u Raised uterine natural killer cells in
presence of autoantibodies can be detected.' The women with recurrent miscarriage has been shown
exact mechanism through which APS causes adverse not to be associated with increased risk of
pregnancy outcome is not known but local miscarriage. However, meta-analysis have shown
inflammatory processes caused by activation of modesi association between cytokine polymorphism
compliment pathways at the maternal-fetal and recurrent miscarriage.'o lt has been shown that
i nterface, uteroplacenta I vascu atu re th rom bosis
I a nd women with recurrent miscarriage have more of T-
inhibition of trophoblastic function and helper-1 cytokine response as compared to women
differentiation, are some of the pathologies through with normal pregnancy that have more of T-helper-2
which antiphospholipid antibodies cause adverse cytokine response.' lt is clearrthat there is need for
pregnancy outcome.' further research in this area.
Anatomlcal Factors Thrombophilic Factors

Women with congenital uterine anomalies such as ln normal pregnancy, there are increased levels of
arcuate or septate uteri are associated with increased coagulation factors and a decrease in the levels of
risk of recurrent miscarriages especially in the second anticoagulant proteins and fibrinolysis. Abnormality
trimester. The prevalence of uterine malformation is of this as seen in inherited thrombophilia can lead to
seen to be higher in women with second trimester thrombosis in the uteroplacentpl circulation, which
miscarriage as compared to women with first can cause recurrent miscarriage and late pregnancy
trimester miscarriages.' There is a wide range of complications.' Factor V Leiden mutation, activated
92
. Miscarriage
protein C resistance, prothrombin gene rrutation and . Screening of inherited thrombophilia should
protein C deficiency have all been shown to be also be offered to wornen with recurrent
associated with recu rrent f i rst tri rne5tef lcq-f .-1.::!, miscarriage and suspected to have
thrombophilia
Assessment of Women wittr Recumeftffi*u .
With many risk factors and assoclafud'M,i€ffions, Treatment
women with recurrent miscarriage are usually offered Women with recurrent miscarriage and their part-
a lot of investigations, even though in majority of ners are usually disturbed and can be very emo-
cases the tests will come out norrnal. Adequate tional. Therefore, adequate counselling by trained
counselling and information sharing is therefore personnel is an essential part of care of such couples.
paramount to the couple being investlgaied for Adequate information should be given to the woman
recu rrent m isca rriage. and her partner, forthem to make informed decision.
Definitive treatment of women with recurrent
. Historyof environmental riskfactor. miscarriage will depend on the identified cause of the.
. Adequate history should be obtained in all miscarriage. [t is important to mention here that in
women with recurrent miscarriage to identify majority of cases of recurrent miscarriage no cause
any environmental risk factor as well as will be identified.
symptoms that may suggest any medical
condition such as diabetes, thyroid diseases Treatment of Antiphospholipid Syndrome
and PCOS.
. Cytogenetic analysis of the product of Treat with Low Dose Aspirin and Heparin.
conception should be offered and in the Aspirin and unfractionated heparin have been shown
presence of unbalanced chi'omosomal to have significant increase in the live birth rate
abnormality the parents should have their among women with antiphospholipid syndrome.
peri phera I blood karyotypi ng. Low molecular weight heparin in combination with
. A woman with recurrent miscarriage should aspirin have similar efficacy and safety compared
also be screened for endocrine disorders. with unfractionated heparin and aspirin in the
( Haemoglobin A1c for women with dlabetes treatment of women with antiphospholipid syn-
r
I
mellitus, thyroid antibodies for thyroid drome.' lt is important to note some of the side
t
diseases and gonadotropins (LH, FSH) for effects of heparin which include bleeding, hypersen-
f
f women with suspected PCOS. sitivity reactions. thrombocytopenia, osteoporosis
I
i . Pelvic ultrasound is also indicated for women and vertebral fractures. The advantages of using low
I
with suspected uterine anomaly. molecular weight heparin are that it causes less
t Hysterosalphingography can also be offered. heparin induced thrombocytopenia and less heparin
( Where hysteroscopy 1s available, it can serve induced osteoporosis and can bd given on a daily
l-
!
!
both as diagnostic as well as for therapeutic basis. Adverse effects of pregnancies of women with
purposes. ln addition, laparoscopy alone or in antiphospholipid syndrome include recurrent
i combination with hysteroscopy can be used miscarriage, pre-eclampsia, fetal growth restriction
for diagnosis of uterine anomalies. and preterm birth. Studies have shown no improved
. Antiphospholipid syndromescreening. birth rate in the treatment with corticostetoid or
. Antiphospholipid antibodies screening immunotherapy of women with antiphospholipid
I should be offered to all women presenting syndrome and recurrent miscarriage.T
with recurrent first trimester miscarriage. The
2 antibodieS screened are lupus anticoagu- Treatmentof Women with PCOS
lant and anticardiolipin antibodies. Two The association between PCOS and recurrent
positive tests at least 12 weeks apart for miscarriage has been linked to insulin resistance and
I
lupus anticoagulant or anticardiolipin hyperinsulinemia found in women with PCOS.
i
antibodies of immunoglobulin G and/or Metformin which is an insqlin sensitizing agent is
l used for the treatment of PCOS. However, the
J
immunoglobulin M class are diagnostic of

anti phosphol i pid synd rome.'/ evidence to evaluate the effect of metformin
supplementation in pregnancy to prevent a miscar-
l
93
t'
riage in women with recurrent miscarriage is insuffi- miscarriage has been shown to have no effect and
cient.' therefore is not recommended.'
Treatment with Hormones Controversies

Treatments with progesteroneor human chorionic The management of miscarriages is associated with
gonadotrophins (HCG) supplementation have been a lotof controversies. Someof which are:
given to women with recurrent miscarriage. However,
there is insufficient evidence to evaluate the effect of
1. The use of progesterone or progestogens for the
treatment of threatened miscarriage. A lot of
either progesterone or HCG in preventing recurrent
women with threatened miscarriage are treated
miscarriage.'
with progesterone or progestogens in order to
Treatment of Women with Genetic Disorders reduce the risk of miscarriage' However there is
Patients with abnormal parental karyotype should be inconclusive evidence in the literature on the
referred to the clinical genetist, who will provide effectiveness of its use, although result of meta-
detailed genetic counseling. They should be given analysis of small studies showed the use of
adequate information regarding the prognosis of progestogens is better than placebo''
subsequent pregnancies. Recently, invitro- Multicenter randomized controlled trial ar
fertilization and pre-implantation genetic screening needed to address this controversy.
and diagnosis is offered to wornen with recurrent
miscarriage and parental karyotype abnormality. 2. Another area of controversy is in the timing and
Although studies have shown the chance of a number of repeat ultrasound to ascertain the
successful pregnancy is not better in women treated
viability of an intrauterine pregnancy. In some
instances, ultrasound is repeated within a week
with IVF and pre-implantation genetic screening and
whilst some repeat after 14 days and some may
diagnosis as compared to women with no treatment''
have repeated ultrasounds within the 2 weeks'
Treatmentof Women with Uterine Malformations Generally, it is believed that 14 days is usually
Women with congenital uterine malformation can be enough time to ascertain the viability of a foetus'
offered surgical correction. Uterine septum can be Studies are needed to actually determine the
treated with uterine septum resection either via cost effectiveness of the different timing and
laparotomy or transcervical hysteroscopy where number of rePeat ultrasounds.
available. However, there is no evidence of its benefit
in the literature and it can be associated with post- 3. The different options of management of a
operative infertility and risk of uterine scar rupture woman with miscarriage is another area of
during pregnancy.' controversy. lt is difficult to ascertain which of
the options of management is best for a particu-
Treatmentof Women with Cervical lncompgtence lar woman, especially in early first trimester
Women with history of second trimester miscarriage miscarriage. Therefore, the woman is to be
and history suggestive of cervical weakness should offered the choice of expectant, medical or
be offered cerclage. ln addition, a short cervix with a surgical management. There is the need to have
cervical length of less than 25mm detected by studies that look into the different options of
transcervical ultrasound should also be offered management and iheir psychological and
cerclage. ln majority of cases cerclage is inserted as a emotional impact on women with miscarriages'
prophylactic procedure, even though a Cochrane
review revealed no conclusive evidence that prophy- 4. There is the need to conduct more research in the
lactic cerclage reduces the risk of pregnancy loss and use of metformin in women with recurrent
preterm delivery.'u Previous failed vaginal cerclage miscarriage and PCOS. The evidence in the
and very short or scarred cervix is an indication for literature is still not conclusive
transabdomi nal cerclage' " 5. More studies are also needed to evaluate the
place of uterine surgery in women with uterine
Treatment with I mmunotheraPY malformation
The use of immunotherapy for women with recurrent
94
I
L
Miscarriage
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Farquason RG. Sponfaneous 11. LiTC, Spuijbroek MD, Tuckerman E, Anstie B,
miscarriage, Dewhurst textbook of obsfefrics Loxley M, Laird S. Endocrinological and
and gynaecology. 7'o ed. /edited by D.Keith endometrial factors in recurrent miscarriage.
Edmonds; 2007: 94-99. BJOG 2000; 107 : 1 47 1-9. 6
2. Ectopic pregnancy and miscarriage :diagno- 12. Salim R, Regan L, Woelfer B, Backos M,
sis and initial management. CG159, NICE Jurkovic D.A comparative study of the mor-
2012 phology of congenital uterine anomalies in
3. Nre/sen S and Hahlin M. Expectant manage- women with and without a history of recurrent
ment of first trimester spontaneous abortions. first trimester miscarriage. Hum Reprod
Lancet 1995;345:84-86 2003;18:162-6.
4. Wood SL & Brain PH. Medical management of 13. Ugwumadu A, Manyonda l, Reid F, Hay P Effect
mrssed abortion: a randomized clinical trial. of early oral clindamycin on late miscarriage
Obstet Gy n aeco I 2002 ; 99 (4 : 563-566 and preterm delivery in asymptomatic women
5. Verkuyl DA. Suction yersus conventional with abnormal vaginal flora and bacterial
curettage in incomplete abortion: a randomized vaginosis: a randomised controlled trial.
controlled trial. S.Afr Med.J. 1993;83: 13-15 La ncet 2003;361 r983-8.
6. Raj Rai. Recurrent miscarriage, Dewhurst 14. Bombell S, McGuireW. Cytokine
textbook of obstetrics and gynaecology. 7th ed. polymorphisms in women with recurrent
/edited by D.Keith Edmonds;2007: 100-105 pregnancy loss:meta-analysis. Aust N Z J
7. The lnvestigation and Treatment of Couples Obstet Gy n aeco I 2008 ; 48 : I 47 -5 4.
with Recurrent First trimester and Second- 15. Rey E, Kahn SR, David M, Shrier l.
tr i m este r M i sca rr i a ge G ree n-top G u ide I i ne N o. Thrombophilic disorders and fetal loss: a meta-
17 April2011. a na lysi s. La ncet 2003 ; 36 I :90 1-8.
B. Nybo Anderson AM, Wohlfahrt J, Christens f, 16. Drakeley AJ, Roberts D, Alfirevic Z. Cervical
Olsen J, Melbye M. Maternal age and fetal cerclage for prevention of preterm
loss:population based register linkage study. delivery:meta-analysis of randomized trials.
I BMJ 2000;320:1708-12. Obsfet Gynecol 2003; 102:621-7. Erratum in:
9. Kesmodel U, Wisborg K, Olsen SE
l-^
I
Obsfet Gy necol 2004; 1 03 : 20 1.
HenriksenTB. Secher NJ. Moderate alcohol 17. Gibb DM, Salaria DA. Transabdominal
intake in pregnancy and the riskof spontaneous cervicoisthmic cerclage in the management of
'
a bortion. Alcohol 2002; 37 : 87-92.
i recurrent second trimester miscarriage and
i
10. Lashen H, Fear K, Sturdee DW. Obesity is preterm delivery. Br J Obstet Gynaecol
assocrated with increased risk of f irst trimester
1995;102:802-6.
i
and recurrent miscarriage: matched
a
;'
case-control study. Hum Reprod
i
2044;N:1644-6.
h
a
I
-
95
95
CHAPTER
Ectopic Pregnancy
EY Kwawukume and BA Ekele
lntroduction KEY:
Ectopic pregnancy refers to the implantation of A = Ampullary
t-
I
l-. fertilized ovum outside the endometrium. Ectopic B: lsthmic

pregnancy is a more appropriate name than C: Fimbrial
extrauterine pregnancy because pregnancy may be D : lnterstitial (cornual)
located in the uterus and yet be ectopic, as in cervical
E: Abdominal
and interstitial pregnancies. Ectopic pregnancy is a
F: Ovarian
G: Cervical
common gynecological emergency in sub-Saharan
Africa and has become a public health problem of Combined intrauterine and extra-uterine pregnancy
epidemic proportions. lt still continues to exert its toll is very rare and occurs in approximately 0.0^ to
on human reproduction contributing to increasing 0.
0.007 percent of pregnancies '' There is a:e
morbidity and mortal ity. o.The
report from one of our units incidence of
bilateral ectopic pregnancy has not been properly
The most common site is the fallopian tube forming
documented but isolated cases have been reported
ninety-seven Q7%) percent, while two (2%) percent
in the literatureu''.
I are uterine ectopic pregnancy (interstitial). The
i
remaining lwo Q%) percent include abdominal, Epidemiology
ovarian and cervical Majority of ectopic The incidence of ectopic pregnancy in developing
I
pregnancies occur in the distal one-third of the countries is rather high as compared to developed
( fallopian tubes'. countries. lt is 1 in 24-44 deliveries in Ghana''' and
I
I lin37-43 deliveries in Nigeria'o'"'"'. ln the United
L
( Fig 1: Diagram of possible sites of Ectopic States of America the incidence is 1 in 241 deliveries
rI
I
Pregnancy. from 1 in 280 deliveries". The increase in the
r
incidence might be due to the increasing incidence of
I pelvic inflammatory disease and assisted reproduc-
I
tive techniques.
r
t
a
The most common form of presentation is ruptured
a
I
ectopic although a few cases of unruptured ectopics
are increasingly being diagnosed. The latter is largely
due to increased index of suspicion. Also the use of
transvaginal ultrasound scan has increased our
I
diagnostic yield.
)
Pathophsiology
The fallopian tube serves as the passage for the
;
97
'-_ -----:---.1
Compreherisive Gynaecology in the Topics
.,.:
sperm, ovum and zygote. The ovum passes through 2. Previous eetopic pregnancy
the fimbiial end of the tube and the fimbrial mucosa 3. Previous tubal surgery
and the cilia serve to pick up and transport the ffim a. Tubal anastomosis following
previous tubal ligation
into the fallopian tube where fertilization *ffi'$@ b, Adhesiolysis
in the ampullary site, in the inner $urka d the
4. Use of assisted reproductive techniques
lumen. The zygote spends approximately 72 hsurs
before it is transported tothe isthmus of thetube,
5. IUD use. Most pregnancies conceived with
IUD in-situ are likely to be ectopic. This is
probably due to the relative efficiency of the
When eetopic embryo outgrows its blood gupply, four
device in preventing intrauterine gestations
different processes may occur. There is formation of a
rather than from a direct relationship of the
tubal blood mole, in which the blood flows around
IUD to ectopic gestation,
the chorionic sac, over distend the tube and leads to
intraluminal rupture of the sac into the tube, On the
6. Exposure to diethylstilbestrol (DES).
other hand, there may be tubal abortion of the tubal Dlagnosis of ectopic pregnancy
blood mole through the fimbriated end of the tube, Features generally depend upon the evolution of the
either completely or incompletely into the abdominal pathology. From the asymptomatic state of the
cavity. Thirdly, there may be re-absorption Ef the unruptured early ectopic gestation; chronic pelvic
conceptus as a result of either erosion of ehorionic pain in the slow leaking variety to sudden collapse of
villi or mechanical over-distention of the tube. ae ute ruptured ectopic gestation.
Normally the fetilised ovum eventually reaehes the
uterus in about 80 hours. Any woman of reproductive age presenting with
pelvie pain or bleeding should have ectopic preg-
Majority of ruptured ectopic gestation oceurs in the nancy ruled out. Lower abdominal pain and a period
ampullary site, probably because the tissue between oJ amenorrheea are the most common symptoms of
the lumen of the tube and the serosa is comBosed of ectopic pregnancy, therefore adequate history of
loose adventitia and represents the path of least abnormal bleeding that may occur at the expected
resistance. Expansion of the zygote in the ampullary time of menses should be taken. Most patients might
portion results in tubal damage and destruction by interpret abnormal bleeding as menses and the
the invasive trophoblast. Pre[lnancy continues at this diagnosis of ectopic gestation may be missed. Major
site and the developing villi might erode into the bleeding is uncommon but the amount, timing and
blood vessels resu lti ng in.bleeding. character of the bleeding should not obviate the
possibility that ectopic pregnancy could be the
The isthmus portion of the tube has different ana-
diagnosis.
iomic features. The tissue between the epithelium of
the lumen and the serosa is compact, composed Few patients present with atypical picture of ectopic
mostly of muscularis. This compact structure pregnancy and presentation might be variable,
prevents the ectopic pregnancy from eroding into the
ranging from asymptomatic patient to dizziness or
space between the serosa and the tubal epithelium. syncope to the patient in hypovolemic shock. A slow
The zygote develops within the lumen of the tube leaking ectopic pregnancy with pelvic hematocoele
itself causingdestruction of the lumen. might present with pain on defecation, the so called
'bathroom sign'.
Risk factors
1, Pelvic inflammatory Disease (PlD) Clinical signs include lower abdominal tenderness,
o Tuhalfibrosis
palpable pelvic mass and positive cervical excitation
. . Scarring of intraluminal structures
tenderness. Distended abdomen might be due to
o Altered cilia
haemoperitoneum with shoulder pain which is
. . Abnormaltubo-muscularaction
. Chronic pelvic infection
referred pain from haemoperitoneum causing
. Narrowing of the tube, this may result in irritation of the diaphragm,
transport dysfunction because of tubal
constriction.
98
Ectopic PleSnancl
Ditferential diagnosis suggest the possibility of an eftra-uterine

1. Normal intra-uterine pregnancy gestation'0.
2. Pelvic inflammatory disease (PlD)
3. Ruptured ovarian cyst r ,,: l However, a meta-analysis has con rm6'd that a
4. Threatened or incomplete affiffi, single b-hCG level cannot be used in isolation to
5. Degenerating uterine fibroldr . predict an ectopic pregnancy'u.
6. Bleeding corpus luteuftl ef,''s normal
i ntrauteri ne pregnaRcy The initial serum b-hCG level is a keyprognostic
7. Appendicitis indicator for the success of conservative manage-
8. Endometriosis ment (expectant and medical) in cases of ultrasound
9. Dysfunctional uterine bleeding visualised tubal ectopic pregnancies'u.
Pelvic lnflammatory Disease (PlD) is the most 2. Progesterone Assay. Serum progesterone assay is
common condition confused with ectopic pregnancy,
no longer useful in predicting ectopic pregnancy ".
especially when PID is associated with anaemia.
Pelvic lnflammatory Disease is not seen in preg- 3. Ultrasound Scan. The sonographic evaluation of
nancy because the decidua and membranes effec- ectopic pregnancy should begin with a
tively seal off the uterine cavity preventing organisms transabdominal scan to assess for any masses that
from ascending. Therefore, if a patientof reproductive might be out of the plane of vaginal transducer.
age presents with amenorrhoea and signs arld Transvaginal ultrasound scan is superior to abdomi-
symptoms akin that of PlD, think of ectopic preg- nal scan in the diagnosis of ectopic pregnancy.
nancy and investigate as such. A high level of
suspicion is needed to diagnose ectopic gestation. Transvaginal ultrasound is the diagnostic tool of
".
choice for tubal ectopic pregnancy
Laboratory Diagnostic Tests
1. Serial values of human chorionic gonadotropin can Tubal ectopic pregnancies should be posil ely
be measured in the serum within 8-12 days after identi ed, if possible, by visualising an adnexal x
fertilization. that moves separate to the ovary (Figures 2 and 3).
. Serum b-subunit of HCG is positive in 100%
of ectopic pregnancies Fig 2: Transvaginal ultrasound picture of unruptured
' Urine pregnancy test for HCG is positive in ectopic pregnancy.
only 50% of cases with proven ectopic
gestation
. The serum HCG level doubles every 2 days in
a normal pregnancy, which does not occur in
ectopic and blighted ovum pregnancies.
. At a discriminatory zone of about 6,500
mlU/ml of HCG an intrauterine gestational
sac should be seen by an abdominal ultra-
sound at 42 days of gestation. HCG value of
1,000 mlU/ml (some authorities use 1,500)
at 35 days of gestation with a transvaginal
ultrasound scan is also diagnostic. Failure to
detect fetal echoes within the uterus should
I
i
/
i
99
Figure 3:Unruptured ectopic pregnanc!; First arrow shows gestation sac with fetal pole
outside the uterus; Second arrow is on the bulky empty uterus with pseudodecidual reaction
The majority of tubal ectopic pregnancies should be An empty extrauterine gestational sac will be present
visualised on transvaginal ultrasound. Transvaginal in around 2O-4O"/. of cases. While an extrauterine
ultrasound has reported sensitivities of 87 .O-99.0% gestational sac containing a yolk sac and/or
and speci cities of 94.0-99.9% for the diagnosis of embryonic pole that may or may not have cardiac
ectopic pregna ncy'u'
.s' 20' 21' 22
. The majority of ectopic activity will be present in around 75-20% of cases"'
pregnancies will be visualised on the initial
u ltrasound exami nation"''0. Free uid is often seen on ultrasound, but is not
diagnostic of ectopic pregnancy. A small amount of
A non-homogeneous or noncystic adnexal mass is the anechoic uid in the pouch of Douglas may be found
most common nding in around 50-60% of cases. in both intrauterine and ectopic pregnancies.
100
Ectopic Pregnancy
Echogenic uid has been reported in 28-56% of treatment include: haemodynamically stable, beta
pregnancies26'27 . lt may sign,ify'tutial rupture,
ectopic HCG less than 3000 lU/1, gestation sac on
ultrasound less than 4cm, no contraindication for the
* mbrial end of thefallopian tube. ' :i. use of methotrexate and patient is compliant with
.": follow-up visits.
4. It is important to advice such patients to avoid sexual
Diagnostic laparoscopy - used'tE
standard when in doubt of the diagnosis. intercourse during treatment and take some form of
Laparoscopy is no longer the gokf=il$fiGidttfur contraception for three months after methotrexate
diagnosis. Fa lse-negative lapa roscopies' (5.0-4. 5%) treatment
have been reported when the procedure isperformed
SurgicalTreatment
too early in the development of an ongoing ectopic
pregnancy"''n.
1. Radical surgery in ruptured ectopic
pregnanc!: Salpingectomy. This is the most
Treatment common surgery in our hospitals. The whole
Ectopic pregnancy can be managed using expectant, tube is removed.
medical or the surgical approach. Unfortunately, 2. Conservative surgery with unruptured
most of the cases seen in the West African sub-region ectopic pregnancy.
a. The pregnancy is milked from the
I have already ruptured and are therefore treated by
surgery in most of our hospitals.
fimbrial end of the tube. lt must
however be noted that failure rate can
We need massive public health education for our be high due to persistence of
women to report to health care centres as soon as trophoblastic tissue.
they miss their menses. Early treatment can then be b. Linear salpingostomy, either by
started and attempt can be made to utilize the least laparotomy or laparoscopy, even if the
invasive method to manage the disease and conserve tube is dilated as much as 4cm ". This
fertility if desired. is usually done for ampullary ectopic
pregnancies. A linear incision is made
Expectant Treatment: on the antimesenteric side of the tube
Expectant management is based on the assumption with a scalpel, electrocautery, carbon
that a significant proportion of all tubal ectopic dioxide or argon laser, The products of
?
pregnancies will resolve through regrlffiln or tubal conception a re extruded, a nd
i abortion without apy treatment. t'nti option is haemostasis is achieved. This
suitable for patients that are haemodynamically technique is employed if the tube is
{ stable and asymptomatic. Other criteria for expectant going to be allowed to heal by
l. secondary i ntention'0.
management include beta HCG level less than 1000
I
lU/L and dedicated unit with facilities available for
I
( trans-vaginal scan and beta HCG monitoring. Cervical Ectopic Pregnancy
r Cervical pregnancies arerare IFigure 4J, accounting
Subsequent pregnancy rate is as high as 80%'0.
I
t
Medical Treatment for less than 1% of all ectopic gestations'u. De ned
i Many agents have been used to medically treat a criteria have been described for diagnosing cervical
i
t carefully selected sub group of patients with ectopic ectopic pregnancies'u't'.
I pregnancy but the most popular is methotrexate.
I
I
I Methotrexate is a folic acid antagonist and it inhibits The following ultrasound criteria have been
( described in the diagnosis of cervical ectopic
F DNA synthesis in trophoblastic cells. lt can be
pre$nanc!:
administered as a single intramuscular injection 3' or
I
t
r in a multiple fixed dose regimen calculated from the
r 1. Empty uterine cavity. 2. A barrel-shaped cervix. 3.
patient's body surface area as 50 mg/m' . ln one of
( A gestational sac present below the level of the
our units, 2 doses bf methotrexate are given 48 hours
I internal cervical os. 4. The absence of the 'sliding
f. apart once the criteria for medical treatment are met
( sign'. 5. Blood ow around the gestational sac using
,t
with very good outcome ".The criteria for medical
colour Doppler.
I
I
I
I 101
;
f
The'sliding sign' enables cervical ectopic As it can be dif cult to distinguish ovarian ectopic
pregnancies to be distinguished from
miscarriages pregnancies from corpus luteal cysts, tubal ectopic
that are within the cervical canal. When pressure is pregnancy stuck to the ovary, a second corpus
applied to the cervix using the probe, in a luteum, ovarian germ cell tumours and other ovarian
miscarriage, the gestational sac slides against the pathologies, diagnosis is usually con rmed
endocervical canal, but it does not irr an implanted surgically and h istological ly.
cervical pregnancytt.
Abdominal Pregnancy
Figure 4. Cervical Ectopic Pregnancy Abdominal gestation is also rare but probably the
most serious of the extra-uterine gestations. lt can be
classified as primary or secondary' Most abdominal
pregnancies are secondary, resulting f rom early tubal
absrtion or rupture and subsequent implantation of
the pregnancy into abdominal structures.
Primary abdominal pregnancy must satisfy the thr"-

oo.
critical defined by Studderford
1. Both tubes and ovaries must be in normal
condition with no evidence of recent or
remote injurY
2. No evidence of uteroperitoneal fistula should
be found
Ovarian Pregnancy 3, The pregnancy must be related exclusively to
Ovarian pregnancy is rare and for diagnosls one must the peritoneal surface and must be early
satisfy Spiegelberg's criteria as: enough in the gestation to eliminate the
1. The tube, including fimbria ovarica, must be possibility of secondary implantation
intact following primary implantation in the tube.
2. The gestational sac must occupy normal
ovarian position Diagnosis of Abdominal PregnancY
3. The sac must be connected to the uterus by . Historyof recurrentabdominal discomfort
the utero-ovarian I igament . Fetal movement beneath the abdominalwall
4. Ovarian tisque must be identified . Presence of fetal movements high in the
histologically in the wall of the gestational upper abdomen
SAC . Cessation of fetal movement
. Vomiting late in Pregnancy
There are no speci c agreed criteria for the . Fetalmalposition
ultrasound diagnosis of ovarian ectopic pregnancy' . Closed and uneffaced cervix
Findings suggestive of an ovarian ectopic pregnancy . Hysterosalpingography if the uterus can be
on transvaginal ultrasound with an empty uterus are palpated differently from the fetal parts'
a wide echogenic ring with an internal anechoic area . Failure of oxytocics to stimulate the
on the ovary. A yolk sac or embryo is seen less gestations mass
commonlytt'". lt is not possible to separate the cystic . Abdominal x-ray with fetal small parts in the
structure or gestational sac from the ovary on gentle lateral position overlying the maternal spine.
palpation (negative sliding organ sign). The corpus . Ultrasonography isthe most reliable'
luteum should be ldenti ed separate from the
suspected ovarian pregnancy. Colour Doppler may
aid detection of a fetal heart pulsation within the
ovary. A complex echogenic adnexal mass with free enhanced bY the balloon of FoleY
uid in the pouch of Douglas can represent a catheter in the uterus)o'
ruptured ovarian ectopic pregnancy.
t02
Ectopic Pregnancy
.
diagnostic facilities are readily available, vaginal
empty uterus. examination in women with suspected ectopic
pregnancy is of little value and it should not be
Managementqf Abdominal Pregnanef :'' routinely employed' (Dewhurst 20 1 2 edition) !
{ Abdominal pregnancy is not uncommon in the
ffim poor
developing countries"'o'. Fetal outconre ig ll.
Paracentesis abdomrnrs (abdominal tap) or
with eongenital malformations like'faeiat and jsint culdocentesrs i n ectopic pregna ncy.
deformities, torticollis and hypoplasla of the Paracentesis abdominis or culdocentesis has a place
extremities. in the diagnosis of ectopic gestation especially in
areas where radiological or ultrasound support is noi
Management of the plaeenta remains controvqrsial. available in a timely fashion. However, it has been
ln one of our units, after delivery of the baby, the cord argued by some authors that it is unwise to perform
is clamped leaving the placenta in -situ. The the procedure if autologous blood transfusion is
abdomen is then closed. A corrugated drainage or a anticipated in the patient. ln centers with accurate'
self-retaining catheter is left in the peritoneal eavity serum HCG values and trans-vaginal ultrasound
and the patient is given a broad spectrum antibiotic probe, abdominal tap is less frequently used.
cover. Some authorities would administer Culdocentesis is said to be positive if non-clotting
methotrexate to hasten trophoblastic degeneration. blood is aspirated. The blood obtained is non-
Pregnancy after the wound is completely healed is clotting because there is lysis of blood ihat has
encou ragi ng a nd patients ca n del iver vagi nal ly. clotted previously. lt should also be noted that un-
elotted blood in the Pouch of Douglas does not mean
Sometimes, if the placenta is not attached to any vital that ectopic pregnancy has ruptured this could be
structure the whole placenta can be removed after bleeding from ruptured corpus luteum or any
clampingoo and it is also easierto removethe placenta abdominalorgan.
if there is alreadyfetal demise. ln fact that isthe more
common experience in the second unit! lll. Autologous Blood Transfusion
lntra-operative blood salvage is one of the four
Discussion and Controversies modes of autologous blood transfusiOn. The others
are pre-deposit, intra-operative haemodilution and
l. Demonstrating shifting dullness in ruptured postoperative salvage. Autologous transfusion
ectopic gestation? procedure is not new in some of our hospitals ou but
The act of demonstrating 'shifting dullness' or fluid proper documentation has not been done to
thrill in a patient with ruptured ectopic pregnancy as ascertain its merits and demerits in modern medical
/ often reported in Casebooks submitted for post practice. Autotransfusion of blood can be
graduate examination by trainees is very disturbing. lt accomplished by using a simple system consisting of
is either not a true report or an unkind (wicked) act if a blood collectingdevice, an in-linefiltersystem, and
truly done. The excruciating tenderness associated a container for anticoagulation, usually with citrate
with acute or ruptured ectopie gestation is such that phosphate dextrose.
the patient would not permit sue h an exercise except
she was deeply comatose! ln fact that aspect of the There are various equipment for collecting, washing
abdominal examination should be completely and filtering shed blood before reinfusion. Some of
avoided in modern practice. Similarly, aggressive these are Cobe Cell Saver, Solcotrans Plus and lD set.
internal examination is very unpleasant for women The last two do not incorporate washing, are
even with those with normal intra-uterine gestation relatively simple and suffice for clean flowing blood
talk more of those with ectopic pregnancy. Some as seen in ectopic pregnancies. However, if there is
authors have therefore argued rightly that the cellular debris, fat and other contaminants in the
/ application of significant pressure on a tube swollen operative field, washing is recommended.
t with an ectopic pregnaney during such an
I examination could facilitate tubal rupture '. ln The principles involved in intraoperative blood
modern clinical practice, where ultrasound salvage are as follows:
a
r
I
I 103
r
Shed blood is suctioned at 80-100mm HG hospital or national protocol to all RhD-negative

into a bag containing anticoagulant, citrate women who have surgical removal of an ectopic
or heparin in a ratio of l:7 to 1:10 citrate to pregnancy, or where bleeding is repeated, heavy or
blood. associated with abdominal pain.
The anticoagulated blood is filtered using a
40/60 -micron blood filter , ,: V. What support and counseling should be offered to
The filtered anticoagulated blood is re- women undergoing treatment for ectopic
infused using a blood givingset pregnancy?
Women should be advised, whenever possible, of the
The main dangers about autologous transfusion are advantages and disadvantages associated with each
i
infection and possible amniotic fluid embolism. approach used for the treatment of ectopic
However, the necessary infection prevention pregnancy, and should participate fully in the
technique should be practiced to make transfusion selection of the most appropriate treatment.
safe and beneficial. ln addition, old clotted blood
should not be transfused and haemoperitoneum Vl. What are the long-term fertility prospects
should be properly sieved before transfusion. Blood following an ectopic pregnancy?
could be taken for cutture and sensitivity and patient ln the absence of a history of subfertility or tub-.
should be given broad-spectrum antibiotic as pathology, women should be advised that there is no
prophylactics. difference in the rate of fertility, the risk of future tubal
ectopic pregnancy or tubal patency rates between
It has been argued that if autologous transfusion is the different management methods.
mastered and practiced according to standard
protocols, diseases such as HlV, hepatitis and other Women with a previous history of subfertility should
blood related infeciions could be prevented. be advised that treatment of their tubal ectopic
pregnancy with expectant or medical management is
lV. Do rhesus D (RhD)-negative women with an associated with improved reproductive outcomes
ou.
ectopic pregnancy require anti-D immunoglobulin? compared with radical surgery
It is recommended to offer anti-D prophylaxis as per
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20. Atri M, Valenti DA, Bret PM, Gillett P Effect of 32. Ekele B A and Audu L R. Medical treatment of
transvaginal sonography on the use of invasive e cto p i c p re gn anI m eth otrexa te.
cy u s i n g p a re n te ra
' procedures for evaluating patients with a clinical West African Journal of Medicine, 2001; 20G):
dragnosrs of ectopic pregnancy. J Clin Ultrasound 181-183.
2003;31:1-8. 33. Vermesh M, Silva E et al: Management of
I
21. Braffman BH, Coleman BG, RamchandaniE Arger unruptured ectopic'gestation by linear
PH, Nodine CE Dinsmore BJ, et al. Emergency sa I p i n gostomy : A p rospective ra nd om i zed c I i n i ca I
department screening for ectopic pregnancy: a trial of laparoscopy versus laparotomy Obstet
"I05
Gynaecol1989;.73(Pt1):400byballoonofFoleycatheter.Actaobstetriciaet
34. DeCherney AH, Kase iurgical Gynecologica Scandinavica 2OO5; 84 (7): 701-
rV; The conservative
ObstetGynaecol. 1979;54:451. ', ., 42. Sunday-Adeoye l, Twomey D, Egwuatu EV, Okonta

35. ushakov FB, EtchatalU, AcemanPJ, ScfteffirlG. Pt. A 3}-year review of advanced abdominat
Cervical pregnancy: past and future, OFsfef pregnaQcy at the Mater Misericordiae Hospital,
GynecolSurv1997;52:45_59.Akpo,southeasternNigeriafi976_200O,Arch
36. Jurkovic D, Hacket E, CampbellS. Diqgnosls and GynecolObstet20j.l;283:19-24.
treatment of early cervical pregnanc!: a reltiew 43. Opare-Addo HS, Deganus S. Advanced abdominal -
and a report of two cases treated conservatively. .pregnanc!: a study of 13 consecutive casesseen f
lJttrasoundObstetGynecollgg6;8;373-80. in 1993 and 1994 at Komfo Anokye Teaching :
37. Timor-Tritsch lE, Monteagudo A, Mandeville EO, Hospital, Kumasi, Ghana. Afr J Reprod Health
Peisner DB, Anaya GE Pirrone EC. Successfu/ 2000;4:28-39. :
managementof viablecervicalpregnancybylocal 44. lsah AY Ahmed Y, Nwobodo El, Ekele BA.
injection of methotrexate guided by transvaginal Abdominal pregnancy with full term live fetus -
ultrasonography. Am J Obstet Gynecol 1994; case report. Annals of African Medicine, 2008;
170:737-9. 7(4): 198-99.
38. Comstock C, Huston K, Lee W. The Selo-OjemeDO \
ultrasonographic appearance of ovarian ectoplc 45.', Feyi-Waboso PA. Sa/vage autotransfusion t"..
pregnancies. ObstetGynecot 2005; L05:42-5. yersus homologous blood transfusion for iuptured
39. Shtau CS, Hsreh Cl" Chang MY. Primary ovarian ectopic pregnancy. lnlJ9ynaSep!_gbstet 2007;
pregnancy.lntJGynaecolObstet2OOT;96:127. 96(2):108-11.
40. Studderford WE. Primary peritoneal pregnancy, 46. Kirk E, Condous G, Van Calster B, Van Huffel S,
Am J Obstet Gynaecol 1942; 44: 487. Timmerman D, Bourne T. Rationatizing the fotlow-
41.EkeleBA,AhmedYNnadiDCandlshakuK.upofpregnanciesofunknownlocation.Hum<
Abdominal Pregnancy: ultrasound diagnosis aided Reprod 2007; 22:1744-SO.
106
cHAPTER
I
Vulvovaginitis
l. O. Koranteng, R. Acquaah'Arttin, E.Y. Kwawukume
INTRODUCTION Vaginal discharge is mainly composed of water with

. electrolytes, microorganisms, epithelial cells, and
Vulvovaginitis, also known as infectious vaginitis or organic compounds such as fatty acids, proteins,
vaginitis, is an inflammation of the vagina and and carbohydrates.'Vaginal fluid is largely derived
possible vulva. lt can result in discharge, itching and from serum transudate in. vaginal beds that seeps
pain, and is often associated with an irritation or from capillaries through intercellular channels.
4 infection of the vulva. lnfected women may also be Smaller amounts of fluid are derived from Bartholin's
asymptomatic. glands, cervix, endometrium, and fallopian tubes.
Cellular elements represent sloughed cells from
It is usually due to infection.Traditionally, the 3 cervical columnar and vaginal squamous
classic entities of vaginitis include bacterial vaginosis epithelium. White blood cells are presdnt only in
(bacterial), vaginal candidiasis (fungal), and smal I numbers, among women without vagi nitis.
I
trichomoniasis (protozoal). A woman may have any

combination of vaginal infections at one time. Estrogen and the pH are two irhportant factors that
influence the types of bacteria present in the vaginal
Vulvovaginitis affects all age groups from flora. Vaginal lactic acid content provides an acidic
premernacheal to the postmenopausal. lt can result pH of less than 4.5 in adult women. Lactic acid is
in a lot of psychological imbalances to the patient produced from the metabolism of Lactobacillus and
especially if the correct diagnosis has not been made by vaginal epithelial cells through the breakdown of
and different medications are prescribed for recurrent glycogen. The low pH favours the growth of
7
conditions. acidophilic organisms such as Lactobacillus, but it
!
inhibits the growth of most other bacteria.
PHYSIOLOG ICAL VAG I NAL DISCHARG E
Lactobacillus appears central in limiting the growth
of other bacteria.'Lactobacillus are also capable of
About 70% of women with complaints of a vaginal
producing lrOr,' which inhibits the growth of
discharge have a physiologic increase in the amount
of normal cervical mucus or normal vaginal fluid bacteria that do not contain catalase. The
combination of a halide ion such as chloride present
exudate. Women with a physiologic discharge usually
in abundance in the vagina with peroxidase, present
have no vulvar abnormality and a white floccular
(clumpy) vaginal discharge. The discharge is very in endometrial and vaginalfluid,a and HrO, produced
by certain strains of Lactobacillus forms a potent
thick, and it tends to pool in the inferior portion of the
inhibiting system for certain bacteria in the vagina
vagina. The vaginal and cervical epithelial surfaces
and of HIV and othervlrus in vitro.l
are a normal pink colour.'The pH of normal discharge
{ is usually less than 4.5, and there is no amine odour
i
when KOH is applied.
t07
I Comprehensive Gynaecalogy in the Topics
NORMAL VAGI NAL M ICROORGAN ISMS Less common causes include; atrophic vaginitis with
secondary bacterial infection, foreign body with
The normal vaginal flora consists of gram positive secondary bacterial infection, HIV-associated
rods, predominantly aerobic lactobacilli sp e.g. idiopathic vaginal ulceration, allergic contact
doderlein's bacilli which forms 62-887o, gram dermatitis, desquamative inflammatory vaginitis,
positive cocci such as staphylococcus epidermidis, Psoriasis, erosive lichen planus, traumatic
staphylococcus aureus, beta-haemolytic dermatitis, dermatitis artifacta, Reiter's disease,
streptococci and Gardnerella vaginalis. Also present Bechget's disease and Pemphigus vulgaris.
are gram-negative organisms such as Escherichia
coli and klebsiella. ln addition, there are anaerobes CANDIDIASIS
such as bacteroides and peptococcus. Other
organisms, candida and mycoplasmas, are also Candida albicans causes 80% to 90% of vaginal
commonly seen.t fungal infections, and other Candida species;
Candida glabrata, Candida tropicalis and Candida
M ECHAN ISMS OF VAGI NAL I NFECTION krusei, cause the remai nder.'
When the complex balance of microorganisms lmmunosuppression from HIV infection is associated
changes, potentially pathogenic endogenous with candidiasis and increased rates of esophageal
microorganisms that are part of the normal flora, and perhaps vaginal Candidiasis. Uncontrolled
such as Candida albicans in cases of candidiasis and diabetes, pregnancy and hormone replacement
G. vaginalis and anaerobic bacteria in cases of BV, therapy are associated with candidiasis, particularly
proliferate to a concentration that causes symptoms. with unresponsive infections.
Little is known about factors that contribute to the
overgrowth of normal flora. Pathogenic exogenous Candidiasis is common in women of childbearing
sexually transmitted microorganisms such as age. Pruritus is the most common symptom. This is
Trichomonas vaginalis, N. gonorrhoeae, and C. accompanied by a thick, odourless, white vaginal
trachomatis can also cause infection. discharge (with an appearance similar to that of
cottage cheese), which can be minimal. Usually,
CHANGING PH LEVELS OF THE VAGINA associated vulvar candidiasis is present, commonly
with vulvar burning, dyspareunia, and vulvar dysuria
Before birth and for several days afterward, the (a burning sensation arising when urine comes into
neonate has a high oestrogen levels acquired from contact with vu lva r ski n ).
the mother. Vaginal pH'iat birth is 4.b-4.5 and this
persists up to four weeks after delivery. The flora at Symptoms of candidiasis often begin just before
birth is mixed but lactobacilli, which are the most menses. Candidiasis is usually not contracted from a
common bacteria, soon become predominant. Blood sexual partner.
oestrogen levels decline slowly and the epithelial
cells exfoliate with thinning of the epithelium. Physical findings in vaginal candidiasis may show a
Cellular glycogen is also lost and vaginal acidity well-demarcated erythema of the vulva with satellite
decreases to pH 6.0-7.5. Staphylococcus, lesions (discrete pustulopapular lesions) surrounding
streptococcus and coliforms are also present but the redness. The vulva, vagina, and surrounding
hypo oestrogenism persists until puberty. The vaginal areas may be edematous and erythematous,
epithelium gradually begins to thicken and glycogen possibly accompanied by excoriations and fissures. A
increases. Lactobacilli is then re-established and thick, adherent, cottage cheese-like vaginal
acidiiy approaches normal adult level of 3.8 to 4.2.6 discharge may be seen. The cervix usually appears
normal.
ETIOLOGY
TRICHOMONIASIS
The three common infections are Candlda sp (yeast,
Monilla), Trichomonas vaginalis and Bacterial T. vaginalis infection, the third most common cause
vaginosis. of vaginitis, is caused by trichomonads. T vaginalis is
108
Vulvovaginitis
an oval-shaped or fusiform-shaped flagellated cervix, or colpitis macularis, is highly specific for

protozoan that is 15 pm long (the size of a leukocyte). Trichomonas infection, and 2-5% of patients will
have this finding on examination.
T. vaginalis is a ubiquitous, sexually transmitted,
anaerobic parasite. T. vaginalis has been associated Because diagnosis o'f Trichomonas infection on the
with vaginitis, atypical cytologic smears, and other basis of clinical signs and symptoms is unreliable,
sexually transmitted infection. Up to one ha{f of laboratory confirmation is mandatory.
women with gonorrhea also have trichomoniasis.t
lnflammation caused by Trichomonas may increase BACTERIALVAGINOSIS
the transmission of HlVtwofold to threefold.e
BV is the most common cause of vaginal infection.
T. vaginalis is exclusively transmitted by sexual BV appears to cause upper genital tract infection,
intercourse. The organism exists in the vagina, which contrasts with other forms of vaginitis, and
urethra, bladder, and Bartholin and Skene glands. this trait further confirms the importance of BV. BV
lnfection is most common in young, sexually active could be caused by an overgrowth of certain bacteria
women, particularly with a new partner. A significant in the vagina, but it could also be caused by the
number of men carry the organism for a prolonged failure of Lactobacillus to provide an inhibitory
time, although some men are cured without control over other vaginal flora. The end result is an
treatment. overgrowth of potentially virulent microorganisms in
the vagina that causes the increased vaginal
T. vaginalis elicits a cellular and humoral immune discharge and odour and an increase in upper genital
response. However, these responses do not protect tract infection.Bacterial vaginosis is caused by an
against repeated infection, which are common. overgrowth of organisms such as Gardnerella
vaginalis (a gram-variable coccobacillus),
Many patients with Trichomoniasis (20-50%) are Mobiluncus species, Mycoplasma hominls, and
asymptomatic. lf discharge is present, it is usually Peptostreptococcus species. While the infection
copious and frothy and can be white, gray, yellow, or involves a number of bacteria, it is believed that most
green (the yellow and green colors are due to the infections start with Gardnerella vaginalis creating a
presence of white blood cells tWBCsl). Local pain biofilm, which allows other opportunistic bacteria to
and irritation are common. Dysuria (2O%), pruritus thrive.'o Risk factors include pregnancy, intrauterine
(25%), and postcoital bleeding due to cervicitis are device (lUD) use, and frequent douching.
other possible symptoms. Symptoms often peak just
after menses. Bacterial vaginosis is asymptomatic in up to 50% of
women. lf a discharge is present, it is typically thin,
Trichomoniasis is associated with risk factors for homogeneous, malodorous, and grayish white or
other STDs; accordingly, a history of multiple sexual yellowish white in color. Vaginal pain or vulvar
partners should be elicited. lnfection during irritation is uncommon. Pruritus mayoccur.
pregnancy has been associated with preterm
deliveries and low-bi rth-weight infants. Bacterial vaginosis is common in pregnant women
and is associated with preterm birth. ln pregnant
Trichomoniasis is rare in prepubertal children. Sexual women with symptomatic bacterial vaginosis who
abuse should be suspected if symptoms are present. have a history of preterm birth, administration of
Symptoms include a copious frothy discharge, local treatment early in pregnancy has been shown to
pain, irritation, and, occasionally, pruritus. decrease the incidence of preterm birth.
ln trichomoniasis, the vulva may appear Physical findings in bacterial vaginosis include a
erythematous and edematous, with excoriation. Look homogeneous, frothy vaginal discharge that is
for a copious, frothy, homogeneous vaginal discharge grayish-white to yellowish-white in color. The
that can be white, gray, yellow, or green. Small discharge appears adherent to the vaginal mucosa.
I
punctate cervical and vaginal hemorrhages with Typically, no underlying erythema exists. As many as
ulcerations may be observed. So-called strawberry
109
50% of women with bacterial vaginosis are The clue cell is a vaginal epithelialcell to which such
asymptomatic. a large number of bacteria aftach that the cell border
is obscured and has a serrated appearance. ln
Bacterial vaginosis can be diagnosed if 3 of the women with BV 5%b 5A"/" of the vaginal epithelial
following4 Amsel criteria are present (seeWorkup).i cells are clue cells.
. Homogeneous, white, adherent diBeharge
r Vaginal pH higherthan 4.5 GRAM STAIN
. Amine (fishy) smell from vaginai distharge
when potassium hydroxide (KOH) is added Vaginal Gram stains can be used in place of the wet
(whiff test) mount to detect WBCs, predominant bacterial flora,
. Clue cells on wet mount and yeast forms. The Gram stain is not useful for
detecting trichomonads. Patients with BV have a
DIAGNOSIS predominance of small grarrr-negative bacillus flora
(e,g. Gardnerella spp,, anaerobes) and a relative
pH
absence of large gram-positive bacillus (e.g.
Simple office analysis of the vaginal discharge is
Lactobacillus morphotypes. The Gram stain is more
helpful and inexpensive. Results allow the placement
sensitive than the wet mountto identify Candida.
of patients in one of the two major diagnostie
categories of normal discharge/candidiasis if the pH
VaginalCultures
is normal or BV/trichomoniasis/desquamative Vaginal bacterial cultures are of limited benefit to
vaginitis if the pH is elevated. The pH paper should diagnose vaginitis. Cultures should be used only in
have a range between 4 and 6. The pH should be specific circumstances. Cervical tests for N.
tested by placing a drop of the vaginal discharge on gonorrhoeae and C, trachomatis should be obtained
pH paper or rubbing the paper on the vaginal wall. for any woman with a purulent cervical exudate.
Cervical mucus must be avoided, because it has a Gonorrheal and chlamydial infections are also
basic pH. A normal pH virtually excludes BV. common among women with trichomoniasis. DNA
detection tests (i.e. polymerase chain reaction or
AMINE ODOUR
ligase chain reaction) are the most sensitive and
available."
A drop of 10% potassium hydroxide (KOH) mixed
with normal vaginal fluid on a glass slide does not
Vaginalcultures for Candida organisms are usefulfor
produce an odour." A fishy trimethylamine odour
women with suspected candidiasis but normal KOH
occurs in women with BV and in many women with
preparation results. Candi.da cultures should be
trichomoniasis. The fish odour is caused by the
obtained from women without hyphae on the KOH
volatilization of mostly trimethylamine, which is a by-
smear who have pruritus, an erythematous vulvar
product of anaerobic metabolism.
rash, vulvar fissures, or white vulvar plaques and
from those unresponsive to antifungal medication.
Microscopic Analysis of wet mount
An approximately 1:4 ralio of vaginal discharge to
Trichomonas cultures on Diamond's media can be
normal saline is mixed on a glass slide and covered
obtained in cases of a purulent vaginal discharge
with a coverslip to make a saline wet rnount. A larger
when repeated microscopic examinations fail to
Zl ratio of vaginal discharge to 10% KOH is mixed, identify the organism. Wet mounts identify only 50%
the amine odor is smelled, and the sample is covered
with a coverslip to make the KOH wet mount. The
to 7O% of asymptomatic women with
trichomoniasis.13
microscopic examination should be performed within
a few minutes of preparing the slide.
However, these cultures are not readily available in
many cl i n ical setti ngs.
Hyphae is identified in patients with candidiasis, clue
cells are found in patients with BV and oval-shaped Vaginal cultures for G. vaginalis, other normal
or fusiform-shaped flagellated motile trichomonads vaginal flora bacteria, or genital mycoplasmas are of
are seen in patients with trichomoniasis.
almost no benefit to diagnose vaginitis. G. vaginalis
110
Vulvovaginitis
are isolated from about 50% of asymptomatic Regimens for pregnant women with bacterial
women without vaginitis so their presence csrrelates vaginosis include the following:
poorly with vaginitis and BV. o Metronidazole 500 mg orally twice a da,y tor
7 days
. Metronidazole 250 mg orally 3 times a day
torT day
Treatment of vaginitis may include sitz baths and . Clindamycin 300 mg orally twice a day for 7
instruction regarding proper toilet and hygiene day
techniques. Many women assume vaginal symptoms
are the result of a sexually transmitted disease ($TD), Pregnant women should have a follow-up visit 1
which is often not the case. A patient's idea of vaginal month after completion of treatment.
normality may be inaccurate and result in increased
or unnecessary treatment seeking. Also educate Treatment regimensin patients with HIV are the
patients regardi ng the following: same as in patients without HIV but bacterial
. Avoiding irritants in the vaginal area, such as vaginosis appears to be more persistent in women
perfumes, soaps, and panty linErs, among who are HIV positive.
others,
. After swimming or exercise, whieh keeps the Therapy is not recommended for male partners, but
vaginal area moist, air-drying the area or female partners of women with BV should be
changing the underwear. examined and treated.
. Always cleaningthe area from frontto back.
Vaginal candidiasis
Pharmaeologic Therapy For the purposes ilf treatment, vaginal candidiasis,
also referred to as vulvovaginosis candidiasis (WC),
Bacterial vaginosis may be broadly classified as either complicated or
Recommended regimens for bacterial vaginosis uncomplicated, as fol lows:
include the followingr
. Metronidazole 500 mg orally twice a day for . Uncomplicated - Sporadic or infrequent
7 days WC; mild-to-moderate WC likely to be
. Metronidazole gel 0.75"/o, 1 full applicator caused by C albicans and occurring in
(5 g) intravaginatly, once a dayfor 5 days non immunocompromised women
. Clindamycin cream 2"/o, I full applicator (5 . - Recurrent WC; severe WC;
Complicated
g) intravagina'lly at bedtime for 7 days WC caused by b species other than C
albicans or occurring in
a Alternative regimens include the following: immu nocompromised women
. Clindamycin 300 mg orally twice a day for 7
days Recommended regimens for intravaginal agents are
. Clindamycin ovules 100 mg intravaginally asfollows:
once at bed time for 3 days r Butoconazole 2"/o iream 5 g intravaginally
for 3 days
Patients should be advised to avoid alcohol . Clotrimazole Lo/o cream 5 g intravaginally for
consumption during and 24 hours after treatment 7-14 days
with metronidazole. Clindamycin cream is oil-based r Clotrimazole 100 mg vaginal tablet for 7
might weaken latex condoms and diaphragms for 5 days
days after use. Clindamycin should not be used in the . Clotrimazole 100 mg vaginal tablet, 2
second half of pregnancy. tabletsfor3 days
r Miconazole 2% cream 5 g intravaginally for
Routine follow-up visits are unnecessary. Routine 7 days
treatment of sex partners is not recommended. The . Miconazole 100 mg"vaginal suppository, 1
: recurrence rate is 20-40% after 1 month. Twice suppository for 7 days
weekly metronidazole gel for 6 months may reduce . Miconazole 200 mg vaginal suppository, 1
recurrences. suppositoryfor3 days

a
111
'"'-- - i
. ' Miconazole i2b0 nig vaginal suppository, 1 preparation; therefore, use of the gel is not
suppositoryfor l day recommended. Sex partners of patients with f
o Nystatin 100,000 unit vaginal tablet, 1 vaginalis infection should be treated, and intercourse
tabletfor 14 days should be avoided until both partners have been
treated and are asymptomatic. Pregnant women
The recommended regimen for the oral agent with trichomoniasis may be treated with 2 g of
fluconazole is a 150 mg oral tablet in a.single dose. lt metronidazole in a single dose.
should be kept in mind that the oil-based cream and
suppositories might weaken latex condoms. Lactating women should withhold breastfeeding
during treatment and for 12-24 hours after the last
Patients are instructed to return only if symptoms dose of metronidazole. For women taking tinidazole,
persist or recur within 2 months of the onset of initial breastfeeding should be interrupted during treatment
symptoms. Routine treatment of sex partners is not and for 3 days after the last dose.
indicated.
Topical treatment with nonoxynol-9 and povidone-
Recommendations for complicated VVC are as iodine douches has been shown to be effective in
followsr treating T vaginalis infection in women unable to u
. Recurrent WC ( >4 episodes of symptomatic metronidazole. Further studies are needed to confirm
WC in 1 y) - 7- 1 O days of topical therapy or a this preliminary finding.
100 mg or 150 mg oral dose of fluconazole
every third day for a total of 3 doses (days 1, A vaccine containing killed "aberrant lactobacilli" is
4, and 7); for maintenance, oral fluconazole available in Europe. This vaccine has not been
100 mgor 150 mgweeklyfor6 months evaluated in well-controlled, double-blind
. Severe VVC - 7-14 days of topical azole prospective trials.
therapy or 150 mg of oral fluconazole
repeated in 72 hours; adjunctive use of Complications
nystatin cream or low-potency steroid cream Bacterial vaginosis has been associated with pelvic
may be beneficial inflammatory disease (PlD), endometritis, and
. Non- albicans WC - 7-14 days of non- vaginal cuff cellulitis when invasive procedures have
fluconazole therapy; 600 mg of boric acid in been performed. Such procedures include
a gelatin capsule vaginally twice daily tor 74 endometrial biopsies, cesarean section, uterine
days curettage, and intrauterine device (lUD) placement.
. WC in compromised hosts - 7-74
days of During pregnancy, bacterial vaginosis and
topicaltherapy trichomoniasis are associated with an increased risk
. VVC in pregnant patients - 7 days of topical of premature rupture of membranes, preterm
agents; fluconazole is contraindicated labor,'ulow birth weight, and preterm delivery.
Systemic disease resulting from the spread of
Trichomoniasis gonorrhea may occur.
Recommended regimens for f
vaginalis infection
include the following: DISCUSSION AN D CONTROVERSI ES
. Metronidazole2 g orally in a single dose (or
500 mg orally twice a dayfor 7 days) Although safe sexual practices have not extensively
. Tinidazole2gorally in a single dose evaluated as means of preventing vaginitis, they may
play a role'in reducing the incidence of bacterial
Metronidazole is the treatment of choice both for f
vaginosis and vaginalis infections. Good hygiene,
patients who are immunocompetent and for those avoiding tight undergarments, wearing IOO% cotton
who are immu nocompromised. underweal and keeping the area dry also may play a
role in preventing candidal infections.
Because trichomonads often infect the urethra and
the Skene and Bartholin glands, metronidazole gel is No studies show any benefit to douching as a
considerably less efficacious than an oral treatmerit or prevention for vaginitis; douching may
tt2
Vulvovaginitis
actually exacerbate symptoms. Tampon use does not contact do not increase the rate of candidiasis.'u
seem to be associated with vaginitis. Candidiasis appears weakly related to high-dose
estrogen contraceptive pills. Sexual intercourse with
Acidophilus supplements in the diet may help the use of nonoxynol-9 spermicide appears to
prevent vaginitis, especially if patients aY€ ,taking increase colonization with Candida." Douching with
antibiotics. ln addition, an increase in the intdke of commercial products appears to temporarily alter
garlic seems to help vaginitis symptoms and vaginal flora and intermittently has been associated
prevention. with recurrent Candida infection.
Patients should be instructed to abstain from sexual Antibiotics have been strongly related to
activity and from douching until a diagnosis has been candidiasis," and this association may be especially
made.'o Patients also should abstain from important for women with recurrent infection. lt is
unprotected sexual activity (sexual activity without not clear whether antibiotics kill bacteria such as
proper male condom use) untilthe infection has been Lactobacillus that may inhibit the growth of Candida
treated. or use other mechanisms.
Reducing simple carbohydrates, refined foods, and Diet may play little in the role of candidiasis. Hygiene
alcohol helps to reduce frequenVpersistent yeast practices, including frequent bowel movements,
infection. wipe direction after bowel movement, type of
menstrual protection, underclothing fabric, and tight
The frequency of intercourse is related to candidiasis.
clothingappearto play no role in candidiasis."
The number of sexual partners and oral-genital
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human vaginalsecretions. Am J 2bstet M icrobiologica. 36: 229-238.
Gynecol 1976;126:129 8. Vazquez F et al. Gonorrhea in women
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; microflora. Rev lnfect Dis 1990;12:856 1991;18:5
a 3. Eschenbach DA, Davick PR, Williams BLet al. 9. Wasserheit N. Epidemiological slnerg!:
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I
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Klebanoff SJ, Hillier SL, Eschenbach DA et al. 10. Clark, Natalie; Tal, Reshef; Sharma, Harsha;
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a 7. Mastromarino, Paola; Vitali, Beatrice; Mosca, of the adults. ln Holmes KK, Sparling PF,
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Obstetricians and
May. 12 p. GCOC Practice
tt4
CHAPTEilO
HIV/AIDS and 6ther Sexually

Transm itted I nfections
Richard Offiong and G.O Akaba
INTRODUCTION constitute a group of infections referred to as sexually

transmitted infections.u The greatest burdens of
The World Health Organization recommends that the sexually transmitted infections are linked to eight
term sexually transmitted disease (STD) be replaced pathogens out of which four are currently curable
by the term sexually transmitted infection (STl). The (syphilis, gonorrhea, chlamydia and
term sexually transmitted infection has been adopted trichomoniasis).The other four which are all viral
since 1999 as it better incorporates asymptomatic infections are currently incurable but have available
infections. ln addition, the term has been adopted by treatments towards improving patients quality of life
a wide range of scientific societies and publications.' (Human lmmuno deficiency virus (HlV), hepatitis B,
Sexually transmitted infections (STls) refers to herpes simplex virus (HSV) and human papiloma
infections that are predominantly transmitted from virus (HPV)).' These eight shall be extensively
one person to another through sexual contact, discussed in this chapter. Other less common STls
including vaginal, anal and oral sex.' include chancroid, lymphogranuloma venereum,
Donovanosis (granuloma inguinale), scabies and
Sexually transmitted infections are a major public human lice.
health problem worldwide because of their ability to
negatively affect quality of life leading to increasing According to the World Health Organization
morbidity and mortality. The direct impacts of (WHO),"more than one million sexually transmitted
sexually transmitted infections on reproductive and infections are acquired every day worldwide and
:
child health are felt through their role in the causation each year, there are an estimated 357 million new
of infertility, cancer and pregnancy complications infections with one of four STls: Chlamydia, gonor-
while the indirect effect is felt through its impact on rhoea, syphilis and trichomoniasis". Majority of the
national and individual economies.' burden associated with sexually transmitied infec-
tions is unfortunately borne by sub -Saharan Africa.u
i
Sexually transmitted infections are a significant
public health burden in developing countries predom- The inability of stakeholders and governments
,
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inantly due to their adverse impact on reproductive particularly in developing countries to focus atten-
and child health and their role in facilitating the tion on prevention and control of other sexually
sexual transmission of Human immunodeficiency transmitted infections apart from HIV may have
virus (H lV) infection.o contributed to the increasing prevalence as well as
i-
5 social, psychological and economic consequences of

Currently, more than 30 different bacteria, viral, and sexually transmitted infection in the Africa.''o
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parasitic pathogens are transmissible sexually artd
115
HUMAN IMMUNODEFICI ENCY VIRUS (HIV) lymphoid tissues which serve as rest cells or sanctu-
ary sites for the virus'.T-helper cells or T4 lympho-
The Human lmmunodeficiency Virus is a relatively cytes are important immune cells that orchestrate
new sexually transmitted infection, first i#*!!&d the functioning of other immune cells. The progres-
amongst homosexual men in the United Stffi of sive destruction of these cells results in the gradual
America in the early 1980s. lt has since spte*d to decline of host immunity. This process goes on for a
become a global pandemic with a reputatlon of period of between 2 and 10 years, described as the
notoriety, stigma and fear, because it is incurable and phase of clinical latency. During this phase, the
associated with sexual promiscuity. ApproxlmaMy infected person remains largely asymptomatic. At
40 million persons are currently infected worldwide the end of this course of events, the immune system
and 50% of them are women. ln sub-Saharan Africa, is completely decimated (CD4<200), giving rise to
a higher percentage of women (58%) are infected opportunistic infections and AIDS defining illnesses
due to biological and socioeconomic vulnerabilities. including cancer of the cervix, Kaposi sarcoma and
Transmission of HIV occurs principally by the sexual non- Hodgkins lymphoma.
route. ln the tropics heterosexual transmission is
predominant. The virus can also be transmitted, A close relationship exists between HIV and other
through the medium of unsterilized needles common sexually transmitted infections. Not only are they
with injection drug users, unscreened blood and commonly found in association with one another, but
blood products and verticallyfrom motherto child. they increase the risk of HIV transmission both
vertical and horizontal. lnitial and subsequent
Two subtypes of the virus are recognized. Globally, clinical assessment of the HIV infected woman must
HIV 1 is more prevalent and also more virulent. HIV 2 include screening for other sexually transmitted
is found primarily in West Africa. lt is less easily infections.
transmissible and there is a longer period between
iniiial infection and development of HIV illness. HIV Clinical manifestations
is an RNA virus and typically cannot replicate of its The clinicalfeatures of HIV infection vary depending
own accord, but requires a human host for its on the clinical stage of the disease. At the onset of the
replication. Once the virus invades the human host infection, flu-like symptoms are experienced as a
which occurs by membrane fusion across mucous result of the initial extreme viraemia associated with
membranes', its genetic material (RNA) undergoes a new HIV infection. Subsequently the infected
transcription to DNA. This process is mediated by the individual remains asymptomatic (WHO stage I
reverse transcriptase enzyme present in the viral disease).

core. The viral DNA inte$rates into the host DNA and
this transforms the host cell to a production unit for At a later period of the clinical spectrum the infected
new viral RNA and viral proteins. Both are needed for individual may experience moderate unexplained
the production of new viral particles which eventually weight loss (below1O"/o of body weight) ,recurrent
bud out of the host cell aided by the protease enzyme. respiratory tract infections, Herpes zoster, angular
HIV has an enormous ability to undergo mutation chelitis, recurrent oral ulcerations, papular pruritic
during this process to the extent that the HIV copies eruptions, seborrhoeic dermatitis and fungal nail
in the infected person are not all identical but a infections(WH0 stage 2 disease).
complex mixture of mutant and recombinant
genomes'.this is due to the error prone nature of the ln WHO stage 3 diseases, more severe weight loss
(above 10% body weight) may be experienced,
reverse tra nscri ptase enzyme.
unexplained chronic diarrhea lasting longer than 1
The human immunodeficiency virus targets specific month, persistent oral candidiasis. Oral hairy
cells of the human immune system that bearthe CD4 leukoplakia, pulmonary tuberculosis, severe bacte-
molecule which serves as a receptor site. The rial infections(e.g. pneumonia, empyema, meningi-
principal target is the CD4 T-lymphocyte, while tis, pyomyositis, bone and joint infections, severe
others are macrophages and dendritic cells. Early pelvic inflammatory disease),acute necrotizing
during the infective process the virus invades the stomatitis, gingivitis or periodontitis, unexplained
lymphatic system and especially the Gut associated anaemia, (<8grams/dl), neutrophilia
116
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r HIV/AIDS and other Sexually Transmitted lnfections

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( < 0. 5x 1 Oe/l itre), th rom bocytopenia( < 50x 1 0e/ /ml. ln practice it is used morefor monitoring
t litre). than diagnosis. Viral load can be so low that
r
it is "undetectable",i.e the machine is
Diagnosis unable to pick it. This occurs at values less
A large number of individuals are unaware of their than 50 copies I ml or 20 copies/ ml,
t
HIV status. The implication is that many infected depending on the sensitivity of the machine.
(
individuals are absent from any kind of care and are
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therefore at risk of morbidity and mortality from Treatment of HIV lnfection
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a opportunistic infections as the disease progresses. HIV infection is incurable and there is also yet no
t
They also pose a risk to other individuals and society effective vaccine against the virus. However treat-
at large. A programme of universal testing for HIV is ment with anti-retroviral drugs using the Highly
the positive direction out of this dilemma.ln the Active Anti-Retroviral Treatment (HAART) regimen
healthcare setting, the provider initiated testing as has been found to be very effective in achieving viral
(
l
opposed to the voluntary approach has been shown suppression, preventing development of drug
to improve upiake of HIV testing among antenatal resistance, im proving general wellbeing and prolong-
f
attendeess. The provider must however obtain clear ing life. A reduction of AIDS related deaths in
consent to carry out the test. developing countries coincided with the introduction
of HAART. Treatment requires a multidisciplinary
Testingfor HIV involves use of thefollowingtests: approach led by the infectious disease specialist
1. Rapidtestkits: physician, and involves laboratory scientists, nurses,
These have the advantage of simplicity and adherence counselors, social workers all of whom
low cost and have been very useful in require some specialized training in the care of the
resource constrained environments of the H lV infected individual.
tropics. Results can be obtained within 10
minutes with a sensitivity of almost 70O% ln many developed countries, therapy with HAART is
and specificity of greater than 99o/". Positive commenced for patients as soon as diagnosis is
results are confirmed with a second rapid made and continued for life as this has been shown
test, and if the second test is negative a third to be consistent with eventual best overall outcome
test ("tie breaker") is performed. Forthe tests reducing the risk of disease progression and
to be credible, the different test kits used death'.This approach is not feasible in developing
must be testing antibodies from different countries with limited resources. ln these countries
portions of the virus. treatment programmes are donor- driven and have
succeeded immensely in improving access to
2. ELISA treatment care and support services. However
This uses a more advanced serological concerns regarding the sustainability of services as
,
{
technique than the rapid test. lt tests a
donorfunds dwindle or become unavailable are often
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number of antibody proteins in combination.
entertained. ln these settings, treatment needs to be
It is also very sensitive but not very specific.
t rationalized in order to reach as many infected
A positive test requires confirmation by a people as possible. The WHO currently recommends
different ELISA test or a Western blot.
: a basic minimum, and this involves initiation of
HAART at CD4 count less than 500/mm3 and as
3. WESTERN BLOT
priority at CD4 less than 350/mm3.
This is the confirmatory test for HIV and it is
very specific.
Commonly first line drugs consist of a combination of
4, DNAPCR
two nucleoside reverse transcriptase inhibitors and
Th is a qua litative test that detects one non-nucleoside reverse transcriptase inhibitor or
intracellular virus and is used primarily for a protease inhibitor. Factors that must be considered
viral detection in early infant diagnosis of HIV before commencing anti-retroviral drugs include
drug adherence, toxicity and resistance. Good
L
5. RNAPCR adherence to the drug regimen is a key factor in
This test measures the viral load in copies achieving treatment success. Adherence counseling
tt7
prior to initiation of treatment and during follow up of contraception. The high contraceptive failure rate
visits must be part of any ARV treatment programme. (15%) associated with typical use of condoms alone
Treatment is also monitored to detect toxicitim mrly make the later more desirable, if the woman must
when they occur by assessing laborator! lfmiem of ach ieve her goal of contraception.
liver, renal and bone marrow function. furFlmirftryu,
treatment is monitored by the assesstrient d vlral Contraceptive implants, lntra-uterine contraceptive
load and the CD4 count at regular intaffAte of devices (long acting reversible methods), surgical
between 3-6 months. By this means tr6Atffiefit methods, and emergency contraception may all be
failure (virological and immunological) are promplly used without restrictions by HIV infected women.The
detected and remedied before clinical failure oceut8. only contraceptives not recommended for use by HIV
positive women are the nonoxynol- 9 spermicide
DISCUSSION AND CONTROVERSI ES which irritates the mucosal surface and causes
genital sores, as well as diaphragms and cervical
A.CONTRACEPTION IN HIV INFECTED WOMEN caps which require adjunct use of spermicides".
Contraception plays an important role in safeguard-
ing the health of HIV infected women and in the Some ARVs speed up liver metabolism and lower
prevention of perinatal transmission of HIV'o. An blood levels of oestrogen, thus reducing meth
infected woman who does not become pregnant effectiveness. The NNRTI, nevirapine reduces the
cannot transmit the virus vertically. Many women blood levels of progesterone by approximately
who are HIV positive become pregnant because they 207"". Method failure has been reported when these
lack access to family planning services. A Rwandan hormonal methods (Oral contraceptive pills and
study showed a significant reduction in pregnancy contraceptive implants) are used with nevirapine
rates after family planning services were offered to contai ning HAART combinations.
HIV positive women, with a corresponding increase
in the use of contraceptives from 76%lo24o/"" . lt used to be thought that hormonal
Finally on this;
contraceptives especially progesterone only might
Women who are HIV infected like any other woman have the effect of speeding up HIV disease progres-
may wish to delay pregnancy, limit her family or even sion but a recent randomized controlled trial has
choose not to become pregnant at all. These women shown that there is no such association"'".
have the right to access any form of contraceptives
they desire. The care provider has the duty of provid- B.POST EXPOSURE PROPHYLAXIS FOR HIV
ing them with the correct information, privacy, FOLLOWI NG SEXUAL ASSAULT
confidentiality and safety in the course of rendering
the service. Post exposure prophylaxis (PEP) involves the
administration of anti-retroviral drugs to avert HIV
The Lactational Amenorrhoea (LAM) method of infection before it becomes established. lt exerts its
family planning is hindered by HIV infection in effect through the inhibition of viral replication after
situations where the guidelines do not support exposure.
breastfeeding or the woman opts not to breastfeed-
ing. ln the tropics where a good number of HIV Post exposure prophylaxis is more generally applied
infected women opt to exclusively breastfeed their in cases of occupational exposure .For example;
exposed babies with the mother continuing on her following a needle stick injuries in the healthcare
HAART regimen, LAM would still be an acceptable setting for which a risk assessment is carried out and
form of contraception. treatment is initiated within 72 hours of the expo-
sure. The same principle is applied to cases of sexual
Dual protection is the use of a method or a combina- assault. The risk of the exposure is assessed and
tion of methods that will ensure protection against depends on the HIV status of the assailant and the
unintended and sexually transmitted infections at the nature of the sexual contact. Treatment involves the
same time, i.e, condom for simultaneous protection use of combination ARVs (tenofovir, emtricitabine,
or condom with an effective hormonal contraception, raltigravir) " for a period of four weeks, A baseline
intrauterine contraceptive device or surgical method HIV test must be carried out prior to treatment
118
HIVIAIDS and other Sexually Transmitted lnfections
initiation and follow up testing after 1 month, 3 reduced risk of infecting his partner". The process of
months and 6 months. "sperm washing" along with insemination of the HIV
negative partner as proposed by Sempriniet al'u may
C.CERVICAL CANCER SCREENING IN HIV POSI- therefore not be necessary.
TIVEWOMEN
For HIV positive women with sero- discordant male
Cervical cancer is classified among the -?lDS partner, the option of self- insemination only around
defining" illnesses. These are serious and life threat- the time of ovulation minimizes the risk of transmis-
ening diseases (some of them malignancies), that sion. Condoms should be used during all other
occur in HIV positive people'.. The presence of an episodes of sexual intercourse. These options of
AIDS defining illness is also indicative of advaneed treatment are controversial and as such extensive
stage of the HIV infection. counseling of the couple would be required before
their application.
ln urban populations with increased .risk sf both
diseases, cervical cancer may be the most common GONORRI.IOEA
AIDS defining malignancy in women'n. lt becomes
imperative to screen any patient presenting with Gonorrhoea is caused by tVelssena gonorrhoeai an
cervical cancer for HIV Similarly, cervical cancer aerobic gram-negative intracellular diplococci. lt is
/ screening of HIV positive women requires gr,eater the second most common bacterial STI and results in
attention and most guidelines recommend more substantial morbidity and economic cost worldwide.
frequent (annual) screening. Moreover, any cytologi- Humans are the only natural host for N. gonorrhoea.
cal abnormality however minor becomes a reason for The organism survives only for a short time outside
colposcopic examination. With regards to treatment the human body. The single exposure transmission
outcomes for cytological abnormalities, HIV positive rate from male to female is higher than from female
patients with normal CD4count do better than those to male because of retention of the infected ejaculate
with lower CD4 counts. within the vagina."'
D.FERTILITY MANAGEMENT IN THE CONTEXT OF Clinical manifestations

HIV INFECTION lnfection with tV. gonorrhoea could be asymptomatic
or symptomatic. ln men, uncomplicated gonococcal
With the advent of potent antiretroviral agents, HIV infection commonly manifests as urethritis for which
infected couples are able to have children free of HIV the patient could present with any of these symp-
and also stay alive and healthy to care for the chil- toms: dysuria, itching or burning sensation at the
dren. urethral meatus, haematuria and muco-purulent
urethral discharge. Gonococcal urethritis when
For couples that are both infected, it is best that they untreated in men could lead to epididymitis, urethral
adopt safer sex practicesin order to reduce the risk of strictu re a nd i nferti I ity.3''?
acquiring or transmitting new viral variants or
resistant strains of the virus. They should only have On the other hand, it is often asymptomatic in
unprotected intercourse around the time of ovulation women and the lack of discernable symptoms results
if pregnancy is desired, in unrecognized and untreated infections that may
lead to serious complications like pelvic inflamma-
Gynaecologists are often consulted by sero- tory disease, ectopic pregnancy and infertility.When
discordant couples who seek counsel on how to symptomatic in women, gonococcal infection
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achieve pregnancy without unduly exposing their manifests mainly as increased vaginal discharge,
uninfected partner. Current recommendations from dysuria, intermenstrual bleeding and menorrhagia. lt
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the NICE guidelines 2012 suggest that the infected is note-worthy to mention that these symptoms may
male partner who is adherent to ARVs, has an occur singly or in combination with other symptoms
undetectable viral load and is free of other sexually and with differing severity. Purulent exudates may
t transmitted infections; can limit unprotected sexual also occasionally be expresied from the urethra,
intercourse to days when their uninfected partner is periurethral glands, orthe Bartholin's gland duct.''"
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ovulating. By so doing, he would be at extremely Rectal and pharyngeal infections in both men and
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119
women have been known to be largely asymptom- cause acute pharyngitis, fever or cervical
atic. Most rectal infections in women result from lymphadenopathy.o Mother to child transmission of
perineal contamination with infected cervical gonococcal infection is associated with development
secretions. When sym ptomatic, presentation range of neonatal conjunctivitis which may lead to blind-
from minimal anal pruritus, mucopurulent dischargB, ness if untreated.'Disseminated gonococcal infection
scant rectal bleeding to symptoms of overt proctitis, (DGl), which is a distinct entity and not a true
including rectal pain, tenesmus and consti:patbn. complication, can occur in both sexes but is rarely
Rectal infection is higher and is a frequent site of encountered.u
infection in homosexual men. Pharyngeal gonococcal
infection may occasionally in less than 10% of cases
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TABLE 10.1: CLINICAL MANIFESTATIONS OF GONOCOCCAL INFECTIONS ,
UNCOMPLICATED GONORRHOEA COMPLICATED GONORRHEA
Urethra r Copious, purulent discharge Male o Penile oedema

. Scant, clear discharge Complications . Cowper's glanG abscess
o Dysuria o Seminal vesiculitis
e Epididymitis
. lnfertility (rare)
Cervix o Red, friable cervical os Female o Endometritis
. Purulent discharge from os Complications o Salpingitis
. Dysuria . Bartholin's abscess
. Salpingitis o Ectopic pregnancy
o Bilateral or unilateral lower o lnfertility
abdominal tenderness
Rectum o Copious, purulent discharge

o Burning/stinging pain
. Tenesmus
o Blood in stools
Pharynx Mild pharyngitis Disseminated Bacteremia
Mild sore throat Gonococcal Fever
Erythema lnfection (DG) . Dermatitis (Skin Lesions
Macu lar, Erythematous,
Pustular, Necrotic
. Haemorrhagic)
. Tenosynovititis
o Joints, septic arthritis
. Endocarditis
. Meningitis
Conjunctiva . Copious, purulent discharge

o Keratitis and corneal
ulceration ; perforation,
extrusion of lens
o Scarring; opacification of
lens
o Blindness
From :( World Health Organization (2013).La,boratory diagnosis of sexually transmitted infections,

including human immunodeficiency virus)
L20
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r H|V/AIDS and other Sexualty Transmitted lnfections
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r Laboratory diagnosis susceptibility to the antimicrobial)
t
r
The diagrosis of gonorrhoea is established by - Ceftriaxone 250mg lM as a single dose.
r i- identificat,on of N. gonorrhoea in genital or extra - Cefixime 400mg orally as a single dose OR
l-
(
genital secretions. Methods include Gr*+r staining - Spectinomycin 29 lM as a single dose.
r
I
and microscopic examination of smear to identify
Additionally, the above dosage regimen for dual
I Gram-negative intracellular diplococci in
r polymorphonuclear leukocytes. This method has a therapy is increased for cases of treatment failure
I
sensitivity of 95% and specificity of 97Y" fOr diagno- and topical ocular prophylaxis for the prevention of
i
r sis of gonorrhoea in symptomatic men with urethral
gonococcal neonatorium at birth is recommended for
t
I discharge. ln women, smears of cervical secretions all neonates. Options includes tetracycline hydro-
I detect only 40-60% of culture positive smears. chloride 15 eye ointment, erythromycin 0.5% eye
I
Culture of N. gonorrhoea is considered the "gold ointment, povidone iodine 2.5% solution(water
t standard " for the diagnosis of both the genital and based),silver nitrate l% solution and
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extra genital gonorrhoea because of its high sensitiv- chloramphenicol 1% eye ointment.
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; ity and specificity, inexpensiveness and importantly

NB: Quinolones are no longer recommended for the
{ culture allows for antimicrobial sensitivity testing
treatment of gonorrhoea due to reported high level
which is crucial towards reducing antimicrobial
resistance.o
resistance.
r(
CHLAMYDIA
I
Although nucleic acid amplification iests (NAATS)
t are available for detection of specific N. gonorrhoea Chlamydia is caused by Chlamydia trachomatis (C.
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DNA/RNA, its use is limited by cost, unavailability in
trachomatis) and are the commonest bacterial STls
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low resource settings and low specificity with worldwide, occurring most commonly among
( suboptimal performance in detecting the organism in adolescents and young sexually active adults. The
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both urogenital and extra genital samples in low World Health 0rganization estimates that in
a prevalence popu lations.5
a 2072,731million new cases of chlamydia occurred
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among adults and adolescents aged 15-49 years

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Treatment
worldwide, with a global incidence rate of 38 per
a Good practice promotes that the choice of treatment
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be based on reliable local data on antimicrobial 1000 females and 33 per 1000 males." C.
1
a susceptibility because of emerging resistance and
trachomatis is an obligate intracellular parasite
which cannot be cultured on artificial media. People
reduced effectiveness of some drugs. Dual therapy is
also preferred over single therapy. The WHO (2016)
with this infection are frequently co-infected with
gonorrhoea.''uC. trachomatrs infection of the genital
STI gu ideline suggests the following options:
tracts are primarily caused by serovars D,
DuaI th e ra py (o ne of th e fo llowing) E,EG,H,l,,J and K. However, D and G serovars are
Ceftriaxone 250mg intramuscular (lM) as a single more prevalent amongst homosexual men who have
dose plus azithromycin 1g orally as a single dose. r6ctal infectionsu.Serovars A-C are mostly associated
- Cefixime 400mg orally as a single dose plus with the endemic blinding trachoma infection of the
azithromycin 1g orally as a single dose. eyes while Serovars L1,L2,L3 cause Lymphogranu-
Single therapy (one of the following based on laoma venereu m(LGV). "'"
recent local resistance data confirming
tzl
TABLE 10.2: Characteristics and infections associated with different Serovars of C. trachomatis
Serovar Characteristics Tissue Tropism/Biovar lnfection
A-C Non-invasive Epithelial cel ls/Trachoma Endemic blinding
(incl, Ba) trachoma
D-K Non-invasive Epithelial cel ls/Trachoma U rogenital, conj unctivitis,
(incl, Da, la, ja) neonatal pneumonia
L1,L2, L3 lnvasive Lympthatic cells/LGV lymphogranuloma

(incl, L2a, L2b) venereum.
From :( World Health Organization (20i3).Laboratory diagnosis of sexually transmitted infections,

including human immunodeficiency virus)
Clinicalmanifestations factor infertility. ln men it could result to prostatitis

Genital infections due to C. trachomafrs are asymp- and epididymitis."'"
tomatic in approxim ately 70"/" of women and 30% of
men. Symptoms of uncomplicated chlamydial Reiters syndrome characterized by urethritis,
infection in women include abnormal vaginal conjunctivitis, arthritis and characteristic
discharge, dysuria, intermenstrual bleeding and mucocutaneous lesions had been related to genital
some instances may present with post coital bleed- infection with C. trachomatis.
ing."'tt
Rectal infection is asymptomatic in most cases but
Common signs on speculum examination include may manifest as a rectal discharge, rectal pain or
cervical friability and discharge .Symptomatic men blood in the stool. Oropharyngeal infections are also
usually present with urethral discharge and dysuria, rare but can manifest as pharyngitis or mild sore
sometimes accompanied by testicular pain. Most throat. ln pregnancy, chlamydial infection is associ-
chlamydial infections of the genital tract would ated with preterm births and low birth weight.
resolve spontaneously with no sequelae but may Mother to child transmission can occur during
result in severe complications, mainly in young delivery resulting in neonatal conjunctivitis and/or
women. Even when chlamydia is asymptomatic, it nasopharyngeal infection. ln the newborn, symp-
can damage the reproductive system resulting in toms of opthalmia include ocular discharge and
complications like pelvic inflammatory disease, swollen eyelids while nasopharyngeal infection can
ectopic pregnancy, chronic pelvic pain and tubal leadtopneumonitis,"'"
TABLE 10.3: Clinical manifestations of lnfection with C. Trachomatis

Genital lnfection Primary Sequelae
Women Cervitis, copious purulent discharge, Pelvic inflammatory disease,
firable cervix, dysuria, pelvic pain, ectopic pregnancy, salpingitis,
cervical motion tenderness tubal factor infertility
Men Urethral discharge, dysuria, Epididymitis, prostatitis
testicular pain
Non-Genital I nfections Primary Sequelae
Rectal Discharge, rectal pain, blood in stool Proctitis
Oropharyngeal Pharyngitis, mild sore throat
Lymph Nodes Lymphatic inflammation
Ocular Conjunctivitis Scaring, blinding trachoma
Neonatal Pneumonia Pneumonia
Note: studies have provided evidence that C. trachomatis infection may facilitate HIV transmission; however the
odds ratios have been relatively low.
From :( World Health Organization (2013).Laboratory diagnosis of sexually transmitted infections, including
human immunodeficiency virus)
t22
r HIVIAIDS and other Sexually Transmitted lnfections
r
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L Laboratory diagnosis Non-amplified nucleic acid hybridization assay

I Methods available for the diagnosis of genital (NAil tests: This approach uses DNA-RNA hybrid-
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r chlamydial infection i ncl ude: ization towards increasing sensitivity by detecting

r chlamydial RNA, e.g(PACE 2,Gen-Probe lnc,
f,*
r lsotation in cell culture: Cell culturc !€: €, gotd USA).The Hybrid capture ll for C. trachomatis
( standard for detection of C .trachafiiaf{gff.,pweral (Digene Corporation, USA) uses a signal amplifica-
tion component to increase sensitivity to approxi-
I
I' years because it is an intracellular,pq@4ff. Cell
r culture is the only procedure that e ifrls the mately 90%of NAATs."'"
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t
presence of viable organisms. Antigens, nueleic acids
or antibodies can be present in the absence of viable Nucteic acid amplification tesfs (NAATs): This is the
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I infectious particles. Most, if not all chtamydia appear current "gold standard" for the diagnosis of C
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( to be able to grow in cell culture if the inoculum is .trachomatis. These methods amplify target DNA or
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centrifuged onto preformed cell monolayer. McCoy, RNA exponentially into billions of copies. Amplified
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,-
HEp-2 and HeLa cells are the most commonly used product is directed by a variety of means, giving each
I cell monolayer for C. tratchomatis. However, the assay a unique performance characteristic. NAATS
are strongly recommended for diagnosis and
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ta
inadequacies associated with cell culture coupled
(
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wlth high cost and difficulties of maintaining organ- screening of chlamydial infections. However, the
t ism viability, stringent transportation and storage choice of test is dependent on the resources available
conditions limited its use."'"'" and level of laboratory support."'"
I Enzyme-tinked immunosorbent assays (ELtSAs)t Serology: These methods identify and in some cases,
r' These detect chlamydial antigens in clinical speci- titrate the level of antibody response to chlamydial
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mens and use either monoclonal or polyclonal antigens. Serology is useful in the diagnosis and/or
7 antibodies to detect chlamydial lipopolysaccharide screening of complicated C. trachomatis infections
I
(LPS), which is more soluble than the major outer (reactive arthritis, PlD, tubal factor infertility), be
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f membrane protein (MOMP). An advantage is that it is diagnostic in neonatal pneumonia and
( suitable for batch processing however it is limited by Lymphogranuloma venereum (LGV) infections, and
its low sensitivity profiles (65%-75%) when com- be valuable in research and epidemiological studies.
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( pared with Nucleic acid amplification tests (NAATS) It is however important to always interpret the
r serological results with caution and not out of
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and low predictive value when applied to low preva-
( lence populations. The appropriate application of context. Therefore chlamydial antibody due to its low
ri confirmatory test increases the specificity trom 97% sensitivity and specificity has limited value for
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to 99.5%."'"''n diagnosis of acute C. trachomatrs infection and thus
r should not be used routinely for diagnosis of uncom-
r
Direct fluorescent antibody (DFil: These assays also
I
I pl icated C. trachomatis infections. "''n
!- :..- utilize monoclonal antibodies directed against
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r
t MOMP or LPS. The anti-MOMP monoclonal antibod- Treatment
ies are species specific with better quality of fluores- Recommended regimes for genital chlamydial
r cence compared to anti-LPS monoclonal antibodies. infection (uncomplicated) is Azithromycin 1g orally
I
The DFA has approximalely 75"/" to 85% sensitivity as single use or doxycycline 100mg twice daily for 7
I
and 98% to 99% specificity compared with culture, days. The latter is also the pieferred in cases of
I
and lower sensitivity compared with NAATS. lt has an anorectal chlamydial infection. Alternatives when
added advantage of providing fast results within 30 involving the genital tract and uncomplicated
r
i minutes but limited because it requires an experi- include: tetracycline 500mg orally four times a day
enced microscopist, the procedure is not amenable to for 7 days, erythromycin 500m9 orally four times a
; automation and thus not suitable for high volume day for 7 days or ofloxacin 200mg - 400mg orally
,,
laboratories. "'"'" twiceadayforTdays."
a
Point of care POC) assays: Point of care assays are ln pregnancy, Azithromycin 1g orally as a single dose
fast to perform and facilitate immediate treatment of or erythromycin 500mg orally four times a day for 7
1-\-' infected patients. Thus could be useful when attend- days could be used with the former being more
ing to a large population. They are however expensive preferred because of its single dosage regimen.
r
I with low sensitivity and specificity of less than
I 7OO"/"." ln neonates with chlamydial conjunctivitis, the WHO
STI guideline recommends using oral azithromycin
I
'7'
i L23
a
ZOm{k{day orally, one dose daily for 3 days over advent of NAATs. lsolates from cases of LGV were
erythromycin 5Omg/kg/day orally, in four divided recognized to grow more rapidly in tissue culture
doses daily for 14 days." cells than non-L chlamydial isolates.5
LYMPHOGRANULOMA VENERUM N uclei c a ci d a m p I if i cati on fests N AATs)

This is the test of choice for diagnosis of chlamydial
Lymphogranuloma venereum (LGU is caused by the infections as already stated earlier in the discussion
distinct'L' biovar of Chlamydia trachomatis, which on laboratory diagnosis of chlamydial infections.
contains serovars (Ll, L2, LZa,L2b, L3) that are These commercially available NAATs are substan-
more invasive than those serovars responsible for the tially more sensitive than the older diagnostic tests
classical eye disease, trachoma (serovars A-C) and However; these tests cannot discriminate between
those causing non-gonococcal urethritis and associ- non-LGV and LGV strains. Subsequently, molecular
ated infections of the genital tract (serovars D-K). assays (e.g., PCR-based genotyping) have been
LGV has worldwide distribution but is more prevalent developed that can differentiate between strains
in tropical and subtropical countries; for exdmple, based on a deletion that occurs in the pmpH gene
endemic in parts of East and West Africa, lndia and only in LGV isolates.
South-East Asia, South America, and the Caribbean.u It is important to stress that appropriate specimen
Lymphogranuloma venereum (LGV) has emerged as collection, transportation, and storage are crucialfor
an important cause of proctitis and proctocolitis in a high sensitivity and specificity of all diagnostic
men who have sex with men.'o methods.u
Clinical Manifestations Treatment

Classically presents as a transient, herpetiform' The recommended regimen consists of:
primary lesion of the external genitalia, but in many Doxycycline 100mg orally twice daily for 21 days
cases the lesion may pass unnoticed or manifest as Erythromycin base 500mg orally four times daily for
an acute non-gonococcal urethritis in men or be 21 days.
completely asymptomatic in women as a result of
primary infection of the cervix. Most cases seek Although clinical data are lacking, azithromycin 1 g
medical attention when the regional lymphatics orally once weekly for 3 weeks is probably effective
become infected, as a result of lymphatic spread of based on its chlamydial antimicrobial activity.'o'"
the causative organism. ln men, swelling of the Fluoroquinolone-based treatments also might be
inguinal and femoral glands often results in the effective, but the optimal duration of treatment has
formation of suppurating buboes on either or both not been evaluated."
sides of the inguinal ligament.
Treatment cures infection and prevents ongoing
Complications or sequelae of untreated cases are as tissue damage, although tissue reaction to the
fol lows; Peria na I a bscesses, recta I strictu res, f istu las, infection can result in scarring. Buboes might require
chronic scarring, and blockage of lymphatic drainage aspiration through intact skin or incision and
of the genitalia or rectum leading to oedama which drainage to prevent the formation of inguinallfemoral
could be severe and termed "elephantiasis".u ulcerations.
Laboratory Diagnosis
Historically, LGV diagnosis has been based on SYPHILIS
clinical presentation coupled with appropriate Syphilis is a bacterial STI caused by the pathogen
serologic findings (microimmunofluorescence titers Treponema pallidum.lt transmitted through sexual
>7:256 or complement fixation titers > 7:64). contact with infectious lesions of the mucous
However, criteria forserologic test interpretation have membranes, abraded skin, and blood transfusion or
not been standardized, nor has test performance transplacentally from a pregnant woman to her
been validated for rectal infections.'o Laboratory fetus."'" The rate of acquisition of syphilis from an
diagnosis could also be achieved by culture or by infected partner during a single sexual contact has
Nucleic acid amplification tests (NAATs) .u been estimated at about 3Oy".u The WHO estimated
that there were 5.6million new cases of syphilis in
Culture 2OL2 occurring amongst adolescents and adults
This was the main method of diagnosis until the aged 15-49 years with a global incidence of 1.5
124
i
r HIV/AIDS and other Sexually Transmitted lnfections
i
r
a cases per 1000 females and 1.5 cases per 1000 during primary, secondary and early latent infection.
I
I males. The burden of syphilis is highest in Africa."'" Mother to child transmission, however, has been
r
When left untreated, the disease runs a chronic cause documented to occur up to several years after initial
r
t\
I
lasti ngfor several years. infection. When left untreated patient may remain in
l- the latent stage or develop clinical sequelae of
I Clinical manifestations tertiary syphilis in approximately 257o of cases.","
I
The disease has been divided into series of stages

7 based on clinical findings. These include: primary
I syphilis (ulcer or chancre), secondary syphilis (skin Tertiary syphilis
rash, mucocutaneous lesions, lymphadenopathy and Clinical onset of late or tertiary stages of the disease
aud itory or ophtha lmic abnormalities), latent syphilis may take 1 to over 20 years from time of acute
(early and late) and tertiary syphilis (neurologic infection.
manifestations: cranial nerve dysfunction, meningi-
tis, stroke, altered mental status, loss of vibration Tertiary syphilis occurs in many clinical syndromes,
sense, and cardiac orgummatous lesions)."'" most conveniently divided into three groups:
neurosyphilis, cardiovascular syphilis and late
Primary syphilis: benign syphilis (gummatous lesions). Neurosyphilis
Classically presents as a solitary painless chancre at can occur at any stage of syphilis infection, even in
the site of inoculation, usually in the vagina, penis or the first few months. Early neurological manifesta-
anus but any part of the body can be affected. This tions include acute changes in mental status,
r usually occurs after a mean incubation period of
21days (range 9-90 days).The papule grows to a size
meningitis, stroke, cranial nerve dysfunction and
i
auditory or ophthalmic and ocular abnormalities.
of 0.5 to 1.5cm in diameter and after about a week Late neurosyphilis occurs 10-30years or more after
r
, ulcerates to produce the typical chancre of primary infection and is characterized by tabes dorsalis and
l
I
syphilis which may go unnoticed by patients. lf general sepsis. Late benign syphilis or gumma is a
r untreated, the disease progresses to the secondary proliferative granulomatous inflammatory process
stage four to eight weeks after the primary lesion. A that may destroy affected tissues. Most Jesions occur
close differential diagnosii is chancroid caused by in the skin and the bones."'"
a Haemophilus ducreyi. Though difficult to easily
.? distinguish from each other on clinical grounds, the Laboratory Diagnosis
latter condition has an irregular border, associated The available laboratory tests for diagnosis of
i
tenderness, yellow exudates and striking inguinal syphilis include:
I lym p h adeno pathy."'"'" - Direct detection methods (dark field
I
Secondary syphilis:
. microscopy, direct fluorescent antibody test
and nucleic acid amplification test).
i It is characterized by generalized mucocutaneous - Serology(ireponemal tests that measure
lesions affecting both skin and mucous membranes. antibodies to infection such as: Treponema
The rash varies widely and mimics other infectious or pallidum haemagglutination assay (TPHA),
non -infectious conditions, but characteristically Treponema pallidum particle agglutination
affects the palms and soles. The rash is often sym- assay(TPPA), fluorescent treponemal
metrical and non-itchy, but may have several mani- antibody absorbed(FTA-ABS) and non-
festations and can be minimal enough to be over- treponemal tests that are indirect markers
looked. ln warm and moist areas of the body, such as measuring host immune responses to
the anus and labia, large white or grey raised lesions infections(including rapid plasma regain
develop as a result of the spread of the treponema (RPR),Venereal Diseases Research Labora-
from the primary lesion."'" tory(VDRL),Toluidine Red Unheated serum
test(TRUST),Rapid treponemal tests for
Latent syphitis syphilis and duaI HIV and syphilis.
ls characterized by positive syphilis serology with no - Examinationofcerebrospinalfluid.
clinical symptoms or signs and can be categorized
into two: early latent syphilis which is defined as Di rect detection method s
infection for less than two years and late latent Dark field microscopy;. Demonstration of
t syphilis which is the presence of disease for two years treponemes with characteristic morphology and
or more.'sexual transmission typically occurs only motility in lesion exudates of tissues by dark field
125
-.--- .-:r--I=-==+:- --------\
--
microscopy is the most specific method for diagnosls diseases like malaria, hepatitis, chicken pox, and
of early stages of syphilis. Dark field mi6ros6opy nreasles or with recent vaceination while chronic
requires specialized equipment and a,lf.3i4ed, false positive reactions may be seen in connective
experienced microscopist, and is thcr*& tissue disorders, malignancies, chronic infections
limited to specialized laboratories. lt is h sueh as leprosy, inilavenous drug abuse and ageing.
which implies that the presence 0f -e
Other limitations include the followingr
spirochetes is diagnostic of an active
gf6itiv-
however limited by its unavailability and low - Tests may be negative for up to four weeks
ity which is less than 5O%.This lrrrSie* thqt a after the first appearance of the lesion of
negative result does not exclude syphilis.s't' primarY syPhilis.
- Tests can be negative in latent phase'
Direct f luorescent arttibody @FN: Thig test ugcs a - Tests may be false negative in primary and
fluorescent microscope to detect splrochetes that secondary syphilis due to prozone reaction
have been stained with fluorescent*lahelled anti' (i.e. interference by high concentrations of
T.pallidum globin. Specirnens are obtained in the antibodies in a speeimen, which can be
same way as dark-field microscopy, but the uncovered with dilution and retesting.
fluorescein-stained organisms are easier to detect
and are not likely to be confused with other organ- A negative non-treponemal test at three months after
isms, leading to a higher sensitivity and specificity for onset of the primary chancre virtually excludes the
the DFA test. lt is however limited by the need to have diagnosis of syphilis.
specialized equipment and also by the faet that the
specific fluorescein conjugate is not commercially to be
Treponemal serological tests are considered
available in most countries.u'" more specific when compared with their non-
treponemal counterparts. Treponemal tests use
Nucleic acid amplification test: This test directly whole cell lysates otT. pallidum orsingle or a mixture
detectf . pallidum DNA by polymerase chain reaetion of recombinant treponernal antigens to detect
(PCR) from specimen of any lesion exLldates, tigsue antibodies agalnst specific treponemal cellular
or body fluid. The sensitivity of the test varies components.
accordingtothe specific PCR assay. lt is interestingto
note that most assays can detect approximately 10 Examples of serological tests for syphilis include:
organism equivalents, although some can detect one Fluorescent Treponemal Antibody Absorption (FTA-
organism per PCR reaction. Cost is the major limita- Abs) test, Treponemal agglutination assays,
tion to its use in the diagnosis of syphilis,u Treponemal enzyme immunoassays (ElAs) and
chemiluminescence assays (ClAs), Treponemal
Syphilis serology western blot (WB) assays, Line immunoassays
Serological tests for syphilis can be non-treponemal (designed to be confirmatory tests) and Point of Care
or treponemal. A presumptive diagnosis of syphilis (POC) tests. The latter provide a rapid indication of
requires a positive result from at least one of the previous exposure to treponemal infection and have
above mentioned types of tests. A confirmed diagno- most convenientiy been used to screen pregnant
sis on the other hand requires positive results from women in developing countries to prevent syphilis.
both types of serologic tests. Use of the POC tests to screen for syphilis in preg-
nancy has been shown to be extremely effective
Specimens for serologic tests include serum, plasma ,Benefits includes its cost effectiveness and the
and cerebrospinal fluid. The latter is used to diagnose ability of the patients to receive treatment on the
congenital and tertiary syphilis. same day of screening.u "
The microscopic Veneral Diseases Research Labora' Treatment
tory (VDRL) and the macroscopic Rapid Plasrna The recommended regimens for the treatment of
Reagin(RPR) tests are the most widely available non- early syphilis (primary, secondary and early latent
treponemal tests. They detect anti-lipid lgM or lgG syphilis of not more than two years duration) include:
antibodies. Non -treponemal tests are not highly Use of benzathine penicillin G 2'4 million units once,
specific and thus can give false positive iesults which intramuscularly. Alternatively, when this cannot be
have been detected in 0.2-0.8% of tests. Acute false used because of allergy to the drug, capsules of
positive reactions are associated with other infectisus doxycycline 100mg twice daily orally for 14 days is
t26
----
TABLEIO.4: Clinical manifestations of trichomonas vaginalis infection
Ful m nate, puru.lepS, or frothY

i
Bartholin's gland infection,
white to yellow disefiarge, dYsuria, endometritis, pyosalpinx, infertility,
pelvic pain itching :
adverse outcomes of PiegnancY,
increased risk of HIV transmission and
acquisition
Urethral discharge, dYsuria, Possible epidydimits and prostatitis

testicular Pain
diagnosis of sexually transmitted infections, including

From :( World Health organization (2013).Laborator,y
human immunodeficienry virus)
Diagostic, USA)'Determination of positive result is

Laboratory diagnosis
These include the followin$; wet preparation achieved by microscopy after 5-7 days post
microscopy, culture, point of care tests for antigen collection. Culture increases the sensitivity beyond
detection, Nucleic acid amplification tests
(NAATS): what is seen in wet preparation microscopy'"
Wet preparation microscoPY Pointof care antigen detection tests:

It is an ideal first-line diagnostic method' When These are apptoved only for female vaginal swab
positive, it provides a definitive diagnosis with high samples. An examples is the OSOM Trichomonas
specificity if adequately performed and interpreted' Rapid test (Genzyme Diagnostic,USA)'Results can
Samples could be vaginal swabs, urethral exudates be gotten in 30 minutes and provides the advantage
or urine sediment from men. Advantages of of offering immediate treatment to patients' Affirm
traditional wet mount includes that the fact that it is VP lll (Becton, Dickinson & Co'; Franklin Lakes, NJ)'
cheap, fast and widely available." However, false a nucleic acid probe test that evaluates for I
negative diagnosis may be due to thefollowing: vaginalis, Gardnerella vaginalis, and Candida
albicans and provides results within 45 minutes is
- Trichomonads are highly temperature also available. Both tests are performed on vaginal
sensitive and lose their motility within few secretions and have a sensitivity of more than 83 %
minutes following sample collection and and a specificity of more than 97 "/o'"''u
since motility is the hallmark feature, this
loss may result in false negative results' N ucleic a ci d a m pl if i cati on tesfs N AATs)
Therefore, microscopy must be performed These tests directly detect T. vaginalis DNA or RNA
and interpreted within 10 minutes for by polymerase chain reaction (PCR) from vaginal or
oPtimalresults. endocervical specimen in women and from urine
- Trichomonads may be obscured or mistaken specimen in both men and womeri' Examples
for white blood cells which have similar sizes include Ampiclor, manufactured by Roche
as trichomonads and the former are often Diagnostic Corporation for detection of gonorrhea
present in i nflammatory processes' and chlamydial infection which has now been
- The organism load may be below the limit of modified for T'vaginalis deiection in the above
detection for microscopy, Highest sensitivity mentioned sPecimens.
is seen in sYmPtomatic women' "''u
The sensitivity ranges between 88-97% and
Culture specificity from 98-99% using wet mount or two

Specimens licensed for culture include: vaginal positive DNA tests as gold standard' APTIMA I
swabs, urethral swabs and Urine sediments for men' va'ginalis Analyte Specific Reagents (ASn'
manufactured by Gen-Probe, lnc') also can detect
il
The method utilizes commercially available culture
kits likelnPouch TV culture system (BioMed
t28
vaginalis RNA by transcription-mediated genitalia and perineal area. The disease, which is of
amplification using the same instrumentation low infectivity, is transmitted between humans
platforms available for the APTIMA Combs2 assay for principally by sexual contact. The incubation time
diagnosis of gonorrhea and chlamyclial infection. may be prolonged, varying between 1-12 weeks.
These methods are limited by cost and unhvallability Donovanosis is caused by K/ebsiella fformerly
of the equipment in most laboratories,in our sub Calymmatobacterium) granulomatis, a Gram-
region."''u negative bacterium (1.5 x 0.7 pm), that can be
observed enclosed in vacuoles in large histiocytic
Treatment cells, where it is referred to as the "Donovan body".5
Metronidazole is the drug of choice for the
treatment of T. vaginalis infection. However, other Ctinical Manifestations
members of the 5-nitroimidazole family (tinidazole The disease starts as an indurated subcutaneous
and secnidazole) have also been shown to be nodule that erodes the skin surface to form a beefy
effective for the treatment of T.vaginalis infection. red, hypertrophic, granulomatous ulcer with a well-
Success rate at cure is as high as 95o/" using any of defined border. The lesion bleeds easily on contact.
the drugs.'u The ulcer progresses slowly and may become painful
when a secondary bacterial infection develops.
CHANCHROID
This sexually transmitted infection is caused by Such secondary infection with other organisms may
Haemophilus ducreyi which is a gram negative contribute to necrotic debris in the ulcer. New lesions
coccobacillus. There is formation of erythematous may be formed by autoinoculation, and inguinal
papules at the entry site within several hours to days lymph nodes may become enlarged as a result of
which subsequently evolve Into pustules in 2 to 3 secondary infection (pseudobuboes). Donovanosis
days and later transforms into painful ulcers in may spread haematogenously to bones, joints, and
anotherfew days to two weeks. the liver; dissemination also may result in cutaneous
lesions at extragenital body sites. Genital and
Clinical manifestations perianal lesions at various stages may resemble
Chanchroid is usually characterized by painful genital lesions formed by other conditions, such as syphilis,
ulcers and suppurative inguinal lymphadenitis. The chancroid, carcinoma, and amoebiasis.u
diagnosis of chancroid is usually suggested by the
presence of these two manifestations. Laboratory Diagnosis
Laboratory diagnosis depends on the visualization of
Laboratory Diagnosis Donovan bodies in stained smears obtained from
The cornerstones of diagnostic tests are culture and clinical lesions or in stained histological sections of
PCR tissue biopsies, The organism can only be cultured
with difficulty in specialist centres using
Treatment
monocyte/Hep-2 cell cultures; it is not yet possible to
Treatment options include the use of macrolides, grow the organism on artificial media. ln-house
quinolones and third generation cephalosporins.
nucleic acid amplification assays have been reported
Effective regimens are a single dose of azithromycin 1
in the literature but such assays are not available in
g orally or ceftriaxone 250 mg intramuscularly,
most countries for routine diagnostic purposes.
ciprofloxacin 500 mg orally twice a day for 3 days, or
erythromycin base 500 mg orally three times a day Treatment
for 7 days." Azithromycin has emerged as the drug of choice and
should be used if the diagnosis is confirmed or
suspected." Azithromycin 1 g orally once per week
DONOVANOSIS (GRAN U LOMA I NGU I NALE)
or 500mg daily for at least 3 weeks and until lesions
have completely healed has been recommended by
Donovanosis, also referred to as granuloma
inguinale, is a chronic infection involving the skin,
CDC(20i5).Alternative regimens include
:Doxycycline 100mg orally twice daily for at least 3
mucous membranes, and lymphatic system of the
weeks and until all lesions have completely healed or
t29
Ciprofloxacin 750 mg twice daily for at least 3 weeks usually causes herpes simplex genitals. Genital
and until all lesions have completely healed or diseases caused by either of these viral types are
Erythromycin base 500mg orally for tinles a ddy for clinically indistinguishable. Herpes infections are
at least 3 weeks and until all lesions have completely most contagious when symptoms are present but
healed. can still be transmitted to others in the absence of
symptoms. lt is note-worthy to also mention that
infection with HSV-2 increases the risk of acquiring
HERPES SIMPLEX VIRUS (HSV) TNFECTIONS
and transmitting HIV infection.'e
Herpes simplex virus type 1 (HSV-1) and type 2

Infection occurs via inoculation of virus onto
(HSV-2) are large double-stranded DNA viruses.
susceptible mucosal surfaces (e.9. the nasopharnyx,
HSV-1 and HSV-2 share a similar genome structure,
cervix, conjunctivae) or through cracks in the skin.
with 40% of sequence homologies and 83% Concomitant with initial infection, HSV ascends
homology of their protein-coding regions, which
peripheral sensory nerves and enters sensory or
explains numerous biological similarities and
autonomic nerve root ganglia where latency is
antigenic cross-reactivity between the two
established.'o'" Latency can be established after both
serotypes.u Both HSV-I and HSV-2 are lifelong. A
symptomatic and asymptomatic initial infection.
publication showed that in 2012,419 million people
Recrudescence of disease may be clinically
aged i 5-49 years were living with HSV-2 worldwide,
symptomatic or asymptomatic. Primary infection is
of whom 267 mrllion were women. The highest
often worse in intensity and duration in women than
burden was in Africa."
in men.
HSV type 1 traditionally causes oral lesions (cold

sores) and can also cause genital lesions. HSV type 2
clinical manifestations: These are summarized in table 10.4 below.

TABLE 10.4: Clinical manifestations of genital herpes infection
Genital Symptoms Signs Complications

lnfection
Men - Papular or vesicular lesions on Papular, vesicular, Aseptic meningitis
genitals, perjgenital areas, or pustular lesions followed Extensive vesicular
extragenital areas (thigh, by ulcerations on penis, skin rash
eye, buttock, finger) perineum, thigh Urinary retention
- Pustular lesions Urethral discharge Sensitive radiculopathy
- Genital ulceration Urethritis by
- Perineal pain involvement of
- Dysuria sacralnerves
- lnguinal discomfort or pain Transverse myelitis
(peri-adenitis)
lncreased risk for
- Pharyngeal infection (oro-genital acquiring HIV by
contact) sexual exposure
lncreased risk of sexual
transmission
of HIV in HIV/HSV-
coinfected ind ividuals
Neonatal herpes
after vaginal delivery
130
', . " - '*
,
Genital Symptoms Signs Complications

lnfection
Women All the above plus: - Papular, vesicular, Same as above.
- Vaginal or cervical dischargg pustular lesions followed
r - Dyspareunia by ulcerations on vulva,
perineum, thighs.
r - Vaginal or cervical
r discharge
I
t - Cervicitis
r
I
- Hyperemia of the
I mucous membranes of
( vulva and vagina
t
I
r-
- Urethral discharge
I
- Urethritis
t
t
ft From :( World Health Organization (2013).Laboratory diagnosis of sexually transmitted infections, including human
I im m u nodeficiency vi rus)
I
r Laboratory Diagnosis 3. Viral culture by isolating HSV in susceptible

I Genital herpetic infection often is diagnosed on cells. The specificity is almost 100% and
has additional advantages of allowing for
1
t clinical grounds as a result of the presence of a cluster

7 of vesicular lesions.u Laboratory confirmation of the isolation of the virus. lt is currently the "gold
i
I
i diagnosis may be necessary to differentiate it from standard" and "preferred" test. There is
I
other causes of genital ulcers. Laboratory methods simplicity of sampling, virus typing and
I
1
used for the diagnosis of HSV infection include direct testing for resistant phenotype is possible
r detection of HSV in materialfrom lesions and indirect using this method. lt is however limited by
r
I
serological methods. the facts that it takes 2-7 days for the result
I
to be ready, it is less sensitive to PCR, it is
iI Directdetection of HSV in materialsfrom lesions. expensive and needs specialized laboratory
I
I and sample storage greatly influences

r 1. Cytological examination using Tzanck sensitivity.5
t smears, Papanicolaou (Pap), or Romanovsky
I
stain. Cytological examination could also be 4. Molecular biology using the following
; done by detecting infected cells by direct principles; HSV DNA detection and/or
f immunofluorescence. Samples could be quantification by NAAT, including in-house
from skin, mucosal lesions, biopsies, classical PCR, real time PCR and
conjunctival/corneal smears, smears from commercial assays. This technique is highly
i-
i tissues section and base of vesicle. Has an sensitive and specific(98% and 700%
i
advantage of being inexpensive but limited respectively).This method is only possible in
by low sensitivity and specificity.5 specialized laboratories and is also quite
expensive.u
a-
2. Virat antigen detection by either immune
'- peroxidase staining, capture ELISA I nd i rect se rol ogi ca I method s
/ technique or by the use of Rapid device. This involves the use of serological assays to screen
.
Samples could be swab, vesicular fluid or for exposure to HSV by detecting HSVtype specific
a. exudates from vesicle. lmmune peroxidase antibodies. Serological testing is recommended as
;\- staining has a moderate sensitivity but high an aid to diagnosis of genital herpes in patients with
r
1
specificity (>95%).lt is also inexpensive but recurrent genital symptoms, atypical lesions, or with
t time consuming and labour intensive. That of healing lesions and negative HSV cultures. ln the
i
a
Rapid devices is yet to be fully evaluated.u
131
Corhprehensive Gynaecology in the Topics
absence of lesions or with negative virus detection marker present after vaccination. The presence of
tests, serological testing can be useful for the HBsAg and total anti-HBc, with a negative test for
management of sex partners of people with genital lgM anti-HBc, indicates chronic HBV infection. The
herpes and for identifying.s ' . presence of anti-HBc alone might indicate acute,
resolved, or chronic infection or a false-positive
Treatment resu lt.t'
Antivirals, such as acyclovir, famciclovir, and
valacyclovir are the most effective medications Virological evaluation of HBV DNA is used to monitor
available for people infected with HSV. These can progression of the disease as well response to
help to reduce the severity and frequency of antiretroviral therapy and a rise may indicate the
symptoms, but cannot cure the infection.'e emergence of resista nt va ria nts.t'
HEPATITIS B VIRUS INFECTION Treatment

No specific therapy is available for persons with
This is one of the non curable sexually transmitted acute hepatitis B; treatment is supportive. Persons
infections of viral origin. Hepatitis B infection is with chronic HBV infection should be referred for
caused by the hepatitis B virus (HBV), an enveloped eva luation to a provider experienced in the
DNA virus that infects the liver and causes management of chronic HBV infection. Antiviral
hepatocellular necrosis and inflammation."The agents (lamivudine, adefovir, entecavir, telbivudine,
incubation period from time of exposure to onset of tenofovir, emtricitabine, standard and PEG-IFN) are
symptoms is 6 weeks to 6 months. The highest approved forthetreatmentof chronic hepatitis B viral
concentrations of HBV are found in blood, with lower infection and have been shown to delay the
concentrations found in other body fluids including progression of cirrhosis, reduce the incidence of
wound exudates, semen, vaginal secretions, and hepato-cellular carcinoma and improve long-term
saliva." HBV infection can be either acute or chronic, survival.t''t'
and may range from asymptomatic infection or mild
disease to severe or rarelyfulminant hepatitis .31 Prevention of HBV infection
Three main strategies are available for the
HBV is spread predominantly by percutaneous or prevention of HBV infection: (1) behavior
mucosal exposure to infected blood and various body modification to prevent disease transmission, (2)
fluids, including saliva, menstrual, vaginal, and passive immunoprophylaxis, and (3) active
seminal fluids, which have all been implicated as immunization
vehicles of human' transmission. Sexual
transmissions of hepatitis B also occur, particularly in HUMAN PAPILOMA VIRUS (HPV)
unvaccinated men who have sex with men and
heterosexual persons with multiple sex partners or The human papilloma virus is a DNA virus. Over 100
contact with sex workers. Accidental inoculation of serotypes of the virus are recognized. lt is the
minute amounts of blood or fluid during medical, commonest sexually transmitted infection affecting
surgical and dental procedures or use of 50% all sexually active individuals at some point of
contaminated materials amongst those who abuse their lives'. lt is transmitted by skin to skin contact
drugs could be alternative sources of transmission.32 during sexual intercourse irrespective of whether
Diagnosis is used or not. Types
barriers like the condom
6,11,16,18,31,35,45 show predilection for the
This is achieved mainly by the use of HBV serological genital skin. Types6 and 11 are classified as low risk
markers. The presence of lgM antibody to hepatitis B and are the causative agent for
condylomata
core antigen (lgM anti-HBc) is diagnostic of acute or accuminata (genitat warts).Types 16,18,31,33,45
recently acquired HBV infection since HBsAg is are ctassified as high risk and are oncogenic."''o
present in both acute and chronic infection."
The human papilloma virus has been implicated as
Antibody to HBsAg (anti-HBs) is produced after a the causative agent for both premalignant and
resolved infection and is the only HBV antibody malignant disease of the cervix. lt is also thought to
L32
be responsible for dlverse other malignancies of the gonorrhea is an infection spread by contact,
vulva, vagina, anus penis, and the larynx even though immediate physical contact with the mucosal
these occur more rarely. lnfection with the HPV is surfaces of an infected sexual partner is required for
usually without symptoms during the early'phase. transmission.3
lndeed most individuals with an intact immune
system will clear the virus within 1-2 years of B.TREATMENT OF ASYMPTOMATIC RECTAL
becoming infected. However a minority of women CHLAMYDIAL INFECTIONS
retain the high risk HPV (hr HPV) within the genital Treatment of asymptomatic rectal chlamydial
epithelium which can potentially cause cellular infections is shrouded in controversies especially as
changes and even carcinoma. Types 16 and 18 are it relates to the use of azithromycin in the treatment
responsible for 7O% of all cervical cancer. Research of this group of patients. Previous studies
findings from Africa suggest that hrHPV other than documented persistent positivity of chlamydial
those traditionally recognized may be more infections in patlents treated with doxycycline and
prevalent'o
to'to even azithromycin however the rate of persistent
positivity was comparatively higher in the
Diagnosis azithromycin group when compared to
HPV infection is usually asymptomatic only d oxycycl i n e( 7 6%-2O%vs l%- I 0%) .'o Th is su ggests
becoming clinically evident when cellular changes or that, additional research is required to clarify the
growths in the genital areas are observed. Diagnostic optimal treatment regimen for patients with
test for HPV are not routine, but are done as part asymptomatic rectal ch lamydial i nfection,
cervical cancer screen i ng.
C.SINGLE VERSUS MULTIDOSE FOR
Samples of exfoliated cervical cells are obtained from TREATM ENT OF T.VAG! NALIS INFECTION
the cervical os with the aid of a cyto-brush and There have only been a few randomized trials with
processed by the DNA polymerase chain reaction good follow-up that have compared single-dose
technique. metronidazole to multidose. ln these trials, cure
rates for singe versus multidose metronidazole have
Prevention of HPV lnfection been shown to be similar (82-88 versus 92-94%).
Primary infection involves educating adolescent boys Both studies found that the single dose had higher
and girls on responsible sexual behavior. The rates of side effects (notably nausea and vomiting)."
immature cervical transformation zone in
adolescents makes it more susceptible to HPV D. HSV SEROLOGY AND PREGNANCY
infection with cellular changes occurring more Testing of asymptomatic pregnant women is not
:
frequently. routinely recommended, but is indicated when there
a
is a history of genital herpes in the partner.HSV-1
1
HPV vaccine bivalent vaccine (cervarix), and andlor HSV-2 seronegative women should be
quadrivalent vaccine (Gardasil) and the more recent counseled about strategies to prevent a new infection
9- valent vaccine, are recommended for with either virus type during pregnancy.u
administration to boys and girls between the ages of
9-26years and have been shown to significantly E.HSV SEROLOGY IN THE CONTEXT OF HIV
reduce the risk of infection. However use of the INFECTION
vaccine does not preclude routine cervical screening. Testing of HIV-infected patients is not routinely
Presently, use of these vaccines in the tropics is recommended. Although HSV-2 seropositivity
limited by theircost considerations. increases the risk of HIV transmission and frequent
HSV recurrences augment HIV replication, there is
DISCUSSIONS AN D CONTROVERSI ES limited evidence to inform the managemeni of HSV-
2 co-infection in HIV-infected patients without
I A.TOILET SEATS AS SOURCE OF TRANSMISSION symptoms of genital herpes. Limited data suggest an
OFGONORRHEA increased risk of perinatal HIV transmission among
L
There is no evidence that natural transmission occurs HSV-2 seropositive HIV-infected women. As
from toilet seats or similar objects. Because evidence is not consistent, testing of HIV positive
133
Chlamydia trachomatis and vaginal infections

u
pregnant women is not routinely recommended.
caused by Trichomonas vaginalis, Bacterial
F. THE ROLE OF HPV VACCINES IN HFV vaginosis and Candida albicans, the authors
INFECTION PREVENTION reported that the diagnostic performance to identify
The role of HPV vaccines in HPV infection prBvention cervical infections was low and resulted in a high
has been a matter of discussion, lnitial soneerns proportion of over and missed treatment. There was
about safety appear to have been largely SvereCIme also inconsistency in the treatment performance of
and its increasing acceptability in the developed the three flow charts. " Initially, it was thought that
world is not in doubt. This is a huge contrast to the the finding of vaginal discharge would be indicative
situation in resource poor tropical countries where of both vaginal and cervical infection' However, it has
the vaccines are most needed, hut remain become clear that while vaginal discharge is
unaffordable to the majority of boys and girls, ln spite indicative of the presenee of vaginal infection, it is
of this, the appropriateness of the available vaccines poorly predictive of cervical infection (gonococcal
for prevalent HPV in Africa has raised questions" and/or chlamydial), particularly in adolescent
some of which may have been angwered with the females.'
introduction of the 9-valent vaccine.
Furthermore, some of the risk assessment questions
F.SYNDROMIC MANAGEMENT OF 9TIS based on demographics, such as age and marital
Syndromic management of STls is the reliance on status, tend to classify too many adolescents as
identification of consistent, easily recognizable signs being at risk of cervical infection, This has led to
and symptoms to guide treatment. lt provides a
suggestions on the need to identify the main STI risk
standardized evidence based approach using elinical factors for adolescents in the local population and
management algorithms, and flow charts that can be tailor the risk assessment accordingly.'The
used consistently across providers, so that syndromic management of STls guideline is gazetted
healthcare providers in resource-poor settings can to be undergoing review/update as at the time of this
deliver appropriate and effective STI treatment based write up''''
on observed syndromes (e.9., vaginal discharge,
urethral discharge, genital ulcers, and abdominal G.PREVENTION AND CONTROL OF STI
pain). This involves using a multi prong approach that
incl udes the fol lowi ng:
Syndromic maRagement is simple, assures rapid,
same-day treatment, and avoids expensive or - Promotion of safer sexual behaviour
unavailable diagnostic tests. However, this approach - Promotion of early health-care-seeking
misses infections that do not demonstrate any behaviour
syndromes. Syndromic management of STls relates - lntroduction of prevention and care activities
closely to case management of STI which takes a across all primary health-care programmes,
holistic approach to management of the syndrome or including sexua! and reproductive health and
diagnosed STI by ensuring adequate history, clinical HIV programmes.
examination, correct diagnosis, early and effective
- Successful and cost-effective integrated
programmes for sexually transmitted infection
treatment, advice on sexual behaviour, promotion
and/or provision of condoms, partner notification and and HIV
treatment, case reporting and clinical follow-up as
- A comprehensive aPProach to case
management that encomp?ssoS: identification
appropriate.'
of the sexually transmitted infections
synd rome, ppropriate a nti microbia I treatment
Flowcharts for vaginal discharge have limitations, a
particularly in the management of cervical for the syndrome, education and counselling on
(gonococcal and chlamydial) infections.'A recent ways to avoid or reduce rlsk of infection with
systematic review and meta-analysis" to evaluate sexually transmitted pathogens, including HIV
the performance of the vaginal discharge syndromic promotion of the correct and consistent use of
management flow chart in managing cervical condoms and partner notification .tt
infections caused by Neisseria gonorrhoeae and
134
HIV/AIDS and ather Sexually Transmitted lnfections
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27 :7 87 Wijesooriya NS, Unemo M, Low N, et al. Global
11. Stringer EM, Giganti M, Carter RJ, El-Sadr W, , Estimates of the Prevalence and lncidence of
Abrams EJ, Stringer JS. Hormonat contraception Four Curable Sexually Transmitted lnfeetions in
and HIV progressron.- a multi-cauntry cohort 2012 Based on Systematic Review and Glabal
a na lysi s of MTCT- pl usi n itiative. Al DS Reporting. PtoS ONE ,2015; 10(12):
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14'
- tz. MitchelHS, Stephens E. Cantraceptive choice doi : 1 0. 1 37 1 ljou rna l. pone.0
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20A4;80:167- 173, Hoelscher lvl, Mmbanda D, Samky E, Lyamuya
r( 13. Miller CH HIV Prophylaxis for Victims of Sexual E, Mabey D, Grosskurth H, Hayes R Srng/e-dose
Assau/t; Guideline and Commentary. HIV azithromycin yersus penicillin G benzathine far
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Clinical Guidelines: NYS Department af Health the treatment of early syphilis. N Engl J Med.
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Vyankadorendera J, lngabire C, Ntirushua J,
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and Microbiotogicat Aspects of Trichomonas
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vagi nat i s.Ct i n M icrobiot Rev. 1 998; L 1 Q):@:, infectionin HIV positive andHlV- negative
317. women in Kigati, Rwanda. BMC infectious
Kissinger P Epidemiology and Treatrnent of. diseases 2011, 11:333.
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Roncin L, Toure B, Coffie P, Minga E et al-
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0/en/.Accessed 20 I 1 2 I 20 1 6. vaginosrs .Am J ObstetGynecol.20ll Mar;
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Treatment Guidel ine. Avai lable at: Latif A, et at. The Performance of the Vaginal
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Accessed 22/12/2016. Vaginal and Cervical lnfection: A Systematic
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32. Bernard HtJ, Burk RD, Chen Z. Van Doorslaer K, strategy for the prevention and control of
HausenH , de Villers EM. Ctssification of sexuailly transmitted infections: 2006 - 2015:
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2010.400:70-79.
135
CHAPTE{1
Pelvic Inflammffiry
Disease (P. l.D)
r
J DSeffah
I
The anatomy and the physiology of the fallopian tube

should be reviewed in chapter 3, the Female EP!DEMIOLOGY
I Reproductive Organs, for better understanding of this
I
chapter
Howard Kelly discovered the relationship between
t- sexual activity and the development of PID in 1898.
After the introduction of laparoscopy in the 1960s,
I
I
I DEFINITION
f research on pelvic inflammatory disease proliferated
r
I Pelvic inflammatory disease (PlD) refers to acute through the 1970s, 1980s, and 1990s, leading to
I
infection of the upper genital tract structures in major breakthroughs in the understanding of the
{
I women, involving any or all of the uterus, oviducts, microbial causes of the disease and its relationship
and ovaries; this is often accompanied by to reproductive disability, as well as enabling the
rI involvement of the neighboring pelvic organs. standardization of anti microbial treatment.
I
r lnvolvement of these structures results in

I endometritis, salpingitis, oophoritis, peritonitis, The true incidence of PID is unknown because of
perihepatitis and tu bo-ovarian abscess. inaccuracy of diagnosis. ln USA, there are 750,000
cases of PID each year in the United States, mainly in
Recamier in France practised vaginal drainage of women 75 lo Zgyears of age'.A crude marker of PID
!
? pelvic abscess between 1830 -1840 and Lawson in resource-poor countries can be obtained from
,. Tait in England performed the first abdominal reported hospital admission rates, where it accounts
i removalof tubo-ovarian abscess in7872. Afterthis it for 17% to 40% of gynaecological admissions in
was common knowledge that pelvic abscess resulted sub-Saharan Africa, 15% to 37%in Southeast Asia,
i
from primary infection of the fallopian tube. Neisser and 3"/o to 10% in lndia'. At the Korle-Bu Teaching
in L879 discovered Neisseriangonorrhoea. Hospital, Pl.D. caused 272outof 3,830 admissions
Westerman, Wertheim, and Curtis at different periods in1997 thusgivinga ratio of l:7lo
showed the pathogenesis of the disease in the
1920's'. P.l.D. is a major public health problem. C.
trachomatis organisms are difficult and expensive to
The advent of antimicriobial therapy and the culture. N. gonorrhoea has a short incubation period.
identification of asymptomatic carriers and the role of There is therefore a lack of natural or acquired
surgery became important in the control of pelvic resistance to these organisms. Many men and
infections. But as the incidence of UNSAFE women have been found to be asymptomatic carriers
I AB0RTIONS i ncreases, so does that of PL D. and there is significant resistance of gonorrhoea to
penicillin.
:
137
RISK FACTORS associated with PlD, whether the incidence of PID

can be reduced by identifying and treating women
R i sk factors for STD i ncl ude : with BV is unclear'.
Age lessthan 25years '^:
Young age atfirst sex Clinical Classification
N on-ba rrier contracePtion Acute (<30 days' duration), clinically diagnosed
New, mu lti ple, or symptomatic sexual pelvic inflammatory disease is caused by
partners spontaneous ascension of microbes from the vagina
Oral contracePtion or cervix to the endometrium, fallopian tubes, and
Cervicalectopy
adjacent structures. More than 85% of infections are
due to sexually transmitted cervical pathogens or
Factors that potentially facilitate PID include:
Previous episode of PID bacterial vaginosis-associated microbes, and
Sex during menses approximately 15% are due to respiratory or enteric
Vaginal douching o.rganisms that have colonized the lower genital tract
Bacterial vaginosis
Other sources of Pelvic infection Subclinical pelvic inflammatory disease has causes
-
lnfection caused by the introduction of foreign similar to those of acute pelvic inflammatory disease
bodies into the uterus. Causes include: and may be twice as common.
lntrauterine device use, Hysterosalpingo-
gram, Tubal insufflation, Dilation and Chronic (>30 days' duration) pelvic inflammatory
curettage and, Pregnancy interruption disease is defined as chronic infection due to
- Pelvic infection following major gynaecologic M ycoba cte r i u m tu bercu losls or acti nomyces species
surgery. rather than as chronic recurrent pelvic pain, which
- Puerperal and postabortal infections, septic remains common after the treatment of acute pelvic
pelvic thrombophlebitis, pyometra. inflammatory disease. (see Table 1 )
- lnfections in the pelvis due to primary
pathology in the gastrointestinal tract. CLINICAL PRESENTATION
- Tuberculosis
The classic high-risk patient is a menstruating
MICROBIALCAUSES woman younger than 25 years who has multiple sex
partners, does not use contraception, and lives in an
Sexually transmitted .organisms, especially N. area with a high prevalence of sexually transmitted
gonorrhoeae and C. trachomatis, are implicated in disease (STD). The abrupt onset of severe lower
many cases. Recent studies suggest that the abdominal pain during or shortly after menses has
proportion of PID cases attributable to N. been the classic symptom used to identify acute
gonorrhoeae or C. trachomatis is declining; of women pelvic inflammatory disease, although it is now well
who received a diagnosisof acute PlD,lessthan 50% recognized that both the onset and severity of
tested positive for either of these organismsu' symptoms can be more ill-defined and subtle.
Microorganisms that comprise the vaginalflora (e.g., Atypical, milder clinical manifestations have become
anaerobes, G. vaginalis, Haemophilusinfluenzae, more common as rates of N. gonorrhoeae infection
enteric Gram-negative rods, and Streptococcus have fallen6.
agalactiae) have been associated with PlD. ln
addition, cytomegalovirus (CMV), M. hominis, U. The symptoms associated with acute pelvic
urealyticum, and M. genitalium might be associated inflammatory disease include pelvic or lower
with some PID casesu. All women who receive a abdominal pain of varying severity, abnormal vaginal
diagnosis of acute PID should be tested for HIV as discharge, intermenstrual or post-coital bleeding,
well as gonorrhea and chlamydia, using NAAT. dyspareunia, and dysurian. Fever can occur, but
systemic manifestations are not a prominent feature
Screening and treating sexually active women for of pelvic inflammatory disease. Occasionally, right-
chlamydia reduces their risk for PlD. Although BV is upper quadrant pain suggestive of inflammation and
138
Pe lv i c I nf I a m matory Drsease e. l. D)
adhesion formation in the liver capsule (peri-hepatitis the potential for damage to the reproductive health of
or the Fitz-Hugh-Curtis syndrome) can accompany women, health-care providers should maintain a low
pelvic inflammatory disease'. l
threshold for the diagnosis of PID'. Hagar and
associates'ohave developed diagnostic criteria for
Many episodes of PID go unrecogn#d..,Fffitrough acute salpingitis. The following recommendations
some cases are asymptomatic, others are not for diagnosing PID are intended to help health-care
diagnosed because the patient or the health-care providers recognize when PID should be suspected
provider fails to recognize the implications of mild or and when additional information should be obtained
nonspecific symptoms or signs. Even women with to increase diagnostic certainty. (Table 2)
mild or asymptomatic PID might be at risk for
infertility?. Because of the difficulty of diagnosis and
Table 1: Clinicat Classification of PElvic lnftammatory Disease and Likely Microbial Causes
Clinical Syndrome Causes
Acute PID Cervical pathogens (N gonorrhoeae, C trachomatis, and M genitalium)

(<30 days duration)
Bacterial vaginosis pathogens (peptostreptococcus, bacteroides, M.
r
I
hominis, Ureaplasmaurealyticum, and clostridia species)
I
I Respiratory pathogens (H influenzae, Strep pneumoniae, GAS, and Staph
aureus)
r
I Enteric pathogens (E coli, Bacteroidesfragilis, GBS, and campylobacter
r
I species)
I
t-
f'
I
Subclinical PID o C. trachomatis and N. gonorrhoeae
rr' Chronic PID . Mycobacterium tuberculosis and actinomyces species

r
I
(>30 days'duration)
r
rI Adopted from: Campion, E. W., Brunham, R. C., Gottlieb, S. L., &Paavonen, J. (2015).Pelvic lnflammatory
Disease. N EJ M,37 2 ; 2039-2048. 6)
f
I
fade 2.
v CRITERIA RECOMMENDATION
I
i
f MINIMAL Presumptive treatment for PID should be initiated in
I
cervical motion tenderness sexually active young women and other women at risk
or for STDs if they are experiencing pelvic or lower
uterine tenderness abdominal pain, if no cause for the illness other than
or PID can be identified, and if one or more of the following
{
adnexal tenderness. minimum clinical criteria are present on pelvic
examination.
'i
The requirement that all three minimum criteria be
present before the initiation of empiric treatment could
result in insufficient sensitivity for the diagnosis of PlD.
ADDIT!ONAL One or more of the following additional criteria can be

I . oral temperature >101'F (>38.3"C); used to enhance the specificity of the minimum clinical
. abnormal cervical mucopurulent criteria and support a diagnosis of PID:
139
CRITERIA RECOMMENDATION
discharge or cervical friability;

o presence of abundant numbers of WBC
on saline microscopy of vaginal fluid;
. elevated erythrocyte sedimentation rate;
. elevated C-reactive protein; and
. laboratory documentation of cervical
infection with N. gonorrhoeae or C.
trachomatis.
DEFINITIVE
. endometrial biopsy with histopathologic A diagnostic evaluation that includes some of these
evidence of endometritis; more extensive procedures might be warranted in some
. transvaginalsonography or magnetic cases. Endometrial biopsy is warranted in women
resonance imaging techniques showing undergoing laparoscopy who do not have visual
thickened, fluidjilled tubes with or evidence of salpingitis, because endometritis is the only
without free pelvic fluid or tubo-ovarian sign of PID forsome women.
complex, or Doppler studies suggesting
pelvic infection (e.9., tubal hyperemia);
or
. laparoscopic findings consistent with
PID.
Adopted from: CDC. Pelvic inflammatory disease: STD treatment guidelines. 2075 U)
The gold standard for diagnosis of

P l. D. is by laparos- might not detectendometritis or early tubal
copy when pelvic inflammation can be confirmed and inflammation". lnaddition, it is an invasive surgical
microbiological study of tubal/peritoneal fluid made. procedure that is not readily available in many
settings and is not routinely performed, especially in
It is always necessary to exclude an ectopic preg- women with mild-to-moderate symptoms.
nancy. Hager and associates have suggested a Transcervical endometrial aspiration with
grading system for acute salpingitis based on histopathologicalfindings of increased numbers of
la pa rosci pic f i nd i ngs. plasma cells and neutrophils is more commonly used
to confirm the diagnosis of pelvic inflammatory
Grade 1-Uncomplicated salpingitis or salpingooo-
disease, and these findings are often seen in associa-
phoritis, unilateral or bilateral Without pelvic
tion with laparoscopically confirmed salpingitis.
peritonitis With pelvic peritoritis
However, endometrial biopsy is somewhat invasive,
requires skill for the pathological interpretation of the
Grade 2- Complicated salpingitis, salpingoophoritis,
sample, and results in a delayed diagnosis".
pyosalpinx, or tubo-ovarian abscess, with inflamma-
tory adnexal mass(es); unilateral or bilateral Without
Current CDC Recommendations for Antibiotic
pelvic peritonitis With pelvic peritonitis
TreatmentT
Guidelines for the treatment of pelvic inflammatory
Grade Large (8cm in diameter), tubo-ovarian or
3-
disease have been developed by the Centers for
pelvic abscess(es), spread of infection to upper
Disease Control and Prevention (CDC) on the basis of
abdomen, or ruptured tubo-ovarian abscess.
the results of clinical trials and the consensus
recommendations of expert clinicians.
Although laparoscopyhas been considered the
standard for the diagnosis of pelvic inflammatory
The treatment of PID is empirical and involves the
disease, it has high interobserver variability and
use of broad- spectrum combination regimens of
140
Pelvic lnflammatory Disease (PLD)
antimicrobial agents to cover likely pathogens. weeks of therapy.
Treatment should cover the principal pathogens, N. Alternative Parenteral Regimen

5 gonorrhoeae and C. trachomatis, regardless of the . Ampicillin/Sulbactam 3 g lV every 6 hours
L resu lts of testing. PLUS Doxycycline 100 mg orally or lV every 12
t
hours
Treatment should be initiated as soon as the pre-
sumptive diagnosis has been made, because preven- Intra m uscu ar lOral Treatment
r
I
tion of long-term sequelae is dependent on early lntramuscularloral therapy can be considered for
women with mild-to-moderately severe acute PlD,
tr administration of appropriate antibiotics. When
selecting a treatment regimen, health-care providers because the clinical outcomes among women
I
should consider availability, cost, and patient treated with these regimens are similar to those
I
acceptance. ln women with PID of mild or moderate treated with intravenous therapy'. Women who do
I not respond to lM/oral therapy within 72 hours
I
I
clinical severity, parenteral and oral regimens appear
to have similar efficacy. The decision of whether should be re-evaluated to confirm the diagnosis and
f
I
hospitalization is necessary should be based on should be administered intravenous therapy.
provider judgment and whether the woman meets
Recom mended I ntra m us cular I Oral Regi mens
any of the suggested criteria. .Ceftriaxone 250 mg lM in a single dose
r PLUS Doxycycline 100 mg orally BD for 14
t The criteria for in-patient admissions for PID include
i
t
. surgical emergencies cannot be
days
WITH* or WITHOUT Metronidazole 500 mg
r excluded;(e.g., appendicitis, peritonitis)
orally twice a day for 14 days
I
I . tubo-ovarianabscess;
I
( . pregnancY; (see controversies)

OR
. Cefoxitin 2 g lM in a single dose and
I . severe illness, nausea and vomiting, or
Probenecid, 1 g orally administered concur-
high fever;
rently in a single dose
I
r
I
. unable to follow or tolerate an outpatient
PLUS Doxycycline 100 mg orally BD for 14
,r oral regimen; or
. no clinical response to oral antimicrobial
days
WITH or WITHOUT Metronidazole 500 mg
I
therapy.
orallytwice a dayfor 14 days
I o Teenagers, since they have a long repro-
OR
. Other parenteral
I
J ductive life to protect (see controversies) third-generation
cephalosporin
Recommended Parenteral Regimens
(
I
.Cefotetan2glY every 12 hours
(e. g., ceftizoxi me or cefotaxi me)
PLUS Doxycycline 100 mg orally BD tor 74
PLUS Doxycycline 100 mg orally or lV every
day
12 hours
WITH or WITHOUT Metronidazole 500 mg
OR
. Cefoxitin 2 g lV every 6 hours
orally twice a dayfor 14 days
PLUS Doxycycline 100 mg orally or lV every
Other Management Considerations
12 hours
To minimize disease transmission, women should be
OR
: . Clindamycin 900 mg lV every 8 hours
instructed to abstain from sexual intercourse until
PLUS Gentamicin loading dose lV or lM (2 therapy is completed, symptoms have resolved, and
. sex partners have been adequatelytreated
a
mg/kg), followed by a maintenance dose
(1.5 mg/kg) every 8 hours. Single daily
Complications and Management
dosing (3-5 mdkd can be substituted.
- Transition to oral therapy can usually be initiated
Fitz-H ugh Curtis Syndrome
Perihepatitis is an inflammation of the liver capsule
t within 24to 48 hours after clinical improvement, and
which is followed by adhesions between the liver and
oral therapy should be continued to complete 2 the parietal peritoneum. The treatment is achieved
L4t
Comprehensive Gynaecology in the
Topics
failure' Shocl<
may enlarged vascular space or cardiac
with antibiotics. The differential diagnosis J.r.[pt in 25%-50%of patients w ith gra m negative
pyelonephritis and
in.frO. pneumonia, cholecystitis, from 40% to
rnay be bacteraemia, and the mortality ranges
appendicitis' Laparoscopy or laparotomy tubo-ovarian abscess'
60o/o" .lt may follow ruptured
needed to exclude anY ofthese' gram-negative organ-
Endotoxins are produced by
isms such as E coli, B' flagils' Proteus mirabilis'
Chronic P.l.D.
it-lir t.trftt from inadequate treatment for acute AerobacteraerogenesorPseudomonasaeroginosa.
exotoxins which
Pl.D. The manifestations include chronic
pelvic pain' Cram positive organisms produce
perfringes
Jysmenorrhoea, dyspareunia and
infertility due to *rV .rut. lethaf effect e'g' Clostridium
The pelvis and S. aureus.
biocked tubes and peritubal adhesions.
be matted
may be frozen as all the organs may endotoxins cause
involves Reactingwith the endothelium' the
togettrer in dense adhesion' Treatment cells' They
the adhesions or damage and desquamation of endothelial
anitgesics and surgery to release forming platelet and
interact with blood components'
correct the tubes. capillary
leucocyte aggregates' This increases
purrn.uOitity- preferentially in the
postcapillary-
Acute Pelvic Abscess
This may follow acute exacerbation
of chronic PID' venules.
The patient is admitted to the hospital' lntravenous control of infections
antibiotics The treatment should target the i
fluids should be administered' Parenteral of impaired

and blood transfusion tocorrect anaemia
must be with antibiotics and the correction of
of the serum hemodynamic state with the administration
administered. Careful correction
of the intravenousfluid,andpossiblybloodproducts'The
electrolytes and frequent clinical appraisal resuscita-
patients a re necessarY'
rnunuga*.nt therefore requires intensive
Care Unit
tion and maintenance at the lntensive
(lCU). Vasoactive drugs including a-adrenergic
Surgical management are more
PosLrior colpotomy is done for an
abscess that blockers and B-adrenergic stimulants
Dopamine' a
presents in the cul-de-sac' The criteria
are: the beneficial than potent vasocontrictors'
so; it should be B-adrenergic stimulant, given at
3mg/kg/min is a
abscess must be midline or nearly mesenteric
adherenttothecul-de-sacperitoneum;itshouldbe vasodilator and improves splanchnic'
produce positive
cystic or fluctuant' Prolonged drainage
by inserting and renal perfusion' Corticosteroids
with
Malecot catheterfor 48-72 hours is
advisable' inotropic effect, promote gluconeogenesis
intense
gtr.ot. made available to the CNS; inhibits
Extraperitoneal abdominal drainage
is necessary if inflammatory reaction mediated by
the complement
lt is There should be
the abscess does not present in the cul-de-sac' cascade and leucocyte aggregation'
in ruptured tubo-ovarian abscess' control the release
indicated removal of the focus of infection to
performed for tubo- should be
Salpingooophorectomy must be of exotoxin. Septic products of conception
or bilateral evacuated 4-6 hrs after initiating
therapy'
ovarian abscess. This may be unilateral
and may be accompanied by hysterectomy
TUBERCULOSIS
SepticPelvicThromboPhlebitis .
of antibiotics
The current treatment is the application Pelvictuberculosisislimitedtothereproductivetract
as septic tube' The
and heparin. The response is dramatic particularly the endometrium and fallopian
and tuberculosis' This
multiple thrombi develop in the hypogastric infectious agent is Mycobacterium
veins is now out of peritonitis is
common iliac veins' Ligation of the runs a chronic course' Tuberculous
vogue. associated with tuberculosis of
the pelvis' The
malaise' pelvic
clinical manifestatiolls dre: general
pain, menstrual irregularity and infertility'
Pelvic
SePtic Shock
failure that -20% of woman with
Shock is a state of generalized circulatory tuberculosis is found in 10%
results in decreased tissue perfusion'
lt involves pulmonary tuberculosis "' The diagnosis
is certain
inadequate cardiac output due to
reduced venous smaller' irregular
on HSG-calcified lymph nodes' or
abnormally
return; diminished circulatory volume'
L42
Pelvic I nflammatory Disease (P. l.D)
calcifications in the adnexal area, obstruction of the geographic regions. Though chlamydia appears
fallopian tubes, multiple constrictions, endometrial more benign, inadequate treatment causes extensive
adhesions and lymphatic extravasation of contrast inflammation. The recommendation to do HIV
;
material. Premenstrual endometrial curettings screening after pre-counselling for all patients with
should be submitted for microbiolog{eal stldies. PID may raise an ethical issue.
Treatment protocols involving isoniazid, rifampicin,
streptomycin, ethambutol and pyrazinamide should 3. Contraception: For the prevention of STD'S, the
be strictly adhered to for therapeutic success. Family Planning Clinics may prescribe barrier
methods.
Surgery is indicated forr . A woman's risk of pelvic inflammatory
1. Persistence of enlargement of adnexal mass disease (PlD) is not increased by IUD use.
after 4-6 months of anti-tuberculosis The progestin IUS (Mirena) may decrease
antibiotics risk by decreasing ascending infection due to
2. Persistence of pelvic pain thickening of the cervical mucus. The
3. Primary unresponsiveness and evidence of copper IUD does not affect risk'/. The historic
continuous endometrial infection on biopsy association between lUDs and PID origi-
4. Difficulty in obtaining a patient's cooperation nated with the Dalkon Shield, an IUD used
forcontinued longterm therapy ". in the 1970s that had a braided filament
string that was associated with increased
PREVENTION
risk of PlD. Modern lUDs have monofila-
The most important public health measure for the ment strings that do not share this risk. But
prevention of pelvic inflammatory disease is the placement of an IUD at the time of an active
prevention and control of sexually transmitted pelvic infection does increase risk of devel-
infections with C. trachomatis or N. gonorrhoeae. oping PlD.
Many high-income countries have implemented
o The PILL decreases the risk for acute
gonococcal PID while it increases the risk for
programs to screen and treat women for asymptom-
atic C. trachomatis infection, on the basis of evidence
acquiring cervical chlamydia'u. The pill in
from randomized controlled trials indicating that addition does not protect against tubal
damage and may have a harmful effect'u.
screening for and treating cervical C. trachomatis
infection can reduce a woman's risk of pelvic inflam-
4. Laparoscopy though not common in many centres
matory disease by approximately 30 to 50% over 1
in the sub-region, is the gold standard for the
yearu. Primary prevdntion with comprehensive sex
definitive diagnosisfor PlD. Causative organisms can
education, promotion ofthe use of condoms, and
be cultured from the exudatesfrom the tubes.
provision of condoms are cornerstones of the preven-
tion of sexually transmitted infection globally and also 5. The isolated organisms have proven differentfrom
have benefits for the prevention of pelvic inflamma- the isolates from the endocervix, thus invalidating
tory disease. thefactthat PID is always an ascending infection.
6. Culdotomy for the drainage of pelvic abscess has
CONTROVERSIES AND DISCUSSION
its drawback because the offending organ cannot be
removed.
1. UNSAFE ABORTION: lt is common in our commu-
nities. The complications include PID and its 7. Ultrasound guided aspiration of small pelvic
sequelae. The Abortion Law of Ghana'o should be
abscesses has been performed in selected cases.
reviewed especially the limit of gestational age for
Combined with potent antibiotic administration, the
legal abortion. When practitioners are well trained result has been good, elsewhere but has not been
and the surgery is performed in hygienic conditions,
duplicated in Ghana.
the incidence of PID would reduce.
8. PID is not common durlng pregnancy but if it
2. Gonorrhoea and chlamydia are major causes of occurs, it is usually within the first 12 weeks before
PID and cervicitis. Their prevalences vary from
143
the mucous plug can act as an adequate barrier' for treatment of PlD, and the clinical response to
Pregnant women with suspected PID should be outpatient treatment is similar among younger and
hospitalized and given parenteral antibiotics. PID older women. The decision to hospitalize adoles-
during pregnancy increases the risk of fetal wastage, cents with acute PID should be based on the same
preterm delivery and increases maternal criteria used for older women'.
morbidity".However, others have argued that in
practice, if PID occurs in the first trimester, the 10. Some studies have demonstrated that
patient is more likely to present as a result of the Chlamydia Antibody titres (CATs)are of predictive
value in the detection of tubal damage and are
complication of the inflammatory process with
quantitatively related to the severity of damage' For
conditions like Threatened, lnevitable, lncomplete or
practical clinical purposes, Chlamydia serology is
Septic Miscarriagesl8; while in late pregnancy we
useful mainly as a screening test for the llkelihood of
would be talking about Chorioamnionitis rather than
tubal damage in infertile women and may facilitate
PlD. lt is therefore unusual to make a diagnosis of
decisions on which women should proceed with
PID in pregnancyl
fu rther i nvestigations without delay"'
9. No evidence is available to suggest that
adoles-
cents have improved outcomes from hospitalization
REFERENCES
1. John D. Thompson, Michael R Spence Pelvic 2039-2048.

lnftammatory Disease ln: TeLinde's Operative 7. Centers for Disease Control and Prevention. Pelvic
Gynaecology, 7th edition Thompson and Rock inflammatory dlsease; STD treatment guidelines.
J.B. LippincottCo (1992) 24: 555-560 Atlanta: Department of Health and Human
Services, 2015 (http:llwww 'cdc .govl std/ treat-
2. MY Sternberg M, Zaidi A, St Louis ME,
Sutton mentl2015/pid .htm).
Markowitz LE. Trends in pelvic inflammatory
drsease hospital discharges and ambulatory visits, 8. Paavonen J, Westrom L, Eschenbach D. Pelvic
tJnited States, 1985-2001. Sex lransm Dis. inflammatory disease. ln: Holmes KK, Sparling PE
2005;32:778-784 Stamm WE, et al., eds. Sexually transmitted
4th ed. New York: McGraw-Hill, 2008-
drseases.
3. RossJDC. Pelvic inflammatory disease BMJ Clinical
Evidence.2013. Retrieved f rom 9. Eschenbach D. Acute pelvic inflammatory dtsease'
http : / lwww. n c b i.n I m. n i h. gov / p u b m ed I 2 43 307 7 1 Gtob.Libr. Women's Med., 2008; 1756-2228.
http : I /d oi. orgl 1 0. 3 843/G LOW M. 1 0029
4. Kwame-Aryee RA, SeffahJD. Pelvic lnflammatory
Dlsease ln: Handbook of GynaecologyA practical
l1.Hager WD, Eschenbach DA, Spence MR, Street
Guide to student and Practitioner Max Ass ltd
RL. Criteria for diagnosis and grading of
1998;6;36-39
Salpingitis.ObsGynecolJ 983: 61; 113 - 114
5. Burnett AM, Anderson CE Zwank MD. Laboratory-
confirmed gonorrhea andlor chlamydia rates in 11. Jaiyeobao Soper DE. A practical approach to the
diagnosrs of pe I v i c i nf I a m m a to ry d i sea se. I nf ecti o u s
.ctinicalty diagnosed pelvic inflammatory disease
and cervicitis. Am J Emerg Med 2012;30:1114 7 ' Dtseases in Obstetrics and Gynecology, 2011,
753037.
6. Campion EW, Brunham RC, Gottliebsl. Paavonen
J. eO15). Pelvic lnflammatory Disease.New 12. John D Thompson and MichaetR Spence "septic
England Journal of Medicine, 2015; 372: Shock". ln TeLindes Operative Gynaecology 7th
t44
f_lm
ri
I
c
Pelvic I nflammatory Disease (P. l. D) I
i
,.J
J
Edition Eds: Thompson and Rock.!B Ltd 17. Blanchard AC, Pastorek JG, Weeks T. Pelvic
(199? 24:588-590 inflammatory disease during pregnancy. South
Med J. L987; 80(11):L363-5.
13. John D. Thompson, Michael S,
i
Pe lv ic tu berculosis dl'sease 18. Lara-Torre E, Pinkerton JS. Viable intrauterine i$
ti
Gynaecology, 7th edition pregnancy with acute salpingitis progressing to
LippincottCo (1992); 24: 5 septrc abortion: a case report. J Repro Med. 2002; .
47(11):959-61.
14. Abortion law in Ghana ;
t{
L9. Akande VA, Hunt LE Cahill DJ, Caul EO, Ford 5
15. Senanayake E Kramer DG WCL, Jenkins JM. Tubal damage in infertile I
J
J,,
etiology of PID: New wotn€n: prediction using chlamydia serology.
obstetGynecol 1 980; J 38; 852- Human Reproduction (Oxford, England), 78, $
2003;18: 1841-7. 1 ::
16. IPPF Handbookon lnfertility
I
l-
t.'
lt
I
:
!.
f-
i
r
a
II
I
{
t
F
F
I
t
r
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r
I
r
rr
I
I
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r
rt
rt
rt\
f
t
{I
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(
I
I
145
i
f
(
t46
CHAPTE{2
Abnormal Uterine Bleeding

B. A. Ekele
INTRODUCTION related to patterns of uterine bleeding. These

concerns led to the formation of the Menstrual
Abnormal uterine bleeding (AUB) in non-pregnant,
Disorders Working Group within the lnternational
reproductive-age women is a common gynecological
I
Federation of Gynecology and Obstetrics (FIGO),
I
symptom. lt can be defined as any menstrual which has subsequently become a standing
r
I
bleeding from the uterus that is abnormal in volume
committee, the Menstrual Disorders Committee.
I (excessive duration or heavy), regularity, timlng
I This group has developed internationally supported
r (delayed or frequent) or that is non-menstrual like
recommendations on definitions and terminology for
I
inter-menstrual bleeding (lMB), post coital bleeding
I
I AUB symptoms ''u as well as a new classification of
r (PCB) and post-menopausal bleeding (PMB). u.
underlying causes of AUB in the reproductive years
Most of the text in this chapter is from the
I
I Historically, there has been a wide range of poorly

r defined terms used to describe AUB symptoms and Com m ittee's recom mendations
u.
r
I
I etiologies. The beginning of conflicting terminology
r for AUB is said to date back to the late 1700s when Descriptive terminologies recommended that
(
t
I William Cullen, Professor of Physic at the University should be used in history are shown in Table 1.
Ir of Edinburgh, Scotland, began to write his medical They include: Heavy Menstrual Bleeding (HMB),
t research texts in English rather than in Latin '. Light Menstrual Bleeding (LMB), Heavy Prolonged
However, he was fohd of demonstrating his classical Menstrual Bleeding, lrregular Menstrual Bleeding,
I language skills to his students and coined the Latin Absence of Menstrual Bleeding (Amenorrhoea),
I
r term menorrhagia, meaning "to burst forth monthly," lnfrequent Menstrual Bleeding, Prolonged Menstrual
r
I
to describe the excessive bleeding that many of his Bleeding, Shortened Menstrual Bleeding and
i patients experienced. irregular non-menstrual bleeding like IMB and PCB.
r{
I
The varied use of terminology to describe AUB
I Table 1: Preferred Terminologies
l symptoms has led to difficulties in documenting
I symptoms; reaching consensus on the use of various Volume Heavy Normal Light
diagnostic techniques and medical and surgical Regularity lrregular Regular Absent
therapies; design and interpretation of basic, Frequency Frequent Normal lnfrequent
Duration Prolonged Normal Shortend
r translational, and clinical research; and attempts to
I conduct multicenter or multinational clinical trials '''' Other Intermenstrual, Premenstrual,
Post-coital, Unscheduled bleeding (in
association with the use os sex steroids)
r
i\_ Over the past 5years there has been a major
:
( international discussion aimed at reaching
l. agreement on the use of well-defined terminologies to
I
describe the normal limits and range of abnormalities
t
:,
a
L47
.-------:------\
Terminologies to be discarded include: . Polymenorrhoea

. Menorrhagia . Menometrorrhagia
. Hypermenorrhea . Metrorrhagia
. Hypomenorrhea . Dysfunctional uterine bleeding (DUB)
. Oligomenorrhoea
Suggested "normal limits" for uterine bleeding in the mid-reproductive years are shown in Table L below.
Table 2: Suggested Normal Limits for Uterine Bleeding (Ref 7)
rrera HndffiidH
rerrr
*E{tt6nry I ,{{** d8r$
24-3t d.yt
. :.. .. ,..
>38 dryE
*qr$i&y Ilo bhcdtng
',,,,,'l:{3S,&rB nrrMa* In t2 m
..: >2O @s varffion In 12 rn
o(@r' >8 days
:, ,,!L}*-S dil?qf
.:
,. r ,,dryx'
fibt ,.,'l .ml
.1,, .,'.$ .'rrrl
', rr{3 ml
CAUSESOFAUB facilitate the development of sub classi cation

systems, as necessary. lt was envisioned that the
FIGO Classi cation'u' most straightforward parts of the system would be
The basic classi cation system is as shown below in used at a primary care level and that the sub
Figure 1. There are nine main categories, which are classi cations would be most relevant at specialist
to the acronym PALM-COEIN
arranged according and research levels.
(pronounced "pahm-koin"): polyp; adenomyosis;
leiomyoma; malignancy and hyperplasia; The term "DUB," which was previously used as a
coagulopathy; ovulatory dysfunction; endometrial; diagnosis when there was no systemic or locally
iatrogenic; and not yet classi ed. In general, the de nable structural cause for AUB, is not included
components of the PALM group are discrete in the system and should be abandoned. Women
(structural) entities that can be measured visually who t this description generally have one or a
with imaging techniques and/or histopathology, combination of coagulopathy, disorder of ovulation,
whereas the COEIN group is related to entities that or primaryendometrial disorder-the lastof which
are not de ned by imaging or histopathology (non- is most often a primary or secondary disturbance in
structural). local endometrial hemostasis.
The categories were developed based on the group

recommendations and each was designed to
L48
Abnormal Uterine Bleedi ng
"endometrial" tissue beneath the endometrial-

myometrial interface, as determined via hysterec-
tomy- an approach that has limited value in a clinical
classification system. Consequently and because
there exist both sonographic " and magnetic reso-
nance imaging (MRl)-based diagnostic criteria 'o''u,
adenomyosis has been included in the
classi cation system. Recognizing women's limited
access to MRI worldwide, it is recommended that
sonographic criteria for adenomyosis comprise the
minimum requirements for assigning an individual
the diagnosis of adenomyosis in the PALM-COEIN
Figure 1. Basic classi cation system. Thehasic system classi cation system 'u. As is the case with polyps
comprises four categories that are de ned by.objective and leiomyomas, adenomyosis is a disorder that
structural criteria (PALM: polyp; adenomyosis; should have its own sub-classi cation system ".
leiomyoma; and malignancy and hyperplasia), andfour
that are unrelated to structural anomalies (COEI:
Leiomyoma
coagulopathy; ovulatory dysfunction; endometrial; (AUB-L)
iatrogenic), and one reserved for entities that are not yet
classi ed (N).
Benign bromuscular tumors of the myometrium are
known by several names, including "leiomyoma,"
Source; FIGO tRet 61 "myoma," and the frequently used " broid."
"Leiomyoma" is generally accepted as the more
accurate term and was selected for use in the
present system. The prevalence of these lesions (up
Polyp (AUB-P) to 70% in Caucasians and up to 80% in women of
There is no controversy regarding the inclusion of African ancestry ", their spectrum of size and
>
/ endometrial and endocervical polyps. These epithe- location (subendometrial, intramural, subserosal,
lial proliferations comprise a variable vascular, and combinations of these), and the variable number
glandular, bromuscular and connective tissue of lesions in a given uterus require that they be
component and are often asymptomatic, but it is afforded a separate categorization in the system. Like
) polyps and adenomyosis, many leiomyomas are
i generally accepted that at least some contribute to
I
I the genesis of AUB '.

The lesions are usually benign asymptomatic, and frequently their presence is not
but a small minority may have atypical or malignant the cause of AUB. Furthermore, leiomyomas have
features
n''0. widely varying rates of growth, even in a single
individual".
t^
For the basic classi cation system, polyps are
i
categorized as being either present or absent, as The primary classi cation system re ects only the
v presence or absence of one or more leiomyomas
de ned by one or a combination of ultrasound and
hysteroscopic imaging with or without regardless of the location, number and size. lt is
i histopathology. recommended that the criteria for determining the
I
I
presence of leiomyomas would require only
I Adenomyos is sonographic examination con rming that one or
(AUB.A) more such lesions are present.
I
The relationship between adenomyosis and the

I
genesis of AUB is unclear and therefore extensive ln the secondary system, the clinician is required to
additional research is required ". Estimates of the distinguish leiomyomas involving the endometrial
-
I
prevalence of adenomyosis vary widely, ranging from cavity (submucosal [SM]) from others (O) because it
;\*
5% to 7O"/o " which in part, is probably related to is generally considered that submucosal lesions are
r
I
inconsistencies in the histopathologic criteria for the most likely to contribute to the genesis of AUB. ln
t diagnosis. Generally, these criteria have been based addition to the primary classi cation system, both
I
I
r on histopathologic evaluation of the depth of secondary and tertiary classi cation systems for
I
r
I
r
!
149
,.
I
I
j
r
leiomyomas have been developed and have potential clinical applications and for clinical investigation (Fig. 2).
r*dr$*H{,d}stilr#
l$d*{m*xh&rffi
Figure 2
Source; FIGO tRet 7l
The root of the tertiary classi cation system is a associated with AUB. High quality evidence
design for sub-endometrial or submucosal demonstrates that approximately L3% of women
leiomyomas with HMB have biochemically detectable systemic
disorders of hemostasis, most often von Willebrand
Malignancy and hyperplasia (AUB-M) disease'0. However, it is not clear how oftenthese
Although relatively uncommon, atypical hyperplasia abnormalities cause or contribute to the genesis of
and malignancy are important potential causes or AUB and how often they are asymptomatic or
ndings associated with AUB and must be minimally symptomatic. lt is important to consider
considered in nearly all women of reproductive age. such disorders, partly because they probably do
The present classi cation system is not designed to contribute to some cases of AUB and partly because
replace those of WHO and FIGO for categorizing evidence indicates that relatively few clinicians
endometrial hyperplasia and neoplasia. consider systemic disorders of hemostasis in the
Consequently, when a premalignant hyperplastic or differential diagnosis of women with HMB ".
malignant process is identi ed during investigation of For some women of reproductive age group, chronic
women of reproductive age with AUB, it would be anticoagulation is a necessary and life-preserving
classi ed as AUB-M and then sub-classi ed using intervention but one that may result in the
the appropriate WHO or FlG0 system. undesirable adverse effect of AUB, most often HMB.
Although such AUB could justi ably be considered
Coagulopathy GUB-C) iatrogenic but it is recommended to classify affected
The term "coagulopathy" encompasses the spectrum women as having a coagulopathy (AUB/HMB-C)'
of systemic disorders of hemostasis that may be
150
Abnormal Uterine Bleedi ng
Ovulatory dysfunction (AU B-O) avai lable to clin icians.

Ovulatory dysfunction can contribute to the genesis of There may be other primary endometrial disorders
AUB, generally manifesting as a combination of that do not present as HMB per se, but instead
unpredictable timing of bleeding and varia*ah.amount may cause IMB or prolonged bleeding, the latter
of ow (AUB), which in some cases resuB ++l.tlMB *. of which may be a manifestation of de ciencies in
ln many regions, ovulatory disorders corryi@,the the molecular mechanisms of endometrial repair.
vast majority of cases encompassed by the now- Such disorders may be secondary to: endometrial
discarded term "DUB." Disorders of ovulation may in ammation or infection; abnormalities in the local
present as a spectrum of menstrual abnormalities in ammatory response; or aberrations in
ranging from amenorrhea, through extremely light endometrial vasculogenesis. However, the role of
and infrequent bleeding, to episodes of unpredictable infection and other local in ammatory disorders in
and extreme HMB requiring medical or surgical the genesis of AUB is not well de ned and is
intervention. Some of these manifestations relate to sometimes confounded by the normal presence of
the absence of predictable cyclic progesterone in ammatory cells in the endometrium.
production from the corpus luteum every 22-35
days, but in later reproductive years many relate to
latrogenic (AUB-l)
unusual "disturbed" ovulations, which have been
labeled as "IuteaI out-of-phase" events "'". Medical interventions or devices can cause or
contribute to AUB (AUB-l). These include medicated
Ma ny ovu latory d isorders ca n be traced to
endocrinopathies (like polycystic ovary syndrome,
or inert intrauterine systems and pharmacologic
hypothyroidism, hyperprolactinemia, mental stress, agents that directly impact the endometrium
obesity, anorexia, weight loss, or extreme exercise interfere with blood coagulation mechanisms, or
such as that associated with elite athletic training). ln
inuencethesystemic control of ovulation.
some instances, the disorder may be iatrogenic, Unscheduled endometrial bleeding that occurs
caused by gonadal steroids or drugs that impact during the use of gonadal steroid therapy is termed
"breakthrough bleeding (BTB)" and is the major
dopamine metabolism, such as phenothiazines and
tricyclic antidepressants. lt is also well recognized component of the AUB-I classi cation. For the
that unexplained ovulatory disorders frequently occur clinician faced with patients experiencing
unscheduled vaginal bleeding while using gonadal
at the extremes of reproductive age: adolescence and
the menopause transition. steroid therapy, ii is important to ensure that the
bleeding is coming from the endometrium (and
Endometrial (AUB-E) not serious pathology), then be properly equipped to
When AUB occurs in
the context of predictable counsel and, if necessary, treat the patient
and cyclic menstrual bleeding, typical of appropriately.
ovulatory cycles, and particularlywhen no other administered single-agent or
Systemically
de nable causes are identi ed, the mechanism is combination gonadal steroids-including
probably a primary disorder of the endometrium. lf estrogens, progestins, and androgens-impact the
the symptom is HMB, there may exist a primary control of ovarian steroidogenesis via effects on the
disorder of mechanisms regulating local endometrial hypothalamus, pituitary, and/or ovary itself, and
"hemostasis" itself. lndeed, high-quality evidence a
also exert direct effect on the endometrium.
has demonstrated de ciencies in local production of These features of gonadal steroids are exploiied in
vasoconstrictors such as endothelin-1 and the form of hormonal contraceptive agents such as
prostaglandin Fr,, andfor accelerated lysis of oral, transdermal/ vaginal, and injectable progestin
endometrial clot because of excessive production of or estrogen-progestin compounds. When
plasminogen activator '0, in addition to increased estrogen-progestin agents are administered
I local production of substances that promote cyclically, scheduled uterine bleeding generally
vasodilation, slrch as prostaglandin E, and occurs in conjunction with the periodic withdrawal of
.
prostacyclin (lr)'u''u Despite this evidence, some of the steroidal agents. However, when unscheduled
I
t
a which has been available for more than 2 decades, bleeding occurs in the context of cyclic
I tests measuring such abnormalities are not currently administration, the woman may be considered to
I
I have BTB and be categorized as AUB-1. Combined
i'
I 1s1
estrogen-progestin preparations may be venous malformations and myometrial

hypertrophy
administered continuously (in the case of progestin- have been poorly de ned, inadequately examined,
only agents such as depo medroxyprogesterone or both. There may be other disorders, not yet
acetate, continuous administration is the nonn) with identi ed that would be de ned only by biochemical
the goal of achieving amenorrhea. ln such insBnces, or molecular biology assays. Collectively, these
any bleeding may be considered to be unsc?ffittfud entities (or future entities) have been placed in a
and therefore, classi ed as AU B-1. category termed "not yet classi ed'" As further
evidence becomes available, they may be allocated a
Agents that interfere with dopamine metabolism a{so separate category or be placed into an existing
have the potential to cause AUB secondary to category in the system.
d isorders of ovu lation. Tricycl ic anti-depressants
(e'g.
General assessment
amitriptyline and nortriptyline) and phenothiazines
lf a woman of reproductive age with either acute or
belong to a group of drugs that impact dopamine
chronic vaginal bleeding suspected to be AUB
metabolism by reducing serotonin uptake.
presents, the clinician should perform a careful
evaluation to ensure that the bleeding was not related
HMB is a relatively common consequence of the use
to an undiagnosed pregnancy and emanates from the
of anticoagulant drugs such as warfarin, heparin, and
cervical canal, rather than another location. The
low molecular weight heparin. The mechanism
presence of a pregnancy may be reliably determined
seems to be straightforward because, in such
instances, there is impairment of the formation of an
with a combination of directed history and
urine/serum assay for the B-subunit of human
adequate "plug" or clot within the vascular lumen.
chorionic gonadotropin. Women with both acute and
Women using such agents essentially have a
chronic AUB should be evaluated for anemia with
systemic disorder of hemostasis that is similar in
hemogl ob n esti mation andl or hem atocrit ( prefera bly
manifestation and management to inherited
i
a full blood count, including platelets). Once the

disorders of hemostasis. Consequently, this type of
bleeding has been con rmed or, in the absence of
iatrogenic AUB should be placed in the AUB-C
any other identi able source, suspected to be of
category.
uterine origin, the clinician would proceed in a
Notyetclassi ed (AUB-N) systematic fashion, designing the assessment to
Several uterine entities might contribute to, or address each of the components of the
cause, AUB in a given individual; however, this classi cation system (Figure 3).
has not been demonstrated conclusively because
these entities-such as chronic endometritis, arterio-
t52
Abnormal Uteri ne Bleeding
*luileilil
jl*{F&dffin
I
r
t
I
I
I
a
I
I
I
Enrtai
I
I
i
I
lkr
I
I
T
t
I
t
I
rxh
I
I
I
I
v
I
atffiar
I
t
r
I
I
Figure 3
I Source: FIGO tRef 7l
r
r
I
t
rI MANAGEMENT detailed menstrual calendar with a precise record of

t the amount of menstrual or other blood loss for three
r Treatment is dependent on the results of evaluation months. Many cases of abnormal uterine bleeding
r
I and the cause. lt is important to know that some will resolve spontaneously and no specific treatment
cases of menstrual abnormality resolve will be required, as earlier mentioned.
-
I
spontaneously and that treatment should only be
r given where indicated by the findings on examination 2. Specific treatment will depend upon the cause
f
I and investigation. ln such patients, reassurance may (as discussed in the relevant chapters)
I
r be enough as there may be spontaneous resolution.
r Principles of management should be borne in mind,
I ABNORMAL UTERINE BLEEDING IN POST-
I namely, general measures and treatment of the MENOPAUSALWOMEN
r specific cause when identified.
r
I
The flow chart below (Figure 4) is a guide for the
r 1. General Measures
I management of AUB in post-menopausal women.
i Explanation of the situation and reassurance of the
( Most cases are either as a result of malignancies,
patient is one of the most important steps in
r atrophy or prolapse and definitive treatment is as
management particularly in adolescents. lf in doubt,
outlined in the relevant chapters that address the
t a useful measure of the exact nature and amount of
disease entities.
i-- the bleeding pattern is to ask the patient to keep a
i
a
i.
I
a
I
r.
I
153
i
. ;----!
Figure 4: Flow chart for management of a woman with postmenopausal bleeding
Biopsy & treat as Ultrasound &

Treat with topical Reduce with Avulse with
cervical screening
oestrogen or surgery forcep (histology) appropriate (HPV VIA, PAP)
Abnormal cervix screen

Treat as appropriate
..
CONCLUSION to be fully realized. Accumulation of benefits i
will be proportion to its adoption by clinicians

The FIGO nomenclature and the PALM COEIN and specialists.
classification of Abnormal Uterine Bleeding (AUB) in
the non-pregnant woman in the reproductive age ll. Forthe purpose of the Fellowship examinations
group has simplified and unified terminologies. lt in the West African sub region, candidates are
facilitates clinical and research collaboration. lt also advised not to completely discard the old
serves to enhance and clarify communication within terminologies yet but rather be armed with
and between special ists. both old and new terminologies until such a
time when candidates will be 'on the same
However, AUB in the post-menopausal woman is a page' and level with some of the more senior
different category and is usually sinisterthus requires Fellows and examiners. For instance, in this
systematic evaluation. Second Edition of ComPrehensiYe
Gynaecology in the Tropics textbook, we would
DISCUSS!ON AND CONTROVERSI ES not be surprised if the terms that are supposed
to be discarded are still used generously by
l. Presently the advantages and benefits of this authors of some of the chapters. We are truly in
new classification over the old practice remain transitional period !
REFERENCES
7. Fraser lS, lnceboz US. Def ining disturbances of the terminology and definitions for disturbances of
'menstrual menstrual bleeding. Fertil Steril 2008; 90: 2269.
cycle. ln: O'BrienPMS, Cameron l,
MacLean AB, editors. Drsorders of the Menstrual 3. Fraser lS, Critciley HO, Munro MG. Abnormal
Cycle. lst edn. London: RCOG Press; 2000. p. uterine bteeding: getting our terminologies
L41-152. straight. Curr Opin Ostet Gynecol. 2007 ; 19: 591
2. Woolcock JG, Critchley HO, Munro MG, et al. 4. Fraser lS, Critchley HO, Munro MG et al. A process
Review of the confusion in current and historical designed to lead to international agreement on
154
Abnormal Uteri ne Bleed i ng
terminologies and definitions used to

describe imaging and transvaginal ultrasonography for the
abnormalities of menstrual bleeding. Fertil Steril diagnosis of adenomyosis. Fertil Steri/
2007;87:466. 2001;76(3):5BB-94.
5. Jensen JT Park S, Mellinger U, et al. Effective 17. Gordts S. Brosens JJ. Fusi L, Benagiano G.
I
r
treatment of heavy menstrual blgetling with Erosens / Uterine adenomyosis: a need for
I
estradiot valerate and dienogest: a randomized uniform terminology and consensus
r controlled trial. Obstet Gynecol 201 1 ; 1 17 : 777 classification. Reprod Biomed Online. 2008;
I
6. Munro MG, Critchley HOD, Broder MS, Fraser lS 17(2):244-8.
I
for FIGO Working Group on Menstrual Disorders. 18. Day-Baird D, Dunson DB, Hill MC, Cousins D,
r
I FIGO classification system (PALM-COEIN) for Schectman JM. High cumulative incidence of
I causes of abnormal uterine bleeding in non-gravid uterine leiomyoma in black and white women:
(
I women of reproductive age. lnternational Journal ultrasound evidence. Am J Obstet Gynecol 2003;
t
of Gynecology and Obstetrics 2011; 113: 3-13. 188(1): 100'7.
r
I
7. Munro MG. Suggested'normal limits'for uterine 19. Davis BJ, Haneke KE, Miner K, Kowalik A, Barrett
I
,. bleeding in mid-reproductive years. Rev Enocr JC, Peddada S, et al. The broid growth study:
I Metab Disorder 2012; 13: 225-234. determinants of therapeutic intervention. J
I 8. Lieng M, lstre O, Sandvik L, Qvigstad E. Womens Health (Larchmt) 2009; 1B(5):
Prevalence, 1-year regression rate, and clinical 725-32.
sign ificance of asymptomatic endometrial polyps: 20. t32l Shankar M, Lee CA, Sabin CA, Economides
cross-sectronal study. J Minim lnvasive Gvnecol. DL, Kadir RA. von Willebrand disease in women
r' 2009; 16(4):465-71. with menorrhagia: a systematic review. BJOG
9.
I
I
Anastasiadis PG, Koutlaki NG, Skaphida PG, 2004; 111(7):734-40.
r Galazios GC, Tsikouras PN, Liberis VA. 21. t33l Dilley A. Drews C. Lall:r C. Austin H. Barnhart
I
Endometrial polyps: prevalence, detection and E Evatt B.A survey of gynecologists concerning
malignant potential in women with abnormal
I
r menorrhagia: perceptions of bleeding disorders
r uterine bleeding. Eur J Gynaecol Oncol 2000; as a possible cause. J Womens Health Gend
I 21(2): 180-3. Based Med. 2002; 1 1 (1): 39-44.
(
14. Shushan A, Revel A, Rojansky N. How often are 22. Hale GE. Hushes CL, Burper HG. Robertson DM.
I
1
endometrial polyps malignant? Gynecol Obstet Fraser /S. Atypical estradiol secretion and
I nvest 2004; 58(4) : 2 1 2-5. ovulation patterns caused by luteal out-of-phase
rt 11. Weiss G, Maseelall f Schott LL, Brockwell SE, (LOOH events underlying irregular ovulatory
I
r Schocken M, Johnston JM. Adenomyosis a variant menstrual cycles in the menopausal transition.
rt not a disease? Evidence from hysterectomized Menopause 2009; 16(1): 50-9.
menopausal women in the Study of Women's 23. Hale GE, Manconi E Luscombe G, Fraser lS.
I Health Across the Nation (SWAN). Fertil Steril Quantitative measurements of menstrual blood
I 2009; 91(1): 201-6. /oss in ovulatory and anovulatory cycles in middle
I
I
12. Dueholm M. Transvaginal ultrasound for diagnosis and late reproductive age and the menopausal
of adenomyosis: a review. Best Pract Res Clin transition Obstet Gynecol 2010; 115(2Pt1):
I Obstet Gynaecol 2006; 20(4): 569-82. 249-56.
t 13. BrosensJJ, de Souza NM, Barker FG, Paraschos 24. Gleeson NC. Cyclic changes in endometrial trssue
i
T Winston RM. Endovaginal ultrasonography in plasminogen activator and plasmi nogen activator
,
the diagnosis of adenomyosis uteri; identifying the inhibitor type l in women with normal
predictive characteristics. Br J Obstet Gynaecol menstruation and essentia/ menorrhagia. Am J
i 1995; 102(6): 471-4. Obstet Gynecol 1994; 17 1 ( 1 ): 1 7 8-83.
14. Mark AS, Hricak H, Heinrichs LW, Hendrickson 25. Smith SK, Abel MH, Kelly RW, Baird DT. A role for
i MR, Winkler ML, Bachica JA, et al. Adenomyosis prostacyclin (PGi2) in excessive menstrual
and leiomyoma: differential diagnosis with MR bleeding Lancet 1981; 1(8219): 522-4.
i i magi ng. Rad iology 1987 ; 1 63(2): 527-9. 26. Smith SK. Kelly RW. Baird DT.
lv 15. Togashi K, Nishimura K, ltoh K, Fujisawa l, Noma S, Prostaglandin synthesrs in the endometrium of
a Kanaoka M, etal. Adenomyosis: diagnosiswith MR women with ovular dysfunctional uterine
imaging. Radiology 1988; 166(1 Pt 1): 111-4. bleeding. Br J Obstet^Gvnaecol 1981: 884):
i. 16. Dueholm M, Lundorf E, Hansen ES, SorensenJS, 434-42.
Ledertoug S, O/esen F. Magnetic resonance
155
I
155
c,.,APrE-1
t
3
i
I
r
Bartholin's Gland Cyst
I
( and Abscess
I
r K A Danso,Kareem Mumuni, Theodore Boafor

I
;
I
Bartholin's gland cyst and abscess are common sion of the duct. Causes of duct blockage include
vestibular injury or iatrogenic occlusion from stitches
I benign vulval conditions encountered among women
of reproductive age. Unlike cysts and abscesses placed during surgery, inflammations from specific
found elsewhere in the bodyforwhich simple incision and non-specific infections, congenital narrowing of
{ and drainage are sufficient for treatment, Bartholin's the duct and inspissation of mucus leading to
I
f cyst and abscess require specific surgical procedures plugging. ln ln Bartholin's cyst, the content is
I
l
for treatment. lt is therefore necessary to specially mucoid, clear or translucent and sterile. The cyst
consider Bartholin's cyst and abscess when dealing wal I has transitional or squamous epitheliu m and the
with vulvovaginal lesions. adjacent tissue is free of inflammatory reaction.
Bartholin's abscess results from acute infection of
I
Epidemiology the cyst or an ab initio infection of the gland.
An estimated 2% of adult women develop cystic or Neisseria gonorrheae and Chlamydia trachomatis
1
abscess swelling of the Bartholin's gland.'However, are often associated with the abscess. Staphylococ-
I
I because simple or uncomplicated cysts are generally cus aureus and anaerobic organisms may also be
small and asymptom'atic, they are not noticed by the involved making the Bartholinitis and subsequent
.'
patient and are found incidentally during pelvic abscess formation, a polymicrobial process. The
examinations. adjacent tissues of the abscess show acute inflam-
- matory reaction
Pathophysiolory
The Bartholin's, or greater vestibular, glands are two Diagnosis
structures of cuboidal epithelium each the size of a The normal Bartholin's glands are not palpable.
pea. They secrete clear mucus of alkaline pH during Diseased organs are palpable. Bartholin's cyst is
sexual activity. Each gland is located postero-laterally generally not very large and usually measures 1-3
within the vestibular bulb at approximately the four cm in size. lt is often unilateral and painless. The
and eight o'clock positions.' Each gland is approxi- bulge of the cyst in the labium majus may therefore
mately one-half centimeter (cm) in size and drain by a not be recognized by the patient and found on pelvic
duct of transitional epithelium measuring about 5mm examination conducted for some other reason.
in diameter and 2 to 3 cm in length to open onto the Symptoms however occur when the cyst becomes
vestibule between the hymen and the ipsilateral very large or infected. Patients may at this stage
labium minus atthe 5 and 7 o'clock positions. report of vulval discomfort or pain during coitus or
I
- physical activity.
Blockage at the vestibular ostium of the duct results
in the accumulation of secretions and cystic disten- Bartholin's abscess on the other hand may appear as
L57
alarge, very painful and tender, soft orfluctuant mass ing healing, a new drainage tract for the gland forms
in the labia or lowervestibulararea, occasionallywith and later shrinks to imperceptible size.
erythema, edema, and pointing2 lt restricts wdking
with a typical slow gait with legs widefi llle Word catheterization uses a special small catheter
p reced i n g i nf a m m ato ry p rocess deveLryF-{i,1ffi.
I
with an inflatable bulb, the word catheter. After
days. lf untreated the abscess ruptur ,=*p@ane- sterile preparation of the vulva and infiltration with
ously. BacteriologicaI culture may yield $otlmmalor local anaesthetic, a small stab incision is made into
chlamydial isolates and a variety of other oryqnisnrs the cyst. The contents are allowed to drain and
including those of the normal vaginal flora. loculations broken with an artery forceps. The word
catheter is inserted into the cavity of the cyst and the
Other vulvo-vaginal swellings of epithelial or connec- bulb inflated with water. The free end of the catheter
tive tissues origin or caused by trauma may mimic is tucked into the vagina and the entire catheter left in
Bartholin's gland cyst and abscess. Sebaceous cysts, situ for four weeks during which a new tract forms
fibromas, lipomas, hidradenomas, endometriosis, along the catheter. Following removal of the catheter,
neu rof ibromatosis, Gartner's duct cysts, the new tract shrinks to imperceptible size.
adenocarcinoma and haematoma are all relevant
differential diagnoses of Bartholin's cyst or abscess. Cyst excision is recommended for cases recurring
These conditions can usually be distinguished by the after several episodes of marsupialization or word
typical anatomic location of Bartholin's cyst and catherization. lt involves complete excision of the
i
abscess and the result of histological examination of gland under general anaesthesia. The incision is
the lesions. similarly made inside the hymenal ring. Excessive
intra and postoperative bleeding, local cellulitis and
Management subsequent dyspareunia are complications of cyst
The definitive management of Bartholin's gland cyst excision.
and abscess must employ specific surgical proce-
dures because simple incision and drainage or The management of Bartholin's abscess follows the
aspiration of the cyst results in high recurrence of the same principles: marsupilization, word
cyst and abscess. However, small asymptomatic catheterization or the use of sitz baths in cases of
cysts do not require any surgical intervention. Cysts spontaneously ruptured abscesses, and are all
that rupture spontaneously are treated by warm sitz effective. However, gland excision is not recom-
baths. Antibiotics should be used when infection mended for Bartholin's abscess because of the high
supervenes. risk for further local wound infection and excessive
haemorrhage which may accompany surgery in an
Recommended surgical procedures for dealing with inflamed hyperemic tissue environment. Bacteriolog-
those cysts requiring intervention are: icaltests and the use broad spectrum antibiotics are
. Marsupialization mandatory in the management of abscesses.
. Word catheterization Common antibiotic regimens include ceftriaxone
. Cyst excision
250mg lM stat to cover E.coli and N. gonorrhoeae
plus oral metronidazole 400mg 8hourly x 5 days to
Marsupialization is performed as a minor or office
cover anaerobes.' Oral fuithromycin 1g stat is given
procedure under local anaesthesia. lt involves the
to cover C. trachomatis if indicated by culture results
elliptical excision of part of the cyst wall under sterile
conditions. The excision is made just inside hymenal
or in high risk cases for Chlamydia ,nfection.'z
Analgesics are prescribed for pain relief.
ring but never on the outer labium majus to avoid the
development of a permanent fistulous drainage onto
Discussion
the outer vulval skin. The cyst content is allowed to Word catheterization is less traumatic to the patient
drain spontaneously. Loculations in the cyst cavity in comparison to marsupialization but the catheter is
are broken when necessary. The inner cyst wall and not widely available and cyst recurrence rate is
adjacent labial skin are then appropriated using higher than that following marsupialization which is
interrupted 3-0 delayed absorbable sutures. Follow- between 5 and 70o/".' Marsupialization therefore
158
r f
,.
Bartholin's Gland Cyst and Abscess
I
r
f remains the mainstay of surgical treatment of technique of "window operation".3 The "window"
{ Bartholin's cysts and abscesses with gland excision procedure removes alarger and oval piece of the cyst
being reserved for recurrences. Gland excision has or abscess wall. The larger and oval opening thus
also been recommended as the prirn:qr, .$u{gtcal created prevents occlusion of the newly created
rr procedure in cysts and abscesses in woqlan oer the orifice at the vestibule. Curettage of the abscess
i
,f
40 years because of the ,possibility of
age of cavityo and sclerotherapy with the application of
adenocarcinoma'. However the rarity of silver nitrate stick to the abscess or cyst cavity to
I
adenocarcinoma of the Bartholin's gland makes necrotize the wall ''o'u'u have also been used as
r- routine gland excision after40 years unjustified. alternative techniques to reduce the cyst recurrence
I
i rate. ln the management of Bartholin's abscess if a

I An improvement of the traditional technique of sexually transmitted organism is identified partner
l
I
elliptical excision of the cyst wall in marsupialization counseling and management is important.
I aims at reducing the cyst recurrence rate by the
i
I
T
I
rI REFERENCES
I
r
,l
i
I
1. Herbst AL, Mishell Jr DR, Stenchever MA, Marsupialization yersus incision, curettage and
{ Droegemueller suture under antibiotic cover. A randomized study
rI
W. Comprehensive Gynaecology. 2nd Ed. Mosby with 6 months' follow-up. Acta Obstet Gynecol
I
1992:637-9. Scand 1992; 71-: 59-62.
2. Katherine T Chen. Drsorders of Bartholin's gland. 5. Mungan T, Ugur M, Yallcin H, Alan S, Sayilgan A.
t
r UpToDate version 16.1. January 2008. Treatment of Bartholin's cyst and abscess;
i 3.
www.uptodate.com
Cho JY Ahn MO, Cha KS. Window operation: an
excision yersus silver nitrate insertion. Eur J
ObstetGynecol Reprod Biol 1995;63; 6l-3.
r alternative treatment method for Bartholin gland 6. Yuce K, Zeyneloglu HB, Bukulmez O, Kisnisci HA.
,t
I cysts and abscesses. Obsfet Gynecol 1990; 76: Outpatient management of Bartholin gland
886-8. abscesses and cysts with silver nitrate. Aust N Z J
I 4. Andersen PG, Christensen S, Detlefsen GU, Kern- Obstet Gynaecol 1994; 34: 93-6.
;
I
Hansen P Treatment of Bartholin's abscess.
r
1
!
(
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j
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(
5
r
: 1s9
:
a
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f
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a
I
I
Benign Lesioni d the Vulva
I R.A.Kwame Aryee and T Boafo
r
I
I
I lntroduction
r
I
The vulva is an external organ comprised of many changing of soiled underwear and the avoidance of
different types of specialised and non-specialised chemical irritants for douching or hygienic sprays.
tissues. lt is therefore the seat of many types of
benign lesions including inflammatory or infective,
1. OEDEMA
I cyst formation, ulcerations and tumours.
I
I
Oedema of thevulva may arisefrom thefollowing:
f As the vulval skin arises from ectodermal tissue it
I
I may also share in the common dermatological
. Conditions causing bilateral swelling of the
I
r diseases. Vulval dystrophic lesions also may present

legs such as heart failure, renal failure,
r ascites, anaemia and the presence of large
I
at various stages of life.
i
abdominal tumours.
I
r'
r It is noteworthy that the benign conditions of the
i
a
vulva may not easily lend themselves for easy Pregnancy especially in the presence of
r preeclampsia. Local inflammatory process or as a
I classification. lt may be easier to divide them into 4
I
general reaction to allergy. lymphoedema as a result
r main grou ps as fol lows('):
I
I
of lymphatic obstruction from filariasis.
Dermatoses not uniqUe to the vulva.

nflammatory vulval dermatoses. Treatment
I
I
I
Benign ulcers, cysts and tumours.

. The treatment depends upon the cause of the
r Vulval Atypias previously known as vulval oedema. Treating the underlying cause in
i
dystrophies. heart failure or allergy may cause resolution of
a the oedema.
:
A. DERMATOSES NOT UNIQUE TO THE VULVA
. Symptomatic relief may be achieved by giving
bed restwith thefootend of the bed raised.
,-
The vulva may be subjected to a variety of local
. On rare occasions multiple sharp needle
i-
irritants including vaginal discharge, menstrual punctures of the vulva may be dramatically
fluids, urine and faeces. The secretions from the effective.
sweat glands and sebaceous glands may also cause
irritation when retained. Retention of secretions may 2.INTERTRIGO
occur with tight or ill-fitting synthetic underwear.
This condition occurs commonly in the interlabial
Prevention involves the use of drying agents (such as and intercrural folds due to the presence of moisture
non-perfumed powder or non-medicated corn-starch and continuous apposition of the skin. An inflamma-
baby powder); wearing loose cotton underwear; tory reaction occurs, especially in the obese person,
161
due to the moisture, warmth and chafing. 4. LICHENIFICATION

Secondary infection with bacteria and lor Candida
may occur with resultant reddening and malodorous This condition may be super-imposed on any chronic
discharge from the site. irritant dermatosis. The skin becomes thickened and
leathery as a result of constant scratching.
lnvestigations
1. Swabs should be taken from the site of The skin, then shows fissuring and shallow ulcer-
inflammation for microbiological analy-sis to ation. The condition persists until the itch-scratch-
exclude infection. itch cycle is broken.
2. Oral glucose tolerance test should be
requested for the obese patient to rule out Diagnosis
diabetes mellitus. ln doubtful cases skin biopsy, skin scraping for fungal
elements and swab for culture may be necessary to
Treatment confirm the diagnosis.
The treatment of this condition involves the follow-
ing: Weight reduction in theobese. Wearingof loose Treatment
fitting cotton underwear. Keeping the vulva dry. The treatment depends on the cause of the lesion.
Soothing antiseptic lotion applied to the vulva.
Therapy against bacteria or candidiasis.
5. SEBORRHEIC DERMATITIS AND ATOPIC
DERMATITIS.
3. PSORIASIS
This usually presents as a primary irritant dermatitis
This is a common, generalised skin disorder of or allergic contact dermatitis. Excessive sebaceous
unknown aetiology. lt usually runs a chronic and secretions unto the labial folds may produce a lot of
unpredictable course with spontaneous exacerba- irritation resulting in crushing and scaling of the skin
tions and remissions. Vulval psoriasis usually forms with well-defined edges. This problem is common
part of psoariasis elsewhere in the body.
among obese patients, HIV patients, patients with
cerebro-vascular accidents and patients
Clinical presentation with Parkinsonism'''
The disease is usually a chronic, non-tender, genito-
crural lesion with sharp edges with a bright red, Patients with atopic dermatitis do not tolerate heat
glazed surface. The lesion may extend on to the mons
well due to the low sweat and oil output. They are,
pubis, Scaling is usually absent. Anxiety and embar-
therefore, prone to prickly heat and itching which in
rassment may also characterise the disease. The turn promotes scratching and eczema. Secondary
disease may show familial pre-disposition with 25% infection may occur.
of affected individuals showing positive family
history. Psoariasis may also be the first clinical The aetiology of seborrheic dermatitis may be related
manifestation of HIV infection.
to a yeast infection (Pityrosporum ovale)'') and the
pruritus associated with the disease may vary from
Treatment
mild to severe.
1% Hydrocortisone cream is usually effective. Coal
tar preparations may also be effective. When there is
Treatment
pain the application of a fluorinated steroid cream if one can be
Treatment is directed at the cause
for'4 weeks may be effective. The application of found. Antibiotic corticosteroid cream (such as
systemic steroids may cause a flare-up of psoriasis' Hydrocortisone cream) is the local treatment of
. When treatment fails dermatological choice. ln the acute stage sitz baths with added salt
consultation should be done. or potassium permanganate (1:10 000) sponging
may be useful. Avoidance of local irritants such as
t62
Benign Lesions of therilulva ,
deodorant sprays, detergents and disinfectants are of skin lesion may occur. The common symptoms seen
much help. ln refractory cases, topical application of include vulval tenderness, burning and pruritus.
Ketoconazole cream may be effective.
lmmunotherapy'has not proven to be urtr*u,I. Treatment
Withdraw the offending agent. Wet compresses of
6. CONTACT DERMATITIS Burow's solution (diluted to 1 in 20)'for 30 minutes
several times daily. This is followed by drying of the
The vulval skin is more sensitive to skin irritants than
skin with coolairfrom a hairdryer.
t other parts of the body. The vulval skin, especially ,
the intertriginous areas, is a frequent site of contact
dermatitis.
. Use of lubricating agents such as petroleum
jelly (Vaseline) or Eucerin cream. This would
The disease may present in 2 main patho-physiologic rehydrate the skin and reduce the pruritus'
processes as (1) a primary irritant or non-
immunologic and (2) as a definite allergic or immuno- . Wearing of loose cotton underwear and'
logic process. avoidance of tight fitting clothing. Applica-
tion of non-medicated cornstarch baby
lrritant substances produce immediate symptoms powder may help with the dryness.
(such as stinging and burning) when applied to the
vulval skin and the symptoms may disappear within . Application of steroid creams and lotions
12 hours of the removal of the offending substance. such as, hydrocortisone (0.5-1.0%) and
ln allergic or immunologic contact dermatitis, it may fluorinated steroids (Synalar 0.01%) two to
take 36 to 48 hours for the symptoms to appear and three times daily may control the acute
the symptoms may persist for a few more days after symptoms.
the withdrawal of the offending agent. lt is usually a
manifestation of delayed type of hepersensitivity . Oral steroid therapy may occasionally be
mediated by memory T lymphocytes in the skin. The beneficial.

most common cause is plant exposure such as poison
ivy and poison oak, which contain a sensitising agent, B. I N FLAM MATORY VU LVAL DERMATOSES
urishiole), an oleoresin with the active ingredient
pentadecyl-catechol, which adheres to skin, clothing, 1. VULVAL CANDIDIASIS Aetiology
pets and tools. Thesd may cause dermatitis even after
t prolonged storage. Candida Albicans infection of the vulva is the most
I
r common of the vulval infections. lt usually occurs as

r
I Many types of fluid or agents may be responsible for vulvo-vaginitis. The organism thrives best in acid
t
contact dermatitis. Biologic fluids such as urine and medium, at a pH of 5.0-6.5, which is best provided
I faeces may cause irritation of the vulval skin. Latex by the large amounts of glycogen present in the
I
and semen may on rare occasions excite acute vaginal mucosa under the influence of oestrogen.
dermatitis reaction. Other fluids such as chemicals The predisposing factors for this infection, therefore,
I (cosmetics or therapeutic agents including vaginal include patients receiving oestrogens especially the
1
contraceptives, lubricant sprays perfumes, douches, contraceptive pill and in pregnancy. Other factors
soaps and local anaesthetic creams) may be respon- include obesity, diabetes, prolonged antibiotic use,
i sible for the dermatitis. corticosteroid thera py a nd other i mmu nosu ppressive
i
or immune deficiency states. HIV infection is
Clinical features particularly noted for its association with
The vulval skin ls usually inflamed with reddening candidiasis.
i
and oedema and sometimes the skin would be
t
'weepy' and eczematoid with occasional blister "Complicated" vulvovaginal candidiasis'u' refers to
r
a formation in severe cases. Secondary infection of the severe local or recurrent disease in a woman who is
163
immuno-compromised or whose infection is caused ln resistant cases oral medication with ketokonazole
with hepato-
is advised. This drug may be associated
by a less susceptible fungal pathogen such as
Candida glabrata. Recurrent disease is defined as toxicity. Under these circumstances diabetes
four or more symptomatic lower genital tract infec- mellituswould haveto be ruled out.
tions within 12 months. Such patients reguire
treatmentfor 10-14 days with a topical ororal azole. 2. DIABETICVULVITIS
Clinical features Diabetes mellitus is often associated with Candida

The disease may be asymptomatic' Symptoms, albicans infection. This produces a chronic and
when present, include minimal external discharge extensive lesion associated with pruritus, irritation,
(cheesy and yellowish-white), intense vaginal and burning, dysuria and dyspareunia. The vulva
vulval itching and soreness. Dyspareunia, dysuria, becomes oedematous with the typical beefy-red
vulval excoriations, erythema and oedema are appearance or port-wine colour interspersed with
commonly present. The vulva may appear "beefy white patches.
red".
Treatment
Laboratory confirmation The diabetes must be well controlled. The antifungal
When a specimen of the discharge is suspended in agents named above are all useful.
70-20% Potassium Hydroxide (KOH) and viewed
under the microscope the characteristic filaments,
. Other supportive treatment includes the use of
mycelia, hyphae or pseudo-hyphae are seen. lt is loose, cotton under-clothing, which must be
important to use a cover slip as the KOH can damage changed frequently. Bed sheets must be
the lens of the microspcope. changed daily. Vulval toiletting with saline or
tap water aftervoiding is useful.
Culture of the discharge specimen on Nickerson
medium yields brownish-black colonies within 48 3. STAPHYLOCOCCAL FOLLICU LIT!S
hours. Sabourauds medium for the culture is also
useful. Staphylococcal folliculitis refers to infection of vulval
hair roots. These form small abscesses that are
A 2-minute test, a slide latex agglutination test'u), has associated with pain and vulval erythema. The
been developed with a sensitivity otTO-75%. problem is associated with diabetes mellitus and
shavingof vulvalhair.
Treatment
This consists of: Treatment The problem is treated with oral anti-
.Topical application of one of the synthetic staphylococcal drugs (e.g. flucloxacillin) together
i midazoles (miconazole, clotri mazole,
with vulval antisepsis and topical antiseptic creams'
butoconazole and tioconazole) for 3-7 days'
. One of the triazoles such as topical 4. TRICHOMONAS VU LVOVAGI N IT!S
terconazole or the oral preparation of
fluconazole (Diflucan). Use of the polyenes This disorder is due to the infestation of the vulva and
such as Nystatin for 7-14 daYs. vagina by the flagellated protozoon, Trichomonas
Vaginalis.
These topical agents come as creams or supposito-
ries. The suppositories are suited for vaginal insertion Clinical features
to control the vaginitis and the creams are best suited The disease is associated with a profuse, thin and
for vulval application. Use of these agents for 3-7 watery frothy discharge, which appears grey or
days is likely to control the infection. The vulvitis may yellow-green.
take a little longerto treat.
164
Benign Lesrons of the Vulva
lnvestigation with the formation of abscesses that may burst and

Culture of the discharge specimen or microscopy of a drain. Recurrent abscesses may coalesce to form a
saline drop preparation reveals the protozoa. A hard patch of puckered skin.
stained slide may also be useful.
lnvestigation
Treatment Vulval biopsy would help rule out the presence of
^ Treatment involves the administration of oral anti- carcinoma.
k
trichomonal drugs: Metronidazole (Flagyl) 600-
1000mg dailyfor 5 Treatment
The treatment consists of incision and drainage of
7 days or 2 grams in a single dose. Tinidazole abscesses, administration of oral antibiotics and
(Fasigyn) in a single dose of 2 grams. These drugs are application of topical antibiotics. The prolonged use
associated with nausea and alcohol intolerance. The of oral tetracycline may be helpful.
partner also has to be treated at the same time.
Recurrence of the disease may then refer to the . Oral contraceptives may help reduce the
presence of multiple sexual partners. glandular secretions.
-/
.. 5. SECON DARY I RRITATIVE VU LVITIS . ln resistant or chronic forms partial
vulvectomy with or without skin grafting may
This condition may arise as a result of the use of be necessary.
irritant agents on the vulva such as synthetic under-
wear and chemicals such as deodorant sprays. C. ULCERATIVE LESIONS, BENIGN CYSTS AND
TUMOURS
I
Clinicalfeatures
The symptoms include vulval itching and burning. 1. ULCERATIVELESIONS
The physical signs include reddenlng of the vulva
with oedema formation. Ulceration may be promi- BEHEETSSYNDROME
a
I
nent. This is an ulcerative disease of the vulva and the
I
mouth, which in the well-developed case may

r involve other systems with resultant iritis with
I
lnvestigations
Rule out candidiasis'. Vulval biopsy would confirm hypopyon, arthralgia, thrombophlebitis and neuro-
I
I
non-specific inflammation and the absence of logical abnormalities. The disease also affects males
r carcinoma. in whom it is more common. The internationally
('):
r
I
agreed diagnostic criteria are
I
r Treatment
r The use of the offending agent(s) should be stopped. 1. Recurrent oral ulceration plus 2 of the following:
I
r
Drying of the vulva after washing. Application of Recurrent genital ulcers Eye lesions Skin lesions
r
r
I topical steroid creams (1% Hydrocortisone) tor 3-4 Pathergy test. The pathergy test refers to a non-
weeks to reduce the inflammatory process and to specific skin inflammatory reactivity to any scratches
r reduce the itching. or intradermal saline injection and it is a common
7 and specific manifestation of Behgets syndrome.
; 6. HYDRADEN ITIS SU PPU RATIVA
i
Treatment
:
r This chronic disease that affects both the axilla and The disease may take weeks to heal. Severe cases
may respond to steroids and sometimes thalido-
r the vulva arises as a result of obstruction and subse-
quent infection of the apocrine glands in these hairy mide. Aspirin, colchicines and azathioprine have all
L
areas. The aetiology of this disorder is not known. been used for the vasculitis associated with this
The disease is associated with itching and burning disease.
165
APHTHOUS ULCERS HYPERKERATOSIS
Aphthous ulcers may occur in the mouth a'nd on the Both chronic infections and benign tumours of the
vulva. They are usually painful and have yellofl base vulva such as condyloma acuminata appear white
and red margins. They are most often locatd'on He because keratin absorbs moisture, which reflects
labia minora and healing is usually complete witfiin light back to the observer. Lichen sclerosus (vulval
one week. atypia) is also associated with hyperkeratosis,
epidermal thinning, loss of rete peg architecture,
CHROHN'S DISEASE homogenisation of the underlying tissue and dermal
inflammatory i nfi ltrate.
Chrohn's disease is primarily a gastro-intestinal
disorder. Vulval ulceration may precede gastro- SENILEATROPHY
intestinal ulceration in 25%of cases.
After many years of oestrogen deprivation the vulva
The ulcers are usually slit-like with prominent becomes atrophic and shrinks. The vaginal epithe-
oedema giving a "knife-cut" appearance' Draining lium becomes smooth, thin and dry. This is not
sinuses and fistulae may also occur. symptomatic. lt may benefit from oestrogen periodi-
Vulval blopsy may be helPful. cally. lnfections must be treated.
Treatment 2. BENIGN CYSTS

Steroids may be useful in advanced cases. Surgical
excision of thevulval lesions may be necessary' BARTHOL!NS DUCT CYSTS AND ABSCESSES
The 2 Bartholin's glands are normally rounded, pea-
HERPESS!MPLEX shaped glands, deep in the perineum and are located
at the entrance of the vagina at 5 and 7 o'clock
Genital Herpes, caused by Herpes simplex type 2 positions. The Bartholin's duct is about 2 cm long'
infection, is a recurrent, incurable, sexuallytransmit- The duct commonly gets obstructed at its opening.
ted disease. The disease involves the vulva and may The obstruction may be due to gonococcal infection,
affect the mouth as well. lt is usually a painful other non-specific infections and trauma. Medio-
eruption with periods of relapse and remission. lateral episiotomy and posterior colporrhaphy
sutures may ligate the duct or the duct may be
It is described elsewhere in the book. directly injured.
The glandularfluid may be mucoid orcloudy depend-
WHITE LESIONS ing on the cause of obstruction. The swelling is of the

duct rather than the gland. The swelling ranges from
Vitiligo or leukoderma is a generalised skin condition 1-8cm in diameter.
associated with multiple depigmented white areas of
the body including the vulva. lt is more common in Clinical features
the female. On the vulva it may be associated with The disease is usually seen in the reproductive years.
chronic dermatitis. When it is seen in women over 40 years the rare

adenocarcinoma of the Bartholin's gland should be
Treatment is not required unless the local dermatitis suspected. The initial inflammatory process may
cause local pain and tenderness' When the swelling
cannot be controlled by local treatment. A biopsy
is small or sometimes even when it is large it may be
using Keyes punch may be beneficial in those
un-noticeable by the patient. lt may however cause
circumstances.
superficial dyspareunia. The cyst, which is located at
the postero-lateral aspect of the vulva, may be
palpable on routine vaginal examination of the vulva
165
Benign Lesions of the Vulva
with the index finger.in the vagina and the thumb on CYSTOFTHECANALOF NUCK
the perineum.
This type of cyst corresponds to the encysted
Treatment :
hydrocele of the cord in males. As the round ligament
The treatment of this condition is usually by surgieal passes from the uterine cornu through the internal
drainage (marsupialisation or insertion of a Word and external rings of the inguinal ligament to insert
catheter). Simple incision and drainage is associated into the labium majus, it is firmly attached to a loop
with the tendency for the cyst to recur. of peritoneum (processus vaginalis). The 2 leaves of
Marsupialisation is done by making an elliptical peritoneum are usually adherent to each other. When
incision (or a cruciate incision) just lateral to the the peritoneum loses its attachment to the round
hymenal ring and over the cyst, excising the skin in ligament fluid may accumulate in the peritoneum to
the ellipse, cutting into the cyst, drainage of the cyst form a cystic dilatation in the vulva extending from
and suturing of the cyst lining to the skin using fine the internal inguinal ring to the labium majus.
absorbable sutures. This heals with a large opening of Sometimes a loop of intestine may follow the round
the gland onto the vulva. This procedure may also be ligament into the labium majus forming an indirect
done for Bartholin's abscess. inguinalhernia.
With the insertion of the Word catheter, a small Treatment

incision is made over the cyst followed by insertion of Surgical excision of the cyst is required. An incision is
the catheter into the cyst. The balloon of the catheter made into the mass and the external ring of the
is blown to about 2-3 ml and the balloon left in situ for inguinal ligament is identified by following the round
3-4 weeks allowing the duct so formed to be ligament with a finger into the inguinal canal. The
epithelialised. When the catheter is removed there is peritoneal lining of the cyst is then excised. When
free drainage of the gland on to the vulva. Whenever there is hernia formation excision of the sac (perito-
the Word catheter is available the use of neum) and inguinal herniorrhaphy is done.
tt'
marsulpialisation is not favoured as the Word
catheter can be inserted more easily under local ENDOMETRIOSIS
anaesthesia and coitus can resume very soon.
Endometriosis of the vulva is a very rare condition
Excision of the gland is seldom done, as it is associ- occurring in only 1 in 500 women with pelvic
ated with increased haemorrhage from extensive endometriosis. lt is commonly seen in the area of a
I dissection. lt may be necessary for recurrent cases, healed obstetric laceration, episiotomy site, the site
I
persistent deep infection and in women over the age of surgery for a Bartholin's duct cyst or cyst of the
7
I of 40 years. canal of Nuck.
f
( SEBACEOUSCYSTS The disease may arise as a result of metaplasia,
I
retrograde lymphatic spread or potential implanta-

Sebaceous cysts are found also on the vulva. Either tion of endometrial tissue at the time of surgery or
labium majus may be involved. They are usually uterine curettage '''.
)-
painless nodules measuring 3-4 cm diameter. There
may be secondary infection in these cysts. Clinical features
There is vulval pain as well as dyspareunia. There
Surgical excision may be done if the lesion is more may be an enlarging mass associated with pain or
than 0.5 -1 cm diameter or if there is recurrent discomfort du ring menstruation.
infection.
Treatment
I
a Complete surgical removal of the affected area is
:
L57
advised. Laser vaporisation may also be used. there is severe congestion and oedema, an 8-French
Recurrence of the disease may be due to inadequate feeding tube may be helpful in locating the urethral
excision of all the affected area. meatus "o' Laboratory and radiographic evaluations
are generally unnecessary'for diagnosis.
OTHER ABNORMAL CYSTS Premenacheal urethral prolapse is often associated
The following cysts, which may be of embryonic with fear of sexual assault "". ln a case series from
origin, are very rare and may be found in the area'of Enugu,3 of the 5 cases reported, were misdiagnosed
the vulva: epidermal inclusion cysts, Wollfian duct with the parents suspecting sexual assault"') lt is
cysts and mucinous cysts. therefore imperative to allay the anxiety of parents
through counselling,as part of initial management'
3. BENIGN TUMOURS
URETHRAL MUCOSAL PROLAPSE Definition

This refers to the outer sliding of the urethral mucosa
around the entire urethral meatus or the complete
evaginatlon of the urethra through the urethral
meatus. lncidence and aetiology
This is usually associated with the low oestrogen

years of childhood between ages 3-11 years. The
disease is thought to be associated with increased
intra-peritoneal pressure as may occur with bouts of
vomiting, coughing and excessive crying. lt may,
however, occu r spontaneously.
Typical clinical appearance of a uterine mucosa
Poor development or atrophic changes of the collagen prolapse: ( From lgwebueze Ol & Asimadu EE)
and classic supports of the urethral submucosa
(oestrogen dependent tissues) may predispose to the
disease. Treatment
The treatment is either medical or surgical. Some
authors recommend simple medical management,
Clinical features
avoiding anaesthesia and hospitalization", whiles
The disease may be symptomatic or asymptomatic.
others advocate for su rgical management"'"
The predisposing factor may be present. The
prolapsed urethra is seen at the introitus as a Medical treatment
discoid,erythematous, mass with a small central Pain relief with analgesics, warm sitz baths or warm
depression representing the urethral orifice. The moist compresses to the mass. Application of an
mass may grow and become gangrenous if not oestrogen cream "o'(such as Premarin cream) to the
treated early. lt is associated with a painful vulva, lesion and surrounding vulval tissues 2-3 times daily
dysuria, increased frequency of micturiction, urinary is effective. However, this should not be used on
retention and bloody vaginal discharge. The vulva chronic basis because of absorption of ttre steroid.
may be tender thus rendering examination difficult. Healing is usually complete within 2 weeks without
Urethral prolapse can be diagnosed by its typical scar formation. Recurrence is not commoil. lf there is
clinical appearance and should not be confused with no response to medical management, surgical
other causes of perivaginal bleeding, most impor- removal of the prolapsing tissue becomes necessary.
tantly sexual abLrse''o' lt is important to identify the ln an environment where follow up of the child is
urethral meatus at the centre of the oedematous erratic and difficult, surgical 'resection is recom-
mended from the outset.
tissue and a urethral catheter can then be passed to
help confirm the diagnosis when in doubt. When
168
Benign Lesrons of the Vulva
Surgical treatment postmenopausal vagina. The growth of the caruncle

The different modilaities of sugery include, excision, is due to infection or chronic irritation.
Iigation, cryotherapy a nd electrocautery.
Histological examination of the caruncle reveals a
Excision. This involves the excision of the prohpsed combination of transitional and stratified squamous
tissue (under general anaesthesia) with careful epithelium with a loose connective tissue with large
suturing of the mucosal edges together using fine dilated veins in the submucosa. There are 3 main
absorbable sutures"u'. Too many stitches may histological varieties; papillomatous,
promote scarformation and urinary retention. granulomatous and angiomatous. They are often
infected producing ulceration and bleeding.
The complications include haemorrhage, retraction
of the mucosal edges after excision and stricture The main differential diagnosis is carcinoma of the
formation later. To prevent mucosal retraction 2 urethra. The disease is not premalignant, however, 1
stitches are passed (from 12 to 6 oclock and from 3 to in 40 patients with a caruncle may have an associ-
9 o'clock position) below the base of the prolapsed ated carcinoma of the urethra.
tissue before excising the mass "t'. The central
portions of these stitches are pulled up and cut and Clinical features
this helps tofix the mucosa al 72,3, 6 and 9 o'clock The mass may or may not be symptomatic.
positions. The main symptoms include bleeding
(postmenopausal) and dysuria, frequency of
The main disadvantages of this procedure are the use micturiction and urgency of micturiction.
of general anaesthesia, catheterisation and hospitali-
sation and the presence of complications. lnvestigations
Biopsy under local anaesthesia may reveal the true
Ligation around a foley catheter. This is done by nature of the lesion.
ligating the base of the prolapsed tissue around a
foley's catheter. This may take a few days to become
Treatment
The initial treatment involves the topical application
gangrenous and fall off.
of an oestrogen cream or oral oestrogen administra-
Cryotherapy. After passinga urethral catheter the tion. Asymptomatic cases need no treatment.
prolapsed tissue is frozen. The tissues undergo
lf the caruncle does not regress then local destruction
necrosis. Healing may take up to 2 weeks. The
is indicated. The use of cryosurgery, laser vaporisa-
catheter is kept in for a few days.
tion, fulguration or operative excision is done. To
Electrocautery. This involves the use of low current prevent dysuria a foley catheter is left in situ for 2-3
and low voltage electrocautery to burn off the days. Urethral stenosis may complicate surgery.
prolapsed tissue. The result may be similar to that of Recurrence may be a problem hence follow-up is
cryosurgery. lt may be associated with an increased necessary.
risk of urethral meatal stenosis. lt is usually not
FIBROMATA
advised.
The fibrous tissue in the vulva may give rise to these
U RETH RAL CARU NCLE Definition
benign lesions, which may be small or moderate in
A urethral caruncle is a small, fleshy and vascular
size. When they attain a large size they develop a
outgrowth of the distal edge of the urethra. lt initially
appears as an eversion of the distal end of the
stalk, become pedunculated, oedematous and then
ulcerate.
urethra. The tissue is soft, smooth and bright red. lt is
highlyvascular and nerves may be seen on histology.
Clinical features
The clinical features depend.on the relative size of
Pathology
L the tumour. The complaints may be that of a swell-
The caruncle arises from ectropion of the posterior
: ing, discharge and bleeding. The tumours are usually
urethral wall due to the atrophy and retraction of the
:
169
----=--!
hard. Larger tumours may cause coital difficulty and Congenital haemangiomas are best left alone to
dystocia. allow spontaneous regression. Attemps at surgical
removal may prove mutilating.
Treatment
The treatment for the fibromas is excision. The H I DRADENOMATA (sweat gland tumours)
specimen is examined histologically to rule out
malignancy. This is a rare benign tumour of the vulva arising from
the apocrine sweat glands. Histologically they show
LIPOMATA an intricate papillary adenomatous pattern, which
may be easily confused with carcinoma
These tumours are like lipomas in other parts of the (hidradenocarcinoma).
body. They behave like the fibromas and the treat-
ment is surgical excision. Clinicalfeatures
The lesions are usually found in the labia majora,
NAEVI interlabial folds and in the perineum. They are
usually asymptomatic and may be found accidentally
The naevus or mole is a localised cluster of undiffer- during pelvic examination.
entiated melanocytes arising from the embryonic
neural crest and are present from birth. Naevi are Treatment
quite common on the vulva and may go unrecognised Treatment is by adequate excision.
till puberty when they become pigmented. They are
usually small (less then 2 cm diameter). They may be GRANU LAR CELL MYOBLASTOMATA
ped u ncu lated. The mole may show j u nctional activity
These are rare, uncapsulated, slow-growing solid
which may predispose itto malignantchange.
tumours that originate from the neural sheath and is,
HAEMANGIOMATA therefore, a schwannoma.
The lesions are usually small, often multiple and may

bleed easily with trauma. They must be differentiated
from melanoma and varicosities.
REFERENCES
Ihe drsease affects other parts of the body (especially podophyllin resin, trichloroacetic acid, cautery, laser
the tongue) and is characterised by subcutaneous vaporisation or excision. Lesions that are resrstant to
location, growth to I - Scm diameter and local podophyllin may benefit from immunotherapy with
infiltration. They may ulcerate as they grow. Treatment D in itroc h I orobenze ne or i nte rfe ron ge l.
is by wide excision to remove the inf iltrative processes.

ln pregnancy podophyllin is contraindicated and
VERRUCOUS I.ES'O'VS electrocautery, laser vaporisation or surgical excision
The most common form of verrucous lesion of the vulva may be the treatment of choice.
is the condyloma accuminatum which is caused by the
papiltoma virus. lt must be distinguished from PAPPILOMATA
condyloma latum of secondary syphilis. The papitlomas may grow large and pedunculated with
Treatment depends on the size and number of /eslons irregular surface that may ulcerate.
present. The following may be used: 20-25"/.
170
Benign Lesions of the Vulva
MOLLUSCUM CONTAGIOSUM 7. lnternational Study Group For Behgets Disease;

Ihls /s usually an asymptomatic viral infection that Criteria Of Diagnosis Of Behgets Drsease.
Lancet: 325: 1078, 1990.
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d i a meter w ith a n u m bi I i cated centre.
8. Horowitz l. R., Buscema J. Et Al. Surgical
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V O N R EC K LI N H AUSETV'S D'SEASE And Thompson J. D. Lippincott-
The skin nodules of neurof ibromatosus may affect the Raven. Ph i I adel ph i a. 1 997. Pages 885-9i 0.
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9. PaulT,TedeschiL.G,PerinealEndometriosisAtThe
Site Of Episiotomy Scar. Obstet Gynecol 40:28.
1972.
D.VULVALAflPIAS 10 Shurtleff BT Barone JG Q00D Urethral
Formerly called vulval dystrophieg fhese conditions prol a pse : fou r q u a d ra nt exc i siona I tech n iq ue.
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4:209-211.
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Cutaneous lnfections, Acne and Ather Common Yaokreh JB Kouam6 YGS et al. Urethral Mucosal
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15th Edition. 2001. McGraw-Hill, New York. l3.Adesiyun A G,Samaila M O.Childhood urethral
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San Fillipo J. S.
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gamma Therapy for Atopic Dermatitis. J. Am 15. Kelly H.A., Burnan C. F. 1922. Disease Of
Acad Dermatol. 28: 189. 1993. Kidneys, Ureters And Bladder. Volume 2. New
r 5. Droegemueller W.lnfections Of The Lower York. Appleton. Page 578.
I
Genital Tract. ln: Comprehensive Gynecology. 16. Stewart D. B. 1967. Lesions Of The Urethra. ln:
I
7 Fourth Edition. Edited By: Stenchever, Obstetrlcs And Gynaecology ln The Tropics and
I
I
I
Droegemueller Et Al. 2001. Mosby. Pages 641- DevelopingCountries. Edited by Lawson, J. B.
705. and Stewart D. B. Pages 529-542.
I 6. Rajakumar, R., Lacey C. J. Et Al. Use Of Slide
l. Agglutination Test For Rapid Diagnosrs Of
I
I Vagi na I Ca nd i dosi s. Gen itou ri na ry Med. 63 : 1 92.
I
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1987.
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|.
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t
t
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: t7t
:
:
i
172
cHAPrEtb
--
Uterine Leiomyomas
E.Y. Kwawukume and M. Y. Ntumy
Introduction and definition aetiology of these tumours. Cytogenetic aberrations

Uterine fibroid, also called uterine leiomyoma, or involving chromosomes 6, 7, 12 and 14 constitute
simply myoma, is a benign tumour of the uterus the major chromosomal abnormalities seen in
composed of smooth muscle and varying amounts of leiomyomata. Among myomas with cytogenetic
connective tissue. lt is the commonest neoplasia of abnorma I ities tra nslocations between ch romosomes
the uterus and autopsy studies had shown that 12 and 74 lt{12;74)l have been associated with
between 20-50% of women over30 years old habour larger myomas, and deletions of the long arm of
uterine myomas of various sizes. Since they are chromosome 7 ldel(7)G22q32)1 have been
basically of smooth muscle origin the term fibroid is a associated with smaller leiomyomas'.
misnomer. However, it has become so thoroughly
entrenched through long usage that it cannot be The hormone sensitivity of leiomyomas is indicated
considered objectionable to use fibroids as a clinical by the fact that they develop during the reproductive
designation for these tumours. lndeed many modern (hormonally active) years and regress after
texts now use the terms uterine fibroids, leiomyomas menopause, and also by the fact that hypogonadal
and myomas interchangeably. state induced by treatment with GnRH agonist often
causes shrinkage of myomas. The main hormones
2. Aetiology Exactly what causes the initial implicated are estradiol and progestins and the
development of leiomyomas is not known. lt is population ofreceptors to these hormones, are
hypothesized that leiomyomas originate from increased in myomas. The effects of estrogen and
somatic mutations in myometrial cells, resulting in progestins on myomas are mediated by growth
progressive loss of growth regulation'''. The tumour factors such as EGE, IGF-|, IGF-ll and parathyroid
grows as genetically abnormal clones of cells derived hormone related protein. Receptors to all these
from a single progenitor cell (in which the original growth factors are over expressed in myomas. Also,
mutation took place). Each myoma is monoclonal basic fibroblast growth factor (bFGF), which
and results from a single muscle cell and multiple promotes angiogenesis, is suppressed during
myomas within the same uterus are not clonally premenstrual phase in women without leiomyomas,
related ; each a rises i ndependently. but not in women who have them, indicating that
There is evidence of genetic predisposition for myoma over activity of bFGF may result in excess production
formation, howeverthe pattern of familial inheritance of blood vessel clusters and the growth of fibroids.
has not been well studied. The various clues that
suggest that there might be a genetic liability to the 3. Risk Factors For unknown reasons, uterine
development of fibroid include ethnic predisposition leiomyomas are 2-3 more prevalent in black women
studies, twin studies, and familial aggregation compared with white, Hispanic, and Asian womeno.
b
studies. Cytogenetic and genetic studies have, in Women of African descent leaving elsewhere do not
recent years, advanced our understanding of the appear to have as high incidence as those on the
173
continent - an indication that diet or other Only a small percentage of fibroids develop in the
environmental factors are at work in the development cervix because of the relative sparcity of smooth
of fibroids. Onset of menstruation before th6 age of muscle cells in the cervix.
12 (which prolongs the time a woman is s"S$et to
estrogen) and being overweight (which rahcs Degenerative changes '
Several forms of degenerative changes can occur in

estrogen levels) are two other risk factors. The
molecular genetics of leiomyomas may alm be
the leiomyoma. The most common is hyaline .
degeneration, which is important in that it could be

involved in the relationship between myomas and
mistaken for the coagulative tumour cell necrosis
overweight. High mobility group A2 (HMGA2) is a
transcriptional factor, which is upregulated in
seen in leiomyosarcoma. Red degeneration
(necrobiosis) is a form of degeneration that occurs l
leiomyomas expressing the 12; 14 chromosomal
gene involved in regulation characteristically but not exclusively in pregnancy,
translocation. This is also :
and the process is often the cause of pain and fever' l
of bodyweight and obesity.'
The other forms of degenerations are myxomatous,
1
Women who have never been pregnant are at higher calcific, cystic and fatty degenerations.
risk than women who have children; the risk
ln addition, there are two unusual growth patterns of
decreases with increasing parity and with increasing
leiomyoma that are important to recognize' Both the
age at last term birth4. Women with at least two full
benign metastasizing leiomyoma and disseminated
term pregnancies have half the risk for leiomyomas
peritoneal leiomyomatosis are found outside the
compared with those without any term pregnancy'
uterus, and neither is malignant' Benign
Women who are sedentary have higher risk than
metastastisizing leiomyoma is a rare condition in
those who are athletic. Smoking decreases the risk
which histologically benign uterine smooth muscle
(presumably by decreasing estrogen levels). Data on
tumour acts somewhat in a malignant fashion and
whether oral contraceptive is associated with an
produces benign metastases, usually to the lungs
increased risk of leiomyomas is conflicting. Although
and lymph nodes. The tumours spread by direct
the Nurses' Health study reported a slightly increased
extension within the blood vessels and the
risk when oral contraceptives were first used in early
metastasizing myomas are capable of growth at
teenage yearsu, others found risk reduction of about
distant sites. Experimental and clinical evidence
77o/"wilheach 5 years of oral contraceptive useu.
suggest that these tumours are stimulated by
ln postmenopausal women with a history of oestrogen. Therefore removal of the source either
med ica I ly or su rgical ly, has a mel iorati ng effects.
submucous fibroids and abnormally heavy bleeding,
hormone replacement therapy (HRT) may cause
Uterine leiomyosarcoma isfound in 0.1% to 0.5%ot
recurrence, although HRT does not increase the risk
uterine fibroids removed surgically and this is more
of recurring fibroids in most post menopausal
likely in the post-menopausal woman in the 6'n
women. Epidemiologically, the risk factors for
decade'. The relation between fibroids and this
leiomyoma development are similar to those for
sarcomatous change may be casual rather than
mammary and endometrial carcinoma and are
causal as the peak age of both conditions are
co nsi stent with u no pposed estrogen sti m u lation.
different and fibroids are 200-1000 times more
4. General Characteristics and pathology The size of common than the sarcomas. The presenting
uterine leiomyomas is exceedingly variable. They symptom of leiomyosarcomas is usually post-
may appear as tiny, microscopic growths or may menopausal bleeding. Histologically these tumours
reach huge proportions. Although they do not have a are difficult to diagnose with certainty. Coagulative
true capsule, the margins of the tumour are blunt, necrosis, cytologic atypia, and mitotic counts are all
non-infiltrating, and are usually separated from the important in diagnosing the condition. More than 10
a--
myometrium by a pseudocapsule of connective mitotic figures per high power-field, regardless of
tissue, which allows easy enucleation during surgery.
cellular atypia, pleomorphism .or the presence of
giant cells, is diagnostic. However there is no level of
There is usually one major vessel supplying each
tumour. The cut surface is characteristically whorled.
mitotic activity below which the diagnosis can be
174
Uterine Leiomyomas
excluded. The prognosis depends on the extent of the The possible mechanisms by which fibroids may
disease at diagnosis, mitotic activity and the ca use meno rrhagia i ncl ude:
histological grade of the tumour. a. Enlargement of the surface area of the uterine
cavity.
5. Classification Uterine leiomyomas are classified b. Congestion and dilatation of endometrial
as follows: venous plexuses, By radiographic methods, it
was shown that fibroids arising at various sites
a. Submucosal - At this site the fibroid distorts the in the uterus could cause congestion and
uterine cavity. dilatation of endometrial venous plexuses by
b. !ntramural - the fibroid does not distort the uterine impinging and obstructing veins in the
cavity and less than 50% of it protrudes into the myometrium leading to endometrial venous
serosal surface. ectasia which may play a role in the enhanced
c. Subserosal - Greater than 50% of the fibroid uterine bleeding'. Venous dilatation was most
nodule protrudes out of the serosal surface. lt may marked in relation to large submucous fibroids
be sessile or pedunculated. but it was also present in some intramural and
d. lntraligamentary - The fibroid grows laterally in
also su bserous fibroids.
the fold of the broad ligament. When of large size it c. lmbalance in uterine prostanglandin produc-
may burrow far outwards and form retroperitoneal tions. Fibroids have been shown to release
masses. prostanglandins in vitro,' the principal prosta-
e. Parasitic - The fibroid acquire additional blood glandin produced being 6-keto PGF,, the stable
supply from an adherent omentum. Gradually metabolite of prostacyclin. Since this is a
more and more nutrition comes from the omentum potent vasodilator, it may contribute to
and less and less from the pedicle, which becomes
menorrhagia associated with the presence of
thinner. The tumour may thus be completely fibroids.
weaned away from the uterus by omentum, d. Disturbances in normal myometrial contractil-
1
becoming a floating solid tumour. itv.
a
I
I Submucosal fibroids are further classified as: Chronic pelvic pain.

Type 0 - The fibroid is pedunculated without any
r
r
intramural extension Type 1 -Thefibroid issessile I Dysmenorrhoea, Dysparaunea, and Pelvic
I
r
with intramural extension < 5O%. Type ll - The pressure.
t fibroid is sessile with intramural extension > 50%.
Though the submucosal fibroids constitute the 2 Acute pain may result from torsion of
t
least frequent group (about 5%), they are perhaps pedunculated myoma or infarction or degenera-
I
ri the most important clinically. tion of fibroids. The latter two particularly occur
during pregnancy or in some women using
;
6. Symptomatology combined oral contraceptive pills'..
1. Menorrhagia: Most fibroids cause few or no
symptoms. When they occur, the most com- 3 Urinary symptoms: frequency may result from
mon symptom is prolonged and heavy bleeding extrinsic pressure on the bladder. Partial ureteral
during menstruation. About 30% of women obstruction may be caused by pressure from
with fibroids have been reported to have large tumours at the pelvic brim. Reports
menstrual abnormalities, most often suggest some degree of ureteral obstruction in
menorrhagiau. This figure may be controversial, 30-70% of tumours above the pelvic brim.
as 50% of women who complain of Ureteral compression is 3-4 times more
menorrhagia do not have excessive menstrual common on the right because the left ureter is
loss when this is measured objectively?. lt is protected by the sigmoid colon. Rarely, com-
this symptom that most frequently lead to plete urethral obstruction resulting from the
a surgical intervention. elevation of the base of tne bladder by cervical
or lower uterine leiomyomas with impingement
175
in the region of the internal sphincter, may occur. the infertility be found, suggesting that uterine
fibroids alone are an infrequent cause of infertility?.
4 Rare symptofirs ?ro:
a. rectosigmoid compression leading to When the effect of fibroids on cumulative probability
constipation or intestinal obstruction; of pregnancy in women taking follicle maturing drugs
b. prolapse of a pedunculated submucous without assisted reproductive technology was
tumour through the cervix with associated studied, it was found in general that the presence of
symptoms of severe cramping pain. Subse- fibroids do not adversely affect conception outcome
quent ulceration and infection may lead to for in vivo pregnancies". However, since the majority
irregular bleeding or postcoital bleeding. of the fibroids were small (< 6 cm) and were not
Spontaneous expulsion ma! occur; submucosal and did not compress the endometrial
c. venous stasis of lower extremities and cavity, the authors conceded that larger studies were
possible thrombophlebitis secondary to needed to address specific subtypes of fibroids and
pelvic vei n compression.
ci rcumstances on pregnancy outcome.
7. Diagnosis and differential diagnosis The majority Where fibroids are implicated as the sole factor in
of leiomyomas can be diagnosed based on the history
infertility submucous fibroids cause the greatest
and pelvic examination findings alone. The standard impairment and subserous ones the least. ln a
imaging technique for evaluating the uterus and the
controlled study to determine, in a large group of
adnexal contents is the ultrasound. Other useful patients, whether the presence of subserous,
imaging techniques are magnetic resonance imaging
intramural, or submucosal fibroids has an influence
(MRl), sonohysterography and hysteroscopy, but
on pregnancy rates and live birth rates after IVF-ET
these are expensive and not available in many treatment, it was found that the clinical pregnancy
developing countries. The last two techniques are rate per transfer was considerably lower in the group
used to confirm submucous leiomyomas. MRI is not
of patients with intramural and /or submucous
very accurate in defining the type of fibroid, but it is
fibroids, even when there was no deformation of the
accurate in differentiating between malignant and uterine cavity. The pregnancy rate was not influenced
benign growths. Menstrual abnormalities cannot by the presence of subserous fibroids".
always be assumed to be attributable to fibroids even
if it is present, particularly if there is disturbance in The theories advanced to explain the cause of
the normal cycle pattern in women over the age of 40 infertility in women with fibroid include:
years. Curettage or endometrial biopsy may be 1 Distortion of the endometrial cavity.
indicated in these circumstances to rule out an 2 Greaterdistanceforsperm travel.
endometrial hyperplasia or malignancy. 3 lmpairment of blood supply to the
endometrium.
The differential diagnosis of uterine fibroids includes 4 Atrophy, inflammation or ulceration of the
ovarian tumours (either functioning or non- endometrium thereby preventing implanta-
functioning), adenomyosis, endometriosis, genital tion.
tract malignancies, miscarriage, PID, DUB and 5 Dysfunctional uterine contractility with
endometria I hyperplasia. impaired gamete transfer.
6 Enhanced androgen environment.
8. Fibroids and infertiliW. The role of fibroids as a
causative factor in infertility remains controversial. Fibroids and reproductive outcome
Fibroids are common and certainly occur in both Fibroids are more important feature in pregnancy
normally fertile and infertile women and there is no now than in the past as many women aie delaying
clear'evidence that their mere presence is causally childbirth to their late thirties-the time of greatest
linked to infertility. A review of 677 patients undergo- risk for fibroid growth. Fibroids do not necessarily
ing major operations for preservation or enhance- enlarge during pregnancy. A prospective ultrasound
ment of fertility revealed that in only 2% of patients study showed that 78% of fibroids did not enlarge
undergoing myomectomy could no other cause for during pregnancyu. Fibroids are associated with
higher rate of miscarriage, particularly if implanta-
L76
Uterine Leiomyomas
tion occurs in relation to sub-mucous fibroids. ln a ally ill patients may be poor candidates for such an
review of myomectomies in which pre-operative invasive major surgical procedu re.
miscarriage rate were known to be 4LY", miscarriage
rate significantly reduced to 19% postopgrativelyu. Hysterectomies may be performed by a variety of
Other complications of fibroids in pregnancy ine,lude techniques: abdominal, vaginal, laparoscopic, and
preterm labour, preterm PROM, abdominal pain, laparoscopically assisted vaginal hysterectomy
(LAVH). Clearly, specific circumstances of size,
abruption placenta, placenta prawia, {UGR,
obstructed labour, post-partum haemorrhage and location of myomas and experience of the surgeon
puerperal sepsis. The over-all complication rate had may dictate a particular approach.
been quoted as 10%.
Another issue is the degree to which hysterectomy
Treatment of Leiomyomata need be performed. Recently, thetotal hysterectomy
Although a large array of options exists, there are still has been challenged by the supracervical hysterec-
little data upon which to base decisions regarding tomy, performed either at laparoscopy or at
optimal treatment approaches. About 7O-8O% ot laparotomy, A number of theoretical advantages
uterine fibroids are asymptomatic and are discovered have been raised regarding the supracervical
initially during routine pelvic examinations. For most hysterectomy (Tables 1 & 2).
( of such people explanation, reassurance and reexam-
To date few data exist to accept or refute these
ination at periodic intervals are all that may be
needed.
hypotheses'.. Those studies addressing the issues
are generally small and of poor quality, and most are
Su rgica I treatments i ncl ude hysterectomy, a bdom i na I uncontrolled or only historically controlled. The
myomectomy, laparoscopic myomectomy, and exception is the effect of supracervical versus
myolysis. Nonsurgical treatments include medical complete hysterectomy on urinary function, where
therapy and uterine artery embolization. All have a two prospective trials (one randomized) have failed
small amount of accumulated data, but existing to demonstrate a difference'u''u. However, the sample
studies are generally small. There is a strong need for sizes of these studies were small. Thus, no firm
appropriately designed and analyzed randomized conclusions can yet be drawn regarding the preferred
clinicaltrials. type of hysterectomy for fibroids, and decision
making should be left to the individual and her
Surgical Treatment practitioner. Where there is a technical difficulty in
accessing the cervix, it is better to perform subtotal
Hysterectomy hysterectomy than to inflict unnecessary damage to
The indications for hysterectomy include rapidly contiguous organs in a heroic attempt to remove the
expanding mass especially in post-menopausal cervix. ln developing countries where cancer of the
women, persistent abnormal bleeding, pain or cervix is the commonest cause of death due to
pressure symptoms, and abdominal distortion of gynaecologic malignancy and where there are no
such magnitude as to be embarrassing to the patient. organised screening programmes for cancer of the
i
All these indications must be against the background cervix there may be a strong point for total hysterec-
that further fertility is no more desired. Hysterectomy tomy.
is the "gold standard" for treatment of fibroids, in that
with removal of the uterus the elimination of present- Abdominal Myomectomy
ing symptoms should be extremely high and the When conserving the uterus is desired in the treat-
recurrence risk virtually zero. lndeed, satisfaction ment of uterine fibroids, the most commonly used
rates following hysterectomy exceed 90%". How- procedure is the abdominal myomectomy. The
ever, the procedure is not without problems. First and concept is straightforward: the abdomen is entered,
foremost, reproductive potential is eliminated unless the uterus is isolated, the fundus is incised, the
surrogate in-vitro fertilization is desired. ln addition, myomas excised, and the uterus and abdominal wall
t the procedure has a high rate of minor complications are surgically repaired. However, the uterus (with
and, occasionally, major morbidity. Finatly, occasion- myomas) may have
L77
Table 1. Advantages of TAH

No uterine bleeding
No future cervical cancer No other cervical pathol-
ogy in the future
Lowerfuture cost of health care
Table 2. Advantages of Subtotal hysterectomy

Y lmproved sexual response
Y Less urinary lncontinence
Y Less pelvic floor prolapse
Y Less chance of damage to pelvic structures
Shorter, Iess morbid surgery considerable bulk,
impressive blood supply, and a highly adhesiogenic Fig. 1 shows cut surface of the uterus with fibroids.
tendency when damaged. Thus, technique for The operative field is relatively bloodless
performing abdominal myomectomy may be key to
the results obtained. Table 3: Standard indications Pretreatment of the uterus with a gonadotropin-
for myomectomy in women who wish to maintain myomas after GnRH analog use, the results to date
fertility Menorrhagia assoclated with sub-mucuous are releasing hormone (GnRH) agonist has been
or intramural fibroids. lnfertility associated with evaluated equivocal due to the limited sample size".
uterine cavity distortion after all other avenues have Thus, there in several randomized trials and one
been invested. Recurrent miscarriage associated meta-analysis". do seem to be distinct advantages to
with submucuous fibroids. Pregnancy complications the use of GnRH Pre and postoperative blood counts
associated with malpresentations - with other are significantly agonists as pretreatment prior to
causes excluded. Pressure symptoms on bowel or surgery; however, improved by this medical therapy,
bladder or ureters. and both uterine and potential disadvantages such
as recurrence rate and fibroid volumes are reduced.
Su rgical Technique of Bloodless Myomectomy
Blood loss at surgery and cost have not been
This is performed routinely in our hospital and has
adequately assessed. Table 4 the rate of vertical
been popularised by the first author. After anaesthe-
incisions were also reduced. Although summarizes
sia, either general or spinal, the abdominal cavity is
the advantages and the disadvantages of a trend
entered either by Pfannenstiel or midline incision and
exists toward an increased risk of recurrence of pre-
the uterus lifted out of thd abdominal cavity and freed
operative Gn RH analogue treatment.
from adhesions. A tourniquet is then tied round to
encompass and compress both uterine arteries at the
base of the broad ligament and the vessels in the
infundibulo-pelvic ligament. This will achieve a
relatively bloodless operating field. The fallopian
tubes are lifted and excluded from the tourniquet.
Routine myomectomy can be performed. The general
principles of surgical technique should be applied
making single anterior incisions as much as possible.
After the myomectomy has been completed the
fibroid beds should be closed in layers with non-
reactive absorbable suture materials. The serosa
layer should also be closed with continuous No. 2-0
or 3-0 non-reactive and absorbable suture before Fig. 2 shows the uterus after completion of myomectomy
removing the tourniquet. lncision areas should be with a toumiouet in-situ
inspected for bleeding and individual stitches placed
at bleeding points if necessary to maintain
haemostasis.
178
Uterine Leiomyomas
Table4: Advantages and disadvantages of irreversible damage occurs is unknown. However,

preoperative GnRH analogues treatmentr' because of the risk of accumulation of histamine-like
substances,"the tourniquet time must be monitored
Advantges gained by uterine fibroid. shria*age and kept at minimum. lntermittent release of
tourniquet must be considered if operative time
1. May allow vaginal hysterectomy becomes excessive. Twenty minutes intervals had
2. May decrease intra-operative blood'loss been suggested by certain texts". We use 45
3. May allow Pfannestiel incision minutes interval in our unlt without any obvious
4. May facilitate endoscopic myomectomy
intraoperative and post-operative complications.
Controlled trials are lacking.
Advantages gained by induction of
amenorrhoea
Myomectomy and adhesion formation
Adhesion formation is a significant issue with
i. May correct hypermenorrhagia-menorrhagia'
myomectomy because the vast majority of such
associated anaemia.
patients wish to preserve fertility potential:
i
r 2. May improve ability to participate in

I autologous blood transfusion programme.
Adhesions frequently develop after surgical
I
3. May decrease the need for homologous
procedures are performed for infertility; the
blood transfusion incidence at the time of second look laparoscopy
I
I 4. There may be atrophic endometrium, varies between 55-95"/"'0. lt has been shown that
facilitating hysteroscopic resection of myomectomy itself may decrease fertility, probably
I
I
submucous fibroids as a result of adhesion formation'u. Therefore an

I
infertile woman found to have uterine fibroids must
r be investigated for other causes of infertility and
I
I Disadvantages
I
( myomectomy should be resorted to only when no

r
I
1. Delay to final tissue diagnosis other causes are found and the infertility is long
1
2. Degeneration may blurr the plain of standing.
cleavage, necessitating piece-meal
I
,l enucleation ln deciding to perform myomectomy for an infertile
3. Hypo-estrogenic side effects (e.g., trabecular woman, steps must be taken to minimize
I
done loss, vasomotor flushes) development of adhesions. Some of the
{ 4. High Cost recommended steps to minimize the development of
I 5. The need to self-administer or receive adhesions include adequate surgical exposure,
t- multiple injections in many cases
7
minimal number of uterine incisions, antibiotic
r 6. Approximalely 2% of patient may experience prophylaxis, a careful surgical technique, gentle
I,
vaginal haemorrhage handling of tissues, anteriorly placed uterine

r 7. Higher recurrence rates
incision, prevention of tissue desiccation during the
i
surgical procedure by use of solutions of Ringers
Lactate, liberal use of suction to remove blood from
:
the operation field instead of sponges which will
Another issue with myomectomy is haemostasis
cause trauma to the tissues, avoidance of traumatic
during the procedure. For this purpose, three
instrumentation, minimizing blood soilage of the
techniques have been advocated: a) vasopressin
peritoneal cavity by performing a thorough pelvic
solution injected into the uterus, b) tourniquet
lavage at the end of the surgery, and the use of fine
compression of the uterine vasculature, or c) use of
absorbable non-reactive suture material such as
rubbershod clamps on the uterine and
\s' 20' 21 Polydiaoxone suture [PDS] no. 3-0 to repair the
infundibulopelvic vessels. Vasopressin is
serosal surfaces. Continuous suturing on the serosa
expensive and may not be available in low resourced
is preferable in order to avoid extra knot volume,
institutions such.as ours.
which may contribute to ad hesion formation.
It should be noted that the length of time that pelvic
lntraperitoneal solutions may also be useful in
structures can be without blood flow before
L79
red uci ng ad hesionformation. For exa m ple insti llation judged recurrence by ultrasound if the patient was
of Dextran 70 into the peritoneal cavity has been noted to have an abnormal examination or symptoms
shown to reduce peritoneal adhesions by'eaudrg a of recurrence. All patients were seen at least once a
peritoneal transudase; it also appearc te a year. The cumulative 10-year recurrence rate was
$9
siliconizing effect upon the raw surfaces aid'*ffir 27 "/o, increasi n g with len gth of fol low-u p. There were
fibrin structure'u. lnterceed has also been'fumd no differences observed in recurrence rates by age at
useful for this purpose. diagnosis or site of the myomas, although patients
with more than one myoma tended to recur more
All adhesion barriers have been tested, and all the frequently. The recurrence is also affected by weight
currently available adhesion prevention adjuvants gain after 18 years and uterine size less than 12
such as oxidized regenerated cellulose absorbable weeks atthe time of abdominal myomectomy'.
barrier, expanded polytetrafluoroethylene barrier and
seprafilm membrane (Gore-Tex surgical membrane) Myomectomy and pregnancy rate
have been demonstrated in randomized trials to The crude pregnancy rates after myomectomy for
reduce adhesion formation following myomectomt'" infertility, reported in many studies ranges from 38%
lo 65% and a feature common to most of these
reports is that the majority of the pregnancies were
It is preferable perform the operation in the
to conceived in the first 6 months following the
follicular phase of the menstrual cycle. This avoids proceduret'. ln many of these reportstt the
the chance of encountering an unknown or characteristics of the leiomyomas themselves, the
unsuspected pregnancy and reduces the problems number, the size and the location of the myomas
encountered when a fresh corpus luteum is were found not to have any significant influence on
i nadvertently tra u matized ". post-operative fecundity. Only the coexistence of
pelvic adhesions significantly reduces the pregnancy
Myomectomy at Caesarean Section rate following myomectomy. Most of these reports
Traditionally myomectomy is contraindicated during were however descriptive in nature and subject to the
caesarean section or at laparotomy for ectopic potential biases found in uncontrolled studies.
gestation except for pedunculated subserous ones on Prospective randomized controlled studies are
a narrow stalk that can be clamped, excised and lacking.
ligated without any significant bleeding. With the
development of effective means of minimizing blood Myomectomy and uterine rupture at delivery
loss at myomectomy this standard recommendation Myomectomy has long been considered a risk factor
may be challenged in the near future. A few for obstetric-related uterine rupture. lt has been
literatures have already accrued. ln a prospective hypothesized that if the uterine cavity is entered at
controlled clinical trial " a myomectomy performed the time of surgery, the risk of rupture is increased.
during caesarean section was compared with One study confirms this theory", but no such
caesarean section without myomectomy. Tourniquet association was noted in two otherstt't'.
was used during the myomectomies. There was no
significant difference in the mean blood loss in the Laparoscopic Myomectomy
two categories. Also uterine involution was normal in An alternative to myomectomy at laparotomy is the
all the subjects and there were no significant performance of the procedure via laparoscopy.
complications during the puerperium. Expectedly, Several issues must be addressed when comparing
the period of performing the myomectomy added to the laparoscopic approach to that of open Surger!:
the operative time. time, blood loss, complications, cost, adhesion
formation, and future fertility. Of these, only adhesion
Recu rrence after myomectomy formation has been evaluated with a prospective
Data regarding recurrence following myomectomy trial. ln one study, no difference in adhesion
are sparse. The largest available study is that of formation was seen between the two techniquestu'
Candiani et al '0, who reviewed 622 patients who However, in this investigation, the same size suture
u n derwent myomectomy over a 7 4-y ear period. They (3-0) was used for both surgeries, a situation not
180
Uterine Leiomyomas
likely to be generalisable to the vast majority of Myolysis

gynecologic surgeons. Data suggest laparoscopic The theory behind myolysis is that by destroying
myomectomy is more time consuming, hut recent either fibroid tissue or its blood supply the resulting
advances in instrumentation may nanurv t{rh time shrinkage of the tumor will be sufficient to
gap. The only apparent limitation notlf' aed significantly diminish symptoms. To this end, a
with the laparoscopic approach is fibroid rttfltber; laparoscopic approach using the Nd:YAG laser,
when more than four fibroids are preseilt, most bipolar needles, monopolar cautery, and cryotherapy
surgeons prefer an open surgical approdch. have been demonstrated to be effectiveo'. However,
the length of follow-up is limited, and the long-term
Hysteroscopic Myomectomy recurrence risk is unknown.
A hysteroscopic approach to fibroid resection is
feasible when the tumour protrudes into the uterine Nonsurgical Treatment
cavity (submucous myoma). ln this instance, the use Uterine Artery Embolization (UAE)
of an operative hysteroscope to resect the fibroid is A new technique for the treatment of fibroids is the
quick and easy. This form of treatment is useful for use of uterine artery embolization. This approach'
submucous fibroids, thereby avoiding peritoneal has long been available as a means of stopping
adhesion formation that may occur in a haemorrhage, but it was only recently that it was
transabdominal approach. Pretreatment with GnRH applied in an attempt to shrink fibroids. The
agonist is indicated if the largest diameter of the procedure involves catheterization of the uterine
fibroid is within the endometrial cavity, although no arteries via femoral artery access. Once in place,
data exist to verify the value of this approach. Several polyvinyl alcohol particles are injected into the
dangers of hysteroscopic excision have been noted, arteries to occlude them. Data suggest that in
principally due to the use of hypotonic, hyponatremic experienced hands this procedure is a technical
fluid distension media for the uterust'. The use of an success in more than 95% of womeno''ot. Uterine
automated fluid management system is essential to volume appears to decrease by 40-50%, and
prevent excessive absorption of this fluid under such symptomatic control was achieved in approximately
t'. Currently, resectoscopic devices are 80%.
circumstances
I
being developed that can be used in physiologic
Uterine Artery Embolization is safe and effective in
solutions.
i the treatment of symptomatic uterine fibroids. About
I
The risk of recurrence of myomas following 80-90% of patients will be asymptomatic or have
r
I
I hysteroscopic resect'1on appears to be higher than significantly improved symptoms at 12 weeks with
I r-- that for the abdominal approach, although no direct an associated 40-70% reduction in uterine volume
I
comparisons exist. Using survival analysis, it was within the same periodu'. Almost 3% of patients may
shown that the risk of further surgery following the req u i re hysterectomy aft er UA E a nd 7 -2% of pati ents
r will develop early ovarian failure especially those
I
; procedure is 27% at 4 years". By contrast another
( study documented a 3-year cumulative recurrence aged 45 years and above. A2012 Cochrane review
( that looked at risks and benefits of UAE versus other
I risk of 34o/o". This latter investigation also reported
I medical or surgical management of uterine fibroids
the reproductive success in infertile women
u ndergoi n g the proced u re : the 3-yea r conception rate found no significant difference in the satisfaction rate
was 33-49%, depending upon thetype of lesion. between the 2 groups even though there was higher
Other surgical methods of management include rate of complication and need for re-intervention
u'.
bilateral uterine artery ligation through the vaginal within the UAE group
, route. This is also effective and can be suitable for low
:
resource settings without the sophisticated Studies comparing UAE and myomectomy showed
I
equipment and highly skilled personnel as required similar symptom control and complication rates.
for uterine artery embolization (UAD. lt has been Hospital stay and recovery time were however
found that this mdthod reduces menstrual blood loss significantly shorter after UAE. The rate of re-
I and effectively uterine and fibroid volume to a degree
intervention was howevei significantly higher
similarto results obtained after UAE.'. following UAE, mostly occurring within 3-5years
afterthe procedureu'.
181
=---l
There is as yet no strong evidence in support sf the causes an initial stimulation of gonadotrophins
beneficial effect of myomectomy and UAE in furtility production (the flare) followed by down-regulation.
and pregnancy outcomes. A small str.l4:,h-ourever There is therefore an initial stimulation of ovarian sex
f oundmyomectomytobeassociated.,rti$.E-_--@ steroid production, which last several hours to few
pregnancy rates and fewer miscarriryf days followed by suppression thus creating a 1.
with UAE. On the basis of the current evi@#,b hypoestrogenic/hypoprogestrogenic state, which
impossible to make recommendat.*i.8i:ij#*+st causes uterine and fibroid reduction. A 3 month
treatment (myomectomy or UAE) fcr.Wqtren w+th course of GnRHa will result in 35-60% reduction in
symptomatic fibroids who want to 'r-etain their tumour size and two thirds of patients became
fertility5'. : amenorrheicu'. The hypogonadal state it creates
however limits its long term use and it is
Magnetic resonance-guided focused ultrasound recommended for use for a period not more than 3-6
surgery (MRgFUS) months. The most feared consequence of this
hypogonadal state is osteoporosis and possible
This is a completely non-invasive method of thermal fractures. Hot flashes and other vasomotor
ablation of uterine fibroids. The procedure makes use
symptoms may also result in significant reduction in
of high-intensity focused ultrasound that passes quality of life of these patients.
through the anterior abdominal wall to converge at a
precise target point within the fibroid resulting in Adding back a small amount of hormonal therapy
temperature rise sufficient enough to induce allows minimization of side effects, while hopefully
coagulative necrosis within a few seconds. not impacting upon treatment efficacy. Recently,
Concurrent use of MRI is crucial to allow for precise specific GnRH binding sites-both high and low
tissue targeting and real time temperature monitoring affinity-have been found in fibroids with a common
resulting in controlled localized thermal ablationu'. A site for both agonist and antagonist; this may suggest
major drawback of this procedure is that only fibroids an additional direct effect of GnRH analogues on
located anteriorly, immediately beneath eth anterior fibroid tissue'0.
abdominal wall without bowel interposition or scars
in the area of interest qualify for the procedure. This Several pilot studies have investigated this approach,
requirement limits the number of patients that are each utilizing only a handful of patients 'u'ou. Their
el igi ble for the procedu re. data demonstrate that fibroid volume can be
decreased satisfactorily with GnRH-agonist therapy,
MedicalTherapy and regrowth will not occur with the addition of low-
Medical therapy may 6e employed as preoperative dose sex steroid replacement (conjugated equine
adjunct to control heavy menstrual blood (HMB) loss estrogens O.625 mg/day a nd med roxyprogesterone
and decrease uterine size. lt may also be used for acetate i0 mg 10 days/month). However, higher-
temporary relief of symptoms in patients not suitable dose medroxyprogesterone alone will apparently
for or are unwilling to consent to surgical cause regrowth"u. Unfortunately, follow-up is limited
intervention. Currently, the options available for to 1 year; long-termresults with this approach of
medical management of uterine fibroids are not low-dose hormone replacement are unknown at this
suitable for long term therapy due to concerns of time.
safety and side effects. Gonadotrophin Releasing
Hormone analogues (GnRHa) have long been used to There is no consensus regarding the timing of
alleviate the symptom of HMB, improve haematocrit administration of GnRH analogues in relation to the
and decrease uterine size priorto definitive surgery. menstrual cycle. When the analogue is begun in the
The GnRH agonists are produced by peptide follicular phase there is unopposed oestrogen
substitutions at positions 6 and 10 which make them secretion due to the initial flare effect of the
more potent (about 40-200), increase their binding analogues, and an oestrogen withdrawal bleed
affinity to pituitary GnRH receptors and increase their occurs 10-14 days later. This may be a disadvantage
resistance to proteolytic degradation. The agonist especially if menorrhagia was the reason for the
binds to the pituitary receptors with high affinity and treatment of the fibroid. This time of
L82
Uterine Leiomyomas
commencement, however rules out the'possibility of (Schering) reduces intensity of menstrual bleedings
administration during pregnancy. When begun in the secondary to uterine fibroidso'. There are some
l luteal phase of the menstrual cycle, the eile{#ion of research which allude to the fact that long term use
1., the gonadotrophins and sex steroids,$s::@to of LNG IUD is associated with lower incidence of
th i s p h a se a n d n o rm a Im en stru ati o n ecu,q.p@{. a fibroids in comparison with copper lUCD", and in
subsequent withdrawa| b|eed in tfretsftordfi$ . some cases a reduction in the volume of fibroidsoe.
Other medical treatment The exact mechanism is not yet known but it has
been postulated that these finding may be due to the
Ulipristal acetate effect of levonorgestrel on insulin-like endometrial
growth factors and their binding proteins. The main
Ulipristal acetate, a selective Progesterone receptor
side effect of the LNG-IUD is irregular breakthrough
modulator (SPRM), has been licensed for use in'the
bleeding. This is most common in the first 6 months
preoperative treatment of symptomatic fibroids since
after insertion. Detailed counselling is crucial to
2072. The drug induces apoptosis and
explain this anticipated effect, in order to reduce '
antiproliferative effect on fibroid cells, leading to

unnecessary discontinuation of treatment. After 6
rapid reduction uterine volume and improvement of
months' treatment with the LNG-IUD, 20% of
symptomsuo. ln a short-term (3 months) double
women become amenorrheic, rising to 50% after 5
-blind, non-inferiority trial that randomly assigned years. Again, it is important to explain that this is an
307 women with symptomatic fibroids and excessive
expected phenomenon, that it is not related to
uterine bleeding to either 5mg or 10mg daily of
d isorders of the hypotha lam ic-pituita ry-ova ria n axis,
Ulipristal acetate or once-monthly injection with and that this 'bleed-free' status might indeed be
3.75mg Leuprolide acetate, Uterine bleeding was
viewed as a positive feature in its own right.
controlled in 90% of patients receiving 5mg ulipristal
acetate, 98% in those receiving 10mg UA and 89% Aromatase lnhibitors block the peripheral as well as
in those receiving Leuprolide acetate at 13 weeksuu. ovarian conversion of androgens to estrogen. Several
Both the 5m and 1Omg UA doses were non-inferiorto small studies have shown that these agents are
Leuprolide acetate in controlling uterine bleeding and effective against uterine fibroids by inducing
were less likely to cause severe side effects like hot significant shrinkage of uterine fibroids and rapid
!
flushesuu. Ulipristal acetate is associated with more improvements in symptomsu'. One RCT that
:
rapid cessation of uterine bleeding compared with compared the effects of 3 months of Letrozole (Al) to
i
I GnRHa. After treatment cessation with UA, that of 3 months Triptorelin (GnRHa) on uterine
I
( menstruation usually'returns within 4-5 weeks but fibroid volume showed that Letrozole had the
t
I the observed reduction in uterine volume may last for advantage of rapid onset of action as against the
I
I
II as long as 6 monthsuo. Treatment with UA is initial flare-ups that occur with GnRHa. Both agents
r associated with a benign patern of endometrial were associated with significant reduction in fibroid
I
I
( change termer Progesterone receptor modulator volume and improvement in fibroid related
I associated endometrial changes (PAEC). This not an symptomsut'uu. A major concern with the use of the
I
I endometrial hyperplasia and the changes gradually Al, just as with GnRHa, however is the risk of bone
( resolve after cessation of therapy.
r( loss with prolonged use that may necessitate
I concomitant use of progestins or the combined
rI- A recent study that evaluated intermittent UPA
contraceptives.
L
I treatment with treatment free intervals as an option
t
a for long term medical treatment for symptomatic Gestrinone is a synthetic trienic 19 norsteriod, which
uterine fibroids concluded that, repeated 3-month has marked antiprogesterone, anti-oestrogen and
I
courses of oral UPA 10mg once daily effectively moderate antigonadotrophic properties and is mildly
controlled bleeding and pain, reduce fibroid volume androgenic. lt produces endometrial atrophy.
and restored quality of life to many women with Coutinho et aluo treated 97 patients. Reduction in
I sym ptomatic f i broidsuo. volume occurred in 73"/" of patient overall.
i Alleviation of symptoms, especially of abnormal
? lnsertion of levonorgestrel releasing Mirena IUD
uterine bleeding and pain occurred in95% and 66%
r.,
i
183
respectively. Undesirable side effects mainly due to fibroids in infertility. Typical questions confronting us
androgen excess occurredin 45"/"u' . are: Do fibroids cause infertility? Should women with
infertility who have uterine fibroids as the sole
Discussions and Controversies abnormalityfound, be offered myomectomy?
A number of therapies are currently available fot'tfte
treatment of uterine leiomyomata, each with These must be considered against the background
advantages and disadvantages. This array of that myomectomy itself can lead to reduction in
approaches enables the modern clinician to present fertility either by damaging the fallopian tubes during
the patient with symptomatic fibroids with a variety the procedure or by the development of pelvic
of options; the patient now has been empowered to adhesions. When met with such scenarios in clinical
help select a treatment modality that best fits her situations imaging studies to determine the locations
desires for degree of surgery, risk of recurrence, and of the fibroid nodules may aid decision-making'
need for future fertility. Nevertheless, most Submucous fibroids may be mostly associated with
alternatives to the traditional hysterectomy are new infertility whilst subserous ones hardly interfere with
and poorly studied. Little is known regarding risks, fertility.
costs, and comparative value. Furthermore, many Another consideration is the size of uterus at which
such procedures are still in a state of evolution, with hysterectomy must be performed by all means.
study results having little applicability to the modern Formerly hysterectomy was performed once uterine
performance of such procedures. size was more than 14 weeks. This teaching has
changed ever since ithas become possible to
Ultimately, if the genetic basis for fibroid deve- minimize blood loss at myomectomy using the
lopment andlor the molecular mechanism(s) of tourniquet. Myomectomy had been carried out on
myometrial proliferation are understood, additional uteri as big as 28 weeks.
nonsurgical therapeutic interventions may be
forthcoming. Current clinical needs are to a) Myomectomy had generally been contraindicated
determine an effective prevention strategy in during caesarean section. The fear of excessive
genetically predisposed individuals; b) slow the bleeding intraoperatively has been the main factor
growth of leiomyomata; c) identify the mechanisms accounting for this standard attitude. Some
of infertility; d) improve early detection; e) develop authorities now believe that with the effective use of
better surgical techniques; f) reduce recurrences after tourniquet should be possible to perform
it
myomectomy; g) develop nonextirpative options; and myomectomy in selected cases during caesarean
h) evaluate their long-term results. section. With this new approach myomectomy
during caesarean section might soon become the
Some of the controversies present with regard to the standard practice in this millennium.
management of uterine fibroids include the role of
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Anderson J, Babieri RL. Abnormal gene 4 Marshall LM, Spiegelman D, Babieri RL, Goldman
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Gynaecol DJ. Variation in the in'cidence of uterine
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1
I leiomyomas assocrated with oral contraceptive 24. Diamond MP Surgicalaspects of infertility. ln:
usage. Am J surg Pathol 17, 548-549. Gynaecology and obstetrics led JW Sciarral,
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Exp Obstet Gynecol, 2001, Vol. 28(2). pp. 86-g. fertility. Surg Gynaecol Obstet 1983; 156: 319.
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: Oct. 2000. formation after laparoscopic myomectomy: a
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. operative GnRH analogue therapy before 30. Candiani GB, Fedele L, Parazzini E Villa L. Risk
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Abdominal myomectomy in the treatment of
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32. Roopnarinesingh S, Suratsingh J, pattern and fertility. Obstet Gynecol 94:341347
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-
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705 (1999.
DeGiorgi O, Crosignani PG. Hystero.scoprc
185
CHAPTEil6
Pelvic Relaxatien
SA Obed and MY Ntumy
a
I
3. The
I
L
I
DEFINITION are together known as the pelvic diaphragm
Weakness of pelvic supporting structures may allow muscle floor is defective in the midline where the
I
descent of the pelvic organs into the vagina and faecal urethra, vagina and rectum pass through. The
I
control problems. This process is termed pelvic anterior attachment of the levator is linear and
extends from the body of the pubis to the ischial
I
I
relaxation
I
spine. There is direct attachment to the bone of the
t- !NTRODUCTION body of the pubis lateral to the symphysis and to the
I
Pelvic relaxation leads to genital tract prolapse, stress
I ischialspine.
I incontinence of urine and faecal incontinence. The
r major contributing factor of pelvic relaxation is The levator is conventionally divided into three parts
I
r pregnancy and childbirth 7,2. Pelvic relaxation can

- pubococcygeus, iliococcygeus and ischiococeygus.
r be seen in the nullipara and in this case it may be The pubococcygeus is the most medial. lt is further
i
r associated with developmental failure of the support divided into two parts: a posterior flat muscle
F
t system. inserted into the tip of coccyx and anoccygeal raphe
t
and a thicker anterior part, the puborectalis, whose
r Pelvic relaxation is often widespread and it is not
rI fibres swing medially and join those from the
uncommon for women suffering from genital prolapse opposite side to mingle with the external anal
r
to have impaired urinary and faecal control. The
r
t structure of specialist practice in West Africa is such
sphincter.
r that women with genital prolapse and urinary The iliococcygeus is contiguous with that of the
I
"t incontinence are usually looked after by pubococcygeus. lt partly overlaps the latter to insert
f
gynaecologists while those suffering from ano-rectal below it on the coccyx and the anococcygeal raphe.
r
a
:
problems are cared for by general or rectal surgeons. The ischiococcygeus is often rudimentary. lt arises
ln this book urinary incontinence is discussed from the ischial spine and is inserted into the caudal
,,
elsewhere while faecal incontinence is out of scope. part of the sacrum and upper coccygeal vertebrae.
This chapter is mainly centred on genital prolapse.
: The pelvic floor muscle has a double nerve supply,
ANATOM IC CONSI DERATIONS the pudendal nerve arising from the anterior primary
i The fixed, unyielding support of the pelvic organs is
derived from the pelvic bones, while the major soft
rami of 52, 53 and 54 and direct branches from the
motor roots of 53 and 54 to its visceral surface.
'a
tissue support is afforded by the muscular pelvic floor.
The major component of the pelvic floor is a pair of The striated muscle of the pelvic floor is different
symmetrical striated muscle sheets known as the from limb striated muscle in that it is in a state of
f levator ani muscles. The levator ani muscles are continuous activity even during sleep.
I covered by fascia on the inferior and superior
surfaces. The levator ani muscles and their fasciae The median raphe between the anus and coccyx is
1.
187
called the levator plate. lt is formed by the midline perineal body. The perineum is formed by the union
fusion of the iliococcygeal fibres and the posterior of the levator ani muscles with the bulbocaverosus
fibres of the pubococcygeus muscles from each side' a nd the su perf icia I tra nsverse peri nei m uscles'
ln standing position, the levator plate is horircrful l

Pelvic Organ Support
and supports the vagina and rectum above it. ftffirto
chapter 3, fig 8 showing diagram of the Pelvic Floor
ln addition to the pelvic floor muscles, certain
connective tissues, called endopelvic fascia, play a
The central hiatus where the urethra, vagina and
vital role in pelvic organ support' The endopelvic
rectum penetrate the pelvic diaphragm form the :
fascia is a three-dimensional ligamentous mesentery
weakest portion. The external portion of this weak
of connective tissue that envelopes the pelvic organs
portion receives additional support from the o.
:
and attaches or suspends them to the pelvic walls
urogenital diaphragm also called the triangular
The endopelvic fascia extends from the level of the
ligament. The urogenital diaphragm is composed of
uterine artery to the fusion of the vagina and levator l
two layers of fascia, deep and superficial. The fascial
ani 5. The endopelvic fascia attached to the uterus is
layers surround a number of supporting skeletal
called the parametrium and is composed of the
muscles lying within the triangular area formed by
uterosacral and cardinal ligaments. The uterosacral
the ischial tuberosities and the inferior rami of the
ligaments pass from the cervix to the sacrum and the
symphysis pubis. Within the deep fascial layer are
lateral thickenings in the base of the broad ligament
fat, loose connective tissue, and thin deep transverse
are the transverse cervical or cardinal or Mackenrodt i
perinei muscles. Within the superficial layer lie the
ligaments. The paracolpium is the endopelvic fascia
superficial transverse perinei muscles and the
isch iocavernosus and bu I bocavernosus m uscles.
that supports the vagina and it contains the (
pubocervical and rectovaginal fasciae. The
The superficial transverse perineal muscles arise endopelvic fascia is composed of visceral connective
from each ischial tuberosity and insert into the tissue, which provides the pelvic organs with room
midline of the perineum, posterior to.the vaginal for movement and volume changes while supporting
introitus. The bulbocavernosus muscles arise from them.
the midline of the perineal body, pass over the
The elements of pelvic floor and vaginal support have
vestibular bulb and Bartholin's gland along each side
been shown by De Lancey 6 to be as follows: The
of the vagina, and insert into the interior crus of the
upper paracolpium suspends the apex to thepelvic
clitoris.
walls and sacrum. Damage to this support results in
The vagina creates a central defect between the prolapse of the vaginal apex. At midvaginal level, the
medial aspect of the levator muscles, and it separates vagina is attached to the arcus tendineus fascia of the
the muscles of the urogenital diaphragm into pairs' pelvis and the superior fascia of the levator ani
The bulbocavernosus muscles may be considered as muscles. Distally the lower vagina is fused to the
the superficial vaginal constrictors; the levator perineal membrane, perineal body and levators.
muscles are the deep constrictors. The Urogenital
FACTORS CONTRIBUTING TO PELVIC ORGAN
Diaphragm is well illustrated in Chapter3, Figure 8.
The upper 2-3 cm of the vagina lie in close proximity PROLAPSE
to the pouch of Douglas. The depth of the Pouch of
A combination of factors contribute to the occurrence
Douglas can be extended to about 5cm from the
of genital prolapse. There are congenital factors that
lower uterine segment to the upper third of the
are considered to be the factors that predispose an
posterior vagina where it separates the rectum from
individual to development of pelvic organ prolapse.
the vagina. lf the peritoneal sac extends deeper into
These predisposing congenital factors include
the rectovaginal space, it forms a peritoneal pouch or
skeletal deformities, connective tissue disorders,
enterocele. u'''t''.
neu romuscu la r factors and race
At the lower end of the vaginal canal, the rectum

Pelvic organ prolapse is moie frequent among
diverges posteriorly because of the interdigitating
Caucasians than Asians and Africans. This difference
muscles of the external anal sphincter and the
188
f
I
r
(
l
t
(
(
I may be explained on the basis of inherited racial DISORDERS OF PELVIC RELAXATION
I
r differences in the pelvic architecture, the quality of

supporting pelvic muscles and connective tissue, and The abnormalities that result from pelvic relaxation
the tendency of some races for thicker fibrous tissue include:
I
r to develop following injury. They also may be 1. Cystocele

I
explained by environmental and socio-cultural
2. Rectocele
rf-
practices like reproductive function and care,
3. Enterocele
I
participation in hard physical labour and pelvic

4. Urethrocele
I
5. Uterine Prolapse
r
I
infection
2.
6. Vaginal vault prolapsed after hysterectomy
I
r
I
Repeated acute exacerbations of chronic
pelvic It is unusual to have only one of these conditions. ln
I
I inflammatory disease and severe postabortal or most cases the relaxation affects all the support
i
!
puerperal sepsis can cause induration of paracervical structures of the pelvis. Frequently relaxation of the
I
and parametrial tissues. Dense intrapelvic adhesions urethra, the bladder neck and the bladder
i may form and such patients have reduced risk of
developing genital prolapse.
(urethrocele, cystocele) is associated with urinary
I incontinence, which is covered elsewhere.
t' Vaginal delivery, pelvic surgery and the presence of CLASSI FICATION OF PELVIC ORGAN PROLAPSE
I neurological problems serve as inciting or acquired
( factors for the development of pelvic organ prolapse
u.
Pelvic organ prolapse is classified into five stages by
I
t Obstetric damage is a very important risk factor. the lnternational Continence Society '0. Stage 0: No
Difficultvaginal delivery may result in various degrees prolapse demonstrated
t
t of damage to pelvic support structures, including the
t" ligaments, fascia and muscles and their nerve Stage t: The most distal portion of the prolapse is
I
i
supply'. More damage is caused when the labour is morethan 1cm abovethe levelof the hymen
i
r prolonged, when the fetal head and/or shoulders are
r
I large and when difficult forceps operations are Stage ll: The most distal portion of the prolapse is
t 1cm or less proximal to or distal to the plane of the
1-
required for delivery. Bearing down prior to full
dilatation of the cervix pushes the cervix ahead of the hymen
t
r baby, at times stretching beyond capacity those

Stage !!l: The most distal portion of the prolapse is
rI pelvic connective tissues concerned with support of
more than 1cm below the plane of the hymen but
the cervix and the upper vagina.
protrudes no further than 2cm less than the total
(
i The degenerative charges of aging and menopause vaginal length in cm
I cause loss of oestrogenic support of the endopelvic
{
i fascia and the inability of the tissue to repair
Stage lV: Complete eversion of the total length of the
lower genital tract is demonstrated
a effectively or replicate essential structural
: components. U RETH ROCELE AN D CYSTOCELE
ln the erect position, increased in intra-abdominal Definition

pressure in the female is directed with greater force to Rupture or attenuation of the pubocervical fascia for
the most dependent part of the abdominal cavity, the any reason may allow the descent of the urethra
pelvic diaphragm. Such increases in the intra (urethrocele), bladder neck or bladder (cystocele)
abdominal pressure may result from chronic cough, into the vaginal canal. When cystocele is only
obesity, pelvic tumours, ascites, hard physical present, the patient is generally continent of urine;
a exertion, heavy lifting and straining as seen in chronic while urethrocele usually leads to stress
constipation. These factors serve as promoting incontinence.
u.
I factors in the development of pelvic organ prolapse
r Urethrocele is more common in women with wide
subpubic arches (gynaecoid pelvis), which allow the
189
full force of the fetal head against this area during Differential diagnosis of urethrocele include inflamed
descent in labour. Narrower sub pubic arches such as enlarged Skene's glands and urethral diverticula.
those associated with the android or ffihrqoid lnflamed skene's glands are generally tender, and it
pelvis, seem to protect this region from the OeSWt ot may be possible to express pus from the urethra
I
thefetalhead. when they are palpated. Although diverticula may be
reducible, a sensation of a mass is usually present.
Clinical Presentation Cystoceles must be differentiated from bladder
Urethrocele and cystocele are commonly seen in tumours.
parous women. They can also be seen in nulliparous
women who have congenital malformations or RECTOCELE
weaknesses of the endopelvic connective tissue and
musculature of the pelvic floor. Definition
Rectocele occurs when the musculofascial support
Some women may be asymptomatic and the lesions between the rectum and vagina weakens.
are noticed during pelvic examination. Common lnadequate innervation and congenital weakness of
symptoms include sensation of fullness or pressure the perineal muscle in addition to lacerations of the
and at times a feeling that organs are falling out, fascia of the rectovaginal septum may also be
stress incontinence, urgency and a feeling of important ". Prolonged pressure of the fetal head
incomplete emptying wiih voiding. between the muscles of the pelvic flow, particularly
during a prolonged second stage of labour, weakens
A bulging mass is noticed in the anterior vaginal wall the rectovaginal septum. Strenuous work, straining
by the patient and in some cases, this bulging mass at stool, multiple pregnancies, aging and orthostatic
must be replaced manually before the patient can pressure of the pelvic viscera against the pelvic floor
void. Strain or cough accentuates the bulge. are other factors that may produce weakening of the
musculofascial support, eventually causing
Diagnosis
rectocele. Occasionally relaxed vaginal outlet is
When the patient is examined preferably in the
confused with rectocele. Vaginal outlet relaxation is
lithotomy position, depression of the posterior
simply due to thinning and separation of the muscles
vaginal wall and the patient is asked to strain, the
of the perineal body. Clinical Presentation The
cystocele and urethrocele would be seen and the
symptoms of rectocele include heavy or "falling out"
degree of descent noted. The bladder neck should be
feeling in the vagina, incomplete emptying of the
palpated to find out whether it is well supported.
rectum with defaecation and the need for digital
Generally, if the supports of the bladder neck are
splinting of the posterior vaginal wall to effect a
adequate, the urethra is adequately supported. lf a
bowel movement. Rectocele is noticed by retracting
cystocele and urethrocele are present, it invariably
the anteriorvaginal wall the patient asked to strain. A
follows that the bladder neck is not su pported .
bulge appears in the posteriorvaginal wall.
FEI*-{ CtrSIeCs.E Fisi*-2 HEBffiCELE
190
rI
r
r
t
r
Figl4-2RECTOCELE sac when the patient is asked to bear down by a
t valsava manoeuvre.
t
ENTEROCELE Definition Enterocele is 4 p.er,itoneum
lined sac containing small bowel or iiffi{itum. The
rr common one, posterior type, is located'br$ueen the
vagina and rectum in contrast to the uncomnTon ones
I
I
located anteriorly (anterior enterocele) or lateral
i (pudendal enterocele) to the vagina ".
Enterocele
I
I
may occur with or without coincident uterine
( prolapse or eversion of the vaginal vault. The
l
J
common posterior type is discussed in this section.
r Considering the aetiology of enterocele, it may be
I
classified as -Congenital -Pulsion -Traction -
latrogenic latrogenic Congenital enterocele results
r
i
I
from failure of fusion or re-opening of the previous
fusion of the peritoneum so that bowel-filled cul-de-
sac may extend by dissection all the way to the
perineal body, ln fetal life, the peritoneal cavity
r
I
extends to a point of continuity with the cranial part of Fig 14-3 BITEf,$GELE
I
I the perineal body, but this sac generally becomes

obliterated early in life. lts fused tissues probably
r
I
I constitute a layer of the fascia of Denonvilliers UTERINE PROLAPSE
( adherent to the undersurface of the posterior vaginal
r
t
t
wall. The pulsion type of enterocele probably resuits Descent of the uterus and cervix into or through the
from the pushing and eversion of the vaginal vault by barrel of the vagina is associated with injuries of the
ri chronic increase in intra-abdominal pressure us with
,
endopelvic fascia, including the cardinal and
r heavy lifting. Other causes may include patients who uterosacral ligaments, as well as injury to or
?
I have asthma, chronic emphysema or any respiratory relaxation of the pelvicfloor muscles; particularlythe
I
difficulties. Traction enterocele usually co-exist with levator ani muscles. Prolapse of the uterus may also
r
r cystocele and rectocele. ln this case the vaginal vault result from increased intraabdominal pressure such
I
is pulled down consequent to a general soft tissue as ascites, large pelvic or intraabdominal tumours
[*-
r weakness associated with cystocele and rectocele. super imposed on poor pelvic supports. Sacral nerve
I
The iatrogenic enterocele usually follows a surgical disorders especially injury to S1 to 54 or diabetic
r change in the vaginal axis as in Burch or Marshall-
t neuropathy may occasionally be responsible. Other
f Marchetti-Krantz operation or a ventral suspension. factors that increase tension on pelvic floor
r'l' These procedures leave the Pouch of Douglas musculature such as chronic respiratory diseases
I
I unprotected. including chronic bronchitis, asthma and
bronchiectasis orsevere obesity may be associated.
Clinical Presentation Many patients with minor Congenitally damaged or relaxed pelvic floor
forms of enterocele remain asymptomatic. Patients
i-
supports may cause prolapse in young, nulliparous
i usually complain of feeling of pelvic heaviness and
women.
pressure. The bearing-down sensation, often
exacerbated with prolonged standing, results from
: Majority of the patients are, however multiparous,
the pull of gravity, stretching the mesentery of the sac
bontents. Backache which worsens as the day goes
with the prolapse being at least in part a result of
( childbirth trauma.
on and is relieved somewhat by lying down is also a
1 common complaint. Enterocele is noticed after
replacing all the prolapsed organs and by a recto- Uterine prolapse is almost always associated with
l.
vaginal examination of the index and middle finger; a rectocele and cystocele and, at times enterocele.
:
loop of bowel or omentum is palpated in a peritoneal
r.
191
GRADING OF UTERINE PROLAPSE
Uterine Prolapse is graded in degrees: A prolapse into

the upper barrel of the vagina is termed first degree. lf
the prolapse is through the vaginal barrel to the
region of the introitus, it is second degrce, If the
cervix and uterus prolapse out through the introitus,
it is termed third degree or procidentia. ln
procidentia, the vagina is everted around the uterus
and cervix and completely exteriorised. This may
lead to the vaginal epithelium becoming dry,
thickened and suffer from chronic inflammation.
Stasis ulcers may result as oedema and interference
with blood supply to vaginal wall occur. These ulcers Fie. L4 - 4b PROCIDENTIA
rarely become mal ignant.
Clinical Presentation VAGINAL VAULT PROLAPSE AFTER

The patients usually complain of feeling of heaviness, HYSTERECTOMY
fullness or "falling-out" in the perineal area. ln cases Prolapse of the vaginal stump after either abdominal
where the cervix and uterus are low in the vaginal or vaginal hysterectomy is not a common finding in
canal, the cervix may be seen protruding from the the West African sub region. However, among
introitus, giving the patient the impression that a Caucasians the reported incidence ranges from 0.1%
tumour is bulging out of her vagina. ln procidentia, lo 78.2% ". The prolapse may be total and may be
the patient is aware that a mass has actually accompaniedby a cystocele, a rectocele, or an
prolapsed out of the introitus. Symptoms of cystocele enterocele or some combination thereof.
and rectocele are usually reported as those Occasionally the prolapse only involves one of those
conditions are always associated with uterine entities and not the entire vaginal stump'0.
prolapse. lf the cervix or vaginal epithelium becomes
damaged, the patient may report pain or vaginal Vaginal vault prolapse is probably the result of
bleeding. There is often discharge from the cervix and continuing pelvic support weakness and failure of the
vagina when secondary infection occurs. cardinal and uterosacral ligaments to maintain their
tone or attachment to the vagina.
Clinical Presentation
Symptoms of vault prolapse are similar to those of
uterine prolapse. They include pelvic heaviness,
backache and a mass protruding through the
i ntroitus. Occasiona I ly, stress i nconti nence, u rgency,
frequency and dribbling of urine, vaginal bleeding or

discharge (if there is an ulcer) and depending on the
size of the mass, d ifficulty with sitiing or walking may
occur.
Vaginal examination may help to determine the

contents of the herniation depending or, where the
vaginal scar is located with respect to the protruding
mass and the extent to which the supports of the
pelvis are lost.
Fig. 14 - 4a PROCIDENTIA Rectovaginal examination is often helpful in

delineating an enterocele from a rectocele.
t92
rI
(
I
I
r
t CLINICAL EVALUATION Expectant Management
I
The factors that have to be considered in the Patients with mild degrees of utero-vaginal prolapse
r:
management of uterine prolapse and associated discovered during routine gynaecological
examination with no symptoms need no surgical
( repair. The patient should be informed of her
l -Age -Desire for preservation of reproductive
/ condition and associated problems that could nlake
r
I
function -Desire for preservation of coital function - the pelvic relaxation worse over time, like.zchronic
i General medical status -Previous attempts at cough, obesity and chronic constipation. Measures
s u rgica I correcti o n -Sym ptomatology - Physical
t
t
to prevent or correct these associated problems
I examination findings. should be instituted. Postmenopausal women
( should be advised to accept oestrogen replacement
After a detailed history is taken; a general physical
I therapy unless contraindicated. Patients should also
i
I
examination must be done to assess the patient's
general health status. Occasionally a referral for
be taught the technique of perineal muscle exercises.
L
1-
medical consultation is prudent. A thorough pelvic - Rememberingthatthe uterus is NOTthecause
I
I
examination is essential to delineate the various types of uterovaginal prolapse -
and degrees of the prolapse. Also a bimanual recto- - Repair all relaxations even though they are
vaginal examination is done to detect uterine and minor Whenever possible, attempt to re-create
I adnexal tumours and to be sure the pelvic organs are normal anatomy
free and not restricted by adhesions or other - Narrow the calibre of a large vagina, but not so
I
t pathology. much that intercourse will be difficult, painful
( or
The laboratory investigations usually done include
I
( full blood count, blood urea, creatinine and -Remembering that the uterus is NOT the cause of
r
I electrolytes, urine analysis, and stool routine uterovaginal prolapse -Repair all relaxations even
i though they are minor Whenever possible, attempt
( examination. Chest x-ray and eletrocardiogram are
to re-create normal anatomy -Narrow the calibre of a
i indicated in the elderly and those with cardiac and or
respiratory problems. Lesions especially ulcers on the large vagina, but not so much that intercourse will be
f
rI vagina should be biopsied for histological difficult, painful or Periodic examinations should be
I
examination to rule out carcinoma. done to determine the status of uterovaginal support
r and symptomatology and to re-enforce the patient's
r
t lf a postmenopausalpatient complains of bleeding as motivations to continue preventive measures.
(
well, investigations should be done to determine the
I
I cause. The investigations should include cytology, Pessaries
r biopsyof vaginal and cervical lesions and dilation and
The indications for the use of pessaries include
r tem pora ry measu re in the ea rly months of
I
I
curettage of the endometrium.
pregnancy, patienis who hope to have another child
ra or to postpone operative treatment, Occasionally a
CHOICE OF TREATMENT
!
The options of treatment depend on the varying pessary may be advised when a patient is unfit for an
t
i degrees of uterovaginal prolapse, their aetiologies anaesthetic orwhen the patient refuses an operation.
I
and symptomatology 15. The options include: Before a pessary is inserted a vaginal examination is
a 1. Expectant management done to exclude any other abnormalities and to

I
I 2. Pessaries assess probable size of ring required. The pessary is
3. Surgical management compressed into an ellipse for passage through the
i a. Manchester-Fothergill operation vaginal introitus. As the ring passes into the vagina
. b. Vaginal hysterectomy, anterior and above the pelvic floor, it returns to its circular
colporrhaphy, posterior colpoperi- form. The forefinger guides the upper part of the ring
!-
neorrhaphy a nd enterocelectomy) into the posterior fornix so that the cervix Iies within
c. Lefort colpocleisis the ring. The patient is re-6xamined to make sure
L
d. Trans vaginal sacrospinous colpopexy
that the vaginal walls are not unduly stretched, and
i
i
e. Trans abdominal sacral colpopexy
193
she is then asked to strain down to see that the ring is materials, there was a dramatic fall in mesh-
large enough not to be expelled. augmented vaginal procedures'u''u'".
..
Pessaries should be removed regularly Am anO Traditionally, anterior and posterior vaginal wall
reinserted. This can be done on a mons+B:@t€Eaqd prolapse are corrected with anterior and posterior
the pessary is changed atler 72 months.,fitycil$itsr, if colporrhaphy respectively. Recent advances in
any purulent discharge or bleeding occufs the.-:$ia,ti€tr+t pelvic reconstruction have employed the use of
should report at once, and the ring is renroved before different types of materials (Mesh) to augment the
full investigation. anterior vaginal wall repair. Some data suggest that
anterior vaginal wall repair with Polyglactin mesh
reinforcement was associated with higher success
rates than the traditional anterior wall repair alone.
There was however no difference in the complication
rate between the two techniques '8. Another study
comparing standard anterior vaginal wall repair with
the use of permanent (Prolypropylene) mesh as
overlay found the former procedure to be associated
with lower objective and subjective success. The use
of the mesh was however linked with higher rate of
surgical complications and over 10% rate of vaginal
exposu re'u. Si m i la rly, Col lagen coated Polypropylene
resulted in vaginal exposure in about L3% o'f treated
women 'u'". The current evidence does not support
Ring Pessary in place A ring pessary made of the use of mesh as overlay orfor augmentation during
polyethylene is used. This is flexible. The diameters Posterior vagi na I wa I I repai r for rectocele'u.
are given in millimetres. The correct size for the
patient is the largest size of which she is unaware. lf it Utero-vagi nal Prolapse
is too small it may be expelled the from the vagina on ln women with utero-vaginal prolapsed, vaginal
straining, and if it is too large it will cause discomfort hysterectomy with suspension of the vault is
and may cause pressure necrosis and ulceration of recommended. Prophylactic vault suspension during
the vaginal walls. vaginal hysterectomy aims at restoring normal
vaginal axis and may entail McCall culdoplasty and
SURGICAL MANAGEMENT suturing of the vault to the uterosacral ligament.
Procedures that distort the vaginal axis such as
Surgical management of pelvic organ prolapsed is sacrospinous ligameni suspension may best be
often employed in patients who are symptomatic or
avoided " because of the resultant dyspareunia that
those who decline or fail to respond to conservative negatively impacts on quality of life.
management. The past few decades have witnessed
significant changes in the surgical interventions Surgical management ofutero-vaginal prolapse
available for correction of pelvic organ prolapse. traditionally involved vaginal hysterectomy. There is
These changes largely include the use of synthetic or however an increasing demand for uterine preserving
natural materials to reinforce the weakened pelvic procedures by young women with UVP who have
f loor d u ri n g the pelvic reconstructive su rgery. fertility concerns. A variety of these fertility sparing
procedures exist, however, randomized controlled
Drawing from the success of mesh in the repair of
trials (RCT) comparing these procedures to vaginal
herhias, there was an explosion of different types of hysterectomy are limited. ln one study comparing
materials for use in pelvic reconstructive surgery all in vaginal hysterectomy plus sacrospinous ligament
an attempt to improve the surgical outcomes. suspension with uterine preservation ( Sacrospinous
However, after the United States FDA warning in Hysteropexy), dyspareunia was noted in both arms
2008 and 201 1 about the dangers of these but the sacrospinous ligament suspension was
L94
r
l
)
(
{ associated with more adverse symptoms ". VaginalVault Prolapse
I Surgical repair of post-hysterectomy vaginal vault
{ Abdominal scacro-hysteropexy (Abdominal prolapse can be achieved either vaginally or via the
Sacropexy) is considered the'gold sta'hd of.Pelvic t
abdominal route. Vaginally, e two commonest
organ prolapse surgery with uterine p'reservation. lt procedures are uterosacral ligament suspension
ri
I
has an apical success rate of about 93-99/o with very (USLS) and Sacrospinous ligament suspension
r low recurrent rate "''0. Currently, laparoscopic sacro- (SSLS). Studies comparing the two procedures show
I
I hysteropexy has gained wide acceptability' among similar anatomical and functional as well as adverse
tu.
a urogynaecologists. The procedure has similar outcomes
success rate as the abdominal sacro-hysteropexy. lt
i
has the advantage of less blood loss, shorter hospital Abdominal sacrocolpopexy using a poplypropylene
stay and faster recovery ". Sacro-hysteropexy, mesh is increasingly gaining popularity as a preferred
however, is associated with some postoperative method for correcting post hysterectomy vault
dysfunction that may have a negative impact on prolapsed. Compared to the vaginal procedures
(USLS and SSLS), abdominal sacrocolpopexy i5
t-
patient satisfaction. These include new onset bowel,

i voiding and sexual dysfunction. associated with higher success rate, less post
operative dyspareunia and lower recurrence rate
15'18'21.
ln an attempt to decease these postoperative There is also a gradual shift by
complications, Joukhader et al recently described a urogynaecologists toward laparoscopic and robotic
I
novel laparoscopic sacro-hysteropexy technique sacro-colpopexy as a result of the recent advances in
i using a MR|-visible mesh. This technique was found minimal access surgery. Randomized controlled
r to be safe and showed a favourable anatomical and trials (RCT) comparing abdominal scaro-colpopexy
i
functional outcome with good healing of Stress with laparoscopic sacrocolpopexy showed similar
a urinary incontinence. The authors noted that the MRI anatomic and subjective outcomes. Shorter hospital
r visible mesh was useful in postoperative stay and decreased blood loss are clear advantages
t'.
compl ication management of the laparoscopic tech nique'u'".
r
J
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il
r c,.,APrE-1
f
l
7
Urinary lncontinence
K.A. Danso, F. Ankobea-Kokroe and A. A. Ofori
lntroduction without seeking help.

Urinary incontinence is a distressing condition which
although rarely life-threatening, severely and The reported prevalence of urinary incontinence
adversely affects all aspects of a woman's quality of from the few studies done in the West African sub
life. lt is defined by the lnternational Continence region ranges from 2.8"/" to 4I.5"/".0" This wide
Society, as "the complaint of involuntary leakage of variation results from differences in the definitions
urine".' lt is broadly classified as urethral or non- used, population studied, and the study type.
fistulous urinary incontinence, where urine loss Women, however, experience incontinence of urine
occurs through the urethra; and extraurethral or twice as often as men.' Late complications of
fistulous incontinence, where loss of urine occurs pregnancy and childbirth, post-menopausal estro-
through a communication between the genital tract gen deficiency and the very nature of the female
and the urinary tract. urinary tract anatomy account for this difference.
Older women, more often experience incontinence of
:
The pattern of incontinence of urine in women differs urine.
a greatly between the high income and low income
countries. ln the high income countries urinary Neurophysiology of micturition
incontinence is commonly associated with pelvic The lower urinary tract is innervated by the parasym-
relaxation. ln low income countries including the pathetic, sympathetic and peripheral somatic motor
West African sub region, it is commonly due to and sensory neurons. Preganglionic neurons of the
childbirth related or obstetric injuries which result in parasympathetic nerves are located in the
urinary fistula formation. Such fistulas affect about intermedio-lateral horn of 52, 53 and 54. lmpulses
50,000 - 100,000 women each yeaf'' and these travel via the pelvic nerves to postganglionic neurons
women form part of a complex and difficult inconti- in the pelvic plexus, bladder wall and urethra.
nence group that need specialized care. lncontinence Activation of
parasympathetic nerves causes
from pelvic relaxation, though also found in these contraction of detrusor muscles via cholinergic M2
areas, is viewed as a minor problem compared with and M3 stimulation and relaxation of the urethra via
incontinence secondary to obstetric trauma. Nitric Oxide release.
This chapter will discuss the non-fistulous urinary Sympathetic innervation to the lower urinary tract
incontinence. ln high income countries many women originates in the thoraco-lumbar region of the spinal
will seek treatment for stress or urge incontinence. cord (T10-12). The axons leave the spinal cord via
However in the West African sub region, ignorance splanchnic nerves and travelthrough the hypogastric
and the belief that some loss of bladder control is a nerve to the lumbosacral sympathetic chain ganglia
I
'normal' result of childbirth and ageing make many and enter the pelvic nerves. When activated, they
women suffer from urinary incontinence for years inhibit detrusor muscle via Beta-3 adrenergic
L97
stimulation and causes contraction of urethral inhibitory control of ACG then sends parasympa-
sphinctervia Alpha 1 stimulation. thetic output to the urethra causing it to relax through
nitric oxide release and parasympathetic output to
Somatic innervation of the urethral sphincter is the bladder causing bladder contraction via M3
provided by the Pudendal nerve. Cell bodis are cholinergic activation.
located in the ventral horns of 52, 53 and 54 in a
region called the Onuf's Nucleus. Activation causes Definition of terms
contraction of u reth ra I sph i ncter via acetylcholine. Urinary incontinence often coexists with other lower
urinary tract symptoms. These symptoms are
The most important afferents for the micturition grouped into storage and voiding symptoms. The
process are the A-delta fibres and the C-fibres. They lnternational Continence Society definitions for some
travel in the spinal nerves to the sacral spinal cord. A- of these symptoms are as follows:
delta fibres carry normal sensation of bladder filling
and respond to gradual distension of bladder filling lncreased daytime frequency: lt is the complaint
(5-15 cm of water). C-fibres have a high mechanical that the individual voids too often by the day. During
threshold and responds to chemical irritants and waking hours a normal person voids 4-7 times on the
inflammation of urothelium. They are activated in average. Hence some authorities defined increased
pathologic conditions and exhibit spontaneous firing daytimefrequency as 8 or more voids duringthe day.
when the bladder is empty and increased firing
Nocturia: lt is the complaint that the individual has
during bladder distension. Activation causes bladder
to wake at night one or more times to void.
contraction.
Nocturnal enuresrs: lt is the complaint of loss of
The micturition cycle consists of a storage phase and
urine occurring during sleeP.
a voiding phase. The storage phase is entirely a spinal
cord reflex whiles the voiding phase is controlled by
IJrgency: lt is the complaint of a sudden compelling
higher brain centres. During bladder filling, low desire to pass urine which is difficult to defer.
afferent impulse from the bladder (A- delta fibres)
travels to the spinal cord. This initiates sympathetic Slow stream: lt
is the perception of reduced urine
firing from the spinal cord causing urethral sphincter flow compared to previous performance orto others.
contraction (Alpha 1) and detrusor relaxation (Beta
3). ln addition somatic pudendal stimulation causes lntermittent stream: lt is the complaint of urine flow
contraction of external grethral sphincter. Contrac- which starts and stops one or more occasion during
tion of external urethral sphincter in turn sends micturition.
afferent proprioceptive signal to the spinal cord to
i n itiati ng mictu rition resu lti ng
H esi ta ncy : Diff icu lty i n
inhibit parasympathetic flow to the detrusor muscle
causing relaxation. in a delay in the onset of voiding afterthe individual is
ready to void.
When the bladder is full, high intensity firing from the
A-delta fibres travel to the spinal cord and it is further Straining to void: lncreased muscular effort used to
conveyed to the Pontine Micturition Centre (PMC) initiate, maintain, or increase the u ri nary stream.
and then to higher centres (Anterior Cingulate Gyrus
and Prefrontal cortex). By default the PMC is lncomplete emptyingt The sensation that the
designed to send continuous impulse to the spinal bladder is not empty aftervoiding.
cord to activate micturition. lnhibitory signals from
Classification
Anterior Cingulate Gyrus (ACG) which can be
Urinary incontinence is classified as follows:
overridden by signals from the prefrontal Cortex 1. Sfress urinary incontinence. The complaint of
however keep PMC silent. When the decision to void involuntary leakage of urine on effort or exertion,
is made, signalfrom the Prefrontal Cortex is conveyed or on sneezing or coughing. .
to the ACG to releases the PMC from inhibitory 2. lJrgency incontinence. The complaint of involun-
control. The PMC having being released from the tary loss of urine associated with urgency
198
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t
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I 3. Mixed incontinence. The complaint of involun- The submucosa assists in forming a watertight
r
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{-
tary loss of urine associated with urgeney and also
with effort or physical exertion or on stlezlng or
closure of the mucosal surfaces.
i
r? coughing.
4. Overflow incontinence. This iS t6:.
iffiary
Thestriafed urogenital sphincter is made up of three
parts: the sphincter urethra which partially sur-
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t loss of urine associated with ineilxl@*tTdder rounds the proximal two thirds of the urethra, the
r emptying caused by impaired detrusor co*rtractil- compressor urethra and uterovaginal sphincter
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i ity or bladder outlet obstruction which arch over the ventral surface of the distal one
;
I 5. Functional incontinence. This is involuntary loss third of the urethra. These three parts of the stnated
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I of urine as a result of cognitive, psychological or urogenital sphincter act as a unit. They are com-
r physical impairment that make it difficult to reach posed of slow twitch fibers which maintain constant
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I the toilet or interfere with appropriatetoileting- tone. ln addition voluntary muscle activation
I 6. Transient (Reversible) lncontinence. Urinary increases urethral constriction during times when
i
t incontinence may also arise as a resu[t of a increased closure pressure is needed.
i poientially reversible condition. These reversible
I
lr conditions have been given the acronym The proximal two thirds of the urethra rest on the
DIAPPERS (delirium, infection, atrophy, pharma- anteriorvaginal wall. The anterior vaginal wall gains
I col ogic a gents, psycho logica Id isorders, excessive stability through its lateral attachments to the levator
i
ani muscles and the arcus tendinous fasciae pelvis
r
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urine output, restricted mobility, stool impaction).
For primary care physician, identifying potentially (ATFP) by endopelvic fasciae. The anterior vagina
I
i reversible conditions which can be successfully thus supports the urethra by acting like a sling.'This
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treated may preveni the need for specialist sling effect protects against incontinence during
increases in abdominal pressure by rendering the
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i referral.
r vagina as a firm backboard support against which
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I STRESS UR! NARY I NCONTINENCE the urethra can be compressed and closed.'
;
i Stress urinary incontinence (SUl) is a symptom, a Urinary continence is therefore achieved when there
sign and a condition. As a symptom it is defined as is a well vascularised urethral submucosal tissue, a
; the complaint of involuntary loss of urine on effort or functioning striated urogenital sphincter, and an
I
physical exertion or on sneezing or coughing. Stress intact vaginal wall support. Damage to any of these
rl urinary incontinence becomes a sign when there is structures may cause the urethra not to remain
-{
observation of urinary leakage from the urethra closed at rest or during raised abdominal pressures
r synchronous with effort or physical exertion, or on and stress urinary incontinence occurs. Depending
I sneezing or coughing. lt is considered a condition on which of these structures are compromised, two
; when during urodynamics there is involuntary mechanisms will be responsible for the occu rrence of
:
.l leakage of urine during filling cystometry, associated stress urinary incontinence. These mechanisms are
with increased intra-abdominal pressure, in the ureihral hypermobility and intrinsic sphincter
: absence of a detrusor contraction. This is then termed deficiency.
:
u rody n a m i c stress i nconti ne nce.
,_
Urethral hypermobility occurs when there is loss of
Pathophysiology of stress u ri nary inconti nence the vaginal backboard support to the urethra causing
The female urethra is about 3-5cm long. lt has a the urethra to rotate inappropriately from its
mucosa, a submucosa and three muscle layers. The retropubic position during periods of raised abdomi-
outermost muscle layer is striated and it is called the nal pressure. Urethral closure is prevented and
striated urogenital sphincter. The innertwo muscle urinary leakage occurs. ln intrinsic sphincter
layers are made up of smooth muscle: an outer deficiency, there is loss of coaptation of urethral
circular layer and an inner longitudinal layer. The mucosa as a result of damage to the striated urogeni-
submucosa is a well-developed vascular plexus that tal sphincter or the vascular submucosal tissues or
i
i are formed in a way that flow of blood into large both. lt is important to note that urethral
venules can be controlled to inflate and deflate them. hypermobility and intrinsic sphincter deficiency have
199
traditionally being recognised as two distinct mecha- results from neurogenic, myogenic and idiopathic
nisms causing stress urinary incontinence. Current factors.n
understanding however views the two mechanisms
as a continuum whereby most wome,n ttave a Neurogenic causes results from injury either to the
component of both. cerebral cortex, the mid brain or the spinal cord.
These injuries results in loss of voluntary control of
Riskfactors of stress urinary incontinence micturition leading to OAB (neurogenic bladder).
Anyfactorthat promotes or causes injury to the pelvic When such injury is above the Pons, it induces over
floor leading to its relaxation or destroys the urethral activity by removing voluntary control of micturition
submucosa or the urogenital sphincter has the whiles preserving sensation and coordination of the
potential to singularly or in combination with other sphincter. ln injuries distal to the Pons however, over
injuries cause urinary incontinence and other pelvic activity is mediated by spinal reflexes. This leads to
floor disorders. These factors incl ude: loss of voluntary control of micturition, loss of
bladder sensation and loss of coordination between
. Aging detrusor contraction and urinary sphincter relax-
. Menopause ation. ( Detrusor-Sph i ncter Dyssynergia).
. Pregnancy
. Parturition Myogenic causes occur as a result of altered proper-
. Pelvic surgery
ties of the detrusor muscles leading to increased
. Vaginal or urethral surgery
excitability and increased ability of activity to spread
. Radiation therapy
. lschemic injury from obstructed labour
between cells resulting in coordinated myogenic
. Chronic constipation contractions of the whole bladder. These changes in
. Chronic cough the detrusor muscle may be related to age, bladder
. Pelvic tumours outlet obstruction, local hypoxia or partial
. Obesity denervation of the bladder.'o'"
OVERACTIVE BLADDER SYNDROME The term idiopathic overactive bladder highlights our
present lack of understanding regarding
Overactive bladder syndrome (OAB) was coined to vesicourethral fu nction and dysfunction.
describe a clinical problem of urgency and urge
incontinence from a clinical point of view. The term Evaluation of urinary incontinence
has subsequently been redefined as urinary urgency Evaluation of urinary incontinence is done through
with or without urgency incontinence usually meticulous history taking, physical examination and
accompanied by frequency and nocturia in the laboratory and ancillary i nvestigations.
absence of urinary tract infection or other pathology.'
OAB that occurs with urgency incontinence is known History: The history should clarify the patient's
as'OAB wet' and 0AB that occurs without urgency urinary symptoms, severity, and effect on
incontinence is called '0AB dry'. OAB is a diagnosis of
quality of life as well as identifying any
potentially reversible medical or functional
exclusion hence other pathologies that can cause
urinary urgency and urgency incontinence such as conditions.
a. Urinary symptoms: lt is important to ask
urinary tract infection, interstitial cystitis, foreign
about the type of incontinence, duration of
bodies in the bladder, bladder tumours etc. must be
leakage, frequency of leakage, and amount
ruled out before the diagnosis of OAB can be made.
of leakage. ln addition the patient should be
OAB is often but not always associated with detrusor
asked about the presence of other lower
over activity.S Detrusor over activity, previously
urinary tract symptoms such as frequency,
called 'Detrusor lnstability', is a urodynamic observa-
urgency, nocturia, hesitancy, straining, slow
tion characterised by the occurrence of involuntary
detrusor contractions during filling cystometry which
stream, intermittency, and incomplete
emptying as well as any concomitant bowel
may be spontaneous or provoked.'The
and pelvic conditions which may be contrib-
pathophysiology of OAB is multifactorial and could
utorY.
200
F'
b. Systemic symptoms: lt is important to . Atrophy and any other skin lesion of the
evaluate for potentially serious underlying external genitalia
conditions such as abdominal or pelvic . Obvious leakage of urine from the
pain/mass, haematuria, dysuria, lower external urethral orifice with cough i.e.
extremity weakness, changes:in gait, weight stress u rinary i nconti nence.
changes, changes in mental status, as well . Presence of prolapse '/
as cardiopulmonary and neurologic symp-

. Condition of the perineum
toms.
. Rectal prolapse
c. Potentially reversible current conditions that
After this, palpation of the anterior vaginal wall and
may act to cause/exacerbate symptoms of
urethra is done to elicit urethral tenderness or
urinary incontinence such as vaginal
discharge that may suggest urethral diverticulum,
prolapse, chronic cough, chronic constipa-
inflammatory condition or carcinoma. Adequacy of
tion, stool impaction, infection, diabetes
pelvic support and pelvic organ prolapse is then
mellitus, recreational and occupational
assessed by speculum examination. This is followed
activities should be elicited and if possible
by bimanual examination to evaluate for masses and
corrected. lt is important to get a detailed
tenderness and the cotton-tipped swab (Qtip) test:
medication list and history. Also functional
and cognitive status as well as mobility lnvestigations.' A few basic clinical tests are neces-
should be assessed.
sary for the initial evaluation of women with urinary
d. Effect on quality of life: it is important to ask
incontinence. The aim of these tests is to confirm the
about sexual life of women presenting with
symptoms and findings of the history and physical
incontinence as some women avoid sex
examination and to rule out any complicating
because of fear of leakage or embarrass-
conditions thai may have an impact on treatment
ment. ln addition effect of urinary inconti-
decisions.
nence on the ability of women to undertake
a. Urinalysis should be performed in all patents
normal social, domestic, recreational, and
with urinary incontinence to assess for the
travel activities should be explored. presence of infection, a readily treatable
cause of incontinence; or blood which may
Physical Examination; All incontinent women should
suggest complicated aetiology warranting
have a comprehensive systemic physical examina-
further investigations on the urine. Urine
tion to identify potentially reversible factors and
culture should be performed if urinary tract
underlying serious conditions. ln addition a detailed
infection is suspected .
pelvic examination should be done. The key elements
of the physicalexamination are
b. Urine cytology is indicated if there is
haematuria without infection or if there is
a. General and cardiovascular examination to
suspicion of bladder cancer.
evaluate for signs of fluid overload as well as
changes in gait and mental status.
c. Post void residual: This is indicated in
women with symptoms of urinary retention,
b. Abdominal examination for masses.
recurrent infection, and significant
c. Neurological examinationto evaluate joint
mobility, function, muscle wasting and uterovaginal prolapse and in those being
atrophy and any other neurological problem.
prepared for anti-incontinent surgery.
d. Pelvic examination: Components of the ldeally an individual should be able to empty
pelvic examination must include: at least 80% of her bladder volume. ln
. First the external genitalia is inspected general a post void residual of less than
with the patient relaxed. The labia are 50ml is considered adequate emptying and
gently spread to expose the vestibule and a postvoid residualof greaterthan 200mlis
hymen a nd the patient asked to considered i nadequate emptyi ng.
stiain/cough vigorously (cough stress d. Blood urea and creatinine is not
done
test). Findings that should be noted routinely unless there is suspicion of urinary
include: retention.
e. Urodynamic testing is not part of initial
201
'*
assessment of women with urinary inconti- c. Behavioural therapy. This includes bladder
nence. lt is however indicated in the follow- training to involve frequent timed voluntary
ing situations: voiding and training of central nervous
system and pelvic mechanisms to inhibit
i. Patientswith complicatedhistory urgenc!; and pelvic floor muscle training
ii. Urgency incontinence not responsive to
therapy Specific measures
iii. Recurrent urinary incontinence after
su rgery for stress i nconti nence STRESS URI NARY I NCONTI N ENCE
iv. Nocturnal enuresis not responsive to i, Conservative therapy. This involves the use of
theraPY continence pessaries
v. lncontinence with neurological disorders
vi. Suspected voiding difficulties ii. Medical treatment: vaginal oestrogen appears to
vii. Lower urinary tract dysfunction after help in postmenopausal women. Other medications
radical surgery or radiation therapy such as duloxetine and alpha adrenergic agonist are t
not effective
f. Cystoscopy is reserved for patients with
incontinence who have iii. SurgicalTherapy
i. sterile haematuria or PYuria There are a variety of surgical procedures for women
ii. bladder pain who decline or have insufficient improvement
iii. recurrent cystitis following conservative therapy. These surgical
iv. sub-urethral mass procedures are approached either vaginally in
v. suspected foreign body in the bladder procedures such as the mid-urethral slings, the
vi. when urodynamic testingfails to bladder neck slingsfascial slings and the injection of
duplicate symptoms of urinary inconti-
nence
urethral bulking agents; or abdominally using the
Burch colposuspension, the Marshal-Marchetti-
g. Radiographic image is not necessary for the Krantz (MMK) procedure or the Paravaginal defect
initial evaluation of women with urinary repair.
incontinence. lt is usually done if there is a
a) Mid-urethral sling procedures
suspicion of a neurological problem such as
Mid-urethral slings (MUS) involve the introduction of
a herniated disc.
a polypropelene tape, a form of synthetic mesh,
Management beneath the mid portion of the urethra in a tension-
Treatment of urinary incontinence should aim at free manner. They are also called tension-free vaginal
improving the quality of life of affected individuals. tapes (TVT) because they are in inserted in the
Treatment options for women with incontinence vagina in a tension free manner. They function as a
include general measures and specific measures firm backboard support against which the urethra
based on the cause of the urinary incontinence. can be compressed during increases in
intraabdominal pressure. They are inserted either
Genenl measures through the retro-pubic space exiting through the
a. This consists of treating all reversible abdominal wall in the suprapubic area (Retro-pubic
conditions. For instance, medical conditions Mid-urethral sling /TVT-R) or through the two
and medications that cause incontinence obturator foramens and exit through the skin of the
should be addressed before proceeding to groin area (trans-obturator mid-urethral sling /TVT-
other treatment options O). A third variety is the single incision slings which
b. Lifestyle changes to be made by the patient are shorter and require only a vaginal incision and not
include weight loss, taking adequate but not an abdominal orgroin incision. Aftertheir insertion, a
excessive fluid, avoidance of caffeinated and cystourethroscopy must be done, especially the
carbonated drinks, avoidance of alcohol and retro-pubic type, to make sure that the synthetic
cessation of smoking. material is not accidentally placed in the bladder.
202
rri
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a
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r I b) adder neck/Fasci a l/Pu bo-vagi na I sl ings.
B I two procedures are not popular nowadays because
of poor long term success rate in comparison to the
't,
This involves the placement of a sub*urqthral sling

it
usually of biologic material at the levet:- #te proximal Burch."' " ln the Burch colposuspension, the
urethra and the bladder neck. lt is.@.@
using anterior vaginal wall and paravesical tissues at the
both vaginal and abdominal inciqi@E;'ffii-ilnence is level of the bladder neck are elevated toWards the
I
achieved either by providing a direet- w*lpressive iliopectineal ligament using two to f6ur sutures on
force on the urethra/bladder: RetI{-,'W.by re- each side. ln MMK the paravesical tissues at the
establishing a firm backboard support agAiltst which bladder neck are elevated onto the periosteum of the
the urethra is compressed during rise i* *dominal pubic symphysis. Paravaginal repair aims to close a
pressure. The sling is suspended with fteesutures on fascial defect by reattaching the anterolateral vaginal
each end that are either attached directly to the sulcus with its endopelvic fascia to the
anterior wall muscle or, more commonly, are tied to pubococcygeus and obturator internus muscle and
each other on the anterior surface of the abdominal fascia at the arcus tendinous fasciae pelvis rather
wall. The biologic material used is usually than elevate the tissues at the paravesical area.
autologous, for example rectus abdominis fascia or Burch colposuspension is useful in those with
fascia lata. Other materials that can be used are urethral hypermobility. lt is the procedure of choice
allogenic cadaveric tissue or xenogeneic tissue. for women with stress incontinence who are under-
going an abdominal procedure for pre-existing
Pubo-vaginal sling was initially used as a surgical conditions like fibroid uterus or ovarian tumour. lt is
option forthose with intrinsic sphincter deficiency but also an option forthose who do not want surgery that
it is now used to treat all types of stress urinary uses synthetic material.
incontinence. lt is particularly useful in low resource
parts of the world where synthetic slings are either Outcome of procedures for urinary stress inconti-
not available or beyond the purchasing ability of most nence.
patients. Other indications include women with other A systematic review and meta-analysis of random-
failed anti-continence procedures, women who ised controlled trials from 1990 through April 2013
decline use of synthetic material slings, and for the with a minimum of 72 months follow up was
prevention or treatment of stress incontinence in conducted by Schimpf and colleagues,'o This review
women u ndergoi ng fistu la repa i r or diverticu lectomy. looked at studies that compared one sling procedure
for stress incontinence to another or to Burch
c) Urethral bulking agents. colposuspension and reported as follows:
lnjectable bulking.agents have become a common
therapy for stress urinary incontinence. This therapy M id-ureth ra I sl i ng versus Bu rch colposuspension
works by increasing the bulk or volume within the There was no significant difference between the two
proximal urethral wall between the external sphincter surgical methods with regard to objective cure,
and the bladder neck thereby compressing the subjective cure, quality of life or sexual outcome.
urethral mucosa into the lumen and providing better Whiles MUS showed lower rates of perioperative
coaptation. Postoperative urinary retention is adverse events such as postoperative pain, operating
common but transient with resolution occurring room time, hospital stay, bowel injury, wound
within two days. infection and haematoma, Burch procedure showed
lower rates of long term adverse events such as
d) Retropu bic col posuspensions. return to operating room for retention or erosion,
Retropubic colposuspension is the surgical approach overactive bladdersymptoms and groin pain.
of lifting the tissues near the bladder neck and
proximal urethra in the area of the pelvis behind the P u bov a gi n a/ s/ings versus B u rc h co I posu s pe
n s i on
pubic bones. lt can be done through the open, The evidence favoured sling procedures compared to
laparoscopic or robotic approach. There are three Burch for both subjective and objective cure out-
variations of this surgical approach, i.e. the Burch comes. Meta-analysis of adverse event information
colposuspension, the Marshal-Marchetti-Krantz revealed no significant difference between the two
(MMK) and the Paravaginal defect repair. The latter methods for postoperative OAB symptoms and
203
return to operating room for erosion. There was needle suspensions were more likely to fail than
however a greater risk of return to the operating room open abdominal retropubic suspensions. The
for retention with the pubovaginalslings. subjective failure rate after the first year was
reported as 29"/" compared to 16% for open
Pubovaginals/ings yersus . -,,:;
MUS abdomi nal retropubic suspensions.'u
Meta-analysis of data for subjective cur4, Srtdpmes
favoured MUS compared to pubovaginal sli+gs, 3. Paravaginal repair: Transabdominal paravaginal
Objective cure and satisfaction outcome was not repair is also ineffective for the treatment of stress
done due to limited number of studies. Meta-analysis urinary incontinence. When the Burch procedure
of adverse events showed no significant difference was compared with paravaginal repair in a
between these procedures for postoperative OAB randomised trial, it was reported that Burch was
symptoms, return to the operating room for retention more effective than paravaginal repair. After 1-3
or return to operating room for erosion. When years of follow up, there was a significant differ-
absolute complication rates for the procedures were ence in the subjective and objective cure rates in
compared, the results showed that MUS resulted in favourofthe Burch procedure, 100% versusT2Y"
lower rates of operating room time, blood loss, and 100% versus 61% respectively."
transfusion, wound infection, urinary retention, OAB
symptoms and hospital stay. 4. Marshall-Marchetti-Krantz: MMK and Burch differ
on the site of the endopelvic fascial attachment.
Retropubic MUS versus Obturator MUS Whiles in Burch, the endopelvic fascia is attached
Meta-analysis for both objective and subjective cure to the iliopectineal ligament, in MMK it is
favoured retropubic MUS but were not significant. ln attached to the periosteum of the pubic bone. ln
terms of adverse events, meta-analysis showed that a review of four studies that compared Burch to
postoperative OAB symptoms were more common MMK, it was shown that between one to five
with retropubic slings. There was no difference for years, women treated with Burch were less likely
return to the operating room for erosion or urinary to be incontinenl,23Y" versus 34%, RR 0.72; Cl
retention between two sling procedures on meta- 0.52 to 0.99."
analysis.
URGENCY !NCONTINENCE
Procedures no longer recommended
Since the introduction of the mid-urethral slings, Behavioural therapies such as fluid management,
several procedures that were once widely used are no bladder training, pelvic floor muscle training should
longer recommended due to the fact that more be offered to all patients with 0AB as first line
effective a lternatives h ave become ava i Ia ble. therapy. lf behavioural therapy fails to provide
sufficient relief then use of medications may be
1. Anterior colporrhaphy: This procedure even with offered as second line therapy
the Kelly-Kennedy plication is not an effective
approach to surgical treatment of SUl. ln a review i. Medications such as anti-muscarinics (e.g.
of 8 randomised controlled trials, Glazener et al oxybutynin, tolterodine, darifenacin,
reported that anterior vaginal repair was less solifenacin, or trospium) and beta-3-agonist
effective than open abdominal retropubic suspen- (merabegron) may be offered as second line
sions based on subjective cure rates. The failure therapy. Anti-muscarinics have side effects
rate within one to five years after anterior repair such as dry mouth, constipation, dry eyes,
was 38% as against L7% for open abdominal dyspepsia, blurred vision, urinary retention
retropu bic suspension.'u and impaired cognitive function. Extended
release formulations are preferred to immedi-
2. Transvaginal needle suspensions: The needle ate release because of lower rates of dry
urethropexies, using the Raz, Stamey, or Gittes mouth associated with the latter. Anti-
procedures, have been replaced by other proce- muscarinics are contriindicated in patients
dures. ln a systematic review of randomised and with narrow angle glaucoma and should be
quasi-randomised trials, the authors revealed that
204
used with extreme caution in patients with complicated OAB

impaired gastric emptying or urinary reten-
tion. OVERFLOW INCONTINENCE
il. lntravesical injection of onabotulinum toxin A
(Botox) is used in patients refractory to first The specific measure to be taken depends on the
cause of the impaired bladder emptying in the first
and second line therapy. ln view of the fact
place.
that this treatment may lead to urinary
retention, these patients must be able and
i. Obstruction: Relieving the obstruction usually
wi IIi ng to retu rn for f req uent post-void residua I
solves the problem. For instance obstruction from
evaluation and be willing and able to perform
a large cystocele or uterine prolapse can be treated
self-catheterisation if necessary. The treat-
surgically orwith a pessarY.
ment must also be repeated every 6 to 12
months. ii. Detrusor underactivity: ln this case specific
iii. Electrical nerve stimulation of the sacral or treatment is limited. Potentially reversible cause
percutaneous tibial nerve is also offered as
such as drugs causing impaired detrusor contrac-
third line treatment in patients refractory to tility (e.g. Ca2+ channel blocker) or increasing
first and second line treatments or are unable urethral tone (e.g. alpha adrenergic agonist)
to undertake second line treatment because of
should be addressed. Sacral nerve stimulation
ntolerable side effects.
i
may be beneficial to those with neurogenic
iv. Surgical intervention using augmentation
underactivity. Clean intermittent catheterisation
cystoplasty or urinary diversion may be
can also be used in most situations
offered in patients with severe refractory and
REFERENCES
1. Haylen BT De Ridder D, Freeman RM, Swift SE, 5. Obioha KC, lJgwu EO, Obi SN, Dim CC, Oguanuo
Berghmans B, Lee J, et al. An lnternational TC. Prevalence and predictors of urinary/anal
U rogy n eco I ogi ca Asso c i ati on I incontinence after vaginal delivery: prospective
(ltJGA)llnternational Continence Sociefy (/CS) study of Nigerian women. lnternational
joint report on the terminology for female pelvic lJ rogy necol ogy J ou rna l. 20 1 5 : 1 - 8 "
floor dysfunction. lnternational Urogynecology 6. Ojengbede OA, Morhason Bello 10, Adedokun O,
J ou rn a l. 20 1 0;2 1 (1): 5-26. Okonkwo NS, Kolade CO. Prevalence and the
2. Assessment and treatment of urinary associated trigger factors of urinary incontinence
incontinence. Scientific Committee of the First among 5000 black women in sub Saharan
lnternational Consultation on lncontinence. Africa: findings from a community survey. BJU
La ncet. 2000 ; 3 5 5(922 1 ) :2 1 53- 8. international .2077 ilOT (1 1):1793-800.
Danso KA, Martey J, Wall LL, Elkins TE. The 7. Haderer J, Pannu H, Genadry R, Hutchins G.
epidemiology of genitourinary fistulae in Kumasi, Controversies in female urethral anatomy and
Ghana, 1977-1992. lnternational their significance for understanding urinary
rogy necol ogy J ou rna l. 1 996; 7 (3) : L 1 7 -20.
lJ continence: observations and literature review.
4. Adanu RM, De Lancey JO, Miller JM, Asante A. lnternational Urogynecology Journal.
The physical finding of stress urinary 2002;13(4):236'52.
in Ghana.
incontinence among African women 8. Hashim H, Abrams P. ls the bladder a reliable
lnternational Urogynecology Journal. vvitness for predicting detrusor overactivity? J
2006;17(6):581-5. U rol. 2006; 1 7 5( 1 ) : 1 9 1 -4.
205
9. Banakhar MA, Al-Shaiji TF, llaqsauna MM. 13. Lapitan MC, Cody JD, Grant A. Open retropubic
Pathophysiology of overactive bladder. colposuspension for urinary incontinence in
I n te r n a t i o n a I
Urogyriiiiffiffi-F-. ltu rnaI. women. Cochrane Database SystRev. 2009;74).
2012;23(0:975-82. 14. Schimpf MO, Rahn DD, Wheeler TL, Patel M,
10. Yoshida M, Miyamae K, White AB, Orejuela FJ, et al. Sling surgery for
lnadome A. Management stress urinary incontinence in women: a
in the elderly: changes and systematic review and metaanalysis. Am J Obstet
adenosine triphosphate releae dirru aging. Gynecol. 20 1 4; 2 I 1 ( I ) : 30.
Urology.2004;63$):17-ZZ:' ,,', ,.* r": - 15. Glazener C, Cooper K. Anterior vaginal repair for
11. Steers W, De Groat W. Effect ef Nddr;r outlet urinary incontinence in women. The Cochrane
obstruction on micturition reflac@hways in the Library.2OO1.
rat. The Journal of urology. 1988;14)@):864- 16. Glazener C, Cooper K. Bladder neck needle
71. suspension for urinary incontinence in women.
12. Colombo M, Milani R, Vitobelb D, Maggioni A. A The Cochrane database of systematic reviews.
randomized compar!5on o,f Burch 2013;L2:CD003636-CD
colposuspension and abdominal paravaginal 17. Lapitan MCM, Cody JD. Open retropubic
l
defect repair for female stress urinary
incontinence. American journal of obstetrics and
gynecol ogy. 1 996; L 7 5 ( 1 ) : 7 8-84.
colposuspension for urinary incontinence in
women. The Cochrane Library. 2008. j
l
206
T
CHAPTEilS
Adnexal Masses
K.A. Danso, C.A. Turpin and J.J.K Annan
lntroduction
This chapter will concentrate on masses arising from postmenopausal woman, a malignancy must be
the structures of the uterine appendages. These are excl uded.
the adnexal masses in the strict sense. However non-
adnexal masses that become relevant in differential Classification
diagnosis of adnexal masses will also be outlined' Adnexal masses are classified on the basis of the
Adnexal masses may be of gynaecologic or non- type of process occurring in the organ of origin of the
gynaecologic origin and present as an emergency or mass. lt could be as a result of a physiological
non-emergency conditions found on routine pelvic change, inflammatory reaction, pregnancy related
examinations. Adnexal structures are normally not disorder, developmental anomaly or neoplastic
palpable during clinical pelvic examination unless change. Table I and Table ll.
diseased. A palpable adnexal mass therefore
Table l. The Classification of adnexallnasses
indicates pathological, or occasionally, with the
ova ry, physiological en la rgement.
NON.NEOPLASTIC GYNAECOLOGIC ADNEXAL
Definition and epidemiology MASSES

Adnexal masses are masses found in the pelvis along . Physiological or Functional cysts
the sides of the uterus. These masses may arise from . Follicular cysts of ovary
the fallopian tubes, the ovaries and the ligaments . Corpus luteum cysts of ovary Theca lutein
attached to the uterus, namely, the broad ligaments, cysts of ovary
the round ligaments, the ovarian ligaments and the . lnflammatory masses
i nfundibulo-pelvic ligaments.
. Ovarian abscess
. Pyosalpinx HydrosalPinx T
Adnexal massesare of worldwide occurrence but the . ubo-ovarian abscess
exact incidence and prevalence are unknown. The . Pregnancy related masses
true incidence of adnexal masses is difficult to . Ectopic pregnancy
determine because of spontaneous resolution of most
. Broad ligament haematoma
adnexal masses or cysts without clinical detection.
. Luteoma of pregnancy
. Developmental anomalies
Adnexal masses are found in women of all ages but . Swellings in embryologic remnants eg.
most commonly among women in the reproductive
Parovarian cyst
age. ln all age groups, it is important to consider the Others
possibility of uterine masses orstructural deformities. . Polycystic ovarian enlargements
Pregna ncy-related ad nexa I masses, i ncl ud i ng ectopic
pregnancy, theca lutein cysts, corpus luteum cysts,
and luteomas, must be considered in all
premenopausal women.t'' When present in a
207
T
NEOPLASTIC GYNAECOLOGIC ADN EXAL caused by failure of the corpus luteum to regress.
MASSES: BENIGN AND MALIGNANT
Theca lutein cysts are the least common of the three.
. Ovarian: serous and mucinous They are almost always bilateral. They arise from
cystadenomas, teratomas, prolonged or excessive stimulation of the ovaries by
. serous and mucinous cystadenocarcinoma endogenous gonadotrophins such as occurs in molar
Parovarian cysts pregnancy or choriocarcinoma. When they are
. Pedunculated leiomyoma multiple, as often is the case, they can make the
. Carcinoma of the fallopian tubes ovaries massively en larged.
Table II: Non-gynaecologic adnexal masses

lnflammatory adnexal masses usually arise as a
sequel to incomplete resolution of the inflammation
NON-NEOPLASTIC MASSES
associated with pelvic infection and give rise to
. Appendicular abscess pyosalpinx, hydrosalpinx, ovarian abscess or tubo-
. Diverticulosis of bowel ovarian abscess. Though, it is recognized that
. Adhesions of bowel and omentum sexually transmitted infections are often the cause of
. lmpacted faeces in rectosigmoid colon pelvic inflammatory diseases, certain harmful
. Pelvic kidney cultural practices such as female circumcision has
. Urachal cyst been found to be associated with pelvic
inflammatory diseaset'o and so with inflammatory
NEOPLASTIC MASSES
adnexal masses.
. Carcinoma involving any of the following:
Pregnancy-related adnexal masses are ectopic
Sigmoid colon, Caecum, Appendix and
pregnancy, broad ligament haematoma and luteoma
Bladder
. of pregnancy. Pelvic inflammatory disease resulting
Retroperitonealneoplasm
. Presacral teratoma
in tubal damage is an important predisposing factor
for ectopic pregnancy.un, of the tubal variety. The
Physiological ovarian cysts are the most common ectopicpregnancy may be unruptured or may leak
adnexal masses of ovarian origin. These are the chronicaly into the pouch of Douglas resulting in the
follicular cysts, the corpus luteum cysts and theca formation of a pelvic haematocele. The broad
lutein cysts. These cysts are smooth, mobile and ligament may be enlarged by a haematoma arising
usually less than 6 cm in diameter. from ruptured uterus to form an adnexal mass in the
peripartum period.
Follicular cysts are the most common of the three.
They arise as a result of failure of the developing Luteoma of pregnancy is a rare ovarian tumour in late
ovarian follicle to rupture. They are thin walled and pregnancy that gives rise to an adnexal mass. This
contain watery, clear to straw-coloured fluid. Most of tumour was first described by Sternberg'oas a tumour
these cysts, are asymptomatic and are discovered on composed of large acidophilic "luteinized" cells,
routine pelvic examination. These cysts may be classic of the luteinized theca and grannulosa cells of
hormonally active, associated with elevated levels of pregnancy. Although there have been divergent
oestrogen, and result in menstrual irregularities and opinions as to the neoplastic nature of this tumour, it
abnormal uteri ne bleed ing. is generally thought that they represent z dramatic
reaction of the ovarian stroma to pregnancy
Corpus luteum cysts, though less common than hormones and are not neoplastic.l.-18 They may
follicular cysts, are of more clinical importance however cause hormone induced musculinisaiion of
because they may cause prolonged secretion of the mother and a female fetus." They regress
progesterone or be associated with excessive sponta neously after del ivery.
haemorrhage into the cyst cavity leading to
"giving rise to adnexal
distension and rupture of the cyst, a condition which Developmental anomalies
simulates ruptured ectopic gestation. They are masses are usually the result of swellings in
208
7"
Adnexal Masses
embryologic remnants. During embryologic with bilaterally enlarged ovaries. Many of these
development of the gonads and ducts in the female, patients are obese, have hirsutism and are
the Wolffian system regresses and forms functionless anovulatory. Treatment with ovulation induction
vestiges. These are the epoopheron and drugs such as clomiphene citrate may also cause
paroophoron. Any of these vestigldl::sEtAfures may multiple cysts in the ovary resulting in ovarian
swell and form cysts presenting as adnexal masses. enlargement. Neoplasms involving the fallopian
Swelling of the paroophoron for examplg ploduces a tubes and ovaries may also give rise to an adnexal
parovarian cyst. MASS.
Patients with polycystic ovarian disease willpresent Clinical Presentation and Diagnosis
REFERENCES
1. Clement PB. Tumor-like /esrons of the ovary Pathology Monograph. Baltimore. The Williams
assocrated with pregnancy. lnt J Gynecol Pathol. and Wilkins Co - 1963
1993 Apr. 12(2):108-15. 12. Krause DE, Stembridge VA, Luteoma of
2. Chiang G, Levine D. lmaging of adnexal masses pregnancy. Am J. Obstet Gynecol 1966 95:1-92,
in pregnancy. J Ultrasound Med. 2004 Jun. 13. Mancell GH, Floyd WS, Cohn SL et al; Luteoma
23(6),805-19. of pregnancy. Am J. Clin. Pathol 1967 47:148
3. Rushwan H. Etiologic factors in pelvic 14. Schuker E., Leake FM: Luteoma of pregnancy.
inflammatory drsease in Sudanese women. Am. Obstet Gynecol 1968 32: 637
J. Obstet, Gynecol 1980 138:877 15. Rice BE Woody HB, Barclay DLet a;. Virilizing
4. Shandall A: Circumcision and infibulation of luteoma of pregnancy: Specific Sterol and
females, Sudan Med J. 1976 5:4. steroid hormone content. J.Steroid Biochem
5. Pauerstein CJ, Croxatto HB, Eddy CA, Ramzy l, 1971- 2:183
Walters MD Anatomy and pathology of tubal 16. Thomas E., Mestman J, Henneman C et al:
pregnancy. Ohstetrrcs and Gynaecology. Vol 67 Bilateral luteoma of pregnancy with virilization.
No.3 March J986 301-308 Obstet Gynecol 1972 39;577
6. Kadar N. Recent developments in ectopic 17. Wolf E, Glasser M, Gordon CG, et al Virilizing
pregnancy. Part l: lncidence and Aetiology. luteoma of pregnancy. Am J. Med 1973 54:
Postgraduate doctor - Africa Vol 10 No. 9 257- 229
259 18. Rachman. Tellem M: Bilateral ovarian luteomas
7. Olatunbosun OA and Okonofua FE. Ectopic with tubal pregnancy. Am J. Obstet Gynecol
pregnancy - the African Experience. Obstetrics 1964 88:132
and Gynaecology. Postgraduate doctor - Africa 19. Garcia - Bunuel R. et al. Luteoma of Pregnancy
1986 Vol.8 No. 3 74-78 - Obstet Gynecol - Vol 45. No4, 1975. 407-
8. Dahniya MH, Shoukry lE Balami WL, Fatukasi J 413
l. Simultaneous advanced extra uterine and 20. Padilla LA, Radosevich DM, Milad MP.
intrauterine pregnancy. lnt J. Gynecol Obstet. Limitations of the pelvic examination for
1990 31; 61-65 evaluation of the female pelvic organs. lnt J
9. Wectstein LM: Current perspective on ectopic Gynaecol Obstet. 2005 Jan. 88(1):84-8.
pregnancy. Obstet Gynecol Surv. 1985 40: 259 21. Kim DS, Chung SR, Park Ml, Kim YP:
10. Sternberg WH, Barclay DL Luteoma of Comparative review of diagnostic accuracy in
pregnancy. Am J. Obstet Gynecol 1966 95: 165 tubal pregnancl: A 14 year survey of 1040
11. Sternberg WH Non-functioning ovarian cases. Obstet Gynecol 1987. 70:547,
neoplasms. The ovary. lnternational Academy of 22. Obed SA, Wilson JB, and Elkins T.E. Diagnosing
unruptured ectopic pregnancy. lnt. J. Gynecol
209
'1!
{
!i
Comprehensive Gynaecologlr in the Topics l!
II
fd
ta
ll
:r'l
Obstet 1994 45: 21-25 Batur Y Uslu T et al. Serum, pleural effusion,
23. Sayasneh A, Ekechi C, I
and ascites CA-125 levels in ovarian cancer i
c h a ra cte ri sti c u I tra sou nd and nonovarian benign and malignant
types of ovarian pathology, diseases; a comparative study. Gynecol Oncol.
\_i
\^
I
201 5 Feb. 46(2):445-58. 2002 Apr. 85fi):108-13. 1
24. Mol BW, Bayram N, Lijmet 27.The role of the generalist obstetrician- \: 'i
I
Bongers MY van der Veen gynecologist in the early detection of ovarian T
performance of CA-125 t
cancer. Gynecol Oncol. 2002 Dec. 87G):237- I
d etecti o n of en d o m etr i osis:
9.
Fertil Steril. 1998 Dec. 28. ESHRE Capri Workshop Group. Ovarian and 1
25.Devarbhavi H, Kaese D, --tl
endometrial function during hormonal
contraception. Hum Reprod. 2001 Jul. I
16(7):1527-35. x1
Ctin Proc. 2002 Jun. 776):538.,tf1. I
26.Topalak O, Saygili U, Soyturk,If, /V,
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9
Endometriosis
J I lkimalo and CT John
INTRODUCT!ON ogy and clinical features differ significantly from

endometriosis.
The term endometriosis is associated with John SITES
Albert Sampson who described the clinico-
pathological features of ovarian endometriosis at a The reproductive organs are most frequently affected
presentation before the American Gynaecological with the ovaries, rectovaginal pouch of Douglas and
Society in l92L 'However, Cullen $92O' reported uterosacral ligaments as the commonest sites.
the presence of endometrium-like tissue in the inner Others are outlined below:
third of the myometrium, posterior fornix and 1 Reproductive tract - uterovesical fold,
uterosacral ligaments but described them as rectovaginal septum, uterine serosa, broad
adenomyotic nodules. ligament, fa llopian tubes
2 Urinary tract - bladder, ureters
Endometriosis is one of the most common, puzzling 3 Gastrointestinal tract - sigmoid colon,
and troublesome gynaecologic disease affecting caecum, small bowel, aPPendix, liver
women of reproductive age. Despite extensive
4 Skin - umbilicus, perineum, surgical scars
including episiotomY
research in virtually every aspect of the disease it still
remains an enigma to the gynaecologist. However,
5 Musculo-skeletal - thighs, buttocks,
diaphragm
newer insights into this complex disorder have been
produced in recent research studies and we intend to
6 Pulmonary -lungs
7 Central nervous sYstem -brain
discuss what is generally accepted and highlight
areas of controversy. The gastrointestinal tract is the commonest site of
endometriosis outside the reproductive tract. The
DEFINITION spleen is rarely affected.
Endometriosis is defined as the occurrence and

EPIDEMIOLOGY
growth of endometrial glands and stroma outside the
uterine cavity and myometrium. Metabolic activity in Endometriosis occurs almost exclusively during the
the ectopic tissue is not a stipulated requirement for reproductive years and is most common between 30
the definition of endometriosis.' and 45 years of age. lt is relatively common among
adolescents especially those with chronic pelvic pain
Adenomyosis is defined as thepresence of
or dyspareunia.'However, most cases in girls under
endometrial tissue within the myometrium. lt was 17 years are associated with obstructive Mullerian
previously referred to as endometriosis interna. duct anomalies while the"genital tract is normal in
However, adenomyosis is now regarded as a separate older teenagers.u
disease entity because its pathogehesis, epidemiol-
2tL
r Endometriosis
endometriosis at distant and unusual sites." latro- 3 The anatomical locations of the disease are also
genic dissemination would explain the presence of consistent with retrograde menstruation, in that
endomeirial tissue in surgical scars. This theory fails lesions are most common in dependent areas of
to explain the presence of endometriosis outside the the pelvis."
peritoneal cavity or in premenarcheat iirls who have
not menstruated. However, other factors are required for the initiation
and maintenance of the disease since retrograde
lnduction Theory menstruation occurs in most women but noi all of
This is a combinaiion of the first two theories and them develop endometriosis.'u Suggested
states that unknown substances released from mechanisms include:
endometrium transported to ectopic sites induce
undifferentiated mesenchyma at the ectopic site to 1 An altered immune response, mediated by
form endometriotic tissue.3 cytokines that impairs peritoneal clearing of
endometrial cells. These alterations may be
Stem CellTheory genetically transmitted or environmentally
-
Sterm cell Bone marrow derived stem cells have induced.'uThe endometrial tissue remains in the
been shown to different into endometrial cells and peritoneal cavity longer enabling their adher-
implicated as an alternative origin of some ence to ovarian and peritoneal surfaces.
endometriosis.'n
2 Hormonal stimulation of growth of endometrial
Genetr'cs Theory cells mediated by growth factors. Aromatase,
Familial tendency has been associated with the key enzyme that regulates oestrogen
endometriosis, women who have a first degree family formation is not detected in normal
history of endometriosis, have a 7 times higher risk of
endometrium but occurs aberrantly in
developing endometriosis than women without a
endometriosis where it is stimulated by PGEr."
family history'o This leads to local production of oestrogen,
which induces PGErformation and establishes a
Genetic polymorphisms may lead to aberrantly
positive feedback cycle. The excessive oestro-
expressed genes identified in the endometrium of
gen may then promote the growth of
both human and non-human primates but their
endometrial tissue.
contribution to the aetiology of endometriosis is not
yet defined ". PATHOLOGY
Genetic engineering in some mouse model to sponta- The diagnosis of endometriosis is histological.
neously develop endometriosis has been achievedt'.
Histologic diagnosis is satisfied if two of the following
Epigenetics may eventually allow risk stratification,
three features are identified -endometrial glands,
individualized treatment and personalized medicine stroma and haemosiderin pigment.tt However, these
for endometriosis.
specific histologicalfeatures may be obscured by:
It is generally accepted that retrograde menstruation (a) bleeding into the lesion which can destroy
is of primary importance in the aetiology of the endometrial tissue
endometriosis for the following reasons:- (b) dense adhesions resulting from haemor-
rhage into surrounding tissues and release
of free iron.
1 Endometriosis is associated with increased
exposu re to menstruation Early peritoneal lesions appear to the naked eye as
reddish-blue surface implants, which may be raised
2 lt is commoner among women with excessive or dimpled. They may also appear as nodules,
retrograde menstrualflow due to anomalies patches or cysts. The classical lesions described as
bluish-gray "powder burns" occur later due to
menstrual blood that has been encapsulated by
213
F
fibrotic tissue and haemolyzed to oelow - '

tn 11
release
haemosiderin. With time the lesions rnay become
depigmented and appear as white plaques. Chronic 1 Coital function - Dyspareunia causing reduced
inflammation in surrounding tissues occur:s with penetration and coital frequency
active lesions leading to fibrous reaction with local 2 Sperm function - Phagocytosis by macrophages
scarring and adhesion formation. and inactivation by antibodies
3 Endometrium - lmplantation defects
Ovarian lesions begin as superficial implantssimilar 4 Tubal function -
Alterations in tubal and cilial
to those elsewhere. However, the ectopic motility caused by prostaglandin, lmpaired
fi mbrial oocyte pick-up
endometrium does not erode its way into the ovary
but is actively invaginated. Therefore, the liningof the
5. Ovarian function, Endocrinopathy - Anovulation,
luteinized unruptured follicle (LUF) syndrome,
endometriotic ovarian cyst is actually the ovarian
altered prolactin release, altered gonadotrophin
cortex (Con cept of H u ghesde
"Cycl ic haemorrhage
n ).
midcycle surge, luteolysis due to PGFr" oocyte
results in the accumulation of dark brown fluid within
maturation defects.
the cyst so that the cyst may then be described as a
"chocolate cyst". There is a tendency for blood to leak
6. Early pregnancy failure - lncreased early abor-
tion, Prostagla nd i n-i nd uced or i m m u ne reaction.
out of the cyst resulting in dense adhesions that bind
the ovary to the posterior surface of the broad
Menstrual abnormalities have also been associated
ligament andlor uterus. Peritubal adhesions may also
with endometriosis. Menorrhagia and menstrual
occur leading to distortion or kinking of the tubes.
spotting may be due to subtle defects in ovulation.
However, the tubal lumen is not damaged.
DIAGNOSIS
Usually, oestrogen stimulates ectopic endometrium Making a diagnosis of endometriosis can be difficult
and progesterone inhibits it just like normal even where all facilities exist. This is because the
endometrium. However, they may behave in an patients present with a variety of symptoms and may
unpredictable way and there may be no cyclic have no physical signs. This inevitably delays the
histologic changes characteristic of normal start of effective treatment and prolongs the patients
endometrium.' suffering. ln the USA and UK an average delay in
diagnosis ot8-72years has been observed."ln many
PATHOPHYSIOLOGY
patients, the diagosis is not made at all until surgery'
Pain, infertility and menstrual abnormalities are the

or they receive treatment for some other condition
such as pelvic inflammatory disease."A high index of
main consequences of endometriosis.
suspicion is, therefore, required and endometriosis
Pain may be due to adhesions, nerve entrapment, should be considered in any woman of childbearing
traction on tissues, bradykinin and prostaglandin age with dyamenorrhoea and or pelvic pain.
production especially PGF. The likelihood and
Symptoms
severity of pain has been linked to the site of lesions,
Many patients are asymptomatic. The endometriotic
extent of disease and depth of implant. However, the
lesions are seen during laparotomy or laparoscopy for
precise mechanisms have not been clarified. Many
other reasons. When symptoms occur, they may
women with laparoscopic evidence of endometriosis
strongly suggest endometriosis but none are
do noi complain of pain and no correlation between
pathognomonic. The cyclical nature of these symp-
pain symptoms and severity of disease has been
toms even in the unusual parts of the body should
found.
raise a suspicion of endometriosis.
The mechanism of infertility in women with moderate
1. Pain
or severe endometriosis seems to be readily
explained by disruption of tubal and ovarian anatomy
Pain is the commonest symptom of endometriosis.
and mobility. However, there is no agreement on the
The pain may be localized in the pelvis, lower back,
mechanisms of infertility in minimal or mild disease. perineal region or the lower abdomen. Dyspareunia
Some of the possible mechanism are summarized
2L4
tTT-
Endometriosis
and dysmenorrhea with low back pain that worsens endometriotic tissue itself or complications of its
during menses should raise a suspicion of presence.
endometriosis. Secondary dysmenorrhoea has been On genera I exa m i nation, externa I endometriosis may
observed to occur twice as common in women with be seen in surgical scars and the umbilical area.
endometriosis. These lesions present as tender intradermal nodules
The relationship of the pain to bowel movement, or swelling. lt may be discoloured from underlying
urination, sex and the quality of life need to be haemorrhage and become more painful and enlarged
assessed. Chest and shoulder pain recurring around during menses. There may be abdominal tenderness
the menstrual period can be caused by diaphrag- while inguinal lesions may present as complicated
matic endometriosis. Anxiety, depression, irritability inguinal hernias. Ascites may rarely complicate
and inability to carry out normal work or school endometriosis.oo Pelvic examination may reveal
function may follow. An acute abdomen may result perineal, vaginal and cervical lesions. Tender
from an accident in an endometriotic cyst. nodules may be palpated in the uterosacral liga-
ments and rectovaginal septum. The uterus may be
2. MenstrualAbnormalities/Bleeding retroverted and fixed and there may be localized
tenderness of the pouch of Douglas and adnexae.
Women with endometriosis may present with Adnexal masses may also be palpated in ovarian
irregular or heavy menses. Spotting in between endometriosis, particularly when there is
menses or after hysterectomy can result from vaginal
endometrioma. Finally, a rectovaginal examination
endometriosis. Cutaneous endometriosis may bleed should be performed to look for pelvic floor point
cyclical ly from the skin.
tenderness or rectovaginal nodules suggestive of
deep infiltrating endometriosis.
3. lnfertility
lnvestigations
The association between endometriosis and infertility
Endometriosis may be suspected from history and
is still controversial. There is no cause effect relation-
physical examination but in
ship. The prevalence of endometriosis increases
vestigations are required to confirm the diagnosis.
- 50% in women with
dramatically to as high as 25 1. Laparoscopy with biopsy for histologic confirma-
infertility and 30 - 50% of women with tion is the gold standard for diagnosis of
endometriosis have i nferti I ity.a3 endometriosis. Although laparoscopy alone is
sufficient to make a diagnosis of endometriosis, the
4. Unusualsymptoms
accuracy of laparoscopic diagnosis depends on the
ability of the surgeon to identify the various lesions of
These are the result of endometriosis at unusual sites
a. Bowel-cyclical rectal pain, bleeding, constipation, endometriosis.
diarrhoea. Abdominal pain and vomiting may occur
Other endoscopic examination like cystoscopy,
with bowel obstruction.
sigmoidoscopy and colonoscopy may be used
b. Bladder -cyclical dysuria and haematuria depending on the patients'symptoms and encounter.
c. Lungs -pleuritic chest pain, cyclical haemoptysis, 1. Pelvic ultrasonography - This is useful in
dyspnoea due to pleural effusion or pneumothorax identifying endometriotic ovarian cysts.
d. Surgical scars/umbilicus -cyclical pain and Hyperechogenic fluid representing bloody fluid
bleeding in the ovarian cyst can be distinguished from
e. Limbs/perineum -cyclical pain and swelling ovarian malignancy which has complex cySt
f. Brain -cyclical headaches, seizures with thick walled separation and internal
g. Liver -cyclical pain, jaundice excrescences. Doppler Ultrasonography may be
h. Retroperitonealspace-sciatica used for the diagnosis of pelvic congestion
Trans vaginal ultrasound (TVS) is now consid-
ered a first diagnostic tool of choice before
PhysicalSigns
laparoscopic surgery in endometriosis treat-
There may be no signs on physical examination.
ment.ou'ou This is an advantage for Africa where
Such signs as are present may be due to the
2L5
facilities and expertise for laparoscopy are still

scarce whereas TVS is getting more available and These depend on the pattern of presentation and may
is non invasiveo'. ln Nigeria, many..more public include:
hospitals are slowly taking up the cha.llenge of 1 Pelvic inflammatory disease
end osco p i c su rge ri es i nc Iud i ng laparcncopy.
n' 2 Pelvic congestion syndrome
2. Magnetic resonance imaging - This'is superior to 3 lrritable bowelsyndrome (lBS)
other imaging techniques for the diagnosis of
4 Accident in a ovarian cyst
endometriosis. lt has a high sensitivity and

5 "Grumbling" appendix
6 Bowel cancer
specificity for endometrial cysts. lt may be used 7 Other causes of intestinal obstruction,
to identify endometriosis obscured by pelvic haematuria, dysuria and haemoptysis.
adhesions and in monitoring response to medical
therapy.'lt may be too costlyfor routine use. TREATMENT
3. Measurement of serum proteins - Serum proteins The objective of treatment in patient with symptoms
are being investigated to determine their value in is the removal of ectopic endometrial tissue. How-
screening for endometriosis. CA-125 antigen ever, symptoms may persist because treatment failed
levels are elevated in endometriosis but it is not to remove the lesions or the symptoms were not due
sensitive or specific for the condition. Other to the lesions.u'
proteins being evaluated include placental
protein 14 and antibodies to endometrial tissue.' Symptomatic endometriosis can be treated by
medical, surgical or both methods. The first line of
:
Some other investigations may be necessary because treatment for the pain of endometriosis is by medical
of associated problems. For instance, semen analysis methods. Surgical methods which can be both
and tubal patency tests will be needed in women diagnostic and therapeutic has been shown to be
presenti ng with nferti ity. I
i I affective in decreasing pain and increasingfertility. 1
i I
CLASSI FICATION i STAG I NG MEDICALTREATMENT I

i
Various staging systems have been devised in an Pain relief can be achieved with analgesics or .,J
attempt to identify manifestations of the disease that hormona I therapy. I

I
respond in a predictable way to specific treatments, I
resulting in reproducible outcomes. The most widely Analgesics l'l
used is the revised classification system of the Non-steroidal anti-inflammatory drugs (NSAlDs) -{ !
American Society for Reproductive Medicine such as acetaminophen and opioids analgesics can vl
sometimes be used first for the treatment of mild to
i
(ASRM).4e'50 This staging system scores I
endometriosis according to site and size of the lesion, moderate pelvic pain. The NSAIDs reduces the 'l
1
bilaterality and the severity of adhesion involving the production of prostaglandin in the implants.
I
tubes and ovaries. lt consist of four stages.
HormonalTherapy
Stage I - minimal disease This attempts to alter the menstrual cycle to produce
Stage ll- mild disease a pseudo-pregnancy, pseudo-menopause or ch ron ic
Stage lll - moderate disease anovulation. These hormonal states are thought to
Stage lV - severe disease impair the growth and maintenance of endometriotic
implants.
This classification does not correlate with the severity
of the symptoms, lacks reproducibility and is not Hormonal treatment suppresses the inrplants but
u'.
always accurate in predicting pregnancy rate does not remove them permanently. The various
However, until better staging systems are developed, drugs used induce amenorrhoea and need to be
the revised classification system of ASRM is recom- administered for at least 6 consecutive months.
mended. Medical treatment is of no'use in the management of
endometriosis associated infertility either alone or in
DIFFERENTIAL DIAGNOSIS conjunction with surgery. Furthermore, the period of
216
Endometriosis
u'
a menorrhoea prolongs the period of i nferti I ity. recommended dosage is 400-600mg orally per day
depending on stage of disease, response to the drug
The various drugs are useful in the treatment of pain and side effects.
and are equally effective with 80-85% of patients
obtaining significant pain relief. The difference Gestrinone is a trienic 19-norsteroid (ethylnorgestrin
between the drugs is in their side.'effeets, with some - one) with antiprogestational, antioestrogenic and
being more tolerable than others.u*u' androgenic properties. lt causes a decline in ths
concentration of oestrogen and progesterone
Combined oestrogen and progestogen ol receptors, a 50% decline in serum oestradiol
progestogens concentrations, and a decrease in serum sex hor-
The combined oral contraceptive pills containing mone binding globulin concentrations. lt also
both oestrogen and progesterone can be given attenuates the midcycle gonadotrophim surge but
continuously (ie omitting theT day placebo) for 3 to 4 does not alter basal gonadotrophin levels. The dose
months to minimize menses and treat the pain of range is 2.5to lOmgtwo-threetimesa week.
endometriosis. lt has been shown that this treatment
approach is as effective as leuprolide acetate in the The adverse effect caused by these androgens
treatment of pain associated with endometriosis and include headache, flushing, sweating, atrophic
it also has less side effects.u' vaginitis, breast atrophy, acne, oedema, hairsutism,
deepening of the voice, temporal hair loss and
Progestogens induce preudopregnancy. They cause weight gain. These side effects are worse with
the decidualization of endometrial tissue with danazol and some of them are irreversible therefore,
eventual atrophy. Available preparations include oral danazol is less commonly used nowadays.
medroxy progesterone (10 3Orng/day) megestrol
-
(40mg/day), dydrogesterone, norgestrel and Gonadotrophin releasing hormone (GnRH)
norethisterone (2.5 - 5mglday). lnjectable agonists.
medroxyprogesterone acetate (i50mg every 3 Gonadotrophin - releasing hormones diminish the
months) or megestrol acetate (40mg) are also secretion of follicle-stimulating hormone and
effective in the treatment of pain associated with luteinizing hormone, resulting in hypogonadotrophic
endometriosis. lntrauterine progestin like hypogonadism (pseudo-menopause). The hypo-
levonorgestrel - releasing intrauterine system (LNG- oestrogenic state leads to endometrial atrophy and
IUS) has been used to treat endometriosis related amenorrhoea. The various GnRH agonists may be
pain.tn ad mi nistered i ntranasal ly (nafarel in and buserel in),
subcutaneously (goserelin-zoladex 3.6mg subcuta-
Progestins can cause adverse side effects like weight neously monthly) or intramuscularly (leuprolide-
gain, fluid retention, depression, reduced libido, hyperon, 3.75mg monthly).
breast tenderness, irregular menses, breakthrough
bleeding and amenorrhoea. Return to fertility may The side effects are those of hypo-oestrogenism such
take up to 2 years with prolonged use of progestins as hot flushes, headaches, vaginal dryness,
particularly with the depot preparations. decreased libido, insomnia, depression, irritability,
Synthetic androgens fatigue. Significant osteoporosis occurs after 6
months and limits longer use of the drugs. The use of
Danozol and gestrinone are the drugs commonly used "add-back" oestrogen and progestogen regimens
in this group for the treatment of endometriosis (hormone replacement therapy preparations, OOPs)
related pain. They induce chronic anovulation. allows the use of GnRH agonists for longer periods.
Efficacy of treatment is maintained but majority of
Danazol is the classic drug in this group. lt is an
the side effects including osteoporosis are elimi-
isoxazol derivative of 17q-ethinyltestosterone and
nated.
causes anovulation by attenuating the midcycle surge
of luteinizing hormone secretion, inhibiting multiple GnRH Antagonist
enzymes in the steroidogenic pathway, and increas- The administration of GnRH antagonist like
ing serum concentrations of free testosterone. The
2L7
cetrorelix (3mg/week) over a period of 8 weeks has ablation or excision of the endometriotic deposits
been found to be effective in the treatment of from the body. lt can be done by laparotomy or
endometriosis related pai n. preferably laparoscopy.
Cyproterone Acetate Surgical treatment is the preferred approach for

Cyproterone acetate is a synthet+G, €*eroidal treatment of infertile patient with endometriosis.
antiandrogen with an additional ryssterone like Other indications for surgery includes:-
properties, it is administered (1Omg/day) for2Odays 1. Diagnosis of unresolved pelvic pain, Severe
in a cycleforwomen with endometrissis. incapacitating pain with reduced qualityto
life.
Emerging medical treatment modalities 2. Advanced disease with anatomical distor-
Some novel medical agents are recently being tried tion of pelvic organ
for the treatment of endometriosis. Their applicationd 3. Failure of expectant / medical treatment.
in clinical practice still await further clinical trials. 4. Endometriosis related emergence like
These include:- torsion of endometrioma, boweI or
ru ptu re or
- Aromatase inhibitors like letrozol, ureteric obstruction.

anastrozole or fedrozole which inhibit
Surgery can broadly be classified as conservative, \-
oestrogen synthesis thereby reduce oestro-
gen level to cause endometrial atrophy.
when the reproductive potential is retained or radical \,,1
- Progesterone antagonists like mifepristone when the uterus and ovaries are removed.
(RU-486), 20 The objectives of conservative surgery are the
- 100 m{day, cause a
removal of all visible endometriosis from abdomen
reduction of symptoms and regression of
and pelvis, restoration of normal anatomical rela-
endometrotic lesions.
- Selective oestrogen receptor modulators tions and preservation of reproductive function. lt is
(SERMS) like raloxifene which is an antago- an effective treatment for infertility associated with
nist to oestrogen causing a reduction in all stages of endometriosis.u' lmportant consider-
oestrogen levels and reduction in ations in conservative surgery are,the most appropri-
endometriosis related pain.
ate method of access, instrumentation and method
- Selective progesterone receptor modulators of treating implants.u' There is no difference in
like asoprisnil, an antiprogesterone agent efficacy between laparotomy and laparoscopic
with antiproliferation action on the access to the abdomen and pelvis in the treatment of
endometrium and reduces prostaglandin endometriosis. The laparoscope may be preferred if
productioh. lt has no hypoestrogenic side the required equipment and expertise are available.
effects. A laparotomy may be advisable in the presence of
- lmmunomodulators / anti-inflammatory extensive dense adhesions.
agents like pentoxifylline and loxoribine
Laparoscopic surgery
which prevent the production of prostaglan-
Laparoscopy is the gold standard test in diagnosing
din and other anti-inflammatory agents like
endometriosis in clinical practice. The lesions are
tumour necrotic factor- a (TN F-a)
seen as nodules, vesicles, deposits or lesions, with
- Angiogenesis inhibitors like rapamyin,
blue-black, red or powder-burned appearance.
angiostatin and endostatin which prevent
neovascularization, thereby shrinking
Laparoscopic management of these lesions includes
endometriotic implants.
ablation by laser vaporization or helium thermal
- Myometrial relaxant like vaginal sildenafil
coagulation, electrocoagulation, argon beam
citrate causing myometrial relaxation and
coagulation, harmonic scapel coagulation and
reversing the vasoconstrictive effect of
prostaglandin.uo
endocoagulation. Laparoscopic excision can be
performed with scissors, electrosurgery, CO, or fibre -l
lasers or harmonic scapel. Where there is extensive
SURGICALTREATMENT
Surgical treatment is aimed at the removal by extreme adhesions, lysis of pelvic adhesions,
dissection of the ovaries from the pelvic sidewall,
218
Gl-"r
Endometriosis
freeing tubal adhesions and resection of 6. lncrease in certain types of ovarian cancer
endometrioma, are also performed with the
laparoscope. Complications may also arise from the treatment of
endometriosis. Adverse effect may follow the
Laparoscopic uterine nerve ablation (LUNA) per- medical therapy used as discussed earlier and
formed to interrupt the pain fibres to the uterus complications can follow any of the surgical procj.
combined with ablation of oJherdeposits reduce pain dures. Menopausal symptoms can follow the
associated with deep endometriosis. removal of the ovaries.
Robotic surgery Recurrence

Although experiences with the recently introduced Recurrence of endometriosis is a recognized prob-
robot - assisted laparoscopy is limited, similar lem. Recurrence may occur in up to 50% of patients
outcomes have been demonstrated with the tradi- one year after medical treatment and in 28% of
ut'uoWhen
tional laparoscopy for the management of patients, 18 months after surgery. one or
endometriosis. both ovaries are conserved at hysterectomy, the
recurrence rate may be as high as 33%. Hormone
Hysterectomy with Bilateral replacement therapy may also lead to re-emergence
ngo-oophorectomy
Sa ! pi of endometriosis.
Women with intractable pain who have gone past Biopsy of lesions in recurrent disease is important
childbearing age and in whom other treatments have because of the possibility of malignant transforma-
failed may benefits from abdominal hysterectomy tion.
and bi lateral sa lpi ngo oophorectomy.
DISCUSSION/CONTROVERSI ES
Any other endometriotic lesion seen outside in the
nelvis or peritoneum should be resected to improve Endometriosis has been the subject of extensive
symptoms and reduce recurrence. research for decades but still the diagnostic and
thera peutic cha lenges remai n.
I
Endometriosis outside the pelvis

Abdominal wall and perineal endometriosis should It has been assumed that endometriosis is a single
be treated by local excision. Diaphragmatic entity with progression from minimal to severe
endometriosis is best treated by laparotomy and full disease.uu However; a new concept is the
thickness resection of the affected areas followed by endometriotic disease theory. This hypothesizes that
repai r with non-absorbable suture. superficial peritoneal implants arise because of
implantation but are physiological since they occur
Infertility and Endometriosis in most women.uuOn the other hand, cystic ovarian
lnfertility patients with endometriosis can also benefit
and deeply infiltrating endometriosis are regarded as
from assisted reproductive technology including a disease state and may arise from somatic muta-
superovulation in vitro fertilization (lVF) and intra
tions in genetically predisposed individuals exposed
cytoplasmic sperm injection (lCSl ).
to envi ronmental risk factors.u'
Complication of endometriosis
Endometriosis may be representing a good number
of different diseases with similar histopathological
1. Bleeding can form bands of scar tissue (adhe-
findings. This may explain the divergent clinical
sion) leadingto distortion of pelvic anatomy
2. lnfertility courses and manifestation. The severity of the
3. lncreased risk of miscarriage and pre term disease my not match symptoms and some women
deliveries will continue to have symptoms despite aggressive
4. Haemorrhage or rupture of endometroma treatment. The use of laparoscopy in the manage-
causing severe pain ment of endometriosis is well documented but the
5. Endometriosis of the bowel can cause intestinal management of women with deep infertility disease
obstruction or twisti ng remains controversial. Women with pelvic pain and
2t9
infertility can have several other causes and so decade. lncidence varies widely trom 5-7O"/"
treatment of endometriosis in these women may not dependingon diagnostic criteria. lt was found in10%
yield the desired result. Individual treatment of hysterectomy specimens in a prospective study in
approach based on symptoms, character of the lfe, Nigeria.u' The patients usually present with
disease, age and desire for fertitity should be dysmenorrhoea and menorrhagia and should be
adopted. considered in all women with these symptoms.u'On
examination the uterus is bulky and the condition is ,1
ADENOMYOSIS frequently misdiagnosed as fibroids.'o Transvaginal l

l
J
ultrasonography may aid diagnosis but lesions may I
Adenomyosis is regarded as a separate entity from
be mistaken for fibroids. Magnetic resonance
endmetriosis. However it aetiology and pathogenesis
imaging may be superior where available.
remain uncertain.
Myometrial uterine biopsy at laparoscopy has been
Reported risk factors include, endometrial curretage,
suggested as a means of diagnosing diffuse
previous caesarean section and endometrial hyper- adenomyosis "especially in women with
plasia. lt dysmenorrhoea.
is thought to arise from growth of the
endometrium of the uterine cavity into the
It may be difficult to resect the lesions at surgery and
myometrium. The direct connection to the uterine
hysterectomy is the usual treatment especially as
cavity is eventually lost as the endometrial tissue
most of these women are at the end of their reproduc-
becomes surrounded by myometrium. The lesions
tive career. There may be a place for medical treat-
may be diffuse or localized but they are not encapsu-
ment to induce amenorrhoea and thus provide
lated.
symptomatic relief from menorrhagia and
It is found in multiparous women usually in the fifth dysmenorrhoea.
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combined oral contraceptives for pain assooated community. East Af r Med J 1986; 63:807-812.
with endometriosis. Cochrane Database of 70. Moore J, Kennedy S. Aetiology and medical
Systematic Reviewg lssue 2, 2002. treatment of endometriosis. The Obstetrician and
57. Prentice A, Dreary J, Goldbeck-Wood S, Faquhar 2000 ; 2(3 ) : 2 5 - 28.
Gy naeco I ogi st
C, Smith SK. Gonadotrophin-releasing hormone 71. Vercillini E Trespidi L, Panazza S, Bramante T,
analogues for pain associated with Mauro F, Crosignani PG. Laparoscopic uterine
d o m etr i os i s. Coc h ra n e Data ba se of Sy ste m at i c
en biopsy for diagnosing diffuse adenomyosis. J
Reviews, lssue 2, 2002. Reprod Med 1996; 41:220-224.
58. Guzick DJ, Huang LS, Broadman BA, Nealon
M, Hornstein MD. Randomized trial of -l
222
CHAPTE20
f
I
r
(
l'
Dysmenorrhoea And Premenstrual
Syndrome (PMS)
I
COAimakhuandOOFakeye
DYSMENORRHOEA subsides afler 2 to 3 days. The pain is usually

crampy or sharp and comes and goes (intermittent),
lntroduction but it may be a dull, constant ache. lt sometimes
The term dysmenorrhoea is derived from the Greek radiates to the lower back and legs.
words; dys, meaning difficult or painful or abnormal;
meno, meaning month, and rrhea, meaning flowt. Many women also have headaches, nausea (some-
Dysmenorrhoea, also known as painful periods or times with vomiting) and constipation or diarrhoea.
menstrual cramps, is the occurrence of painful They may need to urinate frequently. Symptoms of
cramps du ri ng menstruation. Premenstrual syndrome (PMS) (such as irritability,
nervousness, depression, fatigue, abdominal
Dysmenorrhoea is considered the most common bloating) may persist during part of or all of the
symptom of all menstrual complaints and poses a menstrual period. Sometimes the menstrual blood
greater burden of disease than any other contains clots. The clots, which may appear bright
gynecological complaint In developing countries'. lt red or dark, may contain tissue and fluid from the
has a major impact'on women's quality of life, work lining of the uterus (endometrium), as well as blood.
productivity and causes activity restrictions. lt is
responsible for considerable economic losses due to Types of dysmenorrhoea
the costs of medications, medical care, and dimin- There are two types of dysmenorrhoea'
ished productivity3, l. Primary dysmenorrhea (ldiopathic or
intrinsic dysmenorrhoea). This is menstrual
Epidemiology pain that is not a symptom of an underlying
Dysmenorrhoea is estimated to occur in20% to 90% gynaecologic disorder, but is related to the
of women of reproductive age '. lt is the most com- normal process of menstruation. Primary
mon menstrual disorder'. Typically it starts within a dysmenorrhoea is the most common type of
t.
year of the first menstrual period (menarche) When dysmenorrhoea affecting more than 50% of
there is no underlying cause, often the paln improves women, and quite severe in about 15%'
with age or following childbirth '. Primary dysmenorrhoea is more likely to
affect girls during adolescence. Fortunately
Nature of the pain in dysmenorrhoea for many women, the problem eases as they
The pain in dysmenorrhoea usually occurs in the mature, particularly after a pregnancy.
lower part of the pelvis a few days before, during, or
Although it may be painful and sometimes
after a menstrual period. The pain tends to be most
debilitating for brief periods of time, it is not
intense aboul 24 hours after periods begin and
harmful.
223
2. Secondary dysmenorrhea (Acquired, . Endometriosis

congestive or organic dysmenorrhoea). This . Pelvic inflammatorydisease
is menstrual pain that is generally related to . Ovarian cysts and tumours
some kind of gynaecologic disorder. Most of . Cervical stenosis or occlusion
J
these conditions can be easily treated with . Adenomyosis
medications or surgery. Secondary . Uterine fibroids
dysmenorrhoea is more likely to affect
. Uterine polyps
women duri ng adulthood.
. lntrauterineadhesions
. Congenital uterine malformations (e.g.
bicornuate uterus, subseptate uterus)
Risk factors o lntrauterine contraceptive devices
The following risk factors have been found to be . Transversevaginal septum
associated with more severe episodes of o Pelvic congestive syndrome
dysmenorrhoea'. . Allen-Masterssyndrome.
. Early age of menarche
. Long heavy periods Almost any pathology that can affect ttre peivic
. Heavy menstrualflow viscera can produce cyclical pelvic pain'.
. Smoking
.J
o Positive family history Diagnosis
A focused history and physical examination are
Pathophysiology usually sufficient to diagnose primary
During a woman's menstrual cycle, the endometrium
dysmenorrhoea. lnformation about the onset,
thickens in preparation for potential pregnancy. After
location, duration, and characteristics of the pain,
ovulation, if the ovum is not fertilized and there is no plus any aggravating or relieving factors, should be
pregnancy, the built-up uterine tissue is not needed
sought from the patient.
and thus shed.
Secondary dysmenorrhoea can occur at any time
Molecular compounds called prostaglandins are
after menarche, but may arise as a new symptom in
released during menstruation, due to the destruction
her 30s or 40s after the onset of an underlying
of the endometrial cells, and the resultant release of
u. causative condition.
their contents Release of prostaglandins and other
inflammatory mediators in the uterus cause the A pelvic examination may be necessary for assessing
uterus to contract. These substances are thought to dysmenorrhoea if information on the onset and
be a major factor in primary dysmenorrhoea. (Prosta- duration of pain suggests secondary dysmenorrhoea
glandin levels are high in women with primary or if previous drug treatments have been unsuccess-
dysmenorrhoea).When the uterus contract, they ful.
constrict the blood supply to the tissues of the
endometrium, which in turn, breaks down and dies. An abdomino-pelvic ultrasound is done if pelvic
The uterine contractions continue as they squeeze examination is difficult or inconclusive or if second-
the old, dead endometrial tissue through the cervix ary dysmenorrhoea is suspected.
and out of the body through the vagina. These
contractions, and the resulting temporary oxygen Patients who are at risk of sexually transmitted
deprivation to nearby tissues (ischeamia), are infection should have appropriate swabs taken.
responsible for the pain "or cramps" experienced
Laparoscopy is indicated if initial measures such as
during menstruation.
use of drugs, have not improved symptoms. lt is also
Compared with other women, women with primary indicated if secondary dysmenorrhoea is suspected
dysmenorrhoea have increased activity of the uterine (for example, associated menstrual symptoms such
muscles with increased frequency of contractionsu, as menorrhagia, inter menstrual or post coital
bleeding, dyspareunia,' andlor abnormal pelvic
Secondary dysmenorrhoea may be caused by the examination) or it the patient has pain management
fol lowi ng pelvic pathologies. problems with disruption of daily living.
224
Dysmenorrhoea And Premenstrual Syndrome (PMS)
Differential Diagnosis the others. For more severe pain, ibuprofen

Differential diagnosis includes adhesions from can be used. These drugs are usually
previous pelvic inflammatory disease (PlD) or commenced at the first sign of the period
su rgery, en dom etri osis, adenomyosis, genfto-u ri nary and taken for a day or two. Gastrointestinal
conditions and use of intrauterifle-contraceptive side effects (nausea, vomiting andlor
devices (IUCD). Others are outflow obstruction, diarrhoea) are of particular concern with
Mullerian duct abnormalities, cervical stenosis and NSA|Ds. Effects are generally tolerable, but
irritable bowel syndrome'. when treating women with risk factors for
NSAID induced ulcerations, the potential
Treatment risk and benefits of using an NSAID should
Treatment for dysmenorrhoea aims to relieve pain or
be considered.
symptoms either by affecting the physiological
mechanisms behind menstrual pain (such as 3. COX- 2 specific inhibitors. The newer
prostagla nd i n prod uction ) or by rel ievi ng sym ptoms. generations of anti-inflammatory drugs have
A sympathetic approach to the patient, including shown that COX -2 (cyclooxygenase - 2)
consideration of psychologist and behavioural specific inhibitors are effective for
elements, will enhance the likelihood of a positive dysmenorrhoea.
outcome to the patient.
4. Oral contraceptive pills. Low dose (or
The treatment options are categorized as Non combined) oral contraceptives have been
Pharmacological, Medical and Surgical methods. shown to reduce pain compared with
Simple analgesics and non-steroidal anti- placebo. lf a woman also wants to avoid
inflammatory drugs (NSAIDs) are effective in up to pregnancy then combined oral contracep-
70% of women'.
tives may be a good treatment option.
Secondary dysmenorrhoea is managed by treating 5. Levonorgestrel releasing intrauterine

the u nderlyi ng pathology.
system. This has been shown to relieve
A) MedicalTreatment
dysmenorrhoea in women with
endometriosis. lt should be noted that non-
Several drugs can reduce or completely eliminate the
pain of primary dysmenorrhoea. Drugs such hormone intrauterine devices may result in
as
paracetamol, aspirin and NSAIDS work by reducing dysmenorrhoea and may require removal if
adequate pain relief is not provided with
the activity of the cyclo-oxygenase pathways, thus
analgesics.
inhibiting prostaglandin production. Treatment such
as oral contraceptives work by inhibiting ovulation.
6. Drug patch containing glyceryl trinitrate.
This drug which has been used in the past to
1. Simple Analgesics. Simple analgesics such
as aspirin and paracetamol may be a useful
ease preterm contractions in pregnant
starting point when NSAIDS are contraindi-

women can ease the pain in
dysmenorrhoea.
cated.
7. Combined drug treatments and less com-

2. Non-steroidal anti-inflammatory drugs
(NSA|Ds). The most popular choices of drugs mon drug treatments. A combination of
analgesics and the oral contraceptive or the
are the non-steroidal anti-inflammatory
Mirena intrauterine device is also an option
drugs (NSAIDs), which prevent or decrease
the formation of prostaglandins. These drugs
in cases that do not respond to a single
treatment.
include aspirin, ibuprofen and naproxen. The
different formulations of NSAIDS have similar
8. Progestogens and antiprogestogens.
efficacy for dysmenorrhea and pain relief is
Progestogens such as med roxyprogesterone
achieved in most women. Some women may
acetate and gestrinone induce ovulation
find that one drug works better for them than
with resulting amenorrhoea and therefore
225
can successfully treat the symptoms of endorphins, which act as non-specific

dysmenorrhoea in _women with analgesics.
endometriosis.
5. Herbal products or medicine, and dietary
g. Gonadotrophin releasing hormones and supplements. Herbal and dietary therapies
danazol. These confer the same degree of are popular as they can be self-administered
pain relief. The side effect profiles of these and are available from health shops,
treatments are different, however, with chemists and supermarkets.
danazol having more androgenic side effects,
while gonadotrophin releasing hormones 6. Transcutaneous electrical nerve stimulating
tend to produce more hypo-oestrogenic (TENS).This involves stimulation of the skin
symptoms. using current at various pulse rates (frequen-
cies) and intensities to provide pain relief.
B. Alternative Therapies
For a small percentage of patients who do not 7. Acupuncture. Acupuncture excites receptors
respond to medical treatment with drugs or to or nerve fibres, which, through a compli-
combination treatment, otheroptions exist. cated interaction with seroton in a nd
endorphins, block pain impulses.
ln all, 10 - 20% of women with primary
dysmenorrhoea do not respond to treatment with 8. Spinal manipulation. This has been tried.
NSAIDs or oral contraceptives'. ln addition, some
women have contraindications to these treatments. 9. Surgery. ln recent years uterine nerve
Consequently, researches have investigated many ablation and presacral neurectomy have
alternatives to d rug treatment. been increasingly used when diagnostic
la pa roscopy has been ind icated for
1. Heat therapy. Heat therapy has been a dysmenorrhoea. These two surgical proce-
traditional home remedy for dysmenorrhoea. dures interrupt most of the cervical sensory
The heat patch (39"C) is effective in relieving nerve fibres (thus diminishing uterine pain).
pain. Women using both the heat patch and Endometrial resection with use of a flexible
n.
ibuprofen experiencethe most pain relief hysteroscope and endometrial ablation are
newer techniques that can be done. These
2. Dietary Qhanges. Dietary recommendations methods are rarely indicated and only after
to ease cramps include increasing fiber, exclusion of possible organic causes.
calcium and complex carbohydrates,
reducing fat, red meat, dairy products, Prognosis
caffeine, salt, and sugar. Recent research Medications should reduce or eliminate pain.
suggests that vitamin B supplements,
primarily vitamin Bu complex, magnesium Prevention
NSAIDs taken a day before the commencement of
and fish oil supplements (omega-3 fatty
n. menstruation should eliminate cramps in some
acids) may also relieve cramps
women.
3. Simply changing the positions of the body
Conclusion
can help ease cramps. The simplest tech-
Dysmenorrhoea is a common gynaecological
nique is assuming the fetal position, with
condition that is underdiagnosed and undertreated.
knees pulled up to the chest and hugging a
Simple analgesics and non-steroidal anti-
heating pad or pillow to the abdomen.
inflammatories are effective in up to 7O% of women.
Oral contraceptives can be considered for women
4. Exercise. Physical exercise may reduce
who wish to avoid pregnancy. For women seeking
dysmenorrhoea. lt is believed that exercise
alternative therapies, heat and dietary changes may
works by improving blood flow at the pelvic
be effective. The possibility of an underlying pathol-
level as well as stimulating the release of p
226
Dysmenorrhoea And Premenstrual Syndrome PMS)
ogy should be considered in women who are refrac- oestrogen excess, oestrogen withdrawal, progester-
tory to med ical treatment. one deficiency, pyridoxine (vitamin Budeficiency)",
alteration of glucose metabolism, and fluid -
PR EM EN STR UAL SYN D RotffiTPilffi) electrolyte imbalances. Current research provides
some evidence supporting the following
lntroduction
Premenstrual syndrome (PMS) is defined as the
aetiologies": :
cyclic recurrence of physical, psychological, or Serotonin deficiency is postulated because

behavioural symptoms that appear after ovulation patients who are most affected by PMS have
and resolve with the onset of menstruationt''0. These
differences in serotonin levels; the symp-
symptoms can be severe enough to disrupt personal
toms of PMS can respond to selective
relationships, social activities, or job performance.
serotonin reuptake inhibitors (SSRls), which
True PMS only occurs during the luteal phase of the
increase the amount of circulating serotonin.
menstrual cycle, with a symptom- free period during
thefollicular phase. Magnesium and calcium deficiencies are
postulated as nutritional causes of PMS;
The most severe presentation of the PMS complex is
studies evaluating supplementation show
known as Premenstrual Dysphoric Disorder (PMDD)
improvement in physical and emotional
in which women with this latter condition have a
symptoms.
higher percentage of psychiatric disorders.
Women with PMS often have an exagger-
Epidemiology
ated response to normal hormonal changes;
Premenstrual syndrome is increasingly recognized as
a medical entity that adversely affects the quality of
although their Ievels of oestrogen and
progesterone are similar to those of women
lifeof about40% of women of childbearingage'.
without PMS, rapid shifts in levels of these
Unlike primary dysmenorrhoea, which is a disease of hormones promote pronounced emotional
female adolescents, PMS is extremely common in all and physical responses.
ages but especially in women aged 30 - 45 years.
The reported prevalence ranges fromS"/"to 95%. lt is
. Other theories under investigation include
increased endorphins, alterations in the
often wrongly attributed to women approaching
gamma-aminobutyric acid (GABA) system
menopause. The age incidence of PMS is said to be
and hypoprolacti neamia12.
due to the faCt that stresses are most severe in the
third and fourth decades". . The result of a large longitudinal study
carried out by Bertone-Johnson et al suggest
A study among Nigerian schoolgirls reported PMS in
20% and symptoms were mainly of that the experience of abuse (emotional,
behavioural
sexual or physical) in early life places
change, arousal and impaired concentration '. The
women at higher risk for PMS in the middle
severe form (PMDD) occurred in 3% to 5% of the
to late reproductive years".
study group. Women with the latter condition, unlike
true PMS become accident prone with increased
Signs and Symptoms
prevalence of suicide and high risk of major depres-
A lot of symptoms have been associated with
sive disorders. premenstrual syndrome. Common emotional and
non-specific symptoms include stress, anxiety, and
PMS can be a cause of much individual misery and
difficulty with sleep, headache, feeling tired, mood
family disharmony, absenteeism and even criminal
swings, increased emotional sensitivity and loss of
acts like murder and suicide ".
libido.
Pathophysiology a nd Aetiology
Physical symptoms dssociated with the menstrual
The definitive cause of PMS is unknown. lncorrect
cycle including bloating, lower back pain, abdominal
older theories about the causes of PMS include
crampsr constipation or diarrhoea, swelling or
227
tenderness in the breasts, acne, joint or muscle pain life style changes may be done before resorting to
and food cravings. The exact sympto{rs,and their medical treatment.
intensity va ry si gn if i ca ntly f rom i nd ividreb@.'even
from cycle to cycle and over time. tr4og-t't&4ry h
A) LifestYle Chinges
1. Diet. Maintenance of a healthy, bal-
PMS experience only a few of the possi tir'q@@ns'
anced diet maY helP to control the
in a relatively predictable pattern. .
sYmPtoms of PMS.
Diagnosis
2. Smoking. Quitting smoking may help to
reduce mild PMS'
The diagnostic assessment of PMS entails a thorough
medical and psychiatric history, prospective daily
3. Exercise. Examples of activities include
walking, swimming and cYcling'
rating of symptom expression across the menstrual
Exercise improves the overall health of
cycle and the exclusion of other medical and psychi-
the patient and can help to alleviate
atric disorders'. The best tool to diagnose PMS is a
depression and tiredness' Stretching
daily symptoms rating calendar which critically
and breathing exercises such as yoga
evaluates symptoms in the latter half of the men-
can help the patient to sleep better and
strual cycle. Studies on PMS often use standardized
reduce stress levels.
screening instruments such as the Moos Distress
Questionnaire for the evaluation of the symptom- B) ComPlementarYTreatment
complex of PMS. To have the diagnosis of PMS, the There are many non-prescribed alternative
symptoms must be severe enough to disrupt normal treatments and supplements that claim to
daily activities. helP treat PMS. Some women maY find
these helpful for easing their symptoms' For
Differential Diagnosis
example supplements of calcium, vitamin D,
The differential diagnosis of this amorphous condi-
magnesium and agnus castus (a herb known
tion includes anxiety disorders, diabetes mellitus,
as chasteberry) may reduce some symptoms
hypothyroidism, major depression and various
of PMS. However, many complimentary
causes of chronic pelvic pain in women in the
therapies and supplements have either not
reproductive age'.
been tested or haven't been proven to be
Psychiatric problems, familial disharmony and affective.
hyperthyroidism may lead to initability and behav-
ioral change. Premenstrual pelvic pain may be
C) PsYchologicalTheraPY
This can be offered if the patient has psycho-
caused by pelvic inflammatory disease or logical symptoms, such as depression or
endometriosis. Underlying breast lesions should be
emotional symptoms. Cognitive behavioural
ruled out in cyclical mastalgia.
therapy (CBD is the term for a group of
therapies designed to help solve problems
Lethargy may be due to hypothyroidism or anaemia
such as anxiety and depression' A cognitive
which must be looked for and treated'
behavioural therapist can help in managing
Treatment the sYmPtoms.
Patient Education
Premenstrual syndrome may cause major morbidity D) MedicalTreatment
for an adolescent. Providing patient education This is for patients with severe Premenstrual
regarding alternative therapies that may alleviate syndrome. However there is no single
some symPtoms is imPortant'
treatment that works for all patients'
Medical treatments for PMS
Behavioural counseling and stress management may
help the patient regain control during the time of 1. Analgesics. Analgesics including
paracetamol ahd non-steroidal anti-
emotionalism. Treatment for PMS may help to
manage symptoms so that they don't interfere with
inflammatorY drugs (NSAlDs) can
relieve some of the painful PMS symp-
their daily life. lf PMS is mild or moderate, diet and
228
toms such as stomach cramps, head- SSRIs also may have negative side
aches and muscle and joint pain. effects that could outweigh their
benefits, such as nausea, insomnia,
2. Oral contraceptive pills. As well as headache and loss of libido.
preventing pregnaney, combined
contraceptive pills will help to relieve 5. Gonadotrophin - releasing hormone
symptoms of PMS in some women by (GnRH analogues). GnRH analogues
preventing ovulation. ln particular, are synthetic hormones that create a
newer types of contraceptive pills temporary menopause and cause
containing certain versions of the amenorrhoea by blocking the produc-
hormone progestogen, such as the tion of oestrogen and progesterone.
Yasmin pill, have been shown to be
effective for treating some PMS symp- GnRH analogues should only be used in
toms, and may even be effective for women with severe PMS when all other
improving symptoms of PMDD. How- treatments have failed. Their side
ever, contraceptive pills don't help all effects include hot flushes, vaginal
woman and they can have side effects dryness and loss of libido and osteopo-
similar to the symptoms of PMS, such as rosis.
breast pain ordepressed mood.
They should be taken alone for up to six
months. lf GnRH analogues are used for
3. Oestrogen - only patches and implants.
Like combined contraceptive pills, longer than this, the patient should
- only patches and implants
oestrogen take hormone replacement therapy
may help improve some symptoms of (HRD to reduce menopausal complica-
PMS by preventing ovulation. tion such as osteoporosis.
Unless the woman has had a hysterec- E) Surgery

tomy, oestrogen patches and implants Surgery is reserved for patients with severe
need to be combined with a low dose of symptoms refractory to medical therapy.
progestogens. This is given to reduce the The potential benefits of bilateral
risk of endometrial hyperplasia which oophorectomy (suppression of cyclical
can lead to endometrial cancer. This may ovarian activity) have to be balanced against
be in the form of progestogen tablets or a the long term disadvantages of induced
progestogen - releasing intrauterine hypo-oestrogenism and the likely long term
system (lUS). Side effects of using an com pl ia nce with oestrogen replacement.
oestrogen patch include skin irritation,

Prognosis
itching and soreness and the additional
Premenstrual syndrome is generally a condition with
progestogen doses can have side effects
susceptible women experiencing the same symp-
simi lar to the symptoms of PMS.
toms at the same intensity in the luteal phase of the
4. Selective serotonin reuptake inhibitors menstrual cycle for years. Treatment for specific
(SSRls). These drugs may be the most symptoms is usually effective.
effective treatment if the patient has
Even without treatment, symptoms tend to decrease
severe PMS or PMDD.
in perimenopausal women. However, women who
SSRls, such as fluoxetine and sertraline, experience PMS or PMDD are more likely to have
are antidepressants that can be taken significant symptoms associated with menopause,
daily to relieve tiredness, food cravings such as hotflashes.
and sleep problems, and combat
depression. However,
229
I
Complications suggests a secondary dysmenorrhoea then investiga- 'l
l. Premenstrual Dysphoric Disorder (PMDD). tions can be considered. Similarly, if symptoms of -
i
This is a more disabling for.,m of PMS in primary dysmenorrhea are not alleviated with either
which mood symptoms efrtl personality NSAIDS or combined oral contraceptive pills or the
disorders predominate. Thc, #Edogy is combination of the two, secondary causes of
\
largely unknown. The prerdrffi i$Mween I
dysmenorrhea need to be considered. Secondary -\ J
3% and 6% of women in the reproductive dysmenorrhea should also be suspected if symptoms
age group. The first line treatment option is initially of primary dysmenorrhoea worsen in
selective serotonin reuptake inhibitors duration (starting premenstrually) and intensity'u.
(SSRls).
2. Premenstrual Magnification of Medical 4. Does pregnancy cure dysmenorrhea? "t
Disorders. Menstrual cycle related exacerba- Child birth often cures dysmenorrhoea possibly 1
tion of some medical disorders Iike migraine, because the parous uterus is more vascular and does {
asthma, irritable bowel syndrome and not become so ishaemic.
l
I
I
diabetes mellitus. jl
B) Premenstrual syndrome (PMS) t

Conclusion
Premenstrual syndrome (PMS) refers to the range of 1. ls PMS a Psychiatric Disorder?
physical and emotional symptoms that some women A correct diagnosis of PMS is important and \-i
those patients without a symptom- free week )
experience in the lead upto menstruation. Symptoms
usually stop during, or at the beginning of the probably have a continuous underlying psycho- iI
menstrual period. There is at least one symptom-free logical problem. They should be referred back to
the general practitioner or, in severe cases, I
week before symptoms start returning. Patients can I
keep a detailed diary for at least two menstrual cycles referred to a Psychiatrist 'u. The most severe I
1
to work out if theirsymptoms are caused by PMS. presentation of the PMS complex is known as j
Premenstrual Dysphoric Disorder (PMDD) in 1
_t
Discussion / Controversies which women with this latter condition have a i
higher percentage of psychiatric disorders. {

:
A) Dysmenorrhoea
1. ls dysmenorrhoea commoner in a particulat race? 2. Should PMS patients be managed by the I
No data suggests that race affects the incidence of Psych iatrist or Gynaecologists? i
t
dysmenorrhoea. Only the most severe patients with clear-cut
PMS requiring medical or surgical intervention
2. What is the aetiology of primary dysmenorrhoea ? \-/ -'
should be referred for secondary care manage-

Until recently, many medical and gynaecological ment. Those with complex psychological
texts ascribed the source of dysmenorrhoea to problems ought to be assessed by the psychia-
I
emotional or psychological problems-for example,

trist. Gynaecologists, preferably those with an
anxiety, emotional instability, a faulty outlook on sex
interest and expertise in the problem, should
and menstruation, and imitation of the mother's only be asked to manage PMS patients when
feelings about menstruation. However, experimental
symptoms are severe enough to justify endocrine
and clinical research has identified a physiological
or surgical intervention.
reason for dysmenorrhoea-the production of uterine
prostaglandins e. 3. What is the first line drug therapy for PMS?
Selective serotonin reuptake inhibitors (SSRls)
3. When is the diagnosis of primary or secondary are the simplest and most effective non-
dymenorrhoea? hormonal approach to treatment. Some consider
The diagnosis of primary dysmemorrhoea is one of
them to be the first Iine medical therapy. Some
exclusion. lf symptoms are typical of primary patients consider this form of therapy to be
dysmenorrhea, a therapeutic trial may be embarked
stigmatizedl6.
on before considering any examination and investiga-
tion especially in adolescents. lf clinical evaluation
230
4. How to differentiate symptoms of PMS from similar to the symptoms of PMS or similar to the
that of Pregnancy changes they experience prior to the menstrual
For certain women, the symptoms of PMS may period. Unfortunately for women wondering
be similar to those of early pregnancy. Many whether specific symptoms are due to PMS or
women do not experience symptoms in early early pregnancy, the only definitive answer
pregnancy, while others may report breast comes with the arrival of the menstrual period or
tenderness, bloating, fatisue, and mood swings. a positive pregnancY test.
These symptoms can be, for some women,
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factors for the occurrence, duration and severity of 13. Emans SJ, Laufer ME Goldstein DP Premenstrual
menstrual cramps in a cohort of college women. sy n d ro me. Paed i a tr i c a n d a d o I esce nt gy neco I ogy :
Br. J. Obstet. Gynaecol. 1996; 103(L1): 1134- 5'n edition, Philadelphia. PA; Lippincott- Raven
1142. \nc.2005; 461-467.
5. Lethaby A, Augood C, Duckitt K, Farquhar C. Non- 14. Bertone-Johnson ER, Whitcomb BW, Missmer
steroidal anti-inflammatory drugs for heavy SA, Mansone JE, Hankinson SE, Rich-Edwards
menstrual bleeding. Cochrane Database Syst' JW. Early life emotional, physical and sexual
Rev. 2007 (4) : CD 000400. abuse and the development of premenstrual
6. Rosenwaks Z, Seegar -Jones G. Menstrual pain: syndrome; a longitudinal study. J Wamens Health
its origins and pathogenesrs. J. Reprod. Med. (Larchmt). 2014; 23(9): 729 - 739.
1980; 25(4 Suppl.): 207 - 212. 15. Horne AW, Critchley H)D. Menstrual problems:
7. Smith RP Cyclic pelvic pain and dysmenorrhea. Heavy menstrual bleeding and primary
Obstet. Gynecol. Clin. North Am. 1993; 20@): dysmenorrhoea. ln: Edmonds DK (Eil Dewhurst's
753-764. textbook of obstetrics and gynaecology 8'n edition'
8. Fakeye O, Olatinwo AWO. Dysmenorrhoea and Btackwett Scientific Publications. 2012; 42:
Pre-menstrual syndrome (PMS). ln: 534-542.
Comprehensive Gynaecology in the tropics. First 76. O'Brien PMS. Premenstrual syndrome. ln:
Edition. Eds: Kwawukume EY Emuveyan EE. Edmonds DK Gd) Dewhurst's textbook of
Graphic Packaging Limited, Accra. 2005; 18: obstetrlcs and gynaecology 8'n edition. Blackwell
168- 173. Scientific Publ ications. 20 1 2; 43 : 543-5 5 1'
9. Proctor M, Farquhar C. Diagnosis and
management of dysmenorrhoea. Brit' Med' J.
2006;332 (7550): 1134- 1138.
23L
r#:
..,
CHAPTE2l
Genital Tract Fistulas

KADansoandATLassey
!ntroduction Analysis of 543 cases reported from Nigeria and

A fistula is an abnormal communication between two United Kingdom by Lawson' showed that of 377
epithelial surfaces or cavities. Genital tract fistulas cases from lbadan, Nigeria, 369 or 97.9o/o were
involve the lower genital tract and adjacent urinary or from obstetric causes. ln contrast, of the 166 cases
alimentary tracts. The result is an uncontrollable from the United Kingdom 116 or 69.9o/" were
leakage of urine into the vagina in the case of genito- related to surgery with only 27 or 72.6% related to
urinary fistu las and of feces into the vagina in the case obstetric causes, Of 164 cases reported from
of recto-vaginal fistulas. Kumasi, Ghanao 150 or 97.5% were due to obstetric
causes and 14 or 8.5% were related to gynaecologic
Genital tract fistulas date far back into history having causes from surgical injury occurring at the time of
been found in the mummified remains of Queen abdominal hysterectomy. Similar results have been
Henhenit who lived in Egypt about 2050 BC'. Genital found in other series from low and high income
fistula was one of the major challenges in gynaecol- countriesu'u.
ogy in ancient times when it was regarded as a
hopeless malady which affected mainly poor and Geographically, obstetric fistulas occur commonly in
underserved women. Major developments in fistula Sub-Saharan Africa from the west coast to the horn
surgery began in the 19th century with contributions of Africa and southwards to east and central Africa;
from persons such as James Marion Sims and in the lndian subcontinent including lndia, Nepal,
Thomas Addis Emmet of New York, Mauris Collis of Bangladesh and Northern Pakistan and in all other
Dublin and Mackenrodt of Berlin. Sims opened the deprived communities where there are poor or
first dedicated fistula hospital, the Woman's Hospital inaccessible maternity services, low literacy rates,
in New York in 1855. The second fistula hospital was low socio-economic status of women and existence
opened in Africa in 1975 in Addis Ababa, Ethiopia by of traditional cultural practices that are inimical to
Reginald and Catherine Hamlin. womenn.
Epidemiology Many obstetric fistula patients are very young,

Genital fistulas occur worldwide but for different primiparous, of short stature, uneducated and come
reasons. They are mainly caused by obstetric factors from rural and deprived areasn''o However, a good
in low income countries and by gynaecologic, number of cases are also found among the older
abdominal and pelvic surgery in high income coun- multiparous womeno'".
tries. Obstetric fistulas were just as common in high
income countries until the end of the nineteenth The true incidence and prevalence of genital tract
century' but have become rare because of high fistulas, particularly obstetric fistulas in low income
literacy rates and improved socio-economic status of countries are difficuli to obtain. Only estimates,
women coupled with access to efficient maternity which tend to be under statements, are available.
services in these countries. However, since the occurrence of obstetric fistula is
233
indicative of the level of available maternity services, practices, difficulties with transportation and
areas with high maternal deaths also tend to have communication are factors that underlie the occur-
high incidence and prevalence rates'. Waaldjik rence of obstetric injury as a cause of genital fistulas.
estimated that there were about 20,000 wornen with These factors may lead to delays by the patient and
fistula awaiting repair in Northern Nigeria alone in relatives recognising ihe need for seeking skilled care
the late 1990s and that one to two women developed during labour, delay in actually deciding to seek
vesico-vaginal fistulas among every 1000 medical care, delay in reaching the medical facilities
deliveries". lt is estimated that between 717 and and delay in actually receiving skilled care at the
1352 new obstetric fistulas occur in Ghana every medicalfacility.
year". The incidence of urogenital fistulas following
hysterectomy is estimated at 1 per 1,300 operations Gynaecologic surgical injury. These may occur as
in England and Wales'^. complications during surgical procedures such as
abdominal, vaginal or laparoscopic hysterectomy for
Aetiology of Genital Tract Fistulas benign conditions including uterine fibroids, dys-
The major causes of genital tract fistulas include functional uterine bleeding, uterine prolapse and
direct causes such as obstetric injury, gynaecologic endometriosis. Procedures for urinary incontinence
surgical trauma and a group of miscellaneous and pelvic cancer surgery may also result in genital
conditions as well as indirect factors which operate tract injury and fistula formation. Such fistulas are a
when there is socio-economic under development or consequence of tears into the bladder or rectum from
deprivation, particularly in the case of obstetric blunt dissection, lacerations during sharp dissection
injury. and necrosis following ischaemia from tightly placed
knots in compromised tissue or prolonged tissue
Obstetric lnjury. These are predominant in low clamping.
income countries and occur under the following
conditions: Miscellaneous causes of genital fistulas. These
include pelvic irradiation for cancer treatment
. Prolonged obstructed labour. The unrelieved causing irreversible endarteritis, tissue necrosis
pressure of the bony presenting part on the which may present even years after the index
bladder against the symphysis pubis results radiation exposure; traditional practices such as the
in ischaemic necrosis of the local bladder 'gishiri' cut performed in some parts of northern
tissue, subsequent breakdown and slough- Nigeria and female genital mutilation; invasive
ingtoform thefistula. cancers of the cervix and rectum; genital tract
infections such as lymphogranuloma venereum and
. Accidental bladder injury that occurs as a
tuberculosis. Coital lacerations and penetrating
complication during operative delivery such
injury from road traffic accidents or falling astride
as caesarean section, repair of ruptured
from trees have all been documented as causes of
uterus or during caesarean hysterectomy,
genitalfistulas.
forceps delivery, vacuum extraction,
craniotomy with fetal extraction and Classification
symphysiotomy. Genital tract fistulas may be classified using two
main parameters: the origin of the leakage and the
. Third degree perineal lacerations which are
anatomic description of the fistula location in the
not properly repaired can lead to recto-
vagina. Thus there are two main categories of genital
vaginal fistula formation.
tract fistulas: urogenital or urovaginal fistulas and
. Unskilled surgically induced abortion which
rectovaginal fistulas. The classification of urogenital
and rectovaginal fistu las are as follows:
becomes complicated with bladder or rectal
injury can result in fistula formation.
L Uretero-vaginal fistglas. These are fistulas
linking the ureter to the vagina. They usually
Socio-economic under-development with its
fol low su rgery for ruptu red uterus.
attendant poverty, ignorance, harmful socio-cultural
234
qtj
ll. Vesico-vaginal fistulas (WF).'uThese are the

most common variety of fistulas. They are
further sub divided into:
1. Juxta-urethral WF. lt invo.fws: bladder neck

and proximal urethra with'the c@ ion into the
vagina. The urethral sphincter rmay be damaged and
the u reth ra I stu m p m ay be occluded.by sca rri n g.
2. Mid-vaginalWF. lt involve a connection from the

bladder to the middle third of the vagina. The bladder
neck and trigone are spared. These are usually the Fig. 21-2 Massive VVF
easiest fistulas to repair.
3. Juxta-cervical WF, The fistula connects the

bladder into the anterior vaginal fornix (Fig. 2l-7).
The fistula is close to the trigone of the bladder and
the ureteric orifices may be present at the edge of the
fistula. lf the cervix is fixed by adhesion behind the
pubis, the fistula may be inaccessible vaginally.
Fig. 21-3 Massive VVF with prolapsed dome

of the bladder
lll.Vesico-cervical or vesico-uterine fistulas. These

fistulas link between the bladder and cervix, or
bladder and uterus. They usually follow caesarean
section or surgery for ruptured uterus.
Fig. 21-1 Simple Juxta-cervical VVF lV. Recto-vaginal fistula (RVD. This is a fistula
connecting the rectum to the vagina. lt results in the
This type of fistula usually follows bladder injury at leakage of faeces from the rectum into the vagina.
caesarean section, surgery for ruptured uterus or They are sub divided into:
irradiation for mal ignant conditions.
1. Low RVF. This involves lower third of the vagina.
4. Massive WF. This type of fistula is a combination 2. High RVF.This involves the upper third of the
of all the three types described. The fistula extends vagina. The fistula may be fixed to the sacral
from the bladder neck to the trigone (Fig. 21-2). The promontory and completely inaccessible from below
ureteric orifices are often at the edge of the fistula and through the vagina.
may be seen spurting urine. The dome of the may be
V. Compound fistulas: This is the situation when
inverted and prolapse through the defect (Fig. 21-3)
there are coexisting urogenital and rectovaginal
fistulas
ln 2004, a new 'and fresh dimension to the

classification of genital fistulas was
introduced.'uThis new approach uses fixed reference
235
FI- l't
points to enable standardisation of description and

comparison by different observers. The external
urethral meatus is used as the fixed refurence point
for genito-urinary fistulas whereas the hyrl&n is used
as the fixed reference point for genito-anorectal
fistulas. The length of the vagina allows assessment
of the relative size and position of the flstula and is
a lso a risk factor for su bseq uent sexu aI dysf u nction.'u
Clinical features
Genital tract fistulas characteristically present as
uncontrollable loss of urine in the case of urogenital
fistulas, loss of faeces in the case of rectovaginal
Fig. 21-4 Vulvo-perineal ammoniacal dermatitis in a
fistulas, or loss of both urine and faeces in compound fistula patient. The VVF is demonstrated by passing
fistulas, through the vagina. The patient may a sound through the urethra into the vagina
therefore smell of urine and/or feces as the case may
be.
and the stench of the subsequent urinary andlor
Depending on the causative injury, the leakage may faecal incontinence severely traumatise her
i
be immediate as in the case of surgical injury, within psychologically. She loses her self-esteem, becomes
'1
days as in obstetric pressure necrosis induced WE, or withdrawn from society'n and may be abandoned by
1
even months or years following radiation induced her relatives including her husband. She therefore
feels and looks dispossessed and impoverished'0.
fistulas. ln urogenitalfistula, the leakage of urine may I
be intermittent or continuous depending on the size,

Diagnosis and lnvestigations .
location, presence or absence of vaginal folds, the fill Diagnosis of genital fistulas is based on a careful and
of the bladder and the position adopted by the detailed relevant history followed by general physical
patient. ln recto-vaginal fistula the faecal leakage and pelvic examinations and investigations. The
may also be intermittent or continuous depending on pelvic examination must confirm that what is being
the size of the fistula and the consistency of the leaked uncontrollably is urine or feces and also
stools. identify the hole through which the leakage is
occurring. The first task is usually not difficult
Other features commonly associated with obstetric because the smell of urine and faeces is obvious. The
fistulas include vaginal scarring, loss of tissue from second task can be very difficult. Usually however, a
the bladder or urethra and vulval encrustations which Sims speculum examination of the vagina in the
result from ammoniacal dermatitis arising from the
clinic will reveal the fistula which may also be
palpable during digital examination. Difficult cases
persistent contact of urine with the vulvo-perineal
require a painstaking examination with dye testing in
skin (Fig. 2I-q. theatre before actual surgical repair is scheduled. ln
some cases, an intravenous urogram is
Amenorrhoea and secondary infertility may also be recommended to assess both the lower and upper
present."The patient may show acquired deformity urinary tracts. These investigations may be
of the lower extremity such as foot-drop. This results of the fistula in
necessary before the evaluation
from crippling neurological injuries to the sciatic and theatre to define or confirm the site of the fistula and
common peroneal nerves" sustained simultaneously plan the details of surgical repair.
during the prolonged obstructed labour. The woman's
experience of the obstetric trauma in the antecedent During the examination in theatre the patient is
prolonged labour often culminating in the loss of her placed in the lithotomy position. A short general
anaesthesia is necessary if the patient is found to be
baby
in pain or cannot relax for details of the fistula to be
determined. A uterine sound., probe, orslender artery
forceps passed through the urethra and guided
through the fistula into the vagina can be used to
236
demonstrate a vesico-vaginal fistula (Fig. 2 1-4). The from neurological disorders or spinal cord injury.
index finger or Hegar dilator passed per rectum can Careful interpretation of the history and physical
also be guided into the vagina iR a recto-vaginal findings usually enables a distinction to be made.
fistula.
lnvestigations for patients with fistula must include a
Dye testing with methylene blrre irdi+hd into the full blood coLrnt, urine and stool laboratory tests to
bladder may be required in somb caes to locate the identify any medical disorders such as bacterial or'
hole in very small fistulas or fistulas_obscured by the parasitic infections which need to be treated before
presence of scarring and mucosal folds in the vagina. the definitive su rgery.
In such cases gauze or cotton wool swabs are placed
in the vagina during the dye testing to help locate the Management
exact position of the fistula by noting whether the The management of genital tract fistula involves the
upper, middle or lower swabs become stained with prevention of new cases from occurring, and the
dye. When the upper swab remains unstained with surgical treatment of existing ones.
the dye but gets wet with urine during dye testing it is
indicative of uretero-vaginal fistula. Patiently Prevention
watching the lateral vaginal fornices when the swabs Genital tract fistulas in general and obstetric fistulas
have been removed may show one or the other ureter in particular are preventable.
spurting urine into the vagina at intervals particularly
if a diuretic has been administered to enhance urine WHO estimates that for each maternal death that
production in the course of the examination. occurs, about 10-15 other women sustain serious
morbidity including obstetric fistula." The
Cystoscopy can be performed to identify very small implication is that programmes that prevent
fistulas if it is not clearly visible during evaluation of maternal deaths will also have positive impact on
the fistula in theatre. However, performing obstetric fistula prevention. Strategies to prevent
cystoscopy when the fistula is large is technically obstetric fistula must involve the prevention of new
difficult because distendingthe bladderwith fluid will cases just as much as the cure for the many already
be problematic. The fistula will be obvious anywayl existing. These must include:
lmportant physical findings to elicit about the fistula . lmproved childhood nutrition and infection
during the pre-surgery evaluation of the patient in control to ensure optimal physical growth in
theatre are the size, location and number of the pelvic size in order to prevent feto-pelvic
fistulas; the condition of the vaginal epithelium and disproportion and prolonged labour later on
the state of the tissue around the fistula, whether in the reproductive life of the woman.
edematous, scdrred, or fixed to bone; the state of the
urethra, whether patent along the entire lengh, . ldentification of women at risk of developing
blocked proximally, distally or partially or totally obstructed labour through effective and
destroyed; the ureteric orifices whether they are skilled supervision during pregnancy, labour
visible at the edges of the fistula in the case of and delivery. Using the partograph for early
massive vesico-vaginal fistulas; and finally the detection of cephalo-pelvic disproportion
accessibility of the fistula for the purpose of surgical during labour will enable intervention to be
repair through the vagina. taken before obstructed laboursets in.
Otherwise alternative positions for the patient . lmprovement in health services in the rural
placement during the repair through the vagina such areas including providing facilities for
as the Lawson position, in which the patient is placed essential and emergency obstetric care so
prone on the theatre table with the ankles supported that caesarean section could be safely
in stirrups and thighs apart,'u is decided upon at this . performed at that level will prevent prolonged
stage. lf the fistula is judged to be inaccessible per obstructed labour, the most important
vaginam and requires that the repair be done per immediate cause of obstetric fistula.
abdomen, it must be decided upon at this stage.
Differential diagnoses of fistulous leakage of urine or . Effective referral and transfer of women in
faeces per vaginam are the non-fistulous urinary and prolonged labour to first referral health
faecal incontinence which are caused by pelvic floor facilities that have been equipped with
relaxation or sphincteric dysfunction which result essential services.
237
. Training of medical workers in basic fistula may be the best anaesthetic option.
repair techniques so that simple cases could
be treated in peripheral centres. Difficuli The route of repair, whether vaginal or abdominal,
cases could then be sent to specialised and the position of the patient during the vaginal
centres for surgery operation must have the objectives of achieving good
access to, and exposure of the fistula, These are
. ldentification of all existing cases of'fiptula for decided upon during the pre-surgery evaluation of
programmed repair at designated centm. the patient before the day of the actual surgery.
Hastily evaluating a fistula patient on the day of
. Comprehensive socio-economic change in surgery must be resisted because it is prone to
the poor, fistula endemic or rural areas to making sub-optimal decisions about the surgery.
include basic universal formal education,
avoidance of early marriages, women ln general, the majority of fistulas can be repaired
empowerment, availability of contraception, vaginally with the patient in lithotomy position, with
skilled attendance during pregnancy and extreme head-down tilt if the need arises. Bladder
delivery so as to eliminate the immediate neck and proximal urethral fistulas stuck behind the
causes of obstetric fistulas. pubic bone may have to be repaired vaginally using
the Lawson position, which is knee-elbow with about
. During surgical procedures involving the 200 head-down tilt of the theatre table. When access
urinary, genital and lower alimentary tracts to the fistula from the vagina is poor as sometimes
surgeons must adopt meticulous techniques occurs with very high, juxta-cervical or vesico-
to prevent accidental lacerations, crushing of cervical fistulas fixed by adhesions, the abdominal
tissues and making knots that are too tight. route is recommended. The fistula can then be
reached by entering the bladder intra-peritoneally or
. lntra- and post-operative signs of bladder extra-peritonea ly th rough the retropu bic space.
I
injuries should be promptly recognized and

dealt with. Each fistula is different and must be approached
. Accurate dosing, placement of radiation ditferently. Step-by-step guides to fistula surgery,
sources and shielding will reduce bladder which is beyond the scope of this book, have been
damage during radiation to adjacent organs. described elsewhere.'u' "''u Sound general surgical
principles as well as special principles applicable to
Surgicalrepair the surgical repair of genital fistulas must be followed
It is standard practice to allow an interval of three to at all times to achieve successful outcomes. These
four months between the injury and surgical repair in principles include:
the case of obstetiic fistulas, about two to three
months in surgical fistulas and about twelve months . An operative and supportive nursing team
in radiation-induced fistulas. This time allows the veryfamiliarwith the care of fistula patients.
tissues to recover from the injury, the inflammatory
response to subside completely, the blood supply to . Adequate access and exposure of the fistula
the tissues to improve and any complicating infection by appropriate choice of patient position,
to clear. This time interval should also be spent route of repair and the use of vaginal relaxing
profitably building up the patient nutritionally and incisions when necessary during vaginal
treati ng any i ntercurrent diseases. repair
Fistula repair surgery is not an emergency. lt should . Adequate light source, appropriate surgical
therefore be well-planned and executed because the instruments and suture materials.
chances for cure are best during the first attempt at
repair. For these reasons, undertaking the repair in . ldentification and catheterisation of the
obstetric fistula cases as soon as the slough has ureteric orifices if they are located at the edge
separated as advocated by other workers" is not of the fistula to prevent ureteric injury during
recommended. General anaesthesia, low spinal both vaginal and abdominal repair.
anaesthesia and epidural are all suitable for use in
fistula surgery. lndeed, in remote areas where the . Adequate flap dissection around the fistula
majority of the obstetric fistulas occur, a low spinal followed by one to three layered non-tension
238
closure with interrupted Lembertsutures with intercourse for at leastthree months to ensure
polyglycolic absorbable sutrrre number 3-0 or firm healing and offering caesarean section in
2-0 to invert the bladder n l layer and a ll su bseq uent deliveries to prevent
achieve a water tight line. ti to endangering, or recurrence of, thefistula.
: excise scarred edges of the after
the flap dissection since it- defect Complications
to be closed and promotes into the Complications of genital fistula repair surgery
bladder after closure. Lim,i.@- eXejsion of include post-operative intra-vesical haemorrhage
scarred vaginal wall is all thal may be causing catheter blockage, bladder distension and
necessary if need be.'u suture line breakdown. Following successful healing,
there may be vaginal scarring and stenosis resulting
Effective i ntra-operative haemostasis. in acquired gynaetresia, small bladder syndrome and
genuine stress or urge incontinence. The fistula may
Strengthening of the fistuta closure line by recur. Juxta-urethral fistulas and partial or total
grafting with borrowed local tissue such as the destruction of the urethra may involve the bladder
"Martius" graft using a pedicle developed from sphincter mechanism and so cause other types'of
the bulbocarvenosus muscle and tissue in the incontinence problems even after the hole has been
labium majus, or the rectus flap developed closed. A method for dealing with such difficult cases
from the rectus abdominis muscle, or the involving urethral destruction has been described in
gracilis flap developed from the gracilis the subregion.'o
muscle during surgery for large, recurrent or
radiation i nduced fistulas. Discussion
Genital tract fistulas rank as the most abhorred
Post-operative continuous bladder drainage morbidity in Obstetrical and Gynaecological
for 10-14 days depending on the size of the practice. ln low income countries obstetric fistulas
fistula or extent of repair and avoiding are the leading cause of urinary incontinence among
blockage of the catheter at all costs. females. lt is the greatest challenge to safe
motherhood after maternal mortality. The patients
Continuous bladder drainage is usually who suffer the condition are usually young or in the
achieved using in-dwelling Foley's urethral prime of their reproductive and economic life. The
catheter. However, in a few special instances, physical, emotional, and psychological trauma as
using drainage through vaginal cystostomy in well as the socio-economic deprivation suffered by
some cases of juxta-urethral fistulas and these women can be prevented by multi-sectoral
supra-pubic cystostomy in the case of programmes towards the overall elevation of the
abdom i nal' repa i rs a re preferred. status of women, socio-economic advancement and
improvement in the health and infrastructuralfacility
Avoidance of post-operative pressure on the base in these countries.
repair line, especially those involving the
bladder neck and proximal urethra, from the The timing of the repair surgery following an injury
bulb of the inflated self-retaining bladder leading to genital fistula is one of the controversial
catheter which can occur through traction on areas of fistula management. Particularly in the case
the catheter itself. This can be achieved by of obstetric fistulas arising from pressure necrosis, a
strapping the catheter to the patient's thigh waiting time of about 3-4 months is deemed
with a plaster whilst ensuring that there is no necessary. This is to allow the tissues to recover,
tension on the proximal part of the catheter in some healing to occur for possible reduction in the
the bladder, or using a non-inflatable rubber size of the fistula and for the tissue planes to be'
drainage tube fixed to the labia minora with restored to favour easy dissection and reduced
a nchoring stitch . bleeding during the subsequent repair surgery. Some
workers, however, advocate for early repair surgery
Adequate post-operative hydration of the as soon as the necrotic tissue has sloughed off. ln
patient.to ensure constant urine secretion by spite of the distasteful nature of genital fistulas for
the kidneys to f low into and flush the bladder. the patient and her relatives, operating too early after
the injury may compromise the success of the
. Abstinence from post-repair sexual surgical outcome. lt is therefore highly
239
recommended to allow a waiting period of about 3 to days of catheterisation was compared to 14 days in
4 months before the repair. women with simple genital fistula.'u lt is our view
that the 7 days should be regarded as special cases
The duration of bladder drainage after fistula repair since it involved simple fistulas. It should therefore
has traditionally been 10-14 days with possible not be seen as benchmark for practice against the
extension to 21 days in very complicated situations. traditional 10-14 days drainage.
Recent studies have reported that the outcome with
shorter durations of drainage is not inferior to the The complications of secondary amenorrhoea and
traditional 14 days of catheterisation.'u''u Nardos infertility, gynaetresia and sexual dysfunction, post-
and colleagues in a randomised trial comparing 10 repair stress incontinence, and the distressing
days of bladder drainage to 14 days revealed that problems of irreparable genital tract fistulas can
there was no significant difference in cure rate indeed be daunting when they do occur. Resolving
between the 10 day group and the 14 day group.'u these challenges will continue to exercise the minds
Similar findings were made by Barone et al. in their of many a fistula surgeon!
multi-centred randomised controlled trial when 7
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of vesico-vaginal fistulae: Zaria experience. consecutive patients. lnternational
240
Urogynaecology Journal. 1994; 5: 12-14. 24. Gosh IS and Kwawukume EY. A new method ol
19. Murphy M. Socialconseguences of vesico-vaginal achieving total continence in vesico-urethro-
fistula in Northern Nigeria. *,r.@Sci
1981; vaginal fistula (circumferential fistula) with total
13: 139-L50. urethral destruction - surgical technique. West
20. Harrison KA. Obstetric #ealanity African Journal of Medicine. Vol 12 No. 3. July'
too many. Br. J. Obstet. E'so,3ss- September,1993.
386
.r;,tl
25. Nardos R, Menber B, Browning A. Outcome of .'"
21. WHO: Call to Action: F*harhood obstetric fistula repair after 10-day versus 14-
Co n f e re n ce. N a i r o b i. Feffi&*, I.S7 day Foley catheterization. lnt J Gynaecol Obstet
22. Waaldijk K. s[4 ''lS $651:sr-
Step-by-s{S: 2012;118(1):21-3.
vaginatfistutas. Edinbwglt r fg$d 26. Barone MA, Widmer M, Arrowsmith S, RuminjoJ,
23. www.glowm.com. Under fislula rn t$e Safe Seuc A, Landry E, et al. Breakdown of simple
Motherhood section, tink to the books i) An female genital fistula repair after 7 day versus 74
introduction to Obstetric Fistula Surgery @ Brian day postoperative bladder catheterisation: a
Hancock. ii) First steps in vesico-vaginal fistula randomised, controlled, open-label, non-
repair by Brian Hancock. iii) Practical Obstetric inferiority trial. Lancet. 2015; 386(9988);56-
Fistula Surgery by Brian Hancock. 62.
241
242
f-
cHAPTE {),
22
Sexual Dysfunction
BAEkeleandANAdamu
INTRODUCTION to 80 years of age found that 39 percent of sexuaily

active women reported a problem with sexual
Human sexuality involves gender identity, sexual activity
n. lt is difficult to accurately determine
object choice, sexual drive and sexual function. prevalence because studies use different definitions
lndividuals display wide variations in these of normal and abnormal sexual function and use
parameters and it is therefore a general principle to heterogeneous populations 'o't'. However, the most
assert that it is the patient who decides whether any common sexual complaint in women is decreased
particular state is a 'problem'. To appreciate this desire, followed by orgasmic dysfunction'n'
group of gynaecological problems, it is important to
remember the normal female sexual response. CLASSIFICATION
Conventionally, the sexual response cycle involves
four phases namely: 1) Desire 2) Arousal 3) Orgasm
to classify and
Sexual dysfunctions are difficult
and 4) Resolution. Female sexual dysfunction is a several dysfunctions may overlap. Sexual
complex and poorly understood condition that affects dysfunctions may be classified according to whether
women of all ages. Sexual function has been re- they are primary or secondary to a period of normal
conceptualized as a cyclic (rather than a linear) function. Female sexual dysfunction is defined as
process that emphasizes social, psychological, lifelong (primary) or acquired (secondary) and as
hormonal, envlronmental and biological factors'. situational (occurs only in certain circumstances or
with certain partners) or generalized (occurs in all
The prevalence of any aspect of human sexuality is situations and with all partners).
not known but complaints about sexual problems are
common and most relate to sexual dysfunction - that Sexual problems may occur in any of the phases of
is, problems of sexual function or interest. There is the sexual response cycle viz: desire, arousal,
ample evidence, nonetheless, that many patients find orgasm and resolution phases (Table 1). The most
it difficult to ask for professional help especially the commonly used classification comes from the
lt is also
female patients in some cultural settings. American Psychiatric Association Diagnostic and
likely that many patients experience sexual Statistical Manual of Mental Disorders (DSM lV) ",
dysfunction but do not regard it as a problem. A where the disorders are classified into four groups as
variety of scientific and unscientific studies from the shown in the table below. However, the revised DSM
West African sub region on general or clinic 5 classification merged the desire and arousal
populations have attempted to quantify the frequency disorder categories into one category as Female
of sexual problems "'''u'u
desire/arousal disorder, and the introduction of the
genitor-urinary/penetration disorder which also
It has been reported that about 43 percent of women includes the former vaginisum and dysperunia
experience sexual difficulties ''
t.
A more recent category.
international survey of 27,500 men and women 40
243
i
Comprehensive Gynaecology in the Topics l
l
l
TABLE 1 CLASSIFICATION OF SEXUAL DYSFUNCTIONS
PHASE OF SEXUAL RESPONSE

DISORDER IN THE WOMAN DISORDER IN THE MAN
CYCLE AFFECTED
Desire / lnterest
ffi tive Sexual Desire Hypoactive Sexual Desire .i
ENeegsive Sexual Desire Excessive Sexual Desire

'l
Arousal/Excitement Fernale Sexual Arousal Disorder Erectile Dysfunction 1
I
Orgasm Female Orgasmic Disorder Premature Ejaculation :r
't
Retarded Ejaculation 1
i
Penetration Vaginismus Erectile Dysfunction \
Dyspareunia Dyspareunia lr
I
1.
1
1
Hypoactive Sexual Desire Disorder (HSDD). lt refers Dyspareunia refers to painful sexual intercourse. lt
to reduced sexual desire in a person or couple to the may be superficial or deep. There is usually an
extent that it is a cause for distress. lt
usually lt is more common in the
underlying organic cause.
presents as a lack or absence of sexual fantasies and female than the male.
desire for sexual activity. For this to be regarded as a
disorder, it
must cause marked distress or Erectile Dysfunction occurs when the man is unable I
interpersonal difficulties. lt was previously termed 1

to have or maintain an erection until completion of
lnhibited Sexual Desire. lt affects both sexes though
the sexual activity. lt is more likely to have a physical
females twice as much. Though the actual l
prevalence is not known but it said to be the cause. Drugs especially alcohol can be a cause. I
commonest sexual dysfunction disorder in females.

Excessive Sexual Desire is also referred to as sexual Premature Ejaculation is persistent or recurrent
addiction. Sexual behaviour in this condition is self- ejaculation with minimal sexual stimulation or
destructive and compulsive. Most sexual addicts shortly after penetration and before the person
come from dysfunctional families and were abused wishes it. The complaint of premature orgasm
as children, sexually, physically or emotionally. Many appears to be limited to men.
exhibit other addictions such as alcohol, drugs or
gambling. Retarded Ejaculation is an involuntary inhibition of
the male orgasmic reflex. ln its acquired form, this
Female Sexual Arousal Disorder (FSAD) is the dysfunction is not uncommon. ln fact the man who
inhibition of the general arousal aspect of sexual can withhold is envied. lt should however not be
response. The woman with FSAD does not lubricate
confused with retrograde ejaculation in which the
her vagina , does not expa nd a nd there is no formation
of the orgasmic platform. She also typically does not
man ejaculates into the bladder instead of out
feel erotic sensations and may find physical contact through the urethra.
repulsive. Some of the most common causes of this
dysfunction are guilt and hostility. CAUSES
Female Orgasmic Disorder is the impairment of Female sexual function is a cyclic process that
orgasmic component of the female sexual response. involves and interplays between physical,
It is important that this is separated from FSAD. ln psychological, social, hormonal, environmental, and
the orgasmic disorder, the woman may be very biologic factors. Sexual dysfunction disorders could
sexually aroused but never reaches orgasm. therefore arise as a result of a disorder at any of these
levels or a combination of levels. Psychological
Vaginismus is an involuntary spasm of the vaginal factors always play a part in sexual dysfunction, even
entrance making intercourse impossible or rendering when physicalfactors are mainly responsible.
it painful. lt appears to be a learned response
triggered by fear of penetration. Vaginismus has no Physical causes of sexual dysfunction
male counterpart. (a) lllness. Any physical or mental illness may be
244
Fi--t
Sexua/ Dysfunction
expected to interfere with sexual life. Chronic be attributed to the disease being treated,
illness, stress, fatigue and depression may be e.g. hypertension or depression.
associated with loss of sexual interest.
Vascular disease and neuropathy as in Psychological causes of sexual dysfunctions
diabetes mellitus may prevent erection. (a) Learning difficulties. Sexual ignorance
Endocrine disorders that reduce free continues to play a small part in sexual
testosterone levels may Ee''associated with problems. Unrealistic expectations may alsb
lack of sexual drive. lt is cornmon for women contribute to sexual dissatisfaction. Couples
to experience a loss of sexual interest after sometimes do not relate their socio economic
childbirth and dyspareunia from an difficulties e.g. living virtually without privacy
episiotomy scar. to the sexual problems they are experiencing.
(b) Age. Although many individuals/couples (b) Sexual anxiety. Sexual anxiety can prevent the
enjoy sexual expression well into old age, physiological changes of sexual arousal and
most will have to adjust to changes in their contribute to premature ejaculation in the
sexual responsiveness as they become older. man. Fear of failure contributes to brectile
Erectile dysfunction is a common complaint in dysfunction in men who may feel that they
men over 50 years which may simply reflect a are expected to "perform". Other men who
general reduction in sexual responsiveness experience premature ejaculation may have
and the need for more tactile stimulation, but an excessive need to please their partner and
organicfactors may also be important. may be so over concerned about this that they
are unable to focus on their own sexual
(c) Drugs. Many drugs can affect sexual pleasure.
functioning. Alcohol probably inhibits sexual
response through central nervous system (c) Personality difficulties. Each partner may
effects. When assessing the possible role of have difficulties which may relate to their
therapeutic drugs in patients with sexual upbringing, past experience and attitudes
dysfunctions, it is often impossible to towards sexuality. Negative sexual
determine to what extent the drug therapy e.g. experiences such as childhood sexual abuse
antihypertensives or anti-depressants, might or rape are increasingly recognized as
be responsible for symptoms which could also contri butors to these d iff icu lties.
245
(")
Another classification of causes of sexual dysfunction is shown in Table 2 below.
fah/'e2: Causes of Female Sexual Dysfunction

Source: FRANK, MISTRETTA, &WEt13 -.
I
CAUSE ilAMPIES SilUAL SYMPTOMS
Hormonal/endocrine Hypothalamic-pitUitary axis dysfu nction, Decreased libido/desire, vaginal

surgical/med ical castration, menopa use, dryness, lack of arousal
chronic oral contraceptive use, premature
ovarian failure
Musculogenic Hyper- or hypotonicity of pelvic floor Hypertonicity: sexual pain

muscles disorders, including vaginismus
Hypotonicity: vaginal
hypoesthesia, coital anorgasmy,
urinary incontinence associated
with sexual activity
.rl
Neurogenic Spinal cord injury; disorders of the central Anorgasmy
or peripheral nervous system (e.g., diabetes,
upper motor neuron injury)
Psychogenic Relationship problems, poor body image, Decreased libido/desire, decreased

decreased self-esteem, mood disorders, arousal, hypoesthesia, anorgasm
adverse effect of psychotropic medication
use
Vasculogenic Diminished blood flow to genitals secondary Vaginal dryness, dyspareunia

to atherosclerosis, hormonal influences,
trauma
The first concern' of the clinician in history-taking interviewing the couple (separately at times) and
must be to accurately identify the area of difficulty, avoiding the temptation to collude with a
i.e. emotional or physical, since it is easy for trouble protestation that it is all the fault of one partner.
in one area to be mistaken for trouble in the other. There may be the need to establish the sexual
Sexual history-taking requires sensitivity and careful orientation of both the client and the partner. Where
attention to details. a partner refuses to come for counseling it is usual to
find that the greater responsibility for the problem
Because of the difficulties felt by patients, sexual lies with the absent partner. Again, one needs to be
problems may not be overtly expressed but may very tactful so that the situation does not deteriorate
present covertly with another complaint which may because of the consultation! The attitude of the
well relate to the sexual organs, their function or doctor is probably more important than any specific
contraception. Careful medical historytaking to find knowledge or skill in treating sexual problems.
organic factors known to affect sexual response, such
as diabetes, major endocrine disorders, alcoholism Clinical examination can be an important part of the
and drugtaking is clearly important, assessment of sexual problems. The main purpose
may be to assess the part played by organic disease
-l
Sexual problems are partnership problems and in any complaint but examination may also serve to
should, whenever possible, be dealt with by educate the patient or to increase his/her sexual
confidence.
246
Sexua/ Dysfunction
Table 3. below presents an overview of abnormal examination findings ". Abnormal findings are more likely
in older women, in women with known gynecologic pathology or chronic systemic disease, and in women
who have not received regular,nndisalcare.
Table 3 Abnormal Physical E{al*Sfis$-on Findings Related to Female Sexual Dysfunction (Ref 13)
FINDING WTH{TIAL CAUSE SEXUAL SYMPTOMS
Genitourinary
Cystocele, rectocele, or Decreased desire (from

uterine prolapse embarrassment), dyspareunia
Fixed, retroverted uterus; Endometriosis Deep dyspareunia

nodules; tenderness
along uterosacral
ligaments
Hypertonicity of pelvic Vaginismus, vestibu litis Dyspareunia

muscles
Sparse pubic hair Low androgen level Decreased desire
Tender points along Vestibulitis Dyspareunia

vulvar vestibule
Vaginal discharge lnfection Dyspareunia
Vaginal or labial atrophy Low estrogen level Dyspareunia, decreased arousal
Vulvar skin abnormalities Lichen sclerosus, Dyspareunia

chronic candidal
vaginitis
Other
Abnormal blood Atherosclerotic peri pheral Decreased arousal

pressure or peripheral vascular disease
pulses
Galactorrhea Prolactinoma Decreased desire
Musculoskeletal Osteoarth ritis, rheu matoid Decreased desire, decreased

abnormalities arthritis, other arousal secondary to difficulty
musculoskeletal with sexual activity or
conditions embarrassment
Neuropathy Neurologic disorder, Decreased desire or arousal,

diabetes anorgasmy
Pallor Anemia Decreased desire or arousal
Thyroid enlargement Hypothyroidism Decreased desire or arousal
247
INVESTIGATIONS a recognized modality and is very widely used.

Laboratory evaluation is rarely helpful in guiding the to improve desire in both
Testosterone is reported
diagnosis or treatment of female sexual dysfunction. males (but not those with normal levels of the
However, a focused evaluation is appropriate, hormone) and in females. lt could be administered in
particularly if the history or examination su,ggests a the form of patches or as oral medication 'u' ".
medicalcondition'0. Androgenic side effects (acne, hirsutism, obesity)
may be encountered in females.
The urine should be tested for glucose in all men
presenting with secondary erectile failure or late - Female arousal disorder. This is the second ,]
onset ejacu latory problems. Su perficial dyspareu n ia commonest cause of sexual dysfunction in females.
in women may indicate the need for a variety of tests Failure of the lubrication/swelling response in women
including a vaginal swab and genito-urinary may result in dyspareunia, Iack of enjoyment,
screening. Pelvic ultrasound or laparoscopy may be resentment and withdrawal from sexual encounters.
needed in the assessment of deep dyspareunia. It may be particularly beneficial to ban sexual
intercourse for a limited time and to encourage
It is customary to measure serum testosterone, FSH, graded pleasuring exercises as a substitute once
LH and prolactin levels in men complaining of loss of
sexual arousal and enjoyment have been re-
sexual interest or erectile dysfunction but the results established the couple may regain the confidence to
are usually within normal limits. Alihough some enjoy intercourse again. The use of topical
experts advocate testing hormone levels in testosterone application is also advocated by some
postmenopausal women or in women with decreased
especially for post-menopausal women; its use in
desire or arousal, there is no reliable correlation pre-menopausal women is still being researched as it
between hormone levels and sexualfunction "''u. is shown to be of minim benefit.
TREATMENT Erectile Dysfunciton (ED). This is mainly a male

The general principles of treating sexual dysfunctions
disorder. Failure to achieve or sustain an erection
include:
could be treated by physical means such as
1. Consider treating the couple irrespective of mechanical aids to erection, or by intracavernosal
which partner presents
injections of vasoactive drugs. Sildenafil (VIAGRA)
2. Define the problem and what the couple
has been shown to work effectively in the treatment
would like to change
of erectile dysfunction. Sildenafil should be used with
3. Aim to reduce sexual anxiety
4. Facilitate communication between the caution because it could cause prolonged erection. lt
partners should also be avoided in persons with heart
problems as it could predispose to heart attack. Side
Specific problems may need specific treatment effects include dizziness, drowsiness, blurred vision,
programs nosebleeds, and difficulty sleeping.
Management of specific problems: Newer approaches to treating erectile dysfunction,

though not all are universally approved, include the
Hypoactive sexual desire disorder use of topical applications of androgel (testosterone)
This will entail management of the underlying cause. and Alprostadil (a vasodilator). A topical application
Endocrine abnormalities will be rare and more often of Viagra is also being considered,
the lack of desire is secondary to stress, fatigue,
depression, physical illness, drugs (e.g. alcohol) or Alternative treatments could also be tried; ginseng,
relationship difficulties. Medical and Medication pomegranate juice, and acupuncture have been
related causes must be sought for and treated. Once shown to improve erectile dysfunction. These
these reduced causes of sexual desire have been measu res a re recom mended especia I ly for those who
excluded attention can then be paid to the treatment wou ld want to avoid medications.
of HSDD. Psychotherapy is one treatment modality
where the expertise is available. Pharmacotherapy is Excessive sexual desire. Sexual behaviour in this
248
Sexua/ Dysfunction
condition is self-destructive and compulsive. Like reduction and re-education to control the ejaculatory
other addictions can lead to loss of family, money, job reflex are the basis for most therapeutic approaches
and even life. Specific management includes long- for men who are distressed by premature
term individual therapy and group therapy. Most ejaculation.
groups function along similar lines to Alcoholics
Anonymous with a 12-step recovery program. Other supportive measures that could assist in the
treatment of sexual dysfunction in both males and
Vaginismus. Treatment should aim to help the couple females are life style changes such as cessation of
to understand the nature of the problem. The wornan smoking, reduction in alcohol intake, eating healthy
should be encouraged to tackle the avoidance which diet rich in fruits and vegetables, and engagement in
is usually exhibited in any phobic condition and regular exercise. An improved communication in the
helped to embark on a system of graded exercises sexual relationship has also been shown to be useful.
(using fingers or dilators) while learning progressively
to gain control and relax the pelvic floor muscles DISCUSSION AND CONTROVERSI ES
(Kegel exercises). The partner's involvement and
encouragement in treatment are usually beneficial. l. Labeling the various dysfunctions has been an
Operative treatment is best avoided. ongoing debate in the field of sexology. Although it
may simply be a matter of semantics, labels are
Dyspareunia. ln male, it is rare but may be caused by important and often have a psychological impact.
lacerations from oversharp IUCD threads, pubic hair For example, most people refer to erectile
or from candida infection which may also affect the dysfunction as impotence. lt is a pejorative term
female partner. Treat the underlying cause. The implying that if the man is unable to have an
causes of female dyspareunia which may require erection, he is without power. Such terms should be
treatment include vulval conditions like herpes avoided.
genitalis, vulval candidiosis, urethral caruncle and
Bartholinitis. Vaginal conditions include atrophic ll.
Some men "compare notes" and patronize native
vaginitis, chemical vaginitis, infective vaginitis and doctors or herbal homes for local aphrodisiacs
vaginal scars. Pelvic conditions like pelvic whenever sexual dysfunction sets in. This perhaps
inflammatory disease, endometriosis and might account to the relatively small number of male
inflammatory bowel disease will deserve specific folks seen at the conventional clinics and hospitals.
treatment.
lll. lnterestingly, some women too especially those in
polygamous marriages use local herbs consumed
Orgasmic dysfunction. Many women do not
experience orgasm during sexual intercourse orally or inserted locally into the vagina to enhance
although some will subsequently'learn'to do so. This sexual performance. ln a culture that accepts
polygamy, women do what they think is right to keep
knowledge may be therapeutic to women who regard
themselves as inadequate because they require their spouses to themselves so as to remain in
additional clitoral stimulation to reach orgasm. The monogamous relationship and where that fails, they
capacity to experience orgasm may be helped by ensure that they win the husbands attention when
encouraging a couple to increase their sexual arousal they are in a polygamous relationship "''n. ln the
and by learning to relax and 'lose control' when high North-west region of Nigeria, it is referred in the local
levels of sexual arousal are reached. dialect as HAKIN MAYE. These alternative outlets of
consultation may also accountforthe apparently low
Premature ejaculation. The complaint of premature prevalence of complaints of sexual dysfunction in the
orgasm appears to be limited to men. After orgasm an orthodox gynaecological cl i nics.
erection is lost rapidly and the man remains
refractory to sexual arousal for a variable period. His lV. A new drug has been approved by FDA and is
being marketed for the treatment of low sexual desire
orgasm therefore usually terminates with sexual
intercourse whereas a woman is capable of multiple in pre-menopausal wcimen. This drug, Flibansterin,
orgasms without a refractory period. Anxiety is a serotonin receptor 1A agonisV2A antagonist that
works on serotonin in the brain. lt is said to be
249
effective in improving female sexual desire though to come out. Will it make our chances of conceiving
some argue that the benefit of using the drug does not less?' Answer is NO! All you need to get pregnant is
outweigh the risk and it should therefore be used with one motile, normal, sperm cell. What normally
caution. lts side effects include tiredness, nausea, happens after intercourse is that a lot of the ejaculate
difficulty sleeping, dry mouth and constipation'0. does leak out. Some of it, however, remains in the
posterior fornix and an even smaller amount makes
V. The husband of a couple that was being managed its way up through the cervix, into the uterus and
for infertility due to anovulation once asked: 'rDoctor, down the fallopian tubes where fertilization occurs.
how do I cope with this mandatory, timed coitus on So, the bottom line is that a woman does not need to
some specified days because my wife is on the lie in bed with her legs up after intercourse to get
Clomiphene drug?" Answer: "Take your own 'plll' pregnant and the fact that there was some semen
(aphrodisiac) on those mandatory days and better leak afterwards, does not decrease the chances of
still if she does not know the source of your new pregnancy. lt one of those myths associated with
strength". The couple reported three months later infertility!
looking excited. Ultrasound confirmed cyesis! (Prof
AAE Orhue, personal communication). Vll. Finally, Sexual Dysfunction is not a popular
examination topic at undergraduate level. However,
Vl. The wife of a couple that was being managed for at the postgraduate examination, a candidate is
lnfertility had this to say: 'My husband and I have expected to sustain some level of discussion on the
adopted the missionary position for best results, but I subject especially at the orals or short note sessions
have noticed that after intercourse the sperm seems when asked.
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25L
252
CHAPTE2S
The Female Breast

A O Omigbodun and T O Ogundiran
INTRODUCTION hormones, insulin, thyroid hormone and local

epidermal growth factor (EGF). The nipple and the
The breasts are secondary reproductive glands that areola enlarge and smooth muscle fibres surround
are a distinguishing feature of mammals. ln the the base of the nipples. The female breast consists of
human female, they symbolize womanhood and 15 to 20 lobes of glandular tissue of the tubulo-
femininity whilst also being the source of the milk alveolar type, with fibrous connective tissue and
that provides the initial nourishment to their adipose tissue lying between the lobes. The relative
offspring. The process of sucking the breast by the amounts of each of these components vary with age
offspring confers significant physiological benefits to and between individuals. The breast reaches the
the mother, provides passive immunity to the young zenith of its development at about 20 years of age. At
and enhances the bonding process between mother this period, there is more glandular tissue and the
and child. non-lactating breast is protuberant, conical and
sitting on a roughly circular base, which measures
DEVELOPM ENTAL ANATOMY OF TH E BREAST about 10 - 12 cm in diameter and 5 - 7 cm in
The breast develops as a modified sweat gland and
thickness. The base is directly on top of the
lies within the two leaves of the superficial fascia of
retromammary space, which forms between the
the anterior chest wall. lt starts as a bud in the superficial deep fascia and the deep (pectoral) fascia
thickened portion of ectoderm known as the milk line
of the thoracic wall. This smooth protuberance is
which courses from the pubis to the axilla in early
supported by the fibrous ligaments of Astley Cooper
fetal life. The milk line soon atrophies, leaving only
that are interspersed between the breast tissues,
the pectoral portion as the future nipple bud. There is
straddling the interface of the deep fascia and the
little or no additional development in both sexes in
dermis of the overlying skin. These ligaments also
the postnatal period. However in the female, further provide support and mobility to the breast. When
development of the breast tissue occurs in correlation
atrophic, they relax their support, the organ drops
with age and the reproductive hormones regulate and becomes pendulous as seen in olderwomen.
these changes.
The adult female breast extends from the second rib
The adolescent breast is composed essentially of
above to the sixth or seventh rib below along the
dense fibrous tissue within which are scattered ducts
midclavicular line and from the lateral boarder of the
that are lined with epithelium. At puberty, new ducts
sternum to the midaxillary line. A small stretch of
and lobular units are formed and the fibrous tissue
breast tissue extends superiolaterally towards the
stroma is replaced Iargely by fat, the main axilla as the axillary tail of Spence. The base of the
contributory factor to breast enlargement. This breast rests on portions of deep investing fascia of
process is under the influence of oestrogens, pectoralis major, serratus anterior, external oblique
progesterone, adrenal hormones, pituitary muscles and upper fibers of the rectus sheath. There
2s3
is more glandular tissue in the upper outer quadrant and nipple pigmentation, nipple enlargement and an
of the breast than does the remaindel of the breast. increase in the number and size of the lubricating
The blood supply to the breast is-derived from glands of the areola. ln late pregnancy, the adipose
branches of internal mamrTrarf:.@l!9, posterior tissue components of the breasts are almost
intercostal arteries and the axillary ffiry. fts venous completely replaced by glandular and ductal
d ra i n a ge fo I ows
I th e a rteri a I d istribtff't#ii elements. After delivery, the breasts begin to secrete
milk under the influence of prolactin and oxytocin. At
The lymphatic network of the b,reast is wide, weaning, the breasts rapidly return to an inter-
extending to the axilla, the internal mammary chain, pregnancy state, with a marked reduction in
the opposite breast and the anterior abdominal wall. glandular elements and an increase in adipose
The summit of the breast is made up of the nipple and tissue.
areola complex which is covered by-deeply At menopause there is gradual involution, regression
pigmented keratinised, stratified squamous of the glandular components, a decrease in the
epithelium. The lobules of the breast are drained by number of ducts and replacement of "the
ductules, which coalesce into a single duct that parenchymal elements by fat and connective tissue.
drains each lobule. The lactiferous ducts are The adipose tissue may or may not atrophy.
arranged radially in the longitudinal axis of the
breast, draining towards the nipple where they CLINICALAPPROACH TO BREAST MASSES
\
terminate in an ampullary dilatation beneath the
areola before opening into the surface of the nipple. A systematic approach to history taking as related to
The ducts are lined by contractile cells, which the breast and its function is essential to
continue into the areola and nipple and facilitate understanding the nature of any pathology that may
nipple contraction during sucking. The areola be present in the organ. The age of the patient is a
contains sebaceous glands, sweat glands and the major determinant of the kind of lesions that are
accessory areolar glands of Montgomery. The glands likely to be found. Detailed questions must be asked
are responsible for the lubrication of the nipples and about nipple discharge, including the type
they help to prevent cracks and fissures in the areolae (spontaneous or expressed), the colour, whether
and nipples. The tip of the nipple contains numerous unilateral or bilateral, whether it affects single or
sensory nerve endings. multiple ducts and so on. The relationship of
observed events to the reproductive cycle and
The non-lactating breast consists of more of fibrous menstruation must be carefully ascertained.
than glandular tissue with very few ducts. Structural
changes occur in the breasts that correlate with BREAST EXAMINATION
physiologic activities of the breast. The breasts, in
most women, undergo periodic changes during the Applying the appropriate techniques in breast
menstrual cycle. ln the premenstrual phase, there is
examination will yield clinical information that may
hyperplasia and hypertrophy of the acinar cells, the
be as valuable as any provided by the most
ductal lumina widen and there is a slight increase in sophisticated ancillary tests. Examination of the
breast can take the form of self-breast examination
breast size and turgidity. These changes are reversed
(SBE) or clinical breast examination (CBE). The
after menstruation.
former has the advantage that it can be done on a
During pregnancy and lactation, striking changes regular basis, by the same person on the same
occur in the glandular tissue and functional activities organs, making it easier to pick up abnormalities
of the breast with a significant increase in the size of early. The downsides include the need to ensure that
the breast. Progesterone from the corpus luteum and, the women are adequately traineci to do it
later on, from the placenta causes marked acinar competently, the problem of compliance and the
hyperplasia and hypertrophy and breast size and possibility of psychological defence mechanisms,
like denial, when a lesion begins to manifest. Women
-i
turgidity increase markedly. The circulating i
I
oestrogens stimulate a rapid expansion of the ductal should be advised to cairy out the process at least
system. There is areolar widening, deepening areolar once a month, after completion of menstrual
bleeding. The examination can commence with the
254
---.----t
The Female Breast
patient facing a mirror to inspect the symmetry of the . Skeletal Surveys and Bone Scans
breasts followed by a systematic feeling around the . ComputerisedTomography
organ. Unusual changes should be reported to health
. Newer investigational techniques such as
care providers prom ptly. Proton MR Spectroscopy', which is
a
particularly useful in differentiating breast
The conduct of the CBE by the clinician demands carcinoma from benign lesions
even more thoroughness. The examination should . Haematological and Clinical Biochemistry
start with inspection for symmetry and anomalies, Iests; These are needed to find out the extent
first with the patient seated with arms by her side, of disease effect on the patients'general state
then with arms pressed against the hips to tense the and to prepare them for major surgical
pectoralis muscles and finally with the arms raised procedures.
above the head. Palpation should start in this sitting
position, with the patient leaningforward and should CLASSIFICATION OF BREAST DISEASES
be completed with the patient in the supine position.
Non-Malignant Breast Diseases
When palpating in the supine position, the patient's
Congenital Diseases of the Breast and Ni pple
arms should be abducted. Each quadrant, the axillary
Amazia: This is a condition where there is absence of
tail and the peri-areolar areas should be carefully the breast. This can occur as an embryologic
scrutinised. Gentle expression of the breasts to
aberration due either to genetic abnormality or
observe nipple discharge should be done and the
maternal exposure to chemical or biological toxins in-
examination should be concluded with an
utero. ll may be associated with absence of the
examination of the axillary and supraclavicular lymph
underlyi ng pectoral is major muscle,
nodes.
Polymazia: There may be extra or accessory breasts,
ANCILLARYAIDS
which may be unilateral or bilateral. These may
Ancillary tests are very helpful in confirming the
develop along the milk streak and may be with or
nature of breast lesions. The modalities that are
without nipples. When it extends to the axilla, it
commonly employed forthis purpose include:
manifests as a prominent axillary tail of Spence.
- - They tend to enlarge when the normally situated
t Ultrasonography: This is being increasingly used
breasts enlarge.
to determine the nature of breast masses.
Biopsy
a
I Fi ne- Need le Aspi ration
Athelia: This is a situation of congenital absence of
one or both nipples. lt is commoner in males.
I
lncisional
!
Excisional
I Biopsy can be guided ultrasonically Polythelia: Where there is presence of more than a
( pair of nipples, with or without supernumerary
(intraoperative ultrasonographically guided
I
excisional biopsy or IUGEB), especially breasts.
I
when the masses are non-palpable'.

Postn ata I Deve lopmenta I Anoma I i es
. Radiological Nipple Retraction: Failure of nipple eversion may
. Mammography - One of the most widely used occur right from birth or may become manifest at
screening tools for malignant breast lesions. puberty when the nipple fails to grow pari passu with
Mammography is reputed to detect breast the breast. lt may affect one or both nipples. Such
cancer earlier than breast self-examination, nipples are prone to excoriation. During lactation, the
and purportedly reduces the risk of death from infant finds it difficult to suck from such breasts,
breast cancer by approximately 30% in women creating a fertile ground for breast engorgement and
over 50 years old '. lts limitation lies in the fact mastitis. Recent onset of nipple retraction in a fully
that cancer, like breast tissue, appears white developed breast may be a manifestation of
on the x-ray and lesions may be difficult to underlying diseases of the nipple or of a scirrhus
t detect in women with very dense breasts, carcinoma.
. ChestX-rays Mammary Hypertrophy; Overgrowth of glandular
255
The Female Breast
Fai Necrosrs; This is a rare breast lesion that is often Breast Neoplasia of l-ow Malignant Potential
presumed to be a result of trauma although less than Cystosarcoma Phylloides; This is considered to be a
half of affected individuals volunteer,a h*s*ory of type of fibroadenoma, but one where the cellular
physical injury to the breast. lt p '*: #.lss component tends to proliferate aggressively. This
I
which is sometimes tender and has an ffi trea may give rise to a mass much larger than is usually
of erythema or ecchymosis. Treatnrmr*,.b .w#ly seen with fibroadenomata. Treatment is usually by
expectant as the mass gradually disaprs. tf the wide local excision, including a margin of healthy
mass persists, a fine-needle aspiration. biqsyor an breast tissue. Although the tumour is rarely
excisional biopsy should be considered. malignant, it may recur locally if inadequately
excised and some have advocated the use of simple
PreMalignant Breast Diseases mastectomy in such situations. ln cases where there
is evidence of malignant change, simple mastectomy
Presu med P re M a I ign a nt Lesion s is usually sufficient to deal with the problem.
Fibrocystic Disease of the Breast: This disease has
several synonyms including cystic mastitis and Malignant Breast Diseases
chronic mammary dysplasia is generally accepted as
the most common non-malignant neoplastic lesion of Carcinoma of the Breast
o
the breast lt is common in women in the latter part Cancer of the breast is rapidly overtaking cervical
of the reproductive years but rare after menopause, cancer as the commonest malignant epithelial
n.
suggesting some relationship to ovarian hormonal tumour in women living in West Africa What makes
activity. the situation more alarming is the fact that it seems
to be afflicting women in a younger age bracket than
The lesions are almost always associated with had hitherto been the case. Other epidemiological
epithelial changes in the breast acini and ducts. Such risk factors that have been identified in this
: changes include adenosis, papillomatosis, ductal environment include obesity, being taller, higher age
epithelial hyperplasia and cyst formation. There is at first pregnancy and lactation, higher total number
also a marked increase in fibrous tissue component in n''0.
of births and previous use of oral contraceptives
I
affected portions of the breasts. Affected individuals ln spite of advances made in identification of high-
usually have ill-defined masses in the breasts. Pain or risk grou ps for screening, detection rates for the early
/
I
I
tenderness may be the triggering factors in treatable stages of the disease are still
recognising the presence of the lumps and the disappointingly low. Specific genetic abnormalities
masses tend to be associated with greater discomfort affecting the BRCA-1, BRCA-2 and other genes,
t
and enlargement in fhe pre-menstrual phase of the which make women more susceptible to developing
I reproductive cycle. ln some women, mastodynia can the disease, have been identified and newer more
I
be quite severe and unrelated to phases of the effective treatment strategies are being devised. Yet,
I
i menstrual cycle. Sometimes, the lumps disappear mortality rate from breast cancer continues to rise.
t
( spontaneously, only to re-appear again after several
months. The main clinical features of the disease are solitary,
I
'| non-tender, firm or hard breast mass, coupled with
Mammography may be helpful in distinguishing bloody nipple discharge, distortion of breast
i
:
fibrocystic disease from breast cancer, but symmetry, axillary lymph-node enlargement and, in
sonography and fine-needle aspiration biopsy the latter stages, ulcerative or fungating breasi
(FNAB) are generally more helpful in distinguishing tumours. Some patients may complain of itchy
between the two. Where there is doubt about the nipples, hardness of the breasts or an axillary
nature of the lesion, an excisional biopsy may be of swelling. Occasionally, lymphoedema of the arm is
fibrocystic breast disease. There is now sufficient the first indication to the patient that something was
evidence to support the contention that the lesions amiss. Majority of the patients seen in West Africa
substantially increase the risk of breast cancer in present very late in the course of the disease " ln the
sufferers and it is important that the patients be re- clinical evaluation of these peltients, it is important to
I
,' examined at regular intervals to ensure that appreciate that breast cancer is essentially a
malignant change has not occurred. systemic disease and the size of the primary tumour
r 257
:
-
should not determine the extent to which sites of

secondary deposits are sought. Even a very small Radiotherapy; Radiotherapy has been shown to be
primary lump in only one breast may be' jated very effective in destroying primary lesions and
with widespread dissemination o1 61t!ffiffi8s. secondary deposits and this, coupled with better
Clinical evaluation should commence':ffit[ im understanding of the biological behaviour of the
assessment of the local lesion and the regbta#Brmh tumours, has led to a radical change in the approach
nodes, followed by a search for occult lesions in the to management of the disease. The general tendency
other breast. Finally, a systematic search for now is to pursue less radical surgery and sterilise the
secondary deposits in other organs should "be remaining tumour deposits by irradiation.
conducted.
Radiotherapy can be used as an adjuvant after
ln taking the history, special attention must be paid to resecting primary tumours or in the neoadjuvant
the reproductive history including menarcheal age, mode for the purpose of local control cum
gravidity and parity, breastfeeding and weaning downstaging before proceeding to other modalities of
practices, a family history of breast or other cancers treatment. lt is also useful in eradicating discrete
and the presence of symptoms such as back pain that metastases and treating locally recurrent disease. lt
may suggest bone metastases. may also be haemostatic in patients bleeding
excessively f rom fun gati n g or u I cerative tu mou rs.
I es of M a n a ge ment:
P ri nc i p Chemotherapy; Chemotherapy is primarily used as
The first step is to determine the clinical stage of the adjuvant therapy in patients who have had surgery
disease using the tools of physical examination and and primary radiotherapy, the objective being to
ancillary tests as enumerated earlier. Thereafter, destroy any occult tumour deposits. Occasionally, it
histological diagnosis should be established as soon assumes a neoadjuvant role, particularly in
as possible. The hormone receptor activity status advanced metastatic lesions. Appropriate
should also be determined. Clear goals of treatment combinations and sequencing of chemotherapeutic
should then be set out. ls it aimed at cure or agents is still a subject of controversy among surgical
palliation? oncologists and several trials are ongoing to try to
resolve some of these issues.
Surgical Treatment:
Surgery can be both diagnostic and therapeutic in Hormonal Therapy: Hormonal therapy may take an
that the full extent of tumour spread may not be additive or ablative form. The use of selective
apparent until surgery isdone. One of the major aims oestrogen receptor modulators such as tamoxifen
of surgery is the extirpation of tumour at the primary has gained widespread acceptance. Hormonal
site and the regional lymph nodes. There may also be manipulation can also take the form of ablative
need for breast reconstruction where the breast is surgery such as bilateral oophorectomy "or the use
being conserved. Breast reconstruction may be of drugs that inhibit steroid hormone biosynthesis
immediate (as is done for most patients) or may be such as aminoglutethimide and aromatase inhibitors
delayed. like letrozole ". For societies where povefi is
prevalent and access to consistent supply of drugs is
The therapeutic surgical options include radical not assured, surgical ablation may be the most cost-
mastectomy (removal of the affected breast, effective approach. Hormonal manipulation is
ipsilateral axillary lymph nodes and the underlying usually more successful in pre-menopausal women
pectoralis muscles), extended radical mastectomy but where oestrogen receptor status is known, it is
(which adds removalof the internalmammary lymph equally effective in pre-menopausal and post-
nodes to the standard procedure) or modified radical menopausal women.
hysterectomy, which omits removal of the pectoralis
muscle. Other options are simple mastectomy' What is Optimal Therapy? This is still a subject of
segmental mastec'tomy, quadrantectomy and considerable controversy. Partial mastectomy with
lumpectomy. With the realisation of the systemic axillary dissection and adjuvant radiotherapy seems
nature of breast cancer, opinion in recent time has to be adequate initial therapy for most patients in
shifted more towards less radical surgery. whom a curative approach is taken. Follow-up
258
T
t
I
The Female Breast
I
f
I chemotherapy to deal with occult tumour deposits is
t
r often employed along with these measures. Radical The other goal of follow-up care is to offer breast
hysterectomy should only be considered when there reconstruction to patients who have undergone
is evidence of tumour infiltration of the pectoralis mastectomy. Such reconstruction ought to be
F muscle and there is no clear-cut evidence,of distant discussed with the patient prior to mastectomy and
t metastases. the appropriate prosthesis selected. This has been
!' shown to improve the psychological health of
t Fotlowup Care: After completing the initial course of patients in the aftermath of the operation.
treatment, patients with carcinoma of the breast have
i to benefit from life-long follow-up care. The main nt Breast Tu mou rs
Other M a I i gna
objectives of such care would include the detection of Other malignant tumours such as sarcomas,
recurrence and the identification of new tumours in lymphomas and metastatic deposits from primary
the contralateral breast, an event that can be tumours in other organs are known to occur, but they
expected in up to 15% of patients. The incidence of are extremely rare and the approach to their:
I
local recurrence varies from 10 to30% depending on management does not differ significantly from that of
the original tumour size, number of axillary and other carcinoma of the breast. Prognosis may however be
lymph nodes involved, the histologicaltype and grade much worse, particularly when dealing with
of the tumour as well as the presence or absence of sarcomas.
pectoral is muscle infiltration by tumour.
{
I
a
r
I
I
f
r
I
I REFERENCES
r
I
)
1. Chen SC Yang HR, Hwang TL, Chen MF, Cheung growth at long-term follow-up. Radiology, 2003;
I
YC, Hsueh S. lntraoperative ultrasonographicalty 229:233-238.
( guided excisional biopsy or vacuum-assr'sted core B. Khanna AK, Tapodar JK, Khanna HD, Khanna S,
fI needle biopsy for non-palpable breast /esions. Khanna A. Behaviour of estrogen receptor,
t
Ann Surg, 2003;238: 738-742. histological correlation, and clinical outcome in
It-
( 2. Wright T, McGechan A. Breast Cancer : new
I
patients with benign breast disorders. Eur J
r technologies for risk assessment and diagnosis. Surg, 2002; 168: 631-634.
r Mol Diagn. 2003; 7: 49-55. 9. Adebamowo CA, Ajayi OO. Breast Cancer in
7
I Tse GM, Cheung HS, Pang LM, Chu WC, Law BK, Nigeria. West Afr J Med, 2000; 19: 179-191.
t
( Kung F\ Yeung DK. Characterization of lesions of 10. Adebamowo CA, Adekunle OO. Case-controlled
{' the breast with proton MR spectroscopy: study of the epidemiological risk factors for
(
comparison of carcinomas, benign lesions, and breast cancer in Nigeria. Br J Surg, 1999; 86:
phyllodes tumors. AJR Am J Roentgenol, 2003; 665-668.
t
;
181: 1267-1272. 11. lkpat OF, Ndoma-Egba R, Collan Y. lnfluence of
Adesunkanmi AR, Agbakwuru EA. Benign breast age and prognosis of breast cancer in Nigeria.
drsease at Wesley Guild Hospital, llesha, Nigeria.
i West Afr J Med, 2001; 20: 146-151.
East Afr Med J, 2002; 79: 651-657
- 12. Omigbodun AO, Adebamowo CA.

Anyanwu SN. Fibroadenoma of the breast in M i n i I a pa rotomy oop ho rectomy for N i ge r i a n s w ith
a
Nigerian /gbos. S Afr Med J, 2000; 90: 1223- breast cancer. Presented at the XVI FIGO World
1226. Congresg September 2000, Washington DC,
El-Wakeel H, Umpleby HC. Systematic review of USA (Abstract FCS.02.09). lnt J Gynecol Obstet,
fibroadenoma as a risk factor for breast cancer. 2000, 70 (Supplement 1); Section 5: Pg 17.
Breast, 2003; 12: 302-307. 13. Goss PE, Strasser K. Aromatase inhibitors in the
b 7. Gordon PB, Gagnon FA, Lanzkowsky L. Solid treatment and prevention of breast cancer. J
I breast masses diagnosed as fibroadenoma at Clin Oncol. 2001;19: 881-894.
,
."
fine-needle aspiration biopsy: acceptable rates of
259
260
:
CHAPTE24
i.'
Endoscopy in Gynaecology
J lkechebelu and J Okohue
Endoscopy is the process of visually examining the formed the first diagnostic laparoscopy on a dog
internal structures of the body with the aid of an using air to achieve pneumoperitoneum.'-' Zollikofer,
endoscope. in 1925 introduced the use of carbondioxide (C0r)
instead of air because it does not supports combus-
HISTORY tion like air.''' The use of C0, paved the way for
therapeutic laparoscopy procedures and C0, has
Endoscopy dates back to 400 BC during the time of
remained the gas of choice for establishing
Hippocrates, he had used speculi to examine the pneumoperitoneum in modern day endoscopy
vagina and rectum of his patients.' Following intesti-
surgery.'
nal obstruction, Hippocrates had advocated the
injection of a large volume of air into the intestines via ADVANCEMENT !N INSTRUMENT DESIGN
the anus as a remedy.' He was known to have
managed several life-threatening conditions using The 20'n century witnessed a rapid advancement in
minimally invasive approaches.' instrumentation to meet up with the unfolding
knowledge.
Giulio Cesare Aranzi was credited as the first person
to use a light source for endoscopic procedures. ln The trocar and cannula was developed by Nordentoft
1585 he began focusing sunlight through a flask of in 1972 and further improved to the pyramidal point
water and projecting the light into the nasal cavity.' trocar by Orndoff in 1920.'3 Janos Veress of Hun-
While Philip Bozzini developed an instrument he gary in 1932 developed a specially designed spring
, called Lichtleiter that could be introduced into the loaded needle which he used while working with
human body to visualise the internal structures. tuberculosis patients to help induce a
Antoine Jean Desormeaux, a French surgeon was pneumothorax. lt was in 1938 when he published
credited as being the first to introduce this instrument his invention that the needle became more broadly
/ into a patient. ln 1853 Desormeaux further devel- known outside of Hungary." Raoul Palmer would
oped the Lichtleiter and termed his device the later introduce the needle in laparoscopy to establish
ENDOSCOPE.,s a pueumoperitoneum. The present day insufflation
needle is called Veress needle after Janos Veress.'
The first hysteroscopic procedure was credited to
Commander Pantaleoni who in 1869 used a modi- The use of diathermy was introduced by William T.
fied cystoscope lit with reflected candle light to Bovie in 1928.'This allowed for tissue cutting and
examine the uterine cavity of a patient with post- coagulation and has advanced into the modern day
menopausal bleeding. He blindly cauterised a electrosurgical unit. Kurt Semm, a German gynaeco-
haemorrhagic uteri ne growth usi ng si lver n itrate.' logist, in 1963 developed the automatic insufflating
i
t-
device that monitored intra abdominal pressure and
:
George Kelling, a German surgeon in 1901, per- gas flow and this greatly overcame the challenge of
a
:
: 26t
using syringe to intermitently introduce gas.2'4 surgery. The old paradigm that'a big incision meant a
big surgeon' has drastically changed as a result of
The endovision system involving the telescope, light endoscopic surgery.
source, camera and monitors evolved slowly with
,..b
contributions from several inventors and company Endoscopic surgery arguably has the following
experts as technology advanced to its present day advantages over the conventional open surgery.''u''
form.''' However, in the 1960s, credit will be given to 1. lmproved diagnosis: Endoscopy allows a 360
Harold Hopkins, a British physicist who first devised degrees view of the abdomen (laparoscopy) unlike
an optic system that used quartz rod-shaped lenses in open surgery where you are limited to the site of
and Karl Storz who built on existing fibre optics to incision. The structures are also magnified making
develop the cold light technology.'This Hopkins rod visualisations better than in normal view used in
lens system is still in use in present daytelescopes. open surgery. Therefore, diagnosis is better with
laparoscopy.
ADVANCEMENT IN ENDOSCOPIC SURGERY
The practice of endoscopic surgery was driven by the 2. Tissue dissection and disruption: Access points or
instrument designs. The first therapeutic laparoscopy port wounds in endoscopic surgery are small with
-adhesiolysis-was performed in i933 bya German minimal tissue damage, unlike the large incisions
Surgeon -Fervers.'Thiswasfollowed in 1936 bythe used in open surgery. Dissection of tissues is also
first laparoscopic sterilization by Bosch. ln 1937, precise in endoscopy compared to the tearing of
Hope diagnosed ectopic pregnancy by laparoscopy.' tissues in open surgery.
ln 1983, Semm, performed the first laparoscopic
appendectomy.' The great leap in gynaecological 3. Wound infection: This is less in endoscopic
endoscopy came in 1989 when Reich and his team surgery because of tiny skin incisions and less
performed the f i rst I a pa rosco p ic hysterectomy.' tissue dissection. The use of C0, pneumoperito-
neum which has antiseptic properties is an added
The first robotic arm was designed in 1994 to hold advantage to endoscopic surgery in the control of
the telescope with the aim of improving safety and infection.
obviating the need for a skilled camera operator. By
the beginning of the new millennium, specifically in 4. Risk of Adhesions: There is less risk of adhesions
the year 2000, the Food and Drug Administration in laparoscopic surgery because the target of
(FDA) in the USA approved the Da Vinci surgical operation is distant from the point of entry. This
system and the following year, the first ever transat- means that the place where the parietal and
lantic surgery was performed.' Michel Gagner and visceral peritonea are breeched are not apposed to
Jacques Marescaux stationed in New York, per- each other unlike in open surgery. ln addition, the
formed a cholecystectomy in a 68-year old woman in trauma to the peritoneal surfaces is minimal in
Strasbourg, France.' laparoscopic surgery.
The development has continued and virtually all 5. Post-Operative Pain: There is less pain post
gynaecological surgeries performed by the open operatively following endoscopy than open
approach can now be performed laparoscopically. surgery due to minimal tissue dissection, small
port incisions and hence minimal damage to
ADVANTAGES OF ENDOSCOPY OVER OPEN nerves and nerve endings.
SURGERY
6. Surgery associated complications: These include:
Open gynaecological surgery is the conventional thromboembolism, pneumonia, fluid mainte-
surgery most gynaecologists are trained on. lt is time nance challenges etc, occasioned by prolonged
tested, less costly to set up and minimally dependent stay in bed and nil orally as common in open
on technology unlike endoscopic surgery which is surgery. These are less in endoscopic surgery due
relatively new and heavily dependent on technology. to early ambulation, early initiation of oral intake
Open surgery is also easier to learn and practice and return to normal activities.
compared with the long learning curve in endoscopic 7. Time of Return to workr Most endoscopic surger-
262
5. Light Source' for the specific function the instrument is meant to

In the past, the Halogen light source was popular but perform and the name is derived from the jaw. Most
this was largely replaced by the Xenon light source of the laparoscopic hand instruments are special
which emits a more natural light. Re@,htost adaptations of ones used in conventional open
endoscopic equipment manufacturers fr *$ryl surgery. Generally, they are reusable instruments
over to the Light Emitted Diode (LED n*rhruHi*mtfts though some of the instruments are available as
white light with more superior quality arid tffiW life disposable.
span.
LAPAROSCOPY
6. Fibre Optic Cable''' ln gynaecological practice, laparoscopy is performed
This transmits light from the light source to the for numerous procedures which traditionally were
telescope. lt contains optical fibreglass which can be performed via laparotomy. The indications can be
easily broken especially if the curvature radius is bent for both diagnostic and operative (therapeutic)
less than 15 cm. Because of the risk of burns to purposes. The conventional or robotic options are
patients, it should never be left on while resting on available.
surgical drapes or patients'skin.
1. lndications for Diagnostic Laparoscopyu' "' "
7. lnsufflator'''o . lnfertility evaluation
This is used to create a carbondioxide . Endometriosis (diagnosis and staging)
pneumoperitoneum during laparoscopy. A special . Chronic pelvic pain
type of insufflator (low flow - hysteroflator) is equally . Evaluation of pelvic/adnexal masses
used to deliver carbondioxide gas into the uterine . Diagnosis of unruptured ectopic pregnancy.
cavity for diagnostic hysteroscopy. Technology has . Evaluation of primary amenorrhoea.
moved from analogue to digital, micro-processor
. Second look in ovarian cancer treatment.
automated insufflators that regulate the intra-
abdominal pressure at a preset value.
2. lndications for operative (therapeutic)
laparoscopyu' "' "
8. lnfusion Pumps'o A. Fallopian tubes
These are of immense importance during o Femalesterilisation
hysteroscopic procedures as they help in delivering o Ectopic pregnancy
distension fluids into the uterine cavity for proper o Salpingectomy, Salpingostomy,
visualisation. There are manual and automated Salpingolysis
pumps. Automated pumps deliver fluids continu- B. Ovaries
ously at a given rate and pressure and are preferred in

o Ovarian cystectomy or Ovariectomy
operative sessions.
o Ovarian drilling in treatment of
PCOS.
9. Trocar and cannulat'n o Su rgery for ovarian mal ignancy

They are the access via which the surgeon estab- o Biopsies
lishes communication with the abdominal cavity C. Uterus
during laparoscopic surgery. They come in different
o Hysterectomy (including radical
sizes (5mm to 10mm) and could be disposable or re-
hysterectomy)
o Myomectomy
usable. The tip of the trocar can be blunt or sharp.
The blunt trocars are used in open access techniques
o Fixation surgeries for Uterine
prolapse
while the sharp trocars (pyramidal or conical tip) are
D. General/Peritoneal
used in closed access entry techniques. Other types
of trocar include the rad ially expanding trocar and the
o Endometriosissurgery.
visual (optical) trocar.

o Operations in early pregnancy e.g.
appendectomy, cystectomy etc
1 0. Hand instrumentsn'"
o Adhesiolysis
These are instruments used in performing the
E. Urinary incontinencesulgeries
surgery. The jaws or working elements are designed

F. Almost any gynaecological surgery per-
264
formed by open approach can be done phrase "Physician know thy limit" is very much
laparoscopically applicable in laparoscopic surgery. You must be well
trained in what you do or the patient is exposed to
3. Contrai ndications'o avoida ble da nger from the su rgeons i ncom petence.
Contraindications are mostly relative B#hp{Eving
skills and better instrumentations h the 4. Patient selection/Preparation
situations where laparoscopy surgery may be A good patient selection is key to a successful
hazardous to the patient. laparoscopic surgery. There must be a clearly
defined indication. The patient should be properly
Relative contrad ictions w i I I i nc I ude : counselled on the procedure and the risk of conver-
Pregnancy. Surgeries are generally avoided in sion to laparotomy disclosed. Obtain a signed
pregnancy except in emergencies. Where surgery is informed consent for the procedure.
indicated, laparoscopy approach is preferred in first
half of pregnancy and chances of continuation of the Bowel preparation priorto laparoscopic gynaecologi-
pregnancy post-surgery is more after laparoscopy cal surgery is optional'u and any umbilical jewellery'
than open surgery. However, in late pregnancy, must be removed before laparoscopic surgery."
laparoscopy wi ll not be feasible.
lr Previous extensive abdominal surgery due to the risk
Positioning includes placing the patient in the Lloyd-
Davies or half-lithotomy trendelenberg position.u'" lt
of adhesions and injury to internal organs (particu- is important to place the patients properly to avoid
larly the intestines) adherent to the anterior abdomi- neural injury. The patients arm are tucked by her
:
, nal wall. Open access techniques and use of Palmer's sides preferablywith the palms facingthe thighs. For
pointforVeress needle insufflation has been shown to ease of uterine manipulation, it is advisable for the
minimize this risk.'u Also experienced surgeons will buttocks to be a few centimetres beyond the edge of
: still gain access and repair any injured intestine. lt is the table. An indwelling catheter reduces the risk of
argued that laparoscopy in these situations are safer bladder damage during insufflation and trocar entry.
? or betterthan open surgery. At start of laparoscopy, the gynaecologist usually
stands on the patient's left side although occasion-
, Pelvic mass greater than 20 weeks gestation due to
I ally he/she might change positions during surgery,
I
limited space for manipulation of instruments.
However, most laparoscopic surgeons will agree that 5. Anaesthesia for laparoscopy surgery
, the primary consideration will be the mobility of the Optimal anaesthetic care of patients undergoing
i
I
mass rather than the 5ize. laparoscopic surgery is vital as challenges may arise
l/
V
I
from the cardiopulmonary effects of
Generalised Peritonitis. This is to avoid dissemination pneu moperitoneu m, CO, a bsorption, extra peritonea I
of the infection that may lead to septicaemia. gas insufflation, venous embolism, and iatrogenic
injuries to intra-abdomi nal organs.'
Severe chronic obstructive pulmonary disease
(COPD). This will affect patients respiratory indices Early detection and prevention of rapid systemic
which are already compromised by the use of changes in these patients during laparoscopic
pneumoperitoneum and trendelenberg position. surgery is essential to safety. To achieve this,
multiparameter monitor (ECG, respiratory rate,
Hypo and hypercoagulable state. ln conditions with
Pulse, Blood pressure, SpOr, Temperature, Cardiac
bleeding disorders, laparoscopy will be life threaten-
r output and EICO,) must be used on all patients
?
I
ing as control of bleeding by coagulation will be undergoing surgery. Standard anaesthetic machines
I
? difficult but not impossible. with ventilator to ensure airway pressure monitoring
I
is indispensable. ln all these, an anaesthetist with
Absol ute contn - i nd icatrons i ncl ude:
experience in endoscopic surgery must be available
One absolute contraindication in our view is inexperi-
\:. enced surgeon.'o One should select patients accord-
to ensure safe laparoscopy surgery.
ing to one's skill and available instruments. This

General anaesthesia with endotracheal intubation
t
lt
t,
7 265
and use of intermittent positive pressure ventilation is the abdominal cavity if the Veress needle is
ideal for operative laparoscopy. ln diagnostic laparos- correctly placed and vice versa.
copy, use of local and general anaesthesiarlrith face (v) lnitial intraperitoneal pressure (manometric
mask alone orsimple ketamine anaesthesla llffibeen test): The most reliable test. lf the gas is
reported to be safe.'n ' , flowing freely inside the abdominal cavity,
there should be a pneumoperitoneum with a
Similarly, regional (spinal) anaesthesia. has Mn slow increase in actual pressure.
reported for both diagnostic and operative laparos-
copy without sign if icant com pl ications.'o Direct access technique. This technique is gaining
acceptance and involves introduction of a sharp
6. Abdom i na I Access sites/ Tech n iques trocar directly into the abdominal cavity via an
There are various access sites into the abdsminal appropriate size skin incision. There is no prior
cavity. The commonest entry site for the primary port creation of a pneumoperitoneum and Veress needle
is through the umbilicus. lt can be trans-umbilical, is not required."'"
inferior or superior crease of the umbilicus ol'supra
umbilical. Othersites includethe Palme/s point (2-3 Open (Hasson's) access technique' This is akin to a
cm below the left coastal margin along the mid- minilaparatomy. A 2cm incision is made around the
clavicular line) and rarely through the vagina or umbilical area and tissue dissection carried out up to
uterus. The entry techniques in use include: the level of the fascia, which is also incised. The
peritoneal cavity is entered and the surgeon uses his
C/osed access technique. Here a Veress needle is index finger to rule out adhesions around the port
inserted blindly to create a pneumoperitoneum site. Two rectus fascial stay sutures are applied and
before introduction of the trocar/cannula."'" lt is tied around the Hasson's cannula."
about the commonest method used by gynaecolo-
gists. A high insufflation pressure(2O - 25mmHg) is Radially expanding access technique. A Veress
now commonly used at the time of trocar insertion. needle in a radially expanding sheath is introduced
Some test can be performed to confirm safe Veress via the conventional means. The Veress needle is
needle insertion and they dre;5'21 then removed (after creating a pneumoperitoneum)
leaving behind the radially expanding sheath,
fl) lrrigation test: lnject 5 - 10 ml of normal another larger diameter trocar is introduced, further
saline via the Veress needle. The fluid should expanding the diameter of the sheath until it is large
flowfreely. enough to accommodate the laparoscope.
(ii) Aspiration test. The fluid introduce during
irrigation test should not be recoverable. Visualaccess technique. This allows the surgeon to
Aspiration of more fluid, blood or faecal visualize all the layers of the abdominal wall during
material indicate wrong Veress needle port insertion, visually confirming when the abdomi-
placement. nal cavity is entered.
(iii) Needle movement test: Veress needle should
move freely when touched gently. Vigorous Two systematic reviews of umbilical entry techniques
movement can result to injury of the internal concluded that there is no evidence that one
organs. approach is superior to another."'"
(iv) Hanging drop/Plunger test. ln the hanging
drop test, a drop of fluid placed at the top of Seandary Trocar placement.' These are the working
the Veress needle should be sucked on lifting ports and the trocar is inserted under direct vision to
the abdominal wall because of the negative prevent injury to internal structures." A surgeon can
intra-abdominal pressure, The Veress needle decide to introduce ipsilateral or contralateral ports.
is wrongly placed if this does not happen. To avoid injury to nerves or blood vessels (ilioinguinal
This same principle holds for the plunger test and iliohypogastric fl€rv€s; superficial and inferior
where the syringe is filled with normal saline epigastric arteries), the lower quadrant ports are best
or sterile water and the plunger removed. introduced approximately 2cm medial and 2cm
The column of fluid will passively drain into superior to the anterior superior iliac spine lateral to
266
the border of the rectus muscle. Other ports are aspiration, hanging drop, plunger or manomet-
placed as deemed necessary. For diagnostic laparos- ric tests.
copy, a single suprapubic or left lateral secondary Step 12. Connect insufflation tube to the Veress
port might suffice. needle to create pneumoperitoneum at preset
pressure of 10 -14mmHg.
7. Diagnostic laparoscopy with Dye test Sfep 13. Stop the gas flow when desired abdominal
This is the cornmonest laparoscopic procedure pressure is attained and remove the Veress
performed by the gynaecologist. The dep by step needle.
description of this procedure is provided here as a Step L4. Extend the stab incision to 1-1.5cm
standard guide to laparoscopic surgery. Step 15. lnsertion of Primary 10mm trocar and
cannula. Hold the trocar in the proper way and
Sfep I. Ensure surgical and anaesthetic team insert through the incision while the other hand
readiness
lifts the full thickness of the lower abdominal
Step 2. Ensure power on all endoscopic units prior to wall. lnsert gradually using rotary movement
i nduction of anaesthesia. directed to the coccyx. Ihis step can be done
Step 3. Patient is placed in the supine position and without prior pneumoperitoneum - direct
selected a naesthesia ad m i n istered trocar insertion as step 10.
Step 4. Patient is repositioned to half-lithotomy or Sfep 16. Feeling of loss of resistance and hissing
Lloyd Davis position. sound (if re-usable trocar) indicates the trocar
Sfep 5. Routine abdominal skin preparation (wet, is in the peritoneal cavity. Then remove the
wet, dry, spiriViodine) and vaginal cleaning trocar and advance the cannula alone.
(wet, wet, dry) is done and sterile drapes Step L7. The insufflation tube is re-connected to the
applied exposing only the peri-umbilical area appropriate channel on the cannula. Then re-
and perineum. start the flow of gas.
I Sfep 6. The surgeon at the time of access should Sfep 18. The laparoscope fitted with the light cable
stand on the left side of the patient (or right side and camera head is introduced via the cannula.
L
if surgeon is left handed). Sfep rg. First examine the site below the entry of the
Step 7. Vaginal procedure: Assistant exposes the primary port, followed by panoramic view of
cervix with a Sims or Graves speculum and the peritoneal cavity and then specific struc-
i
picks the anterior lip with a tenaculum in the tures.
I transverse plane. Sound the uterus and then Step 20. Secondary port may be placed under direct
pass the uterine cannula and anchor to the vision if extra instrument is required for full
tenaculum. Remove the vaginal speculum. exploration of the pelvic organs.
Sfep 8. Assemble all the cables and clip them in Step 2l.lnject methylene blue dye (normal saline or
position (anchored to the drapes). These indigo can be used) via the uterine cannula and
include the light source fibre optic cable, observe for spillage from the fallopian tubes
insufflator tube, camera headlcable, suc- into the peritoneal cavity.
tion/irrigation tubes and monopolar/bipolar Step 22. The dyeifluid in the peritoneal cavity is
cables. sucked out with suction/irrigation apparatus.

Sfep 9. Make a stab incision on the umbilical area Step23. Biopsiescan betaken if required.
(Trans-umbilical, inferior or superior umbilical Step 24. At the end of the examination, remove the
instruments and cannula from the secondary
crease,) with a sharp pointed blade size 11 on
port under vision to exclude bleeding from the
No 3 Bard-Packer handle (Supra-umbilical site
port wound.
or Palmer's point should be considered if there is
Step 25. Remove the telescope and allow gas to
lower abdominal mass or midline scar).
escape. Replace the trocar half way into the
Step IO. lnsert the Veress needle aiming at the
cannula before removing the primary port
coccyx while lifting the lower abdomen with the
cannula (alternatively remove the cannula with
left hand until a'give'isfelt.
l Step 1.1. Perform tests to confirm safe Veress needle
the telescope in situ to prevent herniation of
omentum).
position: vis - Needle movement, irrigation /
Step 26. Close the port wound with staples or
267
absorbable suture material (sub-cuticular 8. COMPLICATIONS OF LAPAROSCOPIC SUR-

suturing is preferred for the skin) and apply GERY.,'',0."
sterile dressing.
As operatlve laparoscopy becomes increasingly
7. Operative (thera peuti c) La pa roscopic Surgery accepted in the West African sub-region, more
The laparoscopic trolley and units are the same as in patients and surgeons are opting for this treatment
diagnostic procedure. Additional hand instruments modality, the complication rate can be expected to
are required as appropriate for the type of surgery rise. Complications may be associated with the steps
being performed. involved in the procedure asfollows:
Sfeps I to 6 are as detailed in diagnostic laparo- A. At induction of Anaesthestb

scopic steps. (i) The use of general anaesthesia comes
StepT: lnstead of uterinecannula, uterine manipula- with its own complications as with other
tor is inserted. Urethral catheter is passed and surgeries.
retained. (ii) The use of steep trendelenburg position
Sfep 8; lncludes additional cables like har- and distension of the abdomen with
monic/lotus cable, morcel lator cable etc. carbondioxide particularly reduces excur-
Sfeps 9 to 1.9 are as detailed in diagnostic laparos- sion of the diaphragm and may cause
copy steps. arrhythmia.
Steps 20; Secondary port placement: This is done (iii) Vasovagal reflex may lead to shock and
using the base-ball diamond concept or fork cardiac arrest
and knife principle. Size 5mm trocarhannula
are inserted with rotary movement under direct B. At induction of Pneumoperitoneum
vision. Two left lateral and one right lower (i) Failed gas insufflation: this is usually due
lateral ports or one left & right lower lateral and to placement of the Veress needle into the
one supra-pubic ports. pre-peritoneal space or even subcutaneous
tissue.
(ii) Surgical emphysema could follow
insufflation with wrong placement of the
Veress needle. Always perform the tests for
safe placementof Veress needle.
(iii) There could be injury to the intestine,
bladder or blood vessel if the Veress needle
inadvertently penetrates any of these
structures.
(iv) Gas embolism can occur with
intravascular insufflation of gas and this may
be fatal.
(v) Puncture of the Liver or spleen. This can
occur if the Veress needle insertion site is the
Step 27: The surgeon operates with the two left supra-umbil ical or Palmer's point.
lateral ports or one lower lateral and supra- (vi) Cardiac arrhythmia can occur from
pubic ports while the first assistant uses the excessive absorption of CO, especially if the
right lower lateral port and the telescope on the flow rate is high.
primary umbl lical port.
Step 22: The second assistant controls the uterine C. At the Primary and secondary trocar inser-
manipulator. tion
Step 23t The appropriate surgery is performed. (i) This is mainly from the primary trocar
Steps 24 to 26 are similar to the diagnostic laparos- which is inserted blindly."Similar injuries like
copy steps. in Veress needle insertion can occur but are
usually of greater magnitude.
268
(ii) The following could be injured; blood (delivers gas in litres per minute). Occasionally,
vessels (both abdominal wall and intra- contact hysteroscopy is performed requiring no
rA,
abdom i naI vessels), i ntesti nes,.,@naeh and distention medium, only tissue that is in direct
V urinary bladder. ;.-:r, contact with the distal tip of the hysteroscope can be
seen.
D. During use of energisedrnstzsne@
(i) The use of electrocautery .p6rticularly 1. lndications for Hysteroscopy
monopolar current can cause burn injuries to There are numerous indications for hysteroscopy.
the intestines and bladder. These could be diagnostic as well as therapeutic and
(ii) Thermal injuries may result from insula- include:
tion failure of energised hand instruments . Abnormal uterine bleeding
and from direct and capacitive coupling. . Amenorrhoea
. Abnormal hysterosalpingogram or ultra-
E. During use of mechanical instruments sound report indicating endometrial polyps;
(i) The use of scissors and forceps can cause submucous fibroids, intra-uterine adhesions
injury to blood vessels and uncontrollable or septum etc. Hysteroscopy will give
haemorrhage. accurate diagnosis and treatment of these
(ii) Use of Morcellator can cause injury to conditions.
multiple organs due to improper application. . Recurrentmiscarriages
(iii) Uterine perforation or cervical tear can . Removal of a missing IUCD or retained fetal
occur from the uterine cannular and manipu- bones
lator application. . Infertility evaluation. lt is gaining accep-
F. Genenl Surgical complications tance as an important evaluation for women
(i) Port wound sepsis
undergoing IVF to ensure a normal uterine
(ii) Peritonitis or Pelvic inflammatory disease
cavity and a healthy endometrium.
(iii) Conversion to open surgery
. Tubalsbrilization (Essure@ )
: . Tubalcannulation,etc.
I HYSTEROSCOPY
i 2. Contraindications to Hysteroscopy
Hysteroscopy is a valuable tool in the evaluation and
i The following are considered as contraindi-
treatment of infertility and many othergynaecological
cations to Hysteroscopy
:
procedures. lts use has relegated blind procedures for . Pregnancy
the investigation and treatment of endometrial . Heavy Uterine bleeding
V
pathologies and in some instances obviates the need . Pelvic inflammatory disease
I
for open surgeries. During hysteroscopy, the uterine . Cervical/ Endometrial malignancy
,
i
cavity is visualized with the aid of a hysteroscope. . Recent uterine perforation
I . Cardiopulmonary disease
t For an effective evaluation of the endometrial cavity, a . lnexperienced surgeon
i
distention medium is mandatory. The distention
i
?
L
medium can either be liquid or gas. Commonly used 3. Diagnostic Hysteroscopy:
r
I
distention fluids include Normal saline; Ringer's This is carried out to evaluate the endocervical canal,
I
lactate; 5% and 10% Dextrose water and 1.5"/" endometrial cavity and tubal ostia. ln addition,
i.
I Glycine. Other less commonly used liquid distention endometrial biopsy can be performed to evaluate for
r
media include Mannitol, Sorbitoland Dextran 7O.For endometrial pathology.
I
I
I gaseous distention, Carbon dioxide (COr) is the gas of
I Diagnostic hysteroscopy can be carried out as an
choice. COrprovides a naturalview of the endometrial
I
cavity but is not useful in cases of bleeding within the office procedure (Office hysteroscopy) using very
endometrial cavity. lt is important to note that Corcan small calibre hysteroscopes (e.g 1.5mm diameter
, only be used for diagnostic hysteroscopy with a hysteroscope). Conventional panoramic
I special insufflator (delivers gas in millilitres per hysteroscopy requires some form of anaesthesia,
I
tr minute) different from that used for laparoscopy while smaller calibre flexible hysteroscopes require
I
I
F
I
I 269
iI
I
r
r
(
little or no anaesthesia. A paracervical block can Step 11. Allow pressure (not more than 150mmHg)
decrease the pain of tenaculum placernent, cervical from the distention medium to distend the
dilatation and hysteroscope insertion through the cervical canal before advancing the
cervix. hysteroscope under vision into the uterine
cavity.
Patient Se/ectron I Preparation. The patient:'is given Step 12. Take a panoramic view and identify both
adequate counselling on the procedure/indicat'ron tubal ostia. View the anterior, lateral (left and
and a written informed consent obtained. The right) and posterior walls of the uterine cavity at i
procedure is best performed during the proliferative the level of the fundus, mid-cavity and lower
phase of the menstrual cycle. Review and ensure that third respectively.
all the necessary investigations are normal. ln cases Step 13. Monitor fluid input and output throughout
of suspected cervical stenosis or in menopausal the procedure and document accurately.
women, 200 micrograms of misoprostol is inserted
into the posterior fornix of the vagina some hours
Step 14. Assess and report any pathology observed.
before the procedure (this may not be required in
office hysteroscopy).
Proceed with therapeutic steps if this is
prepared for or if it is a combined procedure.
4. Techn iques for Diagnostic Hysteroscopy Sfep I5; After the procedure, withdraw the
Sfep l. Ensure operating room is properly set up and hysteroscope and clean up the patient.
all endoscopic units are functioning.
Step 2. Observe the principles of ergonomics (the 5. Operative Hysteroscopy
There are three types of operative hysteroscopy
view of the screen should be in the surgeons line
l. Operative sheafhs with instrument attached
of vision).
through channels or fixed to the sheath.
Sfep 3. The patient should empty her bladder before
lnstruments such as hysteroscopic scissors,
coming to theatre (or it can be emptied in
forceps, tenaculum etc can be introduced via
theatre with a catheter).
Step 4. Carry out the procedure in the dorsal channels within the operative sheaths. Small
lithotomy position. polyps, mild to moderate adhesions, missing
Step 5. The procedure can be done under'conscious IUCDs and some cases of uterine septum can
sedation' (intravenous diazepam 1Omg + be managed this way. Normal saline is usually
promethazine 25mg + pentazocine 30mg) the medium of choice during such procedures.
with/without parapervical block or regional
anaesthesia
ll.Electrosurgery: Resectoscope and Versa'
point. The resectoscope is an electrosurgical
Step 5. Surgical site preparation. Clean the lower
abdomen, inner thighs, perineum, vagina and endoscope. lt consists of the inner and outer
drape the patient exposing only the perineum. sheaths, the working element and the tele-
Step 7. Carry out a bimanual palpation. scope. lt can be used with both a bipolar and a
Step 8. Articulate the hysteroscope, connect the light monopolar electrode. For bipolar cautery,
source, camera head and distention medium. normal saline is the disiention medium of
Step 9. Either use the "no touch" technique of choice as it allows movement of current
introducing the articulated hysteroscope via the between the electrodes. For monopolar
vagina, cervical canal and uterine cavity cautery, electrolyte free media such as 1.5%
without the use of a speculum/tenaculum; or glycine are used. The versapoint is a newer
introduce a bivalve speculum (Grave's bipolar system which is used for cutting and
speculum), hold the anterior lip of the cervix ablation but has the disadvantage of not
with a tenaculum and removethe anterior blade providing tissue for histologY.
of the speculum.
Step I0. lntroduce the hysteroscope via the external lll.Hysteroscopic morcellator. This uses a
cervical os just within the cervical canal with blade and suction to sinlultaneously cut and
the distention fluid running (avoid cervical remove tissue. This improves visibility.
dilatation where possi ble). Unfortunately no energy is applied and
270
therefore bleeding blood vessels cannot be abdominalwall. William Hurd putthis riskat greater
cauterised. than207o."
6. Techniques of Operative Hysteroscopry Strategies have been developed to decrease the risk
{ The steps are generally as perj.,.:q&ryEstic of bowel injury in patients with previous abdominal
hysteroscopy w ith the fol lowi ng exce@qg- surgery. Open access technique as first advocated by
. The procedure is carried out uhdei].-&ienal or Hasson" and use of Palmers point (2 to 3 cm below
generalanaesthesia. ., the left lower margin of the rib cage at the mid
. The cervical canal is dilated with Hega/s clavicular line) have been shown to minimise the
dilators to allow passage of the operative risks'u't'
hysteroscope. Pre-treatment with 200 micro-
grams of misoprostol per vaginam the night However, some laparoscopists still advocate the use
before surgery can be beneficia[, especially in of a closed periumbilical trocar insertion techniques
postmenopausal women. in all patients, regardless of a history of previous
. Whatever option is chosen for a hysteroscopic surgery. This position is based on the finding that .
procedure, it is essential that there is adequate bowel injury is uncommon (approximately 3 cases
fluid management. A good record of fluid input per 10,000 procedures) and open laparoscopy does
and output is mandatory. While the maximum not completely avoid the risk of bowel inju ry."
pressure should not go beyond
fluid
f 150mmHg, the maximum allowable fluid 2. Anaesthesia for laparoscopy surgery
deficit for different fluid distention media are as Laparoscopy surgery is usually performed under
follows: NormalSaline : :
1.5 Litres; Glycine general anesthesia, with endotracheal intubation to
1 Litre; Dextran 70 :25Oml. minimize the risk of aspiration. However, if the
pressure used for peritoneal insufflation is reduced,
7. Complications of hysteroscopy diagnostic laparoscopy can be performed under local
Complications following hysteroscopy are rare and anaesthesia with conscious sedationt''tt and simple
generally higher following operative hysteroscopy. ketamine anaesthesiatn particularly in low resource
Studies show a complication rate of between 0.28 setting or where full general anaesthesia is not
and 7.2Y"."-'n lntrauterine adhesiolysis is associated feasible.
with the highest complication rate compared with
other hysteroscopic surgeries." Prophylactic antibi- Previously, regional anaesthesia (spinal, epidural or
otics are not recommended as a routine. combined spinal-epidural) was relatively contraindi-
cated in gynaecological endoscopy surgery due to
t
Most of the complications occur during the initial the steep trendelenberg positioning of the patient
entry into the uterine cavity and include the and high intra-abdominal pressure increasing the
r following:30 Uterine perforation, Cervical trauma, risk of aspiration and respiratory challenges.
I Fluid overload/Pulmonary oedema, Haemorrhage, However today, there are several studies on the
r Haematometria, lnfections, Vaso-vagal reaction, safety of regional anaesthesia in major rynaecologi-
t Adhesion formation and Anaesthetic complications cal laparoscopy surgery and in patients not fit for
f etc. genera I a naesthesia.'o'"'tu
;
I
r
r CONTROVERSIES IN LAPAROS. Regional anaesthesia does provide numerous
COPY/HYSTEROSCOPY advantages over general anaesthesia in terms of no
risk of intubation-related airway obstruction,
1. Laparoscopy after previous abdominal surgery excellent muscle relaxation, quicker recovery,
r
(laparotomy) effective post-operative pain relief, shorter post-
I'
A history of previous abdominal surgery and in operative stay, a more rapid return of gut function,
particular presence of midline abdominal scar cost-effectiveness and reduced post operative
l
increases the risk of bowel injury associated with nausea and vomiting (PONV).'o''u There is also
h laparoscopy surgery. This is due to possible adhe- evidence that the use of regional anaesthesia in
sions of bowel and/or omentum to the anterior laparoscopy performed on awake patients may
r
27t
produce fewer changes in respiratory mechanics and They allow continuous irrigation which is necessary
arterial blood gases.'u for clear visualisation of the uterine cavity and
operating field. Complications can arise from the
3. Choice of Gas for Laparoscopy proc*rm absorption of distension fluid leading to fluid over-
Carbondioxide (COr) is the gas of choice fs€ffih- load and its sequelae; especially pulmonary oedema,
ing pneumoperitoneum in modern day'ffi-*l@ hypertension and cardiac failure. Hyponatraemia is
surgery. lt does not support combustion, itB tapi.dly of particular importance with the use of L.5%
a bso rbed/exc reted a n d h a s a ntise pti c pr6p?ti8s. glycine. Electrolyte free fluids like glycine, sorbitol,
mannitol etc are used with monopolar current while
Nitrous oxide (NrO) has been promoted as a gwd
electrolyte containing fluids (such as normal saline)
alternative but it supports combustion and cannot be
are used with bipolar current.'o The bipolar genera-
used for operative procedures where electrosurgical
torVresectoscopes are more expensive than the
apparatus will be used. lt's also 68% less soluble in
monopolar devices.
plasma and more expensive than C0r. Its only
The electrolytes in the fluids facilitate the movement
advantage is that it has analgesic properties (NrO is
of current from one bipolar electrode to another,
used as an anaesthetic gas)."
causing heat and the desired effects on the tissues.
This is obviously detrimental with the use of
Some studies have shown that filtered room air can
monopolar current as the electrolytes encourage the
be used only for diagnostic procedures where
dispersal of the current reducing the heat generated
electrosurgery will not be used as it can support
within the tissues and thereby precluding any tissue
combustion.t' This recommendation is for resources
effects.
constrained setting and steps should be taken to
minimise the risk of infection.t' However, caution Challenges with fluid overload are more with the
must be exercised with the use of room air due to the
electrolyte free fluids like glycine and electrosurgical
possible risk of air embolism.'nThe use of low intra-
injuries are more common with the use of monopolar
abdominal pressure and bacterial filters during energy. Hence, the preference of the use of bipolar
procedures with room air pneumoperitoneum is
energy with electrolyte rich fluids in hysteroscopic
recommended. procedures.
4. Access (entry) technique for Laparoscopy

primary port. 7. Cervical dilatation during hysteroscopy
Regarding primary port access techniques, surgeons There is little controversy on the issue of dilatation of
agree that no one approirch is superior to another."'" the cervix during a hysteroscopic procedure. This
Each access technique has its challenges and depends on the size of the hysteroscope/
specific indications for its application or use. lt is resectoscope and sheaths used. lt is generally
recommended that operators use methods they are understood that smaller size instruments may not
well trained on and comfortable with its use to require cervical dilatation while the bigger size
i nstru ments wi I I def
itely requ i re cervical d i latation.
i n
mini mise possi ble compl ications.
The determining factor is the calibre or state of the
5. Gasless laparoscopy cervical os and canal.
The benefits of this approach is limited only to the
avoidance of use of gas and its effects. The instru- The use of misoprostol some hours before the
ments for lifting the abdomen (abdo-life etc.) adds procedure to soften the cervix and facilitate seamless
additional cost to instrumentation and also its side cervical dilatation is not generally accepted. How-
effects like ischaemia of the anterior abdominal wall ever, this has benefit in minimising trarmatic and
and increased risk of injury to the bowel. forceful dilatation and its possible complications
especially incompetent cervix. The area of debate is
the dose of misoprostol used and time interval
5. Distension media challenges with
between insertion and the start of the procedure.
Hysteroscopy
Fluid media are used for hysteroscopic procedures.
272
Endoscopy i n Gynaecology
8. Laparoscopy surgery during pregnancy technique is strongly recommended to minimise

Laparoscopic surgery in pregnancy had been associ- possible i njury to the pregnant uterus.oo
ated with serious complications from injury to the
pregnant uterus and'elevation of CO, levet in the 9. Roboticallyassisted laparoscopy
fetus. However, with more experience and better The benefit of this advanced technology in
instrumentation, these dangers have been virtually gynaecologic surgery is still debated. Robotic surgery
eliminated and the occurrence of complications like a has the great advantage that the robotic arm elimi-
miscarriage, premature labor or fetal death appears nates hand tremors and exhaustion experienced by
to be related to the underlying pathology, independ- surgeons during long hours of surgery. lt also has
ent of the operative intervention.oo lt has also been added wrist motion for improved dexterity and
shown that laparotomy has a relatively higher risk of greater surgical precision. However, the disadvan-
complications, increased pain, and longer hospital- tages include enormous cost and added operating
izations compared with laparoscopy.o'-o' time for assembly and disassembly and the bulki-
ness of the equipment.ou-o'
The incidence of surgery during pregnancies is
I
approximately 0.75%oo and the most common The issue of cost has great relevance in our West
t,
V
indications of laparoscopy in pregnancy are
cholelithiasis, appendicitis, persistent ovarian cyst
African sub-region where patients pay from their
pocket for healthcare delivery. Presently, laparos-
r and adnexal torsion with a good maternal and fetal copy surgery is less accepted because of higher cost
outcome.oo''u lt is best performed within the second than open surgery talk less of the more expensive
I
trimester of pregnancy though some authors have robotic surgery. The improvement in equipment and
I
demonstrated safe laparoscopy surgery at all the more skills will eventually increase the acceptability
trimesters of pregnancy." The open access entry and use of robotics in general.
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3-8. surgery. ln Brown TH & lrving MH (Eds),
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: instrument. ln Textbook of Practical
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:theses
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Laparosc. 2004; 1 1 (4): 537. hysteroscopy: a prospective, multicentre study.
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ln Textbook of Practical Laparoscopic Surgery. Parkar RB, Thagana NG. Hysteroscopic surgery
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New Delhi. 2013. 57 - 66. J, 2004;81(7): 336 - 40
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lkechebelu Jl, Udigwe GO, Obi RA, Joe- Okohue JE, Onuh SO, Akaba GO, Shaibu l,
lkechebelu NN, Okoye lC. The Use of simple Wada l, lkimalo Jl. A 3 years review of
Ketamine Anaesthesia for Day-case Diagnostic hysteroscopy in a private hospital in Nigeria.
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Gynaecology. 2003: 23(6): 650 - 652. 2009;2(2): 26 - 9.

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Sinha R, Gurwara AK, Gupta SC. Laparoscopic Gordon AG. Complications of hysteroscopy. in
Surgery Using Spinal Anaesthesia. Journal of Practical Training and Research in Gynecologic
the Society of Laparoendoscopic Surgeons. Endoscopv. assessed 15th May 2015 at
2008 Apr-Jun; 12(2): I33-J38. http : I lwww. gf me r. c h / B oo ks I E n d oscopv :boo k I C h 2
21. 4
Comolications hvster.html
Mishra RK. Abdominal Access Techniques. ln 31. Hurd WW. Gynecologic Laparoscopy:
Textbook of Practical Laparoscopic Surgery. 3rd lndications.
B roth e rs M ed i ca I
.Ed i ti o n. J ay pee P u b I i she rs. h ttp : I / e m e d i c i n e. m ed sca p e. co m / a r t i c I e I 2 6 5 2 0 1
New Delhi. 2013. 67 - 94. -overview#a6. assess on February, 2077 lst

22. 32. Hasson HM, Rotman C, Rana N, Kumari NA.
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the fact that the evidence for laparoscopic entry Gynecol. 2000 Nov.96(5 Pt 1):763-6.
ls as good as it gets. Journal of Minimal lnvasive 33. Mazdisnian F, Palmieri A, Hakakha B, Hakakha
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microlaparoscopy for female sterilization under 14(4): 375-9.

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126-131. 43. Carter JE Soper DE, Laparoscopy vs. laparotomy

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I Gynaecology. 2005: 25(2): 172- L7 3. Belprano E , Patel HR. Robotic laparoscopic
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of Room Air Pneumoperitoneum for Diagnostic Nefrolosica : The ltalian Journal of Urolopy and
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Practice. 2008. 11(?: 127 - L29. 47. Nezhat C. Saberi NS, Shahmohamady B,
39. Peeters G. Re: lkechebelu Jl. Obi RA. Udigwe Nezhat F. Robotic-Assrsted Laparoscopy in
GO. Joe-lkechebelu NN. 2005. Comparison of Gynecological Surgery. Journal of the Society of
carbon dioxide and room air pneumoperitoneum La pa roen doscop i c Su rgeons. 2006 :
for day-case diapnostic laparoscopv. Journal of 10:317-320
Obstetrics and Gvnaecolosy 25:172-173. J Advincula Af, Song A. The role of robotic surgery in
Obstet Gynaecol. 2009 Oct; 29(7): 678-9. gynecology. Current Opinion in Obstetrics &
Al-Fozan H Gvnecology: -2007 - Volume 19 - lssue 4 - p
40. , Tulandi T. Safety and risks of laparoscopy in 331336
pregnancy. Curr Opin Obstet Gynecol. 2OO2 Aug;
275
276
-'
I
I
)
CHAPTE2S
;,
I
Preoperative Management
AY lsah and O Onafowokan
lntroduction 5. DiagnosticdrTherapeutic
The preoperative review and evaluation prior to 6. Minimal access surgery
gynecological surgery is meant to address issues that
may potentially affect the patient during her surgical The magnitude of preoperative care is dependent on
procedure and recovery. Some post-operative the nature or type of surgery.
I
,7 complications and challenges can be predicted
preoperatively, and minimized or eliminated with a Preoperative Procedures
Traditionally, all surgical patients are hospitalised at
view to having successful procedure outcome. The
? least one day prior to surgery for clinical reassess-
7 surgeon should use this time to review the patient's o
ment and to be evaluated by the anaesthesiologist.
history and physical examination, identify physical
I limitations, gather information required to plan
The current trend however, is for the preoperative
t
I anaesthetic assessment to be performed in an
I surgery, optimize medical status, and educate the
? outpatient visit while the patient is only admitted to
patient about what to expect from the procedure and
t during the recovery period.' With proper evaluation,
the hospital to await surgical procedure.u
I
? the surgeon may down play the aggressiveness and

F On the other hand, preparation for emergency
necessity of the planned operative procedure.
I
surgery has to be carried out rapidly and concurrently
as the patient is admitted to the hospital.
I The goals of preoperative assessment include among
I others':
? History taking
r The importance of re-evaluation by revisiting the
I r ldentifying unrecognized comorbid disease
Il and risk factors for medical complications
history and physical examination cannot be overem-
I
phasized as it remains a veritable tool for safe
I of surgery
preoperative planning. Re-evaluation allows for risk
?
I . Optimizing the preoperative medical
scoring and assessment / management. One way of
I
condition
facilitating an integrated and proactive approach to
r r Recognizing and treating potential compli-
risk assessmenV management is the use of RADICAL
cations
. Working effectively as a member of the
framework, which comprises the following domains
preoperative team in an integrated grid: Raising Awareness, Designing
for safety, lnvolving users, Collecting and Analyzing
Gynaecological operations can be classified into
3: patient's safety data as well as Learning from
1. ElectiveorEmergency patient's safety incidence. u ln this way, the history
r 2. Majoror Minor
3. Day-caseorOut-patient
4. Abdominalorvaginal
must have to go beyond the confine of gynaecological
complaint to include obstetric history, past medical
and surgical history, past and present drug use,
:
277
family and social history and a review of systems. ' geon may predetermine the likelyhood of successful
It is mandatory as part of the re-evaluation to surgery. Systematic examination can therefore not be
comprehensively counsel the patient regarding overemphasised if preoperative patient preparation
alternative treatment options (including axpectant is to be considered adequate.
management) and risks/benefits of theprg@Bre
For some procedures, particularly those that have lnvestigations
variable outcomes and impact quality of life{such as, Traditionally, routine investigations prior to surgery
pelvic organ prolapse repair), patient expettatiens are considered an important element of preanesthe-
and goals should be discussed in detail. 'Anticipato- tic evaluation to determine the fitness for anesthesia
ry guidance during preoperative clinic visits will and surgery. During past few decades, this practice
enhance a patient's acceptance and compliance has been a subject of close scrutiny due to low yield
during the immediate postoperative period and may and high aggregate cost. Performing routine scree-
help to shorten hospital stay. 'This would be followed ning tests in patients who are otherwise healthy is
by obtaining an informed consent. Similarly, exarni- invariably of little value in detecting diseases and in
nation should be thorough paying attention to extra changing the anesthetic management or outcome.' lt
genital systems. Assessment of the surgical and may be safe to advice that investigations be tailored
anaesthetic risks should be made. The importance towards necessity and avoid what could be described
of history taking and physical examination cannot be as 'academic barrels of investigations'. Selective
overemphasized. They are the most important testing has the tendency of reducing cost without
component of pre-operative assessment and dictate sacrificing safety or quality of surgical care especialy
the need for other perioperative measures including in resource poor countries where national health
laboratory tests. insurance may be avaoidably absent. History and
examination directed investigation may be all that is
Examination needed. There are still substantial areas of uncer-
Careful but detailed examination is necessary to tainty in the literature due to the lack of randomized
confirm fitness or to exclude conditions that may prospective trials and relatively low incidence of
suggest significant threat to successful surgical post-operative adverse events. But the medical,
outcome. Pallor and jaundice that may point to the surgical, 'o and anesthesia " literature is replete with
need of further evaluation of the level and cause of reports from studies that have established that
anemia and liver disease can be excluded. Diseases screening tests without specific indication are
affecting the liver may compromise liver, metabolism wasteful. Based on the available data, there is
of anaesthetic agents until corrected. Abnormality of general consensus that only selective tests should be
the pulse and blood pressure may signify referral or advised consistent with the clinical evaluation "
invitation of cardiologist to evaluate the patient as
both may constitute anaesthetic risk. Haemoglobin concentration should be determined in
all patents. The minimum haemoglobin concentra-
Since majority of the anaesthetic agents may need to tion for elective operations has traditionally been
be excreted via renal, respiratory or both systems, 10gdl. However, in an emergency such as ruptured
optimal conditions of all these systems become ectopic pregnancy, a low haemoglobin concentration
paramount to safe surgical preparation. The presence should not preclude or delay surgery since prompt
of features suggestive of acute or chronic renal or arrest of bleeding is the aim and autotransfusion may
respiratory systems deserves prompt treatment and be feasible and lifesaving. " Full blood count may
rescheduling of the planned operation at a later only be indicated in cases where there exist suspicion
period. /
of sub-clinical clinical infection. ln emergency
situations such as ruptured ectopic pregnancy,
Central nervous system abnormalities appear procedure may not necessarily wait for the result
uncommon among .gynaecological patients but where coverage with broad spectrum antibiotic may
careful examination of all preoperative women may be used instead. Platelet count is required where
reveal rare occurrences. When such is detected, co- there may be a likelihood of coagulopathy as in a
management with a neurophysician and or neurosur- missed abortion or prior to suction evacuation of a
278
E
Preoperative M a nagement
molar gestation. Haemoglobin genotype is necessary lnvestigations such as intravenous urogram (lVU)
to determine ihe sickle status of the patient. This and chest X-ray are not considered routine but may
becomes re|evant as Anaesthesia may--ti, ry.:sick|ing be indicated in patient that has pelvic tumour,
in women with sickle cell haemoglob$ that is urinary tract fistulae and metastatic diseases / chest
infections.
r"r '
Blood group and Crossmatch Admission to hospital
These are required for operations where excessive The duration of admission prior to surgery depends
blood loss is a distinct possibility. Howev.er, blood on the type of surgery and the need for in-patient
transfusion is associated with significant risk to the preparation. However, it should not be unnecessar-
patient and should not be undertaken lightly espe- ily long as this has both psychological and economic
cially in this era of widespread infectious diseases implications. Furthermore, bed space is denied
such as AIDS pandemic. Consideration should be other patients who require hospitalization.
given to alternatives to heterologous blood transfu-
sion. These include autologous, blood transfusion Re-evaluation
The patient should be clerked again in detail and
t
tech n iques, ( Predeposit, perioperative haemod i I ution
and intraoperative blood salvage) and plasma investigations checked for completeness. The
diagnosis and intended operation should also be
expanders like haemacel. "
revisited. lmportant points to consider in this re-
Pregnancy test evaluation include but not limited to:
I It may be necessary to exclude pregnancy by serum 1. Has the patient's condition changed since
I pregnancy tests before surgery in selected cases. her last outpatient visit?
i Clinical suspicion of slow leaking ectopic may be 2. Has there been any intercurrent illness?
suspected with a positive test and confirm with 3. ls the procedure still necessary?
demonstration of extrauterine sc on either 4. ls it the best for the patient?
transabdominal or transvagina ultrasonography.

5. ls there any additional procedure that
should be done at the same time?
Examples would include myomectomy, laparoscopy
and dye test as well as preceding hysteroscopy.
Consultations
The medical condition of the patient may necessitate
Serum electrolytes, urea and creatinine may be
the invitation of physicians in other specialties to
considered routine in elective cases as excretion of
review the patient.
some Anaesthetic agents may be via urine. This
become more pertinent especially when there is a A medical consultation is required for women with
known or suspected renal dysfunction, a pelvic mass diabetes mellitus, hypertension or other medical
(obstructive uropathy), ascites, repeated vomiting or
disorder. This may have occurred in the outpatient
diarrhea. ln a similar way, Liver function tests may clinic but it is important to ask for a review when the
not be routine unless there is known or suspected patient is admitted forsurgery.
liver disease or malignancy. Urinalysis may be all that
may raise suspicion of 'occult'diabetic mellitus that Pre-operative consultation with a surgeon should be
would then be confirmed with blood sugar analysis. considered if there is a possibility of bowel surgery or
) All patients should have their urine screened for involvement of abdominal organs. This should be
I glucose. Urine microscopy and culture are necessary anticipated when laparotomy is undertaken for
a if urinary tract infection is suspected. known or suspected malignant diseases or septic
" abortion. Other consultations would also be guided
Ultrasound scan by the patient's condition. Again, routine consulta-
)
. This is common investigative tool in modern
a tions are unnecessary
u
medical practice that has revolutionized medical

diagnosis. Most practicing surgeons may improve Multidisciplinary operations are common in contem-
; their preoperative readiness and counseling by well porary practice. lt is advisable for all participating
I guided ultrasound diagnosis. lt is often useful to surgeons to have a pre-operative group discussion on
f' exclude pregnancy or detect obstructive uropathy. their various roles, the sequence of the different
t,
>
, 279
L
;
!_
surgical procedures and when each specialist Pre-anaesthetic visit

surgeon is to appear in the theatre. Horrrrenrer, the This is undertaken by the anaesthetist and is very
Obstetrician/ Gynaecologist should pla*t tG: tr' important as the anaesthetist is the "final clinical
available throughout the surgery. gatekeeper".' Even in an emergency, the patient
must be seen by the anaesthetist prior to anaesthe-
lnformed consent sia. Anaesthetists often visit their patients in excep-
This is important and is obtained without detess. tional situations characterised by preoperative
Obtaining informed consent involves tr discussion anxiety or distress. Therefore, even brief contact with
with the patient in words she can understand. lf the the patient can be considered intense and meaning-
patient is a minor, consent is obtained from her ful. 'o During the visit, the anaesthetist evaluates
parents orguardian. anaesthetic risk, determines the type of anaesthesia
whether general or regional and also assesses the
The planned procedure, its indication and alterna- need for premedication and prescribes it.
tives is explained clearly, accurately and compassion-
ately to the patient. Anticipated outcome, potential Patient preparation
complications and the sequelae of the disease This involves the measures outlined below with
condition if surgery is withheld is also discussed. variations depending on patient's condition and type
However, care must be exercised not to exaggerate of surgery. Traditionally, recommendations that oral
the benefits of the surgery, neither should the patient intake of liquids and solids be restricted for varying
be terrified or discouraged into rejecting a beneficial times prior to anesthesia aim to minimize gastric
operation. She is allowed to ask questions freely and volume atthe time of surgery.'u This is to ensurethat
express concerns which are handled empathically. the stomach is empty, and reduce the risk of regurgi-
A well informed patient in a stable mental state can tation and aspiration during anaesthesia.' However,
decline the option of surgery. However, where the prolonged fasting is unpleasant and hypoglycaemia
patient makes unacceptable requests the surgeon may occur, therefore; guidelines that will prevent pre-
may choose not to be involved in the case. Where a operative fasting beyond six hours are being advoca-
mentally unstable patient objects to a surgery ted.'u The patient usually has a bath on the morning
considered to be beneficial to her, the surgeon may of surgery. Hair removal should be limited to the
seek legal assistance. Similarly where parents/ area of incision if required. Risk of infection is
guardians of minors object to surgeries of proven reduced if this is done shortly before surgery compa-
benefits to the patient, the surgeon may seek legal red to the previous night. Nail polish should also be
assistance. removed during the pre-operative preparation, as it
may affect pulse oximeter readings during monitoring
ldeally, the consent form should be signed by the in Anaesthesia.'u Because the pulse oximeter works
patient and the surgeon who would have counseled by sensing light wavelengths, anything that interfe-
her earlier, except where the patient is unstable/ res with the light spectrum can prevent proper
unconscious or a minor. The consent given by the functioning of the sensor. Pulse oximeters are
patient should not be restrictive but such that the commonly placed on fingers or toes, and things like
surgeon is able to carry out additional procedures false nails or nail polish can interfere with the light
that may be necessary intra-operatively. sensor. "
Operation list Bowel preparation is not routine. However, mecha-
The operation list identifies the patients for surgery
nical bowel preparation should be considered for
and the order in which they are to be operated upon.
female pelvic floor surgeries involving tl,e posterior
It is produced in agreement with the gynaecologist vaginal walls and anal sphincter or when bowel
and anaesthetist and submitted to the operating surgery is anticipated. 'The patient should empty her
theatre staff well in advance.
bladder when called to the theatre. Bladder cathete-
rization if required should be done with the patient
This enables theatre staff to know the type and
under anaesthesia. Pre-operative cleansing of the
complexity of cases as well as the need for special
vagina is not routine and has demonstrated only
equipmenVmaterial.
280
Preoperative M anagement
limited usefulness. Where indicated such as in vagina onset of action for diffdrent drugs. The optimal time
hysterectomy, chlorhexidine gluconate has shown of administration of majority of preoperative drugs is
more effectiveness than povidone iodltre in decrea- now at 60 minute before surgical incision'u. The
sing the bacterial colony counts ttrat;@ found in exception to the 60 minute rule is the fluoroquinolo-
the operative field for vaginal hystereetcxay. s nes and Vancomycin that requires administration
between one to two hours. These two drugs are to be
Pre-med ication if prescri bed should be'admin istered administered I2O minute before knife on the skin ".
the night before, and / or on the morning of surgery What may generate further debate may be the
according to the anaesthetist's prescription. Patient unusual delays in starting cases in theater suites of
preparation in the ward is mainly the duty of the developing countries. lt may be that a particular drug
nursing staff. Another very important aspect of is administered 60 minute from the ward with the
nursing care pre-operatively is a friendly disposition expectation that the surgery would comence not later
from the staff on the ward. Patient is more relaxed than schedule. From practical point of view however,
and ready for surgery, if the atmosphere in the ward this may not be achievable within schedule.
and the theatre admission rooms are friendly and
relaxed.' ll. Does single dose antibiotic administration
r
suffices for prolonged Surgery?
A good night sleep, friendly faces and a comfortable Available update recommends interval administra-
I
patient are also very important aspects of pre- tions of selected antibiotics for prolong surgeries 'o
operative care. contrary to earlier most popular practice of single
i
t dose pre-i nd uction ad m i n istration. Prolong su rgeries
I Pre-operative antibiotic prophylaxis has been shown lasting for more than six hours requires repeat dosing
to be more cost effective than post-operative therapy as the required serum and tissue concentrations of
F for seven days.'n'" The choice of antibiotic depends the drug would have been overstretched. ln general,
Ir
on local sensitivity patterns.
it seems advisable to administer prophylactic agents
t
in a manner that will ensure adequate levels of drug
E Each patient should also be assessed for risk of deep
in serum and tissue for the interval during which the
I vein thrombosis and prophylaxis administered
?
t
surgical site is open.tn-"
J accordingly. In general, venous thrombo-embolism
t
(VTE) occurs in the form of a deep venous thrombo-
I
?
lll. Duration of preoperative admission for Gynae-
sis or pulmonary embolism. "
Measures include cological operations
r adequate hydration,. graduated compression stock- Practitioners appear to be shifting towards reducing
I v ings and heparin. Prolonged pre-operative bed rest

may increase the risk of post-operative
the over all stay in hospital for surgical cases espe-
cially major Gynaecological operations. They are
/I thromboembolism. unanimous in advocating for effective preoperative
t
?
assessment and preparation with protocol-driven,
Conclusion Nurse-led discharge of duty as fundamental to safe
I 'Choose well, cut well and get well'. The success of
I and effective day and short stay surgery.o Ortiga et al,
I gynaecological surgery is dependent on optimum pre-
? in a review of over 6,000 women admitted for
r operative preparation. This would ensure that the
r various form of surgery reported the reduction of pre-
I appropriate operation is performed with the patient in
surgery length of stay from 0.46 days to 0.29 days
I the best possible condition. lt must therefore, be over a Z-year period.u They also reported significant
carried out meticulously by the team with evidence-
reduction in the total len$h of both preoperative and
I based care.
postoperative stay from 6.2 days to 5.5 days. 5 The
L challenge would be how to achieve such laudable
Discussion / Controversies
intervention in our facilities where there are many
l. Timing of preoperative antibiotic prophylaxis
patients awaiting surgery but fewer resources to
I
The most popular timing of preoperative antibiotic
dose administration appears to be administration cope with long hospital stay. .
before induction of Anaesthesia. " This has posed a
challenge of non-consideration of administration to
t
l
28L
F'
!1--
IK
E;
REFERENCES
1. Mann WJ Jnr. Overview of preopera ' 9. Pasternak LR. Preoperative testing: Moving
evaluation and preparation for gtnecotogia from individual testing to risk management.
surgery. Available on line: Anesth Analg 2009; 108: 393-4.
http:// 10. Traub NL. Preoperative testing. ln: Smith
of - o reope rati ve - ev a I u ati o n - a n d - p re pa rati on - RB, Dobson TE N Spell N, Walker HK,
for-pynecolosic-su rgerv. Last updated Dec editors. Medical management of surgical
21,2016 patients: A text book of perioperative
2. Cohn SL. Overview of the principles of medicine 2006. 4'n ed. England:
med i ca I consu ltation a nd perioperative Cambridge University Press; 2006; 32-37.
medicine. Available on line: 11. Bryson GL, Wyand S, Bragg PR.
http : I /www. u ptod ate. co m / co nte ntsI ove r v i ew' Preoperative testing is lnconsrste nt with
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and - pe ri ope rative- med i c i ne. Last u pdated management. Can J Anesthe 2006; 53:
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King V, Oloukp6de S, et a/. Risk factors and
Packaging Limited, Accra. 2005; 2L1 - prognosrs of ruptured ectopic pregnancy in
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4. Klei WA, Moons KGM, Rutten CLG, lJniversity Hospital of Benin. lnt J Gynecol
Schuurhuis A, Knape JTA, Kalkman CJ, Clin Pract 2015; 2: 111.
Grobbee DE. The effect of outpatient 14. Harm C, Kindler CH. The preoperative
p reo perative eva I u ati on of hosp i ta I anaesthetic visit. Ther umsch
inpatients on cancellation of surgery and 2009;66(7);503-8
length of hospital stay. Anesth Analg. 2002,
15. Crowley M. Preoperative fasting guidelines.
94:644-649. Holt NF (eds) online at www. Preoperative
5. Ortiga B, Capdevila C, Salazar A, Viso ME fasti ng guidel ines. 20 1 6
16. Kuczkowski KM, Benumof JL. A new fashion
Bartolome C, Corbella X. Effectiveness of a
Surgery Admission Unit for patients
in obstetric anaesthesia: bulky occipital
hairpiece as a cause for difficult intubation.
undergoing major elective surgery in a
Proceedings, Second All Africa Anaesthesia
tertiary university hospital. BMC Health
Congress 2001; 115.
Service Research 2010; 10: 23
6. Edozien LC. The RADICAL framework for
17. O'Connel A. Disadvantages of Pulse
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i mplementi ng and monitori ng healthcare
h ttp : / lwww. i vestron g. co m I a rti c Ie /2 442 8 5 -
risk management. Clinical governance: an
I
d i sadva ntapes- of pu I se -oxi - metrv : 20 75

lnternational Journal 2013; 18: 165-75
18. Patrick J, Culligan, MD, Kari K, Miles M,
7. Edozien LC. Risk management in labour and
Backwell L, Snyder J. A randomized trial
delivery ln: Munro kerr's operative
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obstetrics. Baskett TE Calder AA,
chlorhexidine as antiseptics for vaginal
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hysterectomy. American Journal of
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Kamar A, Srivastava U. Role of routine Obstetrics and Gynecology 2005; 192:
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19. Clinical guidelines for antimicrobial
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and Human services 2013.
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P reope rative M a n a gement
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20. Zelenitsky SA, Silverman prophylaxis: an association between

et al. A prospective, i ntraope rati ve a nti b i oti c co n ce ntrati ons an d ']
blind study of single h efficacy. Antimicrob Agents Chemother.
multiple standard 2002; 46: 3026-30.
combination with 22. Shaw HA. Thromboembolism prophylaxis in
gynecologic surgery. Strohbehn K Gds).
I
colorectal surgical
lnfect.2000; 46:13 Available online:
21. Zelenitsky SA, Ariana http : I / e med i c i ne. med sca oe. com I a rti c I e / 209
Antibiotic 8556-overview. 2016
?
I l
tr
7
>
i i
I
l' I
:r I
I
,{
'l
\t
243
Comprehensive Gynaecologyr in the Topics
M
cl, AP,E26
Post-Operative Care
R E Larsen-Reindorf & H S Opare-Addo
lntroduction outlines these mechanisms. Hypovolaemia (from

fr
I
The post-operative period must be viewed to be in blood loss and water from peritoneal surfaces)
continuum with the pre-operative period. lt is the stimulates the sympatho-adrenal system which
period following the end of surgery and continues till results in increase in the release of catecholamines,
the patient is discharged home, though it may antidiuretic hormone (ADH), aldosterone and
sometimes continue after discharge. The overall glucagon (G). Glucagon causes glycogenolysis while
objective of this period is to reduce morbidity and the other hormones help raise the blood volume and
return the woman to her normal activities and prevent maintain homeostasis. Adequate replacement of
death. Events in this period can be anticipated, to a fluid and electrolytes will reduce this response. Pain
large extent, by the pre-operative condition of the impulses from the injured tissues pass to the
patient and the known complications associated with thalamus, then to the hypothalamus and finally to
the particular surgery. Therefore, the pre-surgery the sympathetic centre and result in the secretion of
evaluation must be adequate and the surgeon must adrenocortical hormones (ACTH) from the pituitary
anticipate the kind of problems that may occur to aid and catecholamines from the adrenal medulla,
with adequate pla4ning and counseling of the These adrenocortical hormones now cause
/ woman. This chapter discusses the predictable production of cortisol in large amounts. These stress
physiological alterations' after surgery (Table 1) and hormones, large amounts of cortisol and
/
j the post-operative care for patients who have catecholamines, cause protein catabolism, lipolysis
i
I
undergone gynaecologic surgery for both benign and and gluconeogenesis. They provide substrate for
r malignant conditions. metabolism and plasma protein synthesis such as
: albumin and acute phase proteins (defined as
I
Neuro-endocrine Response to Su rgery proteins whose concentration rise or decrease by at
Ib
Surgical trauma elicits a large number of neural and least 25"/o following trauma and sepsis)'. These
i hormonal responses that result in predictable include C-reactive protein (CRP), serum amyloid A
t physiological alterations.' These neuroendocrine protein, complement components, haptoglobin,
responses help the patient's recovery by maintaining
l, caeruloplasmin, fibrinogen, Factor Vlll, von-
t homeostasis, protecting the circulation, providing
Willebrand factor, ol-antitrypsin, o1-antiplasmin,
energy and aidingwound repair. The nature, intensity, plasminogen activator inhibitor and C1-esterase
i, duration and severity of these responses depend to inhibitor. Although the basis forthis increase in acute
some extent on the surgical injury.
r
phase proteins is incompletely understood, it makes
homeostatic senset.
Pain, hypovolaemia and tissue inflammatory
reactions from surgery cause these neuroendocrine
responses to occuf. The schematic diagram in Fig ( 1)
l
I 285
t
EE-
SURGICAL INDUCED NEUROHUMORAL ALTERATION

Table 1
System/Organ Ghange
Pituitarv A ACTH
6 Prolactin
lfr Growth Hormone
a rSH then I
A Growth Hormone
6 f3-endorphin
lfr Vasopressin
Autonomic Nervous System
'Adrenal ,|. Plasma norepinephine
4. Adrenal catecholamine
d Cortisol
llt Aldosterone
Pancreas A Glucaoon
9 lnsulin thenir
Thyroid {r then9T4, free T4, free T3,{rrTa
Cvtokines lnterleukin 1 (lL-1)
lnterleukin 2 (lL-2)
tnterteukin 4 0L-4)
Miscellaneous A Prostaolandins
* Testosterone
+ Renin
The third stimulus that causes the neuroendocrine The post-operative physiological changes that
responses is inflammatory reaction after the surgical emanate from these neuroendocrine responses can
injury. The inflammatory reaction and their products be summarized into three main systems:
activate macrophages, monocytes and lymphocytes
to produce the cytokines, interleukin 1,2,4, 8, 10 (1) Cardiovascular, the renal/electrolyte
and tissue necrotic factor-s and prostaglandins. The response which are responsible for the
cytokines act mainly locally as part of the haemodynamic, fluid and electrolyte
inflammatory and immune responses, but they may correction;
spill over into the general circulation with consequent
adverse systemic responses such as pyrexia, (D The metabolic system which controls energy
immunosuppression and protein catabolism'. metabolism including fat and protein
Factors and conditions such as wound sepsis which catabolism
excite more inflammatory responses therefore cause
massive stimulation of the neuroendocrine factors via (3) Miscellaneous reactions such as changes in
this pathway. ln the same way, methods and plasma protein, hypercoagulability and
procedures which reduce the inflammatory immunosuppression.
responses such as minimally invasive surgery, use of
appropriate prophylactic antibiotics and wound
debridement would cause less neuroendocrine
responses.
"
2A6
Post-Operative Care
Figure.l
:-
i::2::-+:i.= . : ALDOSTERONE
;: :':::..::]::=::.:
(Renin -angiotensin)
Growth Hormone . r':.*J,1::-=.r;.
.: :;::r::i*:ta:-- Catecholam
_ ':- i':' ' ':
I
1
I
I ACTH.
PITUITARY ADRENAL GLAND
>
1
1
7
Sympathetic Centre Sympathetic Pancreas
Adrenal response
F
I
f
I 1
HYPOTHALAMUS
F
OSMORECEPTORS
1
I
Glucagon
;
I
Activated Macrophag.r,-**orro"*es, Lymphocytes, Endothelium

+
Cytokines : lL- | .IL-z, lL-4, lL-6, IL- 1 0, TNF -a
Modified from The Metabolic /esponse to tnuma ln: Principles and Practice of Surgery lncluding Pathology in the
F
I Tropics. 3'o edition. Editors: Badoe EA, Archampong EQ, da Rocha-Afodu JT. Ghana Publishing Corporation 2000,
p101.
rf
Many of these neuroendocrine changes have been effects of these stress responses during operation
recognized as appropriate responses. However, some include hypertension, hyperglycaemia, fluid and
are detrimental especially under the setting of electrolyte abnorrnalities, malnutrition,
controlled surgical trauma and may adversely affect hypercoagulability, myocardial ischaemia and
the patient. lt is therefore important that dysrhythmias'. The cause of hypertension can be
interventions are put in place pre-operatively, during attributed to the relative imbalance of anaesthetic
the operation itself and postoperatively to minimize depth, surgical stimulation and postoperative pain.
thee alterations. Some of the potential adverse This can lead to sympathetic hyperactivity resulting
287
in increased catecholamine output and hypertension. hypothalamus-pituitary-adrenal axis is initiated by

It can be prevented or ameliorated by a equate just scheduling the operation. lt persists throughout
anaesthesia and analgesia. The hypergl@qi.fia is surgery until at least a week after the operation. This
mediated by increased levels of epl@*iire, adrenergic-corticoid phase may predispose patients
glucagon and cortisol which act syne@ti@ to with cardiovascular risks into problems. Peri-
increase gluconeogenesis and inhibit ps+frrerat operative B-adrenergic blockade is cardio-protective
glucose utilization. Although mild transient in such patientso
hyperglycaemia is of little concern in the non-
diabetic, it can complicate management and I mmediate Post-operative Care
increase morbidity in the diabetic. Prompt correction
of fluid deficits to ensure adequate perfusion of all The first 72 hours after surgery is critical as most of
tissues, provision of enough glucose and early oral the life-threatening complications occur in this
feed i ng su pplemented with a rgi ni ne, gl utam i ne, RNA
period. The post-operative orders should clearly
and omega-3 polyunsaturated fatty acids can guide care in this period. The immediate concerns
minimize fluid/ electrolyte abnormalities and post-operatively differs slightly depending on
malnutrition. Many of these neuroendocrine changes whether the anaesthesia used was regional or
have been recognized as appropriate responses. general; in patients who had undergone general
However, some are detrimental especially under the anaesthesia more attention to the airway to prevent
setting of controlled surgical trauma and may occlusion is required. Therefore an oropharyngeal
adversely affect the patient. lt is therefore important tube must be put in place immediately after
that interventions are put in place pre-operatively, extubation in the operating room to prevent occlusion
during the operation itself and postoperatively to of the upperairway.
minimize these alterations. Some of the potential

lntensive care facility or (in its absence) a recovery
adverse effects of these stress responses during
area fitted with equipment to monitor all the vital
operation include hypertension, hyperglycaemia,
signs must be available. The success of immediate
fluid and electrolyte abnormalities, malnutrition,
post-operative care depends very much on devoted
hypercoagulability, myocardial ischaemia and
and well-groomed nursing staff. Vital signs (blood
dysrhythmias'. The cause of hypertension can be
pressure, pulse, respiratory rate, urine output,
attributed to the relative imbalance of anaesthetic
oxygen saturation and temperature) should be
depth, surgical stimulation and postoperative pain.
monitored at specified times in order to detect
This can lead to sympathetic hyperactivity resulting
changes that call for action: initially every 15
in increased catecholamihe output and hypertension.
minutes for two hours and if the patient remains
It can be prevented or ameliorated by adequate
stable, it must be monitored every 30 minutes for the
anaesthesia and analgesia. The hyperglycaemia is
next 2 hours.
mediated by increased levels of epinephrine,
glucagon and cortisol which act synergistically to
After recovery and movement of the patient to her
increase gluconeogenesis and inhibit peripheral
room or ward, it is desirable and good practice to
glucose utilization. Although mild transient
review her in 6-72 hours after the surgery because
hyperglycaemia is of little concern in the non-
most life-threatening conditions such as
diabetic, it can complicate management and haemoperitoneum from bleeding vessel is usually
increase morbidity in the diabetic. Prompt correction
detected in this early period.
of fluid deficits to ensure adequate perfusion of all
tissues, provision of enough glucose and early oral The care system must ensure that nurses caring for
feed i ng su pplemented with a rgi n i ne, gl utam i ne, RNA post-operative patients know the existing protocols
and omega-3 polyunsaturated fatty acids can and they have been trained to be proficient in its use.
minimize fluid/ electrolyte abnormalities and Standardized chart as the one in Fig 2 is helpful to
malnutrition. There 'is evidence that the neuro- make instructions clear and eqsily visible. lt also
hormonal stress of elective surgery in fact begins well makes docu mentation com plete.
before the skin incision and that activation of the
288
rt
i
Post-Operative Care
a
r The First 12 Hours 5c. Activity:
n
.r --------Bed rest
Approach to the Post-operative gynaecologic patient --------Ambulate
-------Other (specify)
I
The review in the first 12 hours must be conducted in 5d. Diet:
I an orderly manner. The pneumonic 'SOAP' can be NPO
adopted to make the review orderly and systematic. (specifv)
The letter'S' connotes the 'subjective symptoms' of 6a. ntraven;;;l;?Ji"
r
the patient. Following major surgery in gynaecology, 6b. Fluid intake and output chart
pain, nausea and vomiting appear to be the Notify H.O if urine output
<30m|/hr
commonest complaints. lt is imperative to get a good
6c. Catheterize q 6hours, or sooner, if bladder is
understanding of how the patient feels and therefore
full and patient unable to void
a short history exploring any complaint is needed. ln
7a. Pain medication: Specify
this regard, information from nurses andlor nurses' a) Route of administration
progress notes should be taken in account during the b) Dosage
review. Other symptoms that may be present in the 7b. Antiemetic medication: Specify
first 12 hours include: low grade fever, pain in the a) Route of administration
throat, cough, chest pain, headache, thirst and many b) Dosage
more. The possible causes of any of these symptoms 7c. Antibiotics
present should be carefully evaluated to arrive at a 7d. Venous thrombosis prophylaxis
possible cause. For example, pain or discomfort 7e. Other medications
(usually mild) in the throat usually results from 8, lncentive inspirometry q 2 hours while
awake
endotrachea I intu bation that may have been
Encourage deep breathing
traumatic and therefore requires assurance and the 9. Drains
analgesics that are usually given. Similarly, low-grade Type Location Drainage
fever in the first post-operative day is a result of the -*Nasogastric ---Stomach ---Low/intermittent
tissue reaction resulting from surgical trauma and suction
requires observation. The 'O' in the SOAP stands for ---Peritoneal ---Pelvis ---Bulb suction
'objective' assessment by the clinician - physical ---Foleys catheter ---Bladder ---Gravity
examination. This requires examining the relevant
uModified
systems of the patient (including obtaining the vital from Horowitz lR: Post-anesthesia and
t
signs). The general examination must include postoperative care: ln Te Lindes'Operative
examiningfor pallor Gynecology, 8th edition, eds. Rock JA and
Thompson J D. Lippincott- Raven Publishers,
Figure 2 Philadelphia L997, p 153.
Basic Operative Orders: and neck veins for volume status, The cardiovascular
Patient's Name:. system if examined in the pre-operative period and
1. Admit to Ward/Room # found normal is unlikely to change in the immediate
2. Diagnosis: post-operative era. Auscultation of the lung fields is
3. Condition: important in detecting decreased air-entry,
4. Allergies: pulmonary edema and atelectasis. Women who
5a' vital
-q 15 minutes until stabre have undergone general anaesthesia are more likely
to have pulmonary problems than those who had
---q 2 hours for 24 hours
e . --------q 8 hours, if stable regional anaesthesia. The abdomen is examined for
5b. Notify House Officer (H.O) if distension, wetness of the wound dressing and
BP<90/60 > bowel action, which is usually hypoactive in the first
.t' 160/100 12 hours after an open abdomino-pelvic surgery.
I Pulse< 60, > 120 The wound examination for erythema, induration,
Temp.38.0"C tenderness or drainage can be done on the third or
289
fourth day when the wound is opened. Finally, the discomfort. This would enable the woman to start
extremities are assessed for edema, cellulitis at early ambulation, have a sense of control of her body
intravenous sites, and Homan's sign. and for urethral catheter to be removed to allow her
void herself. Adequate analgesia ameliorates the
Having had a good appreciation of the p#entB tissue response from surgical trauma described
complaint(s) and following a physical examirffiion, earlier.
the clinician must be able to foryulqtq an
'assessment' (the 'A' in the SOAP) of the ,patiEntl The inflammation following surgical trauma makes
condition. The overall assessment spells out the pain inevitable. Pain control has been sub-optimal in
cardinal issues, whether the evaluation is normal or many hospitals and this outcome is deeply rooted
there are problems. Good assessment helps in partly in practice culture. Analgesic administration
formulating a plan (the'P') for care. The impression or can be influenced by the ethnicity of the patient''
diagnosis at the end of this evaluation may range Abuse of opioids by health staff has influenced some
from, example'post-hysterectomy with mild pain or health professlonals in restricting the use of opioid
in stable condition' to 'post-hysterectomy with analgesics. A balancing act between achieving good
oliguria or haemoperitoneum'. This approach makes pain control and accountability of issued opioids is
the problems to be solved clear. Using the items in needed.
Figure 2 helps in documenting key clinical
Moderate to severe level of pain are common even in
information.
countries where the full armamentarium of
ln the first 6-18 hours post-surgery, oral fluids with analgesics are available. Clark-Pearson et alu found
liquids can be commenced when the bowels were not 30-40% of patients experiencing moderate to severe
damaged or excessively handled. The delay in pain after surgery. ln a recent study (submitted for
initiating oral liquids has usually been due to nausea West Africa n Col lege of Su rgeons Pa rt I I exa m i nation)
and vomiting which are common side effects of drugs in Komfo Anokye Teaching Hospital involving post-
used in the peri-operative period. The diet can then caesarean section women, 90% of the participants
gradually be made heavier astolerated. experienced moderate to severe pain in the first 48
hours after surgery'. Surprisingly, the level of pain
Patients with significant weight loss prior to surgery control does not affect the overall level of satisfaction
need nutritional assessment for suitability for total of patients favorably, indicating other factors of care
parenteral nutrition (TPN) to promote wound healing play a role.
and recoveryu. Providing.total parentera[ nutrition is
not widely available in resource constrained settings. Post-operative pain control must be initiated towards
ln general, patients with uncomplicated surgery the end of the surgery so that by time of settling in the
should be not restricted from early oral feeds' recovery room, the woman is comfortable. This can
However, in patients with malignancies who have be achieved with intravenous parenteral narcotics
undergone surgery involving the bowels, oral feeds such as pethidine (meperidine), morphine, codeine
are restricted for several days and plans must be and fentanyl. Scheduled dosing (say 4-6 hourly) is
made ahead for nutritional support, preferably total preferred to dosing on demand or at prolonged
parenteral nutrition. ln the absence of TPN, we intervals. The technique which allows patients to
recommehd starting oral preparations with high self-administer small doses of narcotics on demand
protein and energy content (example casilan). is known as the "Patient-controlled Analgesia' (PCA).
It allows titration of measured boluses of narcotics as
The Next 24-72 Hours needed torelieve pain and can provide a more
ln this period, antibiotics that were started about an effective analgesia with manifestation of steady
hour to the su rgery are continued with analgesics and state.
appropriate fluids.
Excellent pain control after major abdominal and
Pain Control pelvic surgery (especially for malignant conditions)
The goal of pain control post-operatively is to ensure can be achieved with continuous epidural analgesia
the patient is pain-free or at worst with minimal
290
i Post-Operative Care
I employing a combination of a local anesthetic and an volume of human traffic during surgery all contribute
opioid. lt offers ex(rellent pain relief whiledecreasing to minimizing surgical site infection and attention
the incidence and side effects ase@ia@ with should be given to these.
,{ systemic narcotic and intrathecal @Sq$esia.
lntrathecal spinal analgesia use sho@,:ffiffied to Fluid Therapy
patients in intensive care unit due.lt$:''itli:ffi*trc of During open abdominal or pelvic surgery, fluid loss
, from the peritoneal surfaces is about 1 litre per hour.
respiratory depression, systemic hyrcterebn ad the
limitation to a single dose so as to redt se He risk of Though most women will require aboul2 to 3.5 litres
! of fluids daily, the duration of the surgery, the volume
central nervous system infections and headactles.
Unfortunately, epidural analgesia is not widely of blood loss and other losses such vomiting should
available in the West African sub-region for reasons of all be factored into calculating the fluid needs of the
post-operative patient.
the skill set in its administration and unavailability or
unaffordabi I ity of the epidural kit.
Fluids given should have adequate amounts of Na*,
i, A combination of parenteral narcotie and non- K*, and Cl and bicarbonates to reflect the
composition of the intracellular and extracellular
t
steroidal anti-inflammatory drugs such as diclofenac
I (eithe r i ntra m u scu I arly or recta I ly) provide synergistic fluid compartments.
effect and good pain control can be achieved for 8-12
Fluid therapy, though basic, is an essential
hours.
ingredient for successful post-operative
ma n agement. Water constitutes a p proxi mate ly 60%
r The sub-optimal achievement of good pain control
requires further training of both physicians and of a young woman's body weight. Fat is composed of
I
nursing staff, first to overcome misconceptions of the less water per gram than muscle. As a woman ages
t use of opioids and, secondly to create the desirable there is increase in fatty tissue and consequently a
F
goals of achieving good pain control. decrease in total percentage of body water. Thus
r while the total body water may be 60% in a young
Antibiotics girl, it may be46% in an olderwoman.
F
't Risk factors for surgical site infection include type of
? surgery (clean, clean-contaminated or dirty surgery), The body fluid is functionally divided into
fi presence of malignancy, duration of surgery, compartments: the intracellular constitutes 40% ot
( prolonged hospital stay prior to surgery and total body weight and extracellular 20% of body
r
?-
concurrent infection. Antibiotic resistant emergence
worldwide (includin| West Africa) poses a big threat.
weight. The extra-cellular compartment is composed
of plasma (5% total body weight), lymphatic (2%
:llrr
) Local antibiotic sensitivity pattern should therefore total body weight) and interstitial (15% total body
i weight). The extracellular compartment (plasma and
r,} guide the choice of antibiotic therapy which should
interstltial fluids) contains a high concentration of
t have activity against broad spectrum of organisms.
+
Whatever the choice of antibiotic, overwhelming sodium, chloride and bicarbonate and low
f
f evidence is for its administration prior to skin concentration of potassium whereas the intracellular
I incisiont, as it has been shown to reduce surgical site fluid has a high potassium, magnesium and
? phosphate and low sodium and chloride.
fI infection. Serum peak concentration of the chosen
antibiotic at the time of incision is needed to kill
, bacteria that may enter circulation. The duration of
Electrolyte composition of the intracellular fluid is in
part related to electrolyte composition of the plasma
: the antibiotic administration depends on the risk
I
factors mentioned earlier. For most gynaecologic
and interstitial fluids. Disturbances in the
: pelvic surgery (clean-contaminated), administration
extracellular fluid are reflected in the patient's
t' symptoms. These facts, combined with the
for 24-48 hours will suffice. The same study by
accessibility of plasma, make the analysis of plasma
T Hemsell showed that short course of antibiotics are
efficacious as longer ones.' Practices such as good
a valuabh guide to therapy. Approximately 30ml/kg
body weight or 2-3litres/day of fluid is required daily
r hand-washing prior to surgery, sterility of surgical
i supplies, operating room air quality, and reduced
by an average adultu''.. This is offset partially by
:,
291
insensible losses of 7.2litres per day which includes maintained over several days, it should be removed
losses from the lungs (600m1), skin (400m1) and by 24 hours after surgery because longer stay it is
gastrointestinal tract (200m1) and the rest by the associated with lower urinary tract infection (UTl).
kidney. ln health, fluid volumes in the extravascular Post-operative lower UTI rates have dropped from
space undergo complex regulation by biood @ite around 35% to 4% with a single dose of peri-
and perfusion of the kidney modulated byantidiuretic operative antibiotics'6'". Lower UTI symptoms
hormone (ADH) and aldosterone. Aldosterone include urinary frequency, urgency and dysuria.
influences the renal absorption of sodium and is Headache, malaise, nausea and vomiting may be
essential in maintaining circulating vascular volume. present when there is upper UTI (pyelonephritis)'
Several factors such as the co-existing medical When UTI is suspected, mid-stream clean collection
condition of the patient, the estimated intraoperative of urine for culture and sensitivity is needed to guide
blood loss, intraoperative fluid replacement, the selection of appropriate antibiotics' The offending
duration of the operation and any ongoing organisms are usually Escherichia coli; less
postoperative fluid losses must be considered before commonly, Proteus, Klebsiella, Enterobacter and
writing postoperative fluid therapy orders. Staphylococcus aureus have been isolated.
Generally, cephalosporins, amionoglycosides,
Fluid administration should be monitored through flouroquinolones, and nitrofuratoin are used in the
fluid input and output chart. Recording of these on a treatment of UTl.
chart makes any fluid deficit or excess obvious on
review for action to be instituted. Should these The incidence of bacteriuria and pyuria is very much
electrolytes be assayed routinely 02-24 hours) post- reduced (from 70 to 15%) in patients receiving
operatively in resource-limited settings? Costs and suprapubic compared to urethral catheterization for
availability of these tests make the authors request more than 72 hoursu. ln operations such as
them when severe vomiting and suspected renal Wertheim hysterectomy, anterior colporraphy,
impairment is present. A pragmatic approach is to Marshall-Marchetti-Krantz, urethral suspension,
have a critical view of all input and output and where where bladder drainage for more than 72 hours is
electrolyte imbalance is strongly suspected efforts necessary, suprapubic drainage is advisedu.
should be made to have these electrolytes assayed to
latrogenic injury to the bladder is in the region of 7-2
help with treatment. Most healthy women after
uncomplicated benign gynaecologic surgery have not
percent of cases". Urinary fistulas after
shown symptoms and signs of electrolyte gynaecological surgery (though forms a
smaller
a bnorma I ities and recovered u neventful ly. number compared to obstetric fistulae) are
troublesome complications, often arising from total
Bladder Care and Urinary Tract Problems. abdominal hysterectomy rather than difficult cancer
operations. Urinary incontinence arising within few
It is not uncommon to have retention of urine after hours of an operation is usually secondary to a direct
gynaecological surgery. For the fear of pain, patients surgical injury to bladder or ureter and immediate
are unwilling to contract the abdominal muscles surgical repair is indicated.
sufficiently enough to initiate voiding. Tenderness,
spasm and edema of the pubo-vesico-cervical fascia The majority of the post-operative fistulas present 8
after anterior colporrhaphy also prevent patients from to 12 days post-operatively and is due to necrosis of
voiding urine voluntarily. Poor pain control makes the tissue resulting from occlusion of the blood
voiding painful, and patients would naturally not void supply from clamping or suture ischaemic ligation.
when there is moderate-to- severe pain at the site of The differential diagnosis of a utero-vaginal fistula
surgery. Adequate pain control makes voiding easier includes spontaneous loss of peritoneal fluid or sero-
and thereby removal of the urethral catheter' sanguinous fluid from the retroperitoneal space.
Repairof such fistulae is not immediate and therefore
Unless it is uro-gynaecologic surgery such as vesico- complete workup to identify the. site and plan the
vaginal fistula (WF) or instances of iatrogenic mode of repair similar to fistula due to obstructed
bladder damage where the urethral catheter is labour is necessary.
292
r
r* fost-Operative Care
I
r Oliguria post-operative period or acute kidney injury can be
evaluated when inadequate fluid intake has been
tY_- Urine production of < 500 mL
in a post-operative patient would
ruled out.
r
k
the causes may be many, the
inadequate fluid replacementi
documented fluid inpuVoutprr,t:
It is worth mentioning that women with pre-existing
renal conditions should not be placed on
rI ascertaining whether the

medications which are nephrotoxic; in cases where it
is unavoidable, the doseshould be reduced,
Ft sufficient fluid. Other causes sueh
tL
or severance, renal impairment 6!@*E the
+
i
;
Figure 3
f Algorithm for Assessing OliEtf,{* & Burggry Without Evidence Of Ureteric Obstruction
I
tt Poor Urine Output
{'i- I
Y
V ls Urethral Catheter in place & Functioning well?
+
Ll
fB
l,l
l yes
(
,
r Ensure Catheter Examine for Cardiac and Pulmonary Status

* is functioning well.
I
{ Y
I Normal
rl. Fluid Challenge test with 500m1 Normat Saline
I
,
?
'*
1
l Good urine output Poor urine output
Evaluate function of the renal, Cardiac and intravascular volume
,r
] +
r Haematocrit
f
rt
t
?
(; Hypotension,FallingHaematocrit LowHaematocrit Normal/increased Output
I
,, lnappropriate
Tachycardia Abdominal distension vital signs & stable Haematocrit

t
c T
Post Operative bleeding
+
Suspect intra abdominal
t
Third spacing
I
Urine creatinine
f-
Haematoma sodium and
osmolality I
t tI
I
!r lmmediate Operative
lntervention
Continue lV Fluids
& Observe
f
r
,r, 293
r
i
Mobilization, Vascu lar complications/ Deep Vein continues postoperatively over varying length of time.
Thrombosis This combined with the hypercoagulable state
induced by surgery are the key factors contributing to
The risks factors for deep vein thrombosis irrelt*de age the development of post-operative deep vein
above 40 years, pelvic surgery, preence of thrombosis. Early ambulation (within 18-24 hours
malignancy, personal risk for thromboth qssades, after surgery) should therefore be encouraged for all
personal medical diseases and the duration af the
-
post-gynaecologic patients this is enhanced by
surgery (Table 2). Essentially the surgeonean harc a achieving good pain control. Options available in
fair assessment of the overall risk of deep vein preventing DVT beyond early ambulation include use
thrombosis (DVT) prior to surgery and appropriate of elastic stockings, external pneumatic
preventive measures can be planned. compression, heparin and combination (heparin and
elastic stockings).
Stasis in the veins of the legs while the patient is
undergoing surgery has been demonstrated and
Table 2
Profile of patients at high risk for Venous Thrombosis
Factor I Condition
Age | >4Oyears
Obesity
Moderate |
I
75-90kg or > 20"/" above ideal weight

Morbid I 2-115 kg or > 30% above ideal weight with reduced
fibrinolysin and immobility
lmmobility
Pre-operative I I
Prolonged hospitalization; venous stasis

lntra-operative I Prolonged operative time; loss of pump action of calf muscle;
compression of vena cava; prolonged bed confinement
Post-operative
Trauma I Damage of wall of pelvic veins

I Radical pelvic surgery
I Release of tissue thromboplastin

Malignancy I Activation of Factor X; reduced fibrinolysin
Prior radiation therapy

Radiation
Diabetes mellitus
Medical Diseases I Cardiac disease; heart failure
Severe varicose veins
Previous Venous thrombosis with or without
Embolization
Chronic Pulmonary disease
294
Post-Operative Care
The use of heparin or low-molecular weight heparin atelectasis (wind), wound infection (wound), deep
in gynaecologic surgical patients has been shown to vein thrombosis from immobilization (walking) and
be beneficial compared to a control group. ln one drug fever (wonder-drugs). Fortunately in many
{F series of women above 40 years undergoing surgery instances, the fever is of low-grade nature and self-
for benign conditions, 23% incidence of deep vein limiting. The clinician must however a rational
t
F thrombosis was found in the control group compared approach to this problem in order to detect infection
rt with 6% in the women receiving low-dose that is starting.
heparinll'12. Should all women undergoing
?
I gynaecologic surgery receive low-dose heparin or Fever < 38"C in the first 24 hours after surgery is
I low-molecular weight heparin? lt should be usually non-specific and rarely traced to infection. lt
r determined on case-by-case basis. For a example, can be monitored closely with 4-hourly temperature
it measurements. Fever that is persistent beyond 24-
woman above 60 years of age undergoing radical
i hysterectomy with lymph node dissection most likely 36 hours or rising requires thorough evaluation to
t
i will require prophylaxis with low-dose heparin or low- determine the cause. Fever resulting from
r
,
molecular weight heparin for prevention of deep vein pneumonia or wound infection does not present in
t thrombosis. Though low-dose heparin is considered the first 24 hours after surgery, as time is required for
to have no measurable effect on coagulation, most microbial inoculum to establish infection, which
t usually takes over 48 hours. Atelectasis, though will
f large studies noticed bleeding complication
especially wound haematoma. Low-molecular not manifest with fever in the first 12 hours, is worth
{
weight heparin have similar deep vein thrombosis considering, especially if it persists beyond 24hours.
i
C rate compared with unfractionated heparin; bleeding
r complications are also simi lartt'to''u Development of pelvic infection with or without
,I abscess following gynaecologic surgery usually
Common Problems occurs after 72 hours post-surgery, and
manifestation of obvious surgical-site infection is
Post-operative Fever usually seen 4 days after surgery.
The differential diagnoses of post-operative fever is
not lengthy and include in order of most frequent- What is plausible as the cause of the fever beyond 24
;
I urinary tract infection (water), pneumonia, hours is therefore not hard to imagine.
:
r
Figure 4
I
Causes DAY
f 1 2 3 4 5 6 1 Week or More
I
Atelectasis
Pneumonia
Wound infection
Streptococcal
-
Or
Clostridial
{
Other bacterial --)
Ovarian abscess
Cuff cellulitis
)
Phlebitis
Superficial
Deep r-
Urinary Tract
infection
Ureteral or
J Bladder injury
i
-)
29s
Pulmonary Complications are useful in such patients.

Gynaecological operations may be complicated by Full-blown atelectasis is readily diagnosed clinically
hypoventilation, atelectasis, pneumonia and (low-grade fever, decreased breath sounds at the
pulmonary embolism. Hypoventilation is defined as bases and inspiratory crepitations) and radiologically
l
the level of alveolar ventilation that is insufflcient to (horizontal lines or plates on a postero-anterior chest
prevent accumulation of carbon
dioxide. X-ray); however micro-atelectasis may be difficult to
Hypoventilation occurs in patients who tend to diagnose clinically and radiologically. Atelectasis is
decrease their tidal volume to avoid pain. Other suspected when there is a fall in PaO, and oxygen
causes of hypoventilation include depression of saturation in the presence of a normal to low PaC0r.
centra I respiratory control f rom obesity, The PaO, can be returned to normal in the initial
neuromuscular disease, restrictive dressing, stages of development by an increase in the inspired
immobility, hypo-mobility and increase carbon oxygen concentration. Chest physiotherapy, deep
dioxide production. breathing, coughing and incentive spirometry is
necessary for established cases. (Where incentive
Patients with obstructive and restrictive respiratory spirometers are not available, balloons or used
impairment are much more likely to develop infusion bags can be used to achieve expansion of t' '
hypoventilation during this critical early lungs.) Positive pressure ventilation and continuo"s
postoperative period. The main indicator for airway pressure is necessary for reversal of the
adequate ventilation is the PaCOr. Such patients process in established atelectasis, while
require pulmonary function tests pre-operatively. bronchoscopy to remove mucus plugs is necessary to
Postoperative pulmonary dysfunction occurs treat extensive cases.
commonly in patients who receive general
anaesthesia. This is because there is airway Occasionally acute respiratory failure occurs. Acute
obstruction from mucus plugs or inappropriate respiratory failure is defined as disturbance in
endotracheal tube placement resulting in collapse of respiratory function that results in a Pa0, of less than
the peripheral small airways of the lung atelectasis. 50 mmHg with or without carbon dioxide retention.u
There is loss of lung volume and difficulty in clearing Adult respiratory distress syndrome (ARDS) is an
secretions. This is often minor except for patients acute respiratory failure that resembles pulmonary
with known risks such as advanced age, obesity, edema; it is a form of non-hydrostatic pulmonary
history of smoking, ASA class lll or higher, pre- edema and represents the final pathways of the lungs
existing pulmonary disease such as asthma and response to acute diffuse alveolar injury for a variety
chronic obstructive pulinonary disease, prolonged of causes as shown in the Table below.u
hospitalization and anaesthesiau'". Such patients at
risk should be educated on the preventive measures The pathogenesis of adult respiration system (Figure
before surgery. They should be counseled on the 5) without evidence of prior lung disease or
importance of deep breathing, coughing and congestion is complex but the final pathway is
incentive spirometry after operation despite post- increased alveolar permeabllity following endothelial
operation wound pain. Special attention should be cell damage. lt is not uncommon and has a high
given to the obese patient with obstructive sleep mortality rate of 50"/"u.
apnea who may suffer airway obstruction after
extubation. Pulmonary consult with the use of
continuous positive airway pressure (CPAP) devices
296
r f
( I
I
Post-Operative Care
It
if
Figure 5
b
F '' "':" Shock Trauma
Ir i:\/
il-
F ':r,@, \ /
:II
W
r1
'''".
tj l€ \.
' / lx ) lrng
F
F
i
s€psi; I virur Pneumonia
I
I
t Comptemtnt activation
/
l
l, I
lncrease C5a
I
I
Aggregation of
I Corticosteriods
granulocytes
F
I
i /
t
lnactivation of Superoxide \ Destruction orcottagen
rI Antiproteases {_ radicals \ prot.ur.s #
f erastin
t \ /
l
\ /
,,
I Endothelial cell \Fibrinoectin

( damage Activation of
t.
complement,
factor, Hageman
$ fibrinogen
I I
I
I
V
,(
/ lncreased capillary permeability
a
-, From Horowitz lR; Post-anesthesia and BostoBentive care ln Te Lindes'Operative Gynecology, 8'n edition, eds. Rock
f JA and Thompson JD. Lippincott-Raven Publication, Philadelphia 1997, p 139.
I
lc
,,
Table 3 Disorders Associated with Adult Respiratory Distress Syndrome
I
Direct lnjury lndirect Causes
Gastric Fluid Aspiration lnfections and sepsis
; Pneumonia
a Pancreatitis
( Thoracic trauma Eclampsia
/ lnhaled toxins including O, DIC
Fat and amniotic fluid embolism Drug overdose
t
/ Acute hepatic failure
L
Massive blood transfusion
I
I 297
..
Table 4: Criteria for the diagnosis of Adult The patient who had received extreme bowel
Respiratory distress syndrome dissection and excision would experience a delay in
the return of bowel action and may sometimes
(1) Clinical history of predisposing require nasogastric aspiration. For such patients,
condition especially those with malignancy, total parenteral
(2) Acute dyspnea nutrition or other alternative should have been
(3) Clinical respiratory distress planned for.
Tachypnea greater than 20
breaths/min Patients on nasogastric suction need the
Laboured breathing
replacement of aspirated gastric contents with
Cyanosis
normal saline or half normal saline containing 20 to
Absence of left-sided heart failure
@) Chest radiograph showing diffuse
40 mmd KCI/I. Patients with marked abdominal
pulmonary infiltrates distension, discomfort, persistently diminished
(5) Pa 0, <50 mmHg or bowel sounds, nausea and vomiting require further
Forced inspiratory oxygen evaluation to determine if it is just a slow return of
concentration. FlO, > 0.6 mmHg normal bowel peristalsis or represents a serious
(6) Pa 0rto FlOrratio < i00:300. condition of bowel obstruction which requires
aggressive therapy. The distinction between
Table 4 summarizes the criteria for diagnosis for postoperative paralytic ileus (adynamic ileus) and
ARDS. The cornerstone of therapy is ventilatory postoperative (dynamic) obstruction is not an easy
support with positive end-expiratory pressure (PEEP) one. This is because dynamic bowel obstruction is
until repair of the capillary damage has occurred. The often accompanied by a paralytic ileus. However,
use of steroids has been controversial. Judicious there are salient differences which are outlined in
management of fluid intake is essential to maintain Table 5. Diagnosis involves a good analysis of the
adequate perfusion of vital organs to avoid further nature of the abdominal pain and physical
complications. examination. Pertinent points of the abdominal
examination should include, assessment for quality
Bowel Control, Ora! Feeding and Gastrointestina! of bowel sounds and palpation in search of
Complications tenderness or rebound tenderness. Pelvic
examination should be performed to evaluate the
Most gynaecologic post-operative women have hypo-
possibility of a pelvic abscess or haematoma that
active to normal bowel sounds and can initiate oral
may contribute to the ileus. Abdominal radiograph in
liquids in 12-18 hours after surgery. ln vaginal
the supine and upright position is helpful. It must,
surgeries where bowels are not handled at all, sips of
however, be noted that free air may collect under the
liquids can be started earlier provided nausea and
diaphragm for 7 to 10 days after a laparotomy so
vomiting are absent. With the increased metabolic
such finding detected after an erect radiography is
activity of the post-operative woman, nutritional
not indicative of perforated viscus in most patients. A
requirement should be provided to aid healing. lt is
key feature of advancing bowel obstruction is
therefore important that the woman returns to her
necrosis of the bowel wall which will cause a
normal diet as soon as practicable, especially with
progressive leukocytosis, along with distension and
the not-too-easy to get total parenteral nutrition peritonitis. Therefore serial monitoring of the white
products in West African countries. ln surgeries
blood cell count and differential count is an
where the bowels were neither damaged nor
important method for differentiating between bowel
excessively handled, liquids (containing calories) can
obstruction and paralytic ileus. The major cause of
be started and gradually move to heavier foods as
morbidity and death with bowel obstruction is delay
tolerated.
in diagnosis with resultant strangulation and
secondary infection.
298
r
t,
Post-Operative Care
Table 5: Differential Diagnosis Between Postoperative lleus Postoperative Obstruction

I
I Clinical Feature.; Postsoerative lleus Postooerative Obstruction
Abdominal Pain Discomfort from Distention but Cramping, progressively severe
not erarnping pains
Relationship To lndex Operation Usual.ly within 4-72 hours ot Usually delayed; may be 5-7 days for
ooeration remote onset
Nausea and Vomitine Present Present
Distention Present Present
Bowel Sounds Absent or hypoactive Borborygmi with peristaltic rushes and
hish-oitched tinkles
Fever Only if related to associated
peritonitis
Abdominal X-Ray Distendetj loops of small and Single or multiple loops of distended
large bowels; gas usually bowel usually small bowel with air-
oresent in colon fluid levels
Treatment Conservation with nasogastric Partial : conservative with nasogastric
suction, enemas decomoression : or Comolete: Sureical
The management of ileus includes gastrointestinal gastrointestinal contrast material rather than barium
decompression and appropriate intravenous can be used to assess the gastrointestinal continuity
replacement of lost fluid and electrolytes. This without causing barium peritonitis. A diagnosis of
involves: intraperitoneal gastrointestinal leakage or fistula
(1) The passage of a nasogastric tube to evacuate the formation requires immediate surgery unless the
stomach of its f luid and gaseous content. fistula has drained spontaneously through the
abdominal wall or vaginal cuff. Conservative
(2) Adequate replacement of lost fluid and management of a small bowel entero-cutaneous
electrolyte. This must take account of sequestrated fistula is feasible if the leakage is small and there is
fluid in the distended bowels and peritoneal cavity. no sign of peritonitis. lt involves nasogastric
Careful monitoring of blood electrolyte is necessary
decompression, fluid and electrolyte replacement
for correct repl acement.
and antibiotics to treat associated mixed bacterial
infection. lf spontaneous closure of the fistula does
lmprovement of severe ileus is recognized by
not occur within the period of two weeks, then
reduction in the abdominal distension, return of
surgical correction will be necessary. Recto-vaginal
I normal bowel sounds, and passage of flatus orstools.
fistulas and faecal incontinence that occur following
When that happens, the nasogastric tube is removed
hysterectomy or repair of enterocele are usually
and liquid diet instituted. lf there is no improvement
located at the upper third of vagina and usually
during the first 48 to 72 hours of medical
follow extensive adhesions in the recto-vaginal
management, then other causes of ileus such as
septum associated with PID or endometriosis. Rectal
ureteric injury, unrecognized gastrointestinal tract
fistula usually present 7-14 days after operation.
injury with peritoneal spill, peritonitis from pelvic
lnitially the patient presents with the rectal passage
infection, or fluid and electrolytes derangement such
of blood clots following a rupture of a haematoma
as hypokalaemia must be sorted out through
into the rectum and then follows involuntary passage
abdominal imaging and electrolytes level and
of gas and faecal material through the vagina.
managed.
lmmediate repair is not advised and one needs 8 to
Gastrointestinal fistulas after gynaecological surgery
12 weeks after the injury to achieve a successful
are rare and are often associated with malignancy,
repair. A small recto-vaginalfistula may be managed
prior radiation therapy or surgical injury to the large or
conservatively with a low residue diet and
small bowel that was unrecognized or improperly
diphenoxylate hydrochloride (Lomotil) in the hope
repaired. The clinical presentation is similarto that of
that decreasing the faecal stream may allow closure
small bowel obstruction or ileus but for the
prominence of fever in this case. Water-soluble of ihe fistula20. lf spontaneous closure is not
299
achieved, repair is undertaken after inflammation wound infections however occur after the 4'n
has resolved. A defunctioning colostomy may be postoperative day when the patient complains of
necessary before closure of a large fistula. feverand pains around the wound. The management
of such wounds are usually mechanical although
Operation Site Complications treatment with antibiotics is often used. The infected
portion of the wound above the fascia is laid open
Most gynaecological operations are clean- and debridement undertaken followed by frequent ie
contaminated and infection rates have been lower 2 or 3 times daily dressing until the wound is clean
than 5o/ou'to The number and virulence of bacterial and filled with granulation tissue when in some cases
contamination and the resistance of the patient are secondary closure is done. Primary closure of
the main factors underlying wound infection. contaminated wound is often done with antibiotics
Bacterial wound contamination/innoculation occurs cover. However, delayed secondary wound closure
during the operative procedure and usually from technique employed for contaminated surgical
endogenous organisms such as gram-positive cocci, wound is known to reduce wound infection by tenfold
aerobic and anaerobic organism. ln clean t7) After closure of the fascia, vertical interrupted
procedures, the number of innoculated organisms
mattress sutures passed through the skin and
are small and bacterial growth is then determined subcutaneous layers are placed 3cm apart but are
mainly by the host resistance. Factors that decrease not tied. The wound above the fascia is thus left
tissue oxygen and also leave the wound with open. Wet wound dressing and care is started
excessive amounts of necrotic tissue, such as poor immediately after surgery and continued until the
tissue handling, are the determinants of the host wound is noted to be granulating well. The wound
resistance to wound infection. Local factors are edges are then approximated by knotting the sutures
haematomas, necrotic tissue, foreign bodies, dead and also inserting a few more sutures or applying
space, use of cautery, and decreased local tissue staples or tapes to obtain good apposition of the
perfusion and systemic factors such as obesity,
edges ofthe wound.
diabetes, liver disease, malnutrition,
immunosuppression, defects in the reticulo- Vaginal cuff cellulitis is not uncommon in its mild
endothelial system, age and the duration of form for patients undergoing hysterectomy but when
preoperative hospitalization. The local factors are there is purulent discharge, fever and leukocytosis
more significant determinants of the host resistance and pelvis pains, then broad spectrum antibiotics
to infection. A woman's preoperative infection cover is necessary. lf a fluctuant mass is present
eightfold''n and corticosteroid therapy affects wound gentle probing of the wound with a blunt instrument
i nfection only i n the first 5 days of wound healing. to let out the pus may be necessary.
A study''' has revealed that wound infection can be Wound dehiscence is the disruption of any of the
reduced by 4-fold if the following are followed layers of a surgical incision. lt is said to be partial
religiously: when the rectus sheath is intact and only the skin has
- Shortpre-operativehospitalstay disrupted, or complete when all layers are disrupted
- Hexachlorophene showers priorto surgery
and bowel is exposed. Complete dehiscence also
- Minimizing shaving of the wound site
termed evisceration, usually occurs between
- The use of meticulous surgical technique
postoperative days 5 and 10 and occurs in
- Decreasing operative time as much as
possible approximately 0.5% to 2% of gynaecologic
- Bringing drains out through sites other than laparotomiesn. The early signs of impending wound
the wound and disruption is the spontaneous passage of
: Finally disseminating information on rate of serosanguinous fluid from the abdominal incision.
wound infections to surgeons. The causes of wound dehiscence include wound
infection and haematomas, sutures either breaking
Streptococcal and clostridial organisms are virulent or cutting or knots untying and tension in suture line
and have been implicated in wound infection because of abdominal distention and chronic lung
occurring from the 1" to 3'o postoperative'day. Most disease. Obesity, malignant diseases and diabetes
300
are systemic causes of of wound dehiscence. Prior employs a far-tarlnear-near suturing in which only
radiation therapy and incision made throtgh an area the anterior fascia is included in the near-near bite.
of a previous incision lend themselves to wound There appears to be Iittle benefit in using interrupted
breakdown. A midline incision is rrm?€ fi risk of primary closure techniques as continuous closure is
disruption than a Pfannenstiel incision. The local significantly fasteru. However, interrupted sutures
causes of wound dehiscence are more important than have been employed for infected wounds and
the systemic factors, although both shquld be following complete wound dehiscence. Closure of
considered in the preoperative management of the the subcutaneous adipose tissue in obese women
patient. Dexon and vicryl are superior to catgat has been shown to significantly reduced wound
because they have predictable absorption rates, dehiscence but the same cannot be said for wound
reduced tissue reaction and greater tensile strength drainageu. Complete wound dehiscence should be
(Table 5). Wound closure with Smead-Jones repaired in theatre where clots, necrotic tissues,
technique is said to result in less dehiscence and sutures and foreign bodies are removed'and
therefore recommended for high risk patients such as i mmed iate re-closu re effected.
obese, infected and malignant cases. The technique
i
Table 5
r
I
I Type Generic Name Raw Material Trade Knot Tensile Wound
I Names Security Strength Security
I
I 50%
f
I ABSORBABLE
I Natural collagen
( Plain Submucosa of + ++ 5-7 Days
i Provoke a lot of catgut sheep
inflammatory instestine
r reponses and
predisposes to Chromic catgut + Buffered +++ ++ 10-14
( infection chromicizing Days
t
f
I
{ Synthetics . Polyiglecaprone 25 Monocryl ++ +++ 7 Days
Minimal
i inflammatory Polyglactin 910
response (Rapide) Vicryl
a
Rapide ++ +++ 5-7 Days
Polyglycolic acid 28 Days

Homopolymer of Dexon, ++++ ++++
glycolide Dexon-S,
Dexon-plus
+ Poloxander
188
Polyglactin Vicryl t4-21
Coating +++ ++++ Days
Copolymer lactic
and glycolic acid Coated
Vicryl
+ Calcium
stearate
Polydioxanone coating PDS
t ++ ++++ 28 Days
Modified from Droegemueller W: Postoperative Complications ln: Comprehensive Gynecology 4'n ed. Edited by
Herbst A, Mishell Jr D R, Stenchever MA, Droegemueller W. Mosby Yearbook, lnc 2001, p.601.
301
Miscellaneous Complaints and Complication
Lymphocyst results from collection of lymphatie fluid b. detailed pre-operative counseling about
within the pelvis following retrograde drainage of indications for hysterectomy, the nature of the
lymph after pelvic node dissection. Small ones operation and the expected post-operative
usually regress spontaneously while lar.ger ones course improves post-operative well-being;
causing pressure symptoms on the uratEr and and
bladder must receive intermittent aspiration Or
insertion of an in-dwelling catheter under ultrasound c. healthy sexual function before surgery is the
guidance. best predictor of healthy sexual function after
surgery.
Femoral neuropathy where patients experienee
numbness, parasthesias and diffieulty wlth gait arise lnformation for Patient
from ischaemic necrosis of the femoral nerve Efforts should be made to make the patient
following continuous pressure from a self-retaining understand type of surgery done and what to expect
abdominal retractor about 4-6 cm above the inguinal in the next 3-6 months. The language used should be
ligaments where the nerve pierces the psoas muscle. simple and explanation can be done with models to
The muscle and sensory functions return aid understanding. lt is frustrating to have a pati''nt
spontaneously over several weeks to months. with operation complication who cannot tell w,.-.
Prevention involves placing folded towels between
surgery has been done. Equally more frustrating is
the skin and the self-retaining retractors.
lack of clinical information from one clinician to the
Sexual Dysfunction other.
Psycho-sexua I dysf u nction after tota I hysterectomy is
a controversial topic. Earlier studies supported an ln surgeries where major complications occurred
increase inpsychosexual dysfunction after such as ureteric injury, should the woman be
hysterectomy but more studies refute this notion'u informed? Existing policies of the department or the
There are three ideas that virtually all researchers'u hospital should guide information to be divulged and
agree on: subsequent counseling, Overall, Brennan and
colleagues found reduced litigation and monetary
a. concomitant removal of the ovaries leads to a compensation in instances where patients were
significant increase in psycho-sexual informed of severe complications; and where
dysfunction in the pre-menopausal woman litigation was pursued, compensation awarded was
(whether hormone replacement therapy can below average compensations paid for medico-legal
reverse this trend is unclear); cases".
302
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Harken AH: The case for beta-adrenergic com pa rative th rom bopl astin yersus dose
Blockade as prophylaxis against heparin prophylaxis of deep venous
perioperative cardiovascular morbidity and thrombosis. BMJ, 7, 1978,272-274.
mortality. Archives of Surgery, 136(3) 13. Borstad E, Urdal K, Handeland G, et al.
2001, pp.286-290. Comparison of low molecular weight
5. Horowitz lR: Post-anesthesia and heparin vs unfractionated heparin in
postoperative care. ln: Te Lindes )perative gynecological surgery ll. Reduced dose of
Gynecology. Eigntn Edition. Eds. Rock JA low molecular weight heparin. Acta Obstet
and Thompson JD. Lippincott-Raven Gynecol Scand 71, 1992 pp. 471-475.
Publishers, Philadelphia, 1997, pp 127- l4.Heilman L, Kruck M, Schindler AE.
55 Prevention of thrombosis in gynecology.
6. Clark-Pearson DL, Alvarex A, Havrilesky L, Double-blind comparison of LMW heparin
?
Laucaster J: Preoperative evaluation and and unfractionated hepari n. Geburtshilfe
postope rative ma nagement. I n : Noyak's Frauenheilkd 49, 1989pp. 803-907.
: Gynecology. 13th Ed., Ed Berek, JS. 15. Kaaja R, Lehtovirta f Venesmaa E et al.
Lippincott Williams & Wilkins, 2002. pp Comparison of enoxaparin, a low-
569-633 molecular weight heparin and
Toglia MR and Weg JG. Venous unfractionated heparin, with or without
Thromboembolsi m d uri ng Pregnancy. New d i hy roergota m i ne, i n abodom i na I
Engl J of Med 1996; Vol (335Q), pp 108- hysterectomy. Eur J Obstet Gynecol
1 14. Reprod Bio, 47, 1992 pp141-145.
16. Hemsell DL. lnfections after gynecologic
8. Azanu, W, Post-operative pain in post- surgery. Obstet Gynecol Clin North Am 16,
caesarean secflon women in Komfo 1989, pp. 381-400
Anokye Teach i ng Hospital. Personal lT.Bartzen PJ, Hafferty FW. Pelvic
Communication. laparotomy without an indwelling catheter.
303
Comprehensive Gynaecologr in the Topics
A retrospective review of 949. Gynecology. 4th Ed. Edited by Herbst A,

Obstet Gynecol 156, L987, Mishell JR DR, Stenchaver MA )
1432. Droegemueller W. Mosby Yearbook. lnc
18.. Hanis WJ: Early 1998. pp 771-821
abdominal and vaginal 21. Studdert DM, Mello MM, Gawande A A, .i
Obstetrical and Gandhi T K, Kachalia A, Yoon C, Puopolo
Q1) 1995. pp 795-8OS A L, Brennan T A. Cldims, erors and
lt
19.. On, Jr. JW, On PF: Compensation Payments in Medical 1
ln: Textbook of ffi5.1i'. Malpractice Litigation. N Engl J Med "lj
ed by Copeland U. BB:9 2006; Vol 354 pp. 2024-2033. l

20. Drregemueller W: hi
complications. ln :
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CHAPTE2T
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Advances in Contraception
JT Mutihir and E EEmuveyan
:
!ntroduction development towards achieving the above goals.
i
Contraception, which is the prevention of conception This chapter reviews development of the established
by methods other than abstinence from coitus', has contraceptive methods with particular emphasis on
been known and has been in use since the early years those areas with recent advances. There are
of human existence albeit at a very primitive level. basically two different methods or broad groups of
Under natural conditions, a high conception rate is coniraceptives, namely, the natural family planning
counteracted by high fetal and maternal death rates methods and the artificial methods. The artificial
and by short life expectancy imposed by disease, methods include coitus interru ptus a nd the
violence or wal hence stabilizing the size of the traditional and modern methods.
family and community.
Natural Family Planning Methods
. However, with the advancement in medicine and Naturalfamily planning is a general term that applies
improved socio-political environment there has been to various methods that have been developed to help
increased survival rates and long life expectancy with women and men determine the fertile and infertile
consequent increase in population. The need to times of a woman's menstrual cycleand can help
;
control this population explosion as well as further either achieve or postpone pregnancies'0. The
improve maternal well-being amongst others, saw natural methods of contraception are based on the
the introduction of family planning or birth control; ability to predict the time of ovulation and so abstain
+
i.e., the use of contraception to limit family size and from sexual intercourse in that relatively short time
age structure, in the early 1950s. This, itself led to when conception is most likely to occur. No drugs or
the contraceptive revolution in the 1960s with the devices are needed in these methods of
introduction of the Pill. lnspite of the introduction of contraception.
family planning services in developing countries over
the years, the fertility rates in these countries are still The Rhythm/CalendarAafe Period Method
high: Nigeria 5.5; Sierra Leone 4.9 and Liberia 4.7'z. This relies on abstinence during the ovulation period
The unmet need for Family planning (the percentage believed to be 14 days before the next menstruation.
of married women who want to space their next birth A good knowledge of the woman's menstrual cycle
or stop child bearing entirely, but are not using analyzed over a72 months period helps to determine
contraception), still remains low particularly in the woman's periods of ovulation. The couple
Nigeria with 15%'. With the increased publicity of abstains from sexual intercourse 5 days before and 5
the use of contraception, there has also been days after the date of ovulation.
imposed the need to provide safe, effective, Basal Body Temperature Method
acceptable and affordable means of contraception.
l' From the daily basal body temperature (BBT) chart,
Different methods of contraception are therefore in
use today'-nand each has over time been undergoing
the ovulation date is determined and coitus is
a
avoided.
305
--t
Cervical Mucus (Billing's) Method and infertile days of their cycle and also monitors
This method relies on the change in the consistency cycle length. The 'Cycle beads' has 32 beads, each
'and appearance of the cervical mucus just before bead representing a day of the menstrual cycle' The
ovulation. Although a lot of publicity has been given red bead represents first day of menstruation and of
to this method by proponents of natural family the cycle, while the white beads represent days when
planning, the extent of its use by the community is a woman can get pregnant when there is sexual
doubtful. intercourse. Therefore the partners and expected to
abstain from coitus during the 'white days'' The
Sympto-thermal Method method has been said to be 95% effective with
' The combination of BBT chart and cervical mucus perfect use".
methods give a more accurate prediction of the time
of ovulation and it is said to be the most effective .Artificial Methods
natural family planning method. Pregnancy rates of A. TraditionalMethods
about 25 per 100 woman years have been reported. These methods involve the use of mixtures of
,
plants & herbs, charms, copper or zinc rings or
Lactational Amenorrhoea Method (LAM): pendants, sponge soaked in vinegar, potassium
' This might be considered a new form of natural salts and even supra-pubic incisions rubbed'
'family planning for postpartum and breast feeding with locally made medicationsu.
mothers. The Bellagio consensus was the finding
from many studies that a woman who is fully or near B. Coitus lnterruptus
fully breastfeeding her baby and who remains This is one of the oldest methods of
amenorrhoeic during the first six months postpartum contraception, and still widely used today with a
has less than 2 percent chance of pregnancy". This failure rate of about 18 per 100 woman years".
was called LAM as a usable new method of
C. Modern Methods
contraception. The absence of any of the three
criteria above, i.e. amenorhoea, fully or nearly fully
1. lntrauterine Contraceptive Devices IUCD)
breast-feeding and first six months postpartum
One of the most widely used contraceptive methods
renders this method ineffective.Breast-feeding lt has undergone a lot of
in the world today.
ultimately leads to anovulation and deficient luteal
development, from the first generation or non-
phase and is said to be dependent on the frequency,
medicated devices dominant in the 1960s to the
duration and intensity of suckling".The present day 3rd generation devices. The second
neuroendocrine mech4nism involved in producing generation medicated lUCDsof the 1970s&80s had
these effects is not clear but include among other primarily copper added to them. The third generation
possibilities the disturbed frequency and amplitude
IUCDs are an improvement on the second generation
of GnRH stimulus, which in turn influences LH devices, and some are impregnated with
pulsatility, inadequate pituitary response to GnRH
progestogen3'r5-17. All the IUCDs except that made of
and heightened sensitivity to estrogen and other steel are impregnated with barium for easy
ovarian products or influences of brain opiates and
radiological identification.
other transmitters.
FirstGeneration IUCDs
"Kitchen" Method These devices include the Lippes loop and Saf-T -coil
Attempts to develop other methods of predicting
made of plastic, the M-device and the Y-device made
ovulation e.g. dipstick to determine changes in
of stainless steel, the Dalkon Shield made of
urinary steroids productionuare also in progress by polyvinyl acetate, the copper 7 (Gravigard ) and
theWHO.
copper-T -200.
Standard Days Method i Cycle Beads: lt is also a

Second Generation I UCDs
natural family planning method. lts use is based on These include the Nova-T (Noncard) and Multiload
the knowledge that the menstrual cycle is made up of 250. The basic difference in the copper devices is in
a fertile phase preceded and followed by infertile the shape and the amount of coPPer.
days. The method helps users to identify the fertile
306
Adva nces i n Contraception
Third Generation IUCDs The Combined Oral Contraceptive Pill

These include coplrer T 380 A, 380 S, 380 Ag, This was the original type of pill produced. To date it
Multiload 375; Copper Safe 300 (Cu-safe 300), remains the most popular method of contraception
Copper-Fix 330 gard 330 and Levonorgestrel- for young women. The initial products contained
releasing IUCD (LNG -lUD or Levonova). high doses of estrogen and progesterone. A link
between combined oral contraceptive pills and
The third generation intrauterine contraceptive venous thrombo-embolism in the 1970s was
devices have been developed to reduce some of the attributed to the estrogen content and also in the
common side effects related to IUCD use as we,ll as 1980s evidence appeared that the progestogen
combine the benefits of IUCD and hormonal content may be important in determining the risk of
contraception in other cases. Some of the devices arterial disease''" Hence the current combined oral
have design modifications to reduce the incidence of contraceptive pills employ the lowest effective dose
pain, spontaneous expulsion and uterine bleeding, of both estrogen and progestogen. Of more concern
Cu-T380A was by far the most popular IUCD in the recently has been the possibility that combined oral
world in the late 1990s. lt has one of the lowest contraceptive pill may influence a woman's risk of
pregnancy rates among all contraceptive methods developing cancer in later life. While the risk of
but still has the problems of bleeding and pain. Cu- carcinoma of the endometrium and ovary is reduced,
T380A will soon be replaced by Nova T380. that of cervical neoplasia is said to the adversely
affected. Regular cervical smears are therefore
Copper-fix or Flexigard 330 has six copper sleeves on
essential for combined oral contraceptive pill users.
a simple filament polypropylene thread with a total
There is also concern about combined oral
copper surface area of 330sq.mmu" Studies so far
contraceptive pill use before the first pregnancy and
have shown a high degree of efficacy but the insertion
the possible risk of breast cancer.
procedure requires some training.
Efforts are still being made to find formulation of
Progestogen impregnated IUCDs include
combined oral contraceptive pill with the minimum
Progestasert, a T-shaped device made of a semi-
metabolic side effects. To this end new synthetic
permeable membrane of ethylene-vinyl acetate
progestogen has been tested in humans with the
wh ich releases progesterone at a rate of 65
possibility of being introduced for clinical use soon.
micrograms in 24 hours for 1 year. Levonorgestrel-
These include gestodene and norgestimate. The
releasing IUCD is a T-shaped device with a reserve of
former is more potent tha n levonorgestrel .
levonorgestrel in the siloxane collar around the
vertical stem from where LNG is released at a rate of The sequential pills contain estrogen alone for the
20 micrograms/day'u. This contraceptive combines first 14 -16 days followed by combined estrogen and
the benefit of hormonal contraception and that of progestogen for 5 -7 days.
IUCD. Another advantage of LNG released in the
uterine cavity is a reduction in menstrual blood loss. The Minipill contains progestogen only and
These devices have a life-span of up to seven years. isparticularly suitable for older women'o'". lt is less
The Gynefix"is a novel, frameless IUCD which effective than the combined oral contraceptive pill
requires specific training to fix as the insertion and causes irregular vaginal bleeding and has to be
technique is quite different to that of conventional taken very regularly. Hence its use is far less than
lUCDs. thatof the combined oral contraceptive pill.
2. Hormonal contraception B. Vaginal Contraceptive Pills (VCP): A major line of

contraceptive pill development is the development of
A. Oral Contraceptive Pill (OCP) the vaginal contraceptive pill based on the
The introduction of the oral contraceptive pills (OCP)
observation that the regular oral contraceptive pills
in the early 1960s was the beginning of a
inhibited ovulation when administered by the vaginal
i contraceptive revolution. At present there are three routet'''"
basic types of OCPs, namely, the combined, the
sequential and the progesterone-only or minipill.
307
C. lnjectables: Two injectable progestogens generations of implants the first generation being
dominate this category in presenf'day us4e, Depo- Norplant. Norplant-2 and lmplanon are classified as
medroxy progesterone acetate, 150mg (BMPA) and second generation implant systems while Uniplant
N oreth isteron e ena nth ate, 2 00 m g ( N ET-,|SH. +#h le
i and Nestorone (ST-1435) are classified as third
DMPA isgiven every 12 weeks NET-EN ia,Sffiffiffi.y generation systems''".
8 weeks. Both injectables are very effective bts ha{re
a major disadvantage of irregular bl#ifig. Ftew Following the suggestion by Croxatto and Segal on
longer acting esters of synthetic progestogens which the use of sub-dermal capsules of silastic as a basis
at lower doses are able to give contraceptive for long-term contraception, resea rch a nd
protection for period of up to six months have been development was carried out about twenty-five years
developed by the WHO-HRP programme'4. These are ago. After trials with chlormadione acetate and
cyclobutylcarboxylate of DMPA (HRP-001), the megestrol acetate, levonorgestrel proved more
butanoate (HRP-002) and the cyclopropyl- successful leading to the production of the first
carboxylate of LNG developed by the WHO Special contraceptive implant which was Norplant. Norplant
Programme in Human Reproduction. However, consisted of 6 flexible
capsules each containing
irregular bleeding is still the major reason for 36mg of levonorgestrel. The six capsules together
discontinuation. released levonorgestrel at the rate of 85
micrograms/day in the first year of use and 30
Depo-Sub-Q proveralO4'' (Sayana Press): A new micrograms/day by the third, fourth and fifth years of
su b-cuta neous Depot- med roxyprogesterone (D M PA- use. lt was very effective and acceptable, offering
sc) provera has been produced and being used in convenience of use over a 5 year period. lt was
many family planning clinics in Africa. lt is of a low inserted subdermally in the upper arm below the
dose formulation, dose: 104mg for 12 weeks. lt is elbow. lt has however been withdrawn giving way to
given in a pre-filled uniject, meantforself injection. Norplant-2 orJadelle.
Monthly Combined lnjectable Contraceptives (ClC): Norplant-2: is a modification of Norplant and

Addition of short or medium acting estrogens into the consists of two silastic rods each containing 70mg
progestogen preparation has resulted in improved levonorgestrel with an effective lifetime of 5 years.
endometrial bleeding pattern. Two of such lmplanon: a single rod implant developed by
combinations have been developed; one contains low Organon International and launched in 1999
dose DMPA (25mg) and estradiol cyrpionate (5mg1 consists of 1 ethylene vinylacetate (EVA) copolymer
(Cyclofem) while the ottrer contains NET-EN 50mg device containing 68 mg of 3-keto desogestrel, the
and estradiol valerate 5mg (Mesigyna). Also these active metabolite of desogestrel. lt releases the
are given in once monthly doses.New injectable progestin at a rate of 30 micrograms/day and is
delivery systems with 400mg of progesterone only effective for 3 years. lt however has the same
and a 200mg plus 5mg progesterone-estradiol irregular bleeding problems of other progestogen-
combination have been developed. Work is still on to only contraceptives, menstrual irregularity being the
produce improved injectables with 1 to 6 months' commonest indication for early removal'n.
duration of action. Different approaches presently
exist. lmplanon NXT: a newerversion of lmplanon has now
been introduced. lt
is essentially identical to
Macrocrystalline formulation of natural steroids lmplanon except it has 15 mg of BaS04 added to the
including the development of monolithic sustained core and therefore detectable by x-rays when
release system has been developed. Two esters of location at removal poses a challenge. lt has a pre-
NET and LNG, the cyclobutvlcarboxvlatebutanoate, Ioaded applicatorfor easier insertion.
have been shown to effectively suppress ovulation for
up to 9 months at a dose of 50mg. As of now, Sino-implant (ll): a safe, highly effective cheap sub-
12.5mg of these formulations which suppress dermal contraceptive implant consisting of 2 thin
ovulation for 2 -3 months are currently beingtried. flexible silicone rods and marketed under the global
D. Subdermal lmplants: These include three brand name Levoplant. Each rod contains 75mg of
308
f
I
f
{-
r
I
Advances in Contraception
{
I
> levonorgestrel. Like other implants, they are inserted
I A new type of ring containing both an estrogen and a
f under the skin in the upper less dominant arrn of a progestogen has also been developed. lt contains
rr client, lt is manufactured in China by Shanghai Etonogestrel and ethinyl estradiol. lt is left in situ for
Dahua Pharmaceuticals Co., Ltd, Tf,e.ffisif, drive of th ree weeks to in h ibit ovu lation then removed for one
r the Sino-implant initiative has bWr.r,'@ing to week in a pattern similar to COC pill to allow for
t
f increase access and affordability ot hiSl Sralfty long withdrawal bleeding.0ne of the newest
t-
I
acting reversible contraceptive imptants i'n low developments in hormonal contraceptives is the
I
i resource settings. FHI 360 (Family Health vaginal contraceptive ring, also known as the Ring
f I
lnternational), a nonprofit human devetopment and sold under the brand name NuvaRing. Each ring
I organization, provides technical assistance to provides continuous protection against pregnancy
I
i,
facilitate global introduction of Sino-irnplant and for up to one month.
I supports the World Health Organization (Wt{O) pre-
( qualification application process. ln November Progesterone vaginal Ring (PVR) is a progestogen-
t 2076, United Nations Populations Fund (UNFPA) only ring that exerts its contraceptive effect by local
( approved Sino-implant for purchase by its country action on the cervical mucus and the endometrium.
!
programs through the WHO Expert Review Panel lt is said to inhibit ovulation in about 50% of users.
I
processto. Progesterone diffuses at a continuous flow of 1Omg
F\- per day through the silicone membrane. lt prolongs
*
t Uniplant: another contraceptive implant; a single lactation amenorrhoea and therefore used for
silastic implant systerrr containing 55mg nomegestrel postpartum contraception after 6 weeks of delivery
I
? acetate with contraceptive effectiveness of 1 year and for 3-4 months and then replaced". For now,
duration. use is stopped when menstruation returns, or for a
maximum of 1 year. lt is not removed during
I
( Nestorone (ST-1435): is a relatively new form of

r single implant system with arr efficacy of one and a
i ntercou rse or menstruation.
r
half years'duration.
r G. The Contraceptive Patch: This is a trans-dermal
I combined contraceptive systemsquare, flexible,
j lnsertion and removal of the non-biodegradable extended release matrix patch system. lt contains
i implants is by a minor surgical technique performed
under local anaesthetic. Any of four surgical
norelgestromin (NGMN) and ethinyl estradiol (EE)
for use in a weekly dosing schedule. lt is female-
r techniques3' ,ry be employed in their removal,
{ controlled method and has speedy contraceptive
I namely, the standard method, the l'U" technique, the reversibility. lt allows forsexual spontaneity, is highly
pop-out method orthe Emory technique.
a
t
efficacious and high rates of compliance among
I USETS.
E. Biodegradabte delivery systemsr These can be
i microcapsules, microspheres, liposomes, H. Contraceptive Microchip: A microchip that could
microsponges or implants. €.9., Capronor (1 capsule
(. release controlled amounts of levonorgestrel. A
with LNG yearly) and Annuelle (4 petlets with 90% woman could turn on and off as she likes, and which
r norethisterone and 10% cholesterol) also effective for she can use for many years. The chip, 2Ox2Ox7mm,
: 1 year. These can be delivered intravenously, designed to be released under the skin of the arm,
i ntra m uscu la rly, subcuta neously or i ntra-peritoneal ly.
buttocks or abdomen would provide contraption for
There are trials on local administration to cervix, years. The chip contains tiny reservoirs of
a vagina, uterus, as well as inhalants and nasal sprays.
levonorgestrel, already used in some contraceptives
; E Vagina! rings and lntracervical devices: These are
and releases 30mcg daily, and can hold enough of
impregnated with levonorgestrel and usually made of
the hormone to do this for 16 years. When a woman
Silastic materia13. In vaginal rings, the steroid is
wants to conceive, she sirnply turns off the device
placed in a central core (core type) or in a layer
with a remote, and thus no need for removal of the
(rf' around the core (shell type). The rings are pliable and
l>
I
chip until after 16 years of use have elapsed. A
I similar to inert pessaries used in the management of
titanium hermetic and platinum seal releases the
utero-vaginal prolapse.
hormone by passing an eleetric current from an
309
internal battery which melts it temporarily, allowing introduction for emergency contraceptiont' lt is a
small doses of the levonorgestrel to be released each competitive inhibitor of progesterone acting at
day. The developers of the microchip believe that the the level of the progesterone receptor and is
technology would augment the goal of FP202O, the capable of interrupting early pregnancy up to 10
commitment of a coalition of governments, weeks after missed period. lt is used once a
companies, philanthropies, and non-NGOs to month. Epostane inhibits an enzyme involved in
provide family planning to 120 million more women progesterone synthesis and can also interrupt
and girls by 2020. The MicroCHlPS (an lT start-up pregnancy. However it has to be given for 4 days
Company with links to Massachusetts lnstitute of and may not do so in all cases.
Technology) with the backing of Bill Gates plan to
submit the implant for pre-clinical testing in the (e) Danazol - a synthetic androgen is now also
United States in 2017, and believe that the device used for this purpose. Two doses of 400mg taken
could go on sale by 2018". 12 hours apart are used but three doses at
intervals of 12 hours have also been investigated.
l. Post-coitalcontraception: This is otherwise known However research on its effectiveness has not yet
as emergency or secondary contraception or morning been defin itively concluded.
after pills',. This is used to prevent pregnancy after
unprotected sexual intercourse. Post-coital (0LHRH analogues - Buserelin (intranasal)
contraception can be mechanical or medicinal. Goserelin (subcutaneous), Nafarelin and
Copper IUCD inserted up to seven days after Histrelin have all been investigated.
unprotected sexual intercourse is capable of
(g) Ulipristal acetate - a synthetic progesterone
preventi ng pregnancy f rom bei ng establ ished'u.
agonist/ antagonist. lt is a selective progesterone
Up to 15 medicinal regimens have been described receptor modulator which works by blocking the
but 6 regimens appear more widely used to date. effects of progesterone. lt has therefore been
These are: used to treat heavy or painful menstrual periods
(a) Yuzpe regimen"u- consisting of 200mg (control blood loss) in uterine fibroids, in low
ethynyl estradiol and 1mg levonorgestrel, half is dose of 5mg daily (Esmya*). This stops the
given within 72 hours of exposure and repeated fibroids from growing and they therefore shrink in
12 hours later. sizett. ln higher doses, however, Ulipristal
acetate (30mg Ellaone*) is used for emergency
(b) Levonorgestrel - .the high dose progestin hormonal contraception. lt is effective for up to
regimen. Here 0.75mg levonorgestrel is taken in L2O hours after unprotected sex. The
2 doses 12 hours apart and started within 48 mechanism of action is that it stops or delays
hours of unprotected intercourse. Latest studies ovulation, and may make it harder for a fertilized
have shown a 2.4% failure rate and a ovum to attach to the endometriumtn. The dose is
proportionate reduction in pregnancy of 60%. A 30mg of the active steroid ingredient as a single
recent WHO study'u has indicated that the dose. The most common side effects are
efficacy of these two methods was significantly amenorrohea, headaches and hot flushes.
greater if Yupze regimen or levonorgestrel was
commenced within 24 hours of coitus. 3. Barrier Methods
These are among the oldest and simplest means of
Some other brands of progestogen-only oral fertility control and were the principal methods of
contraceptives can also be adapted for contraception until the 1960soo There are clear
emergency use e.g. Ovrette containing 0.075mg evidences that the use of barrier methods of
norgestrel. contraception may reduce the risk of cervical
carcinomao'.
(c) High-dose oestrogen - These are less tolerated
than the Yuzpe regimen. (a) Male Condom: The Male condom is one of the
(d) Mifepristone - an antiprogestogen also known oldest methods of contraception and is presently
as RU 486 Contraceptive is one of the newer
310
Advances i n Contraception
I
being promoted to prevent the scourge of AIDS and used contraceptive method today, followed by the
other reproductive tract infections. lt has been IUCD and the Pill', However, there's still low usage
a
confirmed that herpes virus and AIDS associated rate in Africa. Surgical procedures are aimed at
retrovirus cannot pass through intact condoms. resecting or blocking the fallopian tubes so that there
I can be no contact between the ovum and the
(b) Female condom: The Female ,condom spermatozoon. The approach to the fallopian tubes
(Femshield) also "Femidom" is a loose-fitting soft can be through the abdomen or the vagina. Earlier
a
thermoplastic polyether poly-urethane sheath made methods of female surgical contraception made use
l to cover the vagina and external genitalia. lt also has of the laparotomy or mini-laparotomy for such
i
I the advantage of disease protection as with the male technique as the Madlener, lrving, Aldridge, Kroener,
condom. Uchida, Leeton, lngelman -Sundberg and Joelsson
techniques as well as the common Pomeroy's
a
(c) Spermicides: These are a wide range of methodt. The commonest safe, effective and
I
substances which chemically immobilize and destroy to
i affordable technique has been found be
.. spermatozoa. These spermicides can be used alone
minilaparotomy under local anaesthesia using the
I or in combination with other barrier methods to modified Pomeroy method of tubal occlusion".
I
increase the efficacy of the methods. Most chemical
,
vaginal spermicides use surfactant or detergent effect Of recent however with the advancement in
which acts by disrupting the cell membrane and the endoscopy, there has also been advancement in the
a
mid-piece of the spermatozoa,leadingto rapid loss of laparoscopic approach to female sterilization. These
t,
motility. Nonoxynol-9, 10 & 11, Octoxynol-9, employ:

; benzalkonium chloride and memfegol are examples. (i) electro coagulation or thermal coagulation of
I Nonoxynol-9 is most widely used''u. unipolar or bipolar currents.
:/
Chlorhexidine is currently being studied as a (ii) mechanical tubal occlusion using silastic band
I
I spermicide'. ln addition, ORF 13904, RS 37367 are techniques (Fallope ring) and tubal clips, viz. Hulka-
new vaginal contraceptive compounds also being Clemens clips, Filshie and Bleierclips.
f tried. The ORF 13904 is a polystyrene polymer and
appears more effective than Nonoxynol-9, and acts Also tubal occlusion is now possible without surgery
by aggl uti nati ng spermatozoa, a lteri ng sperm-m ucus using the hysteroscope. lntrauterine use of
i interaction and inhibiting sperm acrosin. chemicals or agents such as quinacrine
( hydrochloride, carbolic acid, phenol and
fi*
f
Also being investigated is the contraceptive status of methylcyanoacrylate have been reported. These are
i
propranolol known to inhibit sperm motility and introduced into the fallopian tubes with the aid of a
concentrated in cervical mucus after oral hysteroscope.
administration.
Essure - a micro-coil made up of a spring-like device,
(d) Sponges: Sponges impregnated with Nonoxynol- can also be placed in the uterine end of the fallopian
9 is used also but studies have shown a 17 per 100 tube using a hysteroscope. Scar tissues grow into the
woman years and 25"/" failure rates in America and coil to plug it within 3 months. There is therefore the
Britain respectively. Users have been discovered to need for a temporary contraceptive method in the
have less risk of infection with Chlamydia and first three months. Tubal blockage is confirmed after
gonorrhoea but higher risk of vaginal infection with 3
months with u ltrasou nd, f luoroscopy or
Candida albicans. hysterosalpingogram.lt is considered as a non-
surgical sterilization that uses the trans-cervical
(e) Vaginal exclusive pessaries: Cervical occlusive
route.
cap, vault cap, etc. are also in use e.g. "Contracep";
they can be left in place for up to 3 months. Uterotubal junction blocking devices
I The aim is to secure a blockage of the uterotubal
a 4. Female Surgical Contraception junction with a high reversibility potential. Silicone
This is claimed by some studies to be-the most widely plugs and Mark-7-P block plugs are also used.
311
Ablative surgery with carbon dioxide using laser is a lmmunological ContracePtion

very effective method also being employed currently' lmmunization against pregnancy is difficult to
However, extreme precaution and expertise are achieve. A woman in the child-bearing age can be
necessa ry when performi ng th is procedu re. immunized against spermatozoa and/or the zone
pellucida of the oocyte or against the chorionic
5. MaleContraception gonadotrophin. lmmunization against B-hcG has
There are on-going researches into methods of been tried in lndiauo. Presently an antigen has been
suppressing spermatogenesis without atfecting developed against the c terminal portion of the hCG
libido. However, the male pill is not yet in sighto' coupled to diphtheria toxoid and successfully tested
Gossypol, a derivative of cotton seed oil in animals. The vaccine developed by the World
hasdemonstrated to depress spermatogenesis with Health Organization is undergoing safety checks in
an effectiveness rate of about 99%. However, trials involving sterilized human female volunteers in
Potassium depletion has been reported in some users Australia.
and this may lead to cardiac arrhythmias'
Discussion / Controversies
(a) GnRH analogues inhibit gonadotrophin secretion Contraception in special conditions
after an initial hyper stimulation. lt causes loss of
libido hence it is not suitable for contraception. l. Postpartum IUD lnsertion: The postpartum period
However, when combined with testosterone therapy is a convenient period in which to offer family
it may be able to block spermatogenesis while planning methods to women or couples' The
retaining normal libido. Trials of such combinations postpartum period therefore has been identified as a
are now in progress. suitable and appropriate time to offer postpartum
intrauterine device (Cu T380A, Levonova or Mirena)
(b) Steroids - These cause a fall-in gonadotrogin as contraception particularly in countries with high
concentration hence a fall in sperm count but high unmet need for family planning is desirableou.
doses are needed and that may be toxic' Testosterone lntrauterine devices can be safely and effectively
enanthate and levonorgestrel produce oligospermia inserted within 48 hours of delivery by trained family
but azoospermia in only 50% of cases' Anti- planning service providers, namely doctors, nurses
androgens e.g. cyproterone acetate can produce and midwivesou.
inhibition of spermatogenesis completely but
potency and libido are impaired at the high doses tt.OtderWomen: These are women that are 35 years
required. and oldero'. Here, the ability to conceive continues to
decline until menopause. Therefore there is no need
(c) Gossypol - a yellow pigment obtained from cotton for very effective method of contraception.
seed is an effective anti-fertility agent' However, its Sterilization is a suitable option where family size is
clinical use is limited by side effects and by slowness complete. lntrauterine devices are also suitable.
of recovery after discontinuation of therapy' An Barrier methods / spermicides are also an option here
acceptable regimen is still being soughto'. and offer additional lubrication for sexual
intercourse. lnjections are believed to cause an
(d) Vasectomy - male sterilization has been widely increase in blood pressure in the susceptible older
used in many parts of the world. New methods are woman thus long term use is not recommended,
improving upon the conventional vasectomy by
means of chemical agents that plug the vas and the Itt. Nursing mothers: Contraceptive methods for
non-sca I pel vasectomY. nursing mothers should be effective but not affect the
quantity and quality of breast milk or the health of the
Methods such as percutanous vas occlusion using infant. Lactational amenorhoea, in which the woman
chemical agents, electro-coagulation or thermo- meets the criteria, (amenorrhoea, less than 6 months
coagulation are being'employed' Phenol and cyano- and exclusive breastfeeding) has about 98% chance
acrylate are extensively now being employed in China of not becoming pregnant, and bompares well with
for male sterilization. other forms of contracePtiono'.
3t2
r
I
r
r Advances in Contraception
I
r
r
rI lV. Persons with disabilities: disables persons who sexually activeuo. Like any other woman, may wish to
rr are healthy rep,-oductive-wise also, want to.' get plan pregnancy, limit family or avoid pregnancy. The
married and have children. The ehoie,e of condoms (male and female) provide high degree of
( contraception however will iof protection against HIV sexual transmission provided
f disability, partner support and a fi use - the use is correct and consistentl. Discordant
r on a continuous basis. The rights of trme Fmons partners and the breastfeeding mothers requiring
i
I
should be recognized and respectc$=Sl6-speific contraception that will protect the partner and infant
f m eth od s h oweve r h ave been p rescribed,forthis grou p should consider the use of the condom and other
I of personso'. reliable and effective methods. While condoms have
i
I a significant user and method failure, it prwidesdual
{ V. Sezous MedicalConditions: About 10% of wsmen protection and therefore recommended for effective
t of reproductive age would have or have had serious prevention of unplanned pregnancy and HIV sexual
I chronic medical disorder e.g. heart disease, transmission. Effective prevention is only guaranteed
I. hypertension, diabetes mellitus, renal disease, etc. with consistent and correct use of the.
Medical disorders unfortunately complicate methoduo.Breast feeding also increases the risk of
pregnancy and pregnancy also aggravates the transmission, therefore Lactational amenorrhoea
I
disorder. The Medical Eligibility Cr,iteriao' (MEC - method (LAM) may have to be avoided for a more
I
Wheel ,
2075)o' has simplified the choice of effective method of contraception.
contraceptive methods in most of the medical
conditions and should be consulted. Vlll. Contraception and Young Persons and
i Adolescents: The legal age for consent to sexually
!
Vl. Situations of Humanitarian Czsr's: Situations of activity ls 16 years, but about 1 in 3 teenagers have
humanitarian crisis lead to internally and sometimes had sexual intercourse before this ageu'. Sex
externally displaced persons (lDPs and EDPs). Wars, education at a younger age may be very appropriate.
I
natural disasters, armed conflicts, etc thrust human The fear that sex education will make teenagers /
r beings particularly women and Children, into adolescents more likely to experiment have been
i precarious and vulnerable situations over which they shown to be unfounded /unsubstantiated. Thus, any
have no control, The crises disrupt the health system competent young person regardless of age can
:
and render access to contraception difficult or independently seek medical advice and give valid
impossible. Apart from the women and girls being consent to treatment. That means that contraceptive
:
raped and sexually assaulted, some of them are advice or treatment can be provided to a competent
I
forced into'survival sex'to earn some income. Casual young person aged less than 16 years without
i sex also takes place as a means bf emotional parental consent or knowledge. Age alone should not
support". The dearth of health care providers and llmit contraceptive choices including intrauterine
: trained family planning service providers in particular methods provided that there are no medical
I worsens the contraceptive access problem. However, contraindicationsu'. lt is desirable that:
It
male and female condoms providing dual protection . before menarche - no hormonal method
is most desirable in these circumstances. Oral and should be given
injectable contraception can also be provided. o loung women on hormonal contraception
Emergency contraception also has a place here where also to use condoms to prevent against STls
a woman has been raped. Emergency contraceptive . the combined vaginal ring should not use at
pills and intrauterine devices can be offered to such age less than 18 years
women. lntrauterine device insertions require a
trained provider and on a suitable client. This has the The condoms (male and female) are particularly
added advantage of being left in place for long-term most beneficial to adolescents and young persons for
contraception. the dual protection. Apart from the protection from
pregnancy, sexually transmitted infections are also
Vlt. HlV, HIV Discordant Partner and Contraception: prevented. Most important.in this early age is the
i
Fortunately, fertility is not affected by the virus prevention of human Papilloma virus contact with
infection, and about 7O7" of these persons are the cervix. This has been demonstrated to cause
913
Comprehensivq Gynaecotogy in the Topics
cervical dysplasia which may subsequenUy

develop New developments in contraception have
into ervicalcancer. been very
slow indeed. This parily due to the
fact that users are
lX. Ca ncer a nr d Contrace ption not sick and therefore unlikely
: T hefea r that natu ra lly to tolerate side effects
occurring estrogen and progesterone and comprications as they wourd with
have been disease state.
found to influence the development ln the past, side effects with the intrauterine
and growth of devices
some cancers; 3nd because hormonal attracted law suits and claims made
contraceptives of enormous
amounts, thus slowing down research
contain one or both of these hormones,
the fear could in this
be considered genuine. Overall, tfre -oJ direction for some time. Contraceptive
risf<s development
endometrial and ovarian cancer appear therefore is long, slow, expensive and
to be reduced an uncertain
with the use of oral contraceptives, process, However not all hope
whereas, the risks is lost. The future is
of breast, cervical and liver cancer, appear hopeful.
to be
increasedu'.
Research into contraceptive vaccines
has also been
Conelrsior . very slow. The production of the vaccines
being
A
. plethor4 otcontraceptives are now in the various theoretically possible but the complexity
of the
planning clinics awaiting acceftance research and reduction of funding
lu*t, by by funOers of
prospectilrre clients. There research have stalled the pace for
are new additions in many the meantime.
of the types of contraceptive methods
signally hope
for users who find the other methods
,nrritubl..
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1. Tindall, VR. Contraception ln: Jeffcoate,s

Principles of Gynaecology. Sth
7. Newton, J. Contraception, sterilization
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Ed. Butterworth, a?ortion, ln: Gynaecol. (Straw, et al, eO.)
London. 1987, 40: 59g_.61 6. C!r-n! Livi ngstone, Ed i nburgh. I ggZ, Z
2.
.National
population Commission
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lt !
291_312.
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tCF lnternationat. 2014. Nigeria O.:iiiipni, B. Stee/g S.J. Contraception and Sterilization
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i i! .H ??!t!, S u rve y Z 0 1 3. Rockv i t t e, u1ri'k n a, Ctinicat Gynaecot. (Varma ea.l Uiiia
Arnotd,
USA: NPC and ICF tnternational. London. 1991, 30: gg2_g18.
3. Drife, J.O. New developments in
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iitiadrd.l P^regnancy Termination. tn, Compreiirrlr. -
C!yJ"!r! Livi ngstone. Ed i n bu rgh. rc;;,):
! lyna^e99t Mosby Coy; Washingion, O.C. rcAZ
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Aki n kugbe, A. Ferti I ity Regutation; 10. Natural Family ptanning tJser. A naturaily Health
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9\:t"! & Gynaecot. tvans Eroin";, i;i;;.' 2016.
"!
Pub.)Ltd; tbadan. 1996, 40: qSS_iAb." ""' 11. Shaaban, M.M. Lactational Amenorrhoea
ladipo, O.A. Contraception anO steriizlrtion. tn: Method ftAM): An ttpdate. tn,
Soithio Soutn
Textbook of Obstet. & Gynaecol. i;, Mr;;;;;i
--' Newsletter, (Barbosa ed.) South to Soitn
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12. Howie, p.W. McNeiily,4.S. greasf feeding
6. Shearman, R. p Contraception and sterilization. birth control. ln: progress rn Obsfef.
and
ln: Dewhurst,s Textbook of Obstet. &-
for Postgraduates. (Whiterien ed.I
A Ciil"i"t. Gynaecot. (Studd ed.) Churehitt tiviigstone.
Aticiiiit Edinburgh. 19g3, 3Ql): 136_146.'
Science Ltd, Oxford. /99S, 36i S3g_ii;.-' 13. Research on the standard Days
method _
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Advances i n Contraception
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(
I effecti ve ne: s. https : I / cyc
I e bead s. com pt i v e I m p I a n t of N om e ge strot l' Acetaa te,
Co n tra ce
t Uniplant. ln: Contraception. Elsevier Science
accessed 20 Dec 2016.
14. McCullough, D. Surprising second thoughts on lnc. New York, 1996, 53: 121 -125.
!-? the effectiveness of coitus interr.uptus. The 28. Coutinho, E.M; Athayde, C.; Barbosa, l.C, et al.
Phi ladelphia lnqui rer, 2009. Resu/ts of a User Satisfaction Study Carried out
I in Women Using Uniplant Contraceptive
15. Van Os, W.A.A. lntra-uterine devices. ln: lmplant. ln: Contraception. Elsevier Science
i Progress in Obstet. & Gynaecol. (Studd ed.) lnc. New York. 1996, 54: 313-317.
t' Churchi ll Livingstone, Edinburgh. L983, 3{23): 29. Mutihir, J.7., Nyango, D. D. (20lU. lndications
l 292-302. for removal of Etonogestrel lmplants within two
16. Newton, J. Update on intrauterine devices. ln: years of use in Jos, Nigeria. East African
Progress in Obstet. &Gynaecol. (Studd ed.) Medical Journal. 87(B): 4-7.
Churchill Livingston, Edinburgh. 1993, 1O(14): 30, Sino-implant at FH1360.o19 accessed 20Dec
247-256. 2016.
17. Farr, G. New developments in intrauterine 31. Bromham, D.R. Oloto, E.J. Removal of
Norplant: a short review. ln: Med. Digest. (de-
devices. ln: The Nigerian Famity Practice
I
Glanville ed.) 1995, 22(4): 23-26.

(Aiyelangbe ed.) 1995, 3 (2): 6.
32. Massai RT, Quinteros E, Reyes MV, Caviedes R,
18. Wildermeersch D, Batar l, Webb A, et al. Zepeda A, Montero JC, Croxatto HB. Extended
Gynefix. The frameless i ntrauteri ne use of a progesterone-releasing vaginal ring in
contraceptive implant - an update for interval, nursing wotn€n: a phase ll clinical trial.
emergency and post-abortal contraception. Br. Contraception. 2005; 72: 352- 357.
J. Fam Plann 1999;24: 149-159. 33. McNamee, D. Contraceptive microchip: could it
19. McEwan, J. Hormonal methods of contraception revolutionize global birth control? Women's
and their adverse effects. ln: Progress in Obstet. Health I Gynecology. Last reviewed Tue 7 July
& Gynaecol. (Studd ed.) Churchill Livingstone, 2015. Medicalnewstoday.com accessed 19'n 12
Edinburgh. 1985, 5(17): 259-272. 2016.
20. Gebbie, A. Contraception for the over forties. ln: 34. Ellerston, C. Research in emergency
Progress in Obstet. & Gynaecol. (Studd ed.) contraception. ln: South fo South Newsletter.
Churchill Livins.stone, Edinburgh. 1996, (Barbosa ed.) South to South Cooperation in
12(16): 293-306. Reprod. Health. Salvador -Bahia-Brazil. 1994,
21. Elstein, M. Nuttall, l,D. Progestogen-only 4: 1-12.
contraception. ln: Progress in Obstet & 35. Glazier, A. Emergency postcoital contraception,
Gynaecol. (Studd ed.) Churchill Livingstone N. Engl J. Med 1997; 337: 1058-1064.
Edinburgh. 1982; 2(15): 169-181.
22. Coutinho, E.M., Hanson de Moura, L. New 36. WHO Task Force on Postovulatory Methods of
Leads in Contraceptive Research. Trop. J. Ferti lity Regulation. Randomised controlled
Obsiet. &Gynaecol. 1994; 11(1): 36-40. triat of levonorgestrel yersus the Yuzpe regimen
23. Towobola, O.A.; Otubu, JAM. lnjectable
/ of combined oral contraceptives for emergency
. Contraception. Nigerian Med. J. 19BB; 18G), contraception. Lancet 1998; 352: 428-433.
426--429. 37. WH0 Task Force on Postovulatory Methods of
24. Garza-Flores, J. Advances in lnjectable Fertility Regulation, comparison of three single
Contraceptives. ln: South to South Newsletter. doses of mifepristone as emergency
(Barbosa ed.) South to South Cooperation in
contraception: a randomised trial. Lancet
Reprod. Health. Salvador-Bahia, Brazil. 1994; 1999; 353: 697-702.
4:6-9. 38. {lla Emergency Contraceptive.
25. Mascarenhas L. Newton J. Contraceptive
https: / lwww.d rugs.com accessed 19 Dec
implants. ln: Progress in Obstet. & Gynaecol.
2016.
(Studd ed.) Church i I I Livi ngstone,
39. Gemzell-Danielson K, Berger C, Lalitkumar
Edinburgh.1996, 12: 15: 279-290.
26. Ladipo, O. Coutinho, E.M. Contraceptive - Mechanisms
PGL. Emergency Contraception
of action. Contraception. 2012; 87: 300-308.
implants. ln: Current Opinion in 2bstet. & 40. Himes, NE. Medical history of contraception.
Gynaecol. Current Science Ltd. 1994; 6: 564-
Schocken Books, New York 1970.
569. 41. Conant M, Hardy D, Sernatinger J, Spicer D,
27. Coutinho, E.M; de Souza, J.C; Athayde, C.; Levy JA. Condoms prevent transmission of
I Barbosa, l.C: et al. Multicenter Clinical trial on A/DS-associated retroviruses. Journal of the
the Efficacy and Acceptability of a Single American Medical Association 1986; 255:
-
315
=1+
"
1706. lnternational Conference on Family Conference,

Nusa Dua, lndonesia, 25-29 January 2016;
42. Mutihir JT. Nyango D. D. (2011). euarter.af a Poster 49.
Century of Female Sterilization rn Jc+, =rfel 47. Contraception for special groups. Atlas for
N i ge r i a. Af r i ca n J o u r n a I of ReproductrrE:i!?&Ifh. Contraception. (Pramil la Senanayake and
15(1): 101-106. . . :- '
Malcolm Potts eds.) 2'd edition; lnforma
' Healthcare, UK Ltd. 2008;83-93.
43. Elsimar M. Coutinho, Cetia Athayde,ef,ai 48. World Health Organization Medical Etigibitity
Gossypo/ Blood Levels and tnhibition of Criteria for Contraceptive Use 2015, Edition. A
Spermatogenesrs in ltrlen taking Gossypolasa WHO Family Planning Cornerstone, 2015.
funtraceptive. Contrace pti on 2O0O; 6 j. : 6 I - 67. 49. World Health Organization (WHO Medical
Eligibility Criteria Wheel for Contraceptive lJse
44. Talwar GP et al. Phase I clinical trials with three 2015. A WHA Family Planning Cornerstone,
form u I ation s of a nti - h u na n chorion ic 2015 - Update.
gonadotropi n vacci ne. Contraeeption. l99O; 50. Davis K, Weller S. the effectiyeness of condoms
41: 301-216. in reducing heterosexual transmission of HlV.
-45. Mutihir JT; Nyango DD; Wada PS. Acceptabitity Family Planning Perspectlves.lggg; 31: 272-
of fustpartu m I ntra ute ri ne Contraceptive 279.
Dcvicet afar cry from atbfpated in a Nigerian 57. Larcher V. Consent, competence and
. Tertiary Health Centre. lniernational Canference confidentiality. BMJ. 2005; $A(7487): 353-
on Family Conference, Nusa Dua, lndonesia, 356.
Oral Presentation, 25-29 January 2016. 52. Burkman R, Sch/esselman JJ, Zieman M, Safety
46. Mutihir, JT; Odeku MA. Postpartum lntrauterine concerns and health benefit associated with
Device lnsertion Training: A viable optian for oral contraception. Am J Obstet Gynecol 2004;
improving the High unmet need for Family L90(Suppl. 4)' 55-22
Planning in Low Resource Countries.
316
ts
i
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I
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c,{APrE28
("
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7
I
lnfection Prevention
B.D.R.T. ANNAN and A SAMBA
f
t
t'
l
instance, all pregnant women could be potentially

i
INTRODUCTION
The threat and problems posed by infectious diseases infected as they have had unprotected sexual
have been with mankind for centuries. The advent of intercourse.
antibiotics and other antimicrobials have helped curb
these problems to some extent.
HEALTHCARE-ASSOCIATED I NFECTION
Diseases are constantly in transition with the The health-care associated infections (HCAls) or the
emergence of new diseases such as HIV Ebola and infections acquired from the hospital can be defined
Hep C and the widespread occurrence of Hep B. as the infection which occurs within the 48 hours of
There is also the re-emergence of other diseases like hospital admission or 3 days of discharge or 30 days
tuberculosis, syphilis and cholera. Organisms are of an operation.'The main sources of transmission of
developing resistance to antimicrobial agents and these lnfections are the use of non-sterilize
hospital - acquired infections are continuing and instruments, untrained health care staff or lack of
increasing. awareness in the healthcare staff. As the patients in
the hospitals already have a weak immune system
The reasons for these are complex and varied. There they get easily infected.' Millions of the people die
is rapid population growth and expansion of the worldwide due to these infections and leads to a
population to remote areas. There is increasing significant mortality and financial losses of the
poverty and environmental degradation. lmproved health system. The rate of these infections is high in
transportation means diseases could be transported developing countries than the developed countries;
from one place to the other within hours. The also the newborns are more vulnerable to these
widespread and inappropriate use of antibiotics has infections'.
resulted in development of resistant organisms.
These factors are compounded by poor infection The burden of HAI is already substantial in
control and prevention program in our health developed countries, where it affects from 5% to
institutions. ln addition, the inability to afford L5% of hospitalized patients in regular wards and as
disposable instruments such as, laparoscopy sets in many as 50% or more of patients in intensive care
most centres of the developing countries further units (lCUs)' ln developing countries, the magnitude
compound the problem. of the problem remains underestimated or even
unknown largely because F{CAI diagnosis is complex
These threats are alarming especially because there and surveillance activities to guide interventions
are no treatment or cure for these deadly infections. require expertise and resources. Surveillance
t The obstetrics and gynaecology units are at greater systems exist in some developed countries and
risk because of the clients they deal with. For provide regular reports on national trends of endemic
317
HCAI, such as the National Healthcare Safety INFECTION TRANSMISSION IN HEALTH CARE
Network of the United States of America or the SETTING
German hospita I i nfection su rvei I la nce systEm3.
The hospital setting is ideal for disease transmission.
This is not the case in most developing countries This is because invasive procedures that introduce
because of social and healthcare system deficiencies organisms to parts of body are performed every day.
that are aggravated by econornic problems. Providers perform procedures that expose them to
Additionally, overcrowding and understaffing in the risk of infection, e.g. venipuncture. Clients
hospitals result in inadequate infection control receive treatment in a limited physical space and
practices, and a lack of infection control policies, may be susceptible to or transmit infections to
guidelines and trained professionals also adds to the others.
extentof the problem.'
The provider may be exposed to infectious blood and
HCAIs can develop either as a direct result of other body fluid through needle pricks, mucous
healthcare intervention (such as medical or surgical membrane splash and exposure of non-intact skin of
treatment) or from being in contact with a healthcare health workerto infections like HIV and, Hep B. The
setting. HCAIs arise across a wide range of clinical provider may also spread infection by not wash
conditions and can affect people of all ages. They can hand (client to client) and also when instruments are
exacerbate existing or underlying conditions, delay not properly processed. lmproper medical waste
recovery and adversely affect quality of life. These disposal affects clients as well as the community.
infections can occur in otherwise healthy people, lmproper disposal of medical waste may
especially if invasive procedures or devices are used. contaminate water bodies used for drinking water.
Healthcare workers, family members and carers are Children and hairdressers may have access to
also at risk of acquiring infections when caring for syringes, needles and gloves. Staff may carry
people. A number of factors can increase the risk of infection to family members at home. The Ebola
acquiring an infection, but high standards of infection outbreak in Africa in the past decade was spread
prevention and control practice, including providing throughout the community in part because of poor
clean environments, can minimise the risk and infection prevention practices in health care
prevent about 90% of deaths from hospital facilities'.
infections."
Transmission of infections could be reduced if
The most common types of healthcare-associated infection prevention measures are followed. lt should
infection are respiratory infections (including be understood that everyone is at risk, from the client
pneumonia and infections of the lower respiratory to the provider and ultimately to the entire
tract), urinary tract infections and surgical site community. The observance of proper infection
infections. Each one of these infections means prevention practices:
additional use of hospital resources, greater patient
discomfort and a decrease in patient safety and 1. Prevents post procedure infections
quality of life. ln the past decade, methicillin- 2. Results in high quality and safe services
resistant Staphylococcus aureus (MRSA)and 3. Prevents infection in health care workers
Clostridium difficile infections have been recorded as

4. Protects community
the underlying cause of, or a contributory factor in

5. Prevents the spread of micro-organism that
are resistant to antibiotics
hospital death'.
Lowers cost of services
The World Health Organization WHO) has launched
its Global Safety Challenge promoting'Clean Care is
Safer Care', which identifies the dangers of health
care associated infections. The WHO's'Clean Care is
Safer Care'focuses on clean hands, clean equipment,
clean clinical procedures and clean environment.l
318
r
T
T
t
I
(
r I
THE DI$EASE TRAN$MIS$ION CYCLE care settings by several routes, and the same
f
rr microorganism may be transmitted by more
than one route Transmission ean occur by
{
FlVEmodes. For the purpose of this
(" discussion, common vehicle and vector
I
r borne will be discussed only briefly because

it neither play a significant role in typical
I
r health care associated infections:
,'
r Contact - Contact transmission, the

r most important and frequent mode of
transmission of health care associated
1
infections (HCAI), is divided into direct

t a nd indirect contact tra nsm ission .
i
I
I Fig. 261 TH E DISEASE TRAN$M ISS|ON CYCLE The infectious agent can be
transmitted dlrectly from the reservoir
I
I
The infectious agent survives, grows, and/or to a susceptible host through touch
multiplies in a reservoir and then leaves the reservoir (e.9., staphylococcus), sexual
i
I through a place of exit by a mode of transmission. The intercourse (e.9., gonorrhoea, HIV), or
i infectious agent then enters the susceptible host droplets (e.g., influenza,
r I
through a place of entry. The components of the tuberculosis). Direct contact
I
disease-transmission cycle are discussed in detail:
I
( transmission involves a direct body
r
I The six components of the disease-transmission cycle
surface-to-body surface contact and
t physical transfer of microorganisms
( 3T€:
between an infected or colonized
I
i t. lnfectious agent These are microorganisms person, such as occurs when a health
r care provider turns a client, gives a
r I
that can cause infection or disease. The
I infectious agent can include bacteria client a bath, or performs other client
r? viruses, fungi, and parasites. care activities that require direct
I
i personal contact. Direct contact
2. Reservoir lt is the place where the agent transmission also can occur between
t
i survives, grows, and or multiplies; Beople, two clienis or a visitor, with one
Ir water, soil equipment and instruments serving as the source of the infectious
I microorganisms and the other as a
I
3. Place of exit The route by which the susceptible host. For example a visitor
r infectious agent leaves the reservoir. The must wash his or her hands at the
( infectious agent can leave the reservoir beginning and end of their visit so they
through the bloodstream, broken skin, don't transfer organisms from one
t
/ mucous membranes, the respiratory tract, person to anothers.
r the genitourinary tract, the gastrointestinal
tract, or the placenta by means of blood, lndirect contact transmission involves
r contact between a susceptible host
r excretions, secretions, or droplets that come
from these places. and usually a contaminated inanimate
I
object, such as equipment,
4. Mode sf transmission This is the Way in instruments, and environmental
I
which the infeetious agent moves from the surfaces. This is often the result of
L
reservoir to a suseeptible host. contaminated hands that are not
washed whieh contaminate the object
I
Microorganisms are transmitted in health
or environment.
L
l.
319
;
contact transmission
Vehicle - The infectious agent can be
transmitted indirectly from the 5. Place of entry This is the route by which the
reservoir to a susceptible host bY infectious agent moves into the susceptible
material that maintains the'life of the host. This is usually same as the route of
infectious agent. Such vehicles include exit.
food (e.g., salmonella), blood (e.g.,
hepatitis B, HIV), water (e.g., Cholera, 6. Susceptible host This is a person who can
shigella), or instruments and other become infected by the infectious agent. The
items (e.9., hepatitis B, HlV, susceptible hosts include clients, service
pseudomonas). providers, ancillary staff, and members of
the community
Airborne - The infectious agent can be
carried by air currents (e.g., measles, For infection prevention the disease transmission
cycle needs to be broken and the easiest part is the
tuberculosis).
mode of transmission.
Vector -
The infectious agent can be
lnfection prevention (lP) has two primary
transmitted to a susceptible host obiectives:
through insects and other invertebrate 1,. Prevent major infections when providing
animals (e.g., mosquitoes can transmit services;
malaria and yellow fever; fleas can 2. Minimize the risk of transmitting serious
transmit plague) disease such as hepatitis B and HIV/AIDS to
the woman and to services providers and
- Theoretically, is
Droplet transmission staff, including cleaning and housekeeping
a form of contact transmission. personnel
However, the mechanism of transfer of
the pathogen to the host is quite GUIDING PR!NCIPLES6
distinct from either direct or indirect 1,. lnfection prevention and control strategies
contact transmission. Droplets are are designed to protect clients, health care
generated from the source Person providers and the communitY.
primarily during coughing, sneezing,
and talking, and during the 2. Health care associated infections cause
performance of certain procedures significant morbidity and mortality and at
such as suctioning and administering least 30% of health care associated
nebulized medications. Transmission infections can be prevented by following
occurs when droplets containing i nfection prevention a nd control strategies.'
microorganisms generated from the
infected person are propelled a short 3. A systematic approach to infection
distance through the air (usually less prevention and control requires each health
than one metre) and deposited on the care provider to play a vital role in protecting
host's conjunctivae, nasal mucosa, or everyone who utilizes the health care
mouth. Because droplets do not remain system, in all of its many forms: pre-hospital
suspended in the air, sPecial air settings, hospitals, clinics, offices, home
handling and ventilation are not care and communitY Programs, etc.
required to prevent droPlet
transmission; that is, droPlet 4. Health care providers follow infection
transmission must not be confused prevention and control practices at all times
with airborne transmission. Droplets and use critical thinking and problem solving
can also contaminate the surrounding in managing clinical situations.
environment and lead to indirect
320
r'f
r
I
i
r
I
HIERARCHY OF INFECT!ON CONTROL infection. By applying standard precautions at all
MEASURES times and to all patients/clients best practice
( 't-- becomes second nature and the risks of infection are
i
I
There are important concepts regarding infection m ini mised.'u They include:
prevention and control measures that have been
clarified over the past decade. Wor.king with 1. Achievingoptimum hand hygiene
f
7
I
occupational health and safety gro-t*ps.4nd buitding 2. Respiratory hygiene/cough etiquette.
engineers has created a framework that includes 3. Using personal protective equipment
three levels of control: engineering controls, (gloves, gowns, masks)
administrative controls and personal protective 4. Safe handling and disposal of sharps
measures.
5. Safe handling and disposal of clinical waste
1. Engineering controls are built into the design
6. Managing blood and bodily fluids
(private bathrooms, private rooms, HVAC 7. Decontaminatingequipment
systems) of a health care facility. lnfection
8. Achieving and maintaining a clean clinical
environment
prevention and control professionals should
be involved in the design and planning of new
9. Appropriate use of indwelling devices
10. Managing accidents
facilities. An lnfection Control Risk
assessment should be done to evaluate and
11. Good communication - with other health
care workers, patients and visitors
mitigate potential risks for microorganism
!2. frainingleducation
transmission by means of air, water and
envi ron mental sources.
TRANSM ISSION-BASED PRECAUT!ONS

2. Administrative controls include protocols for Transmission-Based Precautions are intended to
hand hygiene, immunization of residents and supplement Standard Precautions in patients with
ca regive rs, p rotoco ls for m anagi n g ca regivers known or suspected colonization or infection of
and clients during an outbreak and protocols highly transmissible or epidemiologically important
for caring for clients with communicable pathogens. These additional precautions are used
diseases. when the route of transmission is not completely
interrupted using Standard Precautions.' The three
3. Personal protective equipment is the least
categories of Transmission-Based Precautions
1 desirable wqy to control hazards as it does
include: 1) Contact Precautions, 2) Droplet
Precautions, and 3) Airborne Precautions. For
not eliminate them, it merely contains the
diseases that have multiple routes of transmission, a
: hazard and is dependent on its appropriate combination of Transmission-Based Precautions
use by educated, knowledgeable staff'z. may be used. Whether used singly or in combination,
i
they are always used in addition to Standard
STANDARD PRECAUTIONS Precautions.
(The general principles of infection prevention and SP or Routine (in some jurisdiction) practices
control) supercede, and are more encompassing, than
Standard Precautions (formerly known as universal previous bloodborne pathogen precautions or
precautions) are the minimum infection prevention Universal Precautions. Based on the assumption
practices that apply to all patient care, regardless of that all blood and certain body fluids (urine, faeces,
suspected or confirmed infection status of the wound drainage, sputum) contain infectious
patient, in any seiting where healthcare is delivered. organisms (bacteria, virus or fungus), SP Practices
These evidence based practices are designed to both reduce exposure (both volume and frequency) of
protect Health Care Providers (HCP) and prevent blood/body fluid to the health care provider. The key
HCP from spreading infections among to implementing SP Practices is to assess the risk of
patients/clients. transmission of microo;ganisms before any
I interaction with patients/clients/residents. The
Standard precautions (SP) underpin routine safe consistent use of SP Practices will assist in reducing
: practice, protecting both staff and clients from exposure (both volume and frequency) of all
321
blood/body fluid to the health care provider and forms the foundation for limiting the transmission of
transmission to others and the environment. microorganisms in all health care settings. lt is the
standard of care for all patients/clients/residents.
SP Practices are a way of thinking and acting that
a Hnr*lrygllle
t $* x&6m*nt ldM b dcot *ffi c:ar{ nn*s dd&rer} Mdiry *rlcrtktf tsireelisr*
e!relq *xrror rcryerror, ryt4tt* n+ er*r' rxcxlonrrid lsc*tio{s
np1 rc{r*r re&etrircq& rr dprutf ffin.ryFmre f&}, dw$lryo(en*roxlltt&
lersrdf dbinffiign nd ilriilrdon of qrferlt or riry1le usc oquipnnflt welt m:nrgsment
r* *rsnpr trmCln* dirt flrctmtmd h.ail?wtflec gecictl
kuc.ti*r af krlth mme& Sffi*{foltmr*nd$ur*
The recommended SP practices are based on the 2. Hand washing with antiseptic and running
following principles: water
o Every person (patients or staff) must be 3. Alcohol based hand rub (ABHR)
considered potential ly infectious;
. Hand Hygiene is the most practical Use of alcohol-based hand rub as the primary mode
procedure for preventing cross- of hand hygiene in healthcare settings is
recommended by World Health Organization (WHO)
contamination;
. Gloves must be worn before touching because of its activity against a broad spectrum of
anything wet, such as broken skin, mucous epidemiologically important pathogens, and because
membranes, blood or other body fluids compared with soap and water, use of ABHR in
(secretions or excretions) ; healthcare settings can increase compliance with
o Barriers should be used including protective recommended hand hygiene practices by requiring
goggles, facemask or aprons if splashes and less time, irritating hands less, and facilitating hand
spills of any body fluids either secretions or hygiene at the patient bedside. For these reasons,
excretions are .anticipated; transmission alcohol-based hand rub is the preferred method for
cycle and prevent spread of infection from hand hygiene except when hands are visibly soiled
person to person and from equipment, (e.g., dirt, blood, body fluids), or after caring for
instruments and environmental surfaces to patients with known or suspected infectious diarrhea
people. (e.g., Clostridium difficile, norovirus), in which case
soap and water should be use
HAND HYGIENE
Hand hygiene is widely acknowledged to be the Ycur 5 msm*n& for lr*ld hygien*
single most important activity for reducing the spread
of disease, yet evidence suggests that many health
care professionals do not decontaminate their hands
as often as they need to or use the correct technique
which means that areas of the hands can be
missed.'o'" Hand hygiene eliminates all transient
organisms and most resident organisms.
There are three types of hand hygiene:

L. Handwashing with plaln soap and running ban$G n'hr : Ettt'IiE E l[!Ea.a-- rdtG
water (routine or social hand washing)
322
Key recommend:tionsfor hand hygiene: e, lf hands will be moving from a

1. Keysitua,lonswhere hand hygieneshould be contaminated-body site to a clean-body
performeo include: site during patient care
a. Before touching a patient, even if gloves f. After glove removal(because gloves may
r willbeworn have invisible holes ortears)
r) b. Before exiting
l
the patient's ,care area

{ after touching the patient orthe patient's Use soap and water when hands are visibly soiled
t
I
immediate environment (e.g., blood, body fluids), or after caring for patients
I
7 c. After contact with blood, body fluids or with known or suspected infectious diarrhea (e.g.,
I
. excretions, or wound dressings Clostridium difficile, norovirus). Otherwise, the
( d. Prior to performing an aseptic task (e.9., preferred method of hand decontamination is with
I placing an lV; preparing an injecticn) an alcohol-based hand rub
i
t
lsv&dhiltill,q,SfliB
[#rFL! tEYEt: tEl.ct
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Sor&f lhdHfirmc Itrgiprdc{ro@iql Surgiqdrwre
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;-
a It is important to wash hands first on arriving at accompanying individuals who have signs
{ work and last beforg you leave work. and symptoms of a respiratory infection,
beginning at point of entry to the facility and
continulng throughout the duration of the
RESPI RATORY HYG I ENE/COUGH ETIQU ETTE" visit.
Respiratory Hygiene/Cough Etiquette is an element a. Posting of signs at entrances with
of Standard Precautions that highlights the need for instructions to patients/ clienVrelative
prompt implementation of infection prevention
/HCP with symptoms of resPiratorY
measures at the first point of encounter with the
infection to:
facility/ambulatory settings (e.g., reception and
triage areas). This strategy is targeted primarily at
i. Cover their mouths/noses when
patients and accompanying family members or coughing or sneezing
friends with undiagnosed transmissible respiratory ii. Use and dispose of tissues
infections, and applies to any person with signs of iii. Perform hand hygiene after hands
illness including cough, congestion, rhinorrhea, or have been in contact with
increased production of respiratory secretions when respi ratory secretions
entering the facility. b. Providing resources for performing
hand hygiene in or near waiting areas
Key recommendations for Respiratory c. Offering masks to coughing patients
I Hygiene/Cough Etiquette: and other syflrptomatic persons upon
1. lmplementation of measures to contain entry to the facility
respiratory secretions in patients and d. Encouraging persons with symptoms of
323
respiratory infections to sit as far away gown to protect skin and clothing during procedures
from others as possible. lf available, or activities where contact with blood or body fluids
facilities may wish to plaee these is anticipated; use of mouth, nose and eye protection
patients in a separate area whiE,$@ltg during procedures that are likely to generate splashes
for care or sprays of blood or other body fluids. Hand hygiene
is always the final step after removing and disposing
2. Educate HCP on the importance of infuction of PPE.
prevention measures to contain rEsprratory
secretions to prevent the spread of ln addition to protection of HCB face masks are also
respiratory pathogens when examining and effective in limiting the dispersal of oropharyngeal
caring for patients with signs and'symptoms droplets and are recommended when placing a
of a respiratory infection.. catheter or injecting materials into epidural or
subdural spaces, as during myelography or spinal or
Perform hand hygiene after hands have been in epidural anaesthesia. Failure to wear face masks
contact with respi ratory secretions during these procedures has resulted in development
of bacterial meningitis in patients undergoing these
PERSONAL PROTECTIVE EQU I PM ENT procedures',. All HCP at the facility should be
educated regarding proper selection and use of PPE.
Personal Protective Equipment (PPE) refers to
wearable equipment that is intended to protect HCP GLOV!NG
from exposure to or contact with infectious agents.
Examples include gloves, gowns, face masks, Gloves provide abarrier against potentially infectious
respirators, goggles and face shields. The selection of microorganisms in blood, other body fluids and
PPE is based on the nature of the patient interaction medical waste, thus lowering the risk of transmitting
and potential for exposure to blood, body fluids or infections to both health care workers and clients.
infectious agents. Examples of appropriate use of They also protect against hazardous chemical waste.
PPE for adherence to Standard Precautions include: Health care workers should wear gloves whenever
use of gloves in situations involving possible contact they may come in contact with clients' blood and
with blood or body fluids, mucous membranes, non- other body fluids.
intact skin or potentially infectious material; use of a
lllltwr th*re ke r&k s{r0{pof,}r@l**1$ Emmpls:

aonffiwith Hood body flu*trxrd no* . fucdlng*rsidalffiiistt
iaflctr*in. $odal toudr
E(ffid€6r *" Prs*ri*gewh*del*elr
" {hrngln* e dretslftg * Selitr*rirq rrn**l*, mai& lau*rdry
. Cha*gingdiapan * }trv{di*gr*eturx$dmtrv{t&inttrt
* Eucriqg uprn lnmn{p*nt reHoetJell*nt $eln rr,,Kh ar taklfigl lamptratlru
. P*r*amlry maffih(r3
The types of gloves are:

1. Sterile/ surgical gloves -these are used when 3. Utility gloves-when handling used
there is contact with tissue beneath the skin instrument or blood and bodyfluids
2. Examination gloves -used when there is Tokars et al found that surgeons wearing two pairs of
going to be contact with mucus membrane new sterile gloves (double gloving) have about 70%
and non-intactskin fewer blood hand contact than those wearing a single
pair of gloves".This is because of perforations in the
324
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('
I
: gloves. Based on these finding reasonable guidelines o Fastacting
for double gloving would be for long_ -procedures o Least expensive effective HLD
I
lasting more than 60 minutes, or when'operating in o Disadvantages
a
small spaces, which might increase. rci$_k of glove o Corrosive to metal with prolonged
tears and perforation. Double gloves shant(t:also be contact (>20 minutes)
worn where the procedure entails,comlnsi into o lrritating to skin, eyes and
) contactwithlargeamountofblood, .: respiratory tract
ANTISEPTICS AND DIS! NFECTANTS

o Comments
Antiseptics are chemical agents used on the skin and
o Available in liquid and tabletform
mucous membranes to remove or kill o Can be used for decontaminating or
microorganisms without causing damage or irritation disinfection for surfaces (low level)
to the skin and mucous membranes. Antiseptics may o Leaves residue and instrumenfs
also prevent the growth and development of need to be rinsed with HLD water or ...
microorganisms. Antiseptics are not meant to be o So/utio n prepared daily since
used on inanimate objects, such as instruments and potency rs /ost over time and light
surfaces. exposure
G I uta ra I d e hvd e (C i d ext
There are several types of antiseptics and o Antimicrobialactivity
disinfectants depending on the locality. Antiseptics
can be easily contaminated and caution must be o Broad range of microorganisms
taken to avoid this. They must be stored in a cool and includingTB
( dark place. lnstruments must not be stored in o Soaking for 10 hours can kill
antiseptic solutions as this not an effective way of bacterial endospores
processing the instruments and is a waste of the o Advantage
antiseptic. o Notcorrosive
o Disadvantage
Disinfectants are chemical agents used to kill o lrritating to skin, eyes and
microorganisms on inanimate objects, such as
respiratory tract (gloves and well
nstru ments and surfaces.
i
ventilated space and limit exposure to
Disinfectants are not meant to be used on the skin or
mucous membranes. chemical)
)
c Comments
There are two types oJ disinfectants: o Used commonly for medical
equipment which cannot be sterilized
1.. High-level disinfectants-these kill bacteria, (laparoscopes)
viruses, and fungi and some, but not o Used HLD (soaking20 minutes) and
necessarily all, bacterial endospores.Some sterilization (for 10 hours)
high-level disinfectants are also chemical o Leayes a residue; rinse with HLD
sterilants and given sufficient time, will water/ sterile water
destroy bacterial endospores. Bacterial o New solution every 14 days (or
endospores cause such diseases as tetanus sooner if cloudy)
and gas gangrene. They can also be used for o Follow manufacturers instructions
processing instruments and other items. (variation)
Common HLDs 2. Low-level disinfectants-These kill most

Chlorine bacteria, some viruses and fungi, but do not
o Antimicrobialactivity kill tuberculosis-causing microorganisms
o Broad range microorganisms and bacterial endospores. They are used for
including TB. Does not kill all bacterial cleaning surfaces, such as floors and
t endospores countertops. They should not be used for
a
o Advantages processing instruments and other items.
325
IABTI'l: rOry tgrg- BHITECftTilE &r.Sl
Source: Public health ass Canada(PHAC) Hand washing, Cleaning Disinfection and Sterilization Guideline - 1998
Objects will be disinfected depending on the objects Semi critical - objects touch mucous
intended use membrane or skin that is not intact requir
r Critical - objects which enter normally sterile high level disinfection process
tissue of the vascular systems or through Non-critical - objects that touch only intact
which blood flows should be sterile skin require low level disinfection
TIHG I: de**i*brr&r|tbn *e(*ffiXn$ t* as{tbtff! N'l&
&*:i*pd frnn ilr* ,r*ilirli llpl,Y&it'r*dtr Mhri*rtiAft- {*$rr{it{t&r& S*ilnfiFr*,i# d*{ r{,!:*li?*r nf m*iral rarnru*r {ra+61.
The stopper of the m ulti-dose vial must be wiped with likelihood that, during clinical procedures, microor-
methylated spirit before contents are drawn with the ganisms will enter areas of the body where they can
needle. This is because once the seal is broken cause disease. While all infection prevention prac-
organlsms can settle on the rubber stopper, Needles tices contribute to this effort, aseptic technique refers
must not be left in the stopper as this creates a portal to those practices performed just before or during a
of entry for organism. Once the needle is removed the cli nical procedure including:
rubber retracts and seals off the small hole created by
Hand washing Surgical hand scrub Using barriers
the needle.
such as gloves and surgical attire Properly preparing
ASEPTIC TECHNIQUE a client for clinical procedures Maintaining a sterile
field Using good surgical technique Maintaining a
These are practices that help reduce the risk of safer envi ron ment i n the su rgica I a nd proced u re area
postprocedure infections in clients by reducing the
326
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t
Prophylactic antibiotic use does not take the place of ln the surgical area entry must be limited to autho-
t
good infection prevention practices. A prophylabtic rized personnel and clients only. Personnel should
I
agent should be given as a single dose prior to most enter the surgical area through clothes.changing
r operative procedures. lf the operation lasts 3 hours or room. Personnel dress such as clean cover gown,
I
longer, or if blood loss exceeds 1500mls; a second cap, and shoe covers shoes should not be worn
dose may be beneficial, There are two reasons for outside the surgical area. Client clothes or gowns
usingthis regimen: should be provided and if possible the hair or head
i
should be covered because hair sheds skin cells,
1. During this period patients have significant which are contaminated with numerous microorgan-
urine output and these antibiotics are isms. The doors must be kept closed at all times.
actively secreted by the kidney; and
2. lf there were considerable loss of blood DISPOSALOFWASTE
volume, the antibiotic concentration would
The waste generated in the hospital setting can be
be significantly reduced
grouped into biomedical waste, general waste and
Multiple chemo prophylactic doses could lead to chemical hazardous. The medical waste includes
emergence of resistant strains. needles, syringes, gauze, amputated limbs and
many others. lt is usually not bulky compared to the
Hairs should not be removed from the operative site general waste. Sorting out waste at the point of
unless absolutely necessary. If hair removal must be generation is essential to facilitate disposal. General
done, the hair should be trimmed close to the skin waste can be disposed of like any waste but biomedi-
surface immediately before surgery. Shaving cal waste needs to be disposed specially and it is the
increases the risk of wound infection as the tiny nicks responsibility of the facility to dispose off its medical
in the skin provide an ideal setting for microorgan- waste. Medical wastes carry high loads of organ-
isms to grow and multiple." isms. Blood, urine, stool and other body fluids like
liqour have high concentrations of microorganisms.
TRAFFIC FLOW Sharps and needles also could be dangerous if not
well disposed off. . Legislation requires that biomedi-
The number of microorganisms in a designated area
cal waste be handled and disposed of in such a way
tends to be related to the number of people present
as to avoid transmission of potential infections and
; and their activity.la Microbial contamination is
offer protection against accidental injury
;
expected to be high in areas of heavy traffic, such as
waiting rooms and areas where used or soiled Medicalwaste could be solid or liquid. Solid waste is
surgical instruments and other equipment are initially put in a noncorrosive washable container with tight
processed. An important goal of infection prevention fitting lid. lt is disposed off using a utility glove when
is to minimize the level of microbial contamination in the container is about -full. lt has to be collected on
areas where "clean activities" take place such as the regular basis and can be stored temporarily for a
procedure, surgical and work areas. maximum of 24 hours.
327
The two main ways of disposal is by burning or washing then the necessary post exposure
burying. Burning could be done in an incinerator or in prophylaxis can be offered. When there is splash into
a specially designed drum. Burying is donein a Bit, the eyes also wash with lot of water and consider
which should be sited away from the faei{ity'and post exposure prophylaxis. During surgery the
away from water bodies to avoid contamination. The instruments should passed from scrub nurse to
pit is covered with soil when it is % full and another surgeon and vice versa using the hands free
one dug out. lt is very important that children and technique
other people do not have access to medical waste
disposal sites. The waste container should be PROCESSI NG OF I NSTRUM ENTS
decontaminated and hands washed after removal of
lnstruments and other items that are used for a
utility gloves.
procedure must be well processed to reduce or
Liquid contaminated waste is disposed off by pouring prevent the risk of transmitting infection from one
into a drain or flushable toilet whilst wearing utility client to the other and also among service providers.
glove. Rinse the container with water and wash The rationale for each of the infection prevention
hands after removing utility gloves. Avoid splashing processes must be clearly understood by clinic st^+f
when disposing off liquid waste. lt is important to at all levels-from service providers to cleaning a
ensure that the liquid waste is not going to maintenance staff.
contaminate any water bodies. The chemical
The steps of processing instruments are:
hazardous wastes include those generated from
radiology and radiotherapy units and these units have
1. Decontamination
2. Cleaning
a specla I way of d isposi ng off these waste prod ucts.
3. Sterilization or
DISPOSAL OF SHARP OBJECTS
4. High-level disinfection
lnjuries from sharps and needles constitute a major

1. Decontamination is the first and immediate
step in processing instruments and other items for
source of infection for health workers. Sharps like
reuse. Decontamination kills viruses (such as
needles and syringes are disposed off in puncture
hepatitis B, other hepatitis viruses, and HIV)" and
resistant containers. When the container is about 7+
many other microorganisms, making these
full it is disposed off by burning the container with its
instruments and other items safer to handle by staffs
content or by burying in a pit.
that clean them. ln addition, decontamination makes
Avoid recapping of needlls. lf recapping is necessary instruments and other items easier to clean by
preventing blood, other body fluids, and tissue from
then use the one hand technique. Studies have
shown that the risk of disease after exposure to HBV drying on them. Decontamination is performed by
from a needle stick injury ranges from 27 to 377"'u soaking instruments and other items in a O.5%
while the risk following a single needle stick injury to chlorine solution for 10 minutes immediately after
use.
HIV is much lower,0.4%'u
The rate of transmission of HIV is considerably lower

The chlorine solutions come in various
than for HBV probably because of the lower concentrations and it is important for health
personnel to be able to calculate the number of parts
concentration of virus in the blood of HIV-infected
persons. of water to add to any given strength of chlorine
solution to get 0.5% (which is the required strength).
The efficiency for transmission of HBV is high.
Accidental splash into the eye of as little as 10-8 ml
. The formula for calculating chlorine
solution is:
of infected blood can transmit HBV to a susceptible
T"Available-1 : number of parts of
host.7 ln the event of a needle stick injury it is
waterto be added.
recommended that one wash the site with soap and
% Required The required strength is
lot of water. Do not squeeze or immerse the site of
always 0.5%. Some Products have
Injury in methylated spirit or chlorine solution. After
328
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a
I
(
; ihe stren$h in degree chlorum and
I
r tl're conversion factor is: 1' chlorum . Factors that influence the Efficacy of
( :0.3"/" nfection/ steri I ization i nclude
d isi
t-. o Cleaning of the object
1.
2. Cleaning involves scrubbing with a brush, o Organic and inorganic load present
t
f detergent, and water before instruments and o Type and level of microbial
: other items are sterilized or high level contamination
I disinfected to remove blood, other body fluids, o Concentration of and exposure time
: organic material, tissue, and dirt. ln addition, to disinfectanVsterilant
cleaning greatly reduces the number of o Nature of the object
microorganisms on instruments and other items o Temperature and relative humidity
and is a crucial step in processing instruments
and other items. lf instrumertts and other items
. Factors that affect sterilisation by heat
have not first been cleaned, sterilization and are
high-level disinfection (HLD) may not be o Nature of heat - moist heat more
effective, because: effective than dry
o Temperature - temperature and
a. Microorganisms trapped in organic time are inversely proportional
material may be protected and ftemp j time
survive the sterilization or HLD o Number of microorganism - the
:
proc0sS; and greater the number of
b. Organic material and dirt can make microorganisms the higher the
the chemicals used irr chemical temperature or longer the duration
sterilization and HLD less effective. required
o Nature of
microorganisms -
Sterilization is the process that eliminates all depends on spp and strain on
: microorganisms including bacterial microorganisms sensitivity to heat,
endospores. Sterilization is recommended for spores are resistant
instruments and other items that will come in o Types of material - sensitive
contact with the bloodstream or tissues under material cold sterilization
i
the skin. Sterilization can be performed using o Presence of organic material -
steam under pressure (autoclaving or rnoist proteins, sugars, oil, fats increase
heat), dry heat, chemicals or radiation time required
(ionising/non-ionising). The right temperature,
duration and or pressure are critical in ensuring Wrapped sterile packs can be stored for up to one
that sterilisation is complete. Sterilisation can week. Unwrapped items should be stored in a sterile
be monitored using mechanical, chemical or pack or HLD container with a tight fitting lid or used
biological i ndicators. immediately.
o For the sterilization of critical objects 4. Highlevel disinfect ion (HLD)'is the process
(e.g. surgical instruments), the under that eliminates all microorganisms but does
listed methods can bd uSe; not reliably kill all bacterial endospores.
o Steam sterilization HLD is suitable for instruments and other
o Chemicalsterilization items that will come in contact with broken
-Hydrogen peroxide gas plasma skin or intact mucous membranes. HLD can
-Ethylene oxide be performed by boiling, use of chemicals,
-Peracetic acid(O.2%) orsteaming.
-Ozone
I -Vaporized hydrogen peroxide Boiling for 20 minutes or'soaking instruments in
-Steam formaldehyde 0.5% chlorine for 20 minutes is the commonest
o Radiation mode of HLD employed in many centres. The water
must be boiling before timing begins.
,,,
32g
ec!&
HLD by boiling
o Effective,practicalway
o Vegetative form of bacteria
killed by moist heat
. (50-75"C)within 10 mintrtes
o HepB inactivated {N.rr*
r*x#
. 98 "Cfor2 minutes
. 80 "Cfor 10 minutes *ilfr
o Mostspores killed &dq
' 99 "Cfor20-30 minutes
o Clostridium tetani quite *r*
resistant to boiling 15-90 Mry*db
minutes l}rc*x+
o Advantages
o Excellent, inexpensive
Fig.262 FLOW CHART FOR PROCESSING
o Easily controlled
OF INSTRUMENTS
o Requires no dilution and leaves
no chemical residue
DEDICATE RESOURCES TO INFECTION
o Heat source, pan and water
PREVENTION (ADMI NISTRATIVE MEASURES)
available
o Disadvantages lnfection prevention must be made a priority in any
o Correctly perform (timing) for
setting where healthcare is delivered. Those with
effectiveness primary administrative oversight of health care
o Objects cannot be Packaged
facility/setting must ensure that sufficient fiscal and
prior to disinfection human resources are available to develop and
(recontamination)
maintain infection prevention and occupational
health programs. This includes the avaitability of
HLD hy chemicals
o Endoscopes that would be damaged
sufficient and appropriate equipment and supplies
necessary for the consistent observation of Standard
by boiling
. Alcohol and iodophors inexpensive Precautions, including hand hygiene products,
and readily available (not use) injection equipment, and personal protective
. Do not kitl some viruses equipment (e.g., gloves, gowns, face and eye
. Gram negative multiple in iodophors protection).. Jn modern practice no institution can
e Some do not classified these as run without 0.5% chlorine solution.
HLDs
. Use when other HLDs are not Post exposure prophylaxis should also be available
available for accidental needle pricks or injury'
Chemoprophylaxis is recommended for workers with
HLD by steaming highest-risk exposure, such as deep injury with a
. Example-gloves, cannulaefor MVA hollow-bore needle. Chemoprophylaxis should be
. Steamer ---with one to three tiers for offered for lower-risk exposure, such as injury with a
20 minutes solid suture needle from a source patient with
asymptomatic HIV or a btood splash to mucous
membranes. Do not offer chemoprophylaxis for
negligible-risk exposures such as a non-bloody urine
splash. Chemoprophytactic regimen should begin
within 1 or 2 hours afterexposure.
Facilities should assure that at least one individual
330
rr
r
t+
3
r
t+
with training in infe'ction prevention is employed by or laundry, disinfection and sterilization of
tf
rit regularly available to the facility. This individual equipment or use of single use
should be involved in the development of written equipment, waste management, sharps
/ infection prevention policies and have regular handling, client placement and healthy
I; communication with HCP to address specific'issues workplace initiatives
or concerns related to infection prevention. The d. Education of health care providers,
;
:
development and ongoing refinement of infection cl ients and fa m i I ies/visitors/caregivers
prevention policies and procedures should be based
on evidence-based guidelines, regulations, or 3. Hand Hygiene includes handwashing and
standards. These policies and procedures should be use of alcohol-based hand rub (greater than
tailored to the facility and re-assessed on a regular 60% alcohol) before client care, between
basis (e.g., annually), taking into consideration the dirty and clean and when leavingthe client
types of services provided by the facility and the . Screening and assessing clients
patient population that is served. This process must be done to identify any
(referred to as risk assessment by the lnfection communicable disease risks with
Prevention profession) will allow facilities to better the client contact
prioritize resources and focus extra attention on those . Clients are prompted to self assess
areas that are determined to pose greater risk to their when booking appointments
patients. . Clients are educated about
respiratory etiquette
Key ad mi n istrative recommendations:
i.
i t. Develop and maintain infection prevention 4. Risk Reduction Strategies that provide
and occupational health programs reduced exposure in the presence of
I
2. Assure sufficient and appropriate supplies communicable diseases must be used.
necessary for adherence to Standard Those strategies include the following:
Precautions (e.g., hand hygiene products,
personal protective equipment, and injection a. Client placement (segregation)
f
equipment)
b. Personal protective equipment
3. Assure at least one individual with training in
c. Proper use and removal
a infection prevention is employed by or
d. Safe handlingof sharps
r e. Clean client equipment including
I
t regularly available to the facility
sterile medications
4. Develop written infection prevention policies
f. Clean environment
t and procedures appropriate for the services g. Clean laundry
provided by the facility and based upon h. Proper handling of waste
evidence-based guidelines, regulations, or i. Healthy workplace practices that
standards keep staff and clients safe including
the need for immunization and
SUMMARY OF INFECTION PREVENTION AND education on when to stay home
CONTROL BEST PRACTICES from work in a health care setting
plus clear follow up protocol for
L. Basic infection prevention measures are
exposure to blood and body fluids
based on a knowledge of the chain of
transmission and the application of Sp 5. Providing health care provider and client
Practices in all settings at all times education on infection prevention and
control strategies is required
2. The elements of SP Practices include:
a. Hand Hygiene ANTI M ICROBIAL STEWARDSH I P
b. RiskAssessmentof clients Antibiotic resistance poses a significant threat to
L c. Risk Reduction Strategies through use of
public health, particularly because antibiotics
personal protective equipment, cleaning
underpin routine medical practice in both primary
the environment and equipment,
331
and secondary care. To help prevent the development acquired infections to be one of the major infectious
of current and future bacterial resistance, is it diseases having a huge economic impact worldwide
important to prescribe antibiotics according to the [. These infections affect about 2 million people
principles of antimicrobial stewardship, such as annually resulting in 5% to 15% of them requiring
prescribing antibiotics only when they are needed hospitalization Surgical site infections (SSls) are
(and not for self-limiting mild infections such as colds known to be one of the most common causes of
and most coughs, sinusitis, earache and sore throats) nosocomial infections worldwide and account for
and reviewing the continued need fot'them, These nearly 20% Io 25% of all nosocomial infections
principles should be set out within local antibiotic Surgical site infection rates are reported to range
guidelines and pathways and be consistent with the Irom 2.5"/o to 41.9% globally resulting in high
loca I a nti biotic form u la ry. Local antibiotic formu la ries morbidity and mortality. SSls result in increased
should indicate a range of antibiotics for managing len$h of stay, mortality and cost Approximately 2%
common infections, and permit use of other to 5% of the 16 million people undergoing surgical
antibiotics only on the advice of the microbiologist or procedures each year develop surgical site infection
physician responsible for the control of infectious with more recent data putting it at two-thirds of
diseases. patients who undergo operations The situation is
more severe in developing countries where resources
The approach to prescribing in line with the are scarce and staffs are always in short supply. A
principles of antimicrobial stewardship wide range of factors have been proven to influence
recommended is as follows: wound infection. Some of these factors include pre-
existing illness, wound class, wound contamination,
Do not start antibiotics without clinical evidence of extremes of ages, malignancy, metabolic diseases,
bacterial infection. malnutrition, immunosuppression, cigarette
lf there is evidence or suspicion of bacterial infection,
srnoking, remote site infection, len$h of surgical
use local guidelines to start prompt, effective operation, emergency procedures and long duration
antibiotic treatment. of pre and postoperative hospitalization amongst
others. Additionally BMl, and maximum intra
Document the following on the medicines chart and
operative body temperature are independent risk
in the person's medical notes: clinical indication,
factors for SSl. Maximum intraoperative body
duration or review date, route and dose.
temperature is the only modifiable risk factor. Subtle
18'1e20'2i'22
differences rnay influence SSI
-
Obtain cultures knowing the susceptibility of an ,tS,mRerature
infecting organism can lead to narrowing of broad-
spectrum therapy, changing therapy to effectively
An SSI is an lnfection occurs within 30 days after
treat resistant pathogens, and stopping antibiotics
surgery (if an implant is left in place, to 1 year if
when cultures
related to surgery and at least one of the following:
Review the clinical diagnosis and the continuing

. Purulent drainage from wound/drain (culture
docu mentation not requ i red
need for antibiotics by 48 hours from the first
antibiotic dose and make a clear plan of action
- the
. Organisms isolated from fluid/tissue of the
wound
'Antimicrobial Prescribing Decision'. The 5 . At least 1 sign of inflammation (e.g. pain or
Antimicrobial Prescribing Decision options ar€: Stop,
tenderness, induration, erythema, local
Switch lV (intravenous) to Oral, Change, Continue,
warmth of the wound)
and Outpatient Parenteral Antibiotic Therapy.
. Spontaneous dehiscence of wound or
deliberate opening of the wound by surgeon
Clearly document the review and subsequent
unless site culture result is negative
decision in the person's medical notes.
. Surgeon or attending physician declares the
SURGICAL SITE INFECTION wound infected
o ldentification of abscess in the
World Health Organization (WHO) describes hospital organlspacelincision site is identified by
3?2
a
lnfection Preventian
I
direct examination or during rsoperation, by awareness of antibacterial resistance are less well
histopathology, or by radialogical established in most of SSA, and therelsre the ability
examination to mitigate their consequences is significantly limited
{ The American College of Obst*tdei*'1,rc and

Gy n a eco og sts reco m m e n d s p ro p hy' affte ffi-bi otl cs
I i PRACTICE REFORMS
within 60 minutes of incision to prffint SSl. The
r Joint Commission has identifled the prauefttten of SSI Manju et al focussed on the widespread use of
I
7 as one of its National Patient Safety Goals.
prophylactic antibiotics. Existing regimens were
replaced with reduced antibiotic schedules and
t prophylactic antibiotics were recommended to be
i Many different drug regimens have bgen rgsorted to
be effective in decreasing post-o.perativa infeetious given only in the oper"ating theatre at the time of
t. morbidity. Since there are an overwhelmlng number ind uction or d irectly before a n operation.
of effeetive drugs available, attempts tp define an Combinations of antibiotlcs were also avoided. Other
t, antibiotic regimen of choice haye been"problematic. practice reJorms ineluded t1aving patients bathe and
b
ldeally, such a drug regimen should ber of proven wea r clea n clothes preoperatively,
l
effect active against the malority of pathogens tikely
controlling diabetes and other comorbidities
f to be involved, attain adequate serum and tissue
levels throughout the procedure not associated with
the development of antimicrobial resistance
preoperatively, using iodine scrubs to prepare
operative areas, replacing shaving of hair in wards
t inexpensive and well-tolerated. ln many aspeets, with limited clipping in theatres, strict
F
penicillin and cephalosporin meet these criteria. implementation of aseptic techniques, haemostatic
Many investigators have used these drugs and have dissection, wound closure monitoring by senior
t recommended that drugs from these classes surgeons, avoidance of frequent postoperative
represent the antibiotics of choice for caesarean dressings of clean wounds, wound surveillance and
I section prophylaxi. The question that remains, shortening of hospitals stays'u
r
therefore, is not whether to use an agent for
r prophylaxis but rather when and which regimen to
Their evidence suggests that with dedicated and
r careful implementation, capitalizing 9n expert, local
rt use?.'o''u
knowledge through a locally owned and locally
r Antibacterial resistance-associated infections are sustained process, audit has the potential to make
r known to increase morbidity, mortality, and cost of considerable contributions to the reduetion of SSls.
#' treatment, and to potentially put others in the
r community at higher risk of infections, ln high income
Burden of endemic health care associated infection
+
r in developing countries is high. There is therefore a

countries, where the burden of infectious diseases is
I need to improve surveillance and infection"'"
t
relatively modest, resistance to first line anti bacterial
( agents is usually overcome by use of second and third
The goals of lP are to minimise post proeedure
i
tn
line agents. However, in developing countries where
infection in clients and to prevent transmission of
the burden of infectious diseases is high, patients
rt life-threatening infections to client, service
with antibacterial resistant infections may be unable providers, auxiliary staff and members of the
,-
to obtain or afford effective second line treatments. In
community.
r subSaharan Africa (SSA), the situation is aggravated
'>
by poor hygiene, unreliable water supplies, civil It is only through the combined effort of all who work
i conflicts, and increasing numbers of immune
.compromised people, such as those with l-llV which
in the hospital setting that this can be achieved
r control practices
facilitate both the evolution of resistant pathogens
and their rapid spread in the community, Beeause of
'( limited capacity for disease detection and
: surveillance, the burden of illnesses due to treatable
bacterial infections, their specific aetiologies, and the
,.
3s3
REFERENCES
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Prevention of Hospital acquired infection*. Hospital Epidimeology August 2010 vol 31
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Allegranzi , Shamsuzzoha B Syed , America 1980 60:27-40
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Organization Scientific Publ ications. 1982
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http:',,ww.who.int'^n/. Medicine 197 8 88:285-293
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it out- Good Practice in infection prevention evidence and case reports of occupationally
and control, 2005, Kimberly Clark acquired HIV and bloodborne drseases.
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Resrstance lnfection Prevention and Control; (suppl.): 1990 558-560.
Bert Practices for lonf term home and 17. Comm Drsease Bulletin, 1990 and AORN,
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7. Tagoe DN, Baidoo SE, Dadzie l, Tengey D,
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acquired infections in the Volta regional Mawufemor KRA, Bugr S. Post Operative
hospital of Ghana. Ghana Med J. 2011; Surgical Site lnfection in a Surgical Ward of
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CDC- National Centre for Emerging Zoonotic lnt J Health Sci Unternetl. 2014
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lnfectious Drsease: Basic infection control Jan3 1 ;2(1 ) :207 - 12. Avai lable from
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http /i =Vol u
setting, 2011 pp1-6 me2&iss=lssuel
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for hand washing and hospital environment Mannerquist K, Nystr\m B lnfection:
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10. Alfred E. Yawson and Afua A. J. HesseHand community care (NICE clinical guideline
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doi : 1 0. 3 85 5 /j i dc. 2422 (20 1 4 epic3: National evidence-based
77. Alex Owusu et af Assesing Hand Hygiene guidel i nes for preventi ng healthcare-
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334
Engl and, recom me ndation SP6 Antibacterial resistance in sub Saharan

21. Anti b ioti c p rop hy I axis for gy neealogic Africa: an underestimated emergency
procedures. ACOG Practice Butletin No. .Annals of the New York Academy of
104. American Coltege of Obstetricians and Sciences Vol ume 1 323, Anti microbiat
Gynecologrsts. Obstet Gynecal, 2W; 1 1 3: Therapeutics Reviews Pages 43-55
1180-9.
22. Nosheen Zaidi, Najma Javed, Surnera Naz, Manju M. Anchalia, Lucia D'Ambruoso
Arshad Mumtaz Gaps in Knowledge and Seekrng sol utions: sca I i ngup
Practices About Health Care Asssciated audit as a quality improvement tool for
lnfections Among Health Care Workers at a infection contral in Gujarat, lndia
Tertiary Care Hospital Journal of lslamabad lnternational Journal for Quality in Health
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:
23. Hanaa Farouk, Aminah Abd El Fatah and 464470

Amal Gaber SA/GIE DOSE PROPHYLACTTC First pubtished online: 11 April 2011
ANTIBIOTIC BEFORE SK//V /NCISIO/V 27. Benedetta Al legranzi, Seprdeh Bagheri
TSUGGESIED REGIMEN PRIOR TO ELECTIVE Nejad, Christophe Combescure, Wi lco
CS lN AL-ZAHRAA HOSPITAL) AAMJ, Vol.9, Graafmans, Homa Attar,, Liam Donaldson,
i
N. 7, January,2011, Suppl Didier Pittet, Burden of endemic health
Ajekweneh A. Eifediyi R.A, Okome G.B.O. care associated infection in developing
; Momoh M, lkheloa J.Okogbenin $ Affussim countries: systematic review and meta
a C.O Alika S. Olowo S. and Ajekweneh V. analysis LANCET Volume 377, lssue 9761,
Eva I uati n g P re- I nc i si on Versus Post 15-21 January 2A11, Pages 228-241
I
f Umbi I ical Cord Clampi ng Antibiotic Stephen Apanga, Jerome Adda, Mustapha
i
Prophylaxis in the Prevention of Post lssahaku, Jacob Amofa, Kuewu Rita Ama
r Caesarean Section lnfections in a Nigerian Mawufemor Epidemiology of Wound
I Specra/rst Teach i ng Hospital I nternationa I lnfection in A Surgical Ward of a Tertiary
I
Journal of Gynecological and Obstetrical Care Hospital in Northern Ghana lnt J Med
t'
I
Research, 2015, 3, 26-38 Health Sci. Oct 2013,Vo1-2;lssue-4
i
25. Samuel Kariuki , Gordon Dougan
7
I
r
I
t
r
r
r
-
I
I
l.
I
(
335
domprefibnsfiie Gyneaeolqey
m t,6 fryie$
#sk
.:
CHAPTE29
r
Abnormalities of'the Female

Genital Tract and Acquired Gynaetresia
APAboyeji andJDSeffah
INTRODUCTION primitive sex cords. Some germ cells may not reach
theirfinal destination during migration, such usually
t
A proper understanding of the congenital undergo atresia, but some may survive to form germ
abnormalities of the ovaries and the duct system celltumor.
I
serving then can best be appreciated by examining
the ways in which these structures are formed during GENETIC DETERMI NATION OF GONADAL SEX
i
I embryonic and fetal development.
I Sex determination in the mammal is determined by
(
Following fertilization, the normal embryo contains the presence or absence of a normal Y chromosome.
rI
I 46 chromosomes, including 22 autosomes derived ''' The Y. chromosome contains a gene sequence on
r from each parent. The concept of mammalian the short arm of the chromosome (.Yp), which
rI
I development is that the 46XY embryo will develop as encodes for Testicular Determining Factor (TDD.
I a male and the 46XX embryo will differentiate into a This gene is known as sex determining region on the
I female. Y (SRY gene). The mechanism through which TDF
induces differentiation seems to depend on a cell
ORIGIN AND MIGRATION OF GERM CELL surface antigen known as H-Y antigen. The H-Y
I
antigen is also located on autosomal chromosomes
;
i
The Gonads which do not acquire male or female and other autosomal genes.
: morphological characteristic until the seventh week
-
a of development appear initially as a pair of Ovarian differentiation is determined by the presence
longitudinal ridges, the genital or gonadal ridges. of two X chromosomes. The ovarian determinant is
- Theyareformed by proliferation of theepithelium and located on the short arm of the X chromosome as
condensation of the underlying mesenchyme. The absence of the short arm results in ovarian agenesis.
germ cells migrate by amoeboid movement during Girls with a single X and no Y chromosome (i.e. 45X0
the fourth week along the dorsal mesentery of the Tuners syndrome) develop ovaries, but their germ
hindgut arriving at the primitive gonads at the cells and ovaries degenerate before birth. Both X
beginning of the fifth week and invading the genital chromosomes must therefore be present for long-
ridges in the sixth week. The migrating primordial term survival of oocytes in meiotic prophase.
germ cells are relatively large, contain few organelles
and have a large spherical nucleus. Just before and PHENOTYPIC SEXUAL DIFFERENTIATION
L
during the arrival of the primordial germ cells, the
It is vital to understand the mechanism and process
epithelium of the genital ridge proliferates and
penetrates the underlying mesenchyme forming the of differentiation of the internal duct system and
337
in the Topics
Comprehensive Gynaecology
disorders TNCIDENCE
proper management of
external gertitalia for
Trre early embryo is congenital genital tract
of sexual differentiaiion' The exact incidence of
iistim
bipotential, with the 'U'f
ity to develop maleorfemale
abnorm al ities i s un t<nown' lt
have some minor or
malor i::l: i: i^:::
gtniitfiu' fnt pri1ll modelof 1 in 200 to 400 women
internal and external
genitalia is iemate' ffll O.Sr."of genital tract
abnormal ities'
development ot ilrE
differentiation requires"the
active secretion 3f l!:
testicular androgen
testosterone''ld, Mullerian AETIOLOGY
a glycoprotein plofluced
lnhibitory Substance trt'lisl' congenital genital tract
to the The precise cause of *'i:tl:Y,"f cases' lt
by Sertoli cetts' resto;;;tt;'gives'rises is unxnoir'rn in vast
duct' which differentiates abnormatities
development" ot woittian genetic and environmental
iiui
*'it *"t'talia and also
the is however pot'inrt of
into the internal devetopment of sorne
factor plays
masculinization of the
cloaca' 'o"
'ott"it"t]ne
these abnormatities'
iamilial Mullerian ducts
defects
of the 13. is usually

Testosterone brings about
masculinization have been 'uoo"tJ' 'risomy defects and
of testosterone to fusion
cloaca through Jon"ttion accompanied by'i'it'inu
enzyme 5 - ati on h as
*u rtot* Pt:i :Ti
Uy ttte action of th occasiona I genital
dihydrotestosterone : "uli of complete vaglna
- reductase' Wolffian structures' however' are capable in trisomy 18' The occurrences suggest an
*itn u 46XX karyotype
directly' Mullerian lnhibitory agenesis in sisters
of utilizing testosterone Mullerian inheritance'
Olvetopment of the a-utosomal mode of
Substance infrinits t-ne of
structures, which
t*t" present and capable
"t
aciion uppt"t to be
unilateral so
Therearebasicallyfourtypes.ofcongenitalgenital
development' rnei
the hormone' which results iir., unnot*alities in thefemale; ducts
that each testis produces i. Failure ottot*uiion of
llt
structures on its own 'y''llt-tian
ducts
in regression of tfre Mullerian to MIS is 2. Failure ottulion of theofMullerian
oi rvrurrerian :ttTtittt the septum between
side. The sensitivitl
8 weeks ofgestation' 3. Failure of ii-ttoi'tion
prl..ntonfV Ouringttretirst the fused ducts
disappear'
the absence of testicular 4' iailure of structuresto
ln a normal female fetus' of the
androgen rt4fi results in degeneration 1. FAILUREOF FORMATION
'nO the development of Mullerian
Wolffian duct and in
to form the upper
structures' The Mullerian duct develops tubes' Failure of
uterus anJtaitopian
vagina, Cervix,
ABNORMALITIES in the absent of the
definitive
CONGEN iTAL TRACT the duct to from resutts of clinical
in Some of tfrese aOnormalities
need to be considered structures.
Three main principles of include: Maver-Rokinta.nskv-Kuster
;;;;;,;;;..
longunital abnormalities of vaginal and
clinical consideration'ot Hauuser SynOrome' 'nttntt
the senital tract; rudimentarY horn'
'i:"""'ir'.r.-rt'ri,rrrtrian and wolffian ducts are so
gross
closely linked embryologically .that are MAYER _ ROKINTANSKY
- KUSTER HAUUSER
uterus and vagina
malformations of the SYNDROME(MRKH)
comfnOnly associateO
with congenital
or
anomalies of the kidney
and ureter'
This syndrome refers
to the congenital aplasia
6t itre gonao is separate of the structures that
Otl*:.t^TT
2. The developtntnt
Normal and functional
severe hypoplasia
the YpP:r t-'iil?:
from that of tftt Juttt'
usualty present when
ir',.-*rr1.tiun ducts; including to occur tn
ovaries are therefore uterus and fallopian
tubes' lt is estimated
are absent
vagina, ute'u' unO fallopian tubes ilirtn'' nnhough developmental
1 in 4000 to s,o0o be
of these structures can
or malformed'
such as the absence
of abnormalitiet of 'o*l role in
3. Gross malfoimation they have .a central
found in other entities' a 46 XX
theuterus'unJ-uuginumaybeassociated uslallV-
chromosomes MRKH. The affectei-pttiltit 'and fve ovarian
with anomalies in the sex chromosome com;ii;ent
normal
make uP of the individual'
338
Abnormalities of the Female Genital Tract and Acquired Gynaotresia
functions. They typically present with primary ,Adaptedfrom the l"edition of thetextbook
amenorrhoea in an otherwise norffiatly developed
F-
I adolescent female. The conditlon is ftquently 3. FAII,URE OF DISSOLUTION
I
associated with malformation o{, u*t and This occurs when there is failure of dissolution of the
tf" median septum after fusion of the separate mullerian
skeletal systems. ln one series rena,Idffit&.Were
rf
present in 30% of the cases with renal 4enwis being duets. The most typical of the abnormality is the
P
1
present in morethan half of theealiebs:;
i' ''' septate uterus. There is a single vagina and cervix
t and an apparently normal single uterus. However
? No definite treatment is currently available for this there is an intrauterine septum that partially or
I
I type of abnormality. However, creation of a nsw completely separates the cavity into two hemi uteri.
I vaginal may be necessary to allow for social relation
Oecasionally an abnormality may be formed by a
when patients are ready for sexual functioning. There
is also a place for assisted reproductive technology in failure of fusion combined with failure of dissolution
I
I
willing patient. of the septum. ln this condition, there is vaginal
)- duplication, two cervices and an externally appareni
I
2. FAILURE OF FUSION single uterus with separate uterine cavities.
I
a- Failure of fusion of the Mullerian duct occurs in gLINICAL PRESENTATION

I varying degrees. Minor degree involves the uterine
shape. This type of malformation is extremely They are often symptomless. They may however
I
i present with the followings depending on the specific
I common and can be demonstrated in 10% of fertile
r
r
women. anomaly.
I
( The classic example of failure of fusion of the A. GYNAECOLOGICAL
i. Dysmenorrhoea in bicornuate uterus or due
I Mullerian ducts is didelphys anomaly in which there
,tr to cryptomenorrhoea in rudimentary horn.
is complete duplication of the female internal
il. Menstrual disorders including
genitalial. lt results in a double (septate) vagina, two
oligomenorrhoea and menorrhagia.
cervices and two separate herhiuteri. Other forms of
r failure of fusion include arcuate, cordiform and
iii. Recu rrent m id trimester m iscarriage
r iv. Rudimentary horn pregnancy which may
bicornuate uterus. rupture simulating ruptured ectopic
r
pregnancy.
t
I
B. OBSTETRIC
Malpresentation; transverse lie in arcuate or
wffi Mffi
I
i.
subseptate uterus, breech in bicornuate,
un icornuate or complete septate uterus.
It. Preterm labour, IUGR, lUD,
iii. Prolonged labour due to incoordinate uterine
action.
Obstructed'labour; obstruction by the non-
M}
iv.
gravid horn of the bicornuate or rudimentary
horn.
Retained placenta and postpartum haemor-
rhage when the placenta is implanted over
I Fig"l. \rtrlour fualon abaomalldaa of tho utlrur llrd y.glna uterine septum.
(a) |hrm* ameaame; (b) amuab findua xilh lil{e*dsr tts *rape of tE cayitf,
(cl Bi&nuat€ utrru6; {d} suhe@ |&rus$i&isrnfllotffm;
ta} rudinmrxqylwn:
{0 lrlsnsdieh}rysi {g} ltlom*l uterusui[r padat qstat$Strrn" DIAGNOSIS
A septate vagina and twocervices may be obvious on

I
vaginal examination. 0n birnanual examination, it
may be possible to feel the two separate uierine
339
Comprehensive Gynaeaology in the Topics
horns or a depression in the fundus. suggest the diagnosis of androgen insensitivity. Also
Hysterosa pi n gogra m, a pa rosco py a nd hysteroscopy
I I male level of testosterone in a girl of appropriate age
are also useful in the diagnosis of these abnormali- or the discovery of an XY karyotype in a phenotypic
ties. female with intra-abdominal testicles establishes the
diagnosis of the condition.
TREATMENT
INVESTIGATIONS
Each case requires separate consideration, Many are
left untreated. Bicornuate or septate uterus causing Laboratory Studies
recurrent miscarriages needs a plastic operation Standard evaluation of primary amenorrhea includes
(metroplasty). Traditionally, the septate uterus is an evaluation of hormone levels of luteinizing
unified with either the Jones or the Tompkins hormone (LH), follicle-stimulating hormone (FSH),
procedures. Term pregnant rates after these proce- prolactin, estradiol, and progesterone should be
dures have approached 80-85%. The scar left after undertaken. ln addition, evaluation of renal function
such surgical procedures are liable to rupture 1n late is prudent because of the association renal anoma-
pregnancy or labour, hence elective caesarean lies in as many as one third of patients with MRKH
section is indicated before term. However, in recent syndrome.
times, uterine septum is now easily and successfully
treated by means of hysteroscopic or resectoscopic lmaging Studies
Ultrasound is the cornerstone of radiologic imaging
incision of the uterine septum. Such patients so
treated may undergo vaginal delivery later. in patients in whom vaginal atresia is suspected.
Abdominal, pelvic and transperineal ultrasound
Strassman metroplasy is the procedure of choice for
images depict the ovaries, Llterus, and proximal
unification of the two endometrial cavities of an
vagina and provide anatomic evaluation of the
externally divided uterus both biconuate and
urinary tract.
didelphic.
4. FAILURE OF DISAPPERANCE
Although magnetic resonance imaging (MRl) is
routinely obtained (in developed countries) to further
Congenital abnormalities may result from the failure delineate the internal anatomy in patients with
of disappearance of a structure that normally does vaginal agenesis, a recent report suggests that MRI
not persist. An example of such is a lateral wall may be only 31% sensitive in detecting uterine
vaginal cyst (i.e. Gartner cyst) that results from structures in patients with vaginal agenesisu
remnants of the Wolffian duct. These cysts are
It is important to communicate with the radiologist
usually of no clinical significance, and should be
regarding the suspected anatomy to optimize the
removed if sym ptomatic.
results of the evaluation. lnsertion of a catheter into
ABSENSE OFVAGINA the urinary tract or identification of the location of the
perineal dimple using a vitamin E capsule may aid
As discussed above, absence of the vagina is gener- anatomic interpretation. Reconstruction of 3-
ally associated with absence of the uterus. Rarely, the dimensional images of the pelvis may facilitate the
uterus may be present and the vagina or a large part operative procedure, particularly when a proximal
of the absent. Vaginal agenesis may be diagnosed in vaginal pouch (e.g., in transverse septum) or when
the newborn period, or during a routine childhood duplication anomalies of the vaginaltract exist.
physical examination, but it is commonly not
diagnosed until the patient presents around the age Ultrasound and MRI are roughly equal at diagnosis
of 16 years with primary amenorrhoea after undergo- but MRI is superior at characterization due to
ing normal secondary sexual development. multiplanar capability and soft tissue resolution and
is preferred for MRKHS and disorders of lateral
The differential diagnosis of cornplete vaginal fusion. The vagina is much more distensible then the
agenesis is androgen insensitivity. Phenotypic uterus allowing distinction by ultrasound of- colpos
findings such as scanty pubic and axillary hair may from- metrocolpos. Ultrasound identifies
340
Y
't
r' Abnormalities of the Female Genital Tract and Acquired Gynaetresia
r
I
haematosa pi nx, wh ich i ncreases the patient's risk for

I insensitivity syndrome (AlS; also termed testicular
:
I endometriosis. Ultrasound, especially transperineal, feminization), karyotype analysis is essential. ln
helps with surgical planning by identifyingthe length patients with androgen insensitivity syndrome,
of the atretic segment to determine if an indwelling physical examination may reveal a shallow vaginal
form must be placed following resectisn.z The atretic pouch, and rectal examination may reveal the
segment tends to be longer with higher septa. Also, absence of a palpable cervix. A46, XY karyotype is
ultrasound evaluates the presenceand patency of the corroborative and initiates an endocrine evaluation.
cervix. With cervical agenesis, the vaginal tapers to a Occasionally, young patients with androgen insensi-
blind pouch. When haematometra is seen, tivity syndrome are indentified in the operating room
nonvisualization of the (fluid-filled) endocervical while undergoing inguinal hernia repair.
canal means the cervix is imperforate. Ultrasound
also aids in the medical management by detecting Diagnostic Procedures
renal anomalies, follow-up of hydronephrosis and lnvasive procedures usually are unnecessary and
endometriosis (complication of detayed diagnosis), should be avoided unless diagnostics radiographic
and documents decompression after surgery. studies are inconclusive. Laparoscopy may be
necessary for evaluation of the uterus and adnexal
Other Tests structures if they are not clearly indentified using
A karyotype is frequently obtained in the evaluation of ultrasound or MRI scan. Patients with a solitary
complex anomalies. Patients with the most common kidney, who are at risks for vesicoureteral reflux,
i presentation of vaginal atresia associated with MRKH should undergo a voiding cystourethrogram to
syndrome typically have a normal 46, XX karyotype. determine the need for antibiotic prophylaxis.
When perineal examination findings indicate ambig-
uous genitalia that may be the result of androgen
Fig 2: Types of Outflow Obstruction (Adapted from First Edition of the textbook
;
34L
Comprehensive Synaecology in the Topics
Acquired Gynaestrasia The that the patients have no vagina

ln the normal anatomical position the anterlor and usually comes as a shock and is almost always
posterior walls of the vagina are in a.Fffi, As followed by a period of depression in which many
such any ulcerating or inflammatory in*ff,to#th patients question their feminity and look upon
mucosal surfaces is likelyto lead to atneslg{tf ffiis themselves as abnormal females. Sometimes they
of the vagina during the healing phase,'OrE d He eontemplate suicide particularly in regions where the
commonest causes of acquired gynaehesia in Afrdca ability to procreate is of fundamental importance to
is the insertion of herbal concoctions with qqrresi\e marriage and soeial acceptance. lt is therefore
properties into the vagina. These herbal coneoqtions important that adequate counseling is offered by
may be inserted either for medicinal purpooes or Wlth tra i ned person nel before d ef i n itive treatment.
the aim of narrowing the vaginal lurnen in order to
enhance sexual performance (called 'maintenaRce of Non surgical methods: Management involves an
the vagina"). Other substances with corrosive integrated health care team: Gynaecologist,
properties that are used for the purpose of "vaginal Paediatric Surgeon, Plastic Surgeon, Paediatric
maintenances" include Potassium permanganate urologist and Counsellor, The timing of creation of a
and alum. new vagina is elective, but treatment should be
deferred until late in adolescent years to allow
Other causes of acquired vaginal atresia include informed consent and compliance.
obstructed labour (in which gynaetresia may co-exist
with VVF); senile vaginitis, radiotherapy to the Co-operation of the patient must be sought right from
vagina, traditional vulvo-vaginal incisions, surgical the commencement of the treatment as the
operations such as combined anterior and posterior treatment may take a long time.
vaginal repairs, Lymphogranuloma venerium,
malignancies and some traumatic conditions. The most commonly used non-surgical method
Childhood diseases such as diphtheria and measles includes Frank' Dilator method and l ngram' method.
The Frank Dilator method involves the repeated use
have been known to be associated with vaginitis and
of graduated Vagina dilators over a period of 6 to 12
can therefore also cause atresia.
months. A vagina dimple of at least 1cm is necessary
The main presenting compla'ints of acquired for this technique to succeed. The procedure is
gynaetresia include absence of menses successful in about 90% of cases with appropriate
(cryptomenorrhoea), cyclical lower abdominal pain, selection '0. Some commonly cited barriers to
and difficulties in copul'ation. The patient may also success have been identified such as cramping and
complain of urinary difficulties such as urinary fatigue of the patients, privacy issues, lack of comfort
retention. lf gynaetresia co-exist with VVF, the patient and time to dilate daily5
may present with cyclical haematuria.
To overcome these obstacles lngram attempted to
Patients with acquired gynaetresia do not need assist the dilatation procedure by using the patient's
extensive radiological and endoscopic assessment own body weight and gravity. He described a method
like those with congenital atresia. Routine systemic of progressively increasing dilatators attached to a
assessment is adequate in most cases. Rectal bicycle seat where patients provide perineal pressure
examination is important as this can reveal the full by sitting and slightly leaning forward. Patients are
extent of the scar and also allow pelvic structures to required to do this for 15 to 30minutes interval for
be digitally examined. Note must be taken of the 2hours per day. The advantages of either method
location of the scar. Scars lower down the vagina are include: No hospitalization, patient control, Cost
easier to access and manage compared to scars effectiveness, m i n i ma I morbid ity a nd com pl ications.
5
higher up.
Surgical Methods:
MANAGEMENT The primary goals of surgical intervention are to: (1)
Patients with vagina atresia require careful relieve obstruction and pain, (2) restore a normal sex
psychological counseling and associated therapy. life, and (3) preserve reproductive potential. The
342
Abnormalities of the Female Genital Tract and Acquired Gynaetresia
timing of surgery depends upon the patient's Williams's vulvovaginoplasty

anatomic configuration and the pres6R6€ 6r absence Williams's vulvo-vaginoplasty is another procedure,
of functionalendometrialtissue. . which is simple, quick and relatively cofifortable for
the patient. lt involves the creation of an external
ln the patient with functional orarian',&.*bll! an pouch by suturing the labia majora to form a short
absent uterus and vagina, genital tract hi&rEUuction vertical "vagina". Functionally, the result of the
is not medically urgent. ln the absencd 6f ffiPiguoqs procedure is good. However, patients may complain
genitalia, gender assignment is not an lBgr,rc and of shortness of ihe vagina, no feeling of penetration,
involving the patient in the decisions regarding future difficult angle for penile penetration, abnormally
surgery is prudent. Girls who are offerBd operation looking external genitalia and pressure on the rectum
require a certain level of psychological and sexual during intercourse. Other procedures beingtried with
maturity to be motivated and compllant with the various success rates include intestinal vaginoplasty,
dilatation regimens necessary for successful Davydov procedure and Vecchietti technique.
outoome. Surgical intervention usually delayed until
age 77 years. There has been reported early development of
vaginal cancer in women with neovagina. They seem
Surgical or medical intervention must be instituted to present in 30s and 40s. lt is therefore important
sooner if a patient presents with vaginal outflow that any of such patients who present with vaginal
r obstruction, abdominal or pelvic pain, or is at risk for discharge and bleeding should be taken seriously. ln
secondary endometriosis. Menstrual suppression future, tissue-engineering techniques where a vagina
{ using continuous progestogens can be considered to
I can be grown in-vitro from a few of the patients'own
r buy time whilst the patient is being prepared. vaginal mucosal cells to serve as an autologous
I
I
I
Attempts at draining should be avoided, as transplant would reduce frustration in these patients
contamination, infection and scarring can be the
t consequences, making definitive surgery more Reconstruction using Sigmoid Colon
i
complex. The best outcome is with the primary lntestinal segments, typically derived from the
I sigmoid colon,
to''u
can also be used and it provides
I
surgery.
some significant advantages over the skin grafts
i
I
Maclndole and Reed Technique used in the Mcindoe operation. Principally, the
I With failed non-surgical techniques, vaginoplasty " " advantages relate to the distensibility and self-
i would have to be performed. Various techniques have lubricating nature of the conduit and the reduced
f
J
been used to create vagina artificially. The most natural contraction resulting in neovaginal stenosis,
widely used being that of Mcindole and Reed". The which allow the patient to avoid the discomfort of
I
procedure involve the creation of a cavity between the long-term dilator use. Disadvantages relate to the
I
bladder and bowel at the site where the natural potential complications encountered in laparotomy
vaginal would have been and the cavity then lined by and bowel resection and to the continuous produc-
i
a split-ihickness skin graft taken from the thigh and tion of mucous secretion that may requirethe use of
I applied to the space on a plastic moved. The an absorptive pad ortampon.
procedure may be complicated by protracted
postoperative pain and fistula formation. There is also HYMENALABNORMALITIES
the possibility of vaginal soreness, dryness and
contracture of the graft unless a dilator is worn or Hymeneal abnormalities 'u typically are isolated
sexual intercourse is performed regularly. "Normal" occurrence without other reproductive tract or
; sexual function has been reported in 80-90% of urinary tract associated abnormalities, The most
treated patients. ln recent time amnion has been common is an imperforate membrane, which may
used to line the neovagina and the result has been exist at the lower end of the vagina, loosely referred
successful. However, the theoretical risk of infection to as imperforate hymen. lf the diagnosis is not made
I
from donor amnion has made this technique less before the onset of menstruation, the patient usually
I(a popular. 14 - 15 years old, presents with cyclic pain, primary
amenorrhoea, a bulging hymen, and
haematocolpos. The patient may also present as an
a
:
343
'----.--_-]
acute emergency if urinary obstruction develops. incompatible with life. lt is thus a rare phenomenon.
Diagnosis is made by the findings of lower abdominal However, anomalies in the development of female
swelling. Rectal examination may reveal a large external genitalia may result from prenatal exposure
bulging mass in the vagina. Occasionally, however, of the genitalia to androgens caused by maternal
diagnosis may be difficult if the vagina is imperforate inadvertent ingestion of oral contraception during the
over some distance in its lower part. Treatment is first trimester of pregnancy, from androgens pro-
usually simple if the membrane is thin and all that duced by the fetus. e.g. congenital adrenal hyperpla-
needs to be done is a simple excision of the mem- sia or the mother (e.g. androgen-producing adrenals
,I
brane and release of the retained blood. However, if or ovarian tumour) during pregnancy
the obstruction is more extensive than as thin
membrane, resection of the thick segment and OUTLOOK FOR FUTU RE FERTI LITY/TREATM ENT
reconstruction of the vagina may be done either by an
The outlook for future fertility depends on whether
End-to-End anastomosis of the vagina or a partial
there are any associated complex anomalies of the
vaginoplasty.
uterus. Those with absent uterus can procreate
LONGITUDI NAL VAGI NAL SEPTUM through the use of surrogate mothers. For those with
isolated atresia of the uterus but with function..
A longitudinal septum (i.e double vagina) usually ovaries and normal active endometrium (compli-
occurs in association with fusion anomalies of the cated by haematocolpos and haematometra), the
cervix and uterus but can occur alone. lt is not outlook for future fertility depends on how early
uncommon. The condition may go unrecognized until diagnosis and intervention are made. lf the patient
coitus is attempted. At this point, coitus may prove presents late, apart from the fact that uterus may
difficult because each vaginal opening is too small. lt become distorted and the tubes damaged, there is a
may also reveal itself during vagina delivery when the high incidence of endometriosis as a result of
narrow hemivagina may be inadequate to allow retrograde menstruation in such patients'u when
passage of the foetus, resulting in serious tear. pregnancy is achieved there is a likelihood of soft
Treatment consists of surgical excision of the septum. tissue obstruction to labour, as there may still be a
ring of scar tissue around the vagina. The use of
VULVAABNORMALITIES bioengineered tissue for creation of a new neovagina
has been recently described and may play a major
Absence, gross underdevelopment and duplication of
role in the nearestfutureu.
the vulva are usually found with other malformations
REFERENCES
t. Simpson J.L. Genetic Control of Sex Malformations AM .J. Obstet. Gynaecol, 1981:
differentiation. Semin. Reprod. Med. 1957 141(B),910-920
5,209-20 5. Laura L, Farah SC, Lisa K, Mayer -Rokitansky-
2. Langman J. Medical Embryology. The Williams kuster-hausersyndrome: a review. lnt. J. Women
and Wilkins Company, Baltimore third edition Health 2015; 7 865-870
1979 160-200 6. Economy KE, Barnewolt C, Laufer MR: MR
3. Tindat V.R. Malformation and Maldevelopment of sensitivity in detecting uterine agenesrs in cases
the genital tract in Jeffcoate's Principles of of vaginal agenesis. Paper presented at the
Gynaecology Tindal VR (ED) Fifth edition Annual Meeting of the North American Society of
1 38- 1 58.
Butterworths London 1987 Paediatric and Adolescent Gynaecology. 1998.
4. Evans T.N, Poland ML, Boving RL, Vagina 7. Scanian KA, et al. Value of Transperineal
344
r Abnormalities of the Female Genital Tract and Acquired Gynaetresia
r i
SonograpfuintheAssessmentofyqi;@Hresia. 13. Mcindole AH, Banister JB, An operation for the

t AJR 1990; 154(3):545-8
Frank RT, The formation of-
cure of the congenital absence of the vagina. Jr.
Obste. Gynaecol Br. Commonwith 1938 45,490-
without operation A.M. J. j
5
7938.35;/053-J055. ..: J: {i
L 9. lngram JM the bicycle

management of vagina
14. Radhakrishnan Colon interposition
vaginoplasty: a modificagion of the Wagner-
Baldwon technique. J Pediatr Surg 1987 Dec:
a
_t
"t
l
preliminary report AM.
r 1981:140(8):867-873.'..:j: 15.
22(12):117 5-6.
Ghosh TS and Kwawukume EY. Construction of an I
i
F 10. Edmonds DK. Congenital'tffi artificial vagina with sigmoid colon in vaginal {
t j
r
ii
geniotat tract. Best pract. Res. m r
Gynaecol. 2003, 17 19-40
agenes,s. lnt. J Gynecol Obstet. 1994, 45:41 -45
16. Rock JA, Zacour HA, Dlugi AM, et al. pregnancy ;
t 1 1. Williams E.A Congenital success following surgical correction of fl
f,t
r simple operation for its relief. imperforate hymen and complete vaginal ;rt
it
I Br. Commonwith (1964 71 571-1.7,, . septu m. Obstet Gy necol I 9 82 ; 59 : 448.

12. Minto CL, Creishton SR y6gra€#i,*sty
Obstetri ci a n a nd Gyn aecologi $ ruS *&i-9o
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Comprehensive Gynaecalogy in the Topics
346
T
I
I
I
t:
('
t
I
t
r CHAPTEEl
r
I
Female Genital tklutilation

Alexander T. Odoi and Edward T, Dassah
:
i
Female genital mutation (FGM) comprises all formed on minors, it violates the Convention on the
procedures that involve partial or total removal of the Rights of the Child. lt is a reflection of the deeply
external female genitalia, or other injury to the female rooted inequality between the sexes and constitutes
genital organs for non-medical reasons'. The practice an extreme form of violence against women''t. FGM
has been variously referred to as "female circumci-
I
poges serious physical, mental, sexual and reproduc-

sion", "female genital cutting" and "female genital tive health risks fot women and girls especially those
i
mutilation/cutting". The term female circumcision who have undergone severe forms of the procedure.
I
has largely been abandoned since it this analogous The majority of girls and women in most countries
with male circumcision. Female genital mutilation is think the practice should be abolished, Overall, the
( the most commonly used terminology; ',mutilation,' practice of FGM has declined over the last three
emphasizes the gravity and harm of the act. The term decades, but rates of decline have been slow and
'cutting' is considered to be non-judgemental and variable, and not all countries have made progress'''.
appears to be more appropriate in discussion and
collaboration towards eliminating the practice'. Both Epidemiology
; terms emphasize the fact that the practice is a Female circumcision was first discovered in ancient
violation of girls' and women's human rights'?. Egyptian mummies in 200 BC. This led to the belief
Eliminating FGM is a global priority, and will contrib- that the Pharaohs practiced FGM and gave
I
ute significantly towards the attainment of Sustain- pharaonic circumcision its nameo. The origin of FGM
able Development Goals 3 and 5. is rooted too distantly in human history to be
FGM is universally recognized as a violation of the fruitfully traced. The ritual probably had multiple
:
fundamental human rights of women and girls. The origins. lt could have originated as an initiation
practice violates several well-established human ceremony of young girls into womanhood4 lndeed in
rights principles, norms and standards including a parts of Egypt today a female is not regarded as
person's rights to health, secqrity and physical having attained full womanhood until and unless she
integrity, the right to be free from torture and cruel, has been circumcised'.The ritual has always been so
inhuman or degrading treatment, and the right to life widespread that it could not have arisen from a single
when the procedure results in death. Consequenily, origin.
FGM contravenes several international treaties and
conventions including; Universal Declaration of FGM has been reported to occur in all parts of the
Human Rights, the United Nations (UN) Convention it is most prevalent in parts of Africa
world, but
(especially in the eastern, north-eastern and western
on the Elimination of all forms for Discrimination
against Women, and the Convention against Torture regions), the Middle East (such as Iraq and Yemen),
I and Other Cruel, lnhuman or DegradingTreatment or Asia (e.g. lndonesia), South America (e.g. Colom-
a
Punishment. Moreover, since it is invariably per- bia), lndia, Malaysia, Oman, Saudi Arabia, and the
a
347
United'Arab Emirates with large variations in terms of recent times a discouraging trend has emerged in
the type performed, circumstances surrounding the some countries where medical professionals are
practice and size of the affected population. The increasingly performing the procedure. For example
practice is also found among certain immigrant in lndonesia, more than half of girls underwent the
communities in Europe, Australia and North procedure by a trained medical professionalu.
America'-t.
TYPES OF FEMALE GENITAL MUTILATION
Although the exact number of giils and There are several forms of genital mutilation.
women worldwide who have undergone FGM
SCARIFICATION
remains unknown, it is estimated that at least 200
million girls and women in 30 countries where
ln some cultures initiation of girls into womanhood
representative data is available have undergone
takes the form of shaving of their pubic hair with a
FGM, and over 3 million girls are at risk of being
special ancestral knife, followed by four cuts made
subjected to FGM annually'-'. The prevalence varies
into the clitoris to let out blood without cutting off any
widely across and within regions and countries
flesh'o
rangingfrom 1% in Uganda and Cameroon to 98%in
Somalia, with ethnicity being the most significani NIPPING
determinant. The prevalence in West Africa ranges
from l"/" in Cameroon lo97% in Guinea; Ghana and ln the first week of life, female babies have their
Nigeria have prevalences of 4% and 25"/" clitoris nipped off by female traditional surgeons
respectivelyu. FGM has also been reported in several using their finger nails. This has been said to be
countries outside Africa but national prevalence data practiced by the Krobo people of Ghana in the Olden
are lacking. Data from the United Kingdom suggests days'o
that prevalence of FGM in England and Wales has
been on the increase in recent years'. More than half SUNNA
a million women and girls have undergone, or are at
risk of FGM in the European Union. The variations in This involves severing-off of the clitoral prepuce or
laws and approaches to FGM across Europe result in hood. This is the counterpart of male circumcision.
cross-border movements of girls to regions were the lnstruments used include hot stone, piece of glass,
procedure could be carried outt. razor blade, piece of broken bottle, or knife. This type
of FGM has largely replaced the more extensive
FGM differs from most forms of gender-based pharaonic circumcision in the Horn of Africa where
violence in that women are not only the victims but the latter was widely practiced'.
also involved in perpetration. A girl's female relatives
are normally responsible for arranging FGM, which, CLITORIDECTOMY
in turn, is usually performed by traditional female
This involves severing-off of the clitoris proper. The
excisers'. FGM is practiced across all educational
clitoris is held in-between the left thumb and index
backgrounds, social classes and among many
finget pulled out or hooked up with a metal hook,
religious groups (Muslims, Christians, and animists),
and then severed in a single stroke (infants and very
although no religion endorses FGM. The practice
young girls) or in three strokes: in right, left and top in
predates both Christianity and lslam'. The majority of
fashion'o'".
girls are subjected to the procedure before age 5,
although it can be as early as a few days after birth or
VULVAL EXCISION
as late as just prior to marriage in some cultures. ln
Yembn, 85% of girls experienced the practice within This involves excision of the clitoris, parts or all of the
theirfirst week of lifeu. labia minora, with or without parts of the labia
majora leaving the vulval opening. This has replaced
FGM is usually carried out by traditional practitio- pharaonic FGM in some Arab countries.
ners, often lay persons with only rudimentary
training. They could be male or femalen. However, in INFIBULAf,ION
348
rr
r
il
Female Genital Mutilation
r
rt ln this case the edges of the labia majora are fastened CLASSIFICATION OF FGM
r together after the excision procedure. lnfibulation
The extent of mutilation of the female genital was
may be mild orsevere. Mild lnfibulation
Here only the two medial surfaces'or edges of the classified into four types:
t?
{ labia majora are excised or scraped with a sharp

instrument, leaving the clitoris and labia minora Type I to Type lV by Shandall"and later by Verzin".
lr
intact. A sliver of stick is then placed in the intioitus More recently the World Health Organization
:
(WHO)''" has adopted the classification of the above
I and the two raw surfaces of the labia majora are
fastened together with thread, some kind of fibre or workers with slight modification:
thorns, or the raw surfaces are smeared with adhe-
sives such as raw egg or flour. Alternately the thighs
Type I FGM: Partial or total removal of the clitoris
andlor the prepuce (i.e. Sunna and clitoridectomy).
are tied together for some days so that the raw labia
See Fig 1.
surfaces heal by scarring and fuse together. Afterthe
sliver of stick is removed a small hole is left in the
Type ll: Partial or total removal of the clitoris and the
introitus to serve as passage for urine and menstrum.
labia minora, with or without excision of the labia
majora (excision), see Fig 2.
2. Severe Infibulation (Pharaonic circumcision)
ln this operation the clitoris, labia minora, and parts
:'
or all of the labia majora are excised and the raw
Type lll: Narrowing of the vaginal orifice with
surfaces of the majora are fastened together after
creation of a covering seal by cutting and
appositioning the labia minora andlor the labia
: putting a small stick in the introitus as in mild
majora, with or without excision of the clitoris
infibulation. The fastened surfaces are left for 30 to
(infibulation). See Fig 3.
40 days. The sewing of the labial edges and tying of
the thighs may be combined in some cases. Type lV:. Unclassified: All other harmful procedures
to the female genitalia for non-medical purposes, for
The practice of lnfibulation has been worldwide.
example, pricking, piercing, incising, scraping and
Severe infibulation was practised in Europe among
cauterization.
members of the sect Spoptsi in Russia and Romania
up to the 20th Century. Both breasts and genitalia About 90% of FGM cases involve clitoridectomy or
were cut off making themselves eunuchs for the sake excision (ie Types I and ll), and around 10% involve
; of the Kingdom of God'o
infibulation, which has the most severe negative
consequencest''u.
I
Defibulation
Deinfibulation refers to the practice of cutting open
REASONS FOR FEMALE GENITAL MUTILATION
the sealed vaginal opening in a woman who has been
infibulated, which is often necessary for improving Numerous reasons have been advanced for perpetu-
health and well-being as well as to allow intercourse ating this ritual, The reasons put forward for the
or to facilitate childbirth' procedure vary from one community to another.
While the Russian and Romanian religious sect do it
Just before the day of marriage the vaginal orifice is
to ensure perpetual virginity, other peoples practise it
opened just enough to make coitus possible. ln some
for some of the following reasons: Tribal traditional
areas a traditional surgeon may measure the size of
practices, modification of socio-sexual attitudes,
the groom's erect penis, make a mould of clay or
superstitious beliefs, religious requirements,
wooden model, and uses the size of this model to
preservation of chastity and as puritanical measures.
make the opening in the introitus. Once the opening is
lnfact, it has been used to improve fertility in some
created the model is inserted into it, and removed
countries. Although often denied, the preservation of
when they are ready for coitus. Before delivery of a 2'a't2'16.
virginity lies in the root of this custom
baby a full opening is created. Reinfibulation is done
I while nursing the child, after divorce, and the death
ofthe husband'0.
349
followed by family, parental influence, cultural and

traditional requirement. The fourth common reason
was superstitious beliefs as stated in Nigeria"'" ln
other areas, within the context of ancient cultural
beliefs it has been suggested that the operation of
female circumcision and giving away part of the
genital organs can be interpreted as offering or
sacrifice to the deity presiding over fertility'n.
However others think the main purpose for this ritual
Fig 1 FGM I Note absence of clitoral hood and prepuct is to attenuate sexual desire in girls and protect their
morals by removing the sensitive parts and constrict
the introitus''n. Hence in parts of Nigeria the cut
edges of the external genitalia are smeared with the
secretions from a snail footpad in the belief that the
snail being a slow animal would influence the
circumcised girl to "go slow" with sexual activities i
f uture'o'",
On the whole, however, the custom is often routlnely

performed as an integral part of social conformity
and in line with community identity'n
Fig 2 FGM ll Note absence of the right labium minus
COMPLICATIONS OF FGM
FGM has no known health benefits. Girls and women

who have undergone the procedure are at great risk
of suffering from its complications throughout their
lives. The adverse consequences of FGM to physical
and mental health are likely to be under-appreciated.
This is because in some places the practice is illegal
and hence victims and the "surgeons" are likely to
Fig3 FGM lll Note the cicaterised over the hide complications originating from it. Secondly in
remaining labia majora
communities where this ritual is practiced any topic
on the genitalia may be embarrassing to the women
Other reasons include: to reduce sexual passion and
hence affected victims may not even complain.
promiscuity; to produce virginal tightening of the The complications associated with FGM may be
vulva, especially when performed afterchild birth; for immediate or long-term. They also pose serious
cleanliness (among the Bantus); to promote fertility physical, sexual functioning and obstetric risks. The
(Madingo); to prevent the mother and the child from
risk of immediate and long-term complications
dying during childbirth (Massai and Swahili); for increases with the severity and extent of the
aesthetic reasons to prevent labial hypertrophy due procedure; type lll FGM has the greatest risk relative
to prolonged masturbation (former Abyssinians and totypes land ll''".
Hottentots); for legal Ie?SoIrs: one cannot inherit The procedure is painful and traumatic and is often
propefi if not circumcised''''n. performed under unsterile conditions by a traditional
practitioner who has little knowledge of female
Some . researchers in Nigeria stated that the anatomy or how to manage possible complications".
commonest reason for FGM was to prevent the future
Shockfrom pain and haemorrhage is commonas well
child's head from touching the clitoris during as infectionn'"'". Moreove( the removal of or damage
parturition", and it was believed that this practise to healthy genital tissue interferes with the natural
would prevent the child from dying. ln Ghana peer functioning of the body and may cause several
pressure was the commonest reason for FGM,
350
Female Genital M uti latian
immediate and iong-term genitourinary health Obstetric tea r#lacerations

consequences. Acute urinary retentloti iS fiaturally lnstrumentaldelivery
quite commofl in the first 2 to 3 days following such Difficult labour/dyStoeia
trauma"'". Damage to the urethra or finus cf,n result Extended maternal hospital stay
from the undeveloped state of thc genitalia (in Stillbirth ahd early neonatal death
lnfant resuscitation at delivery
children), the clandestine nature of thc oBuFatlonl'z,
and the struggling of the victim during the procedttre
Sexual fu nction i ng risks
making the extent of the operatiOn dictated in many Dyspareunia
cases by chance". Decreased sexua I satisfaction
Reduced sexual desire and arousal
ln Eastern Nigeria, female circumcision was fbund to Decreased lu brication d u ri ng sexua I i ntercou rse
be the commonest cause of acquirdd gyfiatresia Reduced frequency of orgasm or anorgasmia
resulting in haematocoipos'u 0r the tormation of
ealculi in the vulva or even the vaginal fornix"''^. Psychological risks
Vulval adhesions were also ndted by other Post-trau matic stress d isorder ( PTS D)
researchers in Nigeria'o'2l'2s. in one study, chronic Anxiety disorders
pelvic infection was found to be three tirnes more Depression
common in Type lll female circumeision compared '
with the other typesl'. Other common complications

Long-term risks
Genitaltissue damage
were implantation dermoid cysts and J<eloids". Vagi nal discharge and itching
Menstrual problems
Since FGM may involve the remova! of sexualiy Reproductive tract i nfections
sensitive structures, including the clitoral glans and Chronic genital i nfections
part of the labia minora, some women report Urinary tract infections
reduction of sexual response and diminished sexual Painfulurination
satisfaction22. lmpairment of sexual function
manifesting as dyspareunia or even apareunia is an A 2006 WHO study that analysed the obstetric risks
inevitable accompaniment of FGM"'". Urethral aSsociated with FGM among 28,000 women
coitus resulting from apareunid and misdirected attending for singleton delivery in 6 African countries
efforts at sexual intercoursehave all been associated (Burkina Faso, Ghana, Kenya, Nigeria, Senegal and
with FGM. Anorgasmia and coital bleeding are not Sudan), concluded that women living with FGM
commonly reporteds. ln northern Ghana, sexual were significantly at increased risks of adverse
dysfunction was found to be more common in FGM obstetric outcomes (caesarean section, postpartum
women compared to non-FGM women"'"' haemorrhage, extended maternal hospital stay,
infant resuscitation and perinatal mortality)
Summary of cornplications associated with FGM compared to those without FGM, and that the risk
lmmediate riske appears to be greater with more extensive forms of
Fear and anxiety the procedure'u. Other studies in the sub-region have
Pain
reported similar findings'u'". The increased risks in
Haemorrhage
these adverse obstetric outcomes and others were
Genital tissue swelling
reaffirmed in a recent systematic review and meta-
lnfections
Urination problems analyses on the subject'8.
Wound healing problems
Death Perhaps the most serious adverse effect of this ritual
is the mental and psychological agony that the victim
Obstetric risks goes through'n. For many girls and women,
Caesarean section undergoing FGM can be a traumatic experience that
Postpartu m haemorrhage may leave a lasting psychological mark and cause a
Episiotomy number of mental health problems. This is deemed
Prolonged labour the most serious complication beeause the problem
351
does not manifest outwardly like the physical 3. Medicalization of FGM (i.e. performance of
complications for any help to be offered. Right before FGM by health-care providers) is never
the procedure the poor child is in constant fear of the acceptable because this violates medical
operation itself. After the ritual she dreads sex ethics since (i) FGM is a harmful practice;
because of anticipated pain, and dreads childbitth (ii) medicallzation perpetuates FGM; and
because of the attendant complications brought by (iii) the risks of the procedure outweigh any
the FGM. However such females never complain but perceived benefit.
end up becoming frigid and withdrawn, resulting in
maritaI disharmony''"'". Recommendations for:
Deinfibulation
Besides the health risks, FGM hinders gynaecological 1. Deinfibulation is recommended for prevent-
examinations, screening and procedures including ing and treating obstetric complications in
those of family planning, due to the anatomical women livingwith type lll FGM
distortions. Regrettably however, most health-care
2. Either antepartum or intrapartum
providers remain unaware of the many negative deinfibulation is recommended to facilitate
childbirth in women livingwith type lll FGM.
health consequences and are inadequately trained to
recognize and treatthese complications". '
3. Deinfibulation is recommended for preve
ing and treating urologic complications -
CARING FOR FGM PATIENTS specif ica lly recu rrent u ri na ry tract i nfections
and urinary retention - in girls and women
Females with FGM require specialized services due livingwith type lll FGM
to the health consequences of the practice.
Obstetricians and Gynaecologists must be aware of MentalHealth
the practice, the various types of FGM, and their Cognitive behavioural therapy (CBT) should be
considered for girls and women living with FGM who
complications. Health workers including midwives in
are experiencing symptoms consistent with anxiety
communities where this is prevalent must be
specially trained to manage these females outside
disorders, depression or post-traumatic stress
pregnancy, during pregnancy, labour and delivery. disorder (PTSD).
These people must be trained to perform
Female Sexual Health
defibulation. ln areas where these cases appear Sexual counselling is recommended for preventing or
occasionally these women must be referred to treating female sexual dysfunction among women
specialists who can manage them.
livingwith FGM.
These females must be handled with sympathy,
Obstetric care
kindness, and in a non-judgmental way. They should Before pregnancy the complications of FGM should
not be forced but rather counselled and encouraged be enquired and managed, especially those
to take appropriate decisions concerning their health concerning sexual problems. De-infibulation must be
care. performed anytime on patient's request, anytime
infibulation is detected or when the patient marries,
A summary of WHO's guiding principles and after counselling and informed consent from the
recommendations for management of the health patient. De-inf ibu lation may be perf ormed
complications of FGM are given below":
antenatally, in the first stage of labour or at the time
of delivery and can usually be performed under local
Guiding principles
1. Girls and women living with FGM have anaesthesia. lt can also be performed perioperatively
' experienced a harmful practice and should after caesa rea n sectionto't'.
During pregnancy it is very essential to perform
be provided quality health care.
2. All stakeholders - at the community, vaginal examination on all patients in communities
national, regional and international level - where the ritual is common. This will enable one to
should initiate or continue acti0ns directed ascertain FGM status, since patients may deny FGM
towards primary prevention of FGM. due to shyness or embarrassment. Knowing the
352
rI
r Female Genitai tiuulation

i
, ,--.
.
,
) status and typ. of FGM enables the health worker to often prefer health-care providers to carry out the
i
tf, assess the likt:lihood of obstetric . complications. procedure if they think it might reduce the risks
rT Fears and anxiety concerning what might occur in associated with the procedure. Regardless of
* .-- labour and delivery must be carefully alldyetl'q31, whether FGfin is carried out bytraditional or mediCal
f
I
Elective deinfibulation after counselling and consent personnel, it represents a harmful and unethical
must be done early to allow full wound healing before practice, with no benefits whatsoever, and should
labour, preferably between 16 and 20. weeks n6t be performed under any circumstances''t'.
i gestation. Also the patient rfiuSt be tdid the
consequences of re-infibulation, and counselling and TrAined heaith pr,ofessionals who perform FGM are
I advice against reinfibulation offered. Should thc vidlating giris' and womefl's human rights and the
patient present late in pregnancy or during labour, fundamentai medical ethic to 'Do no harm'. Yet,
defibulation should be deferred until contractions are medical professionals continue to perform FGM and
well established. Then partial deinfibulation must be the trend afiiiears to be on the increase in some
I done just enough to allow pelvic examination. Full countries. For example, more than a third of girls in
deinfibulation should be deferred until second stapE Sr.idan and half of girls in lndonesia have been
as the fetal head distends the vulva. At this stage the subjected io the practice by trained health
stretching of the fused labia allows a good vidw of the professionals''0. ln Egypt, girls are three times more
line of fusion, reduces blood loss, and the external likely to undergo FGM at the hands of a health-care
urethral meatus tends to be displaced away from the pi'ovider than did their mothers6. Moreover,
fusion line by the fetal head'o'". r€infibulation is being performed as a routine
procedure after ehildbirth in some countries such as
!
i" Due to iricreased nligration of Africans to Europe and
I Sudan, and occdsionally ainohg immigrants in
America there is the need to set up special centres Europe and l\orth America where it is prohibited by
dedicated to the care of these women in areas where law'.
there are significant numbers of Africans who come
a from countries or communities where the ritual is Several factbrs account for the involvement of
prevalent. Such centres have been established in the medical professionals in the practice, including
United Kingdom and have been shown to be prospects of economic gain, pressure and a sense of
successful in meeting the needs of these women3o, duty to serve community requests. ln imirrigrant
Special obstetric problems to be borne in mind and communities, some medicdl personnel carry out
r
I include; increased risk of urinary tract infection, reinfibulation in the name of upholding the perceived
i
difficulty in performing vaglnal examination or culture of the patient and the right of the patient to
passing of urethral catheter, delay in second stage, choose medical procedures, regardless of the
need for anterior eplsiotonty and increased risk of patient's desi re to u ndergo the proced u re''t'.
a perineal lacerations. Therefore, appropriate
counselling must be offered to enhance patients' co- Some health care professionals, governmental and
operation'0 ". nongovernmental organizations consider
medicalization as a harm-reduction strategy that
A flow chart for the triaging and management of reduces some of the immediate risks associated with
pregnant women with FGM in areas where type lll the procedure. However, medicalization does not
FGM is notcommont'isgiven Fig4 below: guarantee hygienic condition or that the procedure
will be less severe, and there is no evidence that it
MEDICALIZATION OF FGM reduces the obstetric or other long-term
The medicalization of FGM refers to situations in complications associated with FGM. Others contend
which the procedure (including re infibulation) is that medicalization is a useful or necessary first step
practised by any category of health-care provider, towards total abandonment, but there is no evidence
whether in a public or a private clinic, at home or to support that view. Furthermore, WHO and other
elsewhere, at any point in time'in a woman's life2. agencies believe that medicalization legitimizes the
While in most cases FGM is performed by traditional practice as medically sound or beneficial for girls and
excisers, parents who subject their daughter to FGM women's health and uphold the practice as medical
353
Comprehensive Gynaecologlt in the Topics
personnel often hold power, authority, and respect in weak morals, indulging 1n teenage and premarital sex
society2'32. leading to teenage andlor unwanted pregnancies
culm.inating in illicit induced abortions and their
Medical licensing authorities and prolf(!q3lg@. attendant complications, sexually transmltted
associations have joined UN organizat€E! ,.P,:: infections including HIV/AIDS leading to loss of
condemning medicalization of FGM. ln 1994, F-@ human and national resources. They argue that what
passed a resolution at its General Assembly humanity gains from strong family ties (brought
prohibiting the performance of FGM by ob5tetrieians about by FGM) outweighs the few unfortunate cases
and gynaecologists, as well as medicalization of the of gynaecological and obstetrical problems which are
practicett. blown out of proportions due to the adaptation of
doctors of the Western world life style'o.
ELIM!NATION OF FGM
Even though traditions and culture are important
Over the past3-4 decades, local communities, aspects of any society by helping to mold the views
governments, national and international and behavioural patterns of the society, some
organizations have carried out a range of traditions and cultural beliefs and practices are
interventions to promote the abandonment of FGM harm:ful and certainly FGM is one of such practices
with varied success''t''tu. Overall, the prevalence of and hence must be abolished. lt is said that old
FGM has declined, but the rate of decline varies customs die hard and there is controversy regarding
widely. Despite some successes, the overall rate of the continuation of the practice. Attitudes towards
decline has been slow and inadequate, and millions FGM vary from country to country. For example,
of girls remain exposed to the risk of FGM in the atthough majority of women in most countries in
future''t''tu. Bringing an end to FGM requires Africa and the Middle East want FGM to end, about
com m u n ity-led mu ltisectoral i nterventions with long- 5Oo/" of females in some other countries such as The
term commitment'. Gambia, Mali, Guinea, Egypt, Somalia and Sierra
Leone want the practice to continue because of their
Some of the popular approaches and methods
beliefs in the ritual practice'.
towards the abandonment of FGM that haye been
evaluated include; health risk approaches, ln some of these communities, interventions have
conversion of excisers, training of health been developed to replace the rite of passage with
professionals as change agents, alternative rituals, FGM, by an alternative rite without FGM, Such
community-led approaches, public statements, and alternative rites programmes are expected to fulfill
legal measures'''o'tu. The main advantages and the cultural tradition of a coming of age ritual, so that
challenges of these popular approaches are girls can be socially accepted without having to go
summarized in Table 1 below. Many interventions through FGM. These interventions are believed to
combine two or more of these approaches and show positive attitude and respect for cultural
methods. traditions and thereby prevent defensive reactions
against efforts to abandon FGM and to facilitate
DISCUSSIONS AN D CONTROVERSI ES
abandonment of FGM by maintaining the ritual
Certain old customs and traditions are held on by
framework. ln some cases, excising rituals are
people and communities in order to survive culturally replaced with a version without FGM (e.g., in Sierra
Leone and Kenya), in others, previously used rituals
amidst the pressures of Western modernization,
have been revitalised, ora newform of education and
values, and life-style. FGM is one such traditional
"marking" has been introducedt'. Other harmless
ritual. Advocates for this practice claim that the
practice has been the binding-force for the nuclear traditions include the 'Dipo' among the Krobo or
'Bragoro' among the Akans of Ghana, which will
family, extended family, the lineage, the clan and
maintain the binding force for the nuclear family,
community solidarity. What happens when this ritual
is banned? Family break-ups leading to child
extended family, the lineage, the clan and
community solidarity.
migratlon with attendant child labour and drug
addition. Such "librated" girls without FGM have
354
=
q
I
I' Female Gen ita I M uti lation
I
Furthermore, the traditional surgeons whose only
i
ir source of irrcome is through FGM must be While it is wrong for medical personnel to condone
r remunerated and redeployed. However, singling out FGM, culture and tradition die hard. lt will take
excisers in such precarious situatioms ,fur financial several years of education, legislation, advocacy and
t.
support and training could contribute !o internal other approaches to curb this practice. ln the interim
conflicts and can boost the role of the excise*- in the what happens to the adherents?
community or contribute to the recruitment of new
: Local and international community should not relent
excisersto.
or give up in fighting this ritual. "... Human behaviors
Another area of controversy is the stand on and cultu ral values, however senseless or destructive
medicalization since there are still adherents to this they may appear from the personal and cultural
practice. ls it not prudent for these adherents to standpoint of others, have meaning and fulfill a
access health care providers for the procedure to function for those who practice them. However,
minimize complications? What should a health culture is not static but is in constant flux, adapting
professional do if after delivery, a defibulated mother and reforming. People will change their behavior
insists that she wants to be reinfibulated by the when they understand the hazards and indignity of
Health professional, inspite of in-depth counselling, harmful practices and when they realize that it is
education, and advice? possible to give up harmful practices without giving
up meaningful aspects of their culture".
"lt is the mission of the physician to safeguard the (A Joint WHO/UNICEF/UNFPA Statement, 1996).
health of the people" (World Medical Association Therefore, continuous education, advocacy,
Declaration of Helsinki, 7964). Trained health enforcement of legislation and other effective
professionals must remember that condoning any approaches willfinally curb this practice.
acts of FGM constitutes a violation of the
fundamental medical ethic to 'Do no harm'. As the
RCOG puts it: "Women should be informed that re-
infibulation will not be undertaken under any
circu msta nce"30.
).
355
4qt
,l
CeFnprehdnsivg eyrtaec1lgfly in the Topics
'1
Eig tt: Care of pr€gnant yt omen with F$frl in areas wfiere [ype ll! and IV are UnGqfnmon"
Its6
I
i
I Female Gen ital Muti lation

I
7
I
I T0ble 1 : A strmmary of the main adyentaget and ghellengeq of popular 4pprqaches towards the abandonment of FGMru
7
I Approach 001il,i"1!i;115,fl[F nts,
Bisks and disadVantages
Measures to overcome risks pnd disad-
yantages
I
i) Stimulate resistan€E
; to FGM prnppg try i) Medicalization
i peopte-refleclip@e€. ii) Change type of FGM
I
don rnent 6911918.U5 6Ed-
iii) Diqbelief i) Ensure health information is locplly
2
F ers-follow poljtigInr adapted commpnicated nonjudg-
I
Health risk info laws and pslieier-health iv) lnadequate quallty of mentally by a reliable source and
I prqvider$-share information combined with cafe for compli€a-
) informatien-denaunce v) Defence reActions tions and experie;lce exchange.
medicalizatien
I vi) Social nqrm overrules
I
ii) lmprove health care fsr health risks
l/ complicationq
I
I i) Does not leduce demand
for FGM
r
i) Reduce availability of
ii) Continue secretly or by i) Ensure thai work with excisers is
apprentices only an aspeet of a wider approach
elercises
Conversion of iii) Others take over task adapted tp their roles in the partic-
exercises
ii) Easy success indiEFtors
ular community.
I iv) Ex-excises unreliable
i iii) Media covgrpge prqyid- ii)
sources against FGM Do not expe€t it to reduce the
ing visibility to isque
demand for FGM
vJ Alternative income may
not motivate abandon-
t
ment
i) lrnploved quelity sf care i) Resistan€e to work

i) Comprehensive training for
prevention and management into
ii) Beftain ts Ferforn'! F.M against FGM
standard curricula
a Training of health iii) Provide informatiqn qnd ii) lnadequate eqntent of
I
professionals counselling training ii) Training target potential accep-
I
tance of the practice.
iv) Build local eyidence en iii) Lack of time and resourc-
iii) Ensure an enabling environment
health consequenqes es to implement
for implementation of knowledge.
I
i
/ i) Facilitatecpmmunity i) Use only where fit into local cql-
ownership and support
i) Only viable in comtrtu- ture
a nities in which FGM is a
I
as it maintains key cultur-
part of a rite of passage
ii) lnclude the whole family and
al practice community
ii) lncreased knpwledge
ii) Limited integration of
Alternative rites iii) Consider alternative measures if
the whole cammunity
I
i and emp9werment of the actual cutting is done at other
girls iii) lnsfficient adaptation times
into the specific socio-
iii) Publicity about change cultural situation of each
iv) Ensure community ownership for
I
I through cornmunity sustainability
community
a celebrations
i.- v
i i) Community own prob-
I lem and solution i) The community might
I
ii) Broader suppot less

decide to ehange, rather i) Ensure community ownership and
than abandon, the prac- adaptation
I resistance
: tice ii) Ensure long-term supportto
Community-led iii) Addressing underlying
causes
ii) Failing to ensure com- secure viabJe and broad change,
l' munity participation and
I rea<hing reluctant abandoners
iv) Reduce/remove FGM as resourcing to traditional and neighbouring cornmunities
a social norm, facilitat!pg 'lecturing'
and stirnulating change
i) Ensure community-wide suppart
r iD Having legislqtion and policies in

i) Createasenseofsocial Public statements by place provides support to people
change among a group subgroups only lack of ready to change
Public statements ii) Facilitate aRd stimulate community ownership
i- iii) Further resgarch is needed to
abandonment for group "Fake"opinions and for inv€stigate the effects of public
members lack of authority statements from single groups,
i eEpecially religious leaders (e.9.
fatwas)
i) Create an enabling
i) Practice can go under- Ensure commqnity support for the
ground law
: Legal measures
ii)
framework
Disrourage FGM
ii) Fearofseeking health Ensure regulations that quarant€e
care for complications care for complications.
357
Comprehen,, z Gynaecology in the Topics
REFERENCES
1. World Health Organization (WHU. Female Danso KA, Kwawukume EY Tagbor H, Asante
genital mutilation: Fact sheet 2016, available at RKO (editors). Kumasi; University Press KNUSI
h t tp : //www. w ho. int / m e d i ac en t re/fac ts heets /fs 2 2014; pp 373-404.
4l/9L/ accessed on J a n ua ry 27, 20 1 7.
2. Office of the United Nations High Commissioner 10. Knudsen C O. Female Circumcision in
for Human Rights (OHCHR), Joint United Nations developing Ghana ln: The Falling Dawadawa
Programme on AIDS (UNAIDS), United Natrons Tree. lntervention Press, Denmark. 1994.
Development Programme (UNDP), United
Nations Economic Commission for Africa 11. Odoi AT. Female Circumcision in Ghana: Extent of
( lJ N EC A), U n i ted Na trons Ed u c ati on a l, Sc i e nti f i c the problem; effects on Sexual function. '? ln:
and Cultural Organization UNESCil, United book of Case Records and Commentaries foi -.,-
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Nations High Commissioner for Refugees Obstetrics and Gynaecology. 1995; pp 434-463.
(IJNHCR), United Nations Children's Fund 12. Shandall AA. Circumcision and infibulation of
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13. Verzin JA. Segue/ae of Female Circumcision.
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WHO. Etiminating female genital mutilation:
14. WHO. Female genital mutilation. Report of a
an interagency statement. Geneva: WHO, 2008.
WHO technical working group, Geneva,17-19
3. UNICEF. UNICEF Data: Monitoring the situation July 1996. Geneva: WHO, 1996.
15. Yoder PS, Wang S, Johansen E. Estimates of
of children and women-Female genital cutting
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ef. org/t opic /chil d- countries and Yemen. Stud Fam Plann. 2413;
ht tp s : //dat a. uni c
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16. Odunjinrin OMT Akitoye CO, Oyediram MA. A
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4. Aziz FA.Gynecologic and Obstetric
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Complications of Female Circumcision. lnt. J.
17. Olamijulo SK, Jouner KT, Oyedeii GA. Female
Gy necolObstet 1 980 ; 1 7 : 560- 563.
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5. Asaad MB. Female Circumcision in Egypt:
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18. Odoi AT, Brody SE Elkins TE. Female Genital
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5. UNICEF. Female genital mutilationlcutting: A
19. Taba AH. Female Circumcision. ln Traditional
global concern. New York: U N ICEE 20 1 6.
practices affecting the health of women and
7. Amasanti ML, lmcha M, Momoh C.
children. WHOIEMRO Technical publication No.
Compassionate and Proactive lnterventions by
2. Alexandria: WHO, 1979: pp 43-52.
Health Workers in the United Kingdom: A Better
20. Akpuaka FC. Vulvaladhesions following female
Approach to Prevent and Respond to Female
circumcision in Nigeria. Postgrad Doct Afr.
Genital Mutilation? PLoS Medicine. 1991;13:98-9.
2016;13(3):e1001982. 21. Okeke T, Anyaehie U, EzenYeaku C. An
8. WHO. Understanding and addressing violence
Overview of Female Genital Mutilation in
against woffiefi : Female genital mutilation.
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Geneva: WHO, 2012
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9. )doi-Agyarko K, Odoi AT. Female genital
22. WHO. WHO guidelines on the management of
m uti I ation i n : Com prehensive Reproductive
health complications from female genital
Health and Family Planning in the Tropics.
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co m p I i cati o n s afte r fe m a I e c i rc umc ision, M J. Societyof Sudan, Khartoum, 74- 18 Feb. 1977.
r 1992;69 (9): 471-82.
EA
30. RCOG. Female genital mutilation and its
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r Nigeria. lnt. J. GynelcolObstet. 1992; (37): 105- London: RCOG,2015.
109. 31. WHO. Management of pregnancy, childbirth and
t 25. WHO study group on female genital mutilation
and obstetric outcome. Female genital mutilation
the postpartum period in the presence of female
genital mutilation. Report of a WHO Technical
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prospective study in six African countries. Lancet.
Consultation, Geneva, 15-17 October 1997.
Geneva: WHO,2001.
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i 2006; 367 (9 525) : 1 835-4 1.

26. Jones H, Diop N, Askew l, Kabore l. Female
UNAIDS, UNDE UNFPA, UNHCR, UNICEF,
UNIFEM), WHO, FIGO, ICN, IOM, MWIA, WCPT
Genital cutting practices in Burkina Faso and WMA. Global strategy to stop health care
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t Mali and their negative health out-come. Stud providers from performing female genital
r Fam Plann. 1999;30(il:219-23O. I ation. Geneva : W HO, 20 1 0.
m uti
t 27. 35. Larsen U, Okonofua FE. Female 33. FIGO. FIGO General Assembly, Montreal, Canada
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circumcision and obstetric complications. lnt. J 1994. London: FIGO, 1994.
Gynecol Obst. 2002;7 7 (3) :255-265. 34. Johansen REB, Diop NJ, Laverack G, Leye E.
r 28. Berg RC, Odgaard-Jensen J, Fretheim A,
( What Works and What Does Not; A discussion of
Underland V, y/st G. An updated systematrc popular approaches for the abandonment of
r review and meta-analysis of the obstetric female genital mutilation. Obstet Gynecol lnt.
a consequences of female genital 2O13;2013: 348248
r! mutilation/cutting. Obstet Gynecol lnt. 35. Berg R, Denison E. Effectiveness of interventions
f 2014;2014:542859. designed to prevent female genital
rI 29. Baasher TA. Psychological aspects of female mutilationlcutting (FGMIC): a systematic review
I circumcision. Paper presented to the Fifth of the best available evidence. Stud Fam Plann.
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359
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Camprehensi Gynaecology in the Topics
360
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CHAPTES2
r
Diagnostic PrOcedures I n
Gynaecology
PH Daru, ET Agida and EY Kwawukume
lntroduction 500,000 new cases yearly and 274,00 deaths

Diagnostic procedures are very important in attributable to it, therefore, making it the second
gynaecology and are premeditated on good clinical most common cause of cancer death among
history, examination and targeted investigations. wornen'. Cervical cancer also accounts for about
lndeed, some are part and parcel of the investigations 72% of all cancers among women, with 80% of
ofthe patient. deaths from cervical cancer occurring in developing
countries'.
There are a myriad r:i diagnostic procedures that are
now available to the modern Gynaecologist. These The incidence of cervical cancer has reduced
procedures appear to be evolving daily. Most of the globally by more than 50% in the past 30 years,
procedures are diagnostic. Others are both diagnostic largely due to cervical cancer screening using
and therapeutic. Some of these gynaecological cervical cytology'. Thus, confirming that cervical
procedures, such as Computerized Tomography scan cancer is preventable. However, most women in the
(CT), Magnetic Re'sonance lmaging (MRl), and developing countries do not have access to effective
Positron Emission Tomographic scan (PET) are screening programs'.
beyond the scope of this textbook. However, in this
: chapter, the following common diagnostic The Pap smear has been the most successful
procedures will be discussed. screening technique in history. Dr. George Nicholas
Papanicolaou discovered the test and thus the
L Papanicolaou smear and other screening screening method was named after him. His work on
procedures for cervical cancer Pap smear began in 1914 while he was in Anatomy
ll. Colposcopy department at Cornell University Medical School in
lll.Examination underanaesthesia (EUA),
New York. ln 1928, Dr. Papanicolaou first presented
Biopsy and D & C, and Fractional curettage
his findings that uterine cancer could be diagnosed
lV. Hysterosalpingography (HSG)
V. Ultrasonography by means of vaginal smears'. And since then pap
Vl. Sonohysterography smear has become the most widely used cancer
screening method in the world. The Pap test is
l. PAPANICOLAOU SMEAR and other screening indicated for the screening of premalignant and
procedures for cervical cancer malignant lesions of the cervix.
l Cervical cancer is the second most common cancer
among women worldwide with approximately Since the introduction of cytology-based cervical
screening using pap smear in the mid-20'n century,
351
pap srnear and other cytological techniques such as

liquid based cytology in the prevention of'cer.vicdl
cancer, there have been overwhalri6,g ahd
convincing epidemiologic data to infer the'irn@ct of
successfully implemented cytology screerfing in
reducingcervicalcancerrates'. ,' '-'r ''
It is currently estimated that systematic screening
can reduce death rates from cervical cancer by 7O"/"
.
or more.5'6 Studies have also suggested that even if
a woman were to be screened for cervical cancer'only
once in her lifetime between the ages of 30 and 40
years, her risk of cancer would be reduced by 25-
367"'.
The Papanicolaou test utilizes the Papanicolaou

Fig. 1: Ayre and Aylesbury spatula
stain, which contains multiple :dyes to stain
differently various components of the cell: ln
preparation for Pap smear, the woman should be
properly counselled for the procedure, not be
menstruating, also avoid intercourse, douching, use
of tampons or medicinal vaginal cream or
contraceptive cream for 24-48 hours prior to the
cervical screening. Also pre-existing cervicitis should
be treated.
Procedure for Pap smear

ln taking the sample, the woman should be in dorsal
lithotomy position with her coccyx at the edge of the
examination table to provide adequate exposure of
the cervix once the speculum is inserted. A bivalve
speculum is inserted into the vagina to expose the
cervix. Specimen is obtained by using a cervical
Fig. 2: Cytobrush (different heads)
spatula (Ayres'spatula) applied at the cervix and then
turned in a single direction of 360 degrees to achieve
Source: Leonardo da Vinci Eurocytology
an adequate sample for cytology''*. The Cytobrush
may also be used and it should be rotated five times
Complications of Pap smear are rare but may include
to ensure adequate sample collection. For
minor bleeding and infection.
conventional cytology, the spatula or Cytobrush i:
smeared on a plane glass slide and then sprayed with The traditional Pap test has survived unchanged for
fixative or placed in 90% alcohol solution. For liquid over 50 years, however during the last 10 years,
based cytology, the spatula or brush is placed side technological advances have come to the forefront.
down into the liquid cytology vial. The speculum is One of these advances has been the liquid based
removed and the woman is helped out of the cytology (LBC) where instead of spreading the
examination coucht''. exfoliated cells on to a slide and fixing it, the exfoliate
cells are stirred immediately into a pot containing
preservative and the cells are then aspirated into a
filter and similarly stained on a glass slideo.
t
The advantage of the LBC over the traditional Pap
362
T !:
I D i agnostic Proced u res I n Gynaecology
r smear is that the slide has a more,homogenous sensitivity, but lower specificity to cervical cytology
spread of the -ells without clumping and obscuring in identifying precancerous lesionse''., this has been
I by white cells. Also the liquid residue can be used for demonstrated in several studies where sensitivity of
: further testing (such as Human papillOrna virus cytology was shown to be between 47 and 62%
testi n g) w ithout req u i ri n g a nothe r cl i n icafiBecirnen. while that of VIA was 45-79%. Though cytology
,,, -.,.
provides higher specificity than VIA'''0.
:
It is claimed that LBC is .ri1di.6'iffi'*ftive than
conventional cytology as shown in a UK pilot study Visual inspection has significant advantage over pap
involving 100,000 women, where reduced it smear especially in low resource settings particularly
inadequate slides by 80% thereby, rbQuirtng,'fewer in terms of screening coverage, follow up and overall
women to
re-attend and increasing laboratory program quality. lt also requires fewer specialized
output8lthough this has been refuted in recent personnel and less infrastructure, training and
systematic review'. ','1, equipment especially in mi-rie remote health care
settings. Results can also be shared among
Chaltenges of cytology screening ''' ' .' practitioners and also with patients immediately.
'
Effective screening programs require high coverage of
This ensures follow up care on the spot and helps
women at risk, quality screening test, and effective
reduce miss-out on treatment.
follow up and treatmentu. All these are often a However like cytology VIA has significant inter, and
challenge to achieve with cytology based programs
i ntra-observer errors.
because pap tests require a doctor or a nurse to
collect a cervical sample, cytotechnician to process Human papilloma virus (HPV) DNA testing
and irrierpret the sample and a pathologist to confirm This is another important cervical cancer screening
positive results. Cytology also requires systems for test, as almost 99.7% of all cervical cancers are
active recruitment of women, monitoring the quality HPV-DNA positive. The HPV-DNA test detects the
of test results and ensuring that all women with presence of cancer causing HPV types in the cervical
a bnorma I resu lts receive a ppropriate treatmentu. or vaginal cells. Though most HPV infections clear
spontaneously, there are however instances where
Limitations of cytology screening these HPVs are found in women 30 years and above
It is subjective and dependent on individual and this indicates the persistence of these viruses in
interpretation. Also due to observed low sensitivity of
their systems and thus considered at high risk of
cytology frequent re-screening every year or more is
l
cu rrent or futu re cervical ca ncer'.
key in order to achieve effectiveness. This further
increases the cost and challenges for developing HPV-DNA testing is often recommended for use
:
countries. There is also the issue of multiple clinic among women aged 30 years and above and also
; visits before final results are obtained. Again in low those tested positive are further evaluated for
resource settings, the time and cost involved with prrcancerolls lesions or cancer and treated as sucht.
multiple visits combined with low levels of awareness ln carrying out HPV testing, cervical or vaginal
of the benefits of screening are also limitations. samples are collected by a trained provider or the
patient herself and then stored in a preservative and
Visual inspection with AceticAcid (VlA) transported to the laboratory for analysis by a trained
This is an important method of cervical screening that perS,;i'101e.
involves inspection of the cervix using acetic acid and
or Lugol's iodine in order to highlight precancerous The HPV testing has been found to be the most
lesions so they can be viewed with the naked eye. sensitive of all screening tests with a sensitivity of
.Such procedures eliminate the need for laboratories between 66-95% in identifying women with
and transport of specimens, require very litile abnormal precancerous lesions'. Unlike Pap smear
equipment and provide women with immediate test and VlA, HPV-DNA results are processed by a
results. Not only doctors, but also nurses or machine and so not susceptible to differences in
I professional midwives can effectivety perform the human interpretation. Large studies have found that
procedure. Visual inspection of the cervix has similar HPV testing is more effective than either Pap smear
353
----._1
or VIA in reducing women's long term risk of cervical is better than cytology in some settings'o. lts main
cancer and overall mortality'.. disadvantage is its high cost, hence may not be easily
r,, , accessible, and affordable in the West African sub-
The challenge with HPV-DNA testing despib its region
effectiveness is that it is very expensive, u6-6"|i@te
the utilization in sub-Saharan Africa is low. Controversies
1. Cervical screening is not without controversies.
Cervicography Some of which are related to when to screen. The
This is a screening method that involves examination recommended age for the initiation of cervical
of the magnified photographic documentation of the screening has undergone significant revision.
acetic acid impregnated cervix. This test detects Formally Pap smear was recommended to begin at
high-grade lesions even though the sensitivity is age 18 years or at the onset of sexual activity, these
lower than cytology and VlA. Specificity is however guidelines were later revised in 2006 to recommend
comparable to that of cytology''n. initiation 3 years after the onset of sexual activity or
at age 21 years, whichever comes first. However in
The main disadvantage with cervicography is that 2009, the recommendation was to commence
because of the equipment involved, it is unlikely to be screening at age 27 years regardless of sexual
used as a primary screening method especially in history. This recommendation was later confirmed
developing countries. again in 2016'.and is therefore the current
recommended period to screen. Despite this, in our
Polar probe
environment where sexual debut is early, as well as
This is another method of cervical cancer screening.
It is a real time electronic device for the detection of
multiple sexual partners a challenge, every
opportunity available to screen should be utilized.
cervical neoplasia. The probe is applied directly to
the cervix with instant recognition of normal and 2.The other controversies are on when to rescreen a
abnormaltissue.
woman who has a normal SrredI: this ranges from
yearly to 2-3 years depending on her age''''o and
Advantage of polar probe is that it may be used in
when to stop screening (60-65 years)''o'u
primary screening or as an adjunct to cytology. lts
sensitivity is similar to that of cytology and specificity
REFERENCES
1. Cervical cancer screening in developingcountries. Silas, O.1., Adesina, O.A., Adewole, l.F. Q01il.
Paper of a WHO Consultation. WHO Geneva Cervical Epithelial Changes ln A Tertiary Hospital
2002. ln Northern Nigeria. Tropical Journal of
2. Niccole WK, Christine l. Pap smear. Web MD LLC )bstetricsand Gynaecology. 30 (1) 109-114
2016; I 6. Quinn M, Babb E Jones J, Allen E. Effect of
3. Dhurba G. Papanicolaou (PAP) Staining: screening on incidence of and mortality from
lntroduction, Principle, Procedure and cancer of cervix in England: evaluation based on
lnterpretation 2016; p. 1-2. routinely collected statistlcs. BMJ 1999; 318
4. IARC. IARC Handbook of cancer prevention. Q 188| :904-908.
Cervical cancer screening, vol 10 lyon France : /. Peto J, Gilham C, Fletcher.O, Mathews EF. The
lnternational Agency for Research in Cancer Press cervical cancer epidemic that screening has
2005. prevented in the UK. Lancet 2004; 364 (9430) :
5. Daru, PH., Pam ,1.C., Musa, J., Daniyan, M.G.,
364
Diagnostic Proced ures I n Gynaecology
249-256. studies; First report to the department of Health

8. Davey E, Barralt A, lrving L, Chan SF,Macaskid f, on evaluation of LBC. Survey: lnstitue of cancer
Mannes f;, et al. Effect OF Stu.g.=€slgn ana Research 2003.
qua t ity on u nsati sfactory r9t9.i:._rc logy 10. Belinson J et al. Prevalence of cervical cancer
I ctassifications and accuracy rn f@,.,#ased and feasibility of screening in rural China: a Pilot
versus conventionat cerviCai:. y; a study for the Shanxy province cervical cancer
systematic review. Lancet 2A06;''3€17'$505) : screening study. lnternational Journal of
122-132. gynaecotogical cancer 1999; 9(5), 411-417.
9. Moss SM, Gray A, Legood R,"''H€irbtoc'k E.
Evaluation of HPVILBC Cervical Screming pilot
il. coLPoscoPY 1925 asa screening tool for cervical cancer'.
Colposcopy can be used both as a screening method lndication for colposcopy include; Abnormal cervical
and also for confirmation of an abnormal Pap smear. cytology smear or HPV positive testing, clinically
It involves examination of the cervix and its related abnormal or suspicious-looking cervix, unexplained
parts such as the yagina, vulva and perianal area. or post-coital bleeding, vulvar or
intermenstrual
Colposcopy is done with the aid of a colposcope, vaginal neoplasia, history of in-utero
which is a magnifying apparatus with good diethylstilbestrol (DES) exposure, condyloma
illumination. The colposcope also views alterations in acuminata, or in cases of rape''t.
)
the underlying stroma, which allows the
identification of early vascular changes in pre- Colposcopic evaluation of the cervix should be a
; cancerous and cancerous lesions'. simple procedure. However, it is associated with
high levels of patient anxiety, which can have
) Colposcopy is the primary technique for the consequences such as pain and discomfort with the
i
evaluation of abnormal cervical cytology smear. procedure and failure to return for follow up.
D Literally translated, colposcopy (colpor vagina; However, providing patients with information
L
SCope: to look) means to look into the vagina. Hans increases knowledge levels and red uces
I
Hinselman of Germany first described colposcopy in psychosexua I dysf u nctiona.

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Fig 3.: Colposcopy

I
examination
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Source: Healthtalk.org
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36s
Comprehens. Gynaecology in the Topics
The evaluation must be performed thoroughly and extends into the cervical canal, the use of an
accurately. Accomplishing this for every patient is endocervica I specu lu m ca n a id in
most reliably done if a systematic repeatable routine visualization. lf the entire TZ cannot be
is developed and followed for each patienL Below is observed, or if the full extent of any lesion
one such protocol5. cannot be visualized, the evaluation must be
considered u nsatisfactory.
. Explain to the patient the indication for and
natu re of the procedure. ldentify and document with drawings and
descripiion the presence of any acetowhite
o Position the patient as comfortably as lesions and their internal vascular patterns.
possible in the lithotomy position.
Use of the green filter at this point can
improve the ability to identify lesion margins
. Carefully insert a bivalve speculum of the
and vascular patterns. Many expert
appropriate size. For patient's comfort, a
Colposcopists also place Lugol,s solution
water-based lubricant thinly applied to the
(dilute iodine) on the cervix after initial
speculum blades can be of benefit. This
examination and before any biopsies - "e
substance should not distort the subsequent
evaluation in any way. Care should be taken
obtained. This is a rather nonspei
staining process. lt can be useful to provide
to avoid any trauma to the cervix on insertion
additional information regarding the extent
or opening of the speculum. Normal
of abnormal epithelial changes.
columnar epithelium and dysplastic
epithelium can be very fragile, and even Biopsy samples should be obtained from all
minor trauma from speculum placement can
abnormal lesions. As noted, the visual
cause enough oozing of blood to obscure
appearance of lesions is a poor predictor of
findings.
degree of dysplastic change. Histologic
. analysis of all lesions is necessary to
lnspect the vagina and cervix visually with
optimize sensitivity of the examination and
the naked eye. Genily remove any excess
minimize the risk of missing a significant
mucus or discharge with a large cotton_
abnormality. With experience, the examiner
tipped applicator moistened with saline.
may become comfortable in determiningif 2
Document any clinical findings on this gross
locations are identical, and therefore not
inspection.
have to biopsy each location. Biopsy
. Liberally apply 3-5% acetic acid with a large
samples can typically be obtained without
cotton swab saturated with the solution or the need for anesthetic, but its use is not
precluded. Biopsy instruments should be of
using an applicator. This must be in place for
at least 60 seconds prior to inspecting for a 2-bladed type (eg, Tischler, Burke,
Kevorkian) and kept sharp and in good
changes. lf the evaluation takes more than 3-
5 minutes, acetic acid should be reapplied working condition. Specimens should be
removed from the instrument and placed in
because the cellular effects,,it,creates are
an appropriate fixative in a labeled container
transient in nature.
and submitted for histologic evaluation.
. Position the colposcope a,nd,focus onr the
Cytological sampling of the endocervix with
cervix with the desired ,rmagnification, (7X-
15X), starting with the lower'magnification;
a Cytobrush, or, alternatively, endocervical
curettage may be used to evaluate the
. lnspect carefully to ensu.re that the entire patient for endocervical pathology. Other
transformation zone IZ) can,bq observed indications for sampling the endocervix
(i.e., that the squamocolumnar,junction is include Pap smear with atypical glandular
visible in its entire circurn,ference), lf the TZ cells, SCJ not visualized or when an
endometrial pathology is suspected. Studies
366
{
I
D ia gnostic Proced u res I n Gy n aecol ogy
I indicate that cytological :endocervical weeks.

; sampling with a Cytobrush has increased
sensitivity but decreased specificity o Results should be reviewed to confirm that
compared with endocervical cu.ieffiage. With they correspond to the cytological reports.
either technique, the sample is subrnitted in The colposcopic examination should be
fixative. Pregnancy,i,s'd relative considered inadequate for any of the
contraindication for such endocervical following reasons
sampling. o The biopsy histology is less severe
. (typically by 2 grades) than that
A hemostatic agent can be a.pplied to each predicted from the cytological
biopsy site immediately after sample sample.
collection. Monsel paste (dehydrated ferric o The endocervical margin of any
subsulfate) and silver nitrate are effective abnormal area cannot be visualized
measures. lf multiple biopsies are indicated, completely.
initial samples should be taken from the o The squamocolumnar junction
inferior aspect of the cervix to prevent cannot be visualized completely.
bleeding or chemical application from o There is evidence of endocervical
running down and obscuring adequate disease not visualized at the time of
visualization. colposcopy.
o Histologic or cytological suggestion
Special precautions should be taken to of invasive disease not confirmed by
optimize hemostasis when colposcopy is biopsy.
being performed on a prregnant woman. As is o Histologic or cytological suggestion
true for non-gravid women, biopsy of the of adenocarcinoma or
cervix should be performed for any lesion adenocarcinoma in situ.
suspected of being invasive.,Bleeding from
even small biopsy sites can be brisk and Abnormal col poscopic findings include''u
persistent, so special preparation for this
likelihood should be undertaken. While
. Leukoplakia or hyperkeratosis-which is an
positioning the biopsy forceps to obtain a area of white epithelium prior to application
sample, a cotton swab saturated with of acetic acid may indicate an underlying
Monsel paste should be readied immediately neoplasia
adjacent to the instrument. As soon as the
. Acetowhiteepithelium
biopsy is taken and before rernoval of the
. Mosaicism or punctuation reflecting
abnormal vascular patterns of the surface
specimen, the swab should be firmly applied
capillaries.
to the wound bed. A large second swab . Atypical vessels with bizarre capillaries with
should be ready to put in place after removal
so called corkscrew, comma-shaped or
of the first. Should this not control bleeding,
spaghetti-like configurations suggesting
equipment for placement of a small suture
early stromal invasion.
should be immediately available. lf proper
precautions are taken, bleeding is seldom a
The colposcope can also be helpful in evaluating
significant problem, even in the case of lesions of the vagina or vulva. The vaginal epithelium
pregnant patients.
is a non-keratinizing squamous epithelium similar to
that of the ectocervix. Acetowhite changes and
The speculum is removed, and patient
vascular patterns can be observed that are similar to
instructions are provided. Spotting and a
those found on the cervical portio. Because vaginal
light discharge can be anticipated. Coitus
lesions do not originate in metaplastic tissue,
should be avoided for 7-LO days, and a
f
I
vascular patterns previously described are not
follow-up examination and discussion of
diagnostically reliable. When premalignant changes
pathologic findings should take place in 7-2
are suspected, all acetowhite lesions should be
367
Comprehens t;vnaecology in the Topics
biopsied. The vagina is more sensitive to pain than the procedure today. Questions concerning who
the cervix, so pre-biopsy injection of local anesthesia should perform the examination and what training
should be considered. requirements must be met before instituting the
procedure on patients. Because of the prevalence of
The vulva is also a potential site for dev€@ etr HPV disease and the frequency of abnormal findings
pre-invasive disease. These tissues a:lm...!ffi+ fuer on Papaniclaou tests, this becomes both an
acetowh ite cha n ges, but, beca use of thethtr*fieg5 cf economic quality issues. Some have recommended
the epithelium and its keratin surface, aeetie acid as many as 200 supervised procedures to gain
should be applied for a greater length of time and in a competence followed by regular performance of at
higher concentration (e.9., 5%) to be effective in least 25 procedures ayear to maintain competence.
bringing about this change. Altered vascular pattems The learning curve undoubtedly is practitioner-
are uncommon on the vulva; but, when they are dependent, and, currently, no adequate studies have
observed, biopsies should be performed liberalty. identified minimum criteria for certification. All
Again, because of the sensitivity of these tissues, all practitioners performing this procedure should put
biopsies should be obtained under local anesthetic. mechanisms in place to ensure their own
competence and safetyo.
Another use of the colposcope is in the evaluation of
victims of sexual assault. This has gained popularity, 2. Various options are available for treatment of CIN
especially in the evaluation of children suspected of ranging from conservative (careful follow up),
being assaulted. At low magnification, the ablative (cryotherapy, electrocoagulation, cold
colposcope can assist in identifying tissue trauma coagulation and laser ablation), excisional ILoop
that might be too subtle to be detected by the naked Electrosurgical Excision Procedure (LEEP), cold knife
eye. Careful, thorough, and gentle examination, conization, laser cone excisionl to radical
especially of hymenal tissues, can usually be (hysterectomy).
accomplished with minimal discomfort. Attached
ca meras for record i ng find ings can be helpfu I f rom a n The primary concern in treating CIN by ablative or
evidentiary perspective. excisional techniques is whether the treatment will
be adequate to eradicate any CIN that has extended
Complications from colposcopic procedures are down into the crypts underlying the neoplastic
exceedingly rare. Occasionally, bothersome bleeding epithelium. The possible depth of crypt involvement
can occur following biopsy. This tends to be increases with the severity of the ClN. A treatment
problematic only with prgcedures performed during that is effective to a depth of 7 mm is necessary to
pregnancy or with large excisional procedures. destroy CIN 3. The total linear extent of the lesion is
lnfection of biopsy sites is also exceedingly rare, a lso a factor to be consid ered .
although it can occurfollowing laser ablation or LEEP

procedures. The most worrisome complication is Loop Electrosurgical Excision Frocedu re (LEEP)
inadequate or inaccurate evaluation leading to the LEEP is a form of excisional method, and is used both
missed diagnosis of invasive cancer. This obviously as a diagnostic, as well as a therapeutic tool. The
can lead to treatment delays and poorer outcomes. indications for LEEP excision are as follows:
Another complication is the overestimation of lesion
. Unsatisfactory colposcopy (the
severity by inexperienced practitioners. This can put transformation zone is not fully visualized),
the patient on a treatment course that may not be especially if a high-grade lesion is
necessary and has the potential for adverse sequelae. suspected,

Many of these sequelae center on future fertility
. Suspected micro invasion,
limi.tations such as cervical stenosis or

. Lack of correlation between the cytology and
colposcopy/biopsies, especially if a high
incompetence.
grade lesion is suspected,
Controversies
. Lesion extending into the endocervical
1. The infrequent but preventable inadequate canal,
evaluation is the only real controversy surrounding
. Endocervical curettage showing CIN or
368
(
I
r
r Di agnostic Proced u res I n Gynaecology
I
I
r
r gland L, lar abnormality, can be easily controlled with electro-cautery or
i
r
r
. Suspec :d adenocarcinoma !n-s!tu, Monsel's solution. ln extreme cases, a suture ligature
rt . Colposccpist unable to rule' out invasive may be required
I \-. disease,
It . . I rla:::. r.
Recurrence after an ablatlrni,,:'of prel/tous
.
Postoperative bleeding can also occur which is

I
r excisional procedure. usually due to the vasoconstrictor solution wearing
(
l
off or inadequate intraoperative hemostasis. Up to
i LEEP should not be performed during 'pregnancy 8% of patients may present with bleeding within 1-2
f unless a strong suspicion of cancer exists. weeks of surgery. This type of bleeding is most likely
i
t
caused by erosion of a blood vessel during healing.
Proceduren'o The use of Monsel's solution, silver nitrate, electro-
After counselling the patient on the procedun and
I
I
cautery, or packing usually provides adequate
obtaining an informed consent, the patient is placed
hemostasisn''0.
in dorsal lithotomy position with a grounding pad
i
placed on the upper thigh. An insulated speculum, lnfection can occur but the risk is very low;'
i i
with the smoke evacuation tube is placed in the prophylactic antibiotics may be indicated. The
t
vagina to gain visualization of the cervix that is reported rate of infection is 0-8%'0. Patients with
infiltrated with an anesthetic/vasoconstrictor infection may present with malodorous discharge
f
I
solution. Acetic acid (3-5%) or Lugol's iodine solution and fever. Treatment consists of oral antibiotics such
{ is placed on the cervix to visualize the entire lesion as azithromycin or doxycycline.
and aid the surgeon in the selection of the appropriate
),
t
r loop electrode. The electrosurgical generator is set at Cervical stenosis and cervical insufficiency, which
I
I
30-50 watts on cut. ldeally the lesion is excised in are late complications, have been reported to be
i
one pass. The loop should be carefully passed between 4.3-7 .7"/".'o LEEP as a cause of cervical
I
simultaneously around and under the transformation insufficiency remains controversial. A recent meta-
t
zone. The entire transformation zone should be analysisof 20 studies showed no increase in
excised to a depth -i 5-8 mm. For best results, the abortion rates, preterm delivery or perinatal
J loop should glide through the cervix. This allows the mortality. ln contrast, a large study published in
cutting current to divide the tissue (consistent power 2009 found an increased risk of preterm delivery at
I
'lensity). lf the loop moves too slowly, excess thermal all gestational ages following LEEP proceduresn'"
; damage occursn. lf the loop is pulled too rapidly
I
I through the cervix, it will drag, bend, or adhere to the Patient Education
tissue, resulting in too shallow specimen. ln patients Patients are instructed to avoid intercourse and place
I
with wide lesions or large cervices, making additional nothing in the vagina for 2-4 weeks. She is followed
:
passes in order to completely remove all abnormal up in 6 weeks to ensure endocervical patency and
tissue may be necessary. ln addition, if the lesion app"rprlate healing.
:
extends into the endocervical canal deeper than 5-8
Laser conization
mm depth, additionaltissue is excised with a smaller
A laser is a device that emits light (electromagnetic
rectangular loop ("top hat"). To decrease the risk of
radiation) through a process called stimulated
cervical stenosis, removing the least amount of tissue
emis:,;;n. The term "laser" is an acronym for Light
possible is important. lncision depths of 1 cm >
Am*lification by Stimulated Emission of Radiation.
increase the risk of cervical stenosis'''0. Colposcopic
Witt, the development of light amplification by
reassessment can be performed after the procedure is
stimulated emission of radiation (LASER) for
finished, to ensure adequacy of excision. An
medical use in early 7970, the carbon dioxide (COr)
endocervical curettage may be performed following
laser was adapted to the laparoscope and
excision but is often unnecessary, as the result does
colposcope, which opened a new era of laser
not change the subsequent management. Bleeding is
treatment for patients with gynecologic diseases.
usually easily controlled with a ball electrode or by
Through the colposcope, the CO, laser was used for
I application of Monsel's solution to the cone bed
vaporization or conization of cervical intraepithelial
Complications include lntraoperative bleeding which
neoplasia (ClN); or vaporization of vaginal
369
- ---:------!
intraepithelial neoplasia (VAIN) and vulvar margins with 0.5- to 1-mm dots produced by laser
i ntraepithel ial neoplasia (Vl N)"'". energy at a power setting of 20-50 W A laser incision
is then performed to connect the dots and extended
lndications include; ablation or excision of dpplasia to a depth of 3-5 mm. Laser, scalpel, or Mayo
in situations in which minimization of tissue scissors may be used to complete the procedure. lf
destruction or removal is desired, cervical treatment laser is used for the conclusion, the stromal edge of
combined with treatment of dysplasia or the incision must be grasped and lifted with a hook to
condylomata of the vulva, vaginal, perineal, or permit penetration of the laser beam towards the
perirectal areas, multifocal disease of the cervix, apex. Bleeders in the raw stump can be coagulated
vagina, or vulva/perianal areas, ablation or excision with defocused 2-mm laser dots or with a diathermy
of endometrial implants or affected peritoneum and coagulator. For CO, laser procedures of the vagina, a
lysis of intra-abdominal or intra-pelvic adhesions Teflon-coated speculum with a built-in smoke
Contraindications to using the carbon dioxide laser evacuator is placed into the vagina and the entire
for the treatment of lower genital tract disease area of interest is visualized, both with the operator's
include; an inability to visualize the area to be treated eye and then via the colposcope. Acetic acid
because of anatomic considerations (e.g. prolapsing application may assist visualization of condylomata,
lateral vaginal sidewall), preoperative histology but Lugol's solution may be preferable for
findings indicative of malignancy, and inadequate visualization of dysplastic areas. Although these
physician training or experience. areas had been preoperatively visualized, careful re-
evaluation in the operating room should be made
After counseling the patient and obtaining an
before using the laser.
informed consent the patient is placed in the dorsal
lithotomy position, speculum (with a smoke
a Pain management following laser procedures to the
evacuator system to remove the vapour plume) of external genitalia, vagina, or cervix may consist of
adequate size is used to fully visualize the cervix. A non-steroidal anti-inflammatory agents (NSAIDS)
speculum with a dull surface that is specifically and narcotics. lnitial dosing should be given
designed to prevent reflection of the laser beam preoperatively with oral medications or intra-
should be used. A speculum of appropriate length operatively with lV medications in the office setting
and width should be chosen to prevent relaxation of and intravenous medications in the operative suite.
the lateral vaginal walls that could limit cervical Pain management of vulva or perianal lesions may
exposure and risk inadvertent laser damage. also be facilitated by topical Xylocaine jelly (2%) or
Alternatively, a vaginal wbll retractor can be used to ointment (5%), silver sulfadiazine cream, ice packs,
retract the lateral vaginal walls. and sitz baths.
Anesthesia for CO, laser treatment of the cervix or Vaginal postoperative care of postmenopausal
external genitalia may be provided by local injection women not currently using systemic or topical
of Xylocaine (lidocaine) with or without hormone therapy, may include small amounts of
adrenaline"'" The patient is draped in damp towels estrogen cream, 0.5-1 g intravaginally at night to
to absorb any misdirected laser beams, and the increase the rate of re-epithelialization of the vaginal
patient's eyes are protected with wet gauze or tissue and decrease the risk of vaginal scars.
protective glasses. All personnel, except the
physician operating the microscope, should also General postoperative instructions include; pelvic
wear eye protection to avoid accidental laser injury to rest (i.e., no tampons, douching, or intercourse) until
the eyes. the sched u led postoperative fol low-u p exa m i nation,
light activity for 3-5 days postoperatively, especially
The cervix, vagina, or vulva is soaked with a 3% no heavy lifting or excessive strenuous activities and
solution of acetic acid, and abnormalities are noted if
instructions to call a foul-smelling vaginal
with the microscope before the laser is fired. discharge, pelvic pain, fever, or excess bleeding
develops for 2-4 weeks.
The procedure is begun by outlining the exo-cervical
370
rI
r Di agnosti c Proced u res I n Gynaecology
i
I
r Com pl ication : associated with excisiona I proced u res required for LEEP is an electrically insulated vaginal
I
{
I performed usit g the carbon dioxide laser include side-wall retractor, or a metallic speculum insulated
rr bleeding, infection, cervical scarring or stenosis, with latex condom to prevent an electrical injury
{ (shock or thermal injury) to the patient or the
[ ..- altered fertility, anesthetic complications, premature
? labou r, a nd cervical i nsufficiency. operator if the loop or the ball electrode accidentally
r
1
touches the instrument. Since a metallic vaginal
f
A randomized trial of cryotherapy, carbon dioxide speculum conducts electricity, it may lead to an
ll
I
I
laser vaporization, and LEEP for ClN, showed electrical injury to the vagina if the loop accidentally
relatively similar rates of disease persistence and comes into contact with these metallic instruments,
r recurrence with each of the modalities over:follow-up
I lnsulated vaginal specula and insulated vaginal
I periods of 6-37 months. Recurrences are more likely sidewall retractors are more expensive than non-
r
to occur in women (aged 30 years or older), r/omen insulated ones. ln contrast to LEEB which is an
I
:- with HPV type 16, and women with prior dysplasia. excisional technique, cryotherapy is an ablative one.
Persistent disease was more common in women with ln practical terms, this means that there will be no
I
Iarger lesions, a factor that in other studies has been pathology specimen to evaluate after cryotherapy
t'
shown to be better managed by carbon dioxide laser which obviously has an immediate cost saving.
I
procedures than other modalities. Many recurrences Proponents of LEEP appreciate the feedback of
of cervical dysplasia are associated with prior positive information if there is a pathological examination of
I ectocervica I or endocervical margins'*. the LEEP-excised tissue. This feedback allows a
{ reassessment of not only the most severe grade of
I
I Of all rvailable and effective treatments of ClN,
I
t lesion present, but also the adequacy of excision
cryotherapy and LEEP are appropriate for both high (whether excisional margins are involved), The main
r
I and low-resource settings for several reasons. First,
I limitation of cryotherapy is that it is not adequate to
t they require the least financial investment for
f treat lesions that are not wholly located on the
equipment, are quickly learned and result in high
I
l
ectocervix, yet involve the endocervical canal. ln
I cure rates and few complications. Cryotherapy does
r contrast, LEEP can adequately excise the majority of
r
I
not require a source of electricity as LEEP does, but
cervical lesions, whether or not the canal is involved.
relies instead on a supply of easily transportable
T
Meta-analysis of randomized clinical trials that
tanks of highly compressed refrigerant gas. After the
7
I evaluated the comparative effectiveness of
vaginal speculum is in place and the cervix has been
cryotherapy with therapies such as LEEE conization
r visualized, both procedures take approximately 15
and laser, have concluded that the above treatments
rt minutes from start to finish. Ancillary equipment is
are equally effective in controlling ClN. From the
required for LEEB blt not for cryotherapy for several
foregoing comparisons and contrasts, it is
!-!
?
I reasons. Although the performance of cryotherapy
( empirically clear that the most practical and cost-
usually does not require a local anaesthetic, LEEP
I
r efflctive method of treatment of CIN in low-resource

I does require several injections of a local anaesthetic
t settings is cryotherapy, provided the lesion is wholly
( into the ectocervix. LEEP generates smoke that
ectocervical in location. LEEP is the treatment of
r remains in the vagina unless it is evacuated by a
I choice if the lesion involvesthe endocervicalcanal.
vacuum system to allow an unobstructed view of the
r operative field. The third type of ancillary equipment
a
I
I
I
:
:
:
371
j
REFERENCES
-t"
. ,,
1. Almonte M et al. Cervical Screening by Visual Gynecol. 1990 Feb. 7 5(2):232-9. [MedlineJ.
inspection, HPV testing, Liquid based and 9. Shaw HA, Shaw J,Loop electrosurgical excision.
conventionat Cytology in Amazonian Peru. /
http : / emedicine.medsc ap e. c om/ arti cle/ 1 9 9 B 0 6 7 -
lnternational Journal of Cancer 2007; 12'1 (4) : overview.[assesed Aug o3. 2016].
796-802. 10. Suh-Burgmann EJ, WhalLStrojwas D, Chang\
Hundley D, Goodman A. Risk factors for cervical
2. Noller K, Wagner A Jr. Colposcopy. Sciarra JL, ed.
stenosis after loop electrocautery excision
Gynecology and Obstetrics. Philadelphia, Fa:
procedure. Obstet Gynecol. 2000 Nov. 96(5 Pt
Lippincott, Williamsand Wilkins;2000. Vol 1:
1):657-60. [Medline]
3. Mesher D, Tristram A, Castanon A, Beer H,
Ashman S, Fielder H, et al. Sing/e negative
11. Heinonen A, Gissler M, Riska A, Paavonen J,
Tapper AM, Jakobsson M. Loop electrosurgical
colposcopy: is it enough to rule out high-grade
excision procedure and the risk for preterm
drsease?. J Med Screen. 2011. 18(3):160-1.
IMedline].
delivery. Obste t Gynecol. 2013 May.
12 1 (5) : 1 063- 8. [Medline]
4. Galaal K, Bryant A, Deane KH, Al-Khaduri M,
12. Gajjar K, Martin-Hirsch PE Bryant A. Pain relief
Lopes AD. lnterventions for reducing anxiety in
for women with cervical intraepithelial neoplasia
women undergoing colposcopy. Cochrane
undergoing colposcopy treatment. Cochrane
Database Syst Rev. 2011 Dec 7. 12:CD006013.
Database Syst Rev. 2012 Oct 17. 10:CD006120.
IMedline].
IMedline].
5. Metz AS, Pattan C. colposcopy ,treatment and
management. 13. Vanichtantikul A, Charoenkwan K. Lidocaine spray
http : / /e med i c i ne. m ed sca pe. co m / a rti cl e I 26 5097 compared with submucosal injection for reducing
- ove rv i ew. [assessed Jan 0 1, 20 1 5] pain during loop electrosurgical excision
6. Chailes EH, Savage EW, Hacker N. Cryosurgical procedure: a randomized controlled trial. Obstet
treatment of cervical intraepithelial neoplasia. Gynecol. 20 1 3 Sep. 1 22(3) : 553-7. [Med I i ne].
Gynecol ancol. 1981 Aug. 12(1):83-8. [Medlinel. 14. Bacon JL. Carbon Dioxide Laser Surgery in
7. Unger JG, Amirlak B. Gynecology
http : / /emed i c i n e. med sca pe. com / a r ti
Cr yothe ra py. http : / /e med i c i ne. med sca pe. com I a rti c Ie /2 7 2 3 82
cl e / 1 1 -ove rv i ew [assessed Jan 29, 20 1 5]
25 B51
-overview lassessedDec 26, 20151
8. Boonstra H, Koudsta'al J, Oosterhuis JW. Analysis
of Cryolesions in the uterine cervix: application
techniques, extension, and failures. Obstet
372
F
i.
Diagnostic Proced u res I n Gynaecology

I
a
I lll. EXAMINATION UNDER ANAESTHESIA, Biopsy the HeLa immotile cell line, a commonly used cell
I for Cervical cancer and Endometrial sarnpling for line in contemporary biomedical research. The Hela
I SuspectedUterineMalignancy l:-,..-... cells were termed immotile because they were seen
I
to divide at a very high rate could stay alive longer in
l*
r Cervical cancer is the third' ..#j #o+l culture for study. The principle of EUA and Biopsy for
I
I malignancy in women worldwide, an$.iffi

tne suspected cervical cancer is based on the simple fact
r leading cause of cancer-related death in'women in that under general anaesthesia the patient is relaxed
I
I developing countries like ours. Cerviea:L:c6ncer is and proper evaluation of pelvic structures is made
a
I
relatively uncommon in the developed world'. More e'asy and more accurately without discomfort of pain.
I
I
I
than 80% of new cases are diagnosed in Secondly, tissues taken can be examined for features
f economically disadvantaged people. Carcinoma of of atypia and metaplasia that can correctly indicate
l
I the cervix grows locally and may extend in continuity the presence of cancer.
( to the paracervical tissues and to the Ellvic organs,
I
t spread to regional lymph nodes, and only later To perform examination under anaesthesia and
metastasize to d ista nt structu res. biopsy for suspected cervical cancer, the patient
f
t would have met the indications: history of abnormal
Examination under anaesthesia is required in uterine/vaginal bleeding in a woman in 3'o to 6'n
situations where comprehensive clinica[ examination decade with post coital or contact bleeding; history
( a
of patients cannot be done due to pain or

(
of abnormal vaginal bleeding with any of the risk
fI psychological discomfort. For patients with factors for cervical cancer such as early coitarche,
+
t
suspected cervical cancer a pelvic examination under multiple sexual partners, high risk male partner,
anaesthesia is usually carried out for staging and cigarette smoking, Human immunodeficiency virus
r t biopsy, and the tissue sent for histopathologic study. (HlV) infection, or presence of clinical features like
t
r The first ever biopsy of cervical lesions was done by foul smelling malodorous vaginal discharge with or
I
I Professor John Williams (1886), which he reported without cervical mass that bleeds easily on contact.
I
in his Harveian lectures. Sir John Williams reported Others include abnormal Pap smear result with or
t eight cervical cancers one of which was equivalent to without human papilloma virus infection (especially
i carcinoma in situ (cervical intraepithelial neoplasia
r high risk type). Contraindications to EUA and biopsy
lll) which he described as the earliest cancer for suspected cervical cancer include: a patient who
possible. ln 1920s, the principles of colposcopy was is haemodynamically unstable due to haemorrhage;
r
r
I
described by Hinselmann, who taught that using a overwhelming sepsis; severely deranged renal
I low power magnifying microscope, smaller lesions function, for example presence of uraemia;
not visible to the naked eyes could be seen and respiratory failure, abnormal liver function
I
I treated. Schiller 1930s, working with dilute iodine precluding anesthesia and when patient declines
solution was able to describe that cervical lesions consent.
I
't progress from a precancerous to cancerous ones. He
called the precancerous lesions "young carcinoma" Before the procedure, the patient is properly
and he treated them by radical hysterectomy the counseled on the purpose of the procedure, the
I'
Wertheim's type followed by radiotherapy. ln 1951 personnel that will be involved (e.g. surgeon,
i Howard W. Jones, a doctor working at the John assistant, Anaesthetist, scrub nurse, resident,
Hopkins Hospital in Baltimore, Maryland, USA medical student), and how the procedure will be
collected cells from Henrietta Lack (1920-1951), an performed, type of anaesthesia, details of part of
i
African American Just four months after her last child body to be examined and possible samples to be
birth when she presented with haemorrhage. During taken. The counseling should also include possible
: .Lack's follow-up treatment, two samples were taken complications and their management. Following
from her without consent or her knowledge, one from this, an informed written consent is then obtained
i healthy cells and the other cancerous cells. The from the patient or any of the close relatives if she is
samples were given to George Otto Gey, a physician unable to do that. As part of the preoperative
i
and cancer researcher at John Hopkins Hospital. The preparation, patient is admitted the day before
cells from the cancerous sample became known as surgery, detailed history and reasonable physical
373
Comprehens \ynaecology in the Topics
examination done, blood is taking for packed cell walls, vaginal fornixes the cervix noting the presence
volume, grouping and cross-match of at least two of indurations, masses and their consistency,
units of blood, electrolytes, urea and creatinine to followed by a bimanual pelvic examination to
determined renal function, and liver functi-on test estimate the uterine size, fixity, presences of masses,
should be evaluated. A chest X-ray, and an W mey and the consistency of the mass. The parametrium
be required. The patient should fast for 6.to 8 hgurs and the pelvic sidewalls are also assessed for
before the procedure because of the risk d rypin*tion involvement, which may be felt as hard mass
with general anaesthesia. She is also reviewed by the obliterating the pouch of Douglas that may extend to
Anaesthetist to ensu re fitness for anaesthesia. the pelvic sidewalls. As the examining fingers are
withdrawn, they are inspected for presence of blood.
On the operation day, patient is taken to the theatre At this point, a digital rectal examination is then
and after administering anaesthesia placed in the performed using the middle finger of the same hand,
lithotomy position. She is then cleaned and draped; checking anal sphincter tone, rectal mucosa for
the urinary bladder is evaluated using a cystoscope presence of any mass which may be comingfrom the
for the presences of abnormal vascularization, cervix or primarily originating from the rectum. The
bleeding or extension of tumour masses. Where a rectal mucosa is assessed for mobility or fixity as
cystoscope is not available, the urinary bladder is case may be. The pouch of Douglas is also examinco
emptied with a metallic catheter,( a clean catch urine at this point for presences of masses, which may be
sample is taken for microscopy for red blood cells) metastatic deposits. ln addition, the involvement of
and at the same time examined on a white piece of the pelvic sidewalls can be assessed at the same
gauze for presence of haematuria or necrotic tissues. time. The recto-vaginal septum is then examined in-
Followingthat, a speculum examination is performed between the indexfinger in the vagina and the middle
gently with a bivalve speculum or an Aurburgs's self- finger in the rectum noting the presence of any
retaining speculum where the cervix is exposed and induration or frank tumour deposits. Lastly, a
inspected for the presence of any abnormal growth, proctoscopy may be required and samples taken
bleeding or malodorous discharge as the case may where suspicious lesions are seen. The patient is
be. At this point, a sample can be taken from any cleaned and anaesthesia is reversed. Patient is then
cervical lesion using any of the following methods: a placed in supine position and transferred to the ward
cold knife cone biopsy including areas of healthy after full recovery from anaesthesia. The disease is
tissue or a wage excision biopsy can be done. Also, staged based on clinical examination findings and
biopsy using the Kevorkian square-jawed cervical proper documentation of all proceedings is done. All
biopsy forceps can also.be done, in this case taking samples collected are properly labelled and taken for
samples from different parts of the cervical lesion histopathologic study. She is given analgesia and
systematically (from 4 to 6 points). These samples antibiotics where necessary and discharged home
are immediately preserved in formalin solution in the following day if all is well to be seen in the clinic
properly labeled containers. The patient is then for review of histology result.
observed for possible haemorrhage and where this
occurs, pressure can be applied with a dry piece of Other methods of EUA and Biopsy for suspected
gauze or gauze soaked in adrenaline if the former cervical cancer involve the use of a colposcope.
cannot arrest bleeding and this can be left in place for Colposcopy is the use of a low power magnification
24 hours or more. Other solutions such as Monsel microscope to visualized vulva, vaginal and cervical
solution, dilute HCL solution can also be used to stop lesions that are not visible to the naked human eye.
bleeding. Again, in some instances an absorbable This procedure is commonly done under sedation or
suture such as the vicryl 2lO may be used to secure no anaesthesia, with the patient in lithotomy
haemostasis. Following collection of samples the position, routine cleaning and draping done. A
speculum is gently withdrawn while the vaginal walls special insulated speculum is used to exposed the
are being inspected for any extension of the cervical cervix, the colposcope is positioned and the cervix is
lesions or any abnormality. Next, a gentle.digital examined for any abnormal.ity which include;
vaginal examination is carried out usingthe index and ulcerations, abnormal vascular patterns, degree of
midd le fingers of the right hand, palpating the vaginal aceto-white epithelium, border characteristics,
374
rt
(
I
Di agnostic Proced u res I n Gynaecology
i
r
I
I
surface pattern and surface area of the lesion seen. shock and even death, tumour embolism with
,( This looks at whether the lesion is irregular, vascular distant metastasis, infection and vaso-vagal arrest
t"
I patterns are coarse, exhibit mosaicism, punctations from manipulation of the cervix, electrocution while
or are annular and large. These together with the doing a colposcopy and biopsy and long term
r findings on clinical examination form the clinico- cervical stenosis or insufficiency. Others are
colposcopic index that could be used to predict anaesthetic complications such as cardiac arrest and
: histological outcome and in planning management of even death on table.
these patients. Biopsy is then taken using any of the
following: sharp instrument like Tischler biopsy Furthermore, the place of examination under
forceps, large loop excision at the transformation anaesthesia and biopsy for suspected cervical
zone (LLETZ) also called loop excision electrosurgical cancer cannot be over emphasized, in view of the
procedure (LEEP); Laser cone Biopsy and Loop cone fact that this disease is more prevalent in developing
biopsy. Haemostasis is achieved by means of countries, like the West African sub region. lf this
electrocoagulation. Tissues from this procedure are procedure is combined with other modalities
sent for histology and the result will then determine if available for the prevention of cervical cancer such
further treatment is required. The advantage of this as the human papilloma virus vaccine for adolescent
procedure over the one described above is that it boys and girls, and other cervical cancer screening
detects early cancers suggested by abnormal Pap methods, the burden of this disease will be greatly
smear, which are curable. minimized.
Cervical cancer is staged following clinical ln coirclusion, examination under anaesthesia and
examination using the FIGO staging system 2074 as biopsy is a major component of management of
follows: stage I which is cervical cancer restricted to cervical cancer, which is the commonness cause of
: the uterine cervix with extension to the uterine corpus gynaecological oncology death in the West African
disregarded, further subdivided into lA1, lA2 and sub-region. Therefore, making this service available
lB1, l82 (lA1: microscopic lesion lessthan 3mm in in our sub-region will go a long way in mitigating the
depth and not more than 7mm in widest spread, magnitude of this problem and save our women from
lA2= microscopic lesion greater than 3mm but less avoidable death.
than 5mm in depth but not more than 7mm in widest
spread; lB1: macroscopic lesion less than 4cm, l82 ENDOMETRIAL SAMPLING
;
macroscopic lesion g.reater than 4cm); while stage ll
is done when pathology,
Endometrial sampling
particularly cancer of the endometrium, is
is defined as extension to the parametrium or
involvement of the upper 213'o of the vagina, also
suspected. lndications for endometrial sampling
includel..:
subdivided into stage llA which is involvement of
upper 213'o of vagina (stage llAl:
lesion less than
.Abnormal uterine bleeding
4cm, llA2: lesion greater than 4cm wide). Stage lll

oPostmenopausalbleeding
. Cancer screening (e.g., hereditary
cancers are defined as extension to the pelvic side
non polyposis colorectal cancer)
wall or involvement of lower 1/3'o of the vagina and or o Detection of precancerous hyperplasia and
hydronephrosis and or nonfunctional kidneys (lllA : atypia
involvement of lower 1/3'o of vagina, lllB: extension . Follow-up of previously diagnosed
to pelvic side wall and or hydronephrosis and or endometrial hyperplasia
nonfunctional kidneys) and finally, stage lV disease . Evaluation of uterine response to hormone
which is subdivided into IVA which describes therapyas in HRT
involvement of contiguous structures like the urinary . Evaluation of infertility
bladder anteriorly and the rectum posteriorly while o Abnormal Papanicolaou smear with atypical
stage IVB is distant metastasis ( involvement of the cells favou ring endometrial origin
liver, lungs orthe brain)
I Methods of sam pl ing the endometrium
Some complications of this procedure include the Over the years, various methods of sampling the
following: uncontrollable haemorrhage leading to endometrium have been applied. The methods are:
375
Comprehensi /naecology in the Topics
. Dilatation and curettage (D & C) type of anaesthesia to be used and its possible side
. Suction curettage : .
effects, and possible complications of the procedure.
- Reusable curettes, 9,8.,i ltlovak The procedure is usually done as a day case;
curette however, patient is often observed for 4'6 hours post
- Disposable curettes, e.g.:lfdbra procedure for possible vaginal bleeding. Antibiotics
aspirator, Karman cahnu'[a' and and enema are not required before the operation, but
syringe, Pipelle endometrial suction prophylactic antibiotics should be given
curette, etc. postoperatively. There might be need for transvaginal
. Endometrial brush biopsy (The Tao brush ultrasound and haematocrit count prior to the
method) operation depending on clinical presentation of the
o Endomyometrial resection biopsy using a patient. Pretreatment with prostaglandin E1 analog
hystero-resectoscope loop (misoprostol) i00ug orally the night before and
morning of the day of procedure will help in softening
Dilatation and curettage for suspected Uterine the cervix and make dilatation easier reducing risk of
Malignancy
cervical laceration and uterine perforation.
Since the invention of the curette by Recamier In
1843, dilatation of the cervix with curettage of the During the procedure in theatre, the patient is plac
endometrium has become one of the most frequently in dorsal lithotomy position under general
performed gynaecological procedures.'.. Diagnostic anaesthesia, regional or l.ocal anaesthesia with
dilation and curettage was originally intended to sedation, as the case may be. The vagina is cleaned
detect intrauterine endometrial abnormalities and and draped. The urinary bladder is then emptied and
assist in the management of abnormal bleeding. a bimanual pelvic examination is performed to
Sampling and histologic evaluation of the assess the size and position of the uterus to allow
endometrium in women with abnormal bleeding may easy and safe placement of instruments in the uterine
disclose infection or neoplastic lesions such as cavity. Following this, a bivalve speculum or vaginal
endometrial hyperplasia, cancer, polyps, or retractor is used to expose the cervix and the anterior
gestational trophoblastic neoplasia. Although used lip of the cervix is grasped with a tenaculum. A
for diagnostic evaluation and treatment of abnormal Simpson's uterine sound is held like a pencil with
uterine bleeding in the last 150 years newer thumb and index fingers and gently introduced into
techniques are now available to assess the uterine the uterus at the same time applying gentle traction
cavity and endometrial findings. However, dilation on the tenaculum to straighten the uterine axis which
and curettage still has a.role in centers where these prevents perforation. The sound is advance slowly
new technologies are not available or when other until a gentle resistance is felt on reaching the
diagnostic modalities are unsuccessful. For example fundus. The distance from the fundus to the external
where abnormal bleeding persists after using vaginal cervical os is marked and this guides the movement
ultrasonography and pipelle aspirator repeatedly of dilators and the curette subsequently to minimize
with normalfindings. the risk of perforation. Sequential serial dilatation is
then done with any of Hager, Hank or Pratt dilators
The Procedure of D & C:
untilthe cervix is open enough forthe curette (usually
Traditionally, dilation and curettage has been
sizes of <8mm) to pass through, holding the dilator
performed in a blind fashion. The procedure can be
with thumb, index and middle fingers while the ring,
performed under ultrasound guidance or in
little finger and the heel of the hand rest on the
conjunction with visualization of the uterine cavity by
perineum and the buttock. Each dilator is advanced
a hysteroscope.
gently through the internal os until selected curette is
During the preoperative preparation of patients for able to pass through the cervical canal and the
sharp dilatation and curettage, an informed written internalos.
consent is obtained following counseling of the
It is important to note that perforation can occur
patient. Counseling entails telling patient why she
during dilatation especially when the instrument has
needs the operation, where and when it will be done,
been advanced beyond the measured depth.
376
r I
r
Diagnosti c Proced u res I n Gynaecology
Because this rrstruments are blunt, the risk of injury the closed forceps is felt as they are pulled awayfrom
to the bowel i:nd other structures is rare and so the uterine wall. Firm traction typically frees the
patients should be observed when th'is happens. polyp. Alternatively, hysteroscopy may be used
Prior to curettage, a sheet of non-adhdrent wound adjunctively with curettage to diagnose and remove
dressing material such as sterile gauze is spread out focal lesions such as polyps.
in the vagina beneath the cervix. The uterine curette
is then inserted and advanced to the fundus, lndicationsfor D & C:
following the long axis of the corpus. On reaching the The indications for dilatation and curettage can be
fundus, the sharp surface of the curette is positioned diagnostic or therapeutic. The diagnostic indications
to contact the adjacent endometrium. Pressure is includes the following: abnormal uterine bleeding;
exerted against the endometrium as the curette is intermenstrual bleeding; postmenopausal bleeding
pulled toward the internal cervical os. After reaching (rule out endometrial carcinoma) and
the os, the curette is redirected to the fundus and menometrorrhagia; others are: abnormal cytology
positioned immediately adjacent to the path of the (endocervical curettage, cone biopsy for cervical
first curettage pass. ln this manner, the surgeon carcinoma); ruling out disease of the endometrium
attempts to sample the entire uterine surface. After
(endometritis, malignancy) at the time of
about four to six stripes of endometrium have been hysterectomy; ruling out pregnancy at the time of
removed the entire cavity would have been curetted laparoscopic sterilizaiion; dysmenorrhea;
and tissues collected in the isthmus region are oligomenorrhoea; amenorrhoea and infertility. While
scraped out onto the sterile gauze or Telfa pad. To the therapeutic indications are as follows:
ensure thorough curettage, the curette is passed from menometrorrhagia; dysmenorrhea; suspected
one cornu to the other over the fundus of the uterus. A i ntrauteri ne pathology ( polyps, i ncom plete a bortion,
small sharp curette may be useful to reach the and molar pregnancy); postpartum bleeding and
corneal regions. Only after the tissue is evacuated retained products of conception. Others include:
should the curette be used as a scrub brush to denude haematometra or haematocolpos; retrieval of "lost"
the endometrium down to the decidual layer and intrauterine device; insertion of radioactive carriers
possibly to detect irregularities suggestive of for management of uterine or cervical malignancy.
submucous fibroids hiding underneath the With advancement in technology as obtained today,
: endometrium. The end of this scrubbing should be most of these indications have alternative modes of
I'/ the detection of a scratching sensation or sound (the management. For example, in ruling out uterine
"uterine cry"), which represents a sharp curette malignancy, the office aspirator has been found to
running over myomeirium. lt should be noted that too produce sample for diagnosis in 85% to 99% as
vigorous a pursuit at this point may lead to formation compared to77%to94% obtained by dilatation and
of uterine synaechia (Asherman's syndrome). curettage. These techniques appear to be more
accurate in detecting endometrial carcinoma than
As with dilatation, the uterus may be perforated curettage.
during curettage. However, the sharp curette has the
potential to
lacerate bowel, vessels, and other Contraind ications:
Contraindications to dilatation and curettage can be
abdominal organs. Accordingly, diagnostic
laparoscopy is suggested to evaluate for such injuries. divided into absolute contraindication that includes:
Because uterine polyps, both large and small, may be
viable desired intrauterine pregnancy; inability to
missed with sharp curettage, uterine exploration with
visualize the cervical os and finally obstructed
Randall kidney stone forceps is warranted in women
vagina. While the relative contraindications are as
undergoing evaluation of abnormal bleeding. Closed
follows: severe cervical stenosis; cervical/uterine
forceps are inserted into the endometrial cavity. On
anomaly; bleeding disorder; prior endometrial
reaching the fundus, the forceps are opened against
ablation; obstructed cervical lesion; acute pelvic
infection (except to remove infected content).
the uterine walls; closed, and then pulled away from
I the endometrium. ln this fashion, anterior, posterior,
These contraindications may be surmounted in some
proximal, and distal cavity surfaces are explored.
cases. For example, magnetic resonance imaging
With capture of a polyp within the jaws, a tug against
377
---!
may define the anatomy of the cervical or uterine sedation is sufficient for the procedure while the
anomaly, allowing safe exploration of the endocervix opponents to this idea advocate the use of general
and endometrium. anaesthesia, regional or local anaesthesia with
sedation. Again, whether the procedure should be
Complications: done in the presence of intrauterine infection is not
Like any surgical procedure, dilatation and eurettage universally accepted. Others believe that dilatation
can be followed by complications, which can be and curettage should be carried in the presence of
immedialelearly or late. The immediate infection only if there is retained products of
complications include the following: haemorrhage conception.
from the lacerated cervix; uterine perforation which
may involve the bowel or pelvic vasculature, and Dilatation and curettage for suspected uterine
could lead to massive haemorrhage, hypotension malignancy is an age long procedure in gynaecology
shock and even death; others are infections; that is still very much relevant in the diagnosis and
trophoblastic embolization and anaesthetic management of several conditions as previously
complications (hypersensitivity, cardiac arrest). described. lts usefulness is much more relevant in
While the late complications include: post procedure the West African sub-region due to unavailability of
uterine synaechia (Asherman's syndrome); many up-to-date facilities that have replaced it in
amenorrhoea and infertil ity. most develop countries. Patients for dilatation and
curettage should be well selected and the procedure
Conclusion: should be performed by an experienced surgeon to
Dilatation and curettage still plays a vital role in the minimize the risk of complications such as uterine
management of uterine and cervical abnormalities in perforation and injury to the bowel and other visceral
the West African sub-region. This is more so because structures.
most of the other techniques that have replaced this
procedure in the developed world are lacking in many SUCTION CURETTAGE (Office endometrial
centres in the sub-region. Therefore, there is the need sampling techniques)
to develop and popularize this skill within the sub- For a long time, D & C was considered as the gold
region to enable Gynaecologists to diagnose and standard for obtaining an endometrial biopsy.'..
properly manage some of the conditions discussed However, D & C was found to have its shortcomings.
above. Endometrial cancer is one of the leading It has been shown that it mayfail to pick up to 10% of
causes of female genital cancer in our environment endometrial lesions. ln addition, it may be associated
after cervical, ovarian cancers, and with complications such as heamorrhage, infection,
Choriocarcinoma.lt can be prevented by diagnosis uterine perforation, intra-uterine synechiae and the
and treatment of precursor lesion such as risk of dissemination of malignant cells into the
endometrial hyperplasia. This can be effectively myometrium. Other limitations of D & C include the
carried out with the aid of transvaginal cost of an operating room and complications
ultrasonography and dilatation and curettage. ln the associated with general anaesthesia.4**'5**'6**
West African sub-region where transvaginal
ultrasonography is not readily available, a blind Over the years, equipment and techniques for office-
dilatation and curettage can be the solution in based endometrial sampling that are reliable,
patients suspected to have this condition. inexpensive and acceptable to both the patient and
Due to the complications that could result from this the physician have been developed.'/..'8.. Advantages
procedure, dilatation and curettage is surrounded by associated with office endometrial sampling
some controversies. Some studies have shown that tech niques i ncl ude:8".
dilatation and curettage causes thinning of the . An outpatient clinic is used, rather than an
endometrial lining that may affect future reproductive operating room
potentials of women and so should not be an option . Anaesthesia may not be needed, except
for those with desire for child bearing. Whether or not occasional use of local anaesthesia
this procedure should be done under anaesthesia is . There is minimal or no cervical dilatation
not universally agreed upon. Some believe that mild needed
378
r
i
r
7
I
D ia gnosti c P roced u res I n Gy n aeco logy
i
r
I
t There is minimal or no risk of uterine Pipelle curette:

ir perforation The Pipelle curette was introduced by Cornier in
r
I a Operating time is very brief 1984 and it is the most popular and most studied
( a It is less expensive endometrial biopsy device.t..'"..|t is constructed of
flexible polypropylene with an outer diameter of 3.1
I
.
Endometrial Suction Devices mm.'..lt is a plastic tube and piston device with a
Several endometrial sampling devices with relatively single side port near the distal end.'u.. it does not
i
high sensitivity and specificity for early diagnosis of require an external vacuum source and can be used
i
endometrial lesions have been developed since 1970 for endometrial sampling in patients with stenotic
for screening for endometrial leions.s..'10*'1r*'12*r3*The cervical canals. lt can also be used without
sampling devices include: analgesia.o..
I 1. Reusable curettes e.g., Novak curette After the tube of the Pipelle curette is introduced
l This is made of stainless steel and used with a syringe
through the cervix to the uterine fundus, suction is
to apply suction. A circumferential in-and-out motion
i obtained by pulling the piston completely back to a
is required to obtain a sample. Samples obtained are
self-retaining stop at the proximal end of the tube in
usually adequate. However, it has some limitations
the lower uterine segment. The endometrium is
which include difficulty with a stenotic cervix, and sampled by combining a corkscrew twisting motion
causing intense pain when the device "catches" the
a nd uteri ne cu rettage.o--''--
myometrium.o..The other example is the Masterson
Endometrial Biopsy System which incorporates a Endometrial Brush
reusable hand-operated pump. lt is more convenient The endometrial brush (e.g., Tao brush) is a
than a syrnge.t'.. disposable device with a brush at the distal end,
similar to the brush commonly used for endometrial
2. Disposable curettes e.g., Vabra aspirator, Karman sampling.'.. The Tao brush has a plastic brush
cannula and syringe and Pipelle curette Vabra measuring 7 mm wide and 35 mm long attached to a
- aspirator: long , flexible wire.'0..
The Vabra aspirator is available as a 4 mm disposable The Tao brush is an office procedure that can be done
plastic or a 2 or 3 mm stainless steel device. Suction without anaesthesia. The cervix ls exposed and
I
is obtained by an external vacuum source, usually an grasped by a single tooth tenaculum.The Tao brush,
electric pump, whictr can be noisy.'u.. lt produces protected by the plastic outer sheath, is inserted
samples comparable to that obtained by D & C.'.. through the os. lt is advanced until the rounded tip
However, it is less comfortable for the patient and reaches the uterine fundus. The outer sheath is then
require use of a tenaculum, cervical dilatation and a withdrawn towards the level of the internal os in
pa racervical block,'u..
order to expose the plastic britles, which are then
rotated about 7 to 10 times against the endometrial
Karman cannula and syringe:
lining.The bristles are then withdrawn into the outer
The Karman cannula and syringe is a high pressure
plastic sheath and the entire device is removed and
device which unlike the Vabra aspirator, does not
immediately immersed in a preservative.'0..
require an external vacuum source."-- The cannula is
made of flexible plastic with two ports at the distal
Endomyometria I resection biopsy
end and usually comes in 4 to 6 mm in diameter.o.. This is where about 3-5 mm deep biopsy of the
endometrium is obtained with hysteron-
".. Suction is provided by a reusable syringe which is
resectoscope loop. lt is to identify adenomyosis or to
connected to the cannula that is disposable.
investigate deep lesions of the endometrium.'..
Specimen is obtained by circumferential in-and-out
motion.o..several studies have shown that specimen
a
t obtained by Karman syringe and cannula is adequate
I
and can be compared with that obtained by D &
C,2**,18*'-22..
379
References
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Examination Under Anaesthesia, Cystoscopy, A diagnostic test for myoinvasion. Am JSurg
Srgmoidoscopy, and Biopsy Techniques, in Pathol 1995;19(4:371-
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Coomarasamy, M.l. Shafi g. W. Davila and . > e ndometri a I cytol ogy i n cl i n i ca I -
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1 0. 1 002197 I 1 1 1 829856 5.ch 1 33 7lx* Vuopala S, Klemi PJ, Maenpaa J, Salmi T,
7. Stock Rl, kanbour A. Prehysterectomy M a ka ra i nen L. Endob rush

curettage. Obstet Gy naecol 1 97 5 ; 45 : 537 -4 1. samping for endometrial cancer. Acta Obstet
7** Thomas J, Zuber M.D. Endometrial biopsy. Am Gynecol Scand 1989;
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2** Rutkow lM. Obstetric and gynaecologic 12xx Tajima M, lnamura M, Nakamura M, Sudo Y
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State, 1979 to 1984. Obstei Gynecol 1986; accuracy of endometrial cytology in the
67:755-59. d ia gnosi s of endometri
aI
3** Payne J. Endometrial Sampling. Available at I 998;

adenocarci noma. Cytopathotogy
pati e nt. i nfo ld octo ile n dometr i a I - sa m p I i n g 69(O:369-80.
Assessed on I 61 1 2120 1 6. 73** van Hoeven KH, Zaman SS, Deger RB,
4*x Koonings Pf; Grimes DA. Endometrial sampling Artymyshyn Rl. Eff icacy of
techniques for the office. Family Physician. the Endo-pap sampler in detecting
Available at en d o m etr i a I /esions. Acta cytol
http : //www. drpl a ce. co m/ E ndo metrial s ampl 1996: 40(il:900-906.
14*x Richart RM, Pringle P Choosing the right
ing techniques for the oflice.16.27792.ht
,m biopsy device. Contemp
Obstet Gynecol 1985; 23:48-7.
Assessedon 14112/2016 l5** Jensen JG. Vacuum curettage . out-patient
curettage without
5** Grimes DA. Diagnostic dilatation and anaesthesia. A report of 350 cases. Dan Med
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Obstet Gy necol 1 982 ; 1 42 : 1 -6.
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D ia gnosti c Proced u res I n Gy n aeco I ogy
t
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f 16** Kaunitz AM, Masciello A, Ostrowski M, Rovira IV, HYSTEROSALPI NGOG RAPHY (HSG)
I
f EZ. Comparism of
f"
l endometrial biopsy with the endometrial Pipelle lntrod uction
and Vabra aspirator. J lnfertility is a public health concern globally, and in
I Reprod Med 1988; 33:427 -3 L many parts of sub-Saharan Africa in particular. This
is not only because of its high prevalence but also
17** Suarez RA, Grimes DA, Majmudar B, Benigno due to the important socio-cultural effect of the
BB. Diagnostic condition on affected couples and families. lt
endometrial aspiration with the Karman accounts for up to 50%-65% of all gynaecological
cannula. J Reprod Med 1983; consultations. Mechanical factors are responsible for
28(1):41-4. approximately 30% of female infertility and various
18** Ekwempu CC. Uterine aspiration using the methods such as trans-vaginal ultrasonography,
Karman cannula and
hysterosalpingography (HSG), hysteroscopy and
syringe. Trop J Obsfet Gynaecol
laparoscopy have been used to investigate these
1
1999;8(2):37-8.
factors.
19** Adinma Jl, Adinma E. Karman's cannula and
I
vacuum aspirator in in
Hysterosalpingography (HSG) is a diagnostic
gynaecological practice. Journal of the
radiological imaging technique that is safe, and
N ation a I Med i ca I Associ ation
1999; 88(1):22-4. simple, and used to evaluate the cervical canal,
20** Ashraf S, Jabeen F. A comparative study of uterine cavity, the fallopian tubes and peritoneal
e ndometri a I aspi ration
cavity by injecting radiopaque contrast medium
a
t
cytology with dilatation and curettage in through the cervical canal under fluoroscopic
patients with dysf unctional guidance. lt is done with the minimum radiation
uterine bleeding, perimenopausal and exposure necessary to provide sufficient anatomic
postmenopa usa I b I eed i ng. J K- details for diagnosis of normal or abnormal findings.
Practitioner 2014; 19 (1-2): 41-5. Despite its low sensitivity, the high specificity of
21** Kaur N, Chahal JS, Bandlish U, Kaul R, Mardi hysterosalpingography makes it very helpful for
K, Kaur H. Correlation ruling out tubal disease, even where endoscopic
I between cytologi ca I a nd
h i stopathologica I evaluation is avai lable.
examination of the
/ endometrium in abnormal uterine bleeding. J The contrast media
i Cyto I 20 1 4; 3 1.(3) : 1 44- The first report on HSG using oil soluble contrast
a 48. (collargel) was published by Carey in 19I4.
22** Sukumaran CS, Omana EK, Prabhu t/S, B/essy Collargel causes significant tissue damage and pain.
MVR. Role of manual Because of these serious adverse events, its use was
vacuum aspiration in the evaluation of abandoned and a tubal insufflation test was
postme no pa u sa I b I e. ed i n g.
introduced by Rubin in 7920. Rubin insufflated
Paripex-lndian Journal of Research 2016;
oxygen (later carbon dioxide) under pressure through
5(10:48-50 the cervical canal into the uterine cavity. Tubal
23** Eddowes HA, Read MD, Codling BW. Pipelle: a
patency was determined by the presence of air under
more acceptable
the diaphragm on X-ray, by auscultation of air flow
technique for outpatient endometrial biopsy.
into the abdomen or a drop in pressure during
Br J Obstet Gynaecol
1990; 97(10:961-62. insufflation. Heuser was the first to report on the use
24** Yang GCH, Wan LS. Endometrial biopsy using of lipiodol in HSGs in7925. Lipiodol (oilsoluble, low
. the Tao brush method. viscosity, less toxic) became widely accepted for
The Journal of Reproductive Medicine 2000; decades. Lipiodol (40% iodine in poppy seed oil
45(2): 109-14. manufactured by Guerbert, France) was gradually
( replaced by water soluble contrast media for several
I reasons including delayed absorption, risk of
{
lipogranuloma formation in case of tubal block or
381
Comprehenst Cynaecology in the Topics
hydrosalpinx, intravasation of contrast and possible cervical stenosis, Because rapid injection may cause
risk of oil embolism and the need for delayed fitrn. lt tubal spasm, a slow injection of usually no more than
however, has the advantages of shalp}@4, 3 to 4 mL of media allows a clear outline of the
minimal pain and doubled pregnancy rate- $ uterine cavity. Generally, only three radiographic
HSGs are done using water soluble contrES,,,Btffi,g$ views are needed preliminary view before injecting
iohexol-omnipaque, meglumine diatrizoete- contrast, a view showing fill of the uterine cavity, and
ffir
u rograff i n, iodob ro m id e a n d grastrograff i n. Tfl6 a third demonstrating spill of contrast from the tubes
soluble contrasts allow for prompt demongtration of into the peritoneal cavity.
tubal patency make the ampullary rugae to be elearly
visualised, get absorbed within hours, without ln carrying out hysterosalpingography the procedure
leaving residue, and very rare risk of granulorna is explained to the patient and an informed consent is
formation, all without the need for a delayed film. obtained. An antispasmodic may be given before the
procedure. The patient is asked to empty her bladder
HSG is usually performed in the late follicular phase immediately before the procedure. The preliminary
of the menstrual cycle to ensure that the patient is not (scout) film is taken and the patient is placed in
pregnant and to prevent false-positive intrauterine lithotomy position. The perineum is cleaned w
filling defects and proximal tubal occlusion due to antiseptic solution (Betadine) and draped with sterrre
endometrial thickening towel. The cervix is exposed using Cuscos or Graave's
speculum and cleansed with povidone-iodine
The use of HSG is not only limited to the evaluation of solution. The anterior lip of the cervix is grasp with
tubal factor infertility but also in the evaluation of tenaculum, the Sparkman's cannula that is made air
pelvic pain, irregular vaginal bleeding, irregular free before administration of contrast. When a Foley
menstrual bleeding, uterine polyps/fibroid, catheter is used, there is usually no need to grasp the
amenorrhea, mullerian abnormalities and/or cervix with a tenaculum. Speculum is then removed
anatomic variants, cervical insufficiency/recurrent and the patient is placed in slight trendelenburg
miscarriages, intrauterine synechiae, position and contrast is slowly introduced, 3 ml
hydrosal pinges, salpi ngitis isthmica nodosum (Sl N), contrast to fill uterine cavity and another 3 ml to fill
and peritubal adhesions, suspected case of genital tube (up to 10 ml) and fluoroscopic films are taken
tuberculosis, prior to or after tubal surgery- selective accordingly. Additional oblique views may be taken
salpingography and tubal recanalization, HSG is also for optimal visualisation of pelvic pathology and
used to assess postoperative uterine cavity integrity, tortuous fallopian tubes (to see retroverted or
such as Caesarean section uterine scar. HSG also anteverted uterus). At the end of ihe procedure an
has a potential therapeutic role in increasing the antibiotic course may be given and patient is
probability of pregnancy especially if oil soluble informed about vaginal spottingfor 1-2 days.
contrast -l i piodol is used.
Care must be taken to expel air from the cannula
The procedure before insertion as these would otherwise cause
Hysterosalpingography is performed between cycle confusion in interpretation from artefacts. Contrast
days 5 and 10, following cessation of menstrual flow medium is injected slowly under intermittent
to minimize infection and the risk of flushing an ovum f uoroscopic control. Ra pid i njection may cause tu ba
I I
from the fallopian tube. lf periods are irregular, urine spasm, a slow injection of usually not more than 5
B-hCG test is done to rule out pregnancy. The mL of media allows a clear outline of the uterine
procedure causes cramping and a non-steroidal anti- cavity. Spasm of the uterine cornua may be relieved
inflammatory drug taken 30 minutes prior to the by giving intravenous glucagon. Films are taken using
procbdure may minimize discomfort. A Leech- the under couch table and as the tubes begin to fill
Wilkinson's cannula, acorn cannula, paediatric anteroposterior (AP), right oblique and left oblique
Foley catheter, or designated injection catheter is views are taken.
introduced just inside the external cervical os and
contrast media is injected. A paracervical btock may There are many variations in the appearance of a
be indicated in selected patients, such as those with normal HSG. The endometrial cavity is usually
382
tr
D ia gnosti c P roced u res I n Gy n aecol ogy
triangular or sometimes T-shaped in the Allergy to contrasts, pregnancy, active uterine

anteroposterior projection. ln the lateral view it is bleeding and active pelvic inflammatory disease are
oblong. The contour of the endometrium is usually contraindications to HSG. HSG is usually performed
t. smooth. lt occasionally appears to have polypoid- in the late follicular phase of the menstrual cycle to
filling defects that can be isolated or diffuse, and can ensure that the patient is not pregnant and to prevent
be difficult to distinguish from endometrial polyps or false-positive intrauterine filling defects and
hyperplasia. lnadvertent injection of air bubbles proximal tubal occlusion due to endometrial
introduces artefact. thickening.
Complications
Complications of HSG are rare but can be serious.
The overall risk of acute pelvic infection serious
enough to require hospitalization is less than 1
percent, but may be up to 3 percent in women with
prior pelvic infection. Because of serious morbidity,
routine antibiotic prophylaxis is given such as
doxycycline orally, 100 mg twice daily, beginning the
day before HSG and continued for 2 more days
thereaf ter. ln add ition, pelvic pa in, uterine
perforation, and vasovagal reactions may occur.
Complications from the contrast include allergic
reactions and entry into the vascular system with
high injection pressures. Embolic phenomena,
pelvic peritonitis, and granuloma formation with oil-
based contrast agents are rare.
Fig. 4 HSG-Normal Anatomy Role of HSG in West African Sub-region

Hysterosalpingography is a valuable technique in the
evaluation of the infertile woman. lt therefore plays a
crucial role in the West African Sub-region in the
evaluation of patients with infertility and the other
indicated gynaecological conditions. lt is of
diagnostic value in the investigation of the cervical,
uterine and tubal factors in female infertility and still
remain the goal standard in terms of imaging
techniques. lt is a cheap, safe and rapid diagnostic
tool. Despite the development of other diagnostic
:
tools such as magnetic resonance imaging,
hysteroscopy and laparoscopy, HSG remains the
main examination for the fallopian tubes in the
developing countries. ln sub-Saharan Africa tubal
diseases is usually due to poorly treated pelvic
infections, including pelvic tuberculosis, pelvic
surgeries and endometriosis. In developing countries
a Fig. 5 Bilateral hydrosalpinges
where complimentary diagnostic test Iike
laparoscopy and chromotubation is not routinely
Source: Dallas IVF
available the diagnostic test of choice for tubal
patency is HSG. Lack of expertise in modern imaging
I techniques and endoscopic procedures also makes
hysterosalpingography a handy tool in the evaluation
383
Comprehens Gynaecology in the Topics
of the uterus, tubes and peritoneum. Western Nigeria. Afr J Med Health Sci
Controversies 2014;13:19-23
1. As vital as hysterosalpingography may be, iE use 4. Tshabu-aguemon C, Ogoudjobi M, Obossou A,
is surrounded by a number of controversies. The use King V, Takpara l, Alihonou E. -.
of antibiotics before and after HSG in patients in Hysterosalpingography and Laparoscopy in
whom no documented genital tract infeetion \a/as Evaluating Fallopian Tubes in the
made is discouraged by the opponents while the
proponents of antibiotic use believe it should be used Republic. Journal of the West African College
of Surgeons 2014;4Q):66-75. !
routinely to prevent the spread of microorganisms
5.
from the lower genital tract to upper genital tract.
evaluation of infertility in the Niger Delta. lnt
2. Opiate analgesics are believed to cause tubal
if
spasm used prior to hysterosalpingography 6. Bend ick AJ. Present status of
procedure. The proponents believe that pain, cervical fertil steril 2013; 83
Hysterosalpingography.
manipulation and rapidity of contrast media (6):1595-606.
introduction rather than opioid analgesic is 7. Elysia M. Techniques Used for lmaging
responsible for the tubal spasm. The opponents Gynecology. ln: Schorge J0, Schaffer Lr,
suggest that non-steroidal anti-inflammatory drugs Halvorson LM, Hoffman BL, Bradshaw KD, \:
or glucagon should be used prior to HSG to prevent Cunningham FG (Eds), Williams'
tubal spasm. HSG in a patient with an intact hymen Gynaecotigy, 2"
edition. IJSA. The McGraw-
being investigated for congenital anomaly is H i I I Compan ies. 2008; 2:
controversial, as some believe is invasion of privacy. 8. Perisinakis K, Damilakis J, Grammatikakis J. '.
Ra d i oge n c r i s ks f ro m hy ste rosa I p i n gogra p hy.

lmprovement of fertility by oil based media is also i
controversial.
EurRadiol 2003; 13:1522-1528. 1
Conclusion
ln conclusion hysterosalpingography plays an
V. ULTRASOUND IN GYNAECOLOGY
important role in the initial diagnostic work up of
couples with infertility. The most common pathology
lntroduction
based on HSG in infertility women in developing ln the evaluation of patients, the Gynaecologist often
country is tubal blockage possibly secondary to employs various tools. A very important investigative
previous unsafe abortion, pelvic inflammatory tool that has found relevance in the practice of
disease and puerperal sepsis. Hence, most of the gynaecology is the ultrasound scan. This tool has
women presented with secondary infertility. evolved over the years; from the simplest of forms, to
highly complex multi-dimensional consoles, that aid
in diagnosis of diseases, treatment, and follow up of
patients. ln this write up, we will discuss the history
References
of ultrasound, and principles governing it's use, as
1. Jonathan K, Daru PH, Ekedigwe J. well as situations where its use is appropriate.
Hysterosalpingographic evaluation of 998
Definition
consecutive infertile women in Jos, Nigeria.
lnternational journal of Gynaecology, FIGO,
Gynecologic ultrasonography or gynecologic
2010; 108:255-257. sonography refers to the application of medical
2. Dasan TA, Basawaraj NG. A comparative study ultrasonography to the female pelvic organs
' of saline infused sonohysterography and (specifically the uterus, the ovaries, and the fallopian
conventional hysterosalpingography in the tubes) as well as the bladder, the adnexa, and the
evaluation of female infertility. West Afr J Pouch of Douglas.
Radiol 2016;23:124-9
3. Danfulani M, Mohammed MS, Ahmed SS, History
Ha ru na YG. Hysterosa I ph i ngogra ph ic f i nd i ngs The history and evolution of diagnostic
in women with infertility in Sokoto North ultrasonography has been founded on the combined
384
{ r
(
).
Di agnostic Proced u res I n Gynaecology
I
I efforts of phvsicists, engineers, computer scientists, transducer is housed, the control panel, the freeze
t
-t doctors, sonographers, physiologists, university frame, measuring facilities and a means of storing
r researchers, as well as large commercialcompanies. images.
t ,\-
I
ln Obstetrics and Gynaecology, the history of

I sonography dates from the classic 1958 Lancet Routes of Ultrasound
;
paper of lan Donald and his team from Glasgow. There are various routes for carrying out ultrasound
Professor lan Donald published in 1958 his use of eXdrTls; depending on the body part to be evaluated,
I ultrasound to detect abdominal tumors and cysts and available technology and the skill of the examiner.
laterwas able to detect a twin pregnancy.
While ultrasound examinations are mostly
Many others have contributed to the development of superficial (e.9. transabdominal), transvaginal
this important device which has evolved over time examinations are increasingly being relied on for
from the days of the A mode to complex 3Dl4D diagnosis in gynaecology. Transrectal examinations
systems now. have also found increased use by urogynaecologists. .
Princi ples of U ltrasound Uses of ultrasound in gynaecology

I
Ultrasound describes sound of frequencies above 20 Ultrasound is the standard-of-care imaging modality
000 Hertz (Hz), beyond the range of human hearing. for initial imaging in obstetrics and gynecology.
Frequencies of 1-30 megahertz (MHz) are typical for Hardly is any gynaecological evaluation complete
diagnostic ultrasound. Diagnostic ultrasound without an ultrasound scan. The reasons for this are
imaging depends on the computerized analysis of the ready availability, non invasive nature and
reflected ultrasound waves, which non-invasively relative low cost of the ultrasound assessment. lts
i
build up fine images of internal body structures. The use is however quite operator dependent: with
resolution attainable is higher with shorter increasing proficiency as more examinations are
wavelengths, with the wavelength being inversely done. As stated by the WHO Scientific Group on
proportional to the frequency. However, the use of Clinical Diagnostic lmaging, "more important than
high frequencies is limited by their greater the equipment is the availability of skills. An error in
attenuation (loss of signal strength) in tissue and thus diagnosis because of inadequate education and
r shorter depth of penetration. For this reason, different experience is as dangerous as being without the
ranges of frequency are used for examination of equipment, and the success of any interventional
difierent parts of the body: procedure is very dependent on the skill and
!
3-5 M Hz forabdominal areas experience of the responsible physician." ln

5-10 MHz for small and superficial parts, as particular, the effective use of an ultrasound scanner,
well as transvaginal, and although less expensive than other imaging
1 0-30 MHzforthe skin orthe eyes. equipment, is very dependent on the physician.
The ultrasound waves are generated from the probe, ln the hands of an experienced operator, ultrasound
and travel through the tissues of the patient, and then has the following potential uses in gynaecology:
return to the probe as they encounter tissues of
different densities. The intensity of the returning echo Diagnostic uses i ncl ude:
determines brightness of the image on the screen. o Evaluation of the menstrual cycle
Strong signals produce white, or hyperechoic, (endometrial thickness, fol I icu lar
images. Weak echo signals returning to the probe development)
transraie into dark, black, or hypoechoic, images on o Monitoring natural or stimulated follicular
the ultrasound screen. Different tissues show varying development during
i nfertility management
shades of gray, from white to black, depending on
their density.
o Localization of an intrauterine device
. Evaluation of abnormal uterine bleeding
I The Ultrasound equipment currently available varies
o Assessment of a pelvic mass (eg,
greatly in size, shape and complexity, but will contain adenomyosis, fibroid, cysts or other
masses)
basic components like the probe, in which the
. Evaluation for sequelae of pelvic infection
385
(eg, abscess, hYdrosalPinx) 175-183 Q010.

. Evaluation of congenital uterine anomalies
2. Campbelt, S. A short history of sonography in
obstetrics and gynaecology. Facts, views &
o Screening for malignancY
vision in ObGYn 5, 213-29 Q013)
Therapeutic Uses
3. Effective choices for diagnostic imaging in
. clinical practice. Report of a WHO Scientific
As an adjunct to ultrasound guided
Group. Geneva, World Health Organization,
procedures such as cYst drainage'
egg retrieval, injection of methotrexate or
lggo (WHO Technical Report Series, No'
79O.
hypertonic saline in unruptured ectopic al'
pregnancY, etc.
4. Barnett SB, Rott HD, ter Haar GR, et The
sensitivity of biotogical tissue to ultrasound'

. High intensity focused ultrasound for the U ltrasound Med B iot' 1 997 ; 23/6) : 805- 1 2'
treatment of fibroids 5. /SUOG Bioeffects and Safety Committee;
Safety statement, 2OOO 1econf i rmed 2002'
Safety of ultrasound in gynaecology lJ ltrasound Obstet Gy necot. 2002; 1 9 : 1 05' 8'
Although no adverse effects of ultrasound scan have lde M. Japanese policy and status of stand-
been reported, bio-effect and safety issues have been ardisation. lJltrasound in Med Biol'
studied and discussed by various medical ultrasound 1986;12:705-8.
organizations. lt is emphasized that, for safe use, 6. Debenedectis, C.M. & Levine, D' lncidental
ultrasonic examinations are only performed when genitourinary findings on obstet-
medically indicated. Secondly, the users are ricslgynecology u!trasound' Ultrasound
responsible for safety and should recognize that q ua rte rtY 28, 293- 8 Q0 1 2)
biological tissues of developing embryos and fetuses 7. Seshadri, S.; El-ToukhY, T'; Douiri, A';
may be damaged by intense ultrasound' The main Jayaprakasan, K.; Khalaf, Y. Q014)' "Diag-
biological effect is the thermal effect due to the nostic accuracy of saline infusion sonography
temperature rise induced by ultrasound absorption'
in the evatuation of uterine cavity abnormali-
ties prior to assisted re productive techniques:
as teratogenicity was reported in fetal animals
exposed to high temPerature.
a systematic review and meta-analyses"'
Non-thermal effects of ultrasound are inertial Human ReProduction lJPdate' 21
cavitation and other mechanical effects. Diagnostic
(2):262-274
doi : 1 O. 1 093 I h u mu Pd ld m u057
ultrasound users are requested to know the
8. Seshadrr, S. et a/. The evolving role of saline
ultrasonic intensity of their devices, the mechanisms infusion sonography (S/S) in infertility'
of ultrasound bio-effects and hence the need to use European Journal of Obstetrics Gynecology
their instruments PrudentlY' and Reproductive Biotogy 185,66-73 Q015)
Conclusion
Ultrasound is a key first line imaging modality ln VI. SONOHYSTEROGRAPHY
obstetrics and gynaecology. lt is cheap, painless,
inexpensive and has a long safety record in lntroduction
pregnancy. lts use as a screening and diagnostic tool Sonohysterography (SHG) is also called saline
is dependent upon the technical skill of the operator infusion hysterograPhY (SlS).
and their ability to interpret the scan findings' lts
proper use no doubt has the potential to allay the It is a technique in which the endometrial cavity is
anxiety of patients and provide useful information for distended with a negative contrast medium during
the healthcare Provider' ultrasonic examination and it permits single layer
evaluation of the endometrial lining and enables the
sonologist to reliably distinguish focal from diffuse
References endometrial pathologic conditions.
It may also be used to assess tubal patency' An

1. Morgan,5., Unipan, A' &Datta, S' Ultrasound
in obstetrics and gynaecology' Obstetrics, increase in the amount of free fluid in the pelvic
Gynaecology and Reproductive Medicine 26, cavity or cul-de-sac at the end of the procedure
385
--
Diagnostic Procedu res I n Gynaecology
indicates that at least one tube is patent. The exposure, a low-tech procedure and easy to
principle of SHG, is based on the use of ster:ile saline performu.
solution (transcervically) as a nggative. csntrast SHG in combination with endometrial biopsy has a
med im i n conj u nction with traditional'tBrwagi nal
u very high sensitivity and specificity in identifying
ultrasound, thereby scanning the uterus, ovaries and anatomic and abnormal pathologic findings.
pelvis at the same time imaging the uterine cavity;
Limitations
this helps to determine whether an abnormality is
The limitations of SHG include time spent (time
endometrial or sub-endometrial.
consuming) about 15 minutes per patient and
patients discomfort'.
The anechoic interface provided by the saline allows
good intrauterine cavity visualizationl,
The techniques and procedural steps ideally should
be performed in the follicular phase of the menstrual
The indicationsforSHG include evaluation of: cycle after cessation of menstruation (between day
1. Abnormal uterine bleeding' 7- 1 0), because the endometri um is thin at this point.
2. Uterine cavity fibroids, polyps and A thin endometrium is critical so that saline can more
synechiae' easily distend the uterine cavity and better
3. Abnormalities detected on endovaginal accentuate endometria I pathology.
sonography such as focal or diffuse
endometrial or intracavitory abnormalitiest Furthermore, irregularities in the contour of the
4. Congenital or acquired abnormalities of the endometrium may be misinterpreted as small polyps
uterus' or focal areas of endometrial hyperplasia.
5. Fertility work upl
6. Recurrent pregnancy loss' Although anesthesia or analgesia is not required, a
7. Suboptimal visualization of the endometrium non-steroidal anti-inflammatory drug may be offered
on TVS' 30mins prior to the procedure to help reduce pain or
8. Screening before an invitrofertilizationo cramping'.
9. Endometrial hyperplasia and orcarcinoma'
10. Women on tamoxifen therapy' A negative pregnancy test must be obtained before
1 1. Women on hormone replacement therapy'
the procedure.
Contrai nd ications i nclude; Active pelvic disease must be treated prior to

1. Pregnancy' procedure. Patient should be counseled about latex
2. Pelvic infection' allergy and or a reaction to betadine or other topical
3. Unexplained pelvic tenderness'
antiseptic before use of the products'.
4. Active/excessive vaginal bleeding'
5. Late luteal phase due to risk of possible early Where there is evidence of non-tender,
cyesiso
6. Presence of IUCD in-situ.'
hydrosalpinges (from a pre-procedural imaging)
consideration may be given to prophylactic
Advantage of SHG over traditional transvaginal administration of antibiotics just priorto procedureo,
ultrasound alone lies in the fact that it is able to
Procedure
identify myomas, polyp, thickened endometrium and
The procedure involves obtaining a verbal consent
able to differentiate between potential causes of a
and brief gynaecological history.
thickened endometrium.
o The patient then empties her bladder, and
{t also has an advantage over hysteroscopy in that it
bimanual pelvic exam is done with the
patient in lithotomy position.
can scan the uterus, ovaries and pelvis at the same
A speculum is used to expose the cervix
time it images the uterine cavity.
which is then cleansed with betadine or
Further advantages of SHG include its low cost, other appropriate antiseptic swab.
A size 5-7 F catheter is then introduced into
tolerability by patients, effectiveness, no radiation
387
the uterine cavity via the cervical os; aided

by a ring forceps. prior to introduction of the
catheter, it is important to flush it with sterile
saline solution to prevent the introduction of
air bubbles, which can be echogenic and
give a false positive resultr.
Other catheter types in use include:

1. 5-7 F catheter with or without an occlusive
balloon'
2. Pediatricfeedingtube,
3. lnsemination catheters2
4. Goldstein sonohysterographycathetef
The catheter balloon tip is inflated with 1_2 mls of
saline. The speculum is then removed. A standard
trans-vaginal ultrasound probe covered with latex
Fig. 7 Saline Sonogram revealing endometrial polyps
condom is inserted alongside with the catheter.
Twenty{orty mls of warm sterile saline is instilled into

the endometrial cavity using a 20ml syringe attached Common technical difficulties
in performing SHG
to the catheter while the transducer is moved from include variable uterine position which way
side to side (cornua to cornua) in a long axis position. complicate catheter insertion, cervical stenosis
which may require dilatation or use of guard wire,
The amount of fluid instilled will vary depending on
and inhibited visualization of endocervical cana18.
distension of the uterus and patient tolerancer.
Accidental air introduction from un-flushed catheter
Normal endometrial findings on SHG include smooth
may lead to an echogenic artifact that can obscure
non-distorted endometrium with uniform ouiline.
abnormalities. Another pitfall that may occur is back
An abnormal endometrial cavity on SHG will flow of saline from around the balloon and out
be
through the cervix resulting in non-distension of the
uterine cavity.
This may be overcome by retracting the balloon to
occlude the internal cervical os. Blood clot,
intrauterine debris, dislodged cervical mucus may
mimic a masso.
Complications
Complications that may result from the procedure
include''':
1. Cramping pelvic pain
2. Nausea
3. Vagal symptoms/response
4. Failure to complete procedure due to
cervical stenosis, scarring, and patulous
cervix
5. Postprocedurefever
6. Post procedure bleeding/spotting
Fig. 6 Normal Saline Sonogram
7 . Post procedure infection
8. Cancerdissemination
Pre and post procedure care includes counseling the
388
{
Di agnostic Proced ures I n Gynaecology
patient on the possibility of pain, inqreased vaginal References

i
spotting and watery vaginal diseharge that are
usually self-l im iting. 1. Parsong Ak, Lense JJ. Sonohysterography
for endometrial abnormalities: preli minary
Sonohysterography is a simple, safe and convenient
resu lts Jcu 1993 ; 2 1 : 87 -95.
technique that is easily and rapidly perf.ormed in the 2. Goldstein SR. Use of ultrasonography for
I
ultrasound room.
triage of perimenopausal patients with
unexplained uterine bleeding. AMJ Obstet
Controversies
Gynecol 1994; 170: 565-570.
Many opponents believe that the procedure has a low
specificity, adds to the patients'discomfort, costs, as
3. Seoud MAF, Johnson J. Gynecologic
tumours in tamoxifen treated women with
well as a potential dissemination of infection and or
breast cancer. Obstet Gynecol 1993;
malignancy, which are in fairness notspecific to SHG.
As convenient and relatively cheap as it is, the 82:165-169.
technique seems to be underutilized in the West
4. Richman TS, Viscomi GN, deCherney A,
j Polon ML, Alcebo LO. Fallopian tubal
Africa sub-region due to7
patency assessed by ultrasound following
- Low number of gynecologist experienced in fluid injection. Radiology 1984; 81:66A-
SHG
664
- The training curriculum does not seem to 5. Syrop CH, Sahakian V. Transvaginal
promote its use sonographic detection of endometrial polyp
- Decreased request for SHG by practitioners with fluid contrast augmentation. Obstet
- Poorsupervisionandaccountability Gynecol 1992; 7 9 : 1 041 - I 043.
- Poor continuing medical education in 6. Cohen JR, Luxman D, Sagi U, Wolman Yl,
traini ng/ monitoring of performance David M P. Sonohysf e rography f or

d i sti ngu i sh i ng endometri a I th icken i ng f rom
SHG can play an important role in the work-up of endometrial polyp in postmen pausal
patients with infertility, abnormal vaginal bleeding or bleeding. Ultrasound Obstet Gynecol
incidental intra-cavity lesions found on routine pelvic 1994;4:227-230
u ltrasonography. 7. Badu - peprah A, Odoi AT, Dassah ET, Amo-
wiafe Y. Sonohysterography: time to step up
The optimal use of SHG technique including ifs use in gynaecologic imaging in West
appropriate balloon inflation, location and Africa. Afr J Reprod Health 2011 Sep; 15
endometrial and endocervical canal distension can G):133-139
preclude the technical pitfalls of SHG and improve 8. Kamel HS, Darwish AM, Mohammed SA.
visualization of the endometrium allowing more Comparison of trans-vaginal
accurate delineation of various endometrial ultrasonography and vaginal
pathologiesu'u. sonohysterography in the dete,ction of
endometrial polyps Acta Obstet Gynecol
Scand 2000; 73:406-11.
:
)
389
f I
r
(
i
i
CHAPTESS
i
:
The Menstrual Cycle
EY Kwawukume and K. Adu-Bonsaffoh
lntroduction physiological changes are described as periodic

Physiological regulation and occurrenceof normal preparations for ferti I ization a nd pregna ncy'.
menstrual cycle is dependent on optimal
coordination of specific components of processes in Comprehensive knowledge of the menstrual cycle
the body such as the hypothalamus, pituitary, ovaries events and mechanisms represents the backbone of
and the uterus. Menstrual disorders including fertility critical appraisal of the pathophysiology and
abnormalities therefore originate from inappropriate management of the reproductive dysfunction such as
regulation and control of this complex system in any infertility and diseases related to the menstrual
of the above organs. ln this chapter we present irregularities.
relevant physiological regulation and mechanisms of
normal menstrual cycle and clinical correlates NORMAL MENSTRUAL CYCLE
associated with specific dysregulation in the
pathway. The normal menstrual cycle is characterized by
normal regularity, volume of blood loss, duration of
Menstrual cycle defines series of regular cyclical menstrual flow and frequencyo. The duration of
i
changes in the ovaries and uterus experienced by normal menstrualflow rangesf rom2-6 dayswith the
non- pregnant women in their reproductive years mean of 5 days whereas the cycle length ranges from
from the onset of menses (menarche) to cessation of 2l-35 days with an average of 28 days. However,
menses (menopause). During the course of a single only about 15 % of women have normal menses with
menstrual cycle, concurrent physiological changes a cycle length of 14 days. The normal menstrual
occur in the both the ovaries and the endometrium blood loss (menstruum) is approximately 30mls and
characteristically referred to as ovarian and the blood loss of 80mls or more is described as excessive
uterine cycles respectively'''. The ovarian cycle which requires evaluation and treatment5'
represents series of physiological changes associated
Menarche describes the first menstrual flow which
with the oogenesis or follicular development,
occurs around the time of puberty with the mean age
ovulation and luteinization and luteolysis. The uterine
of menarche which indicates the onset of maturity of
cycle constitutes the physiological growth of the
endometrial glands and stroma and the conversion of
the hypothalamo-pituitary axis and reproductive
potentia16. On the other hand, menopause describes
the estrogen primed endometrium into secretory
the final menstrual flow which marks the end of the
nature adequately prepared for anticipated
reproductive period. The mean ages at the onset of
implantation of fertilized ovum. ln the course of the
menarche and menopause are 72.8 and 48 years
I
, menstrual cycle, the follicular and luteal phases
occurring in the ovary correspond to the proliferative
and secretory phases in the endometrium and these
391
Comprehensive Gynaecolagy in the Topics
Menstruation marks the beginning of the mcnstrual evidence that eonstaRt, non-pulsatile release of
cycle so that the first day of menstrual flow is GnRH results in suppression of gonsdotrophin
considered the first day of the prolifefltiw Shsde, rel€ase from the pituitary gonatotropes due to
About 75% of menstruum is predominatffi ffi+a{ desensitization or down regulation of pituitary GnRH
with venous blood constituting approxime@ 8S%. receptors with cessatisn of the eascade to the
The menstruum does not normally clot kserffi ft€ ovarlest.
endortetrial tissue contains relatively larEB affiounts
of fibrinolysin which lyses initial clot forrnation so Generally, GnRH is not detectable in the peripheral
menstrual blood does not normally contain clots circulation and therefore pulsatile release of LH is
except when there is heavy menstrual flow. normally studied to provide the necessary
information about the GnRH secretion in
HYPOTHALAMO.PITU ITARY.OVAR!AN AXIS physiological (ovulatory) and pathological conditions
in clinical practice. The pulsatile release of LH which
The optimal and appropriately regulated function of is reflective of GnRH pulses is detectable between l
the hypothalamo-pituitary-ovarian axis constitutes 60-90 minutes during the follicular phase of the
the backbone of the normal menstrual cycle. This menstrual cycle. The use of FSH pulses is nr
complex pathway comprises the hypothalamus recommended due to its longer half-life compared to
which secretes Gonadotrophin releasing hormone that of LH. During the luteal phase of the menstrual
:
(GnRH) in a pulsatile fashion (initiated by GnRH cycle, the amplitude of LH pulsatile secretions are 1
pulse generator), anterior pituitary which produces significantly higher whiles the frequencies are
gonadotrophins upon GnRH stimulation, ovaries markedly lower compared to that of the follicular
produce estrogens and progesterone which are phase. lt
is important to emphasize that the
involved endometrial proliferation and maturation fluctuations in the frequency and amplitude of GnRH
respectively. The menstrual cycle is primary pulsatile release are pivotal in determining the
controlled by the GnRH pulse generator which is a pattern of release of FSH and LH with subsequent
hypothalamic structure that secretes GnRH'''. The regulation of ovulatory ovarian cycleu't.
whole process commences with the synthesis and
release of GnRH from specific neuronal endings of Adequate knowledge of the physiological basis of the
the hypothalamus into the portal vessels to the secretory pattern GnRH and gonadotrophins is vital
anterior pituitary. The GnRH stimulates the to understanding pathophysiology and treatment of
gonadotropes of the pituitary to produce several reproductive disorders such as induction of
gonadotrophins (FSH 'and LH) which in turn ovulation for women who have hypothalamic
stimulate the ovaries to produce estrogens and hypogonadotroph ic hypogonad ism.
progesterone. There are well co-ordinated ovarian
hormonal feedback loops or mechanisms (short and
long) which control the hypothalamic and the TWO CELL-TWO GONADOTROPHIN THEORY
pitu itary activitiess.
Follicle stimulating hormone and luteinizing
GnRH is normally secreted in a pulsatile manner with hormone are the main gonadotrophins that regulate
specific frequency and amplitude that determines the the menstrual cycle by acting mainly on the theca
regulation of the secretion of the gonadotropins and and granulosa cells respectively. Estrogen and
these pulses are different in the follicular and the progesterone are synthesized in the ovaries mainly
luteal phases of the menstrual cycle. The from cholesterol derived from the blood but also to a
gonadotrophins are also released in pulsatile fashion slight extent from acetyl coenzyme A, multiple
as resultant effect of the specific frequency and molecules of which can combine to form the
amplitude of GnRH secretion. This pulsatile release appropriate steroid nucleus.
of GnRt-t and variations in the pulsatility pattern in
During synthesis, mainly progesterone and
different phases of the menstrual cycle are integral
androgens (testosterone and androstenedione) are
characteristics in the optimal physiology resulting in
synthesized first; then, during the follicular phase of
ovulation and ovarian steroidogenesis. There is
392
The Menstrual Cycle
the ovarian cycle, before these two initial hormones activity of which is stimulated by FSH'
can leave the ovaries, almost all the androgens and During the luteal phase of the cycle, far too much
much of the progesterone are converted into progesterone is formed for all of it to be converted,
estrogens by the enzyme aromatase in the granulosa which accounts for the large secretion of
cells. Because the theca cells lack the arornatase, progesterone into the circulating blood at this time.
they cannot convert androgens to estrogens.
However, androgens diffuse out of the theca cells into ln summary, the two cells-two gonadotrophin theory
the adjacent granulosa cells, where they are describes the co-ordinated functions of the theca
converted initially to estrone and then into estradiol cells and granulosa cells of the follicles regulated by
(estrogen) by aromatase in the granulosa cells, the LH and FSH resulting in the biosynthesis of estrogen
in the ovary.
TWO CELL.TWO GONADOTROPHIN THEORY

I
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FOLICULOGENESIS birth. At the time of birth, there are 2 million ova but
50% of these are atretic. The million that are normal
Folliculogenesis describes the process of recruitment undergo the first part of the first meiotic division at
of primordial follicle with subsequent development about this time and enter a stage of arrest in
into a mature graafian follicle capable of ovulation. lt prophase in which those that survive persist until
is a !,:ng process comprising follicular growth by cell u.
adulthoodu Atresia continues during development
proliferation, follicular fluid formation, growth and and the number of ova in both of the ovaries at the
m itosis of th e cel ls fol licle. time of puberty is about 300,000. Only one of these
ova per cycle (or about 500 in the course of a normal
ln humans, no new ova are formed after birth. During
reproductive life) normally reaches maturity. The
t fetal development, the ovaries contain overT million
rema i nder degenerates.
primordial follicles. Many of them undergo atresia
(involution) before birth and others are lost after The follicles are divided into two main types namely
393
preantral and antralfollicles whose development are secondary oocyte. The theca interna cells express LH
gonadotropin independent and gonadotropin receptors and differentiate into theca interstitial cells
dependent, respectively. The preantral follicle capable of undergoing steroidogenesesis whereas
includes the primordial, primary, secondary and the outer layer of thecal cells differentiate theca
tertiary whereas the antral comprises the graafian externa cell containing smooth muscles innervated
and pre-ovulatory follicles. The recruitment of by the autonomic nervous system lt has been
primordial follicle commences with the conversion of hypothesized that the smooth muscle cell in the
granulosa cells from a squamous to a cuboidal cells theca externa with autonomic regulation contributes
and initiation of mitosis in the granulosa ce[[s' to mechanism involved in ovulation. On the other
Folliculogenesis occurs in the ovarian cortex and hand the granulosa cells express FSH receptors
results in the production a single dominant follicular which may be stimulated by plasma FSH. The
growth from a pool of several growing follicles. The oocytes complete its growth at the secondary oocyte
process of folliculogenesis involves recruitment of stage although the follicte attains the size o'f 2cm or
pri mord ial fol icles, preantra I fol icu la r development,
I I more before ovulation. The structure of the
selection of dominant follicle, and atresia of secondary oocyte comprises a zona pellucida
remai n i ng fol I icles''u. surrounding the oocyte, granulosa cells, basal
lamina, theca interna and theca externat.
A primordial follicle is a small primary oocyte,
consisting of a single layer of squamous granulosa The development of the tertiary oocyte is signaled by
cells surrounded by a basal lamina, that has been the occurrence of cavitation and antrum formation
arrested in the diplotene stage of the first meiotic cell with fluid accumulation between the granulosa cells.
division. This structure subsequently differentiates into
graafian follicle consisting of antrum containing
A secondary oocyte is a preantral follicle surrounded follicularfluid or liquorfolliculiwith the oocyte in situ
by a stratified epithelium comprising 2 to 10 layers of as shown in Figure 1. The final structure of the
cuboidal or low columnar cells. The mechanism for graa'fian follicle comprises a central antrum
the transition from a primary to a secondary follicle containing follicular fluid and oocyte surrounded by
involves the acquisition of a second layer of granulosa the granulosa cells, basal lamina, theca interna and
cells through continuous mitotic cell division of the theca externa and basic structure remains the same
granulosa cells. This is followed by the formation of although there may be significant changes in the
the theca layer around the basal lamina consisting of follicular size. The granulosa cells surrounding the
the inner theca interna and outer theca externa. The oocyte in the graafian follicle has four main layers
process of theca formation is accompanied by comprising the innermost cells around the oocyte
angiogenesis with development of blood vessels that called the corona radiata followed by the cumulus
circulates around the follicle to provide nutritive oophorus, then periantral layer and finally the
including hormonal and excretory functions for the outermost cells called the membrana granulosa'
394
rr
The Menstrual Cycle
t7
tF Fig. 1: Follicular development from Primordial follicle to Graafian follicle
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395
r-------:--l
SELECTION OF DOMINANT FOLLICLE follicular phase are primarily controlled by follicle

stimulating hormone (FSH). This FSH is produced by :
A cohort of approximately 20 primordial folliehs are the gonadotropes in the pituitary following prior
recruited to undergo further gro=w"t& A'nd induction by GnRH from the hypothalamus.
differentiation for ovulation at the comrxq$@1+!06 OVULATION
each menstrual cycle. Usually only oii6]-S.'-@f
follicles is finally selected and prepared as the Ovulation describes the release of mature viable
dominant follicle for ovulation. The fol]icle that haS svum from the Graafian follicle in the ovary. lt is an
developed most FSH receptors and therefore megt essential transitional event that separates the
sensitive to FSH is intrinsically selected as thQ follicular and luteal phases of the menstrual cycle.
dominant follicle for the ovulatory cycle because of its The whole process of follicular development,
ability to produce most estrogen and inhibin through ovulation and luteinization is integrated in the
hypothalamlc-pituitary-ovarian (HPO) axis with
i
i ncreased a romatase activity3.
specific roles played by the gonadotropin releasing-
lncreasing levels of estrogens and inhibin B resuft in .hormone (GnRH), FSH, LH, estrogen and
negative feedback effect on the hypothatamus and prggesterone with contribution from inhibin and
the pituitary with subsequent drastic reduction in the activin. The major processes preceding ovulation
secretion of FSH from the pituitary. ln such adverse include recruitment of multiple follicular
environment of markedly reduced circulating FSH development, dominant follicular selection (by day
l
levels, the follicle that has developed the most FSH 7) and further growth, positive feedback mechanism
receptors and hence most sensitive to FSH cont.inues involving the estradiol and the pituitary and
to thrive and survives by producing most estrogens hypothalamus with the resultant LH surge which is
and becomes the dominant follicle which will be followed by ovulation within 24-36 hoursu'''. Some
ovulated. The remaining folticles succumb to the women experiences lower abdominal pain in the iliac
short period of starvation undergo atresia while the fossa during ovulation and this is characteristically
dominant follicle continues with the journey of called mittelschmerz pain which may be due to
fol I i cu I a r development to pre-ovu latory stage. peritoneal irritation by the blood from the ruptured
follicle or from ischemia due to excessive stretching
OVARIAN CYCLE of the ovarian capsule priortofollicular rupture.
The ovarian cycle represents a parallel series of The mechanism of ovulation is not clearly
events of the reproductive cycle occurring in the understood. However, there evidence that the
ovary and is subdivided into the three phases ovulatory process begins with swelling of the outer
namely; the follicular phase, ovulation and luteal follicular wall close to the site of the oocyte resulting
phase. During the iourse of the ovarian cycle the in the formation of a small central nipple like
endometrium also undergoes successive changes protrusion called stigma. Progressive fluid
which are parallel but reflective of the events accumulation resulting in increased intrafollicular
occurring in the ovary. pressure is a major contributory factor. Other
proposed mechanisms include proteolytic enzyme
Follicular phase
activity on the follicular wall, morphological changes
The follicular phase of the ovarian cycle commences
in the stigma, perifollicular ovarian smooth muscle
on the first day of the menstruation and ends with
contractions and perifollicular vascular changes'..
ovulation of mature graafianfollicle. Characteristic of
Fluid exudation occurs from the follicle through the
the follicle phase is the recruitment and development
stigma which shortly ruptures openly with release of
of between 15 to 20 primordialfollicles, selection of
viscid follicular fluid containing the ovum and the
the dominant follicle through the process of
surrounding corona radiate cells. The ovum is then
folliculogenesis (described above), preovulatory LH
picked up by the fimbria ovarica, a specialized long
surge from the positive feedback from follicular
fimbria, and directed in the ampulla of the fallopian
estradiol production resulting in ovulation''u. The
tu be for possi ble ferti I ization''u.
events associated with folliculogenesis in the
396
The Menstrual Cycle
The oocyte resumes the first meiotic cell division just luteum in the process called luteolysis resulting in
before ovulation after its development had been the formation scar tissue called corpus albicans. The
arrested in the diplotene phase from.the,.embryonic process of luteolysis describes the loss of luteal
i
lf- life. Further oocyte development to the function and subsequent involution of the corpus
metaphase ll phase and the second rneffie division luteum with characteristic decrease in the synthesis
r is finally completed and spermatozoon pendrates the of progesterone. The luteal phase is therefore
ovum. relatively constant (approximately 14 days) as it is
r closely linked to the life span of the corpus luteum
r Luteal phase: compared to the wide variable associated with the
I The luteal phase represents the second half of the follicular phase depending on the menstrual cycle
ovarian cycle and commences after ovulation length3''0.
following LH surge and ends with the onset of
If menstruation which represents the beginning of the ln clinical practice optimal concentration of
{ next menstrual cycle. Preovulatory surge of progesterone is essential for endometrial preparation
Luteinizing Hormone (LH) from the pituitary gland for implantation and embryonic survival and
r due to positive feedback loop results in induction of therefore inadequate progesterone production by the
LH receptor activation on the follicular cells with corpus luteum constitutes a major etiology of
{t subsequent initiation of ovulation. The remaining i nfertil ity and miscarriage.
structure ovulated in the ovary is initially transformed
( into blood-filled structure called corpus ENDOMENTRIAL CYCLE
{
i hemorrhagicum and then to the corpus luteum by LH

r through a process referred to as luteinization. The The endometrium is dynamic target tissue which
I
I corpus luteum is formed from remaining structure undergoes both anatomical and physiological cyclic
(the granulosa and theca cells) of the dominant changes during the menstrual cycle controlled by
t'
follicle following ovulation with the primary function estradiol and progesterone produces by the ovaries.
of ovarian steroidogenesis'. The major hormone The endometrial changes that occur during the
I' produced by the corpus luteum is large amounts of menstrual cycle are limited to the functional layer of
I
progesterone and, relatively, small concentrations of the endometrium consisting of the stratum
relaxi n, i n h i bi n, estrad iol, oxytoci n, prostaglandi ns. compacta and the spongiosum whereas the basal
I
layer remains intactfor regeneration of thefunctional
r
I Human corpus luteum has two distinct steroidogenic layer following menstruation. The endometrial
J
cell types namely; granulosa lutein cells and theca changes during the menstrual cycle comprise the
lutein cells which are derivatives of the granulosa and proliferative and the secretory phases, converted by
i the theca cells of the original graafian follicle. The ovulation, based differential hormonal dominance
granulosa lutein cells are generally large in size and with resultant physiological and anatomical
I not sensitive to LH but secrete high quantities that changesu'". The occurrence of the endometrial cycle
: account for basal progesterone production in the first changes is synchronous with the ovarian cycle
half of the luteal phase. On the other hand, the theca changes with ovulation signaling the transition from
lutein cells are small in size, receptive to LH the proliferative to the secretory phase. The
stimulation in the second half of the luteal phase endometrium represents the final target for the
resulting in pulsatile fluctuations of progesterone hypothalamic-pituitary-ovarian hormonal axis and
levels in the blood". adequate knowledge of the complex pathway has
clinical importance in the management of patient
The life span of the corpus luteum is about 14 days if with anovulation and other endocrine disorders.
. pregnancy does not occur but its secretory function
declines after reaching functional maturity after Proliferative Phase
approximately 8 days post-ovulation. There is a The proliferative phase represents the first half of the
significant reduction in the concentrations of endometrial cycle and jt
is characterized by
I
progesterone after the mid-luteal phase if there is no proliferative changes in the endometrial glands,
fertilization and this leads to regression of the corpus stromal cells, and vasculature resulting in thickening
397
of the endometrium. The proliferative phase begins endometrium into secretory tissue during the
with the onset of the menses and ends at the time of secretory phase following ovuJation. The function of
ovulation. During the menstrual phase endgrrtttrial progesterone in the secretory phase is enhanced by
lining undergoes rapid degeneration'aHd postovulatory estradiol production by the corpus
regeneration of the functional layer' tif ihe luteum. Therefore, withdrawal of both estradiol and
endometrium. The endometrial glands ganerally progesterone through luteolysis in the absence of
undergo increased mitosis with decreased lur-nens fertilization results in degeneration of the
and pseudostratified nuclei stimulated by estradiol. endometrial mucosa which breaks down with
Mitosis and DNA synthesis is markedly higher in the subsequent initiation of menstrual flow.
fundal area and the corpus compared to the isthmic Regeneration of the endometrium commences with
and the conual regions of the uterus. Also, the the onset of menstruation which signifies the
nuclear DNA activity is more pronounced in the upper beginning of the proliferative phase of the next
third compared to the lower two thirds of the endometrial cycle.
functional layer of the endometrium. This differential
arrangement has physiological implications as Menstruation
lf ovum is not fertilized, the corpus luteum begins tc
implantation and nutrition of the blastocyst is
degenerate about 4 days before the next menses
facilitated mainly by the upper functional layer
(24*n day of the cycle) and forms corpus albicans
whereas the secretory function and integrity of the
(scar tissue) and estrogen and progesterone drop,
endometrium is provided by the lower functional
There is marked increase in lymphocytic infiltration,
layer. The functional activities of the proliferative
phase are controlled by estradiol produced in the vasospasm and necrosis leading to menstruation.
The average blood loss is about 30 to 80mL and the
ovaries followi ng FSH stimulation'''.
menstrual blood is nonclotting because of
The proliferative phase starts with the onset of fibrinolysin. Presence of clot is clinical evidence of
menstruation following luteolysis of the corpus uterine pathology
luteum in the preceding menstrual cycle and ends
Relationship of LH, FSH leading to production of
when ovulation occurs after which secretory phase
Estrogen and Progesterone
begins.
Secretory phase
The secretory phase of the endometrial cycle
commences following ovulation and is primarily
regulated by progesterone which causes secretory
changes in the estradiol-primed endometrium. Large
amounts of progesterone secreted by the LH after
ovulation results in the conversion of the endometrial
lining of the uterus from a proliferative type into a
secretory endometrium in preparation for embryo
implantation. From day 14 to 16 the epithelial cells
still undergo mitosis and show pseudostratification of
the nuclei. Mitosis in the glandular epithelium stops
after this but still occurs in the stromal cells. The
presence of pseudostratification and subnuclear
vacuoles around day 16 is the first sign of ovulation in
the endometrium.
During the endometrial cycle estradiol produced by

the growing follicles promotes endometrial
proliferation during the proliferative phase whereas
progesterone converts estradiol-primed
398
|r
1
I
The Menstrual Cycle
Ovarian and Uterine changes during the menstrual cycle(')
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REFERENCES
1. Jabbour HN, Kelly RW, Fraser HM, Critchley HO. Reproductive Development and Function of the
Endocrine regulation of menstruation. Endocrine Female Reproductive System. Ganong's Review
rev iews. 2006 ;27 ( 1 ) : 1 7 -46 of Medical Physiology. Mc Graw Hill Lange. 2012,
Barrett, KE, Brooks, HL, Boitano, S. and Barman, 22:391-418
SM (201O Ganong's Review of Medical Physiology 6. Ferin M. The Hypothalamic-Hypophyseal-Ovarian
(Twenty Fourth Edition). McGraw-Hill Medical, Axis and the Menstrual Cycle. Glob. libr. women's
USA, Chapter 25 med., (/SSN; 1756-2228) 2008; DOI
Erickson G. Follicle Growth and Development. 10.s843|G1OWM.10283
Glob. libr. women's med. (/SSIV: 1756-2228) 7. Kwawukume EY, Ghosh fS, Wilson JB.
2008; DOt 1 0. 3843 lc LOW M. 1 0289 Menopausal age in Ghanaian Women. lnt J
4. Fraser lS, Critchley HO , Broder M , Munro MG. The Gynaecol Obstet L993 40: 151-155.
FIGO recommendations on terminologies and 8. Ferenczy, A, Mutter G. The endometrial cycle.
definitions for normal and abnormal uterine Glob. libr. women's med ,
bleeding. Semin Reprod Med (/SSN: 1756-2228) 2008; DOI
I
2011;29:383-390 10.384?/GLOWM.10293
5. Barrett KE, Barman SM, Boitano S, Braoks HL. 9. Gibson M. Corpus luteum. Glob. libr. women's
399
Comprehensive Gynaecologt in the Topics
med. (/SS/V; 17 56-2228) 'r. Metabot6,5:1L92, 1987

10.38431G1OWM.10291 :.: 12. Murray MJ, Meyer WR, Zaino RJ, Lessey BA,
L0. Homburg R. The Mechanism of Novotny DB, lreland K, Zeng D, Fritz MA. A critical
HR. libr. women's med. analysis of the accuracy, reproducibility, and
20 1 4; DOt 10. 3843/GLOW M. clinical utiliU of histologic endometrial dating in
11. O'Hara A, Mari T, Taii' S., e.fj
1
',' {ertile women. Fertility and steritity. 2OO4 May

differentation in 31;81(5):1333-43.
luteal cells isolated from 1
lutea of menstrual cycle.

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I
I CHAPTES4
,F
E
I
I
F
i
Puberty
El Nwobodo and K Tunau
r
i
7
lntroduction
Puberty is a developmental process
by which a fully
competent adult reproductive capacity
is
(thelarche) occurring around
the age of 10.
Thelarche is followed by pubic and axiilary
development (adrenarche) at the age of
hair
established.'lt is characterized by the deveiopment 11.
of Adrenarche is subsequenily follow.O
secondary sexual characteristics, onset Oy tt,.
of attainment of peak growth velocity (gcmlyear)
menstruation and changes in psychological at the
ouilook age of12 and then menses (menarche) at the age
from childhood to adulttype., of
13. On the average it takes 2.5 years from
the onset
The age at the time of puberty is variable; of breast budding to the first period.lncrease
in Europe in linear
and United States, it has been declining growth velocity can be appreciated
aithe rate of l_2 yearsprior to
1-3months for over 175 years. ln recint years, breast budding, heralding the onset of juberty.
the Final
puberty has be occurring between height is. usua lly atta ined two yea rs ter
the agei of g and af
13 years in girls and 9 and 14 years menarche.','
in boys in United
States.s ln Nigeria, puberg o.iurc
between 9 and 13 The age at menarche varies between and
years in girls and 9 and 15 years within
in boys.o,u
countries. ln United States, menarche
I occurs at a
) Physicat changes occuiring in puberty mean age of 12.9 years and is usually
earlier among
African-Americans compared to the white
- Breast development (thelarchre)_ americans.'ln WestAfrica the mean age of
menarche
Pu bic hair growth(adrenarche) varies from 12.6 years in Ghanau,,, 13.g years
in
Cameroon',-13.9 years in Nigeriar,,o.,,to
- Axillary hairgrowth 15.3 years
in Gambia" occurring earlier in girls from higher
- Growth spurt (maximum growth rate)
social class and living in urban setting
compared to
those from low socio-economic class and
living in
- Onset of menstruation ( menarche) ruralsemi-urban setting. Marshall and
Tanner in
1 969 proposed a S-stage
system to grade breast and
The first srgn of puberty is usually pubic hair development and a 3_stage
breast budding system to
assess axillary hair development in girls.,.They
are
outlined in Tables 1 & 2.
401
Tab le 1: Tanner stages of breast & pubic hair development

Stage Breast Pubic hair
Elevation of papilla on$ pubertal) No pubic hair
il Breast budding Scattered labial hair
ilt Enlargement of breast uffimfi areola Hair spreads to mons pubis
separation
IV Secondary mound formd by areola Slight lateral spread
V Mature breast with single contour of Hair spreads to medial thighs
breast and areola
Table 2: Tanner stage of axillary hair development

Stage Axillary hair
No hair (infantile)
il Some hair present but growth is incomplete
ilt Fully developed hair
\
l
Emotional changes during puberty addition, oestrogen promotes fusion of the
The physical changes that occur during puberty give epiphyseal plates. This is why patients with
rise to a variety of social and emotional changes as precocious puberty have early growth advantage but
well. The ongoing physical maturation process ultimately have short stature due to premature
directly affecis the body and brain to alter the epiphyseal closure if left untreated. The adrenal
children's needs, interests and moods. ln general the glands start to produce increase quantities of
emotional changes during puberty include feeling androgens - dihydroepiandrostreone (DHEA),
overtly sensitive about physical appearance, dihydroepiandrostreone sulphate (DHEAS) and
searching for identity, feeling uncertain about the androstenedione which stimulate pubic and axillary
future, peer pressure, conflict of thoughts, mood hair growth. Adrenal androgens are primarily
swings and sexual feel i ngs." responsible pubic and axillary hair growth; however
some androgens from the ovaries play contributory
Endocri nology of pu berty' role.'''
During childhood, the levels of GnRH, FSH and LH
are very low due to the suppression of hypothalamo- Factors influencing the onset of puberty
pituitary-ovarian axis by a neural mechanism. The exact mechanism determining the onset of
However, from the age of 8 to 9 there is increase in puberty is not clearly known. The hypothalamus
pulsatile secretion of GnRH with increasing functions throughout fetal and prepubertal life as
amplitude and frequency. lnitially the increase is evidenced by early FSH secretion. However, why low
sleep related (occurs only at night) but later occurs prepubertal level of GnRH occurs is unexplained.
throughout the day. GnRH stimulates secretion of Recent evidence suggests that a neural mechanism is
FSH and LH from pituitary gland which in turn operating during the period from birth to puberty to
mediates follicular growth and steroidogenesis in the prevent normal pulsatile release of GnRH. However,
ovary. The oestrogen and progesterone from the the exact nature of this mechanism remains
ovary initiate breast development. Oestrogen is unknown. lt has also been hypothesized that
primarily responsible for the growth of the ducts neurotransmitters, endorphins, interleukins, leptin
while progesterone is primarily responsible for the and other paracrine and autocrine factors modulate
growth of the lobules and alveoli. Oestrogen also the onset of puberty.'
stimulates growth hormone secretion from pituitary
gland which in turn stimulates insulin-like growth Several factors have been recognised to influence the
factor resulting in increased somatic growth. ln onset of puberty and they include race, heredity,
402
r f
r
I
Puberty
I
r
I
bodyweight, exercise, altitude and blindness. Management of precocious puberty involves
r. Puberty occurs earlier in girls who have family history meticulous history, clinical examination and
of early puberty, African descent, live at lower investigations aimed at determining the cause
altitudes, live in urban settings, are obese or are followed by specific treatment to eliminate the
f
I
blind. ln contrast, girls with diabetes mellitus, causative factor. The history should include growth
I
extreme obesity, poor nutrition, excessive stress or and pubertal milestones, family history of
L
involved in excessive exercise tend to have delayed reproductive tract abnormalities, exogenous
I
puberty. ''"The critical body fat theory of Frisch states hormonal drug ingestion, symptoms of thyroid
r
that 17-22% body fat is necessary to initiate disease and neurological symptoms or history of
i puberty.'u lt is now thought that leptin, the satiety- CNS insult. Physical examination should be tailored
hormone secreted by the fat cells, may be the link towards height and weight ( relating them to
i between body weight and puberty. Excessive body fat percentile for age), Tanner staging, thyroid,
I leads to increase secretion of leptin resulting in neurological, skin and abdominal examination and
r suppression of appetite while low body fat mediates pelvic/rectal examination. Pertinent laboratory
f reduced secretion of leptin resulting in increased investigations may include oestradiol, LH,FSH, TSH,
I
i appetite.' X-ray of the left wrist bone to assess skeletal

maturation, pelvic ultrasound, CT scan, skull X-ray
Disorders of puberty and MRl. ln cases of idiopathic precocious puberty,
J
(a) Precocious puberty
i the clinician is faced with the problem of reversing
,
I
It is the onset of puberty before the age of eight in a
I the normal onset of puberty. The treatment of choice
I girl or nine in a boy.'u It consists of two types : GnRH
is the use of GnRH analogues which are extremely
?I dependent (central, complete or true) and GnRH
effective at obliterating FSH production by the
I
I
independent (
peripheral, incomplete or pseudo)
pituitary. Following treatment with this agent, there
precocious puberty. ln the former, there is early
r activation of the hypothalamic GnRH pulse generator
will be re-establishment of pre-pubertal state and the
;
child can be on this therapy until aged about 11.5-
by lesions such as cerebral tumours (eg 12 years when the therapy can be withdrawn and
I craniopharyngioma). However in majority U5%) ot
j normal onset of puberty will ensue. Any breast or
cases there is no identifiable cause.' ln GnRH pubic hair development that has occurred prior to
r independent precocious puberty, sex steroid
diagnosis will usually be reversible as the hypo-
production occurs independent of hypothalamo-
rI oestrogenic state prevents further growth and in
pituitary-gonadal axis. Possible causes include
most cases this results in resolution of early change.
t functional ovarian .cyst, granulosa cell tumour,
However, if the secondary sexual characteristic
I
t
autonomous oestrogen production from the ovary due
changes have been much greater and development is
f to genetic mutation, McCune-Albright syndrome also
beyond tanner stage 3, little effect can be expected
called polyostotic fibrous dysplasia (characterized by
by this therapy. Children with ovarian, adrenal or
i multiple bone lesions, caf6-au-lait spots and gonadotrophin secreting tumours should be treated
precocious puberty), adrenal tumours,
surgically.''"
t
I
hypothyroidism and exogenous oestrogen ingestion.
I
;
(
t
a
403
puberty
Table 3: Aetiological Classification of precocious
( | ) Gonadotroph i n dependent(centra l, compffig or true)

precocious Puberty
- ldioPathic ','"t'
- Cerebral tumours (eg craniopharyat*loma)
- HyPothalamichamartoma
- HydrocePhalus
- Post-meningitis
(l I ) Gonadotrophi n i ndependent (peripheral, incomplete
or
pseudo) Precocious PubertY
- FunctionalovariancYst
- Granulosa celltumour
-Autonomousoestrogenproductionfromovaryduetogeneticmutation
- McCuneAlbrightsYndrome
- Adrenaltumours
- HyPothYroidism
Exogenous oestrogen
(a) DelaYed PubertY clinical examination and investigations which may

include serum FSH, serum LH, pelvic ultrasound'
Absence of signs of secondary sexual characteristics skull X-rays, CT scan of the brain, MRI and
by age of 14 years.'u lt is due to either central defect karyotype. Treatment is directed towards the cause'
(hypogonaOotrophic hypogonadism) or a failure of Constitutional delay requires no specific treatment
gonadal function ((hypergonadotrophic and as such counselling and follow-up are of utmost
importance. Central causes are treated with
pulsatile
hypogonadism). Central causes include constitu-
tional delay, excessive exercise, anorexia nervosa, gonadotrophin administration or low doses of ethinyl
Kallman's syndrome, pituitary tumour and chronic oestradiol 1-2ug per day for 3-6months' Primary
illness. Causes of gonadal failure include Turner's gonadal failure requires oestrogen replacement'
tt't'''o
syndrome (45XO), /rX (pure) gonadal dysgenesis and combi ned with progesterone.
premature ovarian failure.''t''u Premature ovarian
failure may be idiopathic , autoimmune or due to use
of chemotherapy/radiotherapy for treatment of
childhood cancer. "Evaluation of delayed puberty
involves careful history (with emphasis developmen-
tal milestones and family history of delayed puberty),
404
r f
r Puberty
iI
r
{
r' Table 4: Aetiological Classification of delayed puberty
{
il
F-
( | ) Centra I Ca uses ( hypogonadotropic hlpogonad ism )
- Constitutional
"k- - Excessive exercise '' . '' '
1
I
l.
- Anorexia nervosa
- Kallman's syndrome
I
I
- Pituitarytumour
I
a
- Chronic illness
(
', ( II) Gon ada I ca uses ( hypergonadotropic hypogonad ism )

- Turner's syndrome
r - XX (pure) gonadal dysgenesis
- Premature ovarian failure
i
I
i.
II
D iscussion/Controversies adolescence lasts longer tha n puberty.

L Puberty is often called adolescence but differences
I
; exist between the two. The former refers to the period ll. ln the female, the usual order of puberty is
I
I
when the endocrine and gametogenic functions of the thelarche (breast bud), pubic hair, axillary hair,
I
I gonads first develop to the point where reproduction growth spurt and menarche. Sometimes, variations
i I
is possible while the latter refers to the period of final do occur. Tanner stages are a uniform way to
I
I
maturation of the reproductive system including describe breast and pubic hair development.
psychological adjustment to adult life. Thus
l
I
!
r
I
{
I
t
(
REFERENCES
It
rr.-
i-
I
rI 1. Sawin SW. Puberty. ln: Bader TJ @d) OBIGYN Nigerian boys. West African Journal of
i Secrets. Elsevier lnc 2008; 5:29-34. Medicine L997; 16(1): 6-11.
Edmonds DK. Puberty. ln: Edmonds DK (ed) Aryeetey R, Ashinyo A, Aduik M. Age at
Dewhurst's Textbook of Obstetrics & menarche among basic level school girls in
:
Gynaecology. Blackwell Publishing 2007; 37: Medina, Accra. African Journal of Reproductive
I
: 366-8. Health 2011; L5(3): 103-10.
Ganong WF. Physiology of reproduction in 7. Gumanga SK, Kwame-Aryee RA. Menstrual
-
I women. ln: Decherney AL, Nathan L, Godwin characteristics among some adolescent girls in
I
f TM, Laufer N (eds) Cunent Dragnosrs & Accra, Ghana. Ghana Medical Journal 2012;
r- Treatment Obstetrrcs & Gynaecologlt. McGraw- 46(1):3-7.
Hill Companies 2007; 6: 126-48. Pasquet fManguelle-Dium Biyong A, Rikong-
lwunze AB, Obinwa BN. Pubertal development Adie H, Garba MT, Froment A. Age at menarche
in Nigerian lgbo girls. CIB Tech Journal of and urbanization in Cameroon: current status
Pharmaceutical Sciences 20L5; 4(2): 45-7. and secular trend. Annals of Human Biology
t Ezeome ER, Ekenze SO, Obanye RO, 1999; 26(1): 89-97.
: Onyeagocha AC, Adibe LN, Chigbo J, Onuigbo Ofuya ZM. The age at menarche in Nigerian
Wl. Normal pattern of pubertal changes in adolescents f ro m two d i ffe re n t soc i o -econo m i c
405
c/asses. Online Journal of health Allied menarche and a hypothesis of menarche.

Scrences 2007 ; 6H), 1-4. Archives of Drsease in Childhood 1971; 46:
10. Panti AA, Ekele BA, Nwobodo El, 695-701.
age at menarche amongst 16. Mong A, Dobbs S. normal and abnormal sexual
girls in Sokoto metropolis, development and puberty. Gynaecology by Ten
Orient Journal of Medicine Teachers. Holder Arnold 2011; 3: 20-26.
42. L7. Mul D, Hughes lA. The use of GnRH agonist in
11. Tunau KA, Adamu AN, Ahmed Y, precocious puberty. European Journal of
at menarche among school girfs Endocrinology 2008; 159: 3-8.
Nigeria. Annals of African fufedicire 18. Henriette AD. Application of gonadotrophin
11(2):103-7 ' ,,-.::-..: .:, releasing hormone in hypogonadotropic
12. Prentice S, Fulford AJ, Jarjou tMA, hypogonad ism- diagnosis and therapeutic
GR, Prentice A. Evidence for a downward aspects. European Journal of Endocrinology
secular trend in age of menarche in rWa'l: 2404; 151:89-94.
Gambia poputation. Annals of Human Bio@nr, 19. Delemarre EM, Felius B, Delemarre HA.
2010; 37(5): 712-21. lnducing puberty. European Journal of
13. Marshall WA, Tanner JM. Variation in the Endocrinology 2008; L59: 9-15.
pattern of pubertal changes in gir,ls.-.Aiehirm of Fothergill D. Menarche and adolescent
Drsease in Childhood 1969; 44: 291-3O3. gynaecology. ln: Luesley DM, Baker PN (eds)
14. Oswa I t A. M e nta U em oti on a I I socia/ cfiaryes Obstefrics and Gynaecology an Evidenced- 1
through puberty. Child and Adolexent, based Text for MRCOG. Edward Arnold 2010;
Development; J uie 20 10. 48:529-32.
15. Frisch R, Revelle R. Height and weight at
406
ri
f
i
I
t
r
tI
r CHAPTES5
l'
r
I
rt
I
F
I
Amenorrhoea
I
E E Emuveyan
;
i
|.
i
t
(
I
lntroduction For normal menstruation to occur, an individual must

t
t
have intact hypothalamo-pituitary-ovarian uterine
Amenorrhoea is the absence of menstrual periods. lt axis with or without an associated disease. This
I
I
is primary if there is no menstruation by the age of 16 accounts for the diversity of causes of amenorrhoea
t
years and it is secondary on the other hand where
r (Table 1)'.
I
i there is absence of menstruation for a period of 6
I
rI
months or more in a woman who previously had Clinical Presentation
I regular menstruation or the absence of menstruation
t
for 12 months in a patient with history of Amenorrhoea itself is not a disease but maybe a
- oligomenorrhoea which is defined as menstrual symptom of a disease. Women with amenorrhoea
I
r
cycles occurring at intervals of more than 35 days but present in various ways. Therefore a complete
r
I
less than 6 months. Other termsfrequenily history (Table 2) must be taken and a full physical
I encounte4red are polymenorrhoea which is examination (Table 3)should be performed.
r
I
menstrual cycles occurring at intervals less than 21
I
I days while hypermenorrhoea is excessive andlor Table 1: The Causes of Amenorrhoea
[-
r prolonged menstruation of over 80mls and over 7
t
I days i n regular intervals of 2 1 -35 days'''''

-
I
I
Class Abnormalities Types (s)
I I Developmental defects of the lower Occlusion of hymen, vagina or cervix
genital tract
i 2. Uterine agenesis andembryological
,-
a. Syndrome of gonadal dysgenesis and variants
abnormalities. b. Pseudo-Turner syndrome
:
i Developmental defects of the upper c. Testicular Feminisation syndrome
genital tract. d. Female pseudohermaphroditism
: 3. Uterine and endometrial causes 1. Tuberculous and suppu rativeendometritis.
:.
2. Asherman's syndrome
4. Ovarian failure Premature menopause

I
5. Ovarian abnormalities 1. Ovarian tumours
a 2. Polycystic ovary syndrome (PCOS)
407
6. Non.gonadal diseases 1. Thyroid disease

a. Hyperthyroidism
b. hypothyroidism
2. Diabetes mellitus
3. Adrenal disease
a. Congenital adrenal hyperplasia I
b. Cushing's syndrome
7. Hypothalamic F Pseudocyesis
2 Persistent corpus luteum (PCL) syndrome
3 Anorexia nervosa
4 Psychogenic amenorrhoea
5 "Post-pill" amenorrhoea
8. Pituilary 1. Galactorrhoea-Amenorrhoea syndrome
a. Pituiltary-Amenhorrhoea syndrome
b. Galactorrhoea and hypothyroidism
2.hypopituitarism
a. Secondary or Hypothalamic 1
1
b. Primary Hypopituitarisim-Sheehan's
syndrome.
Table 2: History in amenorrhoeic patients. 3.Growth and Nutrition history

o Short stature and severe malnutrition
l.Menstrual history . Overand undereating
o Increase or reduction in weight?
2. Medical and surgical history . Acromegaly
. History of chronic illness
. Previous operations 4.Drug history
o Previous radiation treatment . ls the patient on any drug treatment?
. Psychiatric illness and use of psychogenic . lf on any drugs, which drugs and for how
drugs long?
. Previous treatment with cytotoxic drugs 5. SocialHistory
. Symptoms of endocrine dysfunction/ . ls there any background history of
galactorrhoea, hirsutism, diabetes Ol igomenorrhoea,a menorrhoea
mellitus and thyroid disease e.t.c
. Uterine curettage 6. Familyhistory
. Any similar history in siblings?
Table 3: Physical Examination in Amenorrhoiec patients
1. Do a general examination
. Find the body mass index (BMl)
. The habitus of the patient
. Evidenceof chronic illnesses
2. Look out for signs of thyroid diseases (myxedema or thyrotoxicosis)
3, Examine the breasts for their sizes, masses and changes of pregnancy and galactorrhoea
4. Observe for hirsutism.
408
rt
I
r
r Amenorrhoea
I
('
r t
*
I 5. Examr,rechestand heartforairyanomalies. The BP must bechecked
6. Examine the abdomen for mas$ ,striae on the abdomen and other parts of the body. Look for
trunkal obesity :-
7 . Pelvic examination
r
+
. Examine the vulva for hair ffiribution, size of the clitoris. Look for oiher signs of
: masculinization . .:
o
.
I Do a vaginal examination and rlook for signs of oestrogenisation, uterine size and adnexal
f
MASSES.
I
8. Test the visual field.
r The findings on history and physical examination will indicate the appropriate investigations in each particular
t case as with fore thought in a poor resource setting of developing countries, an accurate diagnosis and a result
oriented approach can be adopted with a few relevant investigations. The flow chart in fig. 1 summarises the
I
I
I
outcome of progestogen challenge test and the possible leads, further investigations and recommended
treatment based on results of tests.
{
( Fig. 1: Flow chart of investigations based on result of Progestogen Challenge Test.
lM/oral Progesterone
t
I I
t Positive uterine
+
f
t I
Serum LH
r
i High > 25mlUml
I
Normal
f I
Polycystic ovarian disease

rI Hypothalamic pituitary dysfunction such as
I I
drugs, stress or extreme exercise
Serum DHEAS
II I
lnduce bleedingrevery month with oral

I
Serum Prolactin
f contraceptive pills, dexamethasone or
*"rffi
t I
sprinolactone if androgens are
i elevated
ts
l
lnduce uteeoing eLry nrr" oJt

: Month with progestins prolactinoma
f
i
Progestogen challenge test is usually done with For patients with negative progestogen challenge
I
Primolut N 5mg b.d or t.d.s. for 7 days. The result test, priming with oestrogen before administering
i divides the patients into those with a positive test progestogen is recommended. lf the result is
which means that they have adequate oestrogen stillnegative, this means that the outflow tract is not
levels, responsive endometrium and ns outflow iract normal as may be found in cases of Asherman's
obstruction. On the other hand a negative test implies syndrome. ln these patients hysterosalpinggraphy or
4 that the oestrogen level is low or there may be uterine hysteroscopy is indicated to enable one make the
I
t
adhesions, endometrial atrophy, outflow obstruction diagnosis. Table 4 shows the other investigations
:
or hyperprolacti naemia. which should be done in amenorrhoea patient
409
Table 4: Other lnvestigations in Amenorrhoea Patients
1. Serum gonadotropins: FSH and LH '

2. Serum prolactin
3. Serum thyroid stimulating hormoe (l&{i, T.,,Tn
4. Serum dihyroepiandrosterone (D'HEAI-"
5. Chromosmosal studies (buccal smear and peripheral karyotype)
6. Abdomino-pelvic ultrasound. Trans-abdorhinal in pre-pubertal and Trans-vaginal in adult women
7. Skull X-ray and CT scan MRI of the pituitary
8. Oral Glucose tolerate Test (OGTT)
9. LHRH challenge test
10. Serum cholesterol.
Following history, physical examination and iaboratorytestingthefindings can be united inFig.2 which is a
recommended flow chart for investigation of patients with secondary amenorrhoea
Fig 2:Flow chart for the investigation of patients with Amenorrhoea

-:
Complete History and Physical Examination Abnormal
fossa
Asherman's FSH/LH Prolactin X-ray Pituitary fossa
HSG or High Low/normal High Normal

tossa
Abnormal
fossa
Hysteroscopy
Clomiphene
Adhesiolysis & Tomograms
lnsertion of IUD Ovarian Failed response High TSH
Failure
(menopause) No tumours
Thyroxin
gonadotrophins theraPY Tumour
Bromocryptine
Or Surgery
Lisuride Of radiotherapy
COMMON CAUSES OF AMENORRHOEA cervix can be demonstrated without difficulty. ln

The wide array of amenorrhoea and the possiblo an a,.;equately developed girl, a history of
findings in specific cases make it imperative that monthly recurring cramps in the lower abdomen
at least a brief account of the causes or groups of and a bulging blush membrane in the intriotus
causes, findings of history, physical examination may be present. A more complex problem is
selective laboratory investigations including when the vagina is partly absent. There may be
dynamic pituitary function testing and treatment a shallow vagina, but a transverse septum
be given. occupies a large part of the vaginal lumen. The
internal structures are present and functioning.
A. Development defects of the Lower Genital Tract This condition may be noted early in life since
Occlusion of Hymen, vagina or Cervix and that vagina and uterus become distended by
certain abnormalities e.g. imperforate hymen, watery or mucoid fluid. Alternatively, the
transverse septum of the vagina or those of the patients may present at menarche with
410
fI
t
t"
t
Amenorrhoea
I
t
complain's similar to those of the patient with iii.Other variants
i
imperforat. hymen. ln most cases of the absent
vagina the uterus is only rudimentary, but grossly
r
i
a
abnormal uterine tubes and ovarids may be
found on rectal examination. The precise
The other variants include:
Fema le Pseudohermaqph rod itism
anatomical details should be obtained at

Sex chromatin - positive Variants of gonadal
Dysgenesis syndrome
laparoscopy so that an accurate prognosis may Sex Chromatin -Negative Variants of Gonadal
be given. Dysgenesis syndrome
XY Gonadal dysgenesis and
B. Uterine Agenesis and other Ernbryolgical Female Pseudohermaphroditism
Abnormalities-syndrome of Gonadal
Dysgenesis C. Uterine and Endometrial Causes
This group accounts for a substantial proportion
of all causes of primary amenorrhoea. The i. TuberculousandSuppurativeEndometritis
syndrome of gonadal dysgenesis as its variants
may be viewed on a continuum that ranges from This condition can occur in the absence of systemic
the typical XO phenotype to normal male or tu bercu losis a nd therefore, may not be
female phenotype as briefly show in the recognized on initial evaluation of the patient. lt
following: may be considered in the different diagnosis of
patient who fails to bleed after a course of
l. XO Gonadal Dysgenesis oestrogen-progestogen med ication.
Short stature and sexual infantilism are The diagnosis is made by examination of uterine
invariable features of Turner,s syndrome. Other curettings histologically and by culture.
features include fish-mouth, high-arched palate Suppurativeendometritis may be sequel to abortion
with dental abnormalities epicanthal folds, done by non-sterile technique.
ptosis and low-set or deformed ears, broad
shield-like chest, hypoplastic areolae, short neck B. Trauma
with low hairline, and webbing. Structural Ashermanu is described as a variable amount of
abnormalities of the kidney, extensive naevi, destruction of the endometrial cavity,
tendency to keloid formation and hypoplasstic diminished menstrual flow, infertility and
na ils can be observed. Card iovascular anomal ies repeated pregnancy loss. Many authors believe
are also found in the syndrome. patients are that a history of post-partum or post-abortal
usually small at birth, grow slowly, fail to have curettage is enough to justify the diagnosis even
pubertal growth spurt and end up at a mean when the other criteria (Table 5) are met only
heightof about 742cm. minimally. Uterine adhesions of some degree
exist in all patients treated by curettage within
lt. Testicu la r Fem i nsationSyd rome two months of delivery6.Some authors believe
This is a rare genetic familial disorder. The carrier that whether an endometritis exists prior to or is
is a male possessing a typical female habitus, caused by the trauma usually in the form of a
Breast growth is usually adequate and the curettage is conjectural. Moreover, even genfle
external genitalia are female. public and also suction curettage had been found to be as
axillary hair are scanty or absent. A short vagina provocative as sharp curettage. The main
is present, while all other internal female sex symptoms are infertility, secondary
structures are lacking. The gonads are frequenily a menorrhoea, cycl ica I pa i nfu I hypomenorrhoea,
located in the groin or in the abdominal cavity. A menstrual irregularities and habitual abortion.
negative buccal smear and 46Xy karyotype
) The final diagnosis is by hysterosalpingography
together with the above-mentioned features (HSG) or hysteroscopic inspection of the uterine
i establish the diagnosiso. Malignant changes do cavity, while uterine exploration with a cannula
occur more frequently in these undescended or with a sound to locate the adhesions may be
tests. helpful. Failure to bleed after oestrogen priming,
4Lt
progestogen conversion and withdrawal may be B. Ovarian Disorders

useful in the adhensions or end organ failure, i.e. i Ovarian Tumour
major puerperal or post-abortal curettage is Several types of hormone-producing ovarian tumours
essential and an important historical feature is can disrupt the ovarian cycle, with amenorrhoea as
post-partum endometrial infection. Therapy one manifestation. Usually these tumours are
maybe necessary to restore menstruation, evident on physical and pelvic examination. A
correct infertility, prevent habitual abortion, cure menstrual suggestive of excessive oestrogenic
dysmenorrhea and in rare circumstances to treat stimulation or histology of cystic glandular hyperpla-
haematometra. The best theraPY is sia may raise suspicion of an oestrogen-secreting
hysteroscopy lysis of adhesions followed by the ovarian neoplasm and a history of defeminisation
insertion of an intrauterine device for 2-3 accompanied by physical signs of virilisation may be
months or insertion of a foley's catheter into the an indication of an androgen-producing tumour. The
uterine cavity for 7- 1 0 days postoperatively.? diagnosis is based on finding an ovarian tumour and
a history of abnormal stimulation. ldentification of
Table 5: Criteria for Definition of Uterine Synaechie the specific tumourtype is complex and sometimes it
cannot be established even on histological examina-
tion. The symptoms associated with a virilising
1. Permanent adherence of uterine walls
ovarian tumour such as arrhenoblastoma are
2. Parital or incomplete obliteration of menstrual irregularly, infertility, amenorrhoea,
uterine cavity baldness and breast atrophy. Such masculinization is
3. Variable placement of adhensions
also found in some patients with an adrenal lesion.
4. Clinical symtpoms, i.e An ACTH test and dexamethasone suppression test
Menstrual abnormal ities
are helpful in differentiating adrenal from ovarian
lnfertility
hpernad rogen ism.
Habitual abortion
ia. Polycystic Ovary Syndrome (PCOS)
Polygenic ovary syndrome lncludes polycystic ovary
syndrome', cushing's syndrome, congenital adrenal
A. Ovarian Failure
Patients with ovarian failure have a common diag- hyperplasia, virilising ovary and adrenal tumours and
nostic finding of hypergonadotrophism in which the hyper and hypothyroidism. Historical information
FSH/LH ratio exceeds unity. The presence of second- common to most patients with PCOS may discrimi-
nate it from other causes of chronic anovulation. The
ary sexual characteristics indicates that there has
been some ovarian resistant ovary syndrome (ROS)
hirsutism is a reflection of a hyper-androgenic state
have a particular type of ovarian failure with and is associated with a slight but significant
hypergonadotrophism probably due to ovarian- elevation of all androgenic hormones and their
precursors.
receptor a bnorma ities.
I
The patients with gonadal dysgenesis and premature There is inappropriaiely elevated LH secretion with a
menopause are clearly identified by their greatly relatively constant but low release of FSH. The
raised FSH values in serum. A single plasma FSH excretion of excess amounts of androgen and its
value is sufficient to diagnosis the presence or subsequent peripheral conversion to oestrogen
absence of follicles in every women. However, with constitute the basis for the development of LH to FSH
the reports of pregnancies, post-diagnosis of prema- ratio, fasting insulin, testosterone and
ture menopause by shangoldet al', the limitations of androstenedione are elevated while there is reduced
ovarian biopsies and the dangers of equating raised concentration of sex hormone binding globulin
(SHBG). In a well-developed syndrome there is
FSH values with menopause are becoming obvious.
general enlargement of both ovaries with a smooth
Treatment of patients with exogenous oestrogen in
order to detect those who will resond with the but thickened capsule. Polycystic ovaries are also
present before puberty',. Accurate diagnosis of PCOS
oestrogens are stopped could be reasonable.
is done by ultrasound scan in adults".
4t2
rI
f
(
f Amenorrhoea
I
I
f
I yellow-tinged skin, brittle nails and alopecia. The
i
l Laboratory studies include the determinatlon of LH
r and FSH, insulin, testosterone anq ryx furmone
conventional thyroid function tests may be equivocal
but increased serum cholesterol, prolonged ankle
binding globulin in serum. Cush fi$$@me, jerk reflex, bradycardia and/or specific
r?
t
I
ad ren a I hyperpl asia, vi ri isi ng ova
I riar&ffik& to be electrocardiographic changes should be followed by
t excluded by the usual clinical and:fffi€i"ffiFi'meth- the response of TSH to thyrotrophin releasing
I ods. hormone (TRH) test.
i
I
I
I
The aims of treatment are the establishment of ii. Diabetes
1 fertility and the reversal of hirustism. Clomiphene Prior to the availability of insulin, 50"/" of diabetic
citrate, an anti-oestrogen is effective in.induction of women were amenoorhoea and in additional 15%
I ovulation in PCOS disease. Therapy should however had menstrual disorders. Amenorrhoea in the
f be monitored by serial ultra-sonography of fsllicular diabetic patient may be produced by any of these
I
t
I
response because of the 10% risk of multiple preg- theoretical mechanisms; effect of insulin deficien-
nancy. The "success rate" especially in patiemnts cies on the hypothalamic-pituitary-ovarian axis,
t with substiantial endogenous eostrogen in treatment nutritional deficiencies and emotional disturbances.
I
of PCOS is very high as reported by Adams and A positive family history is found in 50% of patients.
f
Cooke" and Emuveyanet et al". For patients who fail As a routine all amenorrhoea patients should
t to respond to clomphene citrate therapy, ovarian undergo glucose tolerance test.
f diathermy'4. A procedure free from the risk of muttiple
i
I pregnancy and ovarian hyper-stimulation syndrome AdrenalDisease
t (OHSS) and therefore does not require intensive i. CongenitalAdrenalHyperplasia
I
ultrasound monitoring is recommended. manifestation of abnormalities in adrenal cortex
I
steroid production result from the degree of defi-
r
I C. Non-GonadalEndocrineDisease ciency of cortisol and aldosterone formation and
I
from the biological activity of steroid precursors,
r
t
Thyroid Diseases produced in excess as a result of the enzymatic block
I
iii. Hyperthyroidism involved. The pathways of adrenal steroid
rt Hyperthyroidism rarely leads to lengthening of the
the enzymes involved are well
biosynthesis and
I menstrual cycle, scanity periods and amenorrhoea known. ACTH acts at a step between cholesterol and
and the laboratory findings include increased values pregnenolone to stimulate adrenal steroidogenesis.
I
of circulating thyroxiqe (Tr), triiodothyroxine (T.) and
I ACTH production is regulated by the amount of
free thyroxine index (FT1) and lowered serum levels cortisol in circulation through a negative feedback
r of thyroid stimulating hormone (TSH). Cholesterol
I mechanism. The action of cortisol may e directly on
( values are normal to low, phosphorus and uric acid
the pituitary or indirectly via corticotrophin-releasing
I
I may be slightly low; sugar concentration vary from factor (CRF) from the hypothalamus or both. Thus
t
normal to those of a diabetic curve. Serum calcium when the amount of cortisol is decreased, ACTH
rI
t
may be above normal and creatinine excretion is production is increased. ln all the forms of congenital
I
increased. A relative lymphocytosis may occur in adrenal hyperplasia in which genital abnormalities
Grave's disease. High gonadtrophin values and signs
i occur, there is a decreased capacity to produce
of oestrogen deficiency may also be found.
coritsol with compensatory ACTH overproduction.
I With excessive ACTH secretion there will be an
iv. Hypothyroidsm
increased production of steroids in the steps of the
T
a There is a wide range between mild hyo-thyroidism

biosynthesis pathway up to the enzymatic block.
I and frank myxooedma. Abnormal uterine bleeding is
There is a "damming up" of those steroids immedi-
iommon but amenorrhoea may be encountered. The
ately proceedingtheblock and these will be present in
overt symptoms are tiredness, slow mentation, cold
circulation in increased concentration. ln addition to
(
sensitivity, acroparaesthesia and constipation
the decreased cortisol which"stimulates the produc-
I accompanied by non-pitting oedema of the hands,
tion of ACTH, impaired mineralocorticoid formation
: feet and around the eyes, typicalfaciatappearance,
wi I I i ncrease rei n-ango-tensi nogen prod uction.
enlargement of the tongue, hoarse voice, dry, cool,
413
il
Comprehensit Gynaecology in the Topics
plasma coritsol production by 1mg dexamethaosne

Six different types of hydroxysteroid dehydrogenase given in the evening before the test.
deficiencies can occur in the following positions in
the steroid nucleus: carbon 27, 20, 17 , L8, 1 1 and v. Addison's Disease
3. The most common is the 21-hydroxylaFe defi- Adrenal cortical insufficiency is caused by adrenal
ciency which exists in incomplete and complete atrophy in approximately 55% of patients because of
forms. The C-20 hypoxylase deficiency interrferes apparent autoimmune disease, in 40% by tuberculo-
with the conversion of cholesterol to pregnenolone sis of the adrenal gland and in 5% by metastatic
and progesterone. The new born usually succumbs carcinoma, histoplasmosis or trauma. Amenorrhoea
and no survors have been reported. ThefeaturesofC- is an inevitable development. The diagnosis is by
17 hydroxylase deficiency are amenorrhoea, hyper- recognizing the plasma coritsol level which is lower
tension, hypokalaemia and alkalosis. There is no than normal and the inability of the adrenal to
masculinisation but oestrogen deficiency is apparent respond to ACTH.
laboratory test is the demonstration of an excessive
excretion of deoxycritcosterone and corticosterone. A D. Hypothalamic
Various extra hypothalamic centres such as the
defect of C-18 hypoxylation has been described with
amygdalod complex and the hippocampus have
decreased aldosterone secretion but this probably
modulating influence on the hypothalamic induced
does not interfere with gonadal fuction. The C-11
cyclical release of gonadotrophin. There is a compel-
hydroxylase deficiency displays besides virilisation, a
ling evidence from Knboil'uthat profound changes in
hypertension state can increased pigmentation.
Large amounts of 11-deoxycortisol tip off is the
the gonadotrophin occur as a consequence of
disturbances of those brain centres intimately
increased urinary metabolite tetrahydro-S (11-
involved in the control of mood, emotion and
deoxycoritisol). The C-3 dehydroxylase deficiency
behavior.
interferes with the transformation of pregnenolone to
progesterone; virilisation is mild and most patients
iv. Pseudocyesis
die early wioth a salt-losing syndrome.
The psychogenic basis for neuroendocrine abnor-
malities in pseudocyesis is suggested by the immedi-
The essential abnormality in the more severe forms of
ate fall in serum prolactin and LH levels after the
congenital adrenal hyperplasia is the adrenal's
diagnosis is revealed to the patient. lt has been
inability to produce cortisol, the pituitary secretion of
proposed that mental depression is critically involved
ACTH is excessive to the extent that hyperplasia of
in the genesis of pseudocysis, The fantasy of preg-
the adrenal cortex develops. Because of the resulting
nancy appears to function as a defence against such
overproduction of the adrenal hormone precursor, the
depression. The management of patients with this
secretion of pituitary gonadotrophins can be sup-
ailment should be individualised. The psychogenic
pressed and the genital tract becomes exposed to
nature of this disorder should be revealed to the
large quantities of androgens. This excess androgen
husband or patient. Psychiatric care is frequently
is first express in the female fetus in utero, resulting in
necessary in the general management of the patient
masculinisation of the external genitalia of the
and possiblyforthe prevention of suicide attempts.
varying degree. Most common at birth, there is an
enlargement of the clitoris. Because of the excess v. Persistent Corpus Luteum (PCL) Syndrome
androgen, pituitary gonadotropins will be sup- This syndrome may represent a mixture type of
pressed, as a result of which ovarian function will not pseudocyesis.
be stimulated and the patient will have neither
female secondary sexual development nor menstrual i. Anorexa Nervosa
periods. Amenorrhoea in patients with anorexia nervosa is
caused by insufficient gonadotropin which results in
Pituitary-adrenal homestatic mechanism. ln this a state of hypogonadotrophic hypogonadism. The
syndrome laboratory screening tests usually indicate oestradiol secretion by the resting ovary is low but
lack of diurnal variation of plasma cortisol and circulating levels remain in the normalfemale range.
slgnificant suppression (measured in the morning) of However the metabolism of both oestradiol and
4L4
r I
r
Amenorrhoea
I
I
f
II
testosterone is abnormal. ln these patient, the basal The so-called "post-pill amenorrhoea" represents an
i{
t secretion of LH and FSH is low. ConeEntration of ambiguous diagnosis. Researchers have noted an
r
i1
circulating FSH are higher than flmt& 6f LH. ln incidence of 2.2 per 1,00 among 20,000 oral
il \-
F contrast to
individuals with otM''types of contraceptive users in a study. Several recent reports
{t amenorrhoea or with simple weig+it io8s these indicate that in a majority of cases, histories compat-
? patients have a basat secretion of ti{ andftii{,ict,loir. ible with hypothalamic chronic anovulation before
I
I
Concentration of circulating FSH within tfj6'noi.mal the initiation of oral contraceptive may be obtained.
r range. Assessment of pituitary gonddrotrophin
;
response to synthetic LHRN reveals quantitative and Amenorrhoea under these circumstance is self-
,
qualitative abnormalities; LH and FSH release in limiting while spontaneous resolution frequently
a
i
response to large doses of LHRH (100ng) is reduced. occurs.
!
An LHRH does of 10ng induces a peak respohse of

f LH release within the rang for normal women in their E. PituitaryAmenorrhoea
i early follicular phase but the peak response of FSH is
significantly greater than normal. Furthermore, there
i. Galactorrhoea-AmenorrhoeaSyndrome
I
Three separate syndromes-ChiariFrommel,
I is a delay in achieving peak concentrations of
Argonzdel Castillo and Forbes-Abright have been
gonadotrophin. These findings implicate hypotha-
described. These syndrome may present different
( lamic dysfunction in these patients. ln several cases
stages in the same basic disorder- a progression from
when 40% or more of the body weight has been lost
hyperplasia to microadenoma of the lactotrophin,
i
i
in order to prevent severe malnutrition and death by
t with the common denominator of hperprolactinemia
starvation, immediate force feeding is required. Most
f patients seek medical attention before this advanced
due to hypothalamic-pituitary dysfunction. ln
I women with amenorrhoea, regardless of its aetiology
1 phase of the disease and frequenily respond to
15 to 20 percent will have elevated proclactin levels.
r treatment. Psychothiatric problems are the most
f
I
important therapeutic approach.. Behavioural
Galactorrhoea is frequently accompanied by
amenorrhoea (more than 40 percent of patients). ln
modification is now widely used. lncreasing the
I cases of galactrorrhoea with regular menses
I weight is a cardinal feature in the recovery of the
hyperprolactinemia frequently exhibits oestrogen
reprod uction fu nction.
rI deficiency which may lead to hot flushes and
I
ii. PsychogenicAmenorrhoea dyspaeunia. When hyperprolactinemia is detected, it
i This is one of the most common types of is important to exclude pituitary adenoma and
r hypothyroidism hence biochemical assessment of
r .\- amenorrhoea. Fried et al'uconducted a retrospective
study of those factors that characterize patients with thyroid function is always advisable in women with
I
t secondary amenorrhoea. ln comparison with amenorrhoea. ln the case of the relatively large group
I matched control population a significanfly higher Q2%) of patients who develop amenorrhoea-
I incidence of the following factors were found; hyperprolactianemia fol lowing the discontinuation of
( oral contraceptives or in the post-partum period, the
r unmarried, engaged in "intellectual" occupations,
I stressful; life events, consumption of sedatives and underlying cause be pre-existing pituitary adenoma
hypnoticdrugs, under-weight and previous menstrual or hypothyroidism and it is likely that these condi-
irregularities, ln a prospective study by yen etal,, a tions may persist at a subclinical level until exposure
remarkably high proportion of these patients gave a
to high concentration of oestrogen which will then
r
I
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history of psychosexual problems and socio- unmask the causal effects.
environmentaltrauma, occurring either before or
It around the time of puberty. The basal gondotrophin
ii.
Pituitary Prolactin-producing Adenoma
Hyperprolactinaemia occurs in 25 per cent of
concentration in these patients is either normal or
patients with acromegaly and probably accounts for
low. The gonadotrophins released in response to
the menstral dysfunction. The excessive prolactin
LHRH stimulation' are supernormal amenorrhoea
a secretion in the presence of large tumours of any type
I resu lts from cycl ica lgondaotrophi n release.
is thought to be caused by impingement of the
: hypothalamus by an upward extension of the
iii. "post-Pill Amenorrhoea"
415
Comprehensiv Gynaecology in the Topics
turmone. Rarely, acidiphilic adenomas may secrete either neurological complications or other endocrine
excessive amounts of both prolactin aqd,rgtowth disturbances require medical or surgical treatment.
hormone. Prolactinomas are extremely c6--_-_num end Serum prolactin concentrations fall promptly after
accounts for at least 70% of "ch541@ c'' oral admi nistration of bromocri ptine.
adenomas and are either microadm@,or
m a c roa d e as. M a c roa d e n om as a re easy to {rcrt€Gt
no m The degree and duration of suppression are related to
radiologically. The degree of prolactin ebvtr&n,tlr4y the magnitude of the pre-treatment prolactin levels.
offer support to the radiological findings and in Few side effects occur with the dose usually required
general correlate well with the size of theadenomas. to reduce prolactin levels to the normal range. Side
The use of tomography and cornputerized axial effects do occur at the initiation of the treatment;
tomography (CAT) scans and MRI together with these include nausea and vomiting which can be
circulating prolactin levels and absence of response avoided if the drug is taken with food and postural
to TRH stimulation permit the diagnosis of prolactin- hypotension at larger doses which can usually be
producing micro-adenomas with high degree of circumvented by administration of the drug when the
accuracy. Galactorrhoea and amenorrhoea as well as patient retires. Occasionally, constipation is trouble-
'
hyperprolactinaemia can occur in patients with the some but usually responds to a simple change
empty-sella syndrome. The patients usually have diet. The response depends on prolactin levels.
generalized enlargement of the sella and the diagno-
lnduction of ovulation by suppression of prolactin
sis can be accurately made with
levels with bromocriptin as sole therapy has been
pneu moencepha logra phy or CAT scan. I n these cases
it has been suggested that the presence of pituitary
reserved for patients in whome a pituitary
prolactin-producing adenomas is highly probable.
macroadenoma has been excluded. lf ovulatory
cycles rapidly resume the drug should be withdrawn
iii. Galactorrhoea and Hypothyroidism as soon as pregnancy is diagnosed. During preg-
The presence of hyperprolactinaemia and the nancy a pituitary or other parasellartumour can
enlargement of the sella in association with cause visual failure. Usually the deterioration of
amenorrhoea-galactorrhoea in patients with primary vision occurs in the later half of pregnancy and
hypothyroidism may lead the clinician to make recovers rapidly after delivery.
erroneous diagnosis of pituitary prolactin-producing
tumour. This relatively common condition can readily For patients with pituitary adenoma in whom there
be excluded or confirmed by the results of thyroid are no neurological or endocrine indications for
function tests in all patidnts with the galactorrhoea- surgery, several groups have advised that preliminary
amenorrhoea syndrome. The basal FSH concentra- external irradiation followed by treatment with
tions are normal but LH levels are inappropriately bromocriptine should be given.
elevated and display exaggerated response to LHRH
The successful restoration of fertility following
stimulation. Thyroid replacement therapy induces
treatment with bromocriptine has been very gratify-
prompt clinical improvement with reversal of all
ing. ln the United States of America good results
endocrine abnormalities, including the enlargement
were also reported in patients with transphenoidal
of the sella.
microsurgery for the removal of microadenomas. The
The treatment of patients with hyperprolactinaemi- success rate in 60 patients was 757" with no
camenorrhoea depends to a large extent on the cause complications. The prolactin levels invariably fell to
of the syndrome. lf it is due to primary normal range within 24 hours after complete
hypothyroidism, hyperprolactinaemicamenorrhoea removal of the adenoma. These surgical data were
is readily reversed by appropriate replacement obtained before bromocriptine was made available in
the treatment of microadenomas. Since the introduc-
therapy; administration of bromocriptine may be
considered as adjunctive therapy for tion of bromocriptine the use of surgery has dropped
hyperprolactinaemia caused by drugs e.g. tremendously. One disadvantage of administering
phenothiazines, imipramine, reserpine, that cannot bromocriptine is that prolactine levels appear to rise
again as soon as the drug is discontinued- a situation
safely be discontinued. Pituitary tumours producing
416
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i Amenorrhoea
r
i
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r which was argued as being strongly in favour of a coagulation encountered during rOnorrrt pr.g-
i definitive surg;cal extripation of prolactin-producing nancy may be important predisposingfactors. Partial
F
I
pituitary adenomas. However, as the use of surgery or complete spontaneous recovery does take place in
I
l
extended, post-operatively hypopituitarism was some cases and subsequent pregnancy in these
I reported more commonly and hyperproladinaemia patients has been reported. The pituitary response to
r frequently persisted and this means that patients synthetic LHRH stimulation may be normal, dimin-
I
I
were being treated after surgery with bromocriptine ished or absent.
I
t
perhaps cortisol, thyroxine (life long) and HMG and
{ HCG to induce ovulation. These disadvantages Episodic administration of LHRH has been used in
l
disappear when bromocriptine is used as primary patients with this syndrome and has achieved
:
therapy. After tumour shrinkage ovulation induction pregnancies. lnduction of ovulation and resulting
can be successfully used. pregnancy can usually be accomplished readily by
f use of exogenous gonadotrophin.
l
ii. Hypopituitarism
Studies on Amenorrhoea
. Secondary or Hypothalamic Hypopituitarism Emuveyan' studied 104 amenorrhoeic patients at
This condition arises from lack of appropriate the Jessop hospital for Women, Sheffield, by using
hypothalamic releasing factor. the symptomatology method, physical signs and
I selective hormonal investigation including dynamic
.Primary Hypopituitarism pituitary function testing to diagnose all the patients
Primary hypopituitarism may result from surgical or (Table 6). Giwan Osagie and Emuveyanl" reported
radiological ablation. lt also occurs as a result of large the causes of secondary amenorrhoea at the Lagos
i pituitary tumours from infarction or from infiltrating
University Teaching Hospital, Lagos, Nigeria and
I
and granulomatous lesions. Sheehan" described a compared these causes with those of the Jessop
I syndrome of hypopituitarism as a result of acute Hospital for Women in Sheffield, England (Table 7).
f necrosis of the anterior pituitary gland, secondary to These two reports show interesting variation in the
t
postpartum haemorrhage and shock. The causes of secondary amenorrhoea in the populations
!
': neurohypophysis is usually spared but it can be studied which in Lagos included hypotha-
involved in severe cases with accompanying diabetes lamic/pituitary Iesions or malfunctions (58%),
insipidus. Clinical manifestations of hypopituitarism ovarian disorders (79%), and outflow tract abnor-
I
in patients surviving the period of postpartum shock malities (lgb and in Sheffield included hypotha-
+ are early mammary. gland involution and failure of lamic/pituitary disorders (7 4%), ovarian disorders
lactation, fatigue, loss of vigour and hypotension (27%) and outflow tract abnormalities (0%).
f
followed by loss of pubic and axillary hair. Coagula-
?
tion abnormalities of disseminated intravascular
:
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417
a
Table 5: Causes of Amenorrhoea in lO4 ConscuUve Subjects
Group Diagnosis Subgroups Subgroup No. Primary Secondary Per cent

No.
l.Hypothalamic 1.1 weight relatri*1,'. .,*, 64 4 60 67.5
weight loss 33
weight gain 8
1.2 Delayed puberty 3
1.3 Neurological diseasc 3
1.4 Hypothalamie 2
Hypopituitarism
1.5 Others (Psychogenic) l7
2. Ovarian failure 10 10 9.6
3. Ovarian tumour 3.1 Polycystic ovarian 8 9 9 8.6
Disease
3.2 Ovarian tumour 1
4. Pituitary 4. 1 Hyperprolacti naemia 4 8 i 7 7.6

disorders 4.2 Hypopituitarism 4
5.Non gonadal 5.1 Thyroid disease 2 4 1 3 3.8
endocrine disease 5.2 Adrenal disease
a. Congenital adrenal 1
hyperplasia
b. Cushing's 1
syndrome
6. Developmental 6.1 Turner's syndrome 2 8 7 1 7.6
defects of the 6.2 XY female 1
gonads 6.3 Congenital absence 2

of
. Uterus or vagina 1
1.4 lmperforate hymen 2

1.5 Others
7. Miscellaneous Surgery 1 1 0.9
104 13(12.5 700%
%) 9r(87.5"/")
418
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l ""3 t
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Amenarrhoea *
t,
t
-'l i
t iJ
F
I
*econdary amenorhoea in two studies
i
t
F
I
r
?
t CAUSE Number of patients*
I
I
Lagos (a) Sheffield (b)
r (a) Hypothalamic n:27(58%) n:67(67"/o)
I
r i. Weight-retated 4t
7
ii. Hyperprolactifi*cffir,iii 72 7
iii. Post-pill 1
? iv. Trauma 2
a 14 L7
Systemic n=l(2%) n:3(3%)

Thyroid disease 1 3
Adrenal disease
Ovarian disorders n=9(19%) n=19(21"/o
Polycystic orary
syndrome 9
il. Ovarian failurel
Menopause 3 10
(d) Outflow tract abnormality n=9(19%) n:0(0%)
t. Post-trau matic uterin€ E/rrgchiae 8

ii. Tu be rcu lou s endometritis 1
(e) Miscellaneous n-L(2o/") n:2(2"/")
t. Hysterectomy 1 1
ii. Turner's syndrome 1
Total 47(lOO"/o)
91(1oO%)
* Percentage of total in brackets

r (a) Giwa-Osagie, 0.F (ln preparation)
t (b) Adapted from Emuveyan, E.E $982)-
?
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FMCOG Part ll Dissertation
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-419
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Controversies mechanism for the menstrual dysregulation in these

cases since amenorrhoea may sometimes precede
Discussion / Controversies substantial weight loss in some anorexics. Some
L The understanding of amenorhoea requiries a researchers hypothesize that some as-yet
thorough grip of the workings of the hypothalamo- unrecognized neuroendocrine phenomenon maybe
pituitary- ovarian- uterine axis. involved, and the menstrual irregularities may be
related to the biological undergirding of the disorders
Even in the definition of oligomenorrhoea some take
ratherthan a result of nutritional deficiencies.
it as infrequent menstration while others consider it
as a light menstruation'0. lV. Treatment-induced amenorrhoea (TlA) remains
controversial in women with pre-menopausal breast
More strictly, oligomenorrhoea is menstrual periods
cancer according to data from the National Cancer
occuring at interval of greater than 35 days with only
lnstitute of Canada (NCIC), Clinical Trails
four to nine periods in a year. Also menstrual periods
Group(CTG). The anti-cancer drugs include
should have been regularly established previously cyclophosphamide (Cytoxan), epirubicin (Elleme)
before the development of
infrequent flow. The
fluorouracil and methotrexate. Some scholars in thls
duration of such events may vary". Oligomenorrhoea
area agree that the ability of many of these trials to
can be the result of prolactinomas, thyrotoxicosis,
examine the impact of amenorrhoea is poor, And they
hormonal changes in perimenopause, Prader-Willi
therefore suggest that meta-analytic technique
syndrome and Graves disease.
combining from a number of trials or a prospective
interventional study designed and powered to
ll. Endurance exercise such as running, swimming
answer this specific question would be the best way
and dancing (ballet dancers) can affect the
to approach this important issue.
reproductive physiology and can cause such women
to menstruate inifrequently in comparison to that
V. Researchers have also admitted young
nonathletic women of comparable age or not at all
women with breast cancer are often concerned about
(amenorrhoea)." Malina et al (1978)" , have also
maintaining fertility, Kevin R. Fox from the University
shown that menstrual irregularity is more common,
of Pennsylvania has reported that Leuprolide plus
and more severe among tennis players than among
adjuvant chemotherapy may preserve ovarian
golfers suggesting that the degree of menstrual
function in selected breast cancer patients. Loss of
irregularity is directly proportional to the intensity of
ovarian function in these patients is caused by direct
the exercise. Breastfeeding has also been linked to
toxicity to developing follicles and they reasoned that
irregularity of menstrual cycles due to hormones treatment with leuprolide might prevent the problem
which delay ovulation..
by suppressing follicular growth during the time
chemotherapy was bee given. lt is a common
lll. Eating disorders can also result in
agreement that the role of leuprolide in receptor
oligomenorrhoea although this is most strongly
positive women with breast cancer needs further
associated with Anorexia nervosa. Bulimia nervosa
study.
may resutt in oligomenorrhoea or amenorrhoea"
There is some controversy regarding the exact
420
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REFERENCES
d
I
,l .--
r,|
7. Edmonds DK. Primary amenorrhoea, ln Edmsnds L4.Arma NA, McGarrigle HHG, Honor Jw, Holownia
DK. (ed), Dewhurst's Textbook of Obstetrics and f Jacobs HS, Lachetin GCL. Laparo.scopic
i, Gynaecology, Oxford, Blackwellsclence. L999; ovarian diathermy in the management of
,. pp 34-41. anovulatoryinfertility in women with polycystic
''l 2. Emuveyan EE. The investigation of ovaries; endocrine changes and clinical
Amenorrhoea. Part lt (Final) outcome. Fertilsterit 1990; 53, 45-g.
i prssertation,Na tional postgraduate Medicat ll.Knobit E. On the control of gonadotrophin
- cotlege of Nigeria1982. secretion in the rhesus monkey. Recentp/ogress
; S. Emuveyan EE.Amenorrrhoea in perspective. in the Hormone Research 1g74; 3O:1
, L995;
A/igerian Postgraduate MedicalJournal l6.Fries HS, Nillius SJ, Petterson F. Epidemiology of
't'. 2(4).L3Q-L4Q. secondary arnenorrhoea {(. A retrospective
| 4. Judd HL, HamiltonCR,Barlow JJ. Androgen and evaluation of aetiology with speciat regard to
l: gonadotrophin dynamics in testicular psychogenic factors and weight loss. Am. J.
I feminization syndrome. J. Clin. Endocrinol. ObstetGynaecol 1974; l1g: 473
l: Metab. 1972; 34:229. 17.Yen SSC Jaffe RH. ln reproductive
lr 5. Asherman JG. Amenorrhoea traumatics endocrinology. Saunders. Philadetphia 1978;
l. Gtretica). J. Obstet. Gynaecol. Br: Emp. 129.
l. 1948; 55:23. lS.Sheehan HL, Simmond's drsease due to
li 6. Erikson J, Kaestel C. the incidence of uterine a- postpartum necrosrs of the anterior pituitary J.
l, tresia after postpartum curettage. Dan. Med. Med. 1939; g:277.
li Bull. 1960; 7:50. l9.Giwa-Osaeie OE Emuveyan EE. Evaluation of
| 7. Boody KM, Carr BR, Amenoorhoea. tn: Ctinical secondary amenorrhoea Nig. Med. pract. 19g4;
l: HJ, London SN (eds) Menstrual Cycle 7:79 - g2.
l, Disorders, ObstetGynecol Clin N Am.
l. Philadelphia; Saunderg 17; 361 - 87. 20.thefreedictionary.com.>oligomenorrhoea. This
lt'
I'
8. Shangold MM, Turksey RN, Bashford RA, dictionary in turn, is citing:Gate Encyclopedia of
l_ Hammond CB. Pregnancy following the Medicine
li insensitive ovary syndrom. Fort ster. 1977; 28: 2l.Berek JS, Adashi EYHittard PA. Novak's
li I llS. Gyecology (12'n ed). Wiltiams & Wilkins,
ll -- 9. Stein lE Leventhal ML. Amenorrhoea associated Baltimore, 1996
l, ,ith bilaterat potycystic ovaries. Am. J. Obstet. 22.Dale E. GerbachDH,Withite AL. Menstrual
r Gynaecol. 1935; 29: 181. dysfunction in distance runners. Obstet, Gynecol
' TO.Bridges NA, Cooke A, Healy MJR, Hindmarsh PC, 1g79; 540(1): 47-53
' Brook CGD. Standards of ovarian volume in 23.Malina RM, Spirduso WW, Tate C, Baylor AM.
i, ,hildren and puberty. Fertit Steril 1993; 60: "Age at menarche and selected menstrual
456 - 60. characteristics in athletes at different
'. 71.Fox R, Corrigan E, Thomas PA, Hall MGR. The competitive levels and in different sports". Med
. diagnosrs of potycystic ovaries in women with Scl Sports.J 978; 10 (3): 218-22.
- oligo-Amenorrhoea; predictlve power of 24.Abebe, D; Lein, L yon Soest. "The development
" endocrine tests. C/in. Endocrinol 1991; 34, 124 of bulimic symptoms from adolescence to young
'. - 31. adulthood in females and males: A
: 12.Adams M, Cooke lD. Management of anovulation. population-based longitudinal cohort study".
'. ln: Clinical in Obstetrics and Gynaecology. lnternational Journal of Eating Disorders.21l2;
- Cooke lD (editor) saunders, London 1974; 285. 45 (G): 737-745.
i* l3.Emuveyan EE, Odum CC, AyodejiO,Akinkugbe A.
i C,inical features and endocrine profite of the
L polycystic ovary disease. (PCO) in Lagos Nigeria.
West Afr. J. Med. 1984; 3: 201-205.
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CHAPTES6
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Anovulation and lnduction of Ovulation

; O K Ogedengbe and J A Olamijulo
'a
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INTRODUCTION FSH induces development of ovarian follicles and
production of estrogen, while LH modulates the
Ovulation is the central event of the human menstrual secretion of androgens from the ovarian theca cells.
cycle and initiation of conception, lt occurs mid-cycle As the follicle grows, the cohort of granulosa cells
following the LH surge leading to the release of an acquire the necessary receptors to respond to LH
i
oocyte from the Graafian follicle. Anovulation with increased formation of cyclic adenosine
I
I
t
represents a failure to release a mature ovum and is monophosphate (cAMP). ln the mid-cycle, estrogen
characterized by diverse clinical features. lt is the levels in the circulation reach a concentration that
I
commonest cause of abnormal uterine bleeding and causes a positive feedback action on LH secretion
infertility and may be present in up to 40% of cases. leading to a surge. A mature oocyte is extruded from
I
ln studies from Nigeria however it was found to be a the graafian follicle about 36 hours of the LH surge
I
factor in 20% of cases infertility, more common leading to the formation of the corpus luteum. The
r causes being tubal factors, which were found to be
I
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corpus luteum has a lifespan of 10-18 days and in
I
present in34.4%' Most women would experience the the absence of pregnancy undergoes luteolysis
r
I
occasional anovulation cycle. Chronic anovulation, which is associated with a fall in the levels of
t however, is associated with irregular and circulating oestrogens and progesterone.
unpredictable pattern of bleeding ranging from short Withdrawal of this support to the endometrium
cycles with scanty bleeding to prolonged periods of results in menstruation. These events are the
irregular heavy loss. culmination of a well-coordinated interplay between
hormones and their appropriate receptors and
PATHOPHYSIOLOGY proteolytic enzymes and prostaglandins acting in
concert with one another.
Ovulation is the result of the hormonal interplay
involving the hypothalamic-pituitary-ovarian (HPO)
Anovulation may therefore originate from
axis and modulated by other related endocrine, dysfunction at any level of the hypothalamopituitary-
autocrine and paracrine systems. Any alteration may
ovarian axis. Aberration in the pulsatile release of
result in failure to release a mature ovum, leading to gonadotrophin-releasing hormone (GnRH) from the
anovulatory cycles and resultant clinical sequelae.
hypothalamus results in deficiency of the pituitary
Ovulation is dependent on the presence of a secretion of follicle-stimulating hormone (FSH) and
functioning hypothalamic-pituitary-ovarian (HPO) luteinising hormone (LH). Without appropriate
axis. The arcuate nucleus within the hypothalamus is gonadotrophin stimulation and subsequent ovarian
composed of a collection of neurons and, when
folliculogenesis, ovulation will not occur. The
stimulated, releases GnRH into the portal vessels of abnormality observed in ovarian activity
a the pituitary stalk in a pulsatile fashion. GnRH anovulatory cycles may be' due to a failure of
I
stimulates receptors in the anterior pituitary gland to follicular development (inadequate signal) or
produce and secrete both LH and FSH. ln women,
i m pa i red positive feed back.
423
-----------:------
Failure of FollicularDevelopment: Follicular documented irregular intermenstrual intervals may

development insufficient to produce an oestrogen have both ovulatory and anovulatory cycles. The
signal sufficient to induce a luteinizing hormone frequency of anovulation is greater among those with
surge is one of the common reasons for the intermenstrual intervals of 35 to 40 days than
irregularities in a menstrual cycles. Decreased among women with a history of regular intervals.
ovarian activity due to diminished oocyte population Anovulatory cycles are common for 17-18 months
may last weeks. Gonadotropin secretion rise5, since after menarche and again before the onset of
feedback with the ovarian steroids is minimal, and menopause. When ovulation does not occur, no
then declines as follicles develop. The level of corpus luteum is formed, and the effects of
oestradiol may be insufficient to induce endometrial progesterone on the endometrium are absent.
development. Stimulation by oestrogen may be Chronic anovulation usually presents with
unopposed by progesterone for long periods and oligomenorrhoea, secondary amenorrhoea or luteal
cause irregular and unpredictable bleeding. The phase deficiency. When endometrial bleeding finally
mechanism of this bleeding is unknown although it occurs it is unpredictable in frequency and quantity'
may result from the lack of secretory changes in the Oligomenorrhoea is defined as absence of
endometrium. menstruation for more than 35 days and less than 6
months while amenorrhoea is lack of menstruatioti
lmpaired Positive Feedback: Anovulatory bleeding for more than 6 months. Secondary oligomenorrhoea
may be associated with cystic glandular hyperplasia or amenorrhoea generally denotes anovulation.
of the endometrium. This occurs in some older However, a small proportion of women with regular
women and also in pre-pubertal girls where the cycles may be anovulatory.
positive feedback mechanism is absent. lt is normal
for the first few cycles after the menarche to be EPIDEMIOLOGY
anovulatory, scanty and painless. With persistent
anovulation, long periods of amenorrhoea are Almost all women experience anovulatory cycles at
accompanied by endometrial hyperplasia. This is some point in their reproductive lives. lt is difficult to
probably due to multiple follicular developments with determine the frequency of chronic anovulation in
failed or impaired antral follicle formation. Levels of the general population because of underreporting'
oestradiol fluctuate, but levels of FSH are more Estimates of chronic anovulation rates range from 6-
resistant to the negative feedback effects of oestradiol 15% of women during the reproductive years'
due to a defect in either the hypothalamus or Analysis of a study population diagnosed with
pituitary. Thus the mechanism by which a single secondary amenorrhoea associated with chronic
follicle is selected for development each month is anovulation, showed 32%Io be due to hypothalamic
disturbed with a higher than normal level of causes, 77% hyperprolactinaemia and 35% to
oestrogen secretion. The resulting endometrial hyperandrogenic causes' lt could therefore be
hyperplasia may cause excessive bleeding, anaemia, inferred that hyperandrogenic causes such as
infertility and in the long term, even cancer of the Polycystic Ovarian Disease were the commonest
endometrium. ln anovulatory cycles, the cause of anovulation.
endometrium appears to be unable to produce

CAUSES OF ANOVULAT!ON
prostaglandin F2a. This may account for the painless
nature of the bleeds observed in anovulatory cycles.
The World Health Organization (WHO) has broadly
classified anovulatory cycles into 3 etiological
Anovulatory cycles are sometimes diagnosed at the
groups'
extremes of reproductive life, but more commonly
during the investigation of secondary amenorrhoea Group I
and infertility. ln general, many of the acquired Hypothalamic pituitary failure (hypothalamic
causes of amenorrhoea also are associated with amenorrhoea or hypogonadotropic hypogonadism)'
anovulation. ln fact, anovulatory menstrual cycles This group is characterized by low circulating levels
with or without an irregular menstrual interval may of FSH, LH and oestradiol. This can occur In associa-
pr:ecede the onset of amenorrhoea. Women with wellr
424
r
r
(
I
I
r
r tion with abnormal weighi changes, intracranial bleeding may be reported by ovulating women.
t tu mou rs, i rra I iation, Sheeha n's
syndrorne;l allmann Pregnancy needs to be excluded in a woman who
r
r syndrome and idiopathic causes; previously had normal cycles through history andl or
t
naemia can be due to drugs such as, nes pregnancy testing, Other relevant aspects of history
I and metochopramide or preserx.st=ffiitery taking includes the age, lifestyle, weight changes,
I
r microadenoma or m|croadenorna::=,
mrcroaoenoma microadenoma; :€ffi* re+eted rigorous exercise, detailed menstrual history
( @..r'#B**bd
I causes due to stimulus from the hrser centres (menarche, regularity or irregularity, Iength and
I
I
include stress, strenuous exercise, anorexia newosa, amount), symptoms of menopause, past medical
I
severe weight loss, excessive weight.gain, pdst pill and surgical history (anxiety, depression, pelvic
I
r
,; amenorrhoea. Peri-menarcheal anovulation is due to surgery, D&C), drug history (hormones, contracep-
a i m matu rity of the hypotha la mo-pitu ita ry axis tives, antipsychotics ). Other symptoms such as
t
?
headaches, visual impairment, changes in hair
Group ll
I
t Hypothalamic pituitary dysfunction
distribution, deepening of voice, breast secretions
may also be relevant.
/
I
(normogonadotropic)
I This mainly consists of Polycystic Ovarian Disease
t The patient should be examined carefully taking note
I and other idiopathic conditions.
of the general physical appearance, hair distribution
and the body mass index (BMl). She may have
I Group lll
I
Hypergonadotropic hypogonad ism features of obesity, hirsutism, facial acne, or male
I
I Premature Ovarian Failure may be due io genetic pattern baldness. Examination of the thyroid gland,
breasts (for Marshall-Tanner staging, masses and
I
I (Turner's syndrome, fragile X syndrome, gonadal

dysgenesis), iatrogenic (sugery, chemotherapy, galactorrhoea) abdomen and pelvis should be done.
I
I
I radiotherapy), auto-immune (polyendocrinopathy A body mass index (BMl) of less than 79kglm'or
syndrome), infection (viral oophoritis) and idiopathic more than 3Ok{m'is associated with anovulatory
I
r
I causes. cycles. Examination of the abdomen and pelvis
should help to exclude genital anomalies and
r
I CLINICAL PRACTICE possi ble ov arianl uteri ne masses.
t
r Anovulation is physiologic at the extremes of repro- Tests for ovulation

I
ductive age. During menarche, absence of ovulation Commercially available ovulation predictor kits are
is due to immaturity of the HPO axis, leading to an commonly used by women to detect the LH surge
uncoordinated pulsatile secretion of GnRH. During thus predicting ovulation. Traditionally, doctors have
perimenopause, ovarian factors and a dysregulation used procedures such as basal temperature chart
of feedback mechanisms are responsible. When (BTC), cytological studies of exfoliated cervical
chronic anovulation occurs outside of the squames (Papanicolau), and cervical mucus testing
perimenarchal or perimenopausal years, extrinsic (lnsler's score) to detect ovulation but these tests are
and intrinsic causes must be excluded by careful largely unreliable, laborious and have been largely
history taking, physical assessment and systematic abandoned. Other tests such as endometrial biopsy
ancillary investigations. The assessment should also are rather too invasive for routine use. There are now
include the patient's clinical needs in relation to simpler tests which are more accurate and less
infertility, abnormal uterine bleeding, amenorrhoea, invasive for determin ing whether and when ovu lation
underlying and I or related medical problems, and has occurred. The National lnstitute for Health and
other issues. Clinical Excellence (NICE) in the United Kingdom
: has recommended mid-luteal phase progesterone
Menstrual cycles are considered normal if they fall in assay that will show elevated levels following
the range 23-35 days and have a month-to-month ovulationu. A Nigerian study showed mid-luteal
variation in cycle length of <5 days. lt is estimated phase progesterone levels of greater than 1Ong/ml to
r:
that at least 90-95% of women with normal men- be compatible with conception (Giwa-Osagie et al)6.
strual cycles are ovulating o. Primary
I
The definition and significance of luteal phase
1 dysmenorrhoea, mittelschmercz and ovulation deficiency is contentious in the assessment of
425
progesterone levels. lt is usually a retrospective menorrhoea often interspersed with episodes of

diagnosis, the woman presenting either with a short prolonged heavy bleeding, lnitial treatment is
luteal phase, or low progesterone levels. Srygwted medical using progestogens in the form of
management includes progesterone tF@gi.er norethisterone orally for about 21 days. This will
ad m i n istration of H u ma n Chorion ic G6ffitfuhBpt+ln, abortthe bleeding episode and produce a withdrawal
neitherof which have proven to be 100%effi. bleed at the conclusion of therapy.
Folliculometry involves serial monitoring of follieular ln the event of recurrence, a diagnostic curettage
development using transvaginal ultrasound scan. with or without hysteroscopy is indicated if the
Ovulation usually takes place when the follicular patient is perimenopausal to exclude malignancy
diameter is 18-25mm. Ultrasound tracking will and atypical endometrial hyperplasia which may be
detect luteinisation of an unruptured follicle, where a precursor of endometrial carcinoma. Dilatation and
pregnancy does not take place despite hormonal curettage is not justified in the adolescent who may
evidence of ovulation. The use of a trans-vaginal benefit from 3 cycles of oral contraceptive pills to
probe allows very accurate visualization of the regularize the periods.
ovaries and other pelvic organs as well as assessment
of the endometrial plate.
POLYCYSTIC OVAR IAN SYN DROM E
ln cases of anovulation, additional tests are needed to Since the first description of Polycystic Ovarian
unravel the possible causes of failure to ovulate. Syndrome (PCOS) in 1935 by Stein and Leventhal,
Assay of Gonadotrophins levels (LH and FSH) in the this condition has been likened to a "diagnostic
early follicular phase will assist in the diagnosis of basket", and the pathophysiology found to be
Polycystic Ovarian Disease and premature ovarian extremely complex. lt is the commonest cause of
failure. ln amenorrhoeic patients, the tests can be anovulatory infertility accounting for 80-90% of
done at any time. Hyperprolactinaemia is demon- caseso''. Two thirds of the infertile women in the
strated by detection of elevated prolactin level. Other Lagos study had Polycystic Ovarian Syndrome'.
hormone tests which may assist in confirming the PCOS accounts for 80-90% of anovulatory
diagnosis include assessment of the level of serum infertility'. Several studies have been done to
oestradiol, testosterone, sex-hormone binding determine the prevalence of polycystic ovaries in the
globulin, and dehydroepiandrosterone sulphate general population, as detected by ultrasound alone,
(DHEAS), 17 hydroxy-progesterone levels as well as and have found remarkably similar prevalence rates
thyroid function tests.' lnvestigation of anovulation intheorder ot2O-3O%.ln a UKstudyof 224female
may rarely include invasive techniques such as the volunteers between the ages of 18 and 25 years,
laparoscopic visualisation of the ovaries, and other
polycystic ovaries were identified by ultrasound in
internal genital organs. Chromosomal studies may 33%, and the prevalence of PCOS was26"/o' .
also be necessary to obtain a definitive diagnosis in
Patients with PCOS usually present with symptoms
suspected cases of genetic disorders.
of hyperandrogenism (hirsutism, acne, and alope-
PERIMENARCHEAL AND PERIMENOPAUSAL cia), menstrual disturbance, infertility and obesity'.
ANOVULATION Generally, about 50% of women with PCOS are
overweight and a substantial minority are hirsute.
The clinical features observed in these causes of However, women in our environment are found to be
dysfunctional uterine bleeding are the results of the "obese" by Caucasian standards, and women from
effects of unopposed oestrogen stimulation on the some ethnic groups are extremely hirsute, and this is
endometrium, leading to endometrial hyperplasia. usually compatible with ovulatory cycles and normal
This is due to immaturity of the hypothalamo- fertility. Obesity may be accompanied by insulin-
pituitary axis following the menarche, and the resistance, hirsutism, recurrent miscarriages and
gradual physiological ovarian failure in the few years oligomenorrhoea. Rarely there may be clitoral
preceding menopause (climacteric) respectively. lt is enlargement due to the hyperandrogenism.
characterized by bouts of secondary oligo- Oligomenorrhoea or amenorrhoea is experienced,
426
rI
r Anovulation and lnduction of Ovulation
I
I
r
the former L'eing more common. This may be inter- of PCOS especially its association with type ll
r spersed with episodes of heavy bleedir-g due to the diabetes mellitus, dyslipidaemia, hypertension,
r
r action of unopposed oestrogen sectt*ioil eausing ca rd iovascu la r d isease, a nd endometria I ca ncern''0.
l--
l. endo metri a I hyperpl asi a, wh ich may inc#@t& risk
i of endometrial carcinoma in the longterm, !NDUCTION OF OVULATION IN PATIENTS WITH
t
I PCOS
I ln recent years, attempts were made to * itsdize
Medical management is the mainstay of treatment,
I
I the diagnosis of PCOS. The Rotterdam Consensus

( statement on PCOS stipulates that any 2 of the and the drug for first line treatment is Clomiphene
I
r.
follor,rling 3 criteria must be present', Citrate (CC), an anti-oestrogen'0. lt is given orally in a
dose of 50-150mg daily for 5 days. Treatment is

I
t . Clinical andlor biochemical signs of usually commenced on the second day of the cycle,
i
hyperandrogenism and exclusion of other starting with the lowest dose with increments until
I ovulation is confirmed. Seventy-five percent of
I
I
etiologies (eg, congenital adrenal hyperplasia
[CAHl, androgen-secreting tumors, Cushing patients will ovulate using clomiphene citrate. The
r
I syndrome) maximum dose is 250mg bulTO% will ovulate on
t
. Oligo-ovulation or anovulation 50-100mg daily. Higher doses will have increasing
. Polycystic ovaries - Presence of 12 or more anti-oestrogenic effects on the cervical mucus and
l
I follicles in each ovary measuring 2-9 mm in the endometrium, theoretically reducing pregnancy
/ diameter andlor increased ovarian volume rates. Thus those patients needing more than
t
t greaterthan 10 mL on TVS. 150mg are considered by most infertility specialists
f to be resistant to CC. Tamoxifen, also an anti-
I
I The endocrinological parameters in PCOS include oestrogen can be similarly used at a dosage of 20mg
I
raised or normal androgens (testosterone and given on day 2 to 6 of the menstrual cycle.
(
I
androstenedione), normal 1 7 hydroxy-progesterone Clomiphene treatment may be combined with the
t level, raised or normal LH (elevated in 40-50%, administration of Human Chorionic Gonadotrophin
t usually slim women) , normal FSH thus giving 5,00010,000 lU mid-cycle to trigger ovulation
t
( LH/FSH ratio of 2 lo 3, elevated or normal fasting following the confirmation of the presence of a pre-
r insulin (not routinely measured; insulin resistance ovulatory fol licle by ultrasound.
I
( assessed by glucose tolerance test, GTT), reduced or
?
r normal sex hormone binding globulin (SHBG), which ln patients with a BMI of greater than 30kg/m'?,
would result in elevated "free androgen index"
I
r weight loss should be encouraged by dietary advice

calculated by [(T x 100) + SHBG], raised or normal and exercise. There is a positive relationship
I
I
I oestradiol, and raised anti-mullerian hormone between obesity and the dose of CC required to
( (AMH); the prolactin level is usually normal but may induce ovulation. Some obese CC-resistant women
I
I
L
be occasional ly elevated6. with insulin-resistance and compensatory hyper-
insulinaemia may respond to Metformin therapy,
I
i
A testosterone concentration of >Snmol/L should which is given in a dose of 500mg thrice daily.
r prompt further investigations to exclude androgen Bariatric surgery or some form of gastroplasty rnay
I secreting tumours of the ovary or adrenal gland, be an option for morbidly obese women with PCOS
I Cushing's syndrome and late onset Congenital (BMl of 40kdm2 or more or35kglm? or more with
7
i
Adrenal Hyperplasia'. Ultrasound scan (preferably a high-risk obesity-related condition) if standard
i TVS) would demonstrate enlarged ovaries (ovarian weight loss strategies have failed". Patients with
a volL, >10m1) containing >12 follicles of 2-9mm raised DHEAS may ovulate with adjuvant dexameth-
diameter with a peripheral distribution around an asone, The addition of dexamethasone to the
echo-dense stroma on ultrasound (so called beadlike induction regimen of women with ovulatory factor
appearance). However, the ovaries may not be infertility is well known. Glucocorticoid administra-
demonstrably enlarged and distribution of the tion suppresses adrenally"derived androgens in
:
a
follicles could be diffuse. The endocrine changes are women with or without hyperandrogenism resulting
more characteristic than the ultrasound findings. in ovulation. Those with abnormal thyroid function
Much has been written about the long term sequelae
427
tests, will respond totheaddition of thyroxine. clomiphene citrate'u. lt is likely that its use will
increase in the nearfuture.
Most are agreed that Clomiphene citrate,@e not
be used for more than 6 to 12 conseeutfu ept€s Pulsatile administration of GnRH will produce
because of lack of evidence of additionat*ffiffifth ovulation with minimal side effects in women
extended use and concern over the risk G resistant to CC, but it has to be administered subcu-
cancer. Approximately 15% of women do not taneously or intravenously using a pump. There are
respond and are considered to be clomiphene- problems with the logistics of equipment, drug
resistant. Because of its anti-estrogenic effect, supply, storage and compliance in our environment.
clomiphene citrate may also inhibit adequate When given continuously GnRH and its analogues
endometrial development, which may affect implan- have an inhibitory effect by down regulation of
tation. ln addition, reduction in cervical mucus may pituitary receptors.
affect sperm penetration. The other side effects of
anti-estrogens include hot flushes, multiple preg- Women may be treated with gonadotrophin injec-
nancy (2-13"/"), abdominal discomfort and ovarian tions with or without down regulation of the pituitay
hyperstimulation ( 1-6%). using GnRH agonists. This regimen may also be
suitable for women with hypogonadotrophic
The original procedure of bilateral ovarian wedge hypogonadism. FSH may be given in the form of
resection employed by Stein and Leventhal was human menopausal gonadotraphin such as Pergonal
found to result in a resumption of ovulation in the or pure FSH, such as Metrodin, When the required
majority of women treated. But the procedure may diameter of 18-22mm is reached, LH is adminis-
result in loss of ovarian tissue and extensive peri- tered in the form of HCG leading to ovulation 34-36
tubal adhesions. Lunde et al" reported a spontane- hours later. Strict monitoring of the number of
ous pregnancy rate of 76% of women who had maturing follicles using ultrasound scanning is
ovarian wedge resection when followed up for 15-25 mandatory to minimize the risk of ovarian
years. Wedge resection has largely been replaced by hyperstimulation syndrome. Protocols and dosage
laparoscopic ovarian drilling using diathermy, but will be tailored to the individual's needs. The treat-
'
this is usually reserved for drug-resistant PCOS. lt is ment is expensive. Ten percent of women with PCOD
less invasive, and side effects such as adhesion will also have hyperporlactinaemia. The use of
formation are less common than with wedge resec- bromocryptine in the induction of ovulation is
tion. Other advantages of laparoscopic ovarian described below.
diathermy is that it is free of the risks of multiple
pregnancy and ovarian hyperstimulation syndrome HYPERPROLACTINAEMIA
but its obvious drawback is the need for surgery, with
its potential com pl ications. Raised prolactin levels may be found in situations
such as stress, pregnancy, post prandially, and
Aromatase inhibitors such as letrozole (femara) certain drug therapies such as phenothiazines or
traditional used in the treatment of advanced breast metroclopramide, Hyperprolactinaemia may be
cancer have more recently been used for ovulation characterized by galactorrhoea which occurs in
induction. A negative feedback effect on the hypo- about 40% of hyperprolactinaemic patients. How-
thalamus and pituitary gland causes increased ever, about 40% of women with galactorrhoea will
production of gonadotrophins which act on ihe not have hyperprolactinaemia. The raised prolactin
ovaries to stimulate folliculogenesis similar to the levels are usually accompanied by oligomenorrhoea
action of the anti-oestogens. Concerns about fetal or amenorrhoea. Hyperprolactinaemia was found to
cardiac and bone malformations have been raised account for about half of the hypothalamo-pituitary
but more recent data seem to provide reasonable causes in a study of infertile women in Lagos'u. Of
assurance concerning fetal safety4'i1'13'14. Further- women who had secondary amenorrhoea, 347" had
more, a recent Cochrane review demonstrated a hyperprolactinaemia, whi.lst 79.5% had
greater chance of live birth with letrozole and a lower lt may be present in women with
galactorrhoea'u.
rate of multiple pregnancy when compared with regular cycles giving rise to luteal phase deficiency or
428
:
unexplained infertility. However, work {rom Nigeria PREMATURE OVARIAN FAILU RE
suggested that there was no place- routine r
prolactin measurements in women in the,abence of Menopause signifies depletion of the primordial
menstrual i rregularity'7. Prolactin l@a5$ .greater follicles and this normally occurs between the age 45
than 600 mU/L are said to be patheleg[cgtr Levels and 52 years. The average age of menopause is
greater than 1000 mU/L may be indicative of a around 50 years in the Western World. Premature
pituitary adenoma, or prolactin-secreting menopause refers to menopause at or before 40
microadenoma (tumour lessthan l0rn.m).',Much years of age, this could be due to a bilateral
higher level may suggest the presence o:f a ovariectomy, (surgically induced menopause) or
macroadenoma (tumor 10mm or more). Such,results non-surgical loss of ovarian function. ln a study
require follow-up with X-ray of the pituitary fossa, involving 4868 women, Ryan et al reported natural
I or magnetic reso-
computerised tomography and menopause in79% of the women,IOT" had surgical
nance imaging of the sella turci:ca. The menopause and77% of thewomen had menopause
hypooestrogenic state could lead to reduction in bone due to other causes, such as radiation or
density, and thus it may be necessary to monitor the chemotherapy". Around 7.6% of the women in the
bone density. study had a premature menopause and a further
72.8% an early menopause (between the ages of 41
Hyperprolactinaemia can be treated using and 45 years). The climacteric describes the period
bromocryptine, a dopamine agonist 1.25.-2.5mg of 5 years or so leading up to menopause. Premature
twice or thrice daily, until prolactin levels revert to ovarian failure (POF) is characterized by high FSH
normal. Side effects include gastrointestinal distur- levels due to the absence of the negative feedback of
bances which can be reduced by commencing with a oestrogens secreted by the maturing follicle on the
lower dose. Other dopamine agonists such as hypothalamus. Oestradiol levels will be low, and the
Lisuride tablets and cabergoline may also be used patient may show other signs of oestrogen depriva-
.
with possible advantages of fewer side effects and tion. Because the ovaries do not respond to FSH and
better compliance. Lisuride is given at a dose of 0.2 LH (hypogonadism), there is no negative feedback
mg daily while cabergoline can be administered at a creating a hypergonadotropic state. POF is diag-
dose of 0.5 to 1mg twice weekly. Medical treatment nosed with 2 serum FSH levels greater than 40
is used for pituitary tumours in general, surgery rarely mlU/mL at least 1 month apart. Gonadal dysgenesis
being indicated. ln the event of pregnancy, is the most frequent cause of POE two thirds of
bromocryptine may be discontinued where there is a which are as a result of a deletion on an X chromo-
microadenoma, but monitoring of the visual fields is some. Although a normal complement of germ cells
;\-
mandatory, as the tumour may grow, and medication is present in the early fetal ovary, oocytes undergo
may have to be recommenced. ln the case of pituitary accelerated atresia, and the ovary is replaced by a
macroadenomas which usually grow, bromocryptine fibrous streak. Evidence for possible autoimmune
I
will have to be continued throughout pregnancy. disorders is usually sought in women younger than
Correction of hyperprolactinaemia using 35 affected by POF. Management is difficult.
bromocriptine is followed by restoration of ovulation Empirical trial of ovarian stimulation by continuous
in 90% of cases. These drugs do not increase the risk oestrogen administration forthree months have been
of multiple pregnancy or ovarian hyperstimulation made, and rarely pregnancy has been reported. But,
syndrome. Hypothyroidism may be a cause of where pregnancy is desired, recourse to assisted
hyperprolactinaemia with the only abnormality in reproductive techniques (ARD with the use of donor
thyroid function tests being a raised TSH level. ln oocytes is usually recommended. Symptoms of
such instances thyroxine supplements have been oestrogen deprivation such as vasomotor symptoms,
found to reduce hyperprolactinaemia leading to osteoporosis, urogenital atrophy and increased risk
ovulation. Other endocrine disorders which may be of cardiovascular disease may be treated by hormone
linked to hyperprolactinaemia but are uncommon replacement therapy (HRT)." Preparations replacing
:
I
and usually the presenting complaints are the oestrogen given in conjunction with progesterone
Acromegaly, Cushing's Syndrome, and chronic renal have the advantage of avoiding the dangers of
failure. unopposed oestrogen therapy which may increase
429
the risk of endometrial hyperplasia and subsequent lncreased vascular permeability results in fluid loss
endometrialadenocarcinoma. from the intravascular compartment into the third
,.
space thus explaining most of the resultant clinical
COMPLICATIONS ASSOCIATED WITH ffi.* presentations of OHSS. There may be a change in
TION INDUCTION. .
blood volume with increased viscosity due to haemo-

concentration which may lead to thrombo-embolic
The major complications associated with cvdation events. Coagulation disorders may ensue and
induction are ovarian hyperstimulation syndrome, decreased renal perfusion and function. Furthermore
multiple pregnancy, abortion, prematurity, congenital there may be cerebrovascular accidents, liver,
malformations and ovarian torsion. lt is suggested respiratory or renal complications'n''o Moderate or
that the incidence of ectopic pregnancy is increased severe OHSS is reported in 3-8% of IVF cycle s.
to 1-3% as opposed lo 7-2% of the general popula-
tion in women undergoing gonadotrophin stimulated The onset of OHSS may be early occurring within 7
cycles. lncreased risk of ovarian cancer has been days of exogenous hCG administration or late
suggested in women on ovulation induction drugs. occurring after 9 days; the later ascribable to
However, questions remain as to whether this is due endogenous hCG from early pregnancy.
to the incessant ovulation experienced by infertile
The Royal College of Obstetricians and Gynaecolo-
women per se or due to the drugs used in treating
gists (RCOG) has proposed a practical classification
anovulation. Nevertheless, it is considered prudent
of OHSS into mild, moderate, severe or critical". ln
when ovulation drugs are used to employ the mini-
the mild form there is abdominal bloating and mild
mum dose that would provide optimal clinical
discomfort, and ovarian size is less than 8cm. ln
benefits for as short a time as reasonable.
moderate 0HSS, there is more abdominal distension
The risk of ovarian cancer appears to be inherently
increased in women who have incessant ovulation,
and discomfort, nausea and vomiting, ascites on
ultrasound and ovarian size is 8-i2cmin diameter. ln
which is those who are nulliparous (possibly because
of infertility) with an early menarche and late meno- the severe form there is clinical evidence of ascites,
pause, Thus, it may be that inducing multiple hydrothorax or acute respiratory distress. Ovarian
size is greater than 12cm and haematocrit is greater
ovulations in women with infertility will increase their
risk - a notion that is by no means proven.
than 45%. Critical 0HSS presents with tense ascites
Ovarian hyperstimulation syndrome (OHSS) is and or large hydrothorax, oliguria, haematocrit
perhaps the most significant short term complication greater than 55%, thrombotic features or Acute
of ovulation induction. lt is more commonly associ- Respi ratory Distress synd rome (ARDS).
ated with gonadotrophin use than with other ovula-

OHSS is a self- limiting condition but steps are taken
tion inducing drugs. There is some degree of ovarian
hyperstimulation in most women who respond to
largely to monitor and relief patient's symptoms,
maintain her circulation and manage evolving
ovulation induction, but the term OHSS is reserved
complications. ln the mild form treatment is symp-
for a clinical entity which is potentially serious.
tomatic and conservative. With the moderate to
Moderate or severe OHSS has been reported to
severe form the mainstay of treatment is correction of
complicate 3-8% of IVF cycles'n. lt occurs more
circulatory volume and electrolyte imbalance, with
commonly in younger women, those with PCOS,
women with high level of Antimullerian hormone
the maintenance of cardiopulmonary and renal
(AMH), in conceptual cycles particularly with function, and prevention of thromboembolism. Mild
and moderate OHSS can be managed on outpatient
multiple pregnancies. The underlying
basis. The patient is advised to drink to thirst while
pathophysiology of OHSS is increased vascular
her symptoms, weight, abdominal girth and urine
permeability mediated by vasoactive substances
output are monitored. Admission is warranted in
such as vascular endothelial factor (VEGF) and other
worsening cases and intravenous fluid replacement
cytokines. These pro-inflammatory mediators are
may be needed using crystallbids or colloids as
derived from hyperstimulated ovaries exposed to
necessary. Anticoagulant therapy may be indicated if
exogenous or endogenous human chorionic
there is laboratory hypercoagulability or clinical
gonadotrophin (hCG) or luteinizing hormone (LH).
430
r
f
r Anovulation and lnduction of Ovulation
r
t
{
r evidence of th romboem bol ic compl ications. Di u retics l. Anovulation is a major cause of infertility and some
I
r should be avoided as this rR,ay worsen have questioned whether or not infertility can be
?
r haemoco nce ntration. Ad m i n istration.of paraceta mol
, regarded as a health issue. This is more so in
[-- and or codeine is usually sufficient for@fn ndief; use developing countries where the burden of life
I
r of non-steroidal anti-inflamatory dre t$6AlDs) threatening diseases both communicable and non-
t
r should be avoided as they may..wei{$en renal communicable remain daunting, However, the WHO
r fu nction'n. definition of health as "a state of complete physical,
I
I
mental, and social well-being and not merely the
t Rarely, laparoscopy or laparotomy may be indicated absence of disease or infirmity" secures a place for
I
I., for torsion of ovarian cysts, intraperitoneal haemor- infertility as an issue that warrants the attention of
rt rhage or the presence of a concurrent ectopic health commissioners and providers.
t pregnancy'n. lf required, surgery must be performed
I
lF
by an experienced surgeon because the ovary is very ll. Ovulation drugs are generally expensive. Virtually
friable and vascular in these cases. all the drugs are imported and ever increasingforeign
t
r exchange rates drive up cost beyond the reach oT
r With the increasing use of ART the prevention of many patients in developing countries. The gonado-
L OHSS is of paramount importance. Preventive tropins are particularly quite expensive, and the
h strategies include consideration of ovulation induc- debate is further complicated by identifying roles for
t tion using alternatives such as anti-oestrogens, specific types, regimes and level of purity set against
?
I
laparoscopic ovarian drilling instead of the background of cost effectiveness.
I gonadotrophins particularly in cases considered to
I,F
,
have high risk of developing OHSS. Where lll. Obesity is associated with anovulatory infertility
I
gonadotrophins are employed, use of GnRH antago- and some practitioners have recommended that
r
nists instead of agonists, a low dose step up regimen, obese women should not be given ovulatory drugs
I
I
coasting, cycle cancellation, elective freezing of until they have lost 5 to 10 % of their weight. The
r
embryos, and use of progesterone instead of hCG for British Fertility Society guideline recommends that
r luteal phase support are strategies that have been ovulation treatment should be deferred until BMI is
I
P
suggested to reduce the risk of developing OHSS. The 35Kg/m'or less". ls it appropriate to deny treatment
rI use of adjuvant drugs such as metformin and dopa- based on a cut off value of BMI even though the
t mine agonists (bromocriptine, carbergoline, effects of obesity on conception and pregnancy
quinagolide) during controlled ovarian stimulation outcome are known? Even a modest weight loss can
I
r have been reported but their roles need further be difficult to achieve through diet and exercise
rr
i.v evaluation. lnterestingly, OHSS is associated with alone, and drugs andl or surgery have sometimes
I
i increased pregnancy rate. Up lo20% of the pregnan- been employed. Undue delay also has adverse effect
t cies resulting from gonadotrophin stimulation are on the fertility of the female partner.
t multiple compared to 7-2% in the general popula-
t
tion. The majority are twins or triplets, but where lV. lnfertility treatment particularly involving
I
three or more embryos implant, there is an increased assisted reproductive technology can be regarded as
i
pregnancy loss from abortion and prematurity. Such life giving and not lifesaving. As such, the potential
i pregnancies are associated with an increased risk of for complications particularly those arising from
pregnancy-induced hypertension, gestational ovulation induction procedures has generated a lot of
diabetes and other maternal complications. debates. For the infertile woman, multiple pregnan-
cies may seem a welcomed compensation for the
ISSUES AND CONTROVERSIES IN long years of delay, but more is not necessarily better.
ANOVULATION AND OVULATION INDUCTION The risk of miscarriages, early preterm deliveries,
hypertensive disorders and perinatal mortality must
;.\,
Pr-
Given the diverse aetio-pathological and clinical be kept in mind and success should ideally aim
'anovulation,
F.
ramifications of it is not surprising that towards singleton conception. While in developed
I the management is surrounded by controversies. countries, professional and regulatory bodies such
,-
as the Human Embryo Fertilization and Embryo
43L
Authority (HFEA) in the United Kingdom have universal panacea for all cases of fertility delay
provided regulations regarding maximum,number of without proper evaluation of the infertile couple; and
embryos transferred, the field is largely unregulated also by gynaecologists in cases of "unexplained
in developing countries particularly in sub-SiiFi#n infertility". There has been recent debate comparing
Africa. Similarly, controlled ovarian stimutaffon to the safety and efficacy of clomiphene citrate with
p rovi d e m u lti p e ova for ferti ization ca rries'poteritial
I I that of letrozole, an aromatase inhibitor. Some
risk of ovarian hyper-stimulation which thougfr'r'are research works have shown conflicting results but a
had on occasions resulted in death. The useof donors recent meta-analysis suggests that letrozole is
to provide multiple eggs in older women and those associated with slightly better pregnancy rate and
with ovarian failure is generally associated with the initial concerns about congenital fetal abnormali-
better success rate but the welfare of the donor must ties may have been over played '''o'".
be addressed. How much of her contribution should
be altruistic and how much commercial? What gain CONCLUSION
can the donorexpectfor her pain and how should she The management of infertility caused by anovulation
be compensated for time and unwanted effects of is usually very rewarding. Cumulative pregnancy
drugs? Will the female partner totally accept and care rates of 6OY" can be achieved in 6 months, and
for the child in good and bad times knowing that she subsequent cumulative Pregnancy rates of up '
is not the biological mother? 9OY" are experienced with gonadotrophin treated '-i I
women, in the absence of other causes of

V. The risk of ovarian cancer has been widely anovulation. The key to successful ovulation induc-
debated; it would appear that whatever risk exists tion consists of appropriate patient selection and
may be due to the condition of anovulation itself counseling, whereby health is optimized by lifestyle
rather than the medication used for treatment. modification before medicaltreatment is offered. The
However, it makes sense to limit the dose and length overriding principle of ovulation induction should be
of treatment to what will provide optimal benefit to to use the lowest effective dosage of drugs for
the individual. lt is now generally accepted that achieving desired ovulation with minimal risk of
clomiphene citrate should not be used for longer ihan multiple pregnancy and ovarian hyperstimulation
6Io 72 months and this level of use is not thought to syndrome. While research continues towards
be associated with increased risk of ovarian cancero refining the use of available therapeutic agents,
'0. Clomiphene citrate is perhaps the most widely careful clinical and ancillary monitoring is key to
abused "fertility drug" in our environment commonly minimize risks and optimize reproductive gain.
prescribed by nurses and.general practitioners as a
432
i
I
i Anovulation and lnduction of Ovulation

I
f
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I
t
r
r
I
r
r
r
1. Giwa-Osagie OF, Ogunyemi D, Emuveyan EE, 12. Lunde O, Dioseland O, Grottum P Polycystic
i.
t Akinla O. Etiological classification and ovarian syndrome: a follow-up study on fertility

( sociomedical characteristics of infertility in 250 and menstrual pattern in 149 patients 15-25
I couples. lntJ. of Fertility 1984,29(2): 104-lOB. years after ovarian wedge resecticin. Human''n
r
,i 2. Reindollar RH, Novak M, Tho SPT, McDonough Reproduction 2001, 16(7), 1479-1485.
I PG. Adult onset amenorrhoea a study of 262 13. Klement AH, Casper RF. The use of aromatase
I
i
patients. Am J Obstef Gynecol 1986, inhibitors for ovulation induction. Current
155(3):531-541. Opinion in Obstetrics and Gynaecology 2015.
I
3. Rowe PJ, Comhaire FH, Hargreave TB, Mellows 27(3):206-209.
HJ. WHO manual for standardized investigation of 14. Pritss EA. Letrozole for ovulation induction and
r the infertile couple. Cambridge lJniversity press controlled ovarian hyperstimulation. Current
I 1999. opinion in Obstetrics and Gynaecology 2010;
4. Gorthi S, Balen AH, Tang T. Current issues in 22(4):289-294.
I
I anovulation. The Obstetrician and Gynaecologist 15. Franik S, Kremer JA, Nelen WL, Farquhar C.
l.
2012,14:188-196 Aromatase lnhibitors for subfertile wome with
I
5. National lnstitute for Health and Clinical polycystic ovary syndrome. Cochrane Database
I
I Excellence. Fertility:, ssessment and treatment Syst Review 2014; 2:CD)10287

i
for people with fertility problems. London. NtCE; 16. Giwa -Osagie OF, Akinla O, Coker OO, Sanyaolu
I
i
2004 AO. The prevalence of hyperprolactinaemia and
I 6. Giwa-Osagie OF, Ogedengbe OK, Sanyaolu A. galactorrohoea in secondary amenorrhoea. Trop
I Slng/e plasma progesterone levels in spontaneous GeogMed 1983,35: 163.
t conception cycles as a guide to the management 17. Giwa-Osagie OF, Emuveyan EE, Sanyaolu AO,
of anovulatory infertility. West Afri. J Med 1988, Akinla O. The place of routine plasma prolactin
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7(3 &4): 136-139. Measurements in infertile women. J Obst East
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7. Balen AH. Polycystic ovary syndrome (pCOS). The Cent Af r 1983, 2:80.
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Obstetrician & Gynaecologist 2017; 18. Ryan J, Scali J, Carridre l, Amieva H, Rouaud O,
i oOt, 1 0. 1 1 1 1 ltop. 1 2345 lccessed Berr C, Ritchie K, Ancelin ML. The impact of
i 2410112017 menopause on cognitive function in later life.
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B. Rotterdam ESHRE/ASR M-Sponsored pCOS BJOG 20 1 4; 10. 1 I I 1 / I 47 1 -0528. 1 2828
Consensus Workshop Group. Revised 2OO3 19. RCOG Green-top guidelines No 5 2016. The
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I consensus on diagnostic criteria and long-term management of ovarian hyperstimulation
I health risks related to polycystic ovary syndrome syndrome.
eCOg. Hum Reprod 2004; 19:41-47. 20. Balen AH. Polycystic ovary syndrome (PCOS). The
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9. Balen A. Polycystic Ovarian syndrome and Obsietrician & Gynaecologist 2017;
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secondary amenorrhoea. ln Edmonds D K(Ed) D0 I :1 0. 1 1 1 1 /top. 1 2345 Accessed 24/0 1 /20 1 7
Dewhurst's Textbook of Obstetrics & Gynaecology 21. Balen AH, Anderson R. The impact of obesity on
i B'n Edition 2012; pg 512-533 female reproductive health. British Fertility
10. Royal College of Obstetricrans & Gynaecologists. Society Policy and Practice. Hum Fert 2007;
Long term consequences of Polycystic Ovarian 10:195-206
Syndrome. RCOG Green-top guideline No 23 22. TulandiT, Martin J, Al-Fadhli R, Kabli N, Forman
2014 R, Hitkari J, Librach C, Greenblatt E, Casper RF.
11. Balen AH, Morley LC, Misso M, Franks S, Legro Congenital malformations among 911 newborns
n-, Wijegarathne CN, Stener VE, Fauser BCJM, conceived after infertility treatment with
Norman RJ, Teede H. The management of letrozole or clomiphene citrate. Fertil Steril
anovulatory infertility in women with polycystic 2006 ; 85(6) : 1 7 6 1 - I 7 65.
ovarian syndrome; an analysis of the evidence to
support the global WHO guidance. Human
Re prod uction U pdate 20 1 6, 22(6) : 687 -7 08
I
433
434
1\-
CHAPTEST
Polycystic Ovary $ynd rome

lA Yakasai and J Tukur
lntroduction least two of the following are present: oligoovulation

j
It was in 1935 that Stein and Leventhal first or anovulation (usually manifested as
described their findings in 7 women that presented oligomenorrhea or amenorrhea), elevated levels of
with amenorrhea, obesity, hirsutism and multiple circulating androgens (hyperandrogenemia) or
cysts in their ovaries.lThe publication described the clinical manifestations of androgen excess
disorder that later came to be known as the Polycystic (hyperandrogenism), and polycystic ovaries as
ovary disease. The disorder is now known to be a defined by ultrasonography. Polycystic ovaries are
common cause of anovolution associated with defined on ultrasound by the presence of eight or
complex reproductive, metabolic and cardiovascular more subcapsular follicular cysts <10 mm and
u
effects on the affected women. increased ovarian stroma.
Definition and prevalence These criteria acknowledge the condition as

The most widely accepted clinical definition of the functional: polycystic ovaries however need not be
polycystic ovary syndrome is the association of present to make a diagnosis of the polycystic ovary
hyperandrogenism with chronic anovulation in syndrome, and that conversely, their presence alone
a
women without specific underlying diseases of the u
does not establish the diagnosis. The 2003
adrenal or pituitary glands. ' Hyperandrogenism Rotterdam consensus workshop concluded that
presents clinically with hirsutes, balding and acne PCOS is a syndrome of ovarian dysfunction along
with or without obesity. Biochemically, there may be with the cardinal features of hyperandrogenism and
elevated levels of androgens especially testosterone polycystic ovary (PCO) morphology. PCOS remains a
and androstenedione. Typically PCOS is associated syndrome, and as such no single diagnostic criterion
) with elevated levels of Luteinising Hormone (LH) and (such as hyperandrogenism or PCO) is sufficient for
normal or reduced levels of Follicle Stimulating clinical diagnosis. lts clinical manifestations may
Hormone (FSH). lronically, although the early include menstrual irregularities, signs of androgen
description of the disorder was based on ovarian excess, and obesity. lnsulin resistance and elevated
morphology, it is now not considered essential for the serum LH levels are also common features in PCOS.
diagnosis. t An international consensus group PCOS is associated with an increased risk of type 2
proposed that the syndrome can be diagnosed after diabetes and cardiovascular events. '
the eaclusion of other medical conditions that cause
.irregular menstrual cycles and androgen excess.
o
The prevalence of PCOS, like that of any other
This includes disorders such as hyperprolactinemia, complex multifactorial disorder, greatly depends on
thyroid disorders, and nonclassic adrenal hyperplasia which criteria are used to define it. Most past studies
(NCAH)., have defined PCOS using a limited number of
I
features,,particularly morphological evidence of
The diagnosis is based on the deterrnination that at polycystic ovaries. When the presence of PCOS is
435
defined solely by the finding of polycystic ovaries at also raised serum androgen levels (testosterone ,
either surgery or. sonography, between L-ZO% ot dehydroepiandrosterone sulphate and

unselected women have been reported to beaffe.eted. androstenedione) which leads to masculinising
finding is unspecific since many wmen with
''n This features. Prolactin levels may also be elevated.
polycystic ovaries diagnosed on ult#+#-:€,re
asymptomatic. When more strict criteria is used to Thirty Io 40 % of women with PCOS have impaired
define PCOS (oligoovulation, et-in[g,al glucose tolerance, and as many as 10% have type2
hyperandrogenism (i.e. hirsutisnil an.dlor diabetes by their fourth decade. There is increased
hyperandrogenemia, and exclusion of other ielated insulin resistance with the pancreatic B cells
disorders), the prevalence was 4-7o/o.'o'" responding with an increase in insulin secretion. Non
lnsulin dependent diabetes mellitus develops when
Clinical features the compensatory mechanism fails. Fasting
PCOS is an inherited clinical condition which is hyperinsulinemia is present in obese PCOS women
transmitted in an X-linked dominant familial pattern. and this is, in part, secondary to increased basal
Features may be noted initially in the young woman insulin secretion rates. " Acanthosis Nigricans is a
who has just reached puber,ty. Menarche may dermal manifestation of hyperinsulinaemia usually
however be delayed and the patient may also present associated with obesity that represents the severest
with primary amenorrhea. There may be features of forms of PCOS. 'o The lesion is in the form of
androgenism such as temporal balding, acne and hyperplasia and pigmentation of the skin appearing
hirsutes. Features of anovulation include as brown or dark skin lesions that may be seen in the
oligomenorhea or amenorrhea and infertility. ln the axilla, neck, groin and vulva.
African setting, patients with PCOS commonly
present to the hospital due to infertility. Obesity is Women with PCOS are also at risk for dyslipidemia
also a common presentation with the patient having because they have elevated androgen levels and are
a Body Mass lndex (BMl) > 25k{m2. The cause of frequently obese. Women with PCOS have lower
the obesity in women with PCOS is unknown but is high-density lipoprotein (HDL) as well as higher
present in about 30% of patients with PCOS and triglyceride, cholesterol and low-density lipoprotein
could be present in up to 75% of patients, lncreased (LDL) levels and impaired fibrinolytic activity
adiposity especially visceral adiposity reflected by an making them to be at an increased risk of
elevated waist circumference (>88 cm [35 in.]) or intravascular thrombosis. While hyperandrogenism
waist-to-hip ratio, has been associated with is likely to play some role in these abnormalities,
hyperandrogenemia, insulin resistance, glucose insulin resistance is the most important contributor
intolerance and dyslipidemia. 5 Obesity tends to to these abnormalities. "''u Based on the risk profile,
worsen the prognosis of PCOS and its control is a women with PCOS have a 7-fold increased risk of
major target of treatment myocardial infarction.'u
Endocrine changes PCOS and Reproduction

ln PCOS, there could be changes in the secretion of Anovulation is a prominent feature of PCOS. A
gonadotrophins. The usual pattern is that of an common presentation of PCOS is with primary but
increase in Luteinising Hormone (LH) relative to that more commonly secondary infertility. With the high
of the Follicle Stimulating Hormone (FSH) leading to premium placed on fertility in African setting, a large
an increase in the LH: FSH ratio. Because of the number of patients with PCOS will be seen in the
pulsatile release nature of the gonadotrphins, a single hospital due to infertility. Anovulation also causes
blood measurement may not detect the increased oligomenorrhea and amenorrhea and dysfunctional
ratio. "This increase in the pulsatile secretion of LH is vaginal bleeding. Prolonged vaginal bleeding may
thought to be due to a defect in the release of the cause anaemia. Even when patients with PCOS get
Gonadotrophin releasing hormone (GnRFl) from the pregnant, there could be spontaneous pregnancy
hypothalamus. The raised LH leads to a thickening of loss. The spontaneous abortion rate in PCOS is
the ovarian theca cells, thus preventing maturation of approximately one third of all pregnancies. This at
the ovarian follicle and secreting androgens, There is least doubles the rate for recognized early
436
Polycystic Ovary Syndrome
abortions in normal women (72-15%). Reasons for are distressing and may lead to an overall reduction
Ihrs are unc'tear although hypqth.eses include in the quality otlite.'*>=
elevated LH evels, def ici ent proge$r.aee@retion,
I
abnormal embryos from atretic an Clinical diagnosis

abnormal endometrium. " Onee',Sqmarrcy is The diagnosisof PCOS is made by taking a clinical
established, the morbidity increases particulady if hisiory, physical examination and relevant
the woman is obese. Perinatal mortafity is irrc-reased investigations. Patients with PCOS are likely to
at least 1.5 times, and pregnancy complioations,are present to the gynaecology clinic. The patient may
increased including preeclampsia, diabetes, present with any of the clinical features of PCOS as
premature labor, and an increased stillborn rate. already outlined. Common presentations include
Because of these complicatlons and, the increased history of inability to conceive a baby and menstrual
likelihood of delivering a large infant, the C-section abnormalities such as oligomenorrhea, amenorrhea
rate is also increased. Because most patients with or vaginal bleeding. The patient may also have
PCOS have insulin resistance, it is not sur:prising that excessive hair growth, acne, deepening of voice or
the rate of gestational diabetes increases in other masculinisation features. As the condition is
pregnancy. " transmitted in a familial pattern, there may be
history of a similarly affected family member. PCOS
PCOS and Cancer Risk may also present with complications such as
Chronic unopposed oestrogen stimulation occurs in diabetes mellitus, heart disease or endometrial
PCOS due to anovulation. This can lead to cancer. A high index of suspicion is therefore very
endometrial hyperplasia which is a risk factor for the important in orderto detect PCOS in such patients as
development of endometrial cancer. This risk is the underlining primary cause.
increased when the intermenstrual interval is greater
than 3 months. Patients with PCOS should be Physical examination may be entirely normal.
screened for endometrial cancer through However obesity is a common finding with an
hysteroscopy andlor endometrial biopsy even when elevated BMI more than 25 kglm'. Patients that have
they are deemed to be too young to develop the prolonged vaginal bleeding may be pale. There may
condition. Ovarian cancer risk is also increased 2-3 also be hirsutes on the upper lip, jaw, chest or male
fold in PCOS and is commoner in those that are not on pattern of pubic hair distribution. Other findings may
oral contraception and those that are not obese. include frontal balding, acne and demonstrable
Since oral contraceptives protect against ovarian and galactorrhea.
endometrial cancer, they are recommended as a
preventive strategy. " Oral contraceptives will also A number of investigations are helpful in the
lead to regular shedding of the endometrium during diagnosis of PCOS.
menses thus preventing endometrial hyperplasia.
Serum levels of gonadotrophins may demonstrate
The link between PCOS and breast cancer is not
elevated levels of LH and normal or reduced levels of
entirely clear because many of the clinical factors in
FSH. However in consideration of the diurnal
PCOS are also associated with breast cancer such as
secretion of the gonadotrophins, this may not be
nulliparity and obesity. lt is however important to
demonstrated.
monitorthe breast in such patients duringtheirfollow
up.
Transvaginal ultrasonography may demonstrate
PCOS and psychological state
bilateral enlarged ovaries with multiple cysts. The
It has been noted that patients with PCOS may have
cysts are usually 8 or more subcapsular follicular
an above average risk of depression especially in
cysts < 10 mm and increased ovarian stroma. There
'obese and hirsute women. This effect may be
may also be elevated serum levels of glucose and
worsened by other co-morbidities such as infertility
fasting insulin. The presence of polycystic ovaries is
and amenorrhea. ln the African setting such patients
necessary for the development of the syndrome but
may be under pressure by her husband and other
not all women with polycystic ovaries have PCOS.
relations due to her inability to conceive a baby.
The typical polycystic morphology is present in about
Menstrual irregularities especially in younger patients
437
Comprehensive Gynaecolagy in the Topics
ZAa/" of the norma I ferha le popu I atioh ma hy iif Whom secretion fr6Rt the pituitar| glarrd thrOugh d rregative
616 non.hirsute, have regular mense6, dhd rioffnal feedback rhechanism. the androgefilc effect of LH on
serurh concdntrations of testosterone Eind thE ovary is thus ibolished hnd normal ovarian
steroido$enesis restored. Oestrbgen also prombtes
prdduction of sex hormone binding filobulin from the
Serum levels of prolactin and andrdgens liver thus rdducing the amdunt of free testosterone
(tosto6terone, dehydroepiandrostenedione and available, However, the choice of the pills is key in
androst6nedione) may also be elevated. Oiiil gltieose that some progestogens have androgenic properties
toleranee tests may diagnose diabetes meilitus. and should be avoided. Norgestimate and
desogestrel are virtually nonandrogenic
Diegnosis
progestogens. Drospirenone, an analogue of
The diagnosis of PCO is made by excluding other
spironolactone has unique antimineralocorticoid and
diseases such as the ones mentioned below as
antiandrogenic activities and in combination with
differ6ntial diagnosis. Recommended tests are
ethinyl estradiol is potentially ideal fdr the treatment
theiOfore thyroid function tests, serum prolactin and u
of women with the polycystic ovary syndrome.
free androgen index. The diagnosis is made if TWO of
the three following criteria are present: Polycystic Acne and Hirsutes can also be treated using tne
ovaries(8 or more peripheral follicles or increased antiandrogen cyproterone acetate or Dianette a
ovarian volume greater than 10cm3 on ultrasound
combined oral contraceptive with cyproterone
Scan); oligomeorrhoea, anovulation; clinical or acetate as the drug of choice in women with
biochernica I changes of hyperandrogenism.
h i rsutism. Cyproterone acetate com petitively
bits i nh i
the binding of testosterone and its more potent

Differential Diagnosis
conversion product, Sa-dihydrotestosterone, to the
The differential diagnosis includes all other
androgen receptor.
conditions that can cause masculinization. These
include congen ita I ad rena I hyperplasia, PCOS is one of the commonest causes of anovulatory
hyperprolactinaemia, androgen secreting tumors,
infertility. ln the treatment of PCOS related infertility,
thyroid disorders and Cushing syndrome. Other
it is important to check for other factors that could be
differential diagnosis included acromegaly, simple
responsible for the infertility such as tubal or male
obesiiy and virilising adrenal and ovarian tumours.
factors. Thus it is necessary to do other tests such as
hysterosalpigogram and seminal fluid analysis.
Management
The management of PCOS is mainly symptomatic. Treatment of PCOS related infertility is by induction
Apart from managing the symptoms of the patient, of ovulation.
efforts should be made to prevent, identify and

Oligo-or amenorrhoae in women with PCOS may
manage complications.
predispose to endometrial carcinoma. A withdrawal
The management should aim at weight reduction, bleed every three to four months, using cyclical
restoration of normal menstrual pattern and fertility, progestogens , the oral contraceptive pill or Mirena
and identification and treatment of complications.
protects against this risk.
Weight loss is achieved by life style modification in
Inductlon of ovulation can be done through several
the form of dietary management and exercise. Weight
ways:
loss could be managed in consultation with a
dietician. Weight loss significantly reduces
1. Weight loss leads to spontaneous
resumption of ovulation. The mechanism
hyperandrogenism, decrease LH concentration,
has been discussed above. Weight
restbres fertility and menstrual function. "
reduction and exercise also reduce the risk
Normal menstruation can be restored using of developingtype lldiabetes laterin life.
combined progestogen-oestrogen combination (as in

2. Clomiphene citrate is the recommended first
oral contraceptive pills). The same drug also ireats
line treatment for ovulation induction in
acne and hirsutism,. The oestrogen reduces LH
438
Polycystic Ova ry Synd rome
PCOS. " lt is an anti oestrogen which also formation was 25Y,; thus, it involved the
has oestrogenic properties, lt competes risk oJ converting infertility due to an
with oestradisl fsr the 9estrggen regpptors endocrine diqorder to one with a
in the hypothalamus. ln this way, the mechanical cause. A revived surgical
negative feedback effect of the oestrogen on approach to patients with PCOS and
the hypothalamus is removed leading tp infertility is laparoscopic ovarian drilling
pulsatile release of the Gonadotrophin (LOD), introduced by Gjonnaess in 1984.
releasing hormone which then acts on the The technique is used in different sur'gical
anterior pituitary gland to release FSH and settings. Most studies report the result of
LH eventually leading to ovulation. LOD in selected populations, Such as
Clomiphene Citrate-resistant patients, or
3. Though Clom iphene citrate is the concomitantly with Clomiphene Citrate and
recommended first line treatment for FSH treatment. Monopolar electrocautery
infertility in PCOS, obese women with often at 40 W for 2-3 seconds was used bY
require multiple courses and high doses of laparascopy to cauterize the ovary at
clomiphene. There is a positive correlation multiple points. As much as 61%
between obesity and the dose of pregnancy rates have been reporfed after
clomiphene required to induce ovulation. LOD.,O
Since increasing obesity is associatqd with
increasing hyperinsulinemia, the high 5. Assisted reproductive technology could also
degree of hyperinsulinemia in obese women be used to treat PCOS related infertility.
with the polycystic ovary syndrome may This is usually through ln vitro fertilization
account for their poor responsiveness to and Embryotransfer
) clomiphene citrate. Hyperinsulinemia could
adversely affect folliculogenesis and Discussion / Controversies
r
ovulation by increasing intraovarian L Controversies persist on the definition of PC0S and
androgen production altering gonadotropin the role of the presence of polycystic ovaries as
t"
I
secretion or directly affecting follicular criteria for defining the disorder. Most will no longer
development. Metformin is an oral regard the presence of polycystic ovaries as criteria
t
t
hypoglycaemic agent used for the treatment for the diagnosis since polycystic ovaries have been
f observed in asymptomatic patients. However
r of Diabetes mellitus. Treatment with
metformin, significantly decrease the serum majority will agree with the Rotterdam critaria as a
insulin response and leads to marked Gold standard.
increases in both spontaneous ovulation
11. Weight reduction is beneficial and in rare
and clomiphene-induced ovulation. " circumstances where the patient remains morbidly
4. Laparascopic ovarian drilling (LOD): The first obese bariatric surgery may be considered
established surgicaI treatment for women
lll.
Women who have PCO and conceive fqllswing
with polycystic ovary syndrome (PCOS) and
ovulation induction have a higher risk of miscarria1e,
infertility was ovarian wedge resection. The
small for gestational age fetus, pre-eclampsia and
ovulation rate was high after surgery, and
the baby has higher chances of admission to
the pregnancy rate ranged from 25 to 86%
neonatalunit
in different studies. However, the incidence
of postoperativg periadnexaI adhesion
439
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with bilateral polycystic ovaries. Am J Obstet pathogenesis. Endocrine Reviews 1997; lB(G):
Gynecol 1935; 29: 181 -9 1. 774- 800
2. Zawadzki JK, Dunaif A. Diagnostic criteria for 14.Conway SG, Jacobs HA. Acanthosis Nigricans in
polycystic ovary syndrome: towards a rational obese women with polycystic ovary syndrome:
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Med J 1990;66; 536- 538.
Merriam GR, eds. Polycystic ovary syndrome.
15.Wild RA. Obesity, lipids, cardiovascular risk, and
Oxford, England: Blackwell Scientific, 1992:377 - androgen excess. Am J Med 1995;98;27S-32S.
84. 16.Dahlgren E, Janson PO, Johansson S, et al. 1992
3. Franks S. Polycystic ovary syndrome. The New Polycystic ovary syndrome and risk for myocardial
England Journal of Medicine 1995;33 (13): 853- infarction. Evaluated from a risk factor mode,,l
861. based on a prospective population study t..
4. Revised 2003 consensus on diagnostic criteria and women. Acta Obstet Gynecol Scand.
7 1:599-603.
long term health risks related to polycystic ovary
lT.Homburg R, Berkowitz D, Levy T et al. ln vitro
syndrome. Hum Reprod 2004; 19: 41-7. fertilization and embryo transfer for the treatment
5. Franks S. Polycystic ovary syndrome. N Engl J Med of infertility assocrated with polycystic ovary
1995;333:853-861 syndrome. Fertil Steri I 1993; 60;858-863.
6. Erhman DA. Polycystic Ovary Syndrome. The New lS.Carmina E and Lobo MA. Polycystic Ovary
England Journal of Medicine 2005; 352: 1223- syndrome: Arguably the most common
endocrinopathy is associated with significant
36.
morbidity in women. The Journal of Clinical
7. Revised 2003 consensus on diagnostic criteria and Endocrinology & Metabolism 1999; 84 (6): 1897-
long-term health risks related to polycystic ovary 1899.
syndrome. Fertility and Sterility 2004; 81 (1): 19- 19. Sonino N, Fava GA, Mani E, et al. Quality of life of
25. hirsute women. Postgrad Med J. 1993; 69:186
B. Clayton RN, Ogden V, Hodgkinson J, et al. 1992 -189.
How common are polycystic ovaries in normal 21.Polson DW, Adams J, Wadsworth J, Franks S.
women and what is.their significance for the Polycystic ovaries finding in normal
fertility of the population. Clin Endocrinol (Oxf). women. Lancet 1988;- ai:common
870-2.
37:127-134. 21.Le Febvre G, Bringer J, Renard E et al. lnfluences
9. Farquhar CM, Birdsall M, Manning f Mitchell JM, of weight, body fat patterning and nutrition on the
France JT. 1994 The prevalence of polycystic management of PCOS. Human Reproduction
ovaries on ultrasound scanning in a population of 1997; 12(1):72-81.
randomly se/ected women. Aust NZ Obsiet 22.Consensus on infertility treatment related to
Gynaecol. 34:67-72. PCOS. Fertility and sterility 2008; 89 (3): 505-
l0.Krochenheuer E$ Key TJ, Kahsar Miller M et al. 522.
Prevalence of Polycystic ovary syndrome in 23. Nestlar JE, Jacubowikz DJ, Williams SE, Pasquali
unselected black and white women in North R. Effects of metformin on spontaneous and
Eastern United Sfates; A prospective study. The clomiphene-induced ovulation in the polycystic
journal of Clinical Endocrinology 1998; 83 (9): ovary syndrome. N Engl J Med 1998; 338:1876-
3078-3082. 80.
ll.Nestler JE. Polycystic ovary syndrome: a disorder 24.Cleeman L, Lawszus FF, Trole B. Laparascopic
for the generalist. Fertil Steril. 1998: ovarian drilling as a first line treatment in infertile
To,glralz. women with PCOS. Gynecol Endocrind 2004;
l2.Santen RJ, Bardin CW. Episodic luteinizing 18: 138-143.
hormone secretion in man. Pulse analysis, clinical 25.Kevelighan E, Gasson J, Ashraf M. Get Through
interpretation, physiologic mechanism. J Clin MRCOG Part 2: Short answerQuesfions Published
nvest 1 97 3 ; 52: 26 1 7-28
I by Royal Society of Medicine Press 2009.
l3.Dunaif A. lnsulin resistance and the polycystic
440
tf
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r
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CHAPTEE8
(
t
t
r
lnfertility
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t
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(
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: L A Omo-Aghoja and A ldrisa
f
r
{
r
I
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i
I Background more popular in the era of a collapsing and expensive
r\- It is estimated that about 70 to 2O%of couples have health care delivery that is obviously beyond the
I
i d iff icu lty i n conceivi ng successf u I Iy.''' The preva lence reach of the average couple in most developing
r of infertility is particularly high in Sub-Saharan Africa, countries.
I varying from 20% to 46% in some parts of West
t
f Africa where it constitute a significant proportion of Definitions
I
I workload of the Gynaecologists, accounting for 60- lnfertility is defined as the inability of a couple to
t
80% of all consultations.' This high prevalence is achieve a pregnancy within a given time period of
I
I
due in part to an increasing prevalence of sexually regular (at least thrice weekly), unprotected and
t
transmitted disease, post-abortal and puerperal satisfactory sexual exposLlre, usually over one year.'''
!" sepsis and in part to the increase in the number of It is primary if the couple has had no previous
I couples whose infertility problems have remained pregnancy and secondary ifthey have had a previous
I
unresolved for several years.''' Infertility causes pregnancy irrespective of the outcome of the
I
t severe emotional and social distress for couples. pregnancy (abortion or ectopic pregnancy).''' The
Available evidence suggests that women suffer more primary subset is commoner in the industrialized
{
I
than men as the malefactor is usually not recognized countries of the West and the secondary subset is
as a cause of infertility, and indeed, in many areas of commoner in sub-Saharan Africa and other
I
I
Africa as well as other developing countries infertllity developing nations.''' These two entities may further
is a socially acceptable basis for divorce by the be described as unexplained when the couple or
I husband.t''0 ln addition, there is large scale individual have no demonstrable cause of the
I
misinformation regarding the causes of infertility in infertility after evaluation for tubal factors, ovulatory
r indigenous African societies. lnfertility is often factors and seminal fluid analysis.''' Subfertility is a
i
believed to be due to sundry reasons such as synonymous term. Sterility is used where either of
i "witchcraft", "dissatisfaction of ancestors", "sorcery
:
the couple has absolute defect preventing fertility.
from unfriendly neighbors" and "punishment for a Fecundity is the capacity to participate in the
previous infidelity".l lnfertile couples frequenily production of a child and it is defined as the
consult non-medical sources of treatment like prayer probability of achieving a live birth in one menstrual
hoL-*., herbalists, traditional healers and cycle.' The term fecundability rate denotes the
spiritualists as a first line measure, and as a last probability of achieving pregnancy per cycle
resort, orthodox medical help when all these fail.16 attempted. lt is about 20 to 25% in normally fertile
Even when they consult orthodox practitioners, they couples.'
tend to go from one practltioner to the other and most
l. times, combine orthodox with traditional methods of Epidemiology
r treatment.''' This health seeking pattern has become Due to congenital (e.g. chromosomal abnormalities,
44L
Comprehensive Gynaecology in the Topics :
malformations of the genital tract, or abnormal with maximal fecundability. The longer the couple
:
endocrine function) or acquired (e.g. sexually has been trying to produce a child without success,
transmitted diseases/pelvic inflammatory diwse, the greaterthe progressive decline in the conception
post-abortalandpuerperalsepsis)and.rate.Thedeclineisindependentoftheageofthe
variations in the reproductive potentiaf':d.-L*iilmqn parties or the frequency of coital exposure. Overall, :
populations,aproportionofanypopufationt@.'beageisanimportantvariab|ethatimpactsonfertility
infertile. Available data suggest that this p*ryFftion and particularly demonstrated in women and much :
of
or "Core" rate of infertility is between 10 to 2S7o less in men'. Ten percentof women lessthan age 30
the populace.'-' The distribution of infertflityin yearswill presentwith infertility, 15% of women age l
couples on causal basis is 30-40% due to male 30-35 years will present with infertility, 30% of
factor, 30-40% due to female factor, lO-2O% due to women between 35-40 years will present with i
a combination of male and female factors, and infertility and 60%of women over the age of 40 will
another 5-70%unexplained'. presentwith infertility'z. .
lndevelopingcountries,particularlyinAfrica,thereotherintermediatingfactors,thatinfluencethe
appearStobeawidevariationinferti|ity'Theincidenceofinfertilityare:leVelofeducation(from
demographicsituationinAfricapresentsacomplexdelayingtheonsetofchildbearingtoreducingthe v=
sundry of fertility problems as far as the.level and desired number of children), use or non-use of
patterns of fertility are concern. The continent contraception -contraceptive use is reported to i
includes some areas were fertility is relatively very confer protection on fertility, fertility rate
:
low and others were it is normal. One aspect of (paradoxicallyinfertilityiscommonerin regionswith
infertilityinthelowfertilitybeltofAfricaisthatwithinhighfertilityrate)andsocioeconomicfactorssuchas
the same demographic regions, some ethnic groups poverty, smoking, alcohol intake and substance
have higher populations of infertile women than abuse'. l
others.
A thorough diagnostic work-up should identify one or
Cultural practices such as age of marriage, polygamy, more causes of infertility in about 90% of couples.
frequency of coitus, incidence of divorce, and Appropriatetherapywill resultin pregnancyinabout
marriage stability may influence fertilityl''. Other 40%of couplestreated.
socio-cultural factors, including traditional practices 1
suchasdowry,femalecircumcision,..fatheringPathophysiology
room',practices,and.deliveryhavealsobeenlnorderforconceptiontooccur,themanmust
identified as important variables underlying produce a sufficient number of normal, motile -:
infertility1.Pregnancyratesamongunselectedspermatozoainanejaculatemadeupofappropriate<
populations follow a predictable pattern. Half of secretions from the accessory genital glands.
nulliparous patients achieve pregnancy within the Another requirement for conception is the ovulation
I
first 5 months of unprotected intercourse. Fifty of an oocyte that is successfully implanted and then
percentoftheotherhalfwhoarenotpregnantatthesupportedbyanadequatelyfunctioningcorpUS
beginning of each subsequent 5 months will remain luteum. The hormonal events associated with :
non pregnan'. Women who have already completed follicular maturation, ovulation and corpus luteum
one or more pregnancies follow a similar, more rapid formation have profound effects on the entire female '
and predictable pattern. reproductive system. Fertility is possible only when
all parts of this system function so that hormone
the
Fecundability is strongly influenced bythe ages of production is suitable and consistent, follicles '
parties, the frequency of coitus and the duration of develop and mature, ovulation occurs regularly, and l
sexual activity without contraception. ln women, optimal conditions exist for the support of a fertilized
fecundabilityismaximalataboutage24;andafteroVum,e.g.adequatecorpuSluteum,appropriatesite
. ?ge 30 the decline is quite rapid'. ln men, of implantation,amongstothers.5
fecundability is also maximal at age 24-251. Coilal
Transportmechanismsof spermatozoaandsemen in
frequency of about 4-5 times a wiet< is associated human reproduction are complex. Spermatozoa and
442
lnfertility
seminal fluid must both traverse the accessory infertility. Systemic diseases such as severe or poorly
reproductive ducts of the male and be appropriately controlled diabetes, hypo or hyperthyroidism are
ejaculated from the penis. Coitus must occur.so that associated with decreased fertility, often for reasons
the semen is deposited in or near theCi4ryix. ln the that are poorly understood.'
female, initial transport of sperm occr"Hs in the
cervical mucus, which is profoundly altered by the Etiology
presence or absence of estrogen and progesterone. The etiology of infertility is best considered by
lmmunologic incompatibilities (such as active categorizi ng them i nto ma le or fema le factors.2
immune mechanism which induce high levels of anti-
seminal/sperm antibodies) may be manifested as The incidence of the various factors causing infertility
abnormal ities of cervical transport.''u'' varies among different populations. ln females
generally, disorders of ovulation account for about
Uterine transport of sperm is a poorly understood 30%-40% of all cases of female infertility, 30% to
phenomenon. The fallopian tubes transport sperm 40% is caused by pelvic factors mainly tubal
toward the ovary while simultaneously moving ova in occlusion following infectious causes, cervical
the opposite direction. This function is easily factors is estimated to be a cause of infertility in no
disturbed by a prior infection (especially chlamydia more than 5% of infertile couples, and uterine
and gonorhoea)''e with resultant adhesions or by pathologies constitute the etiologic factor in as many
inflammatory process such as endometriosis.2 as i5% of couples seeking treatment and are
diagnosed in as many as 50% of infertile
The endometrial cavity serves as the "incubator" of patients.''''"'"About 30% to 40% is associated with
the fertilized ovum. Endometrial infections or an abnormalities in the male mainly disorders with
inability of the endometrium to respond appropriately sperm production and function T'11'12 The cause of
to endocrine stimulation of the ovary may result in infertility in about lO% of the couples in most
infertility. Distortion of the endometrial cavity by sub- centres cannot be identified.' This group of patients
mucous myomas, synechiae, or congenital uterine is considered as "unexplained infertility". At the
anomalies may not only be an uncommon cause of University of Maiduguri Teaching Hospital, other
infertility but also a frequent cause of pregnancy regions of Nigeria and across some other African
wastage in the first trimester,'o countries, the contribution of partners to the
identified causes of infertility is shown in table 1,
Endocrine disorders.of the pituitary, thyroid and while table 2 shows the identified anatomical sites of
adrenal glands may result in infertility. ln most of abnormalities in female partners.
these disorders associated anovulation causes
Table 1: Contribution of partners to the identified causes of infertility
Countries/Regions
Partner North Southeast Southwest South-south Ghanaa Egypt'u
contribution Nigerial Nigerial3 Nigeria3 N igeriala
Number (%) Number (%) Number (%) Number (%) Number (%) Number (%)
Male only 344 Q8.6) 60Q2.6) 10 (11.1) t4 @.4) r27 (7r.8) 36 G2.7)
Female only 376 (31.3) 93(34,9) 34 (37.8) 78 Q4.3) 168(15.8) 74G7.3)
Both partners 360 (30.0) 64Q4.r) 36 (40) 225 UO.I) Not available Not available
; No cause 121(10.1) 49(18.4) 10 (11.1) 4 Q.2) Not available Not available

D found
TOTAL 1201(100) 266(100) 90 (100) 32 1( 100) 295 (100) 1 10 (100)
443
Table 2: ldentified Anatomica! Sites of Abnormalities in female partners
Regional data in Nigeria

Sites North 'SUtheast Southwest South-south
Nigeriar iligeriar6 Nigeria3
NigerialT
Number (%) Number (%) Number (%) Number (%)
Tubal 468 (63.6) 40ft6.7) 68 (25.8) 79 (s9.5)

occlusion
Ovulatory 217 Q8.7) 5Q.t) 200.6) Not

failure available
Utero-cervical 62 (8.4) 77Q.8) Not 66 (33)

factors available
Hypothalamic- 24G.3) 30(13.8) 26 (9.8) 26(73)

pituitary
ovarian Axis
disorder
TOTAL 736(100) 240 (100) 264 (IO0) 200(100)
FEMALE FACTORS pressure to appear a certain way, some women may

be underweight. A dietary history is therefore
Ovulatory factors essential."
Ovulatory factors account tor 30%-40% of cases of
infertility consultations in developed countries. ln Although an exercise history is easily obtained,
Nigeria, regional reports.show incidence of between factors affecting stress often are not apparent. For
74%to24"/o.". Overall, lt is a less common cause of example, many people hold several jobs to improve
female infertility in sub-Saharan Africa being largely their lifestyle. The stress inherent in such a schedule
submerged by the over whelming problems of tubal is compounded by the need to leave work frequently
disease. It is known that successful ovulation for infertility testing. The death of a parent can result
involves an intact and functional hypothalamic- in inability to conceive; many couples relocate and
pituitary-ovarian axis. Ovulation can be affected by a have no support base in their new homes. Any of
multitude of factors. The most commons ones these factors may result in sufficient stress to impair
include excessive weight loss or weight gain, exces- fertility.o'"'"
sive exercise, and extreme emotional stress. Twenty
percent above or below ideal body weight may affect Other important information to request of the woman
ovulation. Obesity and low body weight can impact includes age at menarche, menstrual history, and if
on reproductive function by causing hormone and when menstrual cyclicity changed. Questioning
imbalances and ovulatory dysfunction, it must be the patient regarding preference for hot or cold
remembered that obese people may be protein weather, changes in mood and energy, hair loss, and
deficient though these people may be eating quite changes in bowel habits may help uncover subtle
well. Furthermore, it must be remembered that obese thyroid disease.'''o She must alwqys be asked directly
I people may be protein deficient and these people about excessive hair growth. Hirsute women may
may be eating quite well. Due to poverty or social spend hours daily removing unwanted hair and thus
444
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lnfertility
I
f
{
1
appear not to have a problem. Acne and oily skin are tive for chlamydia infection have a history negative
(
P other clues of androgen excess. lnformation concern- for PlD. For this reason, testing for evidence of
r ing galactorrhoea must be obtained."@Q.use of its chlamydial infection is an important component of
[ ,._ frequent association with ovulatoryr,@unction. an infertility evaluation.' A seropositive test for
r
'ttl
Other causes of infertility such as cplz1ry,disorders chlamydia heat shock protein with a molecular
may also greatly affect ovulatory funEtiCIn. A good weight of 60KD is strongly correlated with tubal
I history on medical conditions such as siclde cell disease. Previous use of an intrauterine device (lUD)
t
disease, diabetes is also essential as this may affect is associated with as much as a fourfold increased
I
ovulation.'''' '' risk for pelvic adhesions and an increased rate of
PlD. For this reason, testing for evidence of
i
Another condition which is known to affect ovulation chlamydial infection is an important component of
I
r is Thyroid disorders.'o Thyroid disorders are quite an infertility evaluation. Salpingitis could also lead to
prevalent in the population of reproductive age, four abnormal transportation of the fertilized ovum there
I
I to five times more frequent in women than men. Both by increasing the risk of ectopic gestation and the
hyper- and hypothyroidism may result in menstrual need for salpingectomy further compromising the
i
i
disturbances, an increased risk of miscarriage, fertility profile of the woman."'"-
possible long-term health effects in the offspring and
i
!
r
spermatogenetic abnormalities. Thyroid CervicalFactors
autoimmunity (TAt) is more prevalent in infertile Cervical factors accounts for about 5%-10% of cases
rI women, especially in those with endometriosis. The of infertility." Because the cervix is anecessary
I
i
effects of hypothyroidism on female reproductive passage for sperm, however, a careful evaluation is
l hormones include a decrease in sex hormone binding important. Most times, cervical factors as a cause of
I
I globulin (SHBG), decrease in total estradiol and infertility are often neglected, so proper evaluation of
f
I
increase in the unbound fraction of testosterone and cervical factor should be done for complete investi-
I
I
estradiol. These changes may lead to alteration of ihe gation of infertility. Factors that reduce either the
pituitary ovarian axis. Lutenizing hormone (LH) may quantity or quality of cervical mucus may reduce
r
.l
,| increase but still within the normal range and sperm viability and, ultimately, fertility. Previous
pulsatile Gonadotrophin releasing hormone (GnRH) operations on the cervix, particularly an overzealous
r
I secretion required for normal follicular is impaired. cryosurgical procedure, cauterization (LLETZ), or
t'
Hyperprolactinemia is a well-known finding in cone biopsy,, may cause cervical stenosis or destruc-
rI hypothyroidism especially when thyroid under tion of cervical glands with resultant scant mucus.
activity is profound.' Alteration of cervical mucus can also arise from
f.--
I medication like antiestrogen e.g. clomiphene citrate.
I
t Tubo-Peritoneal Factors Postpartum dilatation and curettage (D&C) or

I
Tubal disease following pelvic inflammatory disease previous abortion could result in either cervical
I
(PlD) is the commonest cause of infertility in the stenosis or incompetence and habitual abortion.
female in sub-saharan Africa.''' The damage ranges Growths i.e. polyps or myoma of the cervix may
I
{
t
from mild salpingitis to severe salpingitis with interfere with normal migration of sperm. A history of
hydrosalpinx formation. The PID is usually caused by prenatal exposure to diethylstilbestrol (DES) must be
i
i sexually transmitted diseases with Neisseria elicited because of associated stenosis and other
t
Gonorhoea and Chlamdia trachomatis being the cervical abnormalities. Other anatomical consider-
I common pathogens.t'" Others include sepsis
t
ations would include abnormal positioning of the
following abortions, childbirth and intrauterine cervix as in retroverted uterus with the cervix
f contraceptive devices. Damage to the tube may result positioned away from the posterior vaginal fornix,
i
' also from adhesion following appendicitis, diverticuli- resulting in non-immersion of the cervix in the
(
tis, tuberculosis and pelvic surgery. Endometriosis is seminalpool."
a still seen as a rare cause of tubal damage in sub-
I
F
Saharan Africa, though with the advent of laparos- A chronic vaginal discharge or spotting suggests
copy, its incidence has grown. As many as 30% of chronic cervicitis. lnfection may destroy cervical
t women with pelvic adhesions and who are seroposi- glands or contaminate the mucus with leucocytes.
i.
i
I 445
i
Additional information regarding douching and use of Cigarette smoke is known to contain hundreds of
vaginal lubricant must be obtained becags€ both toxic substances, including nicotine, carbon monox-
practices are associated with potentiaf $i#ffiila| ide; carcinogens and mutagens such as radioactive
effects. The role of immunologicatfacto*.fi polonium, dimethylnitrosamine, naphthalene, and
infertility remains controversial but it is certAinthA methylnaphthalene. Epidemiologic studies have
some women develop antibodies to their'tfusbantfs demonstrated a consistent and highly significant
trend of decreased fertility with increasing numbers
of cigarette per day, especially among women who
Uterine Factors smoke more than 16 sticks of cigarette per day. There
Uterine factors are revealed in about 157o of coupfes is also an increased association of cigarette smoking,
seeking treatment for infertility and ale diagnoSed'in tubal disease and pregnancy wastage such as
as many as 50% of infertile patients. lf present'a,nd sponta neous a bortion a nd ectopic pregna ncy.
tn
untreated lower pregnancy rates are observed in

normal as well as IVF attempted conception. Previ- lnfluence of Alcohol and caffeine
ous D&C or therapeutic abortion may result in The stimulant properties of caffeine have led to its
intrauterine synechiae or cervical incompetence.2 widespread use as a beverage (coffee, tea and sc.r+
Patients with this problem may complain of reduced drinks) and some foods such as chocolate. ,LJ
quantity of menstrual flow. Spontaneous abortion, consumption has been reported to prolong the time
particularly if it is recurrent, could signify cervical to pregnancy; although the mechanism for this is
incompetence, uterine fibroids or congenital abnor- unclear, caffeine may affect female reproduction by
mality of the uterus such as septate uterus. Both targeting ovulation and corpus luteal function
uterine fibroids and polyps are commonly associated through alterations to hormone levels. Caffeine
with increased menstrual bleeding. Leiomyomata of consumption has also been associated with other
the uterus are common and may cause distortion of causes of infertility including tubal factors and
the uterine cavity and or fallopian tubes resulting in endometriosis and increased risk of spontaneous
infertility. lt should however be mentioned that the abortion.tn
exact relationship of fibroid and infertility remains
contentious i.e. whether the association is "causal or Alcohol is a known teratogen and its consumption
casual" still remain unresolved. However what is has been reported to decrease fertility, although the
certain is that if a patient has bilateral cornual fibroid level of consumption associated with risk is unclear."
masses occluding the ostia, this may prevent sperm Alcohol consumptlon at the extreme level is known to
ascent into the tubes and subsequently preclude be dangerous to the unborn child but the effect at
fertilization from occurring. Same may happen with lower levels is less certain. The mechanisms by
huge cervical fibroid occluding the cervical canal. On which alcohol could impair conception are unclear
the other hand, the fibroid may actually be part of the but may include an alcohol-induced rise in estrogen,
syndrome complex of the infertility as it is trite that a which reduces FSH secretion suppressing
uterus that does not bear children will grow fibroid folliculogenesis and ovulation. lt may also have a
from prolonged and sustained estrogenic exposure. direct effect on the maturation of the ovum, ovr-rla-
lndeed, current evidence tend to suggest that tion, blastocyst development and implantation.
infections have a role to play in the growth of fibroids, Moderate levels of alcohol consumption (seven to
and hence widely believed that same infection that eight drinks per week) have been associated with
resulted in the infertility may as well have stimulated reduced fertility and an increased risk of spontaneous
the fibroid growth.ou Endometritis may develop abortion. Levels as low as one drink per week have
following induced or spontaneous abortion,2'zs'za also been associated with reduced conception.''"
childbirth, intrauterine surgery or tuberculosis.'
!nfluence of Age in Reproduction
Acute or chronic endometritis may also occur as part
The tendency to delay child bearing until the later
of PlD. Other uterine conditions associated with
reproductive years is increasingily being observed.
infertility are adenomyosis and luteal phase defect.'?
Factors such as easily available contraception,
Smoking and Reproduction particularly with oral contraceptives, increasing
446
r
I
t lnfertility
t
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|-
r numbers of women pursuing academic and profes- and maturation arrest of spermatogenesis have been
I
I
sional career, changing sexual norms, and the social reported.T
acceptability of delayed marriage contribute to this
r_, phenomenon. The result is that rn are Male factor infertility
faced with a relatively shorter period uf-ffiS-i*flvhich Male factor is the only cause of infertility in 20% of
It infertile couples, but it has been demonstrated to
to conceive.
?
I
account tor 30-40% of cases of infertility in investi-
t
I Reduction in fecundity with increasing age is not gated infertile couples.'o''o 0f these, 57o are due to
{
t azoospermia and about 50"/" are idiopathic, with a
r limited to women.'Only a third of males oider.than
I 40 years impregnate their partners within 6 months large proportion of the idiopathic cases not amena-
t.
compared with men younger than 25 years.u'' ble to routine availabte therapeutic modalities.''"
(
I Although frequency of coitus in all probability is not
I
A careful history from the man is essential. Prenatal
totally accountable for decreased fertility, it is clear
exposure to DES has been associated with anatomic
that less frequent intercourse substantially reduces
I
the percentage of conceptions within a 6 months abnormalities such as epididymal cysts;
period. A sexual history is of particular importance in microphallus, and hypertrophy of the prostatic
I
I
patients of advanced reproductive age. By the time utricle." A history of childhood diseases or unde-
F,
women reach 35 years of age, their fertility is declin- scended testes is important. There is impairment of
I
ing. At an even earlier age, the number and quality of spermatogenesis in the presence of undescended
t testis. A history of childhood mumps is important in
r oocytes decrease but manifest clinically at around 35
!
I years of age. ln addition, the incidence of genetic male infertility, as it is frequently associated with
I
abnormalities and spontaneous abortion increase orchitis after the onset of puberty in affected men.
d
' Such men often have markedly atrophic gonads.'
I
1 observably with maternal dgl.' ,"'"
f
rI Changes in the endocrinologic function of women A history of operations on the bladder neck or
prostate must be sought, particularly for men with
f contribute to reduced fertility. There appears to be a
significant difference in the levels of estradiol, reduced seminal volume and azoospermia or
I
oligospermia. A history of testicular cancer must be

,1
'l progesterone, LH and FSH in regularly menstruating

women u nder the age of 40 and those over the age of explored. Return of sperm production after radiation
r
I
45 years. Such changes are in part due to aging of the therapy or chemotherapy may require 4 to 5 years.
f
ovaries and the Hypothalamo-pituitary axis and to Decreased ejaculatory volume may be due to
r
{ diabetes mellitus. lf the disease is associated with
I altered neurotransmitters. The uterus is also affected
peripheral neuropathy, a lack of emission or retro-
!r-
I
by advancing age. This is reflected by increasing risk
grade ejaculation may occur. Delayed sexual
I
for spontaneous abortion."
t
maturation may be due to hypogonadism
The effect of age in the uterus is also suggested by the ( Kal lmann's synd rome).'
i
r
demonstration of higher pregnancy rates among
i younger than among older oocyte recipients who Special care must be taken to enquire about alcohol
i
share oocytes during an egg donation." ingestion, smoking and drug use. Environmental
: toxins such as pesticides and occupational exposure
ln addition, the absolute frequency of autosomal to toxins may reduce semen values.''" Removal of
dominant disease due to new mutations among these toxins may reverse the adverse effects.
offspring of fathers 40 years or older is at least 0.3% Medication such as sulfasalazine, cimetidine, and
to 0.5%. This risk is many times greater than that nitrofurantoin may be gonadotoxic. Androgenic
among children of young fathers and is similar in steroids are occasionally administered to improve
'magnitude gonadal function, and young athletes more and more
to the risk for down syndrome among the
offspring of mothers who are 35 to 45 years of age.'o commonly are taking anabolic steroids. These
Men also demonstrate endocrinologic and anatomic substances inhibit gonadotrophin secretion and
I changes with advancing age. lnvolution of testicular i nterfere with norma I spermatogenesis.'
function, decreased sperm production and quality, Acute infection of the male genital tract is a common
447
a
in the Topics
Compr:ehensive Gynaecology
Others include exposure
play a part in male infertility'
Gonococcat, chlamydial heat and i nsecticides
cause of male infertility,,,
may cause semen
abnormali- il;;;;.tals, "
and coliform intections must ask the
*uy result in vassal or Finally, the physician "t f lt^li:
ties. tnflammatory Oamagl or or sustaining an erection
or ln
epididymal otoct< wittr iesultant azoospermia difficulty achieving often
t"*ttital abngrmqtities proUtems-of thir nature' are
severe oligosperm'''l' eiaculating'' the
anomalies- (44xry
or
lt is oiitn r"'trptut to interview
(cryptorch cnrlm"**tf
d ism), embarrassing'
ftnit g shows th'e classificationat
i
Tne
in sperm runct'ion'
46xxx) can cause o';;;J;;t oartners separately'
in zo+ infertile men
seen
I
role of varicocele ::lil

n.i'e
intefr]rtv shorrun ruff.;^"i*'rititt Hospital'
unclear.rr..u
't.tt"'t*
Spermatic vein Gation hasieen the U
guri Teaching
niversity of Maidu
in t"pt'* count' :ll!::"Ii
to result in improvem"eni can
and some environmentalfactor
excessive alcohol
Abnormalities
Table 3: Classification of Semen
flata frofil irypVRegions of Nigeria
Southwest I
Egvpt'
Northern Southeast
ilvpe
ot nunormalitY Nigeria36
Nigeria3i I
l
Nigeriall
(%) Number (%)
Number (%) Number (%) Number I \
20 Q.6)
I
6 (3.5) I
7604.2)
eo (12.8)
Azoospermia
189 (26.8) 119 (15,3) I sg tE+.gl I
40(7.5)
OligozoosPermta
r1 (6.5) 2(O.4)
48 (6.8) 41 (5.4) I
TetrazoosPermta
AsthenozoosPermla
56 (8.0) 30(4.8) 45 Q6.6)
7(4.2)
+
\ tzstzz.+l
I Not available
53(7.5) 27 $.6)
Oli go/teratozoosPermla 161(30,1)
24 $4.2)
i a
1 13(16. i) 32(4.2)
O I i go/asthenozoosPerm
10 (5.9) Not available
4i (5.8) 105(i3.9)
la
Tera to/asthenozqosPerm 7(4.2) 8(i.5) 1
ItA {16.2) 165(21.9)

ozoos 1'rc t
0 I i go/teratolasth
en
169(100) 412 (100)
704 (100) 755 (100)
- TOTAL
be investigated'
is infertile and should
when to investigate -
,,nnrotected coitus, a couple
,,ee"t'
rfconceptiondoesnotoccurafteroneyearofunprotectedcoitus'':ffil"."##;;;;r35years,asfertility
The investigution m,yiJinitiated
berore
"#:;;'(n";: :::Iil[,HX"ilili:';un!;;'J,.u,a ke ea rr er
gT;ffi I T;:' il:il *'"' * o' ttr at m av m i
;;ffi *j il*ru11ru'#i |o f i i['',X.;i' "

gation necessary'
initiation of i nvesti
J
448
r 1
f
I
lnfertility
t
f
,l
I
Table 4: History which suggest problems that may impair fertility
{
r Male
Ir 1. Previous historyof,&rmr.rhoea of STD
'I 2. Mumpsorchitis
r
? 3. Surgeryfor undescendedtestes
f 4. Previous history of leprosyor hydrocele
Female
1. Previous history of pe[vic inflammatory disease
I 2. Previous history of puerperal or post abortal sepsis
3. Previoustuberculosis
4. Previous laparotomyforperitonitis, appendicitis
t 5. Previous pelvic-surgery-ovarian cystectomy, myomectomy, salpingostomyetc.
6. Historyof delayed puberty
I
I
Approach to the initial infertili[ investigation

i
I
t
I
I
I
I
The couple is better seen together although certain the BMI of the patient as excessive BMI is linked with
I information may not be obtained in such a set up. causes of infertility such as PCOS.
I
I Such information could easily also be obtained during
r physical examination. Menstrual history, The woman's head and face should be examined for
f documentation of previous pregnancies, temporal balding, acne, or hirsutism. The thyroid
contraceptive history, tests and operations previously gland is examined and signs of hyperthyroidism are
r
i
1
performed and results and general medical excluded if history is suggestive. The breasts are also
{ information should be sought. The age of the couple, examined to ascertain proper development and
I
I
how long they have been married or living together, exclude galactorrhoea. Excessive hair on the trunk
rt coital history in terms of frequency and satisfactory i.e. chest, abdomen and suprapubic region and
I nature, whether they. had previous partners and how cl itoromega ly a re suggestive of hypera nd rogen ism.
t
i t..- long they have been trying to conceive are
I
I ascertained. Careful questioning concerning ethanol Visualization of the cervix includes the physical
f
and drug consumption must be obtained because of appearance if it is blind ending as well as inspection
I the frequency with which these substances are
of the cervical mucus. Copious amounts suggest
t
abused and the potential deleterious effects they may either impending ovulation or high estrogen
t-
have on reproduction. A history of exposure to associated with conditions such as polycystic ovary
l
I
environmental toxins, abortions, pregnancy from a syndrome. ln the presence of cervical mucus, a
i previous partner, STD and discord between the postcoital test may be performed in women whose
i
i partners must be sought. Frequently, more accurate spouses have declined presenting for seminal fluid
information is obtained if these questions are asked analysis or in couples with suspected cervical mucus
I
a separately during the individual examinations. A hostility if intercourse has occurred within the last 24
a hours. Occasionally abundant sperm is found at this
pedigree of both patients should also be obtained to
i
t identify potential genetic diseases. initial visit, and further testing of the cervix can be
eliminated. Attention must be paid to the position of
a
Physical examination the uterus and whether it is fixed or mobile. Nodules
The general physical appearance as well as the may be felt within the vagina which may be a pointer
ts carriage of the woman is important to rule out genetic to endometriotic depositd. Cervical excitation
,- abnormalities such as Turner's syndrome which may tenderness if elicited may also point to a possible
affect infertility. Special attention should be paid to pathology. The size and mobility of ovaries should be
449
determined. A rectovaginal examination should also lnvestigations

be done to determine the presence of uterosacral The initial evaluation of infertility should be
nodularity or tenderness as suggestive of thorough. The various tests should be done
endometriosis, systematically. The rationale and procedure of each
test should be explained to the couple.
Examination of the male includes emphasis on the
genitalia. General physical examination and limb Semi nal F lu id Ana lysis (SFA)
length are evaluated to determine the presence of The result of this test usually determines if male
genetic conditions such as klinefelte/s syndrome. infertility exists or not. The male partner should be
Limited body hair, gynaecomastia, and eunuchoid advised to abstain from coitus for 3-5 days before
proportions may suggest inadequate virilization. The collection of the semen sample.' The sample should
location of the urethral meatus is determined. The be collected by masturbation in a clear wide
scrotal contents are carefully palpated with the mouthed jar without the use of soaps or gels as this
patient standing to determine testicular consistency may affect the viability of sperm cells and alter the
and size to the nearest millimeter. results. Collection by coitus interruptus or with a
latex condom impregnated with spermicidal agent is
The volume of the testes can also be estimated with not recommended. However in cases where the
an Orchidometer. The long measurement should be couple is adverse to masturbation, collection using a
at least 4cm and the volume at least 18ml (15- spermicidal free condom may be accepted. ldeally
35ml).' A small testicular size is often associated collection should take place in hospital where
with impaired spermatogenesis. The epididymis is analysis can be done immediately. Table 5 shows the
palpated for induration or cystic changes and the vas characteristics of a normal semen sample.
deferens is palpated for nodularity. The presence of a Abnormalities of semen parameter include (i)
varicocoele, vascular engorgement of the Azoospermia (no sperm cell present), (ii)
pampiniform plexus, can easily be established by Oligospermia (sperm concentration less than 15
asking the patient to perform a valsava manoeuvre million per ml) (iii)Anthenozoospermia (sperm
while standing. An evaluation plan is then discussed motility less than 50% of cells with forward motility)
with the couple after the detailed physical (iv) Teratospermia (less than 50% sperm cells with
examination. normal morphology) and (v) Aspermia (no
ejacu late).''tu'tt
Table 5: *Recommended Normalvalues for semen parameters (WHO 2010)"
Semen parameters Normalvalues
Liquefaction time 30minutes
pH 7.2-7.8
Sperm concentration 15 X 106 or more per ml
Total sperm count 39 X 106 sperm/ejaculate
Motiliiy 40% (total motility) or
32% lprogressive moti lityl (a + b)*
Volume 1.5 ml or more
Vitality 58% or more live
450
:
I
lnfertility
I
I
I
I
I
WBC <1 X 106iml
I
t MAR test <LO% of adherent particles

I
lmmunobead test <2Oo/" of adherent particles
I
I
I Morphology 4"/" normal (Strict Tygerberg) criterion)
I
t
(
a
i
r
I
l
(
i
A conclusion of normality or otherwise should be vaginal cytology and cervical mucus, and (5) Serial.
based on at least two or three semen analysis 4 to 6 u ltrasou nd fol I icu logra phy.
i
I
weeks apart. lt may also be necessary to subiect the
semen sample to centrifugation and sperm pelleting Basal body temperature tracing has proven to be very
to confirm for certain that azoospermia on routine useful in the investigation of infertility. The woman is
I
SFA is real.'''u normally taught to keep a chart of her body tempera-
I ;
ture taken on rising each day. Biphasic pattern
Additional tests that may need to be undertaken to suggests that ovulation has taken place, the elevated
(t determ i ne the etiology of the red uced semen pa ra me- temperature phase having been produced by the
ters include hormone assay (follicle stimulating thermogenic effects of progesterone, By contrast, in
a hormone, luteinizing hormone, prolactin, progester- non-ovulatory and therefore non-progesterone
i one and testosterone), karyotyping, scrotal ultra- cycles, the temperature pattern is typically
I
sound scan and vasography. Testicular biopsy is no monophasic. A major disadvantage of the method is
.l
longer regarded as being of any benefit in the routine that not many women can keep the dailytemperature
investigation of male infertility. Except when records, either due to the variable and hectic pattern
i testicular spermatozoa on biopsy are needed for use of their work schedules or because of their inability to
F in intra-cytoplasmic sperm injection (lCSl) during in read and interpret a clinical thermometer correctly
{
I vitro fertilization (lVF). Emerging studies suggest an and consistently. However with good counseling and
I the use of digital thermometers, many women are
increased risk of testicular carcinoma in situ (ClS) in
II '-- idiopathic azoospermia. Therefore, it is suggested motivated enough to use the method for continuous
I
I
that except where testicular CIS is suspected, ovulation assessment throughout the period of the
I testicular biopsy should be performed only when infertility management. The disadvantage of this
r adequate microsurgical facilities are available to treat method is the fact that temperature may be altered or
obstruction to sperm transport, and when facilities affected by conditions which may falsely elevate or
are available for cryopreservation of spermatozoa lower the basal body temperature.
andlor part of the excised testicular tissue for further
use in assisted reproduction. Some microsurgeons ln a normal ovulatory menstrual cycle the
prefer that biopsies should be avoided altogether for endometrial histology on day 21 of the menstrual
fear of compromising future microsurgical proce- cycle would reveal a secretory endometrium that has
dures.''t' maturity that is compatible with the day of
endometrial sampling. The ovaries and the ovarian
Tests of ovulation follicles can easily be visualized using a sector
This can be done by (1) measurement of daily basal ultrasound scan with a vaginal probe. The follicle
?
body temperature (BBT), (2) midluteal phase appears as echoluscent circular spots within the
measurement of serum progesterone, and usually on more echogenic ovarian tissue. Ultrasound
{ day 27 of a 28 day cycle, (3) Endometrial biopsy on fotliculography is useful in monitoring ovulation
day 27 of a 28 day cycle, (4) Examination of the during induction of ovulation.
45t
Hormone assay consists of the estimation of serum hysterosa I pi ngogra phy.

Luteinizing hormone, follicle stimulating hormone,
thyroid stimulating hormone, testosterone, prolactin Laparoscopy is usually done in the luteal phase of the
and midluteal phase progesterone which is usually menstrual cycle around day 27 of a 28 day cycle and
day 27 for a 28-day cycle or a progesterone lndex is often combined with an endometrial biopsy for the
(mean value of samples taken on days 20, 27 and histological assessment of ovulation. Laparoscopy is
22). A serum progesterone level of >Snflml best done under general anaesthesia. Local analge-
( i 3 nmol/L) is evidence that ovulation has occurred. sia combined with light sedation can also be used.
Laparoscopy is usually combined with a
ln contemporary practice, the recommended testsfor transcervical methylene blue eye test and
assessment of ovulation are a combination of well- endometrial curettage. Laparoscopy provides direct
timed midluteal phase progesterone assay with visualization of the pelvic organs.
transvaginal ultrasound follicular tracking. Other Hysterosa pi ngogra phy
I a nd la pa roscopy a re com ple-
tests mentioned above are less ideal and less robust, mentaryto each other in investigation of infertility,o'z
fraught with problems of inconvenience and interpre-
tation, and are cumbersome. Fluoroscopic evaluation of the fallopian tubes using
ultrasound scan known as hystero-contrast-
Anti mullerian Hormone assay (AMH) is a good sonography can also be done. Direct visualization of
predictor of ovarian reserve in contemporary gynae- the uterine cavity using a hysteroscope is also a very
cology. lt is important to recognize that a poor result helpful procedure in infertility evaluation.
from ovarian reserve testing does not signify an
absolute inability to conceive and should not be the Newer methods that have found wider use in
sole criteria considered to limit or deny access to developed countries in assessing tubal patency but
infertility treatment. Female age and ovarian reserve almost not available in developing countries include
test results are useful for discussing prognosis and selective salpingography and tubal catheterization,
recommending a treatment plan. Younger women falloscopy (falloposcopy), fertiloscopy and
with diminished ovarian reserve demonstrate salpingoscopy.
reduced oocyte numbers but may have normal oocyte
quality, whereas older women with normal ovarian Postcoital test
This is also termed as Sims-Huhner test. This is used
reserve may have a good number of oocytes but an
age-a p p ro p ri ate d ecrease i n oocyte q u a I ity.
oo'o' to assess cervical factors that may be associated
with infertility and also for women whose spouses
Test of tubal patency refuse to present for SFA.' The test is normally
Tests for tubal patency include (1) performed at the time of ovulation, on day 74 of a
hysterosalpingography (HSG), (2) laparoscopy and normal 28 day menstrual cycle. On this day, the
(3) ultrasound scan in what is known as couple is advised to have intercourse in the early
hysterocontrast sonography. ln hours of the day. Thereafter, usually within 9-
hysterosalpingography, a water soluble dye such as 24hours, the woman would be examined in the
sodium amidozoate (hyapgue) or urographin is gynaecology clinic. Early examination of the mucus
instilled through the cervix into the uterus and spot before 2 hours might be deceptive because comple-
radiological films are then taken at timed intervals. lt ment dependent reactions in mucus which can
is usually performed on day 10 of a 28 day menstrual immobilize sperm may not be apparent for a few
cycle. lt is to be avoided in the presence of acute hours.
pelvic inflammatory disease (PlD) as the procedure
may.cause flare up of salpingitis. HSG should be A bivalve speculum would be passed to expose the
performed with the aid of an image intensified cervix. The cervical mucus is inspected and a
fluoroscopy. HSG woutd outline the inner lining of the sample taken with a clean pipette. The sample is
uterus and Fallopian tubes, intrauterine and tubal then examined for volume, clarity, and stretchability
adhesion and fibroids. Exact site of tubal obstruction between two glass slides (spinnbarkheit). ln addi-
cquld easily be demonstrated with tion, a sample of the mucus would be examined
452
t
I
r lnfertility
I
;
l under light microscopy to determine the presence of during the succeeding month. This concept is known
i
I actively motile live spermatozoa, ln a normal as 'Active management of infertility'. This will help to
r postcoital test, the cervical mucus is dtBn profuse, reduce the emotional distress for the couples and
fr.
) c|ea r, watery, re|atively ace| u Ia r a nd cffifu&rdwn up
I decrease the likelihood that they would seek alterna-
r to 20cm between two glass slides.'st *,.t6rnple tive sources of treatment. A history and physical
I
often demonstrates a good fern test (agffi aflbrisa- examination can be done on the day preceding the
tion pattern can be identified under the mieroscope onset of menses and a semen analysis requested at
r when it is left to dry in a glass slide). Finally, more the same time. With the onset menses, the woman
I than 5 actively motile live spermatozoa arc present can be taught to keep a BBT chart and hormonal
+
1 per high powered field. An abnormal postcoital test assays (serum FSH, and Prolactin) may be done on
usually implies the absence of these parameters and day 2 or 3. A HSG would be done within the first 10
rr may be due to wrong timing of the test and abnormal days of same menstrual cycle, usually 2 to 3 days
cervical mucus such as that produced in patients after the menstrual bleed and a postcoital test at the
tr with chronic cervicitis. Other causes of abnormal midcycle which is usually on day 14 for a 28 day
postcoital test include the presence of antisperm cycle. Finally a laparoscopy, dye test, endometrial
t antibodies either in the woman or in the husband, biopsy and hormone assay (serum progesterone)
semen abnormalities and difficulties with sexual would be performed on midluteal phase usually day
tt- intercourse. Postcoital test can also be used to assess 27 for a 28 day cycle to complete the full comple-
?t the male factor in a situation where the husband had ment of tests.
I
evidently refused to submit himself to a formal semen
I
!
examination.' Treatment
( The treatment of infertility can either be by conven-
I
t
t ln-vitro sperm migration tests are recommended tional methods or by the newer assisted reproductive
rI when the semen analysis is normal but result of the technologies. Regardless of the method chosen,
I postcoital test are poor. The first penetration test was treatment is often prolonged, costly and sometimes
r described in 7928 by Kurzrok and Miller. The frustrating. Thus, at the completion of the investiga-
.! capillary tube mucus penetration test described by tions, time should be taken to explain the result and
Kremer is a more widely used in-vitro test. lt is placed their implications to the couples. ln particular, they
r on a microscopic slide and within a flat capillary should be given realistic and accurate information on
tube, suctioned with negative pressure. The mucus is the anticipated outcomes of the proposed treatment
rt drawn into the capillary tube, care being taken to method,
ensure that no air br]bbles are present. The capillary
! '.- The type of conventional infertility treatment chosen
I tube is then placed vertically into a test tube contain-
ing 1ml of the male partner's sperm, and this tube is depends on the identified causes of infertility, the
r
I placed in a rack for t hour. At the end of that time, the severity and nature of the clinical condition, the age
I
distance the spermatozoa have travelled is mea- of the couples and the length of infertility. Male
?
sured. lt is important to compare sperm penetration infertility presents one of the greatest challenges with
u'''"'o''oo
I of the patient's mucus with that of donor mucus. respect to i nferti ity treatment i n Af rica.
I
I
Bovine cervical mucus is commercially available for
I
this purpose. Failure of the sperm to penetrate the Many of the recommended conventional treatment
I cervical mucus could be due to immunological methods for male infertility, hormone treatment,
factors or immotile spermatozoa. Presence of motile
improvemelt -of nutritional status and surgical
spermatozoa throughout the 30mm column of the
treatment such as varicocoelectomy, amongst others
I
have low effectiveness either in terms of improve-
cervical mucus implies normal migration.
ments in semen parameter or in relation to achieving
i
Ti m i ng of I nvestigations a subsequent pregnancy. This is because a large
The timing of investigations is very important in the proportion of male infertility is either due to unex-
t management of infertility. lnfertility evaluations can plained factors or to irrev€rsible factors such as
be completed during one single month of a menstrual severe testicular failure. Therefore, the trend in
i present day management of male infertility in both
I cycle and the results provided to guide treatment
i
, 453
r
Comprehensivr t)ynaecology in the Topics
developed and developing countries is to have a low available. There is the need for constant monitoring
threshold for progressing to the use of ongef the when a patient is on these drugs.
assisted conception procedures.''ot
= _' ..t., .
Congenital uterine abnormalities, uterine fibroids
Assisted reprod uctive procedu res that asclie*&l +n : and Asherman's syndrome are treated surgically with
the treatment of male infertility include,artifuF*t good results for ferti I ity.
insemination using the husband's full serrpn:or.* ft
ejaculate. Sometimes, the semen may be wal;@4* M a nageme nt of u nexpl a i ned i nfe rti I ity
vitro with artificial media and centrifuged with the lf a policy ofexpectant management is deployed,
hope that actively motile spermatozoa would swim to
that is the couples are untreated a low pregnancy
the surface of the supernatant. The motile spermato-
rate of about 0.9% is achieved per cycle whereas
zoa can then be aspirated and then used either by those that had IVF intervention achieved a preg-
intrauterine insemination (lUI) or for other assisted nancy rate of about 17Y". lt is against this backdrop
technology procedures. This swim up technique of that the concept of expectant management is rapidly
semen preparation has found specific usefulness in
giving way for initiation of empiric therapies in
the treatment of some forms of severe olisospermia couples with unexplained infertility. The treatmen+
especially those associated with antisperm antibody. typically involves superovulation (increasing femal-
gametes); collecting, washing, and concentrating
Donor insemination is also useful in the treatment of
male infertility especially in severe causes of the semen (increasing motile sperm); and bypassing
ol igosperm ia or azoosperm ia.n'-ou
a potential cervical factor using lUl. Superovulation
with clomiphene citrate and lUl is usually the initial
The treatment of bilateral tubal occlusion is equally treatment regimen employed. This therapy is fairly
tasking. When both tubes are found to be blocked efficacious in many couples with unexplained
and or diseased, conventional treatment method is infertility and is less invasive, less expensive, and
macrosurgical or microsurgical repair of the tubes. associated with fewer complications than other
Several tubal repair procedures such as salpingolysis, forms of treatment. However, if clomiphene citrate
salpingostomy, segmental resection and end to end with lUl is unsuccessfulafter3 months of treatment,
anastomosis and cornual reimplantation of the tubes then controlled ovarian hyperstimulation using
have been described. However, these methods have gonadotropin therapy should be undertaken in
uniformly not been found to be associated with conjunction with lUl. lf both these approaches fail to
satisfactory pregnancy rate. Thus a large proportion result in pregnancy, then IVF and lCSl can be
of these women will eventually require some form of performed.ou
assisted reproductive technologies to resolve the
Assrbted Co nception
infertility problem. ln vitro fertilization and embryo
This is essentially all treatments or procedures that
transfer (lVF-ET) was originally designed for the
include the in vitro handling of both human oocytes
treatment of severe tubal infertility treatment world-
and sperm, or embryos, for the purpose of establish-
wide.ou
ing a pregnancy.ou
ln contrast to the poor treatment outcomes often

There are various forms of assisted conception. ln
experienced with male and tubal infertility,
vitro fertilization and embryo transfer t(lVD and
anovulatory infertility has uniformly higher rates of
(ET)1, as well as Gamete intra-fallopian transfer
treatment success. When appropriatdy*treated,
(GIFT), are most common. There are other modifica-
women with infertility due purely to anffition can
tions of IVF such as pronuclear stage tubal transfer
expect to achieve an 80% pregnancy rate within 6
(PROST), zygote intra-fallopian transfer (ZIFT),
months using the presently available treatment
partial drilling of the zona pellucid (PZD), the
methods. Ovulatory regimens are Widely available
intracytoplasmic sperm injection (lCSl) and micro
and they consist of anti-estrogens such as
epidermal sperm aspiration (mesa), ln addition to
clomiphene citrate, tamoxifen and cyclofenil;
the above mentioned entities, gamete and embryo
prolactin antagonists such as bromocriptine and
cryopreservation, oocyte and embryo donation, and
quinagoline and gonadotrophin (pergonal) are also
454
I
{ lnfertility
I
{
i
r
it
gestational surrogacy are forms of assisted concep- gate" and has no genetic tie to the child.ou IVF
( tion. lt should however be noted thatART does not surrogacy is notallowed in the majorityof countries.
i?
i"
I include assisted insemination (artifici# insemina-
[*- tion) using sperm from either a wsrf*aHffier or a Adoption
:l,} This is a viable alternative for most infertile couple,''o'
s pe rm d o n o r. I n vit ro f e rt i i zati on i nvohressBtemova
I I
ll
r of an egg, the collection and purifie&*d-Wm and This option is practiced in various forms in many
the mating of the sperm and egg in the tabordory. lf traditional African societies, ranging from adopting a
I
i fertilization occurs in the laboratory, the developing living or a dead brother's child, a friend's child or the
embryo is transferred into the uterus usually. two or child of a distant relation. Formal adoption or legal
i
three days after, at the 4'n and 8'n cellstage.ou adoption is still very cumbersome in our current
1
r setup. ln centres where the demand exists, the

I The indications for ART include: ffidh and female process of legal adoption is usually either too long or
ta infertility not amenable to conventional rnedical or there are too few children available for adoption.
i surgical treatments, unexplained infertility, women Finally, where adoption is not possible orfeasible, the
r diagnosed of cancer or medical disorders facing couple should be counseled on how to cope with
I imminent treatment with chemotherapy or radiother- childlessness'z
{
f apy, and women with severe medical conditions who
flE Prevention
{ may still be offered the opportunity to have their own
t genetic offspring through the use of gestational The prevention of infertility should be a part of the
f management strategies for infertility in Africa.
surrogate. However, some forms of ART are used in
f combination with pre-implantation genetic diagnosis Prevention strategies are desirable because they can
; (PGD) in fertile couples for genetic reasons or in avert the emotional and economic costs associated
i
r couples who are discordant for certain communica- with infertility treatment, as well as preempt some
t
ble diseases, and more recently in same sex union or infertility that would be wholly untreatable. A
f comprehensive strategy using primary, Secondary
r individuals opting to raise children as single parents.
and tertiary preventive methods have been advo-
1
The cost of Assisted Conception technology remains

too high for most sub-saharan African centres where cated.ot'ot
;
unfortunately, severe tubal disease is common.
r However, over the last two decades, the practice of Primary prevention involves the prevention of
i
Assisted Reproductive Technologies (ART) that assist medical and reproductive health conditions such as
r reproduction, increasing the chances of conception infections that may lead to infertility. These include
I
t has rapidly increased. The number of countries now the prevention of sexuallytransmitted diseases, post-
f.
practicing ART has multiplied many times and it is abortion infections and puerperal infections. Since it
,,
i available throughout Asia, the Middle East, South is now well known that infection accounts for about
{ America, and parts of Africa. Virtually all forms of 85% of infertility in Africa, a policy directed towards
i
ART are now available in Nigeria and other sub reducing the high rate of pelvic infections would
i
regions. substantially reduce the rate of infertility in many
I
I African countries. ln this way, the primary prevention
f
Surogacy of infertility ought to be carefully integrated into the
t
t Surrogacy is an agreement in which a woman full complement of packages aimed at preventing
I
becomes pregnant and gives birth to a child for reproductive tract infections in women and men.
i someone else.ou This is usually indicated in females Clearly three categories of infection currently
I who have congenital or acquired absence of the produce the most severe forms of pelvic infections
uterus,' or who have severe medical conditions leading to infertility in the sub-region. These are
. contraindicating pregnancy and still desires their own sexually transmitted infections, especially Neisseria
genetic children. lf the surrogate's own eggs are used gonorrhea and Chlamydia trachomatis. Second
through alternative insemination or IVE she is known consideration includes abortion related infections.
as the "genetic surrogate." lf embryos are created Thirdly, infections arising from prolonged labor and
using another woman's eggs and implanted in the other complicated child births. Thus, appropriate
surrogate, she is known as the "gestational surro- policies should be developed for preventing these
455
Comprehensi'"' Gynaecology in the Topics
screening and cessation is an important component

various causes of pelvic infections.'u''u
of primary prevention of infertility' Recognition that
The prevention of sexually transmitted diseaaes regular strenuous exercise, rapid weight loss, low
involves the provision of reproductive heaffi'{Wg' body fat, and stress may cause decreased fertility
tion to men and women at all levels, p-ffi'oil (women are at higher risk than men) and as such
abstinence or condoms in those who carffi:'Ah€Stn should be avoided. Environmental and occupational
or who have multiple sexual partners, early tt@trn*nt hazards account for an unknown proportion of
of cases of sexually transmitted diseases, contact infertility and as such should be avoided when
tracing and treatment of infected partners' The possible. Obesity which affects infertility in both
pr.u.ntion of infections arising from complicationg of women and men should also be prevented by eating
childbirth similarly includes the provision of repro- a balanced and nutritious diet, fruits and vegetables
ductive health education to all segments of our (plenty of folates), and maintenance of normal body
society with a view to eliminating dangerous myths weight are associated with better fertility pros-
and beliefs that presently hinder effective utilization pects.'n'oo'uo
be
of maternity services. ln particular, women should
counseled to use clean delivery surfaces for labour
Secondary prevention of infertility is aimed at tl
early recognition and treatment of sexually transmtr-
and delivery and preferably to deliver in hospitals
where asepsis can be guaranteed. Policies directed at
ted diseases, abortion and puerperal infections' As
the prevention of prolonged labout especially the use
with primary prevention, secondary prevention
focuses largely on Sexually Transmitted Diseases'
of partographic labour monitoring, can also effec-
Examples of such approaches include prompt
tively reduce the rate of subsequent pelvic infections'
recognition of signs of urethritis, vaginal infection'
Policies directed at preventing abortion related sepsis pelvic inflammatory disease (PlD), epididymitis' or
profes-
would have the greatest impact in preventing orchitis, followed by prompt evaluation by a
sional, diagnosis, and effective treatment' Locating
secondary infertility in many parts of Africa' Many
countries in Africa currently have restrictive abortion cases of STDS and sexual contacts of infected
laws limitingthe use of abortion only to cases where it individuals is also an important means of secondary
is needed to save the life of the woman' Available prevention since it allows for early diagnosis and
evidence suggests that this policy have not reduced treatment of individuals infected but not yet irretriev-
the rate of abortion; rather, it has driven the practice ably affected by chlamydia or gonorrhea' ln the case
of inflammatory conditions such as endometriosis'
it
of abortion underground and created a situation
where most abortions in these countries are per- should be treated at the earliest possible opportunity
formed by non-professional quacks' By contrast, in either medically or surgically to provide the greatest
oo'ou-uo
ent i nferti ity'
more developed countries of the world where kel i hood of averti n g su bseq
Ii
u I
abortion related sepsis and infertility is extremely low'

Tertiary prevention is the treatment and rehabilita-
A liberal abortion policy backed by measures to preven-
of tion of couples affected by infertility' Tertiary
increase unwanted pregnancies will reducethe role
abortton complications and of subsequent infertility tion includes the use of methods to mitigate the
in many African countries'u'
effects of infertility on couples' These include
systematic counselling and use of conventional
of
Other primary prevention measures include Iife style methods of infertility treatment such as induction
modification of modifiable factors that contribute to ovulation, donor insemination' Where cost is not a
the burden of infertility. lt is known that smoking, as problem, the use of one of assisted reproductive
well as other substance abuse, reduces reproductive techniques is advocated' Besides, couples with
difficult and irreversible forms of infertility should
be
potential. Although smoking is more common in
foster
developed countries, its effect on infertility in the
sub counseled to accept their fate, and to adopt or
children. ln particular, clinicians managing couples
Saharan Af rican region cannot be overlooked '
lnfertility specialists are increasingly aware that with infertility in Africa should be acutely aware of
for
exposure to tobacco products can cause infertility the social consequences of infertility, especially
and interferes with its treatment and that tobacco women and are requested to use innovative methods
456
lnfertilig
to secure ti'e couples' accurate and realistic under- fibroids. There have been no appropriately designed
standing of tlre condition so as to reduce the intensity studies to demonstrate a direct causal relationship
of the social problems. The tertiary Frevention of between the presence of fibroids and infertility. With
infertility has been less than optimal in rnry ppimn such a heterogeneous disorder, studies are difficult to
countries. Though ART successes :lHwe been perform and adequate conclusions difficult to draw.
achieved in some African countries, these nurn'tlers The effect of fibroids on reproduction remains in
are small compared to the high numbers of couple question. Submucosal fibroids seem to have an
who seek specialized infertility treatment. This is as a impact, whereas subserosal do not. lntramural
result of the high cost of the procedures which may fibroids might have an impact, but randomized
be unaffordable in most countries in sub Saharan studies with adequate evaluation of intracavitary
Af rica.'n'oo'o' involvement are necessary to adequately evaluate
whether the benefits of treatment will outweigh the
Discussion and Controversies serious surgical and obstetrical risks that follow
There are numerous areas of the subject matter of myomectomy. Treatment of fibroids should thus be
infertility that has generated debate and controver- individualized.5'
sies of over time. Contemporary aspects of these are
espoused below. lll. Adoption in the management of infertility
Major socio-cultural concerns that have generated
l. Varicocele and infertility contention with the practice of adoption includes
The benefit of varicocele repair to improve male stigmatization associated with adoption, unknown
fertility is still controversial with evidence existing parental background and possible negative genetic
both in favor and against it. Some authorities have composition or inherited diseases (psychiatric or
advocated that varicocele is detrimental to male epilepsy), confidentiality about adopter's decision,
reproductive health and Ieads to a decline in semen future claim by the biological parents, and disloyalty
function. lts treatment may improve sperm function or abandonment by the child especially when the
and chances of conceiving and men ileated for child Iearns that he/she was adoptedo'. The regula-
varicocele may have a favorable impact on assisted
tion on adoption practice varies from country to
reproductive technology outcomes. While others country, and in most countries of our sub-region there
believe that there is no benefit from treatment of are scarcely clear-cut guidelines and statutes on this
varicocele with respect to odds of pregnancy.t''to''u practice.
ll. Fibroid and infertility !V. lmmunological treatment of Fertility problems

The subject of the exact association of fibroids and There has been a lot of debate surrounding the
infertility in a population of women is a controversial immunological factors affecting fertility. Among
subject matter in gynaecology. lt is said that whether infertility experts, there is uncertainty and even
the relationship between fibroid and infertility is controversy as to whether immunological conditions
'casual or causal' is uncertain and this contention has and abnormal female immune functions exert a
been earlier elucidated in an initial paragraph. causative effect upon infertility. There are doctors
According to a study approximately 5% to 1O% of who believe there is no connection, and those who
women presenting with infertility are found to have is. Some researchers and practitioners
believe there
one or multiple fibroids. However, when all other believe that administration of drugs such as
causes of infertility are excluded, fibroids are found in prednisolone, aspirin or heparin can improve success
onlv 1% to 2% of the remaining women. Both rate of implantation and pregnancy through the
infertirity and age have been associated with the inhibition of coagulation, inflammatory and immune
presence of myomas and may therefore confound
systems; while others believe that such systems not
results of studies attempting to clarify the relation- only do they have negative effect on rejecting
.r' ship between fibroids and infertility. Women present- blastocyst and embryo by itself but also are neces-
ing with both fibroids and a history of otherwise sary for implantation and rembdeling of uterine spiral
F
unexplained infertility represent a challenge. These arteries through secreting adhesive and angiogenic
women may or may not be symptomatic from these factors. Such controversies are proposed both in
:
-
457
t'
..- l-==-l
natural pregnancies resulting in spontaneous for IVF or in conjunction with Al have a higher rate of
abortion as well as in successful and/or uns-uccessJul multiple births, and therefore mothers as well as
assisted reproductive technologies G,RTsJwith offspring face risks associated with multiple gesta-
several ltreatments been advocated,=tg,.:ery/S tions occur at higher rates in ART pregnancies
pregnancy rates. Some of these factots, EP compared to singletons. "selective reduction," in
adversely affect fertility include AntiBhqsi id which one or more fetuses are aborted, depending on
a nti bod es, Thyroi d a nti bod ies, Ova rian r'ans@di9,g,
i
the number she is carrying is an option which some
Antinuclear antibodies, Antisperm antibodies, and women choose to prevent these risks. Some
Natural Killer cells. Apart from the treatrnent of countries such as Germany and ltaly do not allow the
Antiphospolipid antibody syndrome (APS), none of destruction of embryos, and thus all embryos
the other treatments been proposed to treat this array created in the IVF process must be implanted in the
of conditions are thought to be supported by strong woman intending to become pregnant. Some
evidence.u''u' countries have adopted a policy of eSET (elective
Single Embryo Transfer) and have shown that in
V. Pre-lmplantation Genetic Diagnosis (PGD)/ Pre' properly selected cases, this policy can be imple-
lmplantation Genetic Screening (PGS) mented without compromising IVF success rates but
Pre-lmplantation Genetic Testing is a technique that significantly reducing the multiple birth rates.
allows a diagnosis of a genetic or a chromosomal However, due to absence of regulation bodies and
abnormality through the biopsy of a single cell from policies in most African countries, a large number of
an embryo prior to implantation. PGD is carried out embryos are transferred leading to high order
for patients at of transmitting a genetic or
r19k pregnancies and its complications.uu-uu
chromosomal abnormality to their children. Pre-
lmplantation Genetic Screening (PGS) is aimed at Vll. Gamete donation
screening the embryos for presence of anueploidy or Genetic material donation refers to donations of
other karyotype abnormality and to transfer only spermatozoa, oocytes (egg/ova), embryos (the
those embryo(s) that have a,normal karyotype in the fertilised egg, usually remaining afler a person's IVF
hope of improving pregnancY rates. treatment) and pre-embryos. Gamete donation is
practised worldwide, although religious and cultural
Since embryos with genetic abnormalities are traditions greatly influence its use. ln most countries
discarded, it requires couples to make a moral that follow lslamic law, donation is not allowed or is
distinction between abortion and the discarding of restricted; sperm donation is not allowed in approxi-
affected non-transferred embryos. lt also raises mately one fifth of countries under statutes; oocyte
concerns in several other areas such as the potential donation is not allowed in one fourth of them; and
for genetic manipulation as it thus becomes possible embryo donation is not allowed in nearly half of these
for parents to choose embryos based on gender and countries.tu
their preferred characteristics. Currently, in the
practice of PGS, there are several inconsistencies. Compensation, influenced by moral and ethical
There is no consensus on the age group in which PGS consideration, is far from being standardised and
should be offered. There is no consensus on the continues to be a challenging issue with several
number of cells that should be biopsied from each countries specifically prohibiting financial compen-
embryo, There are concerns of misdiagnosis due to sation to the donor. The arguments against compen-
mosaicism and there are concerns of costs and the sation for gamete donation include the standpoint
emotional impact of these complex procedures. that the commodification or "buying or selling" of
Furthermore it has not been shown to improve live human gametes is inherently immoral, and, with
birth rates in cases of repeated IVF failures and respect to ooctyte donation, that financial compen-
recurrent miscarriages'and hence the place for PGS sation of oocyte donors may lead to exploitation as
in the current IVF practice is very uncertain.u''uu women may proceed with oocyte donation against
their own best interests, given lhe inherent medical
Vl. Multiple pregnancies risks involved. Another ethical and legal issue
Women taking fertility drugs to stimulate the ovaries surrounding the use of donated gametes is to what
458
lnfertility
extent the a'nonymity of the donor should be pre- couples have bein! unable to adopt or gain citizen-
served. The issue of anonymity as it relatesto gamete ship for their children on returning to their own
and embryo donation is considered by ffi strike countries. Notable bodies such as ESHRE and the
atthe core of self-determination of American Society of Reproductive medicine (ASRM)
human beings to know their genetic' have considered the difficult issue of surrogacy and
sally important. Fifteen countries wift'S@?nd the ethical issues surrounding it.uo
guidelines that on request provideroffsiiring with
identifyinginformation." t' , ' X. Advanced maternal age
Pregnancy at an advanced maternal age has been
Vlll. lntra-Uterine lnsemination (!Ul) controversial and a subject of debate. With the help
The place for lUl has remained and continues to be of in vitro fertilization (lVF) and donor eggs an
controversial. ln the absence of well-designed trials increasing number of women over the age of forty are
with clear answers, it is not surprising that there is no bearing children, Some argue against motherhood
agreement among the fertility specialists in relation late in life on the basis of the health risks involved, or
to the indications, timing and protocols for lUl. The out of concern that an older mother might not be to
latest National lnstitute for Health and Care Excel- give proper care for a child as she ages, while others
I
lence (NICE) guideline on fertility recommends that contend that having a child is a fundamental right
lUl should not be routinely offered for people with and that it is commitment to a child's wellbeing, not
unexplained infertility, mild endometriosis or 'mild the parents' ages, that matters.
male factor infertility'who are having regular unpro-
tected sexual intercourse excluding when people The Ethics Committee of the American Society for
have social, cultural or religious objections to lVF. Reproductive Medicine American in a recent guide-
lnstead, the guidelines recommend considering IVF line on oocyte or embryo donation to women of
as first-line treatment after 2
years of expectant advanced reproductive age recommended that
management. Their recommendation was based on physicians should perform a thorough medical
two randomised controlled trials of lUl that did not evaluation designed to assess the physical fitness of
find evidence of benefit when compared with a patient for pregnancy before deciding to attempt
expectant management. However, despite this transfer of embryos to any woman of advanced
recommendation, a recent UK survey on the adher- reproductive age (>45 years). They also stated that
ence to NICE clinical guidelines by fertility clinics due to concerns related to the high-risk nature of
showed continued variation in the practice of lUl in pregnancy, as well as longevity, treatment of women
the UK, and a general poor response to the guide- overthe age of 55 should generally be discouraged.u'
;\-
lines. The survey respondents highlighted
Xl. Three parent baby
affordability and funding for IVF as influencing
The world's first baby using a new controversial
clinical practice and guideline adherence.u' ln Nigeria
three-parent technique involving use of an egg
I and most other countries of the sub-region, there are
containing nuclear DNA from his mother and father,
no clear cut guidelines and practice is dependent on
i and mitochondrial DNA from a second woman - an
the fertility care provider.
unknown female donor was born in April 2016.un lt is
I
lX. Surrogacy a form of IVF that allows parents affected by rare

Some aspects of surrogacy still remain controversial genetic diseases to have healthy babies. Although
globally and in sub-Saharan Africa, the concept of the donor egg is said to contribute only 7% to the
surrogacy as a management option is still relatively genetic makeup of the child, when examining the
new.u''u' genetic material of these children there are still three
IVF surrogacy is not allowed in the majority of identifiable genetic parents, which opponents to the
countries. ln countries where it is allowed, there are technology argue could cause the child psychological
concerns about the commercialisation of surrogacy, and physical damage. Also concerns have been
exploitation of the hosts and an increase in inter- raised about genetic modification and the suggestion
country "reproductive tourism". This trend has led to that this could lead to'designer babies.u''u'
global concerns and in some cases, commissioning
459
Xll. !nfertility and same sex couple tries and states in America, fertility clinics differ in
Although IVF is hailed as a remarkable technolory their willingness to provide IVF for homosexuals with
and assists many infertile couples in havirg babies, it some denying IVF treatment to homosexuals both
is not without its controversy. There ale c$toems privately and publicly. ln response to objections to
about IVF being used by a group of people knmm as same sex couples as parents, the American Society
the 'socially infertile' which includes those who are of Reproductive Medicine holds that there is no
homosexual (gays and lesbians) and those who are evidence to prove that children raised in families
single.uo with same sex parents are harmed. However it is
estimated that in most countries in Africa, homosex-
There is a wide array of ethical and social concerns uality is outlawed and apart from South Africa, there
regarding the competency of same sex couples as is scarce information on treatment of infertility in
parents.uu The use of IVF for the socially infertile is a same sex couples.
contentious problem a nd a lthough d ifferent cou ntries
adopt different laws and regulation. ln some coun-
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51. SOGC Clinical Practice Guideline: The mitochondilal DNA mutation causing Leigh
Management of Uterine Fibroids in Women With syndrome. Fertility and Sterility. 2016; 106 (3):
Otherwise Unexplained lnfertility. J Obstet e375-e376
Gynaecol Ca n 20 1 5 ; 37 3) : 27 7 -285. 64. Soo C. Babies for the socially infertile: How
52. AhmadiS,4, Shahsavar F and Akbari S. A Review conceivable is it? The New Zealand Medical
on Controversies about the Role of lmmune and StudentJournal. 2010; 12:28 -30
lnflammatory Systems in lmplantation Process 65. Odell J, Abhyankar R, Malcolm A and Rua A.
and Durability of Pregnancy. lnternational Journal Sarne sex relationships, medical care and
of Women's Health and Reproduction Sciences reproductive medicine. Conscientious obiection
2016 ;4 ( 9 96- 102 in the healing professions a readers' guide to the
53.. SHARMA S. Natural killer cells and regulatory T ethicat and social issues. May 17, 2014.- B.
462
----;l
CHAPTEE9
lnfertility Surgery
O K Ogedengbe and O A Baibah
INTRODUCTION involve specialized surgical skills using minimally

invasive surgery provided by laparoscopy and
Approximately one in seven couples experience ultrasound guidance.
infertility. The incidence and their causes depend on
the level of reproductive healthcare in the population' TUBAL DISEASE
Previously, in developed countries factors such as
anovulation and endometriosis, which are associated Tubal disease is found in 29-47 % of cases of
I
with the high socioeconomic status predominated, infertility, and78% of those undergoing laparoscopy
I
and factors such as tubal disease and male factor for infertility in developing countries'''3. lt usually
r infertility secondary to infection were more common results from pelvic inflammatory disease secondary
I
in developing countries. However, PID and its to unsafe abortion, puerperal sepsis and sexually
sequelae are being seen more frequently in western transmitted diseases. Surgical management of tubal
societies secondary to the increasing prevalence of factor infertility is mostly unrewarding due to the
ch lamyd ia and gonococcal infection.
inability to correct the effect of disease on the lumen
I
and its functions. The lumen is narrow and the
The problems associated with infertility have always epithelium delicate. ln developed countries steriliza-
i
been of paramount importance in developing tion accounts for a large proportion of the causes of
r countries due to the cultural norms, which place a tubal occlusion and in such cases the pregnancy
great premium on childbearing. More recently, in rates following surgical correction are much better as
developed countries they are now assuming a greater the functions of the lumen have not been compro-
importance, with the development of increasingly mised by disease.
sophisiicated techniques for its management.
Occlusive tubal disease in the absence of sterilization
Broadly speaking, surgical intervention is included in affects either the proximal or distal parts of the
the management of the major causes of infertility, fallopian tube, or both. Ascending infection or septic
namely tubal disease, anovulation, endometriosis abortion affects the proximal end whilst salpingitis
and semen abnormalities. ln some instances it is of from gonorrhea or bowel organisms causes distal
more relevance than others. Surgery has always occlusions.
played an important role in infertility management,
being the only mode of treatment in several cases Assessment of tubal function includes
such as tubal occlusion and such management is hysterosalpingography, laparoscopy and
J
constantly being refined. The newer technologies for hydrotubation as well as hysterosalpingosono-
graphy, and falloposcopy.
- assisted reproduction in particular have come to
463
The methods of treatment of occlusive tubal disease sively the pelvis is systematically cleared, freeing the
include surgery and use of assisted reproductive tubes, fimbriae and ovaries, with the aid of contact
techniques such as in-vitro fertilization and ernbryo irrigation. Absolute haemostasis and the use of
transfer, which was originally develo@ bM surgical gloves with no added talc further reduce the
patients with irreparable tubal pathologSr- For n*ny risk of adhesion formation. lnjury to the peritoneum
years, conventional macrosurgery was used for the should be avoided and dissection should start at the
treatment of fallopian tube occlusion. The su@ midline and work outwards towards the adnexae.
rates for this type of surgery are poor and apart from Tubal patency is tested after removal of adhesions
the lysis of minimal adhesions, such surgery has and routine post-operative care instituted. A random-
been largely abandoned. Thus, with the current ized controlled trial, which compared open
success rates of assisted conception treatment, many adhesiolysis to no treatment found significantly more
practitioners now believe that tubal surgery is an pregnancies in the treatment group compared with
obsolete procedure and can be dispensed with. ln the control groupu.
some well-selected cases however, tubal microsur-
gery can still give results equal or sometimes superior Salpingostomy
to those achieved by assisted reproductive tech- This involves the creation of an opening in the out
niques. end of the tube to relieve a partial or complere
obstruction, otherwise known as a hydrosalpinx. ln
Tubal surgery is now performed under high magnifi- many instances the fimbriae are intact and enclosed
cation using the operating microscope and very fine by the outer end of the tube. Microsurgical tech-
sutures. Such microsurgery has shown a definite niques are more successful particularly where there
improvement in the restoration of tubal patency, and are complex adhesions to the hydrosalpinges. ln
pregnancy rates. Success rates of 10 - 7O"/" have correcting the abnormality, the tube is first distended
a.
been reported with methylene blue dye via a cervical cannula to
help define the tubal margins. Peri-ampullary and
lmportant prognostic factors are normality'of the pelvic adhesions are removed to free the tube. An
tubal epithelium, extent of adhesions, the spatial opening is then made into the hydrosalpinx at the site
relationship between fimbria and ovary and the of the old ostium. The tube is then dissected to free
remaining length of normaltube. the fimbriae and ensure a proper mechanism for
ovum pick-up.
lndications for surgery include partial or complete
tubal blockage, pathological kinks or sacculation of A variation of this procedure is cuff salpingostomy,
the tube and peritubal and periovarian adhesions, which is much less successful and involves the
particularly if affecting the mobility of the tube or excision of a portion of the outer blocked end of the
ovary. The subsequent occurrence of ectopic preg- tube, ln such cases the fimbriae are usually
nancy is a recognized complication of tubalsurgery. destroyed and not able to be freed by dissection.
Adhesiolysis A meta-analysis of studies investigating the role of

This comprises the freeing of adhesions arising magnification for adhesiolysis and for salpingostomy
external to the tube and ovary, to remove kinks or revealed a statistically significant increase in
blockage of the tube and to effect normal juxtaposi- pregnancy rates and reduction in ectopic pregnancy
tion of the ovary and tube. rateu.
I
ln the past, dissection across the middle of an Adhesiolysis and salpingostomy may be carried out
adhesion band or sheet was considered enough, but using the operating laparoscope and coagulation
adhesions often coil up leaving an ideal nidus for achieved by monopolar electrode or bipolar forceps.
f u rther post-operative ad hesion formation. M icrosu r-
Fimbrioplasty may also be done through the laparo-
gery has given better results by the use of glass rods, scopic route. Results of laparoscopic distal tubal
which protect underlying tissue while cutting the surgery are comparable to those of microsurgery.
adhesion with microelectrodes or CO, laser. Progres- Laparoscopy is superior to laparotomy as a surgical
464
lnfertility Surgery
l
I
treatment choice, and fertility results are best in reported 827" patency rate can be achieved by the
I patients with rrormal mucosa. above method, with an intrauterine pregnancy rate of
I 24% and ectopic pregnancy rate of 3%'. lt is now
i-- Hydrosalpinges have been associated with dccreased recommended by the RCOG and the American
I
implantation and conception in patients undergoing Fertility Society that tubal catheterization be
IVF and embryo transfer, and also increased ectopic attempted before further microsurgery is embarked
pregnancy rates. lmproved implantation rates and upon for proximal obstructione.
pregnancy rates, as well as lower miscarriage rates
have been found after removal. However in some Tubal reimplantation is associated with the highest
cases, performing a salpingectomy may be challeng- pregnancy rates in diseased tubes and
ing due to dense pelvic adhesions. ln such circum- salpi ngostomy for hydrosa I pinges the least.
stances, it is recommended that de-linking the tube
from the uterus would help in improvingthe outcome For patients scheduled for reversal of tubal steriliza-
of assisted reprod uctive tech n iq ues'. tion, several factors need to be taken into consider-
ation. These include the patient's age, method of
Salpingectomy, which can be done laparoscopically sterilization, financial resources and patient's
or by open procedure has remained the main treat- preference. Higher success rates have been reported
r-tr-,
ment modality for hydrosalpinges. However, trials are following reversal of tubal sterilization procedures
still ongoing to assess the effectiveness of other performed using Pomeroy's or Falope's ring tech-
possible treatment options such as laparoscopic niques compared to those performed using tissue-
salpingostomy, laparoscopic or hysteroscopic tubal destructive techniques such as coagulation proce-
occlusion, and drainage of the hydrosalpinx before or dures or Uchida technique'.. The remaining length of
during oocyte retrieva I'. tube after recanalization is also an important
determ i na nt of the success rate of the proced u re".
Tubal Anastomosis
This is indicated where there is a blockage in the Postoperative Ma nagement
central or medial part of thetube. lt is principally used Many surgeons use steroids in the belief that post-
in patients seeking reversal of sterilization and in operative adhesion formation is reduced, and this
whom limited segments of the tube have been has been shown to give improved pregnancy rates.
excised in the management of tubal pregnancy or Most will restrict their administration to those
local tubal disease. Because of the delicate nature of patients with distal tubal disease and adhesions
the tube and its fine lumen, microsurgery provides while others recommend their use for all cases
the best results. regard less of pathology.
Pregnancy rate is higher following reversal of tubal Routine antibiotic therapy is useful to prevent any
sterilization compared with outcome of surgeries on un necessa ry post-operative i nfection. A com bi nation
diseased fallopian tubes as tubal sterilization of a broad-spectrum antibiotic with metronidazole to
procedures often are performed on apparently combat the presence of anaerobes is advocated.
healthy tubes which functions have not been affected
by disease. For diseased fallopian tubes, the preg- Following dischargeif pregnancy has not occurred
nancy rates depend on the severity of damage caused after 6 months, a repeat laparoscopy to confirm
by the disease. tubal patency and also detect adhesion formation is
desi ra ble a nd preferable to hysterosa I pi ngogra phyo.
Proxi::altubal obstruction may occur in the intramu-
ral segment or the uterotubal junction and accounts Couples with infertility resulting from tubal disease
ior IO-25% of tubal factor infertility. Employing have two therapeutic options in order to achieve a
radiological, falloposcopic, hysteroscopic or ultra- pregnancy, reconstructive surgery and invitro
sound imaging using a variety of catheters with guide fertilization. At present, in-vitro fertilization is
wires and balloon systems can be used to attempt tending to replace surgery i'n developed countries,
recanalisation of the proximally obstructed tube. A and only surgeons with the requisite training and
experience carry out tubal surgery in centres with
adequate facilities. Such factors will subsequently subsequent adhesion formation. lncisions on the
affect the outcome, This may soon be the situation in posterior aspect of the uterus should be avoided, as
developing countries, many of which have already they may lead tofixed retroversion. Posteriorfibroids
embarked on assisted reproductive programmes. can be removed through a midline incision going - .
Microsurgery has consistently proved to give better through the uterine cavity. Where posterior incisions
results than macrosurgery, but either may be needed are unavoidable plication of the round ligaments may
to compliment assisted reproductive technolory. The
be a useful adjunct. Bonney's Hood operation is
keyissueistheselectionofpatientsonthebasisofanotherclassicalmethodfordealingwithposterior
accurate evaluation of the severity, site and extent of uterine fibroids.
disease.
Another important factor is to avoid damage to the
ln clinical practice the decision making process fallopian tubes. Any tubal surgery procedure in
should take into account, in addition to tubal factor, excess of adhesiolysis should be postponed to a later
other factors involved such as age, duration of date. Extensive tubal surgery is infact no longer
infertility, male fertility, acceptability, availability and encouraged since the observed success rates with i
costs. ART.
\'-'
UTERINE ABNORMALITIES Asherman's Syndrome or Uterine Synechiae
This is another common uterine abnorrnality and
Uterine Fibroids potential cause of infertility, as well as abortion and
The presence of uterine abnormalities is believed to premature labour. The incidence is relatively high in
only
play a role in infertility. They were found to be the developing countries and is related to the rate of
factor in 3.6% of the infertile women in a Lagos abortion by curettage and puerperal or postabortal
study'. The commonest abnormality is the presence infection.
of uterine fibroids, which are said to be 3-9 times
more common in the black race than Caucasians. ltistreatedsurgicallybyadhesiolysisusingauterine
They were found to be present in 6% of all infertile sound following which either a Lippes loop or a Foley
womenin Lagos'. catheter is inserted for three months or 10 days
As to whether they are the sole cause of the infertility respectively. Follow-up therapy with cyclical steroid
or an incidental finding is debatable as there are hormones and antibiotics to promote endometrial
many instances where the presence of huge fibroids
regeneration is usual. Adhesions may be diagnosed,
is compatible with normal fertility and an uneventful and divided, at hysteroscopy. Uterine adhesions
pregnancy and delivery. However reports have it that
accounted tor 2O%of the lesions detected in a study v '
40% of infertile women had their fertility restored from Jos Nigeria".
fol lowi ng treatment of their fibroids.
Even in the light of this, myomectomy may need to be
Following division of adhesions and IUD insertion,
performed prior to Assisted Reproductive Technology normal menstruation was achieved in 68% of cases
(ART) programmes to provide the optimum environ- in a study from Lagos, Nigeria". The success rate of
ment for implantation. Small submucous fibroids
747" achieved with hysteroscopic lysis does not
may be removed hysteroscopically using specialized seem to have much advantage over coil insertion.
scissors, electrocautery or even laser. However in
mostcasesthefibroidswillberemovedabdominally. The chances of success were found to be greater
The use of gonadotrophin releasing hormone ana- when the adhesions are as a result of curettage rather
logues to shrink the fibroids must be considered in than infection following prolonged labour and
the light of the reversal of its effect, on discontinua- caesarean section.
tion of the therapy. Small fibroids, which may have
been missed at operation, will now reappear follow-
ENDoMETRlosls - -
ing surgery. E-r^*^+-;^^;^ .c a. cause
- Endometriosis ..,^^ thought nai
was +ha,,ah* to faarr
not rA 116 as
feature ^.r rca
The main issue to consider when performing
myomectomv for infertiritv is the prevention of ilrilJillllJ, :r$?ffi:t:n,trr'ilJti."1;*'i?
466
r
t
f
lnfertility Surgery
I
t
r
r severe pelvic adhesions or the erstwhile- "frozen Adhesions may surround the ovary making it densely
t pelvis" being attributed to chronic pel-\ric,inflamma- adherent to the pelvic sidewall. Unfortunately, the
r tory disease rather than "burnt out endometr'rosis". excision of these and tubal adhesions, unlike those
[*- . 'i' produced secondary to infection, does not appear to
I With the introduction of |aparoscopyfgF-W iga improve fertility'u
t
I tion of infertility in these countries rnee cases of
r
endometriosis are being diagnosed. Ttre*@rbHity sf Large endometriomas (> 3cm) must be treated by
I
t endometriosis being associated with *.rhigher cystectomy with cauterization of the base of the cyst
i socioeconomic status or the adoption of the,western using laser or diathermy to prevent recurrence
t'''0.
t habits may also account for its emergenBas a cause Drainage of the cyst or fenestration without destruc-
( of infertility. Nevertheless, the management of tion of the cyst capsule is associated with high
t
endometriosis must be included in the evaluation of recurrence rates of up to 100%, as opposed to 8%
infertility in the subregion. recurrence rate up to 11 years and cumulative
r pregnancy rates of 50-60% when cystectomy and
r
i- Minimal or mild endometriosis, which is confined to cautery is performed. Pre-and post-operative
the peritoneum leaving the ovaries and fallopian medical therapy does not appear to significantly
t
tubes unaffected, has been found to affect fertility,
r
affect the recurrence rates "''u.
and even the pregnancy rate in assisted reproductive
t technology programmes. This is thought to be Excision of lesions in the pouch of Douglas and recto-
secondary to the production of a hostile peritoneal vaginal septum in conjunction with ovarian and tubal
I
I
environment to the normal physiological process of adhesiolysis has been found to improve conception
rates". The potential benefits of such surgery to the
I
r conception.
I patients' quality of life such as reduction in
t Surgical treatment of mild or minimal endometriosis dyspareunia, pelvic pain and bowel symptoms
rI commences with the ablation of endometrial deposits support such surgery.
r found at diagnostic laparoscopy. lt has been sug-
r gested that this procedure not only prolongs the Ablation is not advocated in advanced stage
t procedure, but also may lead to adhesion formation. endometriosis as the extent of the disease cannot be
r It may also miss microscopic lesions. Studies have determined and residual tissue is most often
I
t
shown however, that some 30% of women with retained'u.
minimal or mild endometriosis will achieve preg-
I
nancy in nine months following diathermy of their Surgery should usually be by laparotomy except at
I
specialized centres, as the skills required for effective
Ir-
I
lesions at diagnostic laparoscopyto''u.
laparoscopic excision are not easily acquired.
I
r
Traditionally the surgical management of advanced Nonetheless, the advantages of laparoscopy such as
I stage endometriosis is total abdominal hysterectomy minimal invasion, shorter hospital stay; less postop-
i and bilateral salpingo-oophorectomy. However, this erative pain and rapid return to normal activities are
i" is obviously not an option for a woman whose main wellrecognized.
I
t complaint is infertility. The aims of sur.gical interven-

I tion arethree-fold: There does not seem to be any advantage in using
I
adhesion-preventing agents to improve the preg-
a Restoration of a natomy. nancy rates, and despite meticulous surgical
I
I a Preservation of normal tissue. techniques the recurrence rate in endometriosis is
i
a Excision of diseased tissue. high, Biopsy of apparently normal tissue next to
i deposits has shown active glandular and stromal
i
Unlike as found with the adhesions produced by elements with neovascularisation in 6% of
infection, the lumen of the fallopian tube is unaf- patients".
fected by endometriosis. Thus efforts should be made
- to restore tubal motility by excision of adhesions Although surgical treatmdnt has demonstrated
t produced by endometriosis. Excision is to be pre- benefit in stage l/ll endometriosis as stated in the
:
i ferred to lysis for the benefit of histological diagnosis. European Society of Human Reproduction and
467
Embryology (ESHRE) and Royal Coilege of Obstetri- there was sigrrificant post-operative adhesion
cians and Gynecologists (RCOG) guidetines, the formation fol lowing the operation.
benefit is insufficient to recommend it ,sdely to
increase the likelihood of pregnancy as stffiF ,tHe ln addition the initial favourable response was not
Ame rica n Society fo r Rep rod uctive Medie#t$i1ffifr{) sustained.
guideline. All the three guidelines, howev€r reog-
nized surgical treatment as a possible treatrnent Wedge resection of the ovary as a surgical manage-
moda lity for stage lll/lV endometriosis2o rnent ofPCOD, has since been superceded by
laparoscopic ovarian diathermy and laser therapy.
Repeat surgery has only rarely increased fecundity. Properly trained laparoscopic surgeons should of
The results of a metaanalysis suggested that expec- cou rse perform.such su rgery.
tant management followed by ART may result in a
better prognosis for pregnancy compared with repeat Laparoscopic ovarian diathermy (LOD) appears to be
surgery in women with recurrent endometriosis. as effective as gonadotrophin therapy in the treat-
ASRM has recommended ART for patients who have ment of clomiphene resistant PCOD, and has been
a history of at least one surgical treatmeht. However, suggested as the first option prior to gonadotrophin
if the patients suffers from severe pain or from therapy in these patients". lt is associated with less
endometrioma >4cm, RCOG has recommended that adhesion formation than wedge resection, which is
repeat surgery could be considered'o. proportional to the amount of ovarian tissue
destruction2o . Care has to be taken over the amount
On this basis, artificial reproductive technologies of ovarian destruction to avoid its leading to ovarian
have become the most efficient way of overcoming failure, both with wedge resection and LOD. Laser
endometriosis-associated infertility, particularly in treatment seems to be as efficacious as diathermy,
stage II l/lV endometriosis'o. and it has been suggested that it may result in even
less adhesion formation.
POLYCYSTIC OVARIAN DISEASE
Patients with high basal luteinizing hormone
Polycystic ovarian disease (PCOD) is the most concentrations have a better clinical and endocrine
common endocrine disease affecting women. lts response to LOD. Ovarian diathermy has been
management is primarily medical, by the use of the postulated to sensitize the ovary to the action of
anti-oestrogen clomiphene citrate, which will result follicle stimulation; therefore it is necessary to be
in ovulation in approximately 7a% and conception in cautious in those patients who have received such
about 50% of cases. ln clomiphene resistant cases therapy and who are undergoing subsequent super-
the use of gonadotrophins will achieve a cumulative ovulation for in-vitro fertilization'u. The advantage of
pregnancy rate of about 90% but this therapy is LOD is also that it needs only to be performed once;
associated with complications including an however the duration of effects may only be for 6-12
increased multiple pregnancy rate and the potentially months.
dangerous ovarian hyperstimulation syndrome
(OHSS). Patients with PCOD have an increased risk RECENTADVANCES
of OHSS and their response to ovulation induction is
unpredictable. Recently, ovarian transplant is being performed in
developed countries for ovarian disorders such as
The traditional surgical method of treatment of genetic defects that may render a woman,s ovary
patients with PCOD was wedge resection of the non-functional. This procedure has been carried out
ovaries, which resulted in an average ovulation rate by minilaparotomy on infertile identical twin in some
af 80%and pregnancyrate of 63yo",".ltisfreeof the centres with good result. Healthy ovarian cortical
risk of multiple pregnancy and OHSS, which require tissue is harvested from the fertile twin and trans-
-,.
intensive monitoring for their prevention. This mode planted into the infertile twin. Success in terms of
of treatment went out of vogue with the introduction resumption of menstruation and ovulation and
of clomiphene citrate therapy and the realisation that pregnancy has been reported in a number of cases.
The world's first ovary transplant surgery was
468
t-
I lnfertility Surgery
I
I
t
performed at the lnfertility Centre of St. Louis at St. sperm into an oocyte has revolutionised the treat-
tt, Luke's Hospital in the United State of America in ment of male infertility. ln the U.K. nearly 10,000
t 2004'u. cycles of lCSl were performed between 7997 and
lr- 1998.
r Whole ovary transplant in non-identit*fi #ffi*ru have
r
r
also been successfully performed. Ttth' rilay be Where the obstruction is mechanical being caused
ft suitable in women with premature rnGiTcpause or by vasectomy or iatrogenic following herniorrhaphy,
I
{
I
those undergoing chemotherapy or raffOtfrcrcpy for microsurgical anastomosis of the epididymis to the
various malignancies that may redult ih Cdfitplete vas (vaso-epididymostomy), or vas to vas
I destruction of the ovaries. ln the later, the healthy (vasovasostomy) may be successful. The post-
)
ovary can be removed from the woman and procedure patency rate ranges from68 - 98% and
I
l cryopreserved and later transplanted back after pregnancy rates rangesfrom 37 -g3Yo'n''o. However,
r
( completing the treatment. Whole ov6ry trarisplant is successful reversal of infertility following vasectomy
i technically challenging and requires great sklll as decreases with time, more so in the presence of
r- microvascular anastomosis of blood vessels has to be sperm antibodies.lncreasing obstructive interval is
(
I
performed associated with an increased incidence of
epididymal obstruction and the consequent need for
MALE FACTOR iNFERTILITY vaso-epididymostomy'. Most surgeons consider
t
vaso-epididymostomy to be more technically
i
t
There is no area of infertility that has benefited from
challenging than vasovasostomy due to the added
the fall out of ART than that of male factor disorders.
r
( difficulty of isolating a smaller segment of the
( epididymis and working with the disparity in the size
I
I
ln our environment it accounts for up to 30-40% of
of an epididymal tubule and the vas deferens.
r the causes, second only to tubo-peritoneal factors
i and ranges from oligospermia to azospermia. ln
A recent advancement in vasectomy reversal is the
i developing countries infection plays the major role,
use of robotic-assisted surgery. This has advantage
f
t
usually secondary to gonorrhoea or chlamydia".
over microsurgical vasovasectomy in that it
t Other factors that have been implicated which have
decreases operative time, increases patency rates
i
surgical significance include excessive heat from
j and decreases learning curve. Howeverthe shortfalls
abnormalities such as varicocoele, iatrogenic
r
are that it is more expensive, requires a specialized
r occlusion of the vas following herniorrhaphy and
surgical team, low availability of microsurgical
t
chromosomal disorders. ln about half of the cases, no
t instruments, and the inferior magnification
cause can befound. (x10-15) required for the surgery compared to a
I
I
t microscope (x20-30) which is needed for the
{ Until the upsurge in ART the role of surgery for the
trad itiona I m icrosu rgica I proced u res'n.
;
i
successful treatment of male infertility was reserved
( for obstructive azospermia. Open testicular biopsy
The role of excessive heat in sperm production is
i yielding normal sperms used to be part of the investi-
controversial, but improvement in sperm counts
gation of infertile males 30 years ago. However this
following varicocoelectomy has been reported'8.
r has been largely replaced by needle and Trucut
i Being a relatively simple and inexpensive procedure,
I needle biopsy. Microsurgical epididymal sperm
it is reasonable to perform the operation on patients
? aspiration (MESA) and testicular sperm extraction
I
with varicocoeles, as a first line of therapy.
(TESE) now enable men with obstructive
t
i
azoospermia who are not candidates for reconstruc- ASSISTED R EPRODUCTIVE TECH NOLOGY
a tive surgery to father children. Such sperm is subSe-
quently used for assisted reproduetive technology Assisted Reprod uctive Tech nology (ART) com mence
programmes such as IVF and intracytoplasmic sperm over 30 years ago with the work of Steptoe and
'
; injection (lCSl)". Edwards who developed the process of in-vitro
i fertilization and embryo transfer, primarily for the
-.
ln January 1992 the first child to be conceived by treatment of tubal factor infertility. This technology
i lCSl was delivered. Since then the injection of a single
I
469
has now assumed a major role in the treatment of may offer benefit over hydrotubation fluid without
infertility and the indications have now expanded to anti biotic fol lowing tubal surgery.
cover a wide number of conditions including
endometriosis, male factor infertility, ovarian failure lll.
Cost is another obstacle even for surgery and in
or resistance and unexplained infedility. such cases one may need to perform moderately
extensive su rgery such as treatment of
lnitially oocytes were recovered laparoscopically and hydrosalpinges at myomectomy. Where the skills or
this route was used for gamete intra-fallopian tube equipment needed for laparoscopy are absent, it may
transfer (GIFT) and zygote intra-fallopian tube be necessary to rely on hysterosalpingogram results.
transfer (ZIFT). ln ART procedures the optimum Following macrosurgical procedures, early detection
conditions are aimed for, and they may need to be of pregnancy to exclude ectopic pregnancy is
complemented by other surgical procedures prior to important and patients are warned to report any
the commencement of the program. These may change in menstrual pattern or abnormal pain.
include laparotomy to render the ovaries accessible;
for removal of uterine fibroids; excision of lV. The controversy over whether to treat mild /
hydrosalpinges or diathermy of endometrial deposits minimal endometriosis rages on. lt is suggested that
at diagnostic laparoscopy. The need to access the notreatmentyields equal results as differentfacilitie -
ovaries laparoscopically has largely been abolished are available in different centres. However medical
by the refinement and increasing resolution of management on its own is generally thought to be
ultrasound imaging particularly with employment of ineffectual.
the vaginal probe. Most oocyte recoveries and intra-
V. With advanced endometriosis, surgery should be
fallopian tube transfers are now performed under
offered but although there are no randomized
ultrasound guidance.
controlled trials, the results are poor and ART is
Sperms are now recovered not only from the ejacu- usually the ultimate management. Endometriotic
late but also from the testes and epididymis for cysts greater than 3cm should be treated by
insemi nation and fertil ization. cystectomy and cauterization, although it is postu-
lated that monolocular cysts seen on ultrasound
DISCUSSION AND CONTROVERS! ES scanning may in fact be functional cysts and should
be observed and reviewed after some months. The
L ln considering infertility
surgery, improved preg- issue of destruction of ovarian tissue reserve must
nancy rates are being obtained in developed coun- always be kept in mind. The presence of an
tries where there are specialized centres focusing endometrioma has no effect on the outcome of IVF in
only on these conditions. patients with endometriosis. Thus in such patients
the cysts need only be removed if mechanically
Many of those practicing in developing countries do obstructing the procedure or if the nature is
not have access to some of the sophisticated equip- unknown.
ment required and neither do they have the requisite
skills. Therefore most of the conditions stipulated for CONCLUSION
maximum benefits may not be realistic. Surgery has always formed an integral part of
infertility management. Few conditions can be
ll, Where the infertility is secondary to tubal disease managed solely by medical means.
in the absence of microsurgical equipment, and
availability or affordability of ARI macrosurgery may ln embarking on the appropriate surgical procedure
be attempted, backed up by post-operative steroids however, the type of surgery and extent should take
and .antibiotic therapy. Efforts should be made to into consideration the several factors in the individ-
ensure adequate haemostasis. Meanwhile, there is ual's reproductive history and results of examina-
insufficient evidence to support the routine practice tion, and management tailored to suit the particular
of hydrotubation or second-look laparoscopy follow- patient. The chances of success.of each option and
ing female pelvic reproductive surgery
t'. Postopera- aspects such as cost effectiveness should be consid-
tive hydrotubation with fluid containing antibiotic ered in decision making.
470
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lnfertility Surgery
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REFERENCES
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I 1. Cates W, Faley TMM, Rowe FJ. Waildwide surgery in infertile women with minimal or mild
patterns of infertitity: ls Africa differentt Lancet endometriosis. Canadian Collaborative Group on
1985; 2: 596 -598. Endometriosis. N. Engl. J. Med. 1997;
2. Ogedengbe OK, Giwa-Osagie OE Emuveyan EE. 337:217-22.
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lmplications of the pattern of tubal disease for 16. Hunter DC. The management of advanced-stage
microsurgery or in-vitro fertilisation in Lagos J endometriosis in the treatment of infertility. The
Nat Med Assoc 1987; 75: 510 -512. Obsterician and Gynaecologist 2001 ; Vol. 3. No.
3. Giwa-Osagie OF et al Etiologic classification of 1.4-7.
I infertility and sociomedical characteristrcs of 17. Vercellini E Vendola N, Bocciolone L, Colombo
infertility in 250 couples. lnt J Fertil 1984; 29, A, Rognoni MT Boli G. Laparoscopic aspiration
104-108. of ovarian endometriomas. Effect with
i
4. Varma TR, Female infertility. ln Clinical postoperative gonadotroph i n releasi ng hormone
Gynaecology. Varma TR Eil 1991; 645 -707. agonist treatment J. Reprod. Med. 1992;
5. Newton JR., 2perations for the correction of 37:577-80.
infertility. ln Bonney's Gynaecological Surgery 18. Beretta E Franchi M, Ghezzi E Busacca M, Zupi
9th Edition. 149 -167. E, Bolis P Randomised clinical trial of two
6. Watson A, Vandekerckhove P, Lilford R laparoscopic treatments of endometriomas:
Techniques for pelvic surgery in subfertility. cystectomy versus drainage and coagulation.
:
(Cochrane review) Cochrane library rssue 3, Fertil. Steril. 1998;70: L176-80.
2002. 19. Nisolle M, Paindeveine B, Bourdon A, Berliere M,
7. Panhar M, Mirge A, Hsabe R. Hydrosalpinx Casanas-Roux F et al. Histologic study of
functional surgery or salpingectomy? The peritoneal endometriosis in infertile women.
importance of hydrosalpinx fluid in Assisted Fertil Steril 1990; 53:984-8.
Reproductive Technologies. J Gynecol Endosc 20. Yun BK, Choi YS, Lee BS. Management of
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Su rg. 2009 ; 1 (1 )' 12- 1 6. Endometriosrs-Assocrated lnfertility. J Androl
B. Thurmond AS, Pregnancies after se/ectiye Gynecol. 2014;2(2):7
salpingography and tubal recanalization 21. Goldzieher JW, Axelrod LR. Clinical and
I Radiology 1994; 190:11-13 Petermilton Series biochemical features of polycystic ovarian
Ed. drsease. Fertil Steril 1984; 41 : 20-5.
9. Management of lnfertility for the MRCOG of 22. Stein lE Leventhal ML. Amenorrhoea assocrated
beyond. RCOGPresg 2000. Pg.80-81. with bilateral polycystic ovaries. Am J Obstet
10. Xue E Fa Y. Microsurgical reversal of female Gynecol 1937 ; 2981 -9 1.
:1
sterilization: long term fllow-up of 117 cases. J 23. Kousta E., White DM, Franks S. Modern use of
Reprod Med. 1989; 34:451. clomiphene citrate in induction of ovulation.
11. Jayakrishnan K, Baheti SN. Laparoscopic tubal Hum Reprod Update 1997;3;359-65.
sterilization reversal and fertility outcomes. J 24. Balen A. Surgical of Polycystic
management
Hum Reprod Sci. 20 11 ; 4(3) : 125- 129. Ovary Syndrome: Pros and Cons. The
12. Otubu JAM, Olanrewaju RS Asherman's Obstetrician and Gynaecologist 2000; Vol.2.
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Hospital. T J O G 1993; 10: 30-2. 25. Abdel Gadir A, Mowafi RS, Alnaser HMl, Alrashid
13. Ogedengbe OK, Giwa-Osagie OF, Ayodeji DE AH, Alonezi OM, Shaw RW. Ovarian
Oyeyinka O. lntrauterine adhesions rn Lagos electrocautery versus human menopausal
Nigeria. Journal of Obstetrics & Gynaecology gonadotrophins and pure follide stimulating
1991;11:134-6. hormone therapy in the treatment of patients
14. Wingfield M. Minimal lmild endometriosis and with polycystic ovarian drsease. Clin Endocrinol
t infertility. The Obstetrician and Gynaecologist 199O;33:585-92.
2000. Vol. 2 No. 2:21-24. 26. Silber SJ, Lenahan KM, Levine DJ, Pineda JA,
:- 15. Marcoux S, Maheux R, Berube S. Laparoscopic Gorman KS, Friez MJ, et al. Ovarian transplant
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between monozygotic twins 30. Herrel LA, Goodman M, Goldstein M, Hsiao W,

premature ovarian failure. N EnSl Outcomes of microsurgical vasovasotomy for
353. vasectomy reversal: a metaanalysis and
27. Osegbe DN, Amaku EQ. The systematic review. Urology. 2015; 854);819-
infertility in 504 consecutiw 25.
lnt J Urology and Nephrplogy Duffy JM, Johnson N, Ahmed G, Watson A.
28. Human Fertilisation and fustope rative preced u res for i m prov i ng fe rtil ity
Annual Report. London J999. fo I I ow i n g pe lv i c re p rod ucti ve $u r ge ry. Coc h ra n e
29. Patel AE Smith RP Vasectomy Database Sys Rev 2009 ; 1 5(2) : CD00 I 897.
qpdat.e. Asian J Androl.2O16;
*v2
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{
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cHAPTER
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tt-
t
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t,
40
I
l'
Assisted Repr'oductive Tech nology
I
* O F Giwa-Osagie and ER Efetie
I
I
i.
Assisted Reproductive Technology (ART) comprises Table ll Methods of ART
those methods and procedures used to improve the 1 Artificial lnsemination (Al)
chances of conception. These procedures are also 2 ln-vitro Fertilisation
referred to as 'medically assisted conception' or
3 Gamete lntra Fallopian Transfer (GIFT)
'Assisted Conception'. The World Health Organisation
4 Zygote lntra Fallopian Transfer (ZIFT)
definition of ART does not include artificial 5 lntra Cytoplasmic Sperm lnjection (lCSl)
insemination (Al) but Al is a medically assisted
conception method.
6 Oocyte Donation and Embryo Freezing
Rationale: Choosinga Method of ART

The chances of natural conception following The method of ART chosen for managing infertility in
unprotected intercourse is 80% in 12 months. The a couple depends on the diagnosed cause of
presence of factors causing infertility reduces the infertility, which can only objectively be arrived at
probability of conception occurring such that the after standard, scientific investigation. ln the
i chances are zero if there is no uterus and more than majority of cases a method of ART is combined with
I
that for various causes of infertility. The main causes one or more adjunctive procedures to enhance the
I
i of infertility and the contribution of male and female chances of achieving pregnancy through ART. These
i ..- factors to infertility are summarized in Table l. adjunctive methodsareshown in Table lll.
I
Contribution of Male and Female Factors to lnfertilitv Table lll Adjunctive Methods
i) Control led Hyperstimulation
Table I
ii) Assissted Hatching (Zona Pellucida
Tubal Factor 45-55% Stripping - physical, chemical,
Male Factor 30-40% ultrasonic)
Anovulation 25-35% iii) Gamete and Embryo Freezing
Uterine Factor I5-25"/" iv) Testicu la r/Epididvma I Sperm Aspi ration
lnfertility is usually unexplained in *12% of

ca" - after investigation ARTIFICIAL INSEMINATION (A.l): Artificlal
insemination is the introduction of semen into the
Assisted conception methods or ART are employed to
genital tract of a woman. The semen may be placed
increase the probability of pregnancy during and in the vagina, in the cervical canal or in the uterine
following the treatment of infertility. They are also
cavity (intra-uterine insemination or l.U.l). lf the
t applied in cases of
unexplained infertility or in
semen inseminated is from a woman's partner the
apparently normal couples who have failed to achieve procedure is named Artificial lnsemination Husband
pregnancy, The methods of ART are shown in table ll.
(AlH). lf the semen is from a donor (third party) the
473
process is termed Donor Semen lnsemination (D.l). produced using normal condoms, which have been
Artificial insemination is used to treat male factor washed with soap and water, Semen should be
infertility. lndications for AIH and D.l are listed in collected into a clean sterile container. Semen should
Table lV.
be received in the laboratory within hour of t
production and can be transported by placing the
semen container in the woman's brassiere. To avoid
Table lV- lndications for Artificial lnsemifffi the uncertainties of transportation in developing
countries it may be better to have facilities at the
AIH Donor,lrlffi' clinic for couples to produce the semen on site.
Low Semen
1. 1 Azospermia
Count Semen Preparation: Semen contains spermatozoa,
2. Low Semen 2. Severe 0ligospermia chemicals such as prostaglandin and debris and
Motility with Motility Less some bacteria. ln order to
remove noxious
Than 50%
chemicals, debris and bacteria it is now standard
lncreased Semen Severe
procedure to process the semen samples using one of
3. 3
Abnormal Forms Tetratozopermia
a variety of gradient filters or the "swim-up"
4. lmpotence 4. Genetic Abnormality
procedure. A sample that has been subjected to
Transmitted by the
these procedures usually is free of prostaglandin,
Male Partner
debris and most bacteria. Such a sample can be used
Failed AIH with
Premature
5. Sperm Mucus for intra-uterine insemination (lUl) with very minimal
5.
Ejaculation
Hostility risk of any side reactions. lnsemination of whole
Unexplained semen can lead to severe uterine cramps and
6.
lnfertility
6. Couple's Choice
abdominal pain and collapse due to the
Cervical Anti- prostaglandi n i n whole semen.
7. Sperm
Antibodies Follicle Tracking:
Persistently Poor For successful insemination there should be
8.
Postcoital Tests efficient tracking of follicle development and
impending ovulation. Serial cervical mucus
examination for evidence of increasing volume,
clarity and spinnbarkheit is a cheap method of timing
Artificial !nsemination Using Husband Semen lnsemination '.The indices combined to obtain
(AIH): lnsler's Score can make ovulation prediction more
The most common indications for AIH are low sperm efficient. ln women who have regular menstrual
concentration (less than l0million/ml) Normal cycles the use of a basal body temperature chart and
concentration but low motility (motility less than serial cervical mucus scoring allows very good timing
50% at t hour after ejaculation), low sperm of insemination, Serial measurements of
concentration with low motility, increased abnormal gonadotrophins and plasma oestradiol can also be
morphology (abnormal forms of 50% or more) used to time insemination. ln most fertility clinics
otherwise known as teratozospermia. AIH is also hormone assays are now done by enzyme linked
applied where the male partner cannot get or sustain assays (ELISA) rather than radio-immuno assay'
an erection or suffers from frequent premature Ultrasound machines are increasingly available in
ejaculation. ln impotent men erection can be clinics and hospitals around the world. Transvaginal
stimulated electrically and the semen collected. ovarian sonography allows very good follicular
tracking. Follicules with fertilizable oocytes have
Collection of Semen: been shown to be released usually at follicular
Semen for artificial insemination is preferably diameters exceed ing 1 8mm. Fol lowi ng i nsem ination
collected by masturbation. A high proportion of a furthertransvaginal scan should be performed two
African men find it difficult to masturbate in which or three days after the last insemination to ensure
case the semen may be produced by having sexual that ovulation did occur and thatthere are no trapped
intercourse using special condoms containing no matu re follicles.
spermicidal substances. Semen may also be
474
Assrsted Re p rod u cti ve Tec h no I ogy
lnsemination: some recipients and their partners to request that

The process of insemination is simple. Half a semen from related donors should be used. lf this
millilitre of semen is aspirated in a catft&{ ssch as request is accepted, confidentiality and anonymity
the Rocket "Rolon" mucus samplint ora are breached. Such requests should therefore not
'Medicut' intravenous cann ular wi , fhe
normally be granted and the couple should be
catheter is inserted under direct visign r the
cervical canal and intrauterine' insefiifiation appropriately counseled. The donor must have
performed. lf the semen has not been purlfled by semen indices that are very good with concentration
"swim-up" or by gradient or other methods, the semen exceeding 40million/ml, progressive motility
should not be introduced into the uterus but should exceed i ng 60% atone hou r, with norma I morphology
instead be placed at the vaginal fornix or cervical of 60% or more and there must be no pus cells in the
canal. The patient should rest for 15-30 minutes semen. Having satisfied these criteria, the
before leaving the procedure venue. lt is usual to prospective semen donor is then screened for
inseminate on two or three consecutive days or on
Human lmmuno Deficiency Virus (HlV), Hepatitis B,
two occasions with no A.l on the day between(''.
Syphillis and the Veneral Disease Reference
FollowUp: Laboratory Test (VDRL). lf these tests are negative

There is no scientific evidence to indicate that natural semen samples are then accepted from the donor,
i intercourse after A.l affects the results. There is also analysed, an aliquot is cultured, and the sample is
no evidence that taking coffee, tea, alcohol affects the frozen and stored in the semen bank. The sample(s)
i result of A.l. My opinion is that the couple should will only be used for donor insemination when a
I have normal intercourse as they wish and that this second screening test for HIV and Hepatitis B are
may improve the male partners sense of ownership of
negative at least 2 months after the initial test. lt is
any pregnancy resulting from A.l. The patient should
I
be requested to report for a pregnancy test if her unethical to use fresh semen for donor insemination
I menses are more lhan 7 days late although plasma a because of the risk of transmitting HIV and Hepatitis.
Storage of semen allows screening tests to be
I
I beta HCG pregnancy test can diagnose pregnancy
earlier. An early pregnancy scan should be scheduled repeated to minimize the risk of inseminating semen
I
t
t for those who became pregnant at between eight and from an HIV or Hepatitis positive donor. Fig 2 shows
ten weeks gestation. lf the patient is not pregnant she
r equipment used for storing trozen semen. There is
I should be counselled and further cycles of
r still a very small risk that the donor who was HIV
insemlnation planned.
rI negative on screening may have been in the window
I
period of sero conversion. After screening, donor
t Donor Semen lnsemination:
The usual indications for donor insemination are characteristics such as blood group, height, build,
I
t shown in Table lV. ln Nigeria 7-12% of the male skin colour, educational level and occupation are
partners in infertile couples are azospermic(1). The recorded and the donor given a code name or
f
l standard treatment for azospermia or severe number which is used to mark his semen sample(s)
oligospermia (concentration less than 5million/ml)
I
during storage.
severe asthenospermia (motility less than 2O%) is
i
i donor insemination as the probability of spontaneous
Procedure:
pregnancy in this situation is very low. lf azospermia
I
is due to vasa obstruction, this may be treated by Semen preparation, follicle tracking,
i microsurgery, while ln Vitro Fertilisation (lVF) and insemination and follow-up are as for AlH. Most
lntra Cytoplasmic Sperm lnjection (lCSl) now allow practitioners of D.l would however increase the
r
biological children to be fathered by men with very number of follicles developing by giving the recipient
:
I
poor -prn'T1 concentration and motility. The facilities either oral anti-oestrogens such as clomiphene
for IVF and lCSl are available in selected centers and citrate ortamoxifen or by usinggonadotrophins alone
they are far more expensive compared to donor or in combination with gonadotrophin releasing
insemination'.
t hormone (GnRH) agonists or antagonists. lncreasing
i
t Donor Screening:
the nu mber of developi ng oocytes, and i mprovi ng the
timing of insemination by giving the recipient HCG at
Donors for D.I are cou nselled and will haveconsented
optimal follicle diameter and then inseminating 36
to be anonymous donors. ln Africa it is not unusualfor
lr
. 475
(
and 48 hours later improve the pregnancy rate per women becom ing pregna nt th rough Donor
patient but not necessarily the pregnancy rate per lnsemination within 12 cycles'''. A spontaneous
cycle started. abortion rate of 10-15% is usual and the fetal
abnormality rate is not different from that of naturally
Results Of Artificial I nsemination :
conceived pregnancies. Because these pregnancies,
The results of A.l are summarized in Table V. The are classified as precious pregnancies the attending
normal pregnancy rate from AIH is between'15-30% Doctor may decide to deliver them by elective
of patients who start treatment. The pregnancy rate caesarean section. There is no objective scientific
for D.l is far higher with between 45-65"/" of treated evidence to support this practice.
Table V Results of Artificial lnsemination
Total Cycles Per Pregnancy Total Cycles Per Pregnancy

Cvcles Annum Rate (%) Cvcles Annum Rate (%)
35 77x
Giwa-Osagie et al
(1985) Lagos (6)
Giwa-Osagie et al
1995 - 2000 830 138 22.8 1543 257 58.2
Lagos
Wada et al Abuja
32 25
0D 1999
Robertson et al
100 100 22** 20 30+
Harare 2000
Fraser B Freetown
2000 20 7O++
IN VITRO FERTILISATION (IVF): and Embryo Culture d) Embryo Transfer e) Results of

Successful pregnancy and delivery(ou) following IVF IVF f) Variations of IVF g) Safety and Outcome of
was probably the most spectacular development in Assisted Conception .
female infertility management in the second half of
the 20'n century. The groundwork for the Controlled Hyperstimulation and Follicle Tracking:
breakthrough had been laid by work in animal Several different regimes are used for controlled
models several years before human IVF(.). IVF was hyperstimulation. The objective of controlled
developed initially only for women with severely hyperstimulation is to produce several fertilizable
damaged fallopian tubes some of who had had oocytes. The readiness of oocytes for recovery is
unsuccessful tuboplasty. IVF was also obviously usually determined by measure plasma oestradiol
indicated for women who had had bilateral and follicular diameter. The most popular regime for
salpingectomies for ectopic pregnancy'''. The hyperstimulation uses a gnRH analogue such as a
indications were expanded to include indications nasal spray or subcutaneous injection starting in the
such as unexplained infertility, endometriosis and mid-luteal phase of the cycle preceding the cycle in
male infertility. which egg recovery is planned. For instance,
buserelin can be commenced on Day 2I of a 28-day
The procedure of IVF will be considered in five cycle. A transvaginal scan would be performed on
phases: a) Controlled hyperstimulation and Follicle Day 26 toexclude ovarian cysts and measure
Tracking b) Oocyte Recovery c) Oocyte fertilization endometrial thickness. On the commencement of
476
Assisted Re p rod u cti ve Tec h n o I ogy
menses gonadotrophins such as Pergonal (Serono) or syndrome and the number of ampoules of
Metrodin or Gonal-F are commended by gonadotrophins used and therefore the cost of a
cycle of lVF.
intramuscular injection between Day .1 and Day 3 of
the menses while the buserelin is cersinued.
Oocyte Recovery:
Follicular development is then mogi@@ serial
Once the indices for follicular tracking indicate that
transvaginal ovarian sonographp. Endoeretrial
the follicle is mature, HCG injection is given and
thickness is also measured serially. Flasmaoestradiol
oocyte recovery scheduled for 34-37 hours later.
and progesterone levels are also measured serially.
Oocyte recovery can be performed by laparoscopy
The doses of gonadotrophins given are tailored to
and aspiration of the visible follicles. This was the
each patient and her responses as ind'icated by
technique used for all the oocyte recoveries during
ovarian sonography and plasma oestradiol levels.
the early days of lVF. The oocyte recoveries for IVF in
The goal should be to produce over 6 mature follicles
the pioneering work of Giwa-Osagie and Ashiru in
for recovery and fertilization. Older women, aged
Lagos, Nigeria, in the early 1980s were performed.
more than 37 years, require more stimulation than
younger women particularly less than 30 years of
through Laparoscopy'''. The technique was
performed in a theatre and under general
age. When three or more follicles attain diameters of
anaesthesia. As many of the women requiring IVF
18mm or more and the endometrium is more than
I had had previous pelvic surgery the laparoscopic egg
t 9mm thick and the oestradiol levels(Fig. 3), where
recovery had to be performed with extra care. The
this is measured, is more than 150pg/ml per follicle
presence of abdominal and pelvic adhesions could
t
in some centers, HCG 5000 or 10000i.u is given by
I
also obscure view of the ovaries and preclude
r intramuscular injection and oocyte recovery planned
successful oocyte recovery. lnjury to abdominal and
I
i for 34-37 hours after the HCG injection. Once the
pelvic organs sometimes occurs during laparoscopic
HCG is given no more gnRH analogue is administered
t egg recovery. By the late 1980s and early 1990s
I
t
and progesterone is administered either as an
most units performing IVF had adopted ultrasound
intramuscular iniection (100 -2O0mg daily) or as
guided egg recovery, which was transabdominal,
vaginal pessaries (cyclogest 450 pessaries 1 or 2
1
1
tra nsvesical or tra nsvagi nal. Transvagi nal u ltrasou nd
nocte).
ri guided oocyte recovery is now the standard
I technique. Ultrasound guided techniques were
The stimulation regime described above is the most
popular regime and. is otherwise referred to as the
made possible by advances in sonographic
{
t
"Long Protocol". There are other protocols. ln the
technology and instrumentation with the
l development of transvaginal ultrasound probes.
"Short Protocol" the gnRH analogue is started on the
I Oocyte recovery is now performed as an outpatient
first day of the menses and the gonadotrophin is
procedure and under general or regional analgesia or
started on Day 1 or Day 2 of the menses. Both gnRH
analogue and gonadotrophin are given daily and
with conscious sedation using drugs such as
a- pethidine and diazepam given 30 - 45 minutes
I
follicle tracking performed as previously described.
before the procedure. ln parts of the world where
The timing of egg recovery is as previously described.
severe pelvic adhesions and fibroids are common,
When the "u ltrashort protocol" is used, the
such as in West Africa, anatomical distortions may
stimulatory phase of gnRH analogue action is
employed by giving the gnRH analogue for just 3-5
still hamper transvaginal ultrasound guided egg
recovery. When the patient has responded well to
days starting during the menses and continuing with
hyperstimulation the process of oocyte recovery
gonadotrophins. This regime reduces the total
. nu mber of ampoules of gonadotrophi ns used.
takes on ly 20 - 40 mi nutes.
Oocyte Fertilization and Embryo Culture:

More recently the development and use of gnRH
Once the oocytes have been recovered the success of
antagonist has allowed their application in controlled
,i
hyperstimulation. lt is reported that gnRH
the IVF programme relie3 on the skills of the
Embryologist. The aspirated follicular fluid and
antagonists reduce the risk of hyperstimulation
oocytes are examined on a heated stage using a
.
477
-
binocular microscope under a laminar flow

hood. The cell stage or at about 4g _ 60 hours after egg
oocytes (see Figure 1) are identified and transfErred
recovery. lt makes sense to transfer early rather
into individual culture plates or tubes and incubated than
in culture media at 37oC in a 57" carbon Ai*iU. later if one practices in an environment where
the
atmosphere. After about 3 hours of equitibratioi+ maintenance of ideal conditions can be difficult.
the
oocytes are inseminated with semen corttainirig There is cummulative evidence recommending
100,000 to 200,000 sperms per oocyte an; delayed transfer till blastocyst stage as a means
of
incubated at 37oC in the presence of 5% CarOon reducing multiple pregnancy, reducing abnormal
dioxide. Some embryologists prefer to incubate embryos through wastage and improve pregnancy
each
oocyte under paraffin oil. Various specialized rate per embryo transfer. Embryos to be transferred
media
are used according to the preference of individual are loaded in small volume of media in embryo
units. At the Lagos University Teaching Hospital,
transfer catheters - see Fig 3, which shows examples
Lagos in 1980 - 1989 we used Hams Ft-O
solution, of embryo transfer catheters. The catheters are
which we constituted locally. Nowadays commercial
preparations inserted through the woman,s cervical canal while
of various IVF culture media are
available on order. ln our unit at Lagos we have she is in the lithothomy or knee chest position and
used
Minimum Essential Medium (MEM) and ,,Medicult,, the embryos deposited near the uterine fundus. No
and "Fertipro', media duringthe last 4 years. anaesthesia is required for this procedure. Some
The most l\
important thing is for the Embryologiit to be
satisfied units carry out transfers under transvaginal
with the performance of the media selected. The sonographic guidance. The choice of ET catheters
is
cultured oocytes are examined at intervals and a matter of ind ividual IVF unit choice. Our units
the at the
media exchanged. The ejection of pronuclei and Lagos University Teaching Hospital and at the
cell
division indicate successful IVE which will be
Advanced Fertility Centre, Lagos prefer the Wallace
followed by more cellular divisions. provided
the Catheter or the Rocket Medical ET Catheter. After
embryos are symmetrical, with normal nuclear ET
and the woman rests for about 30 minutes before she
cytoplasm the embryos can be transferred to
the goes home. Post ET advice includes avoidance
patient anytime from 4g hours post oocyte of
insemination. sexual intercourse, as well as vigorous activity, or
diets that may cause diarrheoa. The woman
Figurel- A photograph of a Matured Oocyte. continues use of intramuscular progesterone or
progesterone pessaries till a blood BHCG pregnancy
test can be performed about 14 days after ET. lf the
woman starts bleeding earlier a blood BHCG
pregnancy test is performed to allow rational
management.
Results of IVF:
While it is useful to know that a blood pregnancy test
is positive 14 days after Ef, a more concrete proof
of
pregna ncy is obta ined by demonstrating
a
gestational sac with fetal pole 4 weeks after
ET. We
rely on sonographic demonstration of pregnancy in
our unit. The diagnosis of chemical pregnancies is
of
no use to the patient. The results of IVF may be
presented in various ways. pregnancy rates
may be
expressed "per cycle started,,, ,,per egg recovery,,, ,,per
embryo transfer', or as ,,take home baby rates,, ,per
Embryo Transfer (E.T): cycle started' or'per embryo transfer,. Most IVF units
Pregnancies following IVF have been reported now prefer to express their results as clinical
t after transfer of fertilized oocyte or as late as after pregnancy rates ,,per cycle startedi, and or ,,per
of morulae or blastocyts. Most IVF Units
transfer embryo transfer" and as ,,take home baby rates per
programme perform embryo transfer atthe 2
cell to g- cycle started" and ,,per embryo transfer". lt is
478
Assisted Re p rod u ct i ve Tec h no I ogy
important to take note of the method used to express The true results of IVF in most Units in Sub-Saharan
IVF results when reading reports. Typical results vary Africa, excluding South Africa, are lower than those
from 15% to 35% pregnancies per embryo transfer of IVF Units in developed countries.
with take home baby rates between 12 and 2O% per
embryo transfer. The reported results of IVF in Sub-
Saharan Africa are summarized in table Vl(3).
Table Vl - Reported Results of IVF in SubSaharan Africa
Centres Cycle/Annum Pregnancy Pregnancy Multiple Take Home

Rate/OR Rate ET (%) Pregnancy Baby/ET
Rate (%) (%)
Alfacare, Harare (2001) 28 (frozen
50 15.8
embrvos)
Nisa-Premier (13), Abuja
50 15 27 16.6 t4
(1999)
Advanced Fertility Clinic,
50 16 2t 14.3 t4.1
Lagos (19992000)
Bridge Clinic, Lagos 36
159 19 27.6
(1999-2000)
Providence Hospital, 10 (oocyte 10
40
Laeos (1999) donation)
These lower results may be due to the following indicated, before lVF.
reasons:
VARIATIONS OF IVF:
(i) On average women present for IVF at an older age
in Sub-Saharan Africa than in the developed a) Gamete lntra Fallopian Transfer (GIFT)-
Countries; ln this method recovered oocytes are mixed with
sperm and injected into the patient's tubes. This can
(ii) Prevalence of uterine factors, such as fibroids and only be performed where at least one fallopian tube
uterine synechiae in Africa affect results of lVF. is patent. The sperm(s) and oocyte(s) fertilize in the
:- lnfections may also reduce pregnancy rates; natural environment of the fallopian tube and the
embryo migrates into the uterus and implants. Early
(iii) There are often difficulties in maintaining ideal reports in the mid to late 1980s suggested that GIFT
conditions of infrastructure including water, light and could give higher pregnancy rates than IVF in women
even the quality of medical gases for embryo with patent tubes. Accumulated results of GIFT do
incubation; not sustain that initial optimism. b) Zygote lntra
Fallopian Transfer (Zl FT)(n)
(iv) Most IVF units do less than 100 cycles per
annum. This means that the learning curve for the Fertilized oocyte(s) or zygote(s) are injected into
procedure and any changes in procedure is longer patent tube(s). ln ZIFT we are sure fertilization has
than in the busier IVF units in developed Countries. taken place before transfer to the tube(s) unlike in
GIFT. ZIFT has a special place if we find that failure of
The results of IVF can be improved by: better patient fertilization is a factor in a couple. Most IVF units no
selection; pooling of expertise and resources between longer believe that ZIFT has a significant advantage
IVF centers; offering IVF with donated oocytes from over normal lVF. c) lntracytoplasmic Sperm lnjection
donors below age 37 to IVF clients who are aged flcsr)
t above 40 years; performing routine hysteroscopies,
; and uterine adhesiolysis and myomectomies when ln lCSl each recovered oocyte has a single sperm
479
injected into it
using special pipettes under SAFETY AND OUTCOME OF ASSISTED
microscopic magnification (see Figure.2). The CONCEPTION:
injected oocytes are then incubated as for IVF in
which the individual oocyte is surrounded by about Children conceived through artificial insemination
100,000 sperms any of which may penetr@-ttte are not more likely to have any abnormalities
oocyte. ln lCSl the fertilization rate is significantly compared with children conceived naturally.
higher than in normal IVF especially when the Sperm Children conceived by in vitro fertilization do not
indices are very low have significantly increased abnormalities than
naturally conceived children. There is evidence that
e.g. less than 0.5millioniml concentration and embryos following lCSl, and less so following normal
motility less than 30Y", or abnormal morphology lVF, are more likely to have chromosomal
more than 60%. lCSl is especially indicated when abnormalities. The overall abnormality rate in the
there is obstructive azoospermia where sperms can offspring is not increased prob-ably because embryos
be recovered directly from the epididymis or testes by that are abnormal are not transferred by practitioners
aspiration or microbiopsy. As long as normal and because abnormal embryos fail to implant
sperm(s) can be recovered from a seminalsample or following lCSl or lVF. Long term follow up of tl
directly from the epididymis or testes, lCSl can be offsprings of assisted conception show normal
performed. There have also been reports of mental and psychological development. These are
successful lCSl, fertilization and pregnancy when areas that need to be evaluated continuously. The
immature sperms have been used for lCSl. main dangers of assisted conception are due to
hyperstimulation syndrome and surgical
There have been a few reports suggesting an increase complications during egg recovery such as damage
in embryo abnormalities following lCSl but these to pelvic and abdominal vessels and viscera. These
reports need to be monitored as more information complications can be reduced through proper
accumulates('o'. training and sharing of experiences between centers
and better hormonal monitoring as shown in Figure.3
The pregnancy and take home baby rates for lCSl are with the pattern of Estradiol levels during an IVF
not better than those for normal IVF when the semen treatment cycle.
is normal. lCSl is therefore not a replacement for
normal IVF in all patients requiring lVF. The special
indications for lCSl have been outlined eadier under Garif*rfi lml ln n,tr !ry pry af s{tmr$o.t
this subheading.
att:a7A*lC
&s*Sr&rrsl$o.r
Multiple pregnancy rates are increased by controlled

hyperstimulation regimes used for assisted
conception. The complications associated with
multiple pregnancies, particularly high order births
e.g. triplets and above, can be life threatening and
Figure2- The procedure of lCSl- lntracytoplasmic cost large amounts in funds and longterm care. ln
Sperm lnjection. some Countries such as Finland one embryo transfer
480
Asslsted Re p rod u ctive Tec h n glogy
e
is the norm r,t'hile most IVF units
will agree that two ACCESS TO ASSISTED CONCEPTION:
embryos and i,t the very most not more than three
embryos should be transferred at each embryo The cost of IVF in Sub-Saharan Africa is high
transfer. Transfer of one or two blastocysts has been compared with the earning of the average person
reported to
reduce multiple pregnancy rates and needing lVF. The cost per cycle varies between 1000
increase pregnancy rate, Some centers use natural, US Dollars and 3500 US Dollars in Countries where
unstimulated cycles for egg recovery and or embryo minimum wage of a public employee can be just 60
tra nsf e r, w h i e others tra nsfe r f rozen-thawed em bryos
I
The availability of IVF and related procedures in Sub-
in a natural cycle to reduce multiple pregnancy rate, Saharan Africa is shown in TableVll.
and increase overall pregnancy rate per egg recovery.
Table Vll- IVF and Related Procedures in SubSaharan Africa

EMBRYO OOCYTE
AIH/D.I IVF ZIFTIG'FT lcsl
FREEZING DONATION
A) Lagos 1. Advanced
Yes Yes Yes Yes Yes No
Fertility Clinic
2. Providence Hospital Yes Yes No No Yes No
3. The Bridge Yes Yes No No Yes Yes
B) Abqja 4. NisaPremier
Hospital Yes Yes Yes Yes Yes Yes
C) Harare 5. Alfacare
Yes Yes No Yes Yes Yes
D) National Hospital Yes No Yes Yes Yes
:
Abuja Yes
-
I
I
i
Economic access to IVF can be improved by using tertiary hospitals in Africa. The National Hospital,
I
i
t
cheaper ovarian stimulation regimes such as the use Abuja, Nigeria recently celebrated 10 years of
r
of clomiphene; bulk purchase of drugs and sustained continuous IVF service (see Table Vlll)
t
I
consumables; sharing of facilities and expertise while IVF services have also been on-going at the
between IVF units; use of low cost incubators such as University of Benin Teaching Hospital, Benin-City,
t
modified waterbaths or "submarine" incubators. the Lagos State University and the University of llorin
Assisted reproductive technology has also recently Teaching Hospitals which are ihe most recent public
r
J
become available in a growing number of public facilities to provide this service in Nigeria.
i
NO. OF PATIENTS POSTIVE PREGNANCY

YEAR AND BATCH WITI.I EMBRYO RATE (%)
TRANSFER
2006 1sr Batch 16 43.8
2A07 7'l Batch 70 27.7
2008 1't Batch 23 21.7
2"d Batch l7 47.7
3'd Batch 43 40.5
2009 1't Batch 65 33.8
2nd Batch 33 18.2
2010 1't Batch 46 32.6
481
-'.'_!
Com p relrc n $ive Gy n aeco I ogy i n th*'To pi cs
2nd Batch 4:6 43.5

3'd Batch 46 47.3
2011 1't Batch 79 35.4
2nd Batch 62 54.8
3'd Batch 42 45.2
2012 l't Batch 44 50.0
2nd Batch 66 47.O
3'd Batch 90 28.9
2013 l't Batch 79 35.4
2nd Batch 73 56.2
3'd Batch 68 50.0
2014L.t Batch 87 29.9
2nd Batch 88 41.0
3'd Batch 89 49.4
2015 1't Batch 97 40.0
2"d Batch 100 40.0
2016 1't Batch 36 30.6
2'd Batch 87 31.0
ECENT ADVANCES IN PITUITARY antagonists are pgpltlg molecules that are made up
DESENSITISATION multiple, often synthetically produced amino acids'
Others are small-molecule, non-peptide
USE OF GNRH ANTAGONISTS
compounds. GnRH antagonists which compete with
Gonadotrophin-releasing hormone (GnRH) agonist is
natural GnRH for binding to GnRH receptors, thus
commonly used to prevent cycle cancellation
decreasing or blocking GnRH action in the body.
secondary to a premature luteinizing hormone (LH)
surge, and thereby increase the chance of live birth in Two GnRH-antagonist regimens have been
women undergoing assisted reproductive technology developed for controlled ovarian stimulation,
(ART), while reducing the risk of complications such
involving either single administration or multiple
as ovarian hyperstimulation syndrome (OHSS). administrations. ln the single dose protocol, the
Gonadotrophin-releasing hormone (GnRH) administration of a 3mg dose of GnRH-antagonist on
antagonists are now being seriously considered as a day 7 of the ovarian stimulation was shown to
potential means of achieving better treatment prevent a premature LH surge . ln the multiple dose
outcomes because the protocol is more flexible and protocol, the GnRH-antagonist was administered
antagonists may reduce OHSS more effectively than continuously until the day of hCG, and the minimal
agonists. However, there is the need to evaluate the effective dose to prevent the occurrence of a
benefits as well as the safety of these GnRH premature LH rise was identified as 0.25mg of
antagonist regimens in comparison with the existing . No significant difference in pregnancy
Cetrorelix "'o
GnRH agonist regimens. rates was shown in a randomized controlled trial
which compared single injections of cetrorelix
Gonadotrophin-releasing hormone (GnRH)
acetate (3mg) and a daily dose of ganirelix (0.25mg)
antagonists (receptor blockers) are a class of drugs
in the inhibition of premature LH surge. However, the
that antagonize the gonadotropin-releasing single-dose GnRH-ant protocol has the advantage to
hormone receptor (GnRHR) and thus the action of reduce the number of injections,'although additional
GnRH. Some are similar in structure to natural GnRH daily doses of antagonist are needed in lO% of cycles
(a hormone made by neurons in the hypothalamus)
. Moreover, in some cases a 3mg-dose may result in
but that have an antagonistic effect. These GnRH
482
Asslsted Reprod uctive Technology
excessive and potentially harmful suppression 'of viii. Duration of ovarian stimulation pr0tocolS is
endogenous Ll-l 'o . shortened, i m provi ng patient discomfort.
GnRH antagonists in ovarian stimulation for IVF Disadvantages

The aim of using GnRH antagonists in IVF is the
inhibition of a premature LH rise which could lead to i. GnRH antagonist co-treatment represents a
premature luteinization, follicle maturation arrest and novel approach in ovarian stimulation for IVF
asynchrony of oocyte maturation. The use of GnRH and knowledge accumulation is necessary
antagonists in IVF is characterized both by for its optimization.
adva ntages aisadvantages.
nd d
ii. GnRH antagonists offer less flexibility
Advantages and disadvantages far the use of GnRH regarding cycle programming as compared
antagonists in lVF. with the long, but not with the short, GnRH
agonist protocol.
Advantaees of use of GnRH Antaqonists iii. Most comparative studies report a minor
i. There is moderate quality evidence that the use reduction in pregnancy rates per cycle with
of GnRH antagonist compared with long-course GnRH antagonists as compared with GnRH
GnRH agonist protocols is associated with a agonlsts.
substantial reduction in OHSS without reducing
the likelihood of achieving live birth. " It should be noted that for units that manage starting
,.
dates of cycles to gain an orderly daily volume of
ii. Prevention of premature LH increase is easier oocyte retrievals the use of GnRH agonists has been
and takes less time. GnRH antagonists act within an advantage. With GnRH antagonist protocols,
a few hours after their administration " and thus sufficient flexibility regarding the starting dates and
I
I they can be administered only when there is a the ability to achieve a daily volume control is still
i risk for an LH surge. This is in contrast to GnRH present, although this can be improved by using the
i
I agon ists where pitu ita ry down-regu lation occu rs oral contraceptive pill (OCP) .
t
only after 7-10 days.
r lmportant aspecfs of GnRH antagonist use in
f
I
iii. GnRH antagonists are not associated with an ovarian stimulation for lVFSingle versus multiple
I acute stimulation of gonadotropins and steroid dose GnRH antagonist protocol
hormones, which occurs with GnRH agonist Two GnRH antagonist protocols were developed
r-
administration. involving either multiple or single administration. ln
t
I the multiple dose protocol, the GnRH antagonist was
i iv. The initial stimulation by GnRH agonists can administered continuously until the day of HCG
f induce cyst formation, which is avoided with administration, starting 5days after stimulation with
GnRH antagonists. gonadotropins ". The minimal dose shown to
i prevent the occurrence of a premature LH rise in the
v. No hot flushes are observed with GnRH great majority of patients was shown to be 0.25 mg;
antagonists as their use does not result in The Ganirel ix dose finding study grou p, 1 998). "''o
profound hypo-estrogenaemia observed with
GnRH agonists ". ln the single dose protocol, a 3 mg dose of GnRH
antagonist given on cycle day 7 during ovarian
vi. lnadvertent administration of the GnRH stimulation was shown to prevent a premature LH
analogue in early pregnancy can be avoided as surge ". ln case of the need to delay HCG, low daily
GnRH antagonist is administered in the mid- doses of GnRH antagonists could be added 4 days
follicular phase. after the single antagonist dose.
vii. Requirements for exogenous gonadotropins are Prosforthe single dose GnRH antagonist protocol:
reduced, rendering ovarian stimulation less Potential for fewer injections, although in 10% of
I costly. cycles additional daily doses of GnRH antagonist are
necessary "..
483
Cons for the single dose: Besides inhibiting, I I. NU MBER OF EMBRYOS TINNSTERRED
premature LH surge, the single dose protoeol rusults Whereas the trend now in developed countries is to
in an excessive and potentially harmful suppfpssion transfer a single embryo, particularly in Europe, this
of endogenous LH 'u'u. However, no d* may not be applicable in developing countries due to
difference in pregnancy rates was stlgffi,rffi a the presence of certain factors which may affect the
randomized-controlled trial (RCD whioh eof+rffim *ilnplantation rate and hence success of such IVF
the two antagonist protocols ". treatment cycles. These factors occuring in
_ developing countries include the higher incidence of
CONTROVERSIES/ EMERGING AREAS it{ ANT uterine synechiae and uterine fibroids. Therefore
PRACTICE single embryo transfer (SET) in our environment
could actually contribute to treatment failure in
I. DAYOF EMBRYOTRANSFER prevailing conditions. Another argument against SET
is the age at which women in our environment , seek
The decision to transfer embryos on day 3 or day 5 is
assisted reproductive technology treatment. Most do
one that requires careful thought. ln ieneral,
so either approaching or above the age of 40 years
embryos that have formed blastocysts have a better
when their ovarian reserve and oocyte yield
chance of implanting successfully. Unfortunately, not
subsequently is low. This translates to lower number
all embryos will progress to the blastocyst stage in-
of embryos available for transfer. Added to this is the
vitro. This fact raises the question as to whether the
fact that unlike in developed countries where women
embryos that fail to form a blastocyst would have
in this age bracket( > or : 40 years) would be
initiated a pregnancy if they had been transferied
offered donor oocytes and mostly readily accept, this
back into the uterus on day 3. Some studies have,
is not the case in our environment.
indeed, demonstrated acceptable pregnancy rates
with day-3 transfers of embryos that were of marginal III. SURROGACY
quality and that, based on historical data, would Surrogacy is an arrangement whereby a woman
have been unlikely to form blastocysts in culture ". carries and delivers a child for another woman or
Clearly, the pregnancy rate in the absence of an cou ple. Broad ly there are 2forms of surrogacy.
embryo transfer will be zero, whereas even embryos
of borderline quality, if transferred on day 3, may A. Traditional surrogacy. This is also referred tp as
potentially lead to a pregnancy. 0n the other hand, natural or partial surrogacy.
following normal fertilization inside the fallopian
tube, the human embryg does not arrive into the B. Gestational surrogacy. This is also referred to as
uterus until after day 5 following ovulation. There IVF or Full surrogacy.
may be improved synchronization between the
embryo and endometrial lining when an embryo ln the former, the surrogate is genetically related to
transfer is performed on day 5, possibly leading to the child,. The child may be conceived via home
enhanced implantation rates. Unfortunately, there is artificial insemination using home or frozen
no way to do a study in which the exact same embryo
spermatozoa or impregnated via lUl(intrauterine
is transferred on day 3 and day 5 in order to answer insemination), or lCl (intracervical insemination)
performed at a health facility. ln the latter, the
this question.
surrogate is genetically unrelated to the child. lt
One additional risk of a day-5 transfer is an increased requires the transfer of a previously created embryo
rate of identical twinning. Although recent (by in-vitro fertilization), and for this reason, the
advancements with rapid freezing (vitrification) have process always take place in an appropriately
le.
resulted in excellent survival and pregnancy rates equipped health facility
with blastocysts, not all clinics currently ernploy this
lndications fortreatment by IVF surrogacy include:
technique. We believe that extended culture must go
hand in hand with an excellent cryopreservation
o Advanced maternal age
program in orderto maximize patientsuccess.
. Congenital absence of the uterus or severe
uterine hypolasia
o Severe medical conditions incompatible
484
I
t
I
t
i' AssiSted Re prod uct i ve Tec h no I ogy
I
r
I
r
I with pregnancy imp,rinting in humans has been recognized for
I
t . Repeated failure of IVF treatm€frt several years; however, the magnitude of this risk
t
I
r Recurrent abortion and the spectrurn of imprinting syndromes to which
I
o ' Following hysterectomy fui" n*ffiffitr&gia, the risk applies remain unknown.
t postpa rtu m h aemori.hage 6f 'ffiffi:l'',,
I
I
I
. Controversiaily male intendingry IV. PRE.IMPLANTATION GENETIC TESTI NG
t
I
I
ln-depth counseling of all partie*,€*l@ in Preimplantation genetic testing is a technique used
I
a surrogacy is essential and aims to pfepdre all to identify genetic defects in embryos created
I aprties contemplating this form of treatrnertt to
I through in vitro fertilization (lVF) before pregnancy.
i consider all the facts which will have a lasting Preimplantation genetic diagnosis (PGD) refers
I
I
impact and influence on their lives, specifically to when one or both genetic parents has
i a known genetic abnormality and testing is
i
r performed on an embryoto determine if it also
I
III. INTRACYTOPLASMIC SPERM INJEGIION AND
i carries a genetic abnormality. ln contrast,
CONG EN ITAL FOETAL ANOMALI ES
I
preimplantation genetic screening (PGS) refers to
I
techniques where embryos from presumed

Undebatable well-documented areas in ART are
chromosomally normal genetic parents are screened
I those associating IVF-|CS| pregnancies to be at a
t for aneuploidy.
higher risk for multiple gestation, preterm labor and
I low birth weight. An area of great conflict as well as
I
I
Because only unaffected embryos are transferred to
I
interest is, as to whdther ART is associated with
the uterus for implantation, preimplantation genetic
increased congenital malformations or not.
testing provides an alternative to current
I
I
I
I
postconception diagnostic procedures (ie,
ln a study of a large cohort of children born after
I
amniocentesis or chorionic villus sampling), which
I
I
standard in vitro fertilization (lVF) and are frequently followed by the difficult decision of
intracytoplasmic sperm injection (lCSl) (n : 2840
r pregnancy termination if results are unfavorable.
I and 2955, respectively) the rate of major congenital
I PGD and PGS are presently the only options
malformations was around 4%,'o and another large
r
I prospective study comparing children born after lCSl
available for avoiding a high risk of having a child
I affected with a genetic disease priorto implantation.
with controls conceived spontaneously reported a
relative riskof 1 .24(9.5%Cl, 1.02-1.50)
It is an attractive means of preventing heritable
''.
I
I
l
I
genetic disease, thereby eliminating the dilemma of
I Different types of congenital malformations in
pregnancy termination following unfavorable
I
l
assisted reproductive techniques born babies prenatal diagnosis.
U rogenital malformations
l
I
Edwards and Gardner successfully performed the
I
There is the marked association of urogenital defects, first known embryo biopsy on rabbit embryos in
I
I specifically hypospadias, with lCSl in particulaf'. 1968. ln humans, PGD was developed in the United
I
Kingdom in the mid 1980s as an alternative to
I
i
ln fact, in the mid-2000 years, there were studies current prenatal diagnoses. lnitially, PGD revolved
which reported an increased incidence of around determination of gender as an indirect means
ma lformations i n I CS I -conceived pregnancies versus of avoiding an X-linked disorder. ln 1989 in London,
I the |VF-conceived pregnancies. lt was due to the Handyside and colleagues reported the first
consistent association of hypospadiasis in the lCSl- unaffected child born following PGD performed for
conceived male infant, that lCSl was blamed to an X-linked disorder.
contribute to more congenital malformations than
IVF.,. As of 2006, more than 15,000 PGD cycles have
; been reported '0. PGD is currpntly available for most
F lmprinting disorders and genetic syndromer known genetic mutations. Although the indications
i An association between ART and abnormal genomic for PGD are well established, FGS is a relatively new,
485
evolvi ng tech n iq ue a nd rema i ns controversia l. uterine fibroids in women, which may hamper
lndicationsfor PGD embryo implantation in lVF, there is debate as to
These include the following: whether hysteroscopy should be performed routinely
. Couples with a family history of
X-linked prior to IVF treatment, to properly assess the
disorders (Couples with a family history of X- endometrial lining of women pre-lVF treatment. lt
linked disease have a 25% risk of having an should be remembered however, ihat not all uterine
affected embryo Ihalf of male embryosl.) fibroids are implicated in treatment failure. lt is
. Couples with chromosome translocations,
usually those that are submucosal or intracavitary in
which can cause implantation failure, location that impair implantation; or intramural
recurrent pregnancy loss, or mental or uterine fibroids that are large enough and distort the
physical problems in offspring
normal contour and shape of the endometrial cavity.
. Carriers of autosomal recessive diseases (For
Uterine synechiae can impair implantation but there
carriers of autosomal recessive diseases, the
are other methods of detection, both clinical and
risk an embryo may be affected is25%.)
other less invasive investigations to aid in diagnosis
. Carriers of autosomal dominant diseases
(For carriers of autosomal dominant disease,
of this condition. Presently, most IVF centres would
offer routine hysteroscopy in selected clinical casr
the risk an embryo may be affected is 50%.)
and cases of recurrent IVF failure.
lndications for PGS
CONCLUSION
Presently, there are
no specific indications but
primary candidates for PGS can include the
Advances in assisted conception now make it
following:
possible for couples that would otherwise not have
. Women of advanced maternal age
. Couples with history of recurrent pregnancy
children to do so. There is great unmet need for
assisted conception in Sub-Saharan Africa where
loss
. Couples with repeated lVFfailure there are less than 40 IVF units outside South Africa.
. Male partner with severe male factor This situation which is still an improvement on the
infertility". situation in early 1980s when the IVF unit at the
Lagos University Teaching Hospital, Lagos was the
PGD and PGS are gradually gaining ground in the first to achieve IVF pregnancy in 1983 and a birth
tropics but is not yet widely available. lt would play a from IVF in 1989. Steps need to be strengthened to
helpful role in the prevention and transmission of prevent the causes of tubal disease, which is the
haemoglobinopathies such as sickle cell disease and main indication for lV[, such as sexually transmitted
thalassemia infections, unsafe abortions and childbirth in
unhygienic conditions in particular. There are
However the phenomenon of mosaicism affects test virtually no regulations governing assisted
results occasionally. Sensitivity and specificity of conception in Sub-Saharan Africa, outside South
results can also be affected in some cases where Africa, and this needs to be rectified. Access to IVF in
tropherctoderm biopsy is performed, which may not particular can be improved and results improved
be fully representative of the inner cell mass genetic through steps, which have been outlined in this
milieu. chapter.
V. ROUT!NE HYSTEROSCOPY PRE-IVF
Due to the occurrence of uterine synechiae and
485
Assrsted Re p rod u ctive Tec h no I ogy
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Couples lnternationat Journal of Fertility, 1984, 11. At-lnany H and Aboulghar M (2OO? GnRH
29:104108. antagonist in asslsted reproduction: a Cochrane
review. Hum Reprod 17,874-885.
2. Giwa-Osagie O.E Nwokoro C. Ogunyemi D Donor
lnsemination in Lagos Clinical Reproduction in 12. Diedrich K, Diedrich C Santos E, Zoll C, al'
Lagos Clinical Reproduction and Fertility 1985,^3: Hasani S, Rerssman n T, Krebs D and Klingmuller
305310 D (1994 Suppression of the endogenous
luteinizing hormone surge by the gonadotropin-
3. Giwa-Osagie O.F ART in Developing Countries releasing hormone antagonist Cetrorelix during
With Particular reference to Sub-Saharan Africa ovarian stimulation. Hum Reprod 9,788-791.
t
2002, pg 22-27 ln "Current Practice and
Controversies in Asslsted Reproduction", World 13. Olivennes F, Alvarez S, Bouchard E Fanchin R,
health Organisation 2002, Geneva. Salat-Baroux J and Frydman R (1998) The use of
a GnRH antagonist (Cetrorelix) in a single dose
4. Edwards RG, Steptoe PC, Purdy JM Establishing protocol in IVF-embryo transfer: a dose finding
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Embryos Grown in Vitro British Journal of 13,2411-2414.
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5. Steptoe PC, Edwards RG, Purdy JM Clinical (1997) Comparison of different doses of
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Aspects of Pregnancies Estab/rshed with Cleaving gonadotropin-releasing hormone antagonist
I Embryos Grown in Vitro British Journal of Cetrorelix during controlled ovarian
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Obstetrics and Gynaecology 1980 ,87: 7 57 hy persti m u I ation. Ferti I Steri I 67,9 1 7-922
6. of Rabbit Oocytes in
Chang M.C The Maturation 15...Aboulghar MA, Mansour RT Serour Gl, Al-lnany
Culture and Their Maturation, Activation, HG, Amin YM and Aboulghar MM (2004)
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a
I Fertilization, and Subsequent Development in the lncreasing the dose of human menopausal
gonadotropins on day of GnRH antagonist
I
I Fallopian Tubes'Journal of Experimental Zoology
I
1955, 128:379-405 administration: randomized controlled trial.
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Reprod Biomed On I i ne8, 524-527.
7. Ogedengbe O.K, Giwa-Osagie O.F, Ogunyemi D
i
lmplications of Pattern of Tubal Disease for 16. Albano C, Grimbizis G, Smitz J, Riethmuller-
Microsurgery and ln Vitro Fertilization in Lagos Winzen H, Reissmann T, Van Steirteghem A and
Journal of National Medical Association 1987, Devroey P (1998) The luteal phase of
79,510-512 nonsupplemented cycles after ovarian
superovulation with human menopausal
8. Giwa-Osagie O.F et al Human Oocyte recovery for ln gonadotropin and the gonadotropin-releasing
Vitro Fertilization: The Use of Cervical Mucus and hormone antagonist Cetrorelix. Fertil Steril
Plasma Oestrodiol as lndices of Follicular 70,357-359.
Development West African Journal of Medicine
I
1988,7:136139. 17. WilcoxJ, Potter D, Moore M, Ferrande Land Kelly
E (2005) Prospective, randomized trial
9. Giwa-Osagie et alSuccessfu/ Outcome Following ln comparing cetrorelix acetate and ganirelix
Vitro Fertilization and Zygote lntra Fallopian acetate in a programmed, flexible protocol for
Transfer in a Private Clinic Society of Gynaecology premature luteinizing hormone surge prevention
:
and Obstetrics of Nigeria (SOGOIV) Annual rn assisted re productive t-echnologies. Fertil Steril
I Ge n e ra I Confe re nce 1 999 Abstract 9. 84,108-117.
,
a 10. Current Practices and Controversies rn Assisted 18. Sallam H, Sadek S. Ultrasound-guided embryo
'l
487
Comprehensivt Gynaecology in the Topics ,)
transfer: A meta-analysis of randamleed cantrolled, prospective cohort study. Fertil Steril.

controlled triaIs. Fert| SteriI 2003;80; .1,0#,2--.6,. 2004; 81:1604-16.
19. Efetie ER, Agida TE. Surrogacy. 22. Kallen B, Finnstram O, Nygren KG, Otausson pO. tn
assisfed conception in the tropies. vitro fertilization 0VF) in Sweden: Risk for 1
Aghoja. DERH I REC 201 5; I l congenital malforrnations after different tVF
methods. Birth DefectS Res A elin Mol Teratot.
20. Bonduelle M, Liebaers
l, Deketelae& 2005;73: 162-9
Camus M, Devroey E et at. fleonal
cohort of 2889 infants born 23. Wennerholm lJB, Bergh C, Hamberger L, Lundin i
1999 and of 2995 infants born K, lVilsson L, Wikland M, et at. tncidence of
1 9 99 H u m Re p rod. 2a0 2 ; I 7, 6T 7
-9d..,r.,r,..,,. ", .
congenital malformations in children born after
lCSl. Hum Reprod. 2000; 15:944-8
2L. Katalinic A, Rijsch C, Ludwig /t/. Cerriii,f :IfS,
Follow-Up Study Group. Prqgnancy'Eq4fSe ana 24. Dayal MB, Lucidi RS. pre-implantation genetic
outcome after intracytoplasmic sperm iniwfan, e di agnos i s. E m ed ic i ne. m ed sca pe. com / a rtic lel27 3
415.
t-, I
488
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cHAPTER
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41
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The Climateric and Menopause

O O Ogunbode and A O Arowojolu
f
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f
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i
INTRODUCTION decline continues till puberty when the oocytes
The Climacteric is that phase of a woman's life which number about 400,000. During the reproductive
i.
marks the transition from the reproductive to non- peri:d, multiple oocytes are stimulated per ovarian
reproductive phase and usually spreads over a period cycle with only 7-2 becoming the dominant follicle
of 5-10 years. lt occurs globally and is an irreversible r:hile the remaining undergoes atresia. lt is thus
r aspect of women's aging process, The most visible estimated that only about 500 oocytes are actually
i
event duringthis transition is the menopause which is ovulated during the reproductive lifetime. The
the final menstruation. ln the early part of the depletion of theses oocytes is what primarily leads to
i
I
climacteric period termed "premenopause", the menopause.
:
menses is likely to be infrequent coupled and other
a
I climacteric symptoms may be present. Another factor responsible for menopause is the
l
? decreased responsiveness of the ovarian follicles to
I
Clinically, menopause is diagnosed retrospectively pituitary gonadotrophins, This results into impaired
:
following cessation of menstrual flow for a period of folliculogenesis, elevated gonadotrophins and
twelve consecutive months without any other significant fall in circulating oestrogens.
t
t
f
associated biological or physiological factor.l,2 lt
marks the end of fertility when the woman will not be The age of menopause seems to be genetically
I
1
able to bear further child without any form of assisted predetermined, occurring averagely at the age of 51
t
methods of conception. years and ranging between 45-55 years.*u,ot The
r
i mean age of menopause from Nigerian and
I
Menopause can be natural or induced. Natural Ghanaian studies is between 48-49.5 years.1,7'o'
menopause occurs due to the depletion of the Unlike menarche(age of first menstruation) which is
i
I primary oocytes while induced menopause may influenced by many biological and environmental
follow removal of the ovaries or damaged ovaries factors, only a few factors such as smoking and
following irradiation or medications. lrrespective of malnutrition has been documented to cause
r the type of menopause, the symptoms are the same menopause occurring earlier.S Presently available
but are more abrupt and disturbing to affected evidence has not shown any correlation between age
women fol lowi ng induced menopause.' at menopause and race, socioeconomic status,
r
Oogenesis begins in the human embryo starting from

physical characteristics, age at menarche,
educational status, number of pregnancies, date of
the third week of gestation and reaches its peak about
last pregnancy or confinement, alcohol consumption
f the 20 weeks of gestation, numbering about 7 m i ll ion
r' or use of oral contraceptives.''.u-
t oogonia. Right from this period, a decline sets in and
with about 1-2 million oocytes present at birth. This lf the menses stops spontaneously before the age of
I
t.
:
489
40years, it is termed premature menopause or regular by the age of 25 years. This stability is
premature ovarian failure. The causes include attributed to reduction of the proliferative phase
chromosomal abnormalities (Fragile X carrier, because the luteal phase remains constant
Trisomy and Mosaic), autoimmune diseases, throughout the reprod uctive period.
irradiation, chemotherapy, inborn errors of
metabolism and previous abdominal surgeries.9l0 ln the years preceding menopause, while the
Untreated coeliac disease is associated with early Luteinizing hormone (LH) remains unchanged, there
menopause but if the sufferer is well controlled on is a gradual rise in the level of Follicle stimulating
gluten-free diet her onset of menopause is similar to hormones (FSH) during the early follicular phase and
mid-cycle. This change in FSH is attributed to the
that of her population.l l Abdominal hysterectomy
reduction in the number of gonadotrophin-sensitive
with ovary conservation reduces the onset of
ovarian follicles and the reduced inhibin levels,
menopause in normally menstruating women by an
produced by the granulosa cell of matured follicles.
average of 3.7 years. Early onset of menopause is
lnhibin acts on the pituitary gland via a negative
also observed in women who have had endometrial
feedback mechanism in regulating FSH release but
resection or uterine artery embolization. The reason
with the reduction of oocytes there is a corresponding
for this is unknown but the hypothesis is that
decrease in the lnhibin concentration and resultant
endocrine factors produced by the endometrium
rise in FSH"
may be contributing to the endocrine feedback and
regulation of the ovarian stimulation. Elimination of
During the climacteric period, the menstrual
these factors contribute to faster depletion of the bleeding becomes irregular due to the disordered
ovarian reserve. Reduced blood supply to the ovaries
maturation of the ovarian follicles. The cycles also
that may occur as a consequence of hysterectomy become anovulatory.
and uterine artery embolisation may be
contributory. Gonadotrophins
The levels of gonadotrophins (FSH and LH) are
With the improvement in life expectancy, it is higher in the postmenopausal period, and mainly
projected that women will be spending one-third of due to the reduced levels of inhibin and the loss of the
their life span during the post-menopausal period.3 lt negative feedback effect of ovarian steroids. There
is therefore important for family members to be also appears to be increased response of the pituitary
familiar with their peculiar problems and the likely to the hypothalamic gonadotrophins releasing
increased financial burden. The healthcare workers hormone. This is supported by the observed
will need to anticipate the increased out-patients increased amplitude of the pulsatile burst of
consultations for postmenopausal problems and be gonadotrophins from the pituitary gland. The
conversant with the necessary specialized care. increased levels occurs more with FSH compared to
Some of which may involve multidisciplinary LH. Serum FSH or LH of >40 iu/ml is indicative of
approach. Relevant government agencies will need to menopauser3'14
improve access to quality care which may be best
delivered in dedicated elderly centers. ln addition, Androgens
care must be subsidized since the bulk of these The main androgens in women are androstenedione
women will be in the unemployed segments of the and testosterone. Prior to menopause,
population.l2 androstenedione is the primary androgen produced
by the ovarian follicles however after menopause its
ENDOCRINOLOGIC CHANGES IN THE circulating level is reduced. The reduction may be
CLI MATERIC AND M ENOPAUSE attributed to the loss of follicular activity. The adrenal
During the reproductive period, regular menses is gland also accounts for most of the postmenopausal
ensured by a well-coordinated and functional ci rcu lati ng androstened ione with conti nued min imal
hypothalamo-pituitaiy-ovarian-uterine axis. ln the contribution from the postmenopausal ovary.
early reproductive age groups cycle lengths are
usually longer and irregular, but become shorter and There appears to be only a slight reduction of
490
.--.--:-----!
testosterone after menopause compared to Vasomotor

androstenedior e. This may be due to the fact that The classical vasomotor symptom that has been
testosteron e n prod uced f rom m u lti ple ryfree, such
i observed in women in the climacteric and
as from the peripheral conversion.# @ting menopause is the hot flush.17 The Hot flush is a
androstenedione and also direcsf:rfft5.n, the sudden feeling of warmth which occurs in the face,
postmenopausal ovary. What is houro.rer censistent neck an trunk. lt is usually accompaniedwith
from studies is that the androgen/oestrqpn ratio is episode of sweating and palpitation. Sometimes, it
increased in women after menopause which may may be associated with insomnia. The exact cause is
somehow explain the features of hyperandrogenism unknown but there is growing evidence that the
seen in some olderwomen."'" thermoregulatory center in the hypothalamus is
involved. Gonadotrophins ae also considered to be
Oestrogen involved because of the demonstrated association
The circulating levels of all oestrogens are reduced between when hot flushes occur and the pulsatile
during the postmenopausal period. Oestradiol, being release of LH. The possibility of altered
the commonest circulating oestrogen in women in the neurotransmitters to the GnRH neurons such as
reproductive age group is also the most affected. norepinephrine and opioids as being responsible has
Although, direct ovarian production still continues, it also been postu lated."'t''"
is minimal, with the predominant source now being
from the peripheral conversion of oestrone. Others Reproductive system
sources of oestrogens are the adrenal glands and from During the climacteric there is a change in the
the peri pheral conversion of testosterone.'u inenstrual pattern which may be variable. The
common pattern is gradual development of
Following menopause, oestrone becomes the most oligomenorrhea and hypermenorrhea. However a
predominant oestrogens. Although it circulating few women may experience periods of
levels also declines after menopause but it is not as hypermenorrhea interspersed with intermenstrual
much as the decline in serum oestradiol. The adrenal bleeding or normal menstrual flow. lt is rare for the
glands are indirectly the major source of the oestrone, menses to stop abruptly in natural menopause.
due to the aromatization of the androgens produced
from it. The small amount of androgens produced Oestrogen plays a vital role in the growth of organs in
from the ovary also undergoes aromatization. Most of the reproductive tracts. With the transition to the
the peripheral conversion occurs in adipose tissue hypo-ostrogenic states which occurs during the
and muscle, with the remaining occurring minimally climacteric and menopause, atrophic changes then
in the bone marrow, fibroblast and brain"''o sets in the entire reproductive organs.
Progesterone The vagina epithelium becomes thin and the vagina

ln premenopausal women, the circulating ruggae disappears. The vagina bleeds easily from
progesterone is majorly produced from the corpus minimal trauma. The defense system to local
luteum following ovulation. With the depletion of bacterial invasion becomes compromised leading to
primary oocytes and the absence of ovulation in increased episodes of vaginal discharge. The uterus,
menopausal women, the circulating level of cervix and the ovaries also shrinks in size.'o'"
progesterone falls rapidly. The small amount found is
probably from adrenal origi n. Urinarysystem
The decline in the oestrogen also affects the integrity
EFFECTS OF M ENOPAUSE AND AGEI NG of the endothelium lining of the urogenital system.
The bladder epithelium becomes easily irritated,
Symptoms around menopause (the menopausal leading to urgency and frequency of micturition.
transition period) include irregular unpredictable Stress incontinence is the most prevalent
ffiefiS€s; vasomotor and urogenital symptoms such symptom.lg The prevalence of cystitis is also
I as vaginal dryness and dyspareunia; and changes in increased in postmenopausal women. Occasionally,
sleep patterns and mood swings.16 hematu ria also occu rs."'"
49L
Skin and Hair release, and subsequently reduction of alpha 1,25-

With the onset of menopause, there is loss of dyhydrovitamin D, lowers calcium absorption.
elasticity and the skin becomes thinner andlffie@s. Because the body is deprived of its intestinal source
Wrinkling around the mouth and eyes, ternr&#ffirBe of calcium, the bone becomes the primary source of
becGffiffi.
string" and "crowfeet" respectively calcium. Evidence from some workers indicates that
mairft-a f i
Credence to the role of oestrogen in calcitonin production declines with estrogen
integrity comes from the observation d ostnOgen deficiency and that estrogen receptors are present in
receptors in the skin. Ostrogen also a{ters the bone. Therefore it
is likely that estrogen, like
vascularity of skin, increases collagen,contert and calcitonin, modulates bone remodeling directly by
promotes derma I water retention.'o'tt either inhibiting osteoclast activity or stimulating
osteoblast activity."''o
Bone Metabolism and Osteoporosis
Bone is an active tissue composed of a va,riety of bone With ageing, especially after menopause the rate of
cells and its stability is maintained by the bone bone loss is accelerated, thereby leading to
marrow through a balance between osteoblastic and osteoporosis. Osteoporosis affects all the systems
osteoclastic activities. Osteoblasts and osteocytes and is typified by a reduction in bone mass despite
participate in the creation and mineralisation of normal bone mineral to matrix ratio. This
bone. Bone formations starts with the deposit of an predisposes postmenopausal women to fractures.
amorphous organic matrix termed "osteoid'r by the The fractures can affect all bones but more frequently
osteoblasts, which is hardened by the precipitation of affect the cancellous bones which are located in the
calcium and phosphate complexes. This process is vertebrae body. The bone loss is more prominent
then followed by bone remodeling while osteoclasts and worse in premature menopause, gonadal
also formed in the bone marrow promotes bone a bnorma I ities or fol lowi ng ea rly oophorectomy.
resorption.
Ostrogen deficiency has been established as the
Bone remodeling consists of the formative, factor responsible for osteoporosis in
activation, resorption and reversal phases, and each postmenopausal women, however other risk factors
cycle takes approximately 100 days. Several like advanced age, family history of osteoporosis,
substances such as calcium, calcitonin, vitamin D, ethnicity, sedentary life style, dietary habit, past and
parathyroid hormone (PTH) and interleukin-1 (lL-1) current medications, early menopause, and
are involved in the process. coexisting endocrine diseases should be considered.
The value of exercise in the development and
Calcium plays a crucial rote in maintaining skeletal prevention of osteoporosis is poorly understood.
integrity. Ninety-eight percent of the total body Inactivity produces muscular and skeletal
calcium is contained in bone. PT.H. is the critical degeneration. However, the type and extent of
modulator of calcium balance. lt stimulates renal exercise that will produce a positive bone balance is
hydroxylation of vitamin D intermediates to form 1, still undefined, Cigarette smoking, caffeine
25 - dihydrovitamin D (vitamin D3) which promotes consumption and alcohol consumption appear to be
intestinal absorption of calcium and phosphorous. associated positively with osteoporosis in yet
With long term vitamin D deficiency, the intestinal undetermined ways.
absorption of calcium is reduced and the body
thereby shifts to bone resorption as the main source Osteoporosis is often unnoticed clinically until it
of serum calcium."'" manifests as fracture. Pain may follow minor trauma
and usually localized to the portion of affected bone.
Calcitonin, derived from the C cells or the thyroid However, the pain may radiate to the abdomen, be
gland, inhibits osteoclastic activity, and lowers serum accompanied by muscle spasms or even become
calcium. Estrogen, like calcitonin, opposes the chronic. Women with hip fractures experiences
resorptive action of PTH. Estrogen loss appears to diminished hip range of motion (ROM). Loss of
make the bone more sensitive to the effects of PT.H. lumbar lordosis, kyphosis and tenderness over the
The increase in serum calcium that suppresses PT.H.
492
involved vertebrae may be noticeable on women with established osteoporosis.

examination. Transcutaneous hormone therapy with micronized
estradiol and progesterone is currently the treatment
Bone mineral density (BMD) measurement using T of choice in postmenopausal osteoporosis, as
and Z scores is recommended by the World Health evidenced by bone mineral density and biochemical
Organization (W.H.0) for post-menopausal wornen markers.2O ln both, prevention and treatment of
based on risk factor profile. Dual-energy x-ray osteoporosis, estrogens have a greater effect upon
absorptiometry (DXA) is currently the standard the spine than the hip.
criterion forthe evaluation of BMD. D)G providesthe
patient's T-score, which is the BMD value compared Calcitonin is also beneficial in the prevention and
with that of control subjects who are at their peak treatment of osteoporosis. The most effective dose is
BMD while Z-score is the value matched with 1 milligram thrice weekly. The disadvantages of this
controls for sex and race. Normal T-score value falls new treatment modality include expensiveness of
within 1 standard deviation (SD) of the mean BMD calcitonin and parenteral route of administration.
value in a healthy young adult. T-score of less than
-2.5 SD indicates osteoporosis.l4 Vertebral imaging Osteoporosis has devastating physical,
can also be adopted if BMD is not available. Newer psychosocial, and economic consequences. Hip
methods such as Quantitative calcaneal fractures are very disabling. The affected women
ultrasonography with its low exposure to ration, lower lose their independence and require prolonged
cost and portability offers good prospect in the future skilled nursing. Complications resulting from
but no diagnostic criteria has so far been identified prolonged immobilization have high mortality rates.
yet. Even where hip surgical procedures are available the
economic impact and demands for health care are
Although the exact mechanism by which estrogen tremendous.
prevents bone loss is unknown, several large clinical
studies have demonstrated a causal relationship Psychological
I
between estrogen deprivation, acceleration of bone Post-menopausal women have been shown to have
I
loss and reduced occurrence of fractures in estrogen increased complaint of anxiety, mood swings, sleep
I
treated patients. Cessation of estrogen therapy disorders, dementia, and irritability. The reason
I
results in rapid and progressive loss of bone mineral could be multifactorial but since oestrogen increases
r
content. neurotransmitters in the brain that are involved in
memory and related activities, the low oestrogen in
I
:v menopausal women is thought to play a significant

Oestrogens can be administered by oral,
t percutaneous (as gel), transdermal (from patches), role.
( parenteral (as in plants and injections) and
1
intravaginal routes (as creams or vaginal tablets). Depression also occurs frequently among these
Each route of administration has benefits and women.21 This may be attributed to other stressful
disadvantages but it would appear that many women life events or co-existing chronic medical illness. The
are currently using transdermal patches and negative or lack of supportive attitude to their
:
oestrogen based creams, often unsupervised. The peculiar complaints could also reinforce some of
dosage of estrogen necessary to prevent bone loss these emotional states,
I
depends on its type and route of administration. A Sexualfunction
dose of 0.625 milligrams of conjugated estrogen per Sexual activity involves the phases of excitement,
day, or its equivalent in other estrogen preparation plateau, organism and resolution. lt is thought that
provide adequate protection against the development changes with ageing and menopause can affect the
of osteoporosis for most women.18 sexual behavior and activity. The low osteogeny
Ieads to atrophic changes in the vagina which causes
The role of estrogen in the treatment of osteoporosis easy bruising and pain, theleby resulting into fear of
I
is becoming clearer with new evidences sexual intercourse. Vulvodynia, characterized by
demonstrating improvement in bone density in vulvar redness, edema and contact pain, may
493
progress from the peri-menopausal to menopausal symptoms or none of them. Some women find the
period causing sexual dysfunction in women. There transition barely noticeable while others find it life
could be associated deceased arousal due to altering.1,5 Women who perceive menopause as a
impaired sensory output from the clitoris and also medical disturbance are significantly more
resulting in poor lubrication.22 negatively disposed to the symptoms than those who
perceive it otherwise as a life transition or a symbol of
High prevalence of greater than 70% of Female aging.26 Ethnicity and geographical location seem to
Sexual Dysfunction (FSD) has been documented play roles in the experience and report of menopausal
among sexually active post-menopausal women and effects. Caucasian women are most likely to report
which correlated with the duration of menopause and psychosomatic symptoms unlike African-American
presence of cl i macteric sym ptoms.23 women who are more likely to report vasomotor
symptoms.2T Asian women see menopause as a
Postmenopa usa I dyspareu n ia occu rri ng concu rrently
stage of freedom from pregnancies and social
with vaginal atrophy is strongly associated with a
deprivation, and a welcome experience.28 Globally
lack of estrogen in the genital tract. However, a
over 60% of post-menopausal will have at least one
significant percentage of postmenopausal women
type of symptoms and this varies from one region
experience dyspareunic pain not related to
another. Studies in Africa have also found similar
hypoestrogenism. lt is likely that other types of
rates although with less women seeking medical care
dyspareunia predating menopause are also
due to the lack of understanding of their symptoms.
responsible.22
Rates of 90% have been reported among European
women.29
Cardiovascular system
The risk of cardiovascular diseases such sudden
Counselling is a vital process in the management and
cardiac arrest, ischaemic heart disease, coronary
will resolve some of the concerns of menopausal
artery diseases and cerebrovascular accidents is
women without the need to resort to medication.3O
increased amongst post-menopausal women.
The counselling physician must be patient, caring
Although heart diseases have been shown to increase
and ensure that there is no communication barrier.
with advanced age, the influence of menopause has
The focus of the counseling should be to educate the
been found to be significant when controlled for age
patient that it is a physiologic process, explaining in
and other risk factors like smoking.242u
clear terms possible symptoms and signs, clarifies
Evidence of the role of menopause was strengthened
doubts and myths and allows patients to enumerate
with the observation 'that when oestrogen is
what she had leant in he own words. Since the
administered to post-menopausal women there is a
50% decrease in mortality. Ostogen possibly exert it
women ae elderly and may not be able to
comprehend all information at once, the may be the
effect in multiple ways. Ostrogen increases High-
need for multiple visits. At the end of the counselling
density lipoproteins (HDL) and Triglyceides which
session and initial evaluation (History taking and
have been shown to be cardio protective. Ostrogen
through its action on oestrogen receptors in the heart
Clinical examination), a decision will be made
whether investigations and/or treatment needs to be
and endothelial also increase the production of Nitic
in itiated.
Oxide (NO), which prevents the formation of
atheromatous plaques.
The history taking must be detailed and must
MANAGEMENT OF CLIMATER!C AND
attempt to identify all possible symptoms and
possible aetiology for non-physiologic menopause. A
MENOPAUSAL PROBLEMS
Climacteric and menopausal problems may be check list is helpful as a guide in such circumstances.
The clinical examination must be thorough and cover
identified incidentally when consulting for other
issues, as only a few women will present with all systems. lt should also be used as an
complaints. Every woman's experience of opportunistic screening for .possible medical
menopause is unique, subjective and influenced by condition of significance in the elderly, such as
sociocultural factors; some may experience all of the
hypertension, diabetes mellitus, osteoarthritis and
494
The Climateric and MenoPause
malignancies of the breast and reproductive organs' confirmed by necessary investigations. Some of the
It is important to exclude pelvic pathologies such as useful investigations are highlighted in table 1 below'
ovarian masses, uterinefibroids and uterine polyps'
Depending on ihe problems identified, this must be
TABLE 2: NON-HORMONAL TEATMENT OF MENOPAUSAL SYMPTOMSDiET:
Calcium, Vitamin D and protein fortified diets

i
Exercise: Brisk walking and jogging.
Lifestyle: Exposurb to su nlight; Stopping of smoking
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Biphosphates: Common types are alendronate, Risendonate, lbandronate and etidronate. Not helpful in
preventing hot flushes or cardiovascular disease when used as a single therapy.
- Fluorider Can lead to brittle bones during long term use. Should be used in conjunction with calcium
supplements
Soy protein: helpful in relievingvasomotorsymptoms
: Phytoestrogens: Lowerstheincidenceof vasomotorsymptoms,osteoporosisandcardiovasculardiseases.
Selective estrogen receptor modulators (SERM): Raloxifene is the prototype; increases bone mineral
density, and reduce risk of endometrial and breast cancers. Drawback is the increased risk of
thromboembolism
Clonidine: centrally acting alpha agonist. indicated for hot flushes
Gabapentin: comparable to estrogen in deceasing hotflushes. Sedation is a major side-effect
Thiazides: reduces calcium excretion from the kidneys
Tibolone: synthetic steroid with estrogenic, progestogenic and androgenic properties. lmproves vaginal
lubrication and sexual function. Also improves libido. Lower doses postpones uterine atrophy and reduces
the cut-off value for endometrial thickness
Vaginal royaljelly: Effective in managing vaginal atrophy and also improves the quality of life.
b Vitamin E suppository: lndicated forvaginal atrophy
495
Comprehensive )ynaecology in the Topics
HORMONE REPLACEMENT TH ERAPY gen/progestogen combination and possibly linked to

the dose and duration of therapy longer than 5
Hormone therapy (HRT) refers to the use of estrogen years.39,40 However it is inconclusive and better
or combination estrogen /progesterone treatrnent. lt surveillance using self-breast examination, clinical
has been in practice for over 50 years, initially with breast examination and mammography should be
recommendations based on observational trials, but carried out among older women. Therefore, when
it has now recently been supplemented with the HRT is administered for reduction of menopausal
results from large randomized trials such as Nati6nal symptoms, it should be used for the shortest time
lnstitute of Health (NlH) Women's health lnitiative and at the lowest dose possible. Response to
(WHl), the Kronos Early Estrogen Prevention Study treatment varies in each postmenopausal woman
( KEEPS), Hea rt and Estrogen/progesti n Replacement due to genetic polymorphism in estrogen receptors
Study (HERS) and Women's lnterventional Study of which affects the metabolic response to HRT.
long Duration Oestrogen after Menopause (WlS-
DOM) study.'u HRT especially, combined oestrogen/progestogen
increase the risk of deep vein thrombosis and
The main goals of hormone replacement therapy are pulmonary embolism by 2-3 folds. Oral oestrogen
to prevent the development of osteoporosis, to relief increases the risk of venous thromboembolisn
menopausal symptoms and also to maintain good especially during the first year of trealment. l,4z
quality of life.i5 Women who have premature Administering HRT through alternative routes like
menopause, early bilateral oophorectomy or irradia- transdermal is safer and minimizes the risk because
tion should also be offered HRT because the meno- of the lower doses of oestrogen contained in these
pausal symptoms are sudden and often more severe agents. Coronary heart diseases have been reported
in them, Women taking HRT may experience minor at increased frequency amongwomen using HRT.
side effects such as headaches, nausea, vomiting
and mastodynia. lt is however uncertain whether Oestrogen also increases amount ofcholesterol
these side effects are due to the oestrogen or proges- deposited in bile, leading to more cases of gall
terone component. Recent studies have also shown bladder diseases following HRT. Oestrogen exerts its
that women on HRT do not gain more weight com- effect by decreasing the serum level of
pared to other menopausal women. The major side chenodeoxycholae which is an inhibitor of the
effects or risk are less common but should be enzyme B-hyd roxy-b-methylygl uta ryl-CoA
carefully considered priorto commencing HRT. reductase, the regulatory enzyme of cholesterol
synthesis. The net effect is there an increased
Testosterone, when added to HRI improves sexual secretion of cholesterol. ln rare cases, dementia,
function in postmenopausal women.36 However, Alzheimer disease and pancreatitis have been
this advantage is may be invariably overshadowed by documented in amongst women receiving HRT.
inconsistent unwanted side effects such as hair
growth, seborrhea, acne and weight gain, and a There are no definite conclusive data at present
reduction in high-density lipoprotein (HDL) choles- linking estrogen replacement therapy to the develop-
terol depending on the dose and its modes of admin- ment of hypertension, glucose intolerance, and
istration." thrombophlebitis. These diseases are described as
possible risks.
Risk and Contraindications
Endometrial hyperplasia and cancers have been HRT is contraindicated among women with history of
noted to occur at increased frequency among women thromboembolism, gall bladder disease, known
receiving HRT. Further evaluation of the women oestrogen dependent malignancy, undiagnosed
revealed these conditions to be related to women vaginal bleeding and ongoing liver disease.
receiving estrogen without concomitant progester-
one. lt is therefore recommended that progestogen Methods of HRT and Routes of Administration
should be added to oestrogen replacement therapy in Due to the risk of HRI the goal of therapy should be
women with intact uterus." the administration of the lowest effective dose and
usage over long periods should be avoided. HRT use
A few studies have demonstrated a minimal increase
should not exceed 5 years. HRT should be tapered
of breast cancer among women receiving oestro-
495
down and everilually stopped once there is resolution dydrogesterone(5- 1 0mg dai ly),
of symptoms. medoxyprogesterone acetate (2.5-5.0mg daily),
Norethidone(O.35mg daily) and micronized proges-
Oestrogen only preparations are the earlimt marketed terone (100-300mg daily). ln a few symptomatic
and are useful for symptomatic women who had women with history of breast or endometrial cancer,
undergone hysterectomy. Conjulated' equine and where oestrogen is contraindicated, progestogen
ostrogen 0.3 or 0.625 mg daily is sufficient. Oestro- only preparations may be used and is effective in
gen and progestogen combination could be continu- preventing hot flushes and osteoporosis. Continuous
ous or cyclical, but are indicated for women with oestrogen/progesterone preparations have just
intact uterus. The cyclic use involves the administra- recently been approved for use in the last decade. lt
tion of oestrogen for 25 days while progestogen is has the potential of preventing endometrial hyper-
added for the last 14 days. A daily oestrogen dose of plasia.
0.3mg is sufficient and has minimal side effects but
larger doses may be used occasionally. The common ln an effort to reduce side effects, improve compli-
oestrogen preparations are conjugated equine ance and acceptability, preparations using other
oestrogen(0.3 - 1 .25 mg daily), micronized oestro- modes for administration have been developed.43
gen (0.5-2mg daily), pipeazine oestrone(0.75- These newer methods are shown in table 3.
3.0mg daily)while the common progetogens are
r
Table 3: NON -ORAL ROUTES OF ADMINISTRATION OF HORMONAL THERAPY
Vaginal estrogen rings( Estradiol . lnserted by patient o clinician

0.0075mg released daily) . Can remain in-situ for 12 weeks before being changed
. lndicated for genital dryness and higher dose variety to treat
hot flushes is available
Vaginal tablets and . Low level of estrogen absorption into the circulation
creams(Conjugated equine estrogen . lnitial phase: Applied nocte for 2 weeks
0.625mglg cream, Estradiol . Maintenance dose: twice weekly application
0.lmg/g cream)
Transdermal patches ( Estradiol . Also effective for controlling hot flushes
0.025mg - 0.img/day) . Worn continuously and changed twice weekly
. Occasionally causes skin reactions
. Combined estrogen/progesterone patches are also available
ir- Percutaneous gels ( Estradiol 0.06% o Applied to the skin(Anterior abdomina I wall o thighs)
gel; 0.75mg per pump)
t, Sub-dermal implants . Requires local anaesthesia

. Has to be inserted by a trained personnel
Levonorgestrel i ntra uteri ne system . Requires trained personnel for insertion
(LNG-lUS) 2ouglday . Smaller size delivering 1Oug of Levonorgestrel per d ay is
being used
:
These routes allow the hormonal preparation to reach papanicoloau smear, ultrasound determination of
:
the circulation quicker and in higher concentrations endometrial thickness and mammography.
while also by-passing the first phase metabolism Laboratory assessment of serum estradiol may be
which occurs in the liver. The nausea and vomiting used in monitoring HRT.
:
resultingfrom oral intake is also avoided.

There should be established guidelines for treatment
lrrespective of the method of HRT administered, the with HT. Summary of the South African Menopause
women should have yearly follow-up visits. During Society Council consensus statement on
t
the visits clinical examinations should be done menopausal hormone therapy is shown in Table 4.
coupled with some routine investigations such as
497
Table 4: Summary of the consensus statement by South African Menopause Society Council on Hormone Therapy
..4
ar
!
a
a
a
a
a
a
a
a
DISCUSSION AN D CONTROVERSI ES anticipated future events such as heart diseases,

osteoporosis and dementia. Since then lts use has
From early observational studies, it was evldent that however been trailed with myths and controversies
the oestrogen levels were very much reduced in the attempting to answer a lot of questions such as, what
postmenopausal period and most of the problems in are the actual benefits of HRI does HRT use result
the climacteric or post-menopause were attributed to into adverse risks, should HRT be administered to all
the hypo-oestrogenic state. So several years ago, post-menopausal women, how long should HRT be
when the routine administration of HRT to all post- used for, should HRT use be restricted to certain
menopausal women became a common practice, it regions or ethnicity, are there alternatives to HRT and
was for the purpose of managing ongoing meno- does H RT improve the quality of life.
pausal symptoms/complications and preventing Some researches believed that menopausal symp-
498
r toms and cornplications were uncommon among menopausal women should not use HRT primarily to
I Africans or bla,;k ethnic groups and as such these prevent chronic diseases. Its use should therefore be
F groups of women do not require HRT. REeffi studies limited to symptomatic women and who are also low
l(-
I
in Africa have however dispelled this WSffi: Srmi.lar risk for heart disease, thromboembolism, strokes,
r prevalence rates of menopausalsym@m*hae been and breast cancer. The recommendation also
I
I documented among African but with many women excluded women <50 years who had undergone
I
not seeking care and accepting to cope with it. This surgical menopause. Despite these recommenda-
I
t related to their level of understanding and awareness tions, a safe duration of treatment needed to be
r of the climacteric and menopause. With improved determined.
t educational status of women in many developing
countries, women are now beginning to present to Most menopause study groups or societies across all
r clinicians and being offered HRT. The possibility of regions now recommend limiting the initial use of
r fear of malignancies has been documented as a HRT to a period of 5 years after which continued use
f
possible reason why a few women still refuse HRT or should be assessed. However, a few groups support.
r( even some clinicians decline to offer HRT despite the annual re-evaluation. ln general the risk of oestro-
benefits for symptomatic women. This eventual low gen containing therapy for the first 10 years after
t
use of HRT then gives a false picture of low preva- menopause is very minimal. Treatment beyond this
lence of menopausal symptoms in these regions. period or over the age of 60 years must be individual-
ized taking into consideration the risks and benefits,
2002, HRT was liberally used for all
Prior to the year and such decision must be left to experts clinicians in
post-menopausal women, but with the early termina- conjunction with the patient. Another option is to
tion of the Women Health lnitiative (WHl) study due convert from sequential to continuous combined
to observed risks associated with HRT, this practice hormone therapy for continued use longer than 5
changed abruptly. The WHI trial was the largest ever years.
done regarding menopause, involving about 16,000
relatively healthy women with intact uterus. The There are also concerns on the impact of the type of
study found that women on HRT had a very slightly HRT used in researches on the observed adverse
increased risk of Heart disease, Stroke, Blood clots risks. ln the Women's Health initiative (WHl) and
and Breast cancer, although with a decreased risk of Heart and Estrogen/progestin Replacement Study
colon cancer and osteoporosis fractures. The study (HERS) studies, premarin derived from the urine of
however had its limitations. lt excluded women with horses and Provera- a synthetic progestin were used.
terrible symptoms so'the study was unable to address These hormones are un-identical to the natural
the benefit of HRT for these categories of women. oestrogen/progesterone founds in the body. This
Secondly the average age of the study participants formed the basis of research into the use of
was 63 years which was far higher than the age bioidentical hormones which may have minimal
women start experiencing menopausal symptoms or negative side effects and which may help address
the age of commencement of HRT, making compari- common myths like "Hormones cause cancer," 'All
son with younger women with problematic meno- estrogens are the same," and that 'All progestins are
pausal symptoms difficult. lt was also possible that the same. Bioidenticals should contain hormones
the observed increased risk of some conditions may that are chemically identical to those produced in
be attributed to the ageing process rather than the humans but those presently available for public use
HRT. have variable compositions. Thus, despite the facts
that they have been used since 7978, safety,
With the findings of the WHI study and the known consistency and efficacy concerns about them still
fact that in the majority of women, menopausal exists because they are not subjected to the same
symptoms greatly improve or resolve within five years regulatory approval process as current branded
I
even without medications, a consensus opinion in preparations. Their use therefore has to be done with
L
practice was that the use of HRT be individualized. caution and further research is required ascertain
This opinion was further strengthened with the U.S. their usefulness.
: Preventive Services Task Force recommendation that
499
CONCLUSION Education regarding women's attitudes toward

Many of our women will be living a major part of their treatment should be provided to those physicians
life in the postmenopausal period and will be faced who treat menopausal symptoms in each country
with the problems of menopausal symptoms. There and if possible guidelines should be available to
is the need for concerted effort to identify the women minimize risk and optimize benefits
with bothersome symptoms and comrnence on the
available treatments option, which could vary among
age groups and countries.
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24. Rocca, W. .,Grossardt, B. ., Miller, V. ., therapy, cancer, controversies, and women's
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Society Counci I consensus. Souffr,4M*d.
.j
I
l
r---l
l
i
.a
802
cHAprE"42
Hyperprolactinaemia
CA. KLUFIO & J. COLEMAN
Lactotrophs and Normal Prolactin l-evels high progesterone concentration maintains the
Lactotro phs ( m a m motro phs), the prol acti n -secretory pregnancy.
r
cells of the anterior pituitary, constitute 20% ot Under the influence of a 'lactogenic (mammogenic)
anterior pituitary secretory cells. The other secretory hormone complex', consisting of estrogen, progester-
r
I
I cells are, somatotrophs (50%), corticotrophs (2O%), one, prolactin, growth hormone, insulin, human
(
I
thyrotrophs (5%) and gonadotrophs-FSH and LH placental lactogen, glucocorticoids and local
metabolic hormones, the lobulo-alveolar cells
I
I (5%).Lactotrophs are selectively located in the lateral
I
*i wings of the anterior pituitary gland. This location has undergo secretory differentiation and acquire the
relevance in imaging appearance of lactotroph capacity to synthesize the unique constituents of
I
I
tumours. milk, such as casein, lactoglobulin and lactalbumin.
l
With delivery of the placenta, estrogen and proges-

i
Pituitary prolactin issecreted in a pulsatilefashion, in terone levels decrease sharply. The withdrawal of
r synchrony with LH pulses throughout the menstrual progesterone and estrogen, together with the
: cycle, and in synchrony with FSH pulses in the presence of prolactin, insulin, and cortisol, initiates
I follicular phase. lactation.
I
I
Prolactin concentrations for the same serum sample, ln the weeks and months following delivery, suckling
I can vary from laboratory to laboratory, but for most stimulates sensory nerve endings in the surface
laboratories, for reproductive-aged nonpregnant areas of the nipple and areola, evoking a
women, normal circulating prolactin levels range neuroendocrine reflex, resulting in release of
from2 to 25 ng/mL (2-25mcgll Sl units). prolactin and oxytocin from the anterior and poste-
rior pituitary, respectively. The continued secretion
During pregnancy, serum estrogen and progesterone of prolactin and oxytocin as the baby suckles,
concentrations increase progressively. The rising together with the regular emptying of the breast
estrogen concentrations produce marked hyperplasia
a lveol i d u ri ng breastfeed i ng, ma i nta i ns lactation.
of lactotrophs, and enlargement of the pituitary to
approximately twice its pre-pregnancy size (1). The Prolactin Synfhesis and Secretion and Their
lactotroph hyperplasia results in increasing serum Regulation
prolactin concentrations throughout pregnancy. The Prolactin is a polypeptide hormone consisting of a
magnitude of the increase is quite variable, but at single chain of 198 amino acids.
term and beforedeliverytheconcentration may be 10
times what it was at the beginning of pregnancy Apart from breast-feeding. several physiological
I (1,2); and levels before delivery may be as high as states including, stress, exercise, sexual intercourse,
150 to 300mcg/ml, i.e., 150 - 300 ng/ml (1).The and sleep are known to cause prolactin elevation.
s03
Regulation of prolactin synthesis and secretion is production or interrupts the transport of any of the
multifactorial. Like the other anterior pituitary inhibitors of prolactin synthesis/secretion or counter-
hormones, prolactin synthesis-secretion is under acts the action of any inhibitor, will increase prolactin
hypotha I ic co ntro L H oweve r, whereas, -$.ffi@,is
am secretion. A large nonfunctioning pituitary tumour,
and secretion of the other anterior pituitary honne+res e.g., craniopharyngioma, or granulomatous infiltra-
are regulated by hypothalamic releasing (stimuht- tion of the hypothalamus can cause
ing) factors, the primary and chief hypothalamic hyperprolactinemia if it compresses the pituitary
control of prolactin synthesis and secretion is stalk or damages the dopaminergic neurons.
inhibitory. Tonic (chronic) inhibition by hypotha-
lamic dopamine is the predominant mode by which Notej (a) Any interruption or block at any
prolactin synthesis and secretion is controlled. point in the TIDA pathway will prevent
dopamine from reaching the anterior
Tuberoinfundibular pathway of dopamine IIDA) pituitary and remove dopamine inhibition of
pathway: This is the tract traversed by dopamine prolactin production-secretion, resulting in
from the hypothalamus to the lactotrophs in the hyperprolactinaemia. (b) GHIH is a peptide
anterior pituitary: (a) dopamine is synthesized in the hormone. lt is a regulator of the endocrin
tuberoinfundibular neuroendocrine dopamine system, of neurotransmission and of cell
neurons in the arcuate nucleus of the hypothalamus; proliferation. lt
inhibits gastrointestinal
(b) it travels by anterograde transport down the short motility and inhibits secretion of digestive 1
axons of the neuroendocrine neurons to reach the enzymes and hormones, including, insulin,
median eminence; (c) dopamine is released from the glucagon, and VIP GHIH acts by interacting
terminals of the axons into the portal circulation in with G-protein-coupled GHIH receptors and
the median eminence; (d) it is carried in the portal by inhibition of the release of numerous
vessels that wind around and down the pituitary secondary hormones. (c) Both dopamine
(infundibulad stalk to the anterior pituitary; (e) and noradrenaline are catecholamines with
dopamine diffuses out of the portal blood into the the same chemical structure, except that
tissues of the anterior pituitary; (f) it impinges on D2 noradrenaline has an oxygen atom in the
dopamine receptors on the lactotrophs. Stimulation side chain that makes the hydrogen at this
of the lactotroph receptors causes a decrease in location a hydroxyl (OH). Dopamine is a
intracellular andenylate cyclase activity and reduc- precursor molecule in the biosynthesis of
tion in cyclic AMP This results in tonic suppression noradrenaline. Their biosynthesis begins
of prolactin synthesis arid secretion. Prolactin may with tyrosine, and tyrosine hydroxylase is the
modulate the reproductive axis by acting on specific rate-limiting enzyme in the biosynthesis of
populations of arcuate nucleus neurons that express catecholamines.
the Kissl gene. The Kissl gene encodes
neuropeptides known as kisspeptins. Kisspeptins are Natural stimulators (inducers, releasing factors) of
powerful activators of GnRH neurons (3), and are of prolactin: Natural factors that induce prolactin
critical importance for pubertal maturation and synthesis/secretion include, estrogens, thyrotropin
regulation of reproductive function. The Kissl gene releasing factor (TRH), vasoactive intestinal growth
neurons express prolactin receptors (4). peptide (VlP), epidermal growth factor (EGF),
oxytocin, opioids, and serotonin. Estradiol is the
Other natural inhibitors: Dopamine is the primary main ovarian hormone that stimulates prolactin
prolactin inhibitory factor (PlF). Other natural secretion. Estradiol acts at the pituitary level to
inhibitory factors of prolactin synthesis and secretion modulate prolactin gene expression and at the
inclUde: gamma aminobutyric acid (GABA), hypothalamus to modulate the activity of neurons
gonadotrophin releasing factor associated protein, (3). TRH and VIP are synthesized in the median
somatostatin (growth hormone-inhibiting hormone hypothalamus, Any drug, agent or mechanism that
lGHlHl), noradrenaline (norepinephrine) and stops the production of any of the releasing factors of
triiodothyronine. prolactin synthesis/secretion or counteracts its
Any drug, agent or mechanism that stops the action, will reduce prolactin secretion. Endogenous
504
Hyperprolactinaemia
opioid peptides are involved in the regulation of Types of Prolactin: Macroprolactin and its Clinical
prolactin serretion during pregnancy, and in the Significance
suckling-induced prolactin surge during breastfeed- Prolactin is synthesized as a pre-hormone with a
ing and stress. This surge is blocked by naloxone, molecular weight of 26 kDa. Cleavage of the pre-
proving the importance of opioids (1), Serotonin hormone produces free, monomeric "little prolactin",
physiologically mediates nocturnal surges and molecular weight, 23 kDa. Little prolactin is the
suckling-induced prolactin increases; and it is a most bioactive form of prolactin. Circulating
strong modulator of prolactin secretion (6). prolactin is a heterogeneous molecule. Little
prolactin is the major circulating prolactin and
Prolactin itself provides a powerfulfeedbackthat acts normally constitutes >80% of the total prolactin in
as a safeguard against hyperprolactinemia. Prolactin the circulation. The other molecular forms of
achieves this control in two ways: (a) by modulating prolactin are: (a) a covalently bound dimer of little
the expression and kinetics of tyrosine hydroxylase, prolactin called, "big prolactin" with a molecular
the rate-limiting enzyme in dopamine biosynthesis; weight of 50 kDa; the dimer is much less bioactive
(b) by a fast short-loop electrophysiological effects of than free prolactin; (b) a "big-big prolactin" that is a
prolactin on TIDA neurons in the arcuate nucleus (6). tetramer of little prolactin, with a molecular weight
Elevated prolactin levels and GnRH secretion by > 100 kDa, and with very little biological activity; (c)
hypothalamus;GnRH secretion is pulsatile (pulses at a much larger (>150 kDa) polymeric "big-big
90-120/min); this pulsatile nature is an inherent prolactin" that has no biological activity. This type of
function of GnRH neurons. Raised prolactin levels big-big prolactin is a molecule of > 100 kDaprolactin
abolish or greatly reduce the frequency and ampli- that has been complexed with an anti-prolactin lgG
tude of pulsatile GnRH secretion; following on that, autoantibody. The subclass of lgG in the complex is
the frequency and amplitude of pulsatile LH and FSH lgG4, indicating that chronic antigen stimulation
secretion, particularly LH is greatly reduced. As a may be responsible f or f ormation of the
result: (a) ovarian follicles are not stimulated to autoantibody. Big-big prolactin with molecular
produce estradiol; (b) the estrogenic (proliferative) weight > 150 kDa is called macroprolactin.
phase of endometrial growth is compromised; (c) the Normally, approximately 80-90% of prolactin is
i
estrogen peak whichprovides the positive feedback little prolaclin; 8-2O% is dimeric; and 1-5% is
I on the hypothalamus for the hypothalamus to macroprolactin (> 150 kDa) (2). All prolactin types
I
produce the preovulatory LH surge required for a re i m mu nologica lly reactive.
I
I
ovulation, does not occur; (d) ovulation does not
I occur; therefore there is no corpus luteum to produce Macroprolactinaemia: Macroprolactinaemia is the
1v
i progesterone; (e) progesterone-directed endometrial term applied to the situation in which, in the circula-
i
I ripening to produce a secretory endometrium does tion, macroprolactin preponderates over the other
not occur. This sequence of events produces: (i) prolactin types; Benerally, this is when
anovulatory cycles; (ii) macroprolactin forms >60% of the total circulating
oligomenorrhoea/amenorrhoea; (iii) luteal phase prolactin, with little prolactin constituting <40%
defect;(iv) subfertility/infertility; (iv) U),
osteopenia/osteoporosis from chronic from
hypogonad ism, i.e., f rom ch ron ic hypoestrogen ism. M a c ro p ro la ctin ae m ia p rev a le n ce:
Macroprolactinaemia is present in approximately
Note; The hypogonadism is secondary to failure 4% of the general population, with no difference
of the hypothalamus to produce pulsatile GnRH between the sexes; but prevalence rates increase
to drive the anterior pituitary to produce with age and therefore, it occurs most commonly in
gonadotrophins (FSH and LH). FSH and LH are the elderly. ln patients with hyperprolactinaemia,
gonadotrophins. Therefore, the cause of the the prevalence of macroprolactinaemia is 10 -25%
hypogonadism is absence of gonadotrophins to (8).
stimulate the gonad (ovary) to secrete estradiol.
l.
Hence, this type of hypogonadism is termed, Women and men with macroprolactinaemia are
hy pogon adotro p h i c hypogonad ism. asymptomatic; their gonadal and gonadotrophic
505
functions are normal. Without any treatment for may define a macroprolactin as, "a large
hyperprolactinaemia, women with this diagnmis can (>150 kDa) non-cleaved, physiologically
bear normal babies (8). Macroprolactin may hite no inactive form of prolactin which is bound to
biological activity for various reasons. @'.@*$o-n lgG, and which interferes with prolactin
may be that the molecule is so large thd:i!,ciirtngl immunoassays".
cross the endothelium to leave the circulat'cn and
enter the tissues. lt, thus, cannot reach its receptors. Biological (Normal) Functions of Prolactin
Prolactin is a protein as well as a cytokine with
Another reason may be changes in the net charges of
pleiotropic effects. lt acts by endocrine, paracrine
the macroprolactin molecules. A third reason may
be absence of free epitopes on the macroprolactin
and autocrine mechanisms. The plurality of
prolactin's actions reflects the ubiquitous distribution
molecule. However, it is not impossible for both
macroprolactin and little prolactin levels to be of its receptors-the cell membranes of numerous
elevated in the individual.
and diverse tissues have prolactin receptors.
Additionally, apart from the anterior pituitary,
D n f rom I ittl e pro I acti n :
i sti ngu i sh i n g m acrop rol acti prolactin is synthesized in many and diverse tissues,
Most commercially available immunoassays used to including: mammary gland, placenta, endometrium,
measure serum prolactin concentration cannot ovary, testis, adrenal gland, hypothalamus, cells of
distinguish between free bioactive little prolactin and the immune system, such as macrophages, natural
macroprolactin. Thus, these tests will report killer cells, T- and B-lymphocytes. The biological
hyperprolactinaemia when serum little prolactin functions of prolactin include the following.
levels are normal and macroprolactin levels are
Mammopoiesis and Lactation: The chief function of
abnormally high. Spurious diagnosis of
prolactin is achievement of successful breastfeeding,
hyperprolactinaemia can lead to unnecessary
investigations, treatments, and follow-ups, which
i.e., initiation and maintenance of lactation
(prolactin is derived from "pro-lactation"). When
may be inconvenient, expensive, and even danger-
ous. To avoid this, every case of asymptomatic secreted in normal amounts, prolactin is both
mammogenic and lactogenic. Prolactin acts to
hyperprolactinaemia should be screened for
induce and maintain lactation of the primed breast;
macroprolactinaemia. ln short, the screening
procedure is as follows. Two aliquots are drawn from i.e., the breast that has been prepared by adequate
amounts of estrogen and progesterone. Prolactin is :
the serum sample. The total prolactin concentration
in the first aliquot is rneasured. To the second requisite for branching and re-branching of the
sample, 25% polyethylene glycol is added to precipi-
primary ducts and for formation of the terminal and .-u l
lateral lobules that grow into alveoli during preg-
tate out macroprolactin. lt is then centrifuged. The
prolactin concentration of the supernatant is mea- nancy. After delivery, and underthe influence of high
circulating prolactin levels in response to suckling,
sured. The value obtained is the concentration of
free little prolactin in the circulation. lf the alveolar development is augmented.PRLRs have
been described to be expressed in the granulosa,
supernatant value is less than the total value in the
neat aliquot by more than 40o/", interstitial and luteal cells of the ovaries, and the
macroprolactinaemia is most probably present; in endometrium,myometrium and decidua in the
uterus.ln the ovaries, prolactin acts inconcert with
other words, a PEG-precipitation ratio greater than
go nadotroph i ns to sti m u ate progesteron ep rod u cti o n
60% (i.e., recovery less than 40%) strongly suggests
I
by luteal cells and to induce the increasein progester-

the presence of macroprolactinaemia, and a confir-
matory test for macroprolactinaemia, e.g., gel one receptor expression that occurs in the uterus.
Progesterone produced by the corpus luteum is
filtration chromatography, should be performed.
essential for implantation of the fertilized ovum,
/Votej (a) The possibility that, under certain maintenance of pregnancy, and inhibition of ovula-
conditions, macroprolactin can dissociate tion in the first trimester; i.e.., before placental
into monomeric bioactive little prolactin, and progesterone prod uction is adeq uate.
thus, be a store for monomeric prolactin, has
Maternal behavior involving coordinated actions that
neither been proved nor disproved. (b) We
506
Hyperprolactinaemia
promote ca ri n g for the ba by, i ncl ud i ng bond i ng. concentrations. Therefore, high prolactin levels can
produce impactful hormonal changes in the
Weight gain-storage of energy for lean times. intraovarian environment without these changes
Temporal spacing of pregnancres th@4g .intribition being reflected in maternalserum (2). Plasmin has
of GnRH secretion. Hyperprolactinemia Nffifm the an essential role in rupture of the dominant follicle
frequency and amplitude of pulsatilU FSH wall forovulation to occur. Prolactin may act directly
and LH. This results in anovulation and ffienmrfrea. on the ovary and block ovulation, at least in part,
The actatio na I a m eno rrhea method ttA$flff natura
I t
through inhibition of ovarian plasmin generation.
contraception makes use of this physiol$ealfact. (1 1). These changes in the micro-environment of the
ovary can adversely affect luteal function and
Sexua/ arousal and sexual satisfaction.
fertility. Furthermore, prolactin directly inhibits
lmmunoregulation: Prolactin acts as a cytokine, and
ovarian progesterone and estradiolsecretion and can
exerts endocrine actions on the immune system.
suppressthe responseto hCG and LH (12).
Paradoxically, both lymphocyte and pituitary
prolactin are underthe control of immunefactors. Def i n itio n of Hy pe rprol acti n aem i a
ln women, hyperprolactinaemia is simply defined as
Adrenal glands: All the three zones (glomerulosa, a serum prolactin concentration that exceeds the
fasciculata, reticularis) of the cortex contain prolactin
upper limit of the normal range in nonpregnant,
receptors. Prolactin causes adrenocortical cell nonpuerperal women of reproductive age. For most
i'
hypertrophy. Prolactin stimulation of the adrenal laboratories, hyperprolactinaemia is a serum
directly increases secretion of cortisol, aldosterone, concentration >25 ng/mL (5, 9), which is the same
and dehydroeplandrosterone (DHEA). Evidence as25 mcglL(1). Forothers, the cut-off is > 50 mlU/L
from animal models indicates that PRL interfaces (2), which is equivalentto 20 ng/mL (14).
with the hypothalamus-pituitary-axis (HPA), block-
ing stress-induced increases in corticosterone. ln P reva le n ce of Hy pe rprol acti n a em i a
humans, low scores on the Hamilton anxiety scale Hyperprolactinaemia is a common endocrine
correlate with high PRL levels in healthy lactating disorder that affects the hypothalamic-anterior
women (9). pituitary axis. The prevalence rate of
hyperprolactinaemia has been estimated to range
Note; The Hamilton Anxiety Scale (HAM-A) from 0.4"/" in an unselected adult (male and female)
is a scale designed to measure the severity of population to as high as high as 9-77% in women
anxiety symptomatology in individuals. lt is with reproductive diseases (5, 13), and 77% in
an anxiety.self-test commonly used in women with polycystic ovary syndrome (PCOS)
evaluating psychotropic drugs. lt has 14 (14).Biller et al. found a prevalence rate of 5% in a
items, each defined by a series of symptoms. family planning clinic population, 9% in women with
Each item is rated on a S-pointscale, ranging adult onset amenorrhea, and 17"/" among women
from 0 (not present) to 4 (severe) (10). with PCOS (13).ln an analysis of over 1,600
patients with medically treated hyperprolactinemia,
Ovary: For maintenance of normal ovarian function,
the calculated mean prevalence was approximately
serum prolactin concentrations must be in the
10 per 100,000 in men and approximately 30 per
physiological range. Luteinized granulosa cells
100,000 in women, with a peak prevalence for
produce both prolactin and prolactin receptor.
women aged 25-34y (1). ln the United States, it
Prolactin influences progesterone secretion from
occurs in <l% of the general population (men and
luteinized granulosa cells. Elevated serum prolactin
women) and in 5-74% of patients presenting with
levels are associated with significantly elevated
secondary amenorrhoea. Approximalely 75% of
prolactin levels in antral follicular fluid, a marked
patients presenting with galactorrhoea and
reduction in granulosa cell numbers and decreased
amenorrhoea have hyperprolactinemia. Thirty
concentrations of progesterone and estradiol in percent of patients with the three symp-
follicular fluid. The decreased concentrations of
toms-ga lactorrhoe a,'amenorrhoea, a nd
t progesterone and estradiol in follicular fluid are not
hyperprolactinemia-have prolactinomas (1 5, 16).
reflected in serum estradiol and progesterone
507
Ca u ses of Hy pe rpro I acti n ae m i a hyperprolactinaemia by pressing on the pituitary

Several physiological states including pregnancy, stalk and stopping the transport of dopamine down
breast-feeding, various forms of stress, exercig0, and the TIDA pathway to the lactotrophs in the anterior
sleep can cause prolactin elevation; and so, mn pituitary. This situation, in which the
psychotropic drugs and certain medicatiohB.fhe hyperprolactinaemia is due to disruption of the
pathological causes include intracranial lesions, pituitary stalk, is
referred to as "disconnection
chiefly hypothalamic and pituitary stalk lesions, hyperprolactinaemia". The third reason is that there
primary hypothyroidism, and chronic renal is a large cyst in the tumor, such that, only a small
failure.The listof causes is long (Table 1). proportion of the tumor is functional. A study of a
large series of histologically confirmed cases con-
Pituitary tumours: Prolactin-secreting adenomas of
cluded that, a serum PRL level >2,000 mU/L is
the anterior pituitary are called lactotroph adenomas
almost never encountered in nonfunctioning pituitary
or prolactinomas. They are the most common macroadenomas; and that if values above this limit
secretory (functional) pituitary adenoma, accounting
a re obtai ned, after acromega ly a nd Cush i ng's d isease
for 25 to 30% of functioning pituitary tumors. They
have been excluded, the most likely diagnosis is a
are the most frequent pathological cause of functioning macroadenoma (i.e., a prolactinoma >
hyperprolactinaemia.
10 mm); and that it should be treated with a dopa-
mine agonist without undue delay (17).
A prolactinoma is classified as a microadenoma if it is
< 10 mm in diameter and as a macroadenoma if it is :
Medications-anti psychotics, neuroleptics, SSR/s
>10 mm in diameter. Microadenomas are more
and other drugs: Many common medications cause
common in premenopausal women, and hyperprolactinaemia. Medication-induced
macroadenomas are more common in hyperprolactinaemia is usually associated with
postmenopausal women (2, 5). Prolactinomas are prolactin levels ranging from 25 to 100 mcg/L and
found in 40% of symptomatic hyperprolactinaemia
not higher. However, metoclopramide, risperidone,
patients. Most are microadenomas and more than
and phenothiazinesproduce prolactin levels exceed-
907" are confined to the sellaturcica. They rarely ing 200 mcg/L (1, 18). The use of any class of drug
increase in size overtime, and they are almost always
that affects the TIDA projection andlor D2 dopamine
benign (1). Prolactin levels typically parallel tumor
receptors on anterior pituitary lactotrophs can
size, Most patients with prolactin levels higher than produce hyperprolactinaemia. After tumours,
250 nglL have a prolactinoma. ln individuals with medications are the most common cause of
large adenomas, prolactin .levels can be very high
hyperprolactinaemia (1, 18).
(> 10,000 ng/mL). However, the correlation between
prolactinoma size and prolactin level is not always Antipsychotics; Anti-dopaminergic, antipsychotic
consistent, the prolactin level being much lower than drugs/neuroleptics for treating schizophrenia, e.g.,
would be expected from the size of the prolactinoma. chlorpromazine, thioridazone, risperidone and
There are 3 potential reasons for the dissociation haloperidol, produce a 2 to 10-fold increases in
between prolactin level and tumour size. The first is a serum prolactin concentration by 72 hours' use;
rare artefact called the "high-dose hook effect". The levels may reach as high as 200 ng/mL (1, 5). Forty
hook effect occurs when the concentration of the to 90% of patients taking typical antipsychotics,
antigen (in this case prolactin) relative to the fixed e.g., phenothiazines or butyrophenones, have
antibody is excessively high. ln this case, there is hyperprolactinaemia, as do 50-100% of patients
more than enough antigen to bind both the fixed taking risperidone (1). Some of the newer
antibody and the labelled antibody. This prevents the antipsychotic drugs, e.g., clozapine, may not have
labelled antibody from binding to the fixed antibody, this side-effect. Se/ective serotonin reuptake
giving a ialse negative result or a much lower reading inhibitors (SSR/s): These drugs are widely used for
than the true value. The second reason for the treating depression. Numerous reports have
dissociation between prolactin level and tumour size associated their use with hyperprolactinemia. SSRIs
is that the tumour is a nonfunctioning tumour (a non- may suppress the TIDA pathway indirectly through
prolactin secreting macroadenoma) and it is causing GABA adrenergic neurons near the TIDA dopamine
508
a
I
Hyperprolactinaemia
I
I
cells in the arcuate nucleus. Serotonin may also Acromegaly (Gk. acro:extremities;
I produce hyperprolactinaemia through stimulation of megaly:snlargement): Many patients with
VIP and oxytocin (9). acromegaly have prolactin co-secreted with growth
t
'l \- hormone. ln patients with acromegaly due to GH-
Chronic renal failure; ln chronic renal failure, secreting (somatotroph) tumours, prolactin levels
: hyperprolactinaemia may occur because of impaired are elevated in up to 50%. Therefore, it is important
renal degradation of prolactin and altered central to determine whether patients with
;
prolactin regulation that results in enhanced produc- hyperprolactinemia also have acromegaly
I (1
, 15).
tion of the hormone. Approximately 30% of patients
with chronic renal failure have mild-moderate Hy perprol acti naem i a a nd PCOS
elevation of prolactin levels; 80% of those on ln addition to typically having high LH levels, 77% ot
hemodialysis have moderate elevation of prolactin women with polycystic ovary syndrome (PCOSS)
levels ( 1, 5). Serum prolactin levels do not decrease have hyperprolactinaemia; which is much higher
to normal levels after dialysis, but they normalize than the <1% prevalence rate in reproductive-age
after renal transplantation. Hyperprolactinemia women. The causation of this association is poorly
causes hypogonadism; chronic renal failure is also understood. One suggested theory is that the
associated with hypogonadism. ln chronic renal chronically unopposed estrogen results in increased
failure, treatment of the hyperprolactinaemia may secretion of LH in addition to stimulating the
I improve the hypogonadism (1). lactotrophs to secrete more prolactin. ln addition, it
has been suggested that women with polycystic
Primary hypothyroidrsm; ln primary hypothyroidism, ovary syndrome may have reduced dopamine
the decreased negative feedback of thyroxine (T4) production from the hypothalamus and subse-
results in increased levels of thyroid releasing quently have elevated prolactin concentrations. (2).
hormone (TRH). TRH stimulates both TSH secretion Cushrng's disease; Hyperprolactinemia may occur in
i and prolactin secretion. Primary hypothyroidism may women with ACTH-secreting adenomas (Cushing's
also lead to significant enlargement of the pituitary disease). Probably, this is because of GnRH suppres-
gland due to hyperplasia of thyrotropes, i.e., the sion by the very high cortisol levels in Cushing's
anterior pituitary cells that produce TSH in response disease.
to thyroid releasing hormone ITRHI secreted by the
hypothalamus. Lactotrophs may participate in the rVote; TSH, FSH, and LH are large
hyperplasia and cause elevation in the prolactin level glycoproteins composed of alpha and beta
t (1). Around 4O%- of patients with primary chains. All three have an identical alpha
i
hypothyroidism have mild to moderate subunit, but unique beta chains. The beta
hyperprolactinaemia (5). chain endows each hormone with the ability
to bind to its own receptor.
509
$temic disorders
o Chest-neurogenic chest wall hoficic

' nerves 2-6): trauma, thoracotomy,
'' herpes zoster, breast augmentation -breast
reduction surgery, trauma
o Chronic renal failure
o Hypothyroidism
. Cirrhosis
o Cranial radiation
r Epileptic seizures
o Polycystic ovarian disease
. Pseudocyesis
Phannacological
o Neuroleptics & antipsychotics

. Anesthetics
o Anticonvulsants
o Antidepressants
o Antihistamines {H2)
Antihypertensives-methYl doPa
. Cholinergic agonist
o Catecholaminedepletor
. Dopamine receptor blockers
. Dopamine synthesis inhibitor
. Estrogens: oral contraceptives; oral
contraceptive withdrawal
. Neuropeptides
. Opiates and opiate antagonists
. Selective serotonin reuptake inhibitors
(SSRls)
Ectopic seuetion
. Renal Cell Carcinoma

r Lung Tumour
. Gonadoblastoma
. Ovarian Teratoma
ldiopathic
. lf after thorough investigation no cause is

identified. tt may be due to diffuse
lactotroph hyperplasia. lt is a diagnosis of
exclusion.
510
a
Hyperprolactinaemia
Symptoms of Hyperprolactinaemia: Clinical 3. lnfertility:

Presentation a. Anovulatory infertility
The failure of dopamine to inhibit prolactin secretion b. Subfertility (unexplained infertility)r
is the cause of galactorrhoea. All other symptoms, Because of subtle abnormalities
except the mass effect symptoms,' aie due to restricted to the
intraovarian
hypogonad otrop h ic hypogonad ism. environment, but which have a
deleterious effect on luteal
1. Galactorrhoea: This is nipple
discharge, sufficiency (luteal phase defect) and
either spontaneous or expressed, continuous fertility.
or intermittent, that contains milk. The fact
that the discharge contains milk can simply 4. Decreased libido from hypogonadotropic
be made by a wet preparation on a slide and hypogonadism.
examining the wet mount under a
microscope, using low power magnification. 5. Vaginal dryness because of hypogonadism
(hypoestrogenism)
Detection of fat globules proves that the
discharge is milk.
6. lf it occurs before sexual maturation, it will
/Votei Witch's milk (neonatal milk): ln-utero, cause delayed puberty.
F
the baby is exposed to maternal estrogens,
7. Depending on the size and direction of
progesterone, and prolactin (as the little
extension (growth) of a macroprolactinoma,
prolactin molecule is small enough to pass
the patient may present with symptoms
through the placental barrier). The fetal
caused by mass effects of the tumour:
breasts respond to the high concentrations of
these hormones. ln some babies (male and
a. Headaches from raised intracranial
pressure.
female) born at full term, the breasts are b. Visual field losses, typically,
tr- developed well enough to spontaneously bitemporal hemianopia,Superior
I
r secrete milk. This occurs in approximately
f extensions of pituitary tumours
5% of babies. The mother should be
directly press on the chiasma and
I
I reassured that the condition usually resolves produce bitemporal hemianopia.
I
spontaneously within a few weeks to (*See below). Very large tumours
r months. No treatment or is necessary unless
t may involve the hypothalamus.
I
I
an obvious infection develops and the breast c. Cranial neuropathies (nerve
I becomes warm and/or tender. Expression is defects)
I
2 contraindicated because it is painful and can d. Hypopituitarism
t
: cause infection. ln ancient folklore, this e. Seizures
t
i
neonatal galactorrhea was called 'witch's f. Mortality is not associated with
milk' because it was believed that fluid hyperprolactinaemia. However, if a
leakingfrom a newborn's nipple was a source very large prolactinoma causes
of nou rishment for witches. severe hypopituitarism and the
patient is not treated, adrenocor-
2. Menstrual disorders: These range from luteal tical failure can cause her death.
phase defect with normal menstruation to
ol igomenorrhea and secondary amenorrhea. 8. Osteopenia and osteoporosis (see below).
I
I
' a. Oligomenorrhoea (menstrual cycle 9. Pituitary apoplexy: This is characterized by
>35 days) occurs in 10%. a sudden onset of headache, visual
b. Secondary amenorrhoea (absence of symptoms, altered mental status, and
t menses for >6 consecutive months hormona I dysf u rtction d ue to acute
lt
in a reproductive-age woman) is hemorrhage or ischaemic infarction of a
present in25"/". pituitary gland.
I,
511
Comprehensit Gynaecology in the Topics
Osteope n i a and osteoporos/s 10. Premature menopause symptorns: The

Decreased bone mass is a long-term complication. hypogonadism can cause hot flushes and
Bone mineral density (BMD) significantly d&r€qses vaginal dryness.
i n premen o pa usa I women with hyperproi&ltirffiria
and amenorrhea (relative risk 4.5). Spinat ho{E /Vofej(a) When galactorrhoea alone is
density is decreased by approximaHry SS%. present, prolactin levels will be normal in
Prolactin can directly suppress both prqgesterone 85% of women. When both galactorrhoea
and estradiol secretion by the ovaries (2), contribut- and amenorrhoea are present, the rate of
ing to the hypogonadism/hypoestrogenism seen in hyperprolactinemia is 9O%.
hyperprolactinaemia. However, the chief mecha- Hyperprolactinemia accounts for 10-38% of
nism that causes the hypogonadism- secondary amenorrhoea (14). (b) lt is
/hypoestrogenism operates at the level of the hypo- important to note that galactorrhoea
thalamus. Raised prolactin levels disrupt the depends, not only on prolactin, but also on
amplitude and frequency of the normal pulsatile the sensitivity of the breast to prolactin.
secretion of GnRH, resulting in disruption of normal Menopausal women with
pulsatile secretion of FSH and LH (9). This leads to hyperprolactinemia do not ha''
hypogonadotropic hypogonadism, hypoestrogenism galactorrhoea. This is because {
and its complications, including osteopenia and galactorrhoea to occur, the breast must have
osteoporosis. Once bone loss is established, it may been primed by estrogen and progesterone.
persist af ter successf u I treatment of ln the absence of this priming, as is the case
hyperprolactinaemia. This is of crucial importance in in postmenopausal women, the breast
adolescents with hyperprolactinaemia, since the cannot respond to prolactin.
achievement of peak bone mass in adolescence and
in the early twenties represents an important protec- Bitemponl Hemianopia
tion (a reserve) against osteoporosis. Hence, in The medial half of each retina is responsible for
temporal vision, whilst the lateral half of each retina
adolescents, hyperprolactinaemia deserves prompt
is responsible for nasal vision.
diagnosis and appropriate treatment (1, 5, 9).
Women with hyperprolactinaemia and normal
The optic nerve fibres from the medial side of each
menses have normal bone mineral density (BMD),
retina cross over at the optic chiasma, whilst the
because they do not have hypoestrogenism.
optic nerve fibres from the lateral side of each retina,
Nofe: Approximately 70% o't bone mass is do not cross over but remain on their side of the
mineral matter, mainly calcium, phosphorus chiasma. As a result, the left optic tract is formed by
union of fibres from the lateral (sinistral) half of the
and magnesium. Bone mineral density
(BMD) measures the amount of mineral left retina and by fibres from the medial (sinistral)
half of the right retina. ln otherwords, the left nasal
matter per square centimeter of bones-of
field is seen by the left sinistral retina and the right
spine, femur, humerus, radius. Dual Energy
temporal field by the right sinistral retina. The right
X-Ray Absorptiometry (DXA) is used to
perform the measurement. The result is optictract isformed by union of fibresfrom the lateral
(dextral) half of the right retina and by fibres f rom the
expressed as BMD in T-scores and Z-score.
The T-score compares the individual medial (dextral) half of the left retina. ln other
words, the left nasal field is seen by the left sinistral
measurement with the normal for the
individual's sex and age. A T-score of -1 and
retina and the right temporal field by the right
sinistral retina.
above indicates normal bone density; a score
between -1 and -2 indicates osteopenia; a
From the optic chiasma, the optic tracts run to the
score less than -2.5, e.g., -3.0 or -4.8 or -7 ,
primary optic ganglia. Ten percent of the fibres pass
indicates osteoporosis. ln the elderly, BMD
to the superior colliculus and. from there to the
is very important because it quantifies the
oculomotor nuclei to serve the pupillary light reflex;
strength of the individual's bones and his/her
90"/" are visual fibres and end in the external
chances of sustaining a fracture.
512
I
I
t'
Hyperprolactinaemia
I
I
I
r
geniculate body. From the geniculate body of each prolactin level measurement should be taken 2 hours
t side, fibres of he optic radiation fan out to the visual after waking in the morning (5), because secretion
I cortex of the occipital lobe of the cerebral hemisphere increases with sleep and with stress. Generally, to
I
of its side. establish a diagnosis of hyperprolactinaemia, only

I one prolactin measurement is required. lf the value is
clearly abnormally high (>40 ng/mL),
I
I This arrangement means that fibres from the medial

I
(nasal) halves of the two retinas, which are the fibres

Il hyperprolactinaemia is present. One single value in
I responsible for temporal vision, are located centrally the normal range (8 25 n{ml) excludes the
-
in the optic chiasma. diagnosis; in other words, if the value is normal, the
i
I patient does not have hyperprolactinaemia. How-
Lesions of the pituitary, including prolactinomas, if ever, if from the clinical picture, one would expect a
r
i small, will involve only fibres situated in the c. ntre of significantly elevated value, a high-dose hook effect
{ the chiasma, i.e. the crossing fibres from the medial must be excluded by serially diluting the sample and
I half of each retina, i.e. the temporal vision fibres. repeating the measurement. Values in between
I Both temporal halves of the visual field are lost. This clearly normal and clearly elevated (>25 and <40
I
is bitemporal hemianopia, i.e. tunnel vision. The
nglmL) demand a repeat measurement.
pupil does not react (constrict) when light is thrown
on the nasal retina, but when light is thrown on the Drawing the blood sample: lt is important to obtain
temporal half of the retina, the pupil contracts the blood sample without subjecting the patient to
(Wernicke's sign or hemianopic[hemiopicl pupillary sxces,,iile venipuncture stress because that may
reaction). !ke up the prolactin level, as secretion increases
niith stress.
Ev a I uati on a nd Di a gnostic Workup
The patient usually presents with one, or a combina- Pituitary fossa imaging MRI: Approximately 40% of
tion of the symptoms discussed above under Clinical hyperprolactinaemia patients wlll have a
Presentation. prolactinoma, even when levels are only mildly
elevated. rir.rirrUgh no singletestcan help determine
ln evaluating the condition, it is important to first
the cause of hyperprolactinaemia, nonetheless, a
exclude: (a) pregnancy; (b) medication use; (c) renal
prolactinoma is likely if the prolactin level is >250
failure; (d) hypothyroidism; and (e) acromegaly.
ng/ml and less likely if the level is <100 ng/ml.
Although medications can cause significant eleva-
I
A detailed history must be taken, including; medica-
tions, a level >500 ng/mL is diagnostic of a
I
tion use, menstrual history (oligomenorrhoea,

macroprolactinoma (15). Prolactin levels tend to
amenorrhoea), galactorrhoea, infertility, headaches,
paral lel prolacti noma size.
visual impairment.
:' Use of any of the causal drugs already discussed is
lf up to this point in the evaluation, no obvious cause
very important.
is identified, or if a tumour is suspected on clinical
. Dopamine-receptor antagonists: E.g.,
grounds, imaging of the pituitary fossa is mandatory.
phenothiazines, butyrophenones,
lf a prolactinoma is present, imaging will report it as
thioxanth i nes, risperidone, metoclopram ide
. Dopamine-depleting drugs: E.g., a microadenoma (<10 mm) or a macroadenoma
(> 10 mm)
methyldopa, reserpine
. Other drugs: E.g., danazol, isoniazid,
Magnetic resonance imaging: (MRl) should be
tricycl ic a ntidepressa nts, verapa m i l, opiates,
performed.MRl is the imaging study of choice; it is
H 2-blockers (ci metid i ne)
the most sensitive. MRI can detect adenomas that
are assmall as 3-5 mm (1).
Serum levels of TSH, hCG, blood urea, electrolytes
and creatininemust be measured to exclude or
Cf scan;High-speed helical CT scanners produce
diagnose primary hypothyroidism, pregnancy, and
I very detailed lmages.
renal failu re, respectively.
Serum prolactin /eve[ ldeally, the blood sample for
Plain lateral (sagittal) and frontal X-ray of pituitary
513
fossa:Where MRI and CT scan are not accessible, arthritis, neuropathy, hypertension,
and the patient has mass-effect symptoms, plain X- heart disease, acral and soft tissue
rays may be helpful (Fie 1). The normal'pituitary overgrowth.
gland weighs about 0.69. ln normal pregnanry the o Serum FSH-LH and TSH levels to
pituitary gland increases in volume and enlarges to a exclude a gonadotrophic and a
-
weight of 1 1.5g, a 50% to 70% increase. The thyrotroph ic adenoma, respectively.
enlargement is due to hyperplasia and hypertrophy of o Serum estradiol levels: High
lactotrophs, and recruitment of somatotrophs, to prolactin levels are associated with
prolactin production. During normal pregnancy, this chronically low estradiol lev-
enlargement can cause concentric contraction of the els-chronic hypogonadism. This
visual field, and an increase in the size of the physio- predisposes the woman to
logic blind may spot occur. On plain X-ray, the size of osteopenia, osteoporosis and
the pituitary can be taken to be the size of the fractures. lf serum levels are low
sellaturcica. The normal dimensions of the (<40 pg/mL) hormone replacement
sellatu rcicaare: therapy (HRT) should be instituted.
. Vertical diameter (depth)< 14mm ln HRT with the uterus present, it is
. A-Pdiameter(sagittalplane) <17mm necessa ry to give Provera
. Width (frontal projection) < 19mm 10mg/daily for 10 days in each
month to promote endometrial
Other tests; Any additional tests would be deter- shedding and prevent endometrial
mined by any identified cause and symptoms: As hyperplasia and its attendant risk of
examples: endometrial carcinoma. lnstead of
. Ophthalmological examination: Visual-field
Provera, combined oral contracep-
testing should be performed if imaging tives can be used.
studies show that the macroadenoma
extends outside the sellaturcica, or impinges Management
on, or is close to the optic nerve, or if the ldeally, management should be multidisciplinary and
patient complains of a visual impairment. should include the ophthalmologist, endocrinologist
. A large macroadenoma diagnosed by MRI and gynaecologist. Visual f ield assessment is
may not necessarily be a prolactinoma, i.e., strongly indicated in macroadenomas, but there is no
a lactotroph tumour. lt may be a tumour of need for it in microadenomas, because
one of the other secretory cells of the anterior microadenomas cannot be expected to have any
pituitary that is disrupting the pituitary stalk mass effects.
and, thereby, causing disconnection
hyperprolactinaemia. Therefore, when a Factors Determ i n i ng M a nagement Moda I ity
macroadenoma is identified, it is important The management option elected for a patient will
to perform screening tests to rule out other depend on:
hormone elevations. 1. Severity of sym ptoms present:
o 24h urine collection for free cortisol galactorrhoea, ol igomenorrhoea, secondary
to rule out a corticotrophin-secreting amenorrhoea, infertility, headaches, visual
tumour. impairment, etc.
o Serum insulin-like growth factor-1 2. Size of prolactinoma.
concentration to excl ude a 3. Patient's ferti ity desi res
I
4. Concerns about bone density-osteopenia

somatotrophin-secreting tumour
, and acromegaly.
and osteoporosis.
lf medication is the cause.
5.
o Serum somatotrophin (GH-RH)
6. lf the underlying cause is treatable. lf so, it
concentration to screen for should be appropriately treated. E.g.,
acromegaly. Other clinical features
hypothyroidism should be treated with
of acromegaly include: thyroid hormone (thyroxine) replacement.
hyperhidrosis, glucose intolerance,
Acromegaly treatment includes removal of
5L4
'
Hyperprolactinaemia
:
r
the t'rmor using the trans-sphenoidal thirds if the patient's basal prolactin level is less than
I
I ?ppro?r)h, radiation therapy, and injection of 40 ng/ml (15).
I
growth hormone blocking drugs to desensi-
l*- tize (down - regu ate) hypothalamlUoituitary
I
A patient on watchful waiting should be counselled
t receptors. that osteopenia and osteoporosis may result from
I
I
I prolonged hypoestrogenism. An estrogen-containing
combined oral contraceptive pill (COCP) should be
i
i Treatment modalities
i
I
1. Expectant-watchful waiting--observation considered. COCPs do not produce long-term change
2. Medications: Dopamineagonists' in tumour size; although they may
a. Bromocriptine
i
b. Cabergoline induce a small increase in prolactin secretion, this
a c. Quinagolide effect is not clinically significant ( 1 4, 1 9).
t
{ 3. Surgery
4. Radiotherapy MedicalTherapy
tI
Medical therapy is directed at stimulating dopamine
( Expecta nt M a n a ge ment: Observation receptors. Their stimulation inhibits prolactin
ii Watchful waiting is a valid option:
synthesis and secretion, and inhibits lactotroph
A. ln patients with hyperprolactinaemia and no
r- I
symptoms (idiopathic or with mitosis.
I
microprolactinoma) (1). ln these patients, The drugs in common Llse are:
I
first, hypermacroprolactinaemia should be . Ergot alkaloid derivatives:
t excluded as described above under,"Types of o Bromocriptine(Parlodel@):
Prolactin: Macroprolactin and its Clinical o
1
Cabergoline(Dostinex@)
i Significance", r.rsing screening (precipitation
i .
wilh 25% polyethylene glycol),followed by Apomorphine derived:
gel filtration chromatography or other o Quinagolide
method to confirm the screen positives,
I Bromocriptine
B. ln a patient with all the following present: (a) Bromocriptine is a strong dopamine D2-receptor
i a microadenoma; (b) mild-moderate agonist, and a partial dopamine D1-receptor
hyperprolactinaemia (<100 ng/mL); (c) agonist. lt inhibits prolactin secretion with no effect
galactorrhoea is the patient's only symptom; on other pituitary hormones.
I
I
?
(d)the patient gives informed consent. . Available preparations: 2.5 mg tablets for
oral or vaginal administration; 5 mg cap-
Expectant management is based on the fact that sule.
microadenomas rarely grow (1, 14, 15). As a rule, in . The oral preparation is given with food to
90 - 95% of cases, microadenomas do not enlarge by reduce the possibility of gastrointestinal (Gl)
the end of 7 years'observation; they remain stable or irritation.
shrink (15, 20). ln 34% of cases, elevated prolactin . Dosing:
levels will normalize within 5 years. Additionally, it is o lnitiating therapy: 1.25 mg (half
not likely that a
prolactinoma that has caused tablet) daily nocte, after food;
hyperprolactinaemia will grow significantly without increase dosing every 3 - 7 daYs,
an associated elevation in serum prolactin levels. The usual therapeutic dosage is 5-
Therefore, selected patients can be safely monitored 7.5 mglday, ranges from 2.5-15
wiih 3-monthly serum prolactin measurement. mglday. Vaginal administration of
Repeat imaging is reserved for those with significant 2.5 to 5 mg daily is also effective
serum prolactin elevations or neurological symptoms and may reduce Gl side effects.
(14). One-third of patients with idiopathic . Serum prolactin is checked before increas-
hyperprolactinemia may experience resolution ing dose. Once appropriate dosing has been
:
I without treatment. This number increases to two- established, serum prolactin can be checked
every 3 months.
515
. The most common side effects are nausea, (14, 15). ln a subgroup analysis restricted to the
vomiting, orthostatic (postural) hypotension, hyperprolactinaemia cases, this association disap-
drowsiness, dizziness, syncope, headache, peared. However, other studies reported cases of
constipation, and nasal congestion. in patients receiving lower
cardiac valvulopathy
doses of Cabergoline for the treatment of
Bromocriptine has been used extensively for treating hyperprolactinaemic disorders Q2). On the other
hyperprolactinaemia for more than 25 years. hand, other workers found noevidence of increased
Therefore, compared with other drugs, mitral valve tenting arealheight, valvular thickening
bromocriptine's safety profile, including its use in or significant regurgitation with the long-term
pregnancy, is better established. Bromocriptine is administration of the commonly used doses of
also used for ovulation induction in women with cabergoline to treat prolactinoma Q3). And other
hyperprolactinaemia. Five to 78% of patients are workers found only a significant increase in mild
reported to show bromocriptine resistance, with only tricuspid regurgitation associated with high cumula-
partial lowering of plasma prolactin levels and an tive doses of Cabergoline (24).Until the situation
absence of tumour shrinkage (21). becomes clearer, the following precautionary
measures may be advisable.
Ca be rgol i n e ( Dosti nex@) . Before initiating Cabergoline therapy, all
Cabergoline is a long-acting dopamine receptor patients should undergo a cardiovascular
agonist with a high affinity for D2 receptors. lt exerts
evaluation, including echocardiogram (if
a direct inhibitory effect on the secretion of prolactin
possihr^), to assess the potential presence of
by pituitary lactotrophs. lt has low affinity for valvuiar disease.
dopamine D1, u1- and a2-adrenergic, and 5-HT1- . The lowest effective dose of Cabergoline
and 5-HT2-serotonin receptors. Therefore, should be used for the treatment of
Cabergoline is far more selective in its mechanism of hyperprolactinemia.
action than bromocriptine, and it is better tolerated r Prolactin levels should be checked every 2
than bromocriptine. Because it is long-acting, it is months to reassess the need for continuing
given twice a week.lt is effective in normalizing thera py with Cabergol i ne.
prolactin levels and restoring ovulation in 85-90% of o After achieving a normal serum prolactin
women (i4, 15). level and maintaining it for 6 months, the
drug may be discontinued, with periodrc
Available preparation: 0.5 mg oral tablets.
monitoring of the serum prolactin level to
Dosing:
o determine whether or when to reinstitute
lnitiating therapy: 0.25 mg (half tablet) 2
Cabergoline.
times every week for the first 2 weeks, and
then 0.5 mg twice weekly.
Cabergoline has many advantages over
o Dose may be increased by 0.25 mg every 8
Bromocriptine. Cabergoline has higher efficacy in
weeks or longer up to 1 .O mg2 times/week,
normali; prolactin levels, restoring ovulation and
accordingto serum prolactin le'
o Dosage increases should not oi..,lr il, '-
fi-re i,rl:.. vell as a higher frequency of pituitary
i inor Srrirrri..,.lg0. Results of various studies indicate
rapidly than every 4 weeks, so that . "
;at bromocriptine decreases pituitary tumor size by
patient's response to each dosage level can
approximately 50% in two-thirds of patients,
be properly assessed.
compared with a 9OY" decrease with cabergoline. ln
. The lowest effective dose of Cabergoline
should be used.
a placebo-controlled study of patients with
microadenomas or secondary amenorrhoea,
Side effects: Postmarketing cases of cardiac Cabergoline treatment normalized prolactin levels in
valvulopathy have been reported in patients receiving 95% and restored menses in 82% of women with
Cabergoline for Parkinson's disease and for amenorrhea (1). ln one study, a dosage of 0.5 - 1 mg
hyperprolactinaemia. The dose for Parkinson's cabergoline twice a week was more effective than
disease is far larger (>2mglday) than the 1.0 mg 2.5 - 5 mg of bromocriptine twice a day at restoring
twice a week dose used to treat hyperprolactinaemia ovulatory cycles (72% vs. 52%); and normalisation
516
Hyperprolactinaemia
of prolactinlevels was higher in the Cabergoline successfultreatment. Ovulatory cycles

group (83% vs. 58%) (14). The fact that cabergoline 6 months after discontinuing
persist for
has a higher affinity for dopamine"l!8 receptor treatment. So, pregnancy can occur
binding sites may explain its greatw'$ffimness. after cessation of therapy. Counsel on
Additionally, Cabergoline has a lo{!-fjffiiiee ot contraception.
unpleasant side effects and is thffi better ii. Perform monthly pregnancy tests during
tolerated. lt has a more convenient Oii€ihgscncOule. the period of amenorrhoea.
These propertiei may contribute to bettdr drug iii. After her menses have become reestab-
compliance. Approximately 25% of women are lished, perform a pregnancy test any
resistant to bromocriptine and 80% of these patients time the onset of the next period is
may achieve prolactin normalization on cabergoline delayed.
(1). However, Cabergoline is moreexpensive. iv. lf pregnancy is not desired, advise on
contraception.
Qu i nagol i de (Norprol ac@) v. Discontinue treatment if pregnancy
7
Quinagolide is a strong selective dopamine D2- occurs during treatment. ln patients
receptor agonist with low affinity for D1 reeeptors. lt with microprolactinoma or idiopathic
is used in cases of bromocriptine resistance or hyperprolactinaemia, the risk of disease
intolerance. lt
is a non-ergot dopamine agonist; progression is only 7.6"/". Observational
therefore, the valvular heart concerns studies indicate that during 4-6yrs of
aboutBromocriptine and Cabergoline do not apply to observation, 95% of microadenomas do
it. Quinagolide is used in the UK and Europe, but has not increase in size (20). lnduction of
not, as yet, been licensed in the USA. Because ovulation in women with large
Quinagolide has significantly less side effects than macroprolactinoma is associated with a
Bromocriptine and Cabergoline, and because it has a higher risk of neurosurgical complica-
simpler dosing regimen (once-daily oral tablets and tions, such as optic chiasma compres-
;
rapid titration over just 7 days), Quinagolide may sion during pregnancy (20). Whether
I
improve patient compliance. Quinagolide offers an the drug should be continued or discon-
I
additional benefii for patients wishing to become tinued during pregnancy in such women
pregnant, as it can be used until the point of confir- has not been conclusively answered; but
mation of pregnancy (25,26). Quinagolide has been bromocriptine is safe in pregnancy. The
reported to reduce or eliminate peritoneal risk of re-expansion when the drug is
endometriotic lesions presumably because it inter- discontinued is under 10%. There is less
feres with angiogenesis, enhances fibrinolysis, and experience with the newer drugs.
reduces inflammation (27).Although early studies vi. Re-institute drugtreatment after delivery.
suggested that Quinagolide could be teratogenic, this Caution: Postpartum re-institution of the
finding has not been replicated (28); and the drug d rug may ca use lif e-th reaten ing
continuesto be popular in the UK and Europe. sympathomimetic interactions, usually
hal l-marked by severe headaches.
PatientMonitoring during Dopamine Agonist
Therapy 4. Women with large macroprolactinomas may
1. Four to 5 weeks after commencement of have adrenal insufficiency because of a
thera py, check for galactorrhoea. decrease in ACTH secretion and chronic
2. Although there is no evidence of teratogenic adrenocorticol suppression. This can be a
effects, the effect of dopamine receptor I ife-th reaten i ng cond ition.
stimulants on the fertility of the offspring
exposed in utero to these drugs is unknown. Surgical Management
Therefore: Trans-sphenoidal partial hypophysectomy is the
i. Exclude pregnancy before starting standard of care. ln recenl years, an endonasal
treatment and avoid pregnancy until at endoscopic approach has been used with less
least one month after cessation of morbidity than the trans-sphenoidal approach.
517
---------:----t
General indications for surgery include: Management is the same as for women. Medical
. lnability of patient to tolerate all three treatment is the mainstay of management.
dopamine agonist drugs or inability to Dlscussron a nd Controversies
tolerate the doses required to control the 1. Recently Fenugreek (which is a plant extract
tumour. with many medicinal benefits and many
. Tumors resistantto medical therapy. pharmacological effects) has been linked to
. Patients who have persistent visual-field high levels of prolactin. lt is also widely used
defects despite med ical treatment. in cuisines as herb, spice or vegetable in the
. Patients with large cystic or hemorrhagic Middle East. Fenugreek stimulates prolactin
tumors-these tumours do not respond to because it contains a galactagogue that
medicaltherapy. increases lactation. ln a study in Ankara,
Turkey, the investigators compared the early
The chief complication of surgery is pan- postnatalweight lost and weight regained of
hypopituitarism. Other complications are diabetes infants whose mothers received daily herbal
insipidus, cerebrospinal fluid fistulas, carotid artery tea containing fenugreek with controls
injury, loss of vision, meningitis. The recurrence rate whose mothers' herbal tea did not contai
after surgery for macroprolactinomas is as high as fenugreek. lnfants of mothers on fenugreer
40%within 5years(15). regained their birth weight significantly
earlier than the control infants. The mean
Radiotherapy measured breast milk volume of the mothers
Currently gamma knife radiotherapy (the destruction
who received fenugreek tea was also
of precisely selected areas of tissue using ionizing
significantly higher than the mean volume of
radiation) is used on a limited basis to treat residual
the placebo and control groups. ldentifica-
lesions.Cure rates have been inconsistent. Side
tion and exclusion of Fenugreek use by
effects include hypopituitarism, increased risk of
clients may help reduce prolactin levels
stroke and vision loss. (29). On the other hand, for mothers whose
perceived breast milk is insufficient, this
Clinical Features of Hyperprolactinaemia in the
herb, if available, may prove a boon.
Male
Because women have signature symptoms, i.e.,
galactorrhea and oligomenorrhoea/amenorrhoea, the
2. As already discussed, kisspeptins are
natural powerful activators of GnRH neu-
disease is more obvious in women than in men; and
rons. ln animal and human experiments, it
women present ea rl ier for tr'eatment tha n men do,
was demonstrated that exogenously
Whereas at first presentation most women have a administered kisspeptincan reverse the
microadenoma, because in men there is no signature hypogonadotropic effects of
symptom, most men present with a macroadenoma. hyperprolactinemia. This finding has
Male patients may presentwith: potential therapeutic implications for
1. Decreased libido treatment of hypogonadotroPh ic
2. Erectile dysfunction (impotence) hypogonadism, and restoration of ovulatory
3. lnfertility from low sperm count and other cycles and fertility (3, 4).
sperm abnormalities
4. Gynaecomastia
5. Symptoms of low bone mass
518
Hyperprolactinaemia
REFERENCES
1. Melmed S, Casanueva FE Hoffman AR, Kleinberg 14. Christianson MS, King JA, Zacur HA. ln: Chapter
DL et al. Diagnosis and treatment of 60 pp 929 Hyperprolactinemia; Clinical
hy pe r p ro Ia Society Cl i n i ca I
cti ne m i a : An Endoc r i ne Gynecology. eds: Eric J. Bieber, Joseph S.
Practice Guideline. J ClinEndocrinol Metab 201 I ; Sanfilippo, lra R. Horowitz, Mahmood l. Shafi.
96:273-288 Cambridge, United Kingdom: Cambridge
2. Hamoda H,Khalaf Y Carroll P Hyperprolactinaemia University Press,2015
and female reproductive function: what does the 1 5. Shenenberger D. Hyperprolactinemia. Medscape
evidence say? The Obstetrician &Gynaecologist Endocrinology July 2016 pp;
2012; 14:81-86 http : //emedicine. medscape. com/a rtic,
3. Donato Jr J,FrazSo R. lnteractions between prolactin le / L2L7 8 4 - clinical # b5
and kisspeptin to control reproduction. Arch 16. Lee D-Y Oh Y-K, Yoon B-K, Choi D. Prevalence of
6; 60(6) : 587 -9 5
Endocri nol Metab. 20 1 hyperprolactinemia inadolescents and young
4. Kaiser UB. Hyperprolactinemia and infertility: new women with menstruation-related problems. Am J
insights. J Clin lnvest. 2012; Obstet Gynecol. 2012. 206: 213.e1-5
122(10):3467-3468 17. Karavitaki N, Thanabalasingham G, Shore HCA.
5. Majumdar A,Mangal NS. Hyperprolactinemia. J Do the limits of serum prolactin in disconnection
H um ReprodSci 20 1 3; 6: 1 68-7 5 hyperprolactinaemia need re-definition? A study
6. Lyons DJ,Hellysaz A, Broberger C. Prolactin of 226 patients with histologically verified non-
Regulates Tuberoinfundibular Dopamine Neuron functioning pituitary macroadenoma. Clinical
Discharge Pattern: Novel Feedback Control En docri nol 2006 ; 65 (4) : 524-29
Mechanisms in the Lactotrophic Axis. J 18. Fourman LT, Fazeli PK. Neuroendocrine Causes of
N e u rosc i e n ce 20 12 ; 32(23) : 807 4-83 Amenorrhea-An Update. J ClinEndocrinolMetab
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7. Vaishya R, Gupta R, Arora S. Macroprolactin; a 100: 812-824,2015
Frequent Cause of Misdiagnosed 19.. Paupoo, A, Blackwell, R, Glob. libr. women's
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Hyperprolactinemia in Clinical Practice. J med
7 Reprod I nferti I 20 1 0; 1 1 (3) : 1 6 1 -67 (/SS/V: 1756-2228) 2008; D0l
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B. Shimatsu A, Hattori N. Macroprolactinemia. 10.38431c1OWM.10306
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D ia gnosti c, CIin ica l, an d Path oge n i c S i gn i f i ca nce. 20. ACOG practice bulletin: Management of infertility
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Clinical and Developmental lmmunology 2012; caused by ovulatory dysfunction. lnt J
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i\- 2012. Article lD 167132, 7 pages. GynecObstet 2002; 7 7 : 1 7 7 - 88
http : //dx.doi.org/ I 0. I I 5 5 /2 0 I 2/ I 67 I 3 2 21. Barlier A, Philippe Jaquet P Quinagolide
I -a
I 9. Emiliano ABE Julie L Fudge JL. From galactorrhea to valuable treatment option for
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osteopenia Rethinki ng serotonin-prolacti n hyperprolactinaemia. European Journal of
interactions. Neuropsychopharmacology. 2004; Endocrinology 2006; 154: 187-195
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29,833-846 22. Schade R, Anderson 4 Surssa S, Haverkamp W,
1 10. Hamilton M. The assessrnent of anxiety states by Garbe E. Dopamine agonists and the risks of
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11. Yoshimura Y, Jinno M, Oda T, Nakamura Y. Prolactin 4:356(1):29-38
inhibits ovulation by reducing ovarian plasmin 23. Herring N, Szmigielski C, Becher H, Karavitaki N,
generation. Biology of Reproduction 1994; Wass JAH. Valvular heart disease and the use of
50(6):1223-30 cabergoline for the treatment of prolactinoma.
12. Demura R, Ono M, Demura H, Shizume K, Oouchi Cl i n ica I Endocri nology; 2009 : 7 0( 1 ) : 1 04- 8
H. Prolactin directly inhibits basal as well as 24. Halperin l, Aller J, Varela C, et al. No clinically
gonadotropin-stimulated secretion of significant valvular regurgitation in long-term
progesterone and 17 beta-estradiol in the human cabergol ine treatment for prolactinoma. Clinical
ovary. J ClinEndocrinolMetab 1982; Endocri nology 20 1 2; 77 (2) : 27 5-80).
54(6):1246-50 25. Barlier A, Philippe Jaquet PQuinagolide - a
h
13. Biller BM, Luciano A, Crosignani PG, Molitch M, valuable treatment option for
Olive D, Rebar R, etal. Guidelinesforthe dr'agnosis hyperprolactinaemia. European Journal of
and treatment of hyperprolactinemia. J Reprod Endocrinology 2006; 154: 187-195
Med 1999; 44$uppl 12): 107 5-84
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26. Cotao A. Pituitary tumours: the prolactinoma. Best hyperprolactinaemia and inhibition of lactation.
Pract Res C I i n E n d oc r i no I M eta b 2009 ; 23 : 57 5-9 6 Drug Safety 1996; 1 4:228-38
27. Gomez R, Abad A, Delgado E et al. Efbcts of 29. Turkylmaz C, Onal E, Murat Hirfanoglu llVl, Turan
h y p e r p r o I a ct i n e m i a t r e a t m e n t w i t h the 6ryW-*ere O, et al. The Effect of Galactagogue Herbal Tea on
agonist quinagolide on endometriote @i6g. ln Breast Milk Production and Short-Term Catch-Up
patients with endometriosis-associated of Birth Weight in the First Week of Life. The
hyperprolactinemia. FertilSteril 2Al 1; Journal of Alternative and Complementary
95:882-88 Medicine 201 1 ; 17 (2): 139- 142
28. Webster J. A comparative review of the tolenbility
profiles of dopamine agonrsts in the treatment of
Fig 1. The anatomical basis of the double flooring seen in lateral radiographs of
lactotrophmacroadenomas
A. Lactotrophs are selectively located in the

of lactotroph macroadenomas
lateral winos of the anterior oituitarv.
A. Lactotro-phs are selectivel'i locate'd in the
lateral wings of tle anterior pituitary.
Normal floor of pituitary foss#
B. A large macroadenoma in one side produces

a depression of the floor of sellaturcicaon that
side. Normal floor of pituitary fossa
Secondary
B. A large macroadenomdn one side produces a

depression of the floor of sellaturcica on that
side.
Secondary floor
520
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43
a
Principles of Radiotherapy and

i
I
r
Chemotherapy in Gynaecology Cancers
{
Verna DNK Vanderpuye, Pearl Aba Scott, Hannah Ayettey-Anie
I
<
!ntroduction Primary radiotherapy can provide cure for women

Gynecological tumors commonly encountered in with unresectable, locally advanced disease and for
Sub-Saharan Africa include, cancers of the Cervix, resectable disease when the risk of surgical
Uterus (Endometrium, Carcinosarcoma, sarcoma), morbidity is high. ln metastatic the setting,
Ovaries, Vagina, Vulva and gestational trophoblastic radiotherapy can improve the quality of life of the
d iseases (Choriocarci noma). patient with as high 80% patient reported
improvement in symptom control.
A study on patterns of gynecological cancers in
Ghana ( 1), found cervical cancer was the Primary chemotherapy plays a major role in the
commonest, constituting 57.8%, followed by management of a few gynecological malignancies
ovarian, endometrium, choriocarcinoma and vulvar either in the curative or palliative setting(3).lt can be
carcinoma in that orde(1). A similar study from administered concurrently with radiotherapy to act
Nigeria mirrored the findings in Ghana (2). as a radiosensitizer to improve outcomes compared
I
with radiotherapy alone, or administered in the

Radiation therapy is an essential treatment modality neoadjuvant setting to downstage unresectable
for the cure or control of symptoms or arising from advanced tumors to enable further complete
:' female reproductive tract cancer. The various resection with the aim of improving local control and
treatment modalities for managing cancer including survival. Chemotherapy in the palliative setting is
their sequencing are dependent on the clinical and highly debated especially towards the end of life.
pathological stage of disease as well as the goals of However, for chemo-sensitive tumors such as
therapy; Palliation or curative. metastatic germ cell tumors, chemotherapy for
metastatic disease can provide significant symptom
For early most stage tumors, surgery is the initial
control and occasionally improve survival.
treatment of choice only if complete resection is
achievable with no residual disease and with minimal A multidisciplinaryapproach to the treatment of
morbidities. Post-surgical adjuvant therapies include gynecological cancers is highly recommended in
chemotherapy and radiotherapy. Postoperative current management strategies.
radiotherapy is indicated for large disease, poor
prognostic features, positive margins or other Multidisciplinary care refers to a practice in which
features, which may promote higher chances of physicians from multiple specialties create a
recurrence. Adjuvant chemotherapy is indicated to consolidated plan with the recommendations of all
mop up microscopic disease. for the utmost management of the patien(4). Some
521
proven benefits of multidisciplinary care include: For certain tumors, a combination of external beam
Patient satisfaction, improvement in symptoms , radiotherapy and brachytherapy is required to
survival, quality of Life , appropriate use of r€ssurces control the disease. The use of radiotherapy has
, enhancement of graduate medical ediry@pq , evolved over the years with rapid technological
card4). advancement with the ultimate aim of reducing
:
research and standardization of
normal tissue toxicity whilst achieving maximal
A study by Junor et al, found that cancer tumoricidal doses to the target volume.
ma nagement by a team'at.a-iCIif,t
m u ltidisci pli na'ry
cIinic, directly affects survival(5).,An article Over three decades ago, two dimensional dose
published by Croke et al supports the. belig-f that planning was superseded by three dimensional
multidisciplinary clinical conferences signifieantly conformal dose planning which gave a better
influence clinical decision making and treatment geometrical evaluation of dose distribution within
recommendations in cancer managemen(6). There the gross tumor volume , surrounding margin known
is however little evidence on the positive impact of as the planning target volume and the organs at risk.
patient outcomes with a multidisciplinary This technique has since been expanded to included
approach(7). highly technological dose delivery methods including
intensity modulated radiotherapy, image guided
The basics of Radiotherapy radiotherapy, conebeam, tomotherapy, stereotactic
Also called radiation oncology, this is a medical body radiotherapy and many mord10). These new
discipline which employs the use of high energy technologies come at exorbitantcost in the initial
gamma or x-rays to destroy the DNA of cancer cells stages, maintenance cost and training of skilled
or halting duplication to manage cancer and a few labor. Less than half of the countries in Africa have
times benign conditions. The radiation delivery is functional radiotherapy facilities with the majority
either by brachytherapy or external beam located in the northern and southern part{11).The
radiotherapy. The latter is delivered from a distance prescription and dose planning for radiotherapy
by an external source, either through a linear treatment is depend on clinical factors, tumor
accelerator which emits x-rays of various energies characteristics including anatomical location,
and electrons, proton or carbon ion accelerator or guided by principles based on high level of evidence
gamma rays by a decaying radioactive source such as and normal tissue or vital organ dose constraints.
the Cobalt 60 teletherapy machine. Brachytherapy The prescribed dose of radiotherapy is delivered over
on the other hand delivers radiation using weeks depending on the goal of treatment. Typically
radioisotopes with specific properties within or very few days to weeks for palliative treatments and 4-6
close to the tumor by ingestion, implantation or intra- weeks forcurative treatments. The unit of radiation is
cavity. Examples of radioisotopes used for 100cGy : 1Gy. This spread of the treatment over a
brachytherapy are radioiodine"u, cesiumtt', period of time is to allow healing of normal tissue to
irldium"', cobaltuo, palladiumton, strontium eo, avoid untoward toxicities. Unnecessary
radium"t, samarium'u"'.The rationale behind prolongation of overall treatment is associated with
brachytherapy is that the radioactive isotopes utilized detri mental outcome{ 12 ).
for this therapy emit radiation energy by inverse
square law. This states that, for a point source, the Basics of chemotherapy
radiation intensity (l) at any place varies inversely as These are chemicals used to target the cancer cell
the square of the distance (d) from the source to the and mostly act at various levels of the cell cycle. They
place at which the intensity is being considered(9). include other systemic therapies such as hormonal
treatments and molecular targeted drugs. They are
ln effect, this means, the isotopes deposit their grouped by their chemical structure or mode of
highest radiation energy (l) at the site nearest to the action. The side effect profile may vary with the
source. Hence in brachytherapy, radioactive source group or have may be idiosyncratic. Their chemical
are placed at tumor site, which received high dose of action affects both the cancer cell and the normal
radiation, whereas the surrounding organ receive a cell, leading to dose limiting toxicities which could be
lower (tolera nce) dose. fatal if not properly monitored. The combination,
522
Principles of Radiotherapy and Chemotherapy in Gynaecology Cancers
choice and se'luencing of therapies depend several Staging

factors. These include but not limited to tumor The lnternational Federation of Gynecology and
characteristics, clinical factors including existing co- Obstetrics (FIGO),the most widely used staging
morbidities, toxicity profile,and accessir,=ilily and system for cervical cancer is a clinical staging
guided by proven high level evidence of activity system, whiles the American Joint Committee on
specific to the tumor type.As with other therapies, Cancer (AJCC)staging system less commonly used,
chemotherapy has rapidly evolved with the is a surgical/ pathologic staging syster( 13).
development of newer, complex and more active
drugs and comes at a high cost. The options for Unlike the F|GO system, the AJCC system
managing patients are endless except in low to incorporates lymph node status into its staging.
middle-income countries where access to current However, the surgical staging of pelvic/ para-aortic
chemotherapy recommendations is limited by lymph nodes is considered optional and
ACCESS. controversial even though it gives prognostic
information, and identifies which patient require
adj uvant therapy to the para-aortic nodes
This chapter discusses the role of chemotherapy and
radiotherapy in the management of cervical, The FIGO staging rules only allows for inspection,
endometrial, ovarian, chorio-carcinoma and vulvar
palpation, endocervical curettage, hysteroscopy,
cancers.
proctoscopy, cystoscopy, plain X-ray films of the
lungs and bones, and intravenous pyelography to be
CANCER OF THE UTERINE CERVIX
used forstagin(14).
Work Up
All patients must undergo general clinical Other imaging modalities such as MRI and PET
examination and Examination under anesthesia scans are not allowed by the FIGO staging rules. CT-
(EUA) for accurate staging of the disease by scan in lure of intravenous pyelography is only
examining the parametria, sidewall and lower extent permissible in the presence of hydronephrosis.
of disease and biopsy of cervical tumor. The initial
spread of cervical tumor is laterally into the Even-though the FIGO system is criticized for not
parametria, and thereafter anteriorly and posteriorly allowing the use of modern imaging modalities such
into the bladder and rectum respectively. Spread as MRI and PET scans which may influence staging,
could also occur upwardly into the uterus. it eliminates the disparities that may arise in the
staging of cervical cancer across the world, since
A chest x-ray and abdominal ultrasound even though cervical cancer is more prevalent in the developing
basic gives a lot of information about the state of countries with limited availability of advanced
these organs which may be the first indication of imaging. Advanced imaging is highly recommended
metastases. for radiotherapy treatment plan ni ng.
Cystoscopy and proctoscopy are required where is Lymphangiography ls the best method to explore
there is high likely hood of bladder or rectal pelvic lymph nodes, while para-aortic areas can be
involvement. explored more accurately by using CT scan (with fine
needle aspiration in case of suspicious enlarged
A CT scan of the chest abdomen and pelvis were nodes). MRI provides a good estimate of parametrial
available may give a simple but expensive involvement and is especially useful in determining
assessment of all these organs. which patients are candidates for primary surgical
resection, and its use is recommended by the
Laboratory investigations including full blood count, National Comprehensive Cancer Network (NCCN)
renal and liver function test are essential to pick up (15).
: other medical problems that need to be addresses
a and may alterthetreatment plan. Abdomino-pelvic ultrasonography or a CT-scan is
:
used in ascertaining the extent of the spread of the
523
disease to intra-abdominal and pelvic organs, The stenosis, which renders the insertion of the
use of PET-scan although effective in detecting brachythera py a ppl icators d iff icu lt
distant metastases, and pelvic and para-aortic
nodes, is considered optional by the NCCN External Beam lrradiation (Teletherapy)
guidelines. Teletherapy for early stage cervical carcinoma is
with megavoltage teletherapy faci ities
ad m i n istered I
Laboratory tests that should be carried out pre- as initial therapy. Recommended prescribed dose is
radicitherapy include full blood count, serum urea, 40 -50 Gy.With the aid of simulation films,
creati ni ne, electrolyte a nd I iver fu nction tests. (computed tomography and lymphangiography
guide whenever available) the boundaries for the
GENERAL PR!NCIPLES OF TREATMENT treatment field are determined preferably by
conformal treatment plann i ng.
Treatment of carcinoma of the uterine cervix involves
multiple treatment modalities and depends on the The upper border is Lo- Luinterspace. However, L5-
stage of the disease, patients'preference, S1 interspace may be included in favorably sized
performance status and co-morbidities. The poor carcinomas, which does not require comprehensive
sequencing of treatment modalities usually result in coverage of the upper nodal regions. The lateral
negative outcomes. These include mono or margins extend to 1.5 -Zcm lateral to pelvic margins
concurrent or sequential use of modalities such as; and the lower border is mid-pubis or 4cm below the
lowest extent of the vaginal disease. Radio-opaque
Surgery seeds placed at 6 o clock and72 o'clock in the cervix
Radiotherapy
are used to determine the lower extent of the cervix. lf
Chemotherapy
the cancer has extended to the vagina, the radio
opaque seeds implanted at the lower extent of the
Early Disease: Stages I & ll
Rationale for Radiotherapy as treatment of choice: vagina disease. The central pelvic region is shielded
Advanced age, obesity, hypertension, diabetes, with leaded blocks after 45Gy in 25 daily fractions
vascular disease, chronic lung disease consign a poor and a side wall boost of 10-16 Gy in 5-6 daily
surgical risk group and require radiotherapy as fractions is delivered. The total dose to Point A is 80-
primary method of treatmen(16). 85G(18).
Surgery and radiotherapy yield similar cure rates, Btachytherapy (short distance therapy)
however morbidity is wbrse with the combination Brachytherapy is an important component in the
is management of cervical cancer. Brachytherapy
ofsurgery and radiotherap(17). Mortality rare
allows for repair of sub-lethal damage to normal
during radiotherapy, whereas peri and post-operative
tissue whist delivering high dose of radiation to the
mortality is possible following surgery( 17).
cancer cell{19).lt allows for the delivery of high
Residual macroscopic and microscopic disease, doses of radiation to the cervix and Para cervical
extensive disease and lymph node positive tissues, thereby improving local disease control and
survival. The failure rate and survival rate when
disease are indications for adjuvant chemo- brachytherapy is omitted as part of the treatment
radiatio(17). Radiotherapy management involves plan is high across all stages of cervical cancer
External Beam megavoltage irradiation and especially II lA-l I I H20).
Brachytherapy (intracavitary irradiation with
radioactive isotopes such as iridiumlt', caesium"', Cervical cancer brachytherapy is performed
done
cobaltuo). using either the Low Dose Rate (LDR) brachytherapy
or the High Doe Rate (HDR) intracavitary
For bulky cervical tumors (greater than 4.0 cm),it brachytherapy, A less commonly available technique
preferable to initiate external beam radiotherapy to is the Pulsed.Dose Rate intracavita ry
downstage the tumor followed by brachytherapy. brachytherap(21).
Difficulties are a narrow vaginal canal and cervical
524
T
I
{
I
ln the West African sub-region, low dose rate the parametria) and it is 5cm from the midline, and
I brachytherapy using radioactive caesium"' (ertrits represents the lateral parametrium and the region of
I
! Gamma radiation, 0.66 Mev and B. Farticles the obtu rator node{25).
0.51Mev Half-life is 30 years) is commonly
uoHigh
employed(22). Cobalt dose rate brachltherapy The rectal and bladder points reflect the maximum
is gaining popularity as a more cohvenieht and dose to critical structures, and can be minimized by
/
equivalent outcomes compared low dose rate proper positioning of the applicators and adequate
: brachytherap(23). vaginal packing.Dose prescription reference points
a
i for conformal dose planning are different from 2
The object of the treatment, is to raise to as high a dimensional planning reference points. For example
dose as can be tolerated a relatively thin 'triangle' of to dose lo 2cc of the bladder and rectum are the
tissue (called the Para cervical triangle) where the references points.
uterine artery crosses the ureter and excessive dose
tothis region will result in radiation necrosi{24). H DR I ntracavitary Brachytherapy
-60) is
A single activity soui'ce(lridiu m-792 or cobalt
Point A is the prescription point in this paracervical staggered sequentially through various dwell
triangle and is comparable from ptitient to patient, positions in the applicator to deliver a particular
: and defines the tolerarlce dose(25). The dosd26). The inverse planning system is used to
recommended dose to point A combining both determine these dwell positions and the dose rate
external and brachytherapy doses (not literally) are ranges from 2-3Gylmir(21). Patient treated with
80-90Gy with higher doses recommended for larger HDR brachytherapy undergo several insertions
volume disease. (usually 2-5), each delivering 5-9Gy to point N2O.
The total dose to point A including external beam
A radioactive isotope, usually Caesium-137, is radiotherapy should be at least 80 Gy but may be
introduced directly into the uterine cavity and fornices limited by normal tissue constraints.
of the vagina using applicators (e.g. Fletcher-Suit
Delco's or Henchke applicators) with the patient An advantage of the HDR over the LDR is that
under general anesthesia or conscious sedatio(26). treatment is finished within minutes compared to the
The applicators are loaded with radioactive sources several days for the LDR brachytherapy. This allows
either manually or by a remote after loading the treatment of many patients in a day and
;
technique to minimize radiation exposure to treatment done on outpatient basis. The dose
t!- personnel. The radioactive sources deliver a dose delivered is optimized by adjusting the dwell
the prescribed dose al 0.4-2Gylhr over 36 -72 positions and times of the radiation source compared
hrs.(19). Two to insertions at least few days apart are to LDR.
recom mended to avoid prolonged patient
immobilization which may lead to high morbidity and Pulsed-Dose Rate lntiacavitary Brachytherapy
Patients are treated with pulses of radiation; 10-
mortality f rom venous embolism.
30munites of radiation therapy every hour during the
The dose rate and the total dose are prescribed to a implant coursd2T). lts radiobiological effects are
number of specific reference points in the pelvis; similar to that of LDR brachytherapy. A low activity
points A, B, rectal point and bladder point. ln the iridium-1 92 is usually the source used.
Manchester system, point A is defined as being a
point 2cm lateral to the center of the uterine canal TREATMENTAS PER STAGE OF DISEASE
and 2cm above the mucous membrane of the lateral
Treatment of Stage I (Micro invasive disease)
fornix of the vagina in the plane of the uteru{25).
FIGO stage lA1-
A simple hysterectomy is the treatment of
Anatomically, point A is the region where the uterine
choicd28). Lymph node dissection is not necessary
t artery crosses the ureter and represents the lateral
because of the low risk of lymph node involvement
cervix and medial parametriun(24). Point B gives an
<!Y".Forwomen who wish to maintain theirfertility,
indication of the rate of fall-off of dosage laterally (in
s25
a cone biopsy with removal of the transformation margins, positive parametrium or positive lymph
zone is acceptable. However for patients with nodes) which is invariably associated with higher
contraindication to surgery, brachytherapy alone to a toxicit(17). The treatment of choice for 182 bulky
total dose of 65-75Gy is an acceptable disease is concurrent chemo radiatio(33).
alternativd29).
Stag !V
FIGO stage lA2 Previously, radiotherapy was contraindicated in the
The risk of lymptr node involvement is estimated as management of Stage IVA cervical cancer patients
5%. Treatment consists of modified radical with fistula. lt is however currently recommended
hysterectomy with lymph node dissection (28). For that this group of patients undergo surgical urinary
women who wish to maintain their fertility, radical diversion (if there is
vesico-vaginal fistula) or
trachelectomy and pelvic lymph node dissection is colostomy if there is recto-vaginal fistula, and then
acceptable for tumors less than 2cn(30). When have the full course of chemo radiatio(34).
there are contraindications to surgery, a combination
of external beam radiotherapy and intracavitary Stage lVrCervical Carcinoma
brachytherapy to a total dose to 75-80Gy is Palliative external beam radiotherapy controls 80'
recommendedl5). of local symptoms in incurable diseasd35).
FIGO stage lBl and stage 2A (Nonbulky)- These symptoms include pain, offensive discharge,
Treatment options include external beam radiation bleeding, bone metastases, bladder outlet
therapy plus intracavitary brachytherapy or radical obstruction, consti pation or recta I bl eed i ng.
hysterectomy with pelvic lymph node
dissectio(17).The external beam is prescribed to Other pa I I iative i nterventions req u i red i ncl ude
40-45Gy and the brachytherapy a total dose of 40- Control of pain - with analgesics
45Gy to point A concurrent with cisplatin for stage 2 Control of Hemorrhage - with haemostatic dose of
A disease especiall( 15). radiation
Control of infection - with antibiotic therapy
Adjuvant radiation therapy is indicated in patients Correction of anemia
lmprovement of general nutrition of the patients
with positive lymph nodes or parametrial
involvement or positive margins so as to reduce to the
Contraindications to chemo radiation include
high risk of local recurrencdlT). The adjuvant 1. Moderate to severe renal
radiation therapy consist of external beam therapy of dysfunction
45-50Gy to the pelvis and intra-cavitary 2. Moderate to severe peripheral
brachytherapy of 2OGy to the surface of the ovoids. neuropathy and ototoxicity
3. Very advanced disease
Locally advanced (FIGO stagel 82- IVA)-
For this group of patients, f ive large randomized study
have established that the standard recommended ROLE OF CHEMOTHERAPY IN CERVICAL
treatment is concurrent chemo radiation therapy; the CANCER
chemotherapy used is cisplatin 40m{m'given at
weekly intervals for 5-6 weeks given concurrently The most effective chemotherapy used in the
with radiation therapy, external beam radiation to a management of cervical cancer is cisplatin- based
total dose of 45Gy to the pelvi{31).followed by chemotherapy. lt is usually given as single agent or
brachytherapy to 40-45Gy, This protocol results in with SFlourouracil in combination with radiation
significant overall survival benefit{32). Even though therapy using a weekly or three weekly
some clinicians consider radical hysterectomy and sched Id36).Weekly Single agent cisplati n sched ule
u
pelvic lymph node dissection for some patients with has bettertolerance and response rates and therefore
stage lB 2 and stage llA 2, it must be noted that very popula(37).
majority of such patients may require adjuvant
Recently the use of neoadjuvant chemotherapy prior
radiation therapy (those with positive surgical
526
----l
to surgery for locally advanced disease is a subject of phosphate is useful in managing colicky abdominal
high interest but results have not been confirmed in pain and diarrhea from radiation induced bowel
high level studie{38). lt is currently recommended reactions.
Bladder
Radiation induced cystitis is a common occurrence
Postoperative adjuvant chemotherapy is only in cervical cancer patients.
effective in combination with chemotherapy. featu res i ncl ude u rgency, f req uency, noctu ria
Cl i n ica I
and dysuria.
ln the recurrenVmetastatic setting, single agent Potassium citrate and effercitrate (3 times daily) are
cisplatinmay be effective but with less response in effective in the treatment of cystitis.
patients with prior exposure. Recommended options Antispasmodics forthe bladder may be of help.
include combination cisplatin based chemotherapy
Vagina
doublets which include taxane or topotecan, or single
Acute Desquamation reaction: leading to
agents suchpaclitaxel, vinorelbine, ifosfamide or
formation of occlusive adhesion of the vagina,
irinotecan(39).
Vault Stenosis: lead to pyometrium and inability
Early and Late Effects of Radiotherapy for Cervical examination and sexual difficultie{41).
Local application of estrogen creams improves
Cancer
Both the early and late normal tissue sequelae of natural vaginal lubrication.
r Sexual intercourse or the use of a vaginal dilator
radiotherapy are worsened by adverse general and
should be mandatory during treatment.
Iocal factors such as diabetes, hypertension, previous
Trans-peritoneal surgery, previous pelvic Late effects of Radiotherapy
inflammatory disease, and co-existent conditions Late effects of radiotherapy tor cervical cancer
such as pelvic infection and diverticular disease. The
usually manifest 6- 24 months after completion.
latter condition is quite common amongst older' These include bowel stenosis, malabsorption
patients with cervical cancer, whereas many younger
syndromes and second mal ignancies.
patients have or have had episodes of pelvic
inflammatory disease. Anterior Rectal Wall U lceration :
Present with pain defecation, tenesmus, severe
Early Effects of rectalbleeding.
Brachytherapy and
management options There is high risk of ureteric and vesicular fistula
Early Radiation induced adverse effects include formation following invasive techniques.
I
I proctitis and cystitis lf is best managed by permanent dysfunctioning
Proctitis and Cystitis require short term symptomatic colostomy and occasionally instillation o'f \"/o
:
treatment in some 20% of patients (such as formalin.
prednisolone suppositories for radiation induced
proctitis). Rectovaginal Fistula
Recto-vaginal fistulae are rare in the absence of
Uterus surgical intervention and usually the consequence of
Perforation of the uterus. massive central disease or unusually extensive
Broad spectrum antibiotics may be given and vaginal involvement of the original disease.
subsequent peritonitis almost never occurs.
They are mainly a result of disease progression rather
Bowel than a complication of treatment.
Tenesmus Rarely, it could result from radiation to the pelvis.
Mucus/or blood per rectum. A diverting colostomy and hyperbaric oxygen has
Diarrhea, with or without col icky abdominal pai n.
shown promising results.
lleitis:(40).
I
i Bladder
Oral rehydration, lmodium, Kaolin or Codeine The late effects following radiotherapy encountered
527
in the bladder comprise the following: carcinoma of the cervix post therap;{ ?)t
Stage 0- 93%
i .Telangiectasia of the bladder base mucosa: which Stage lA -93%
might cause repeated episodes of hematuria, !f elets Stage lB-80%
form in the bladder, anti-fibrinolytics may be reguirad StagellA -63%
to stop the bleeding, and cystoscopic evaeuation of Stage llB -58%
the clot may be carried out.
Stage lllA-357o
Stage lllB- 32%
IVA-16%
ii .Vesico-Vagina Fistu la (VVF): is another Stage
Stage IVB-15%
compl ication encou ntered i n ma nagement of cervica I
cancer. WF may be precipitated by multiple biopsies
ENDOMETRIAL CARCINOMA
taken to exclude residual or recurrent disease. ln cancer of the endometrium, surgery is the main
(ileal loop diversion) is performed
Urinary diversion stay of treatment with rad iothera py a nd
to provide relief from perpetual incontinence. chemotherapy been reserved for cases with adverse
pathologic featu re{43 ).
SmallBowel
Chronic Diarrhea: 10 - 15% sufferfrom persistent or
Staging
intermittent attacks of diarrhea, accompanied by FIGO recommends upfront surgical staging for
abdominal pai(40) endometrial cancer. Each patient undergoes
exploratory laparatomy, peritoneal washings for
Bowel Strictures: Often times, localized bowel cytology TAH and BSO as well as assessment of the
strictures of the small bowel are formed(40). pelvic and para-aortic lymph node{43).
Palliative surgery in form of a by-pass will enhance
relief forthe patient. The depth of myometrial invasion should be
assessed both clinically and pathologically to
Ovary determine the extent of pelvic and para-aortic lymph
Premature ovarian failure and the estrogen deficiency
node sampling(44).
are manifest within 3 months.
Ethnyloestrodial (100-300mg daily alleviate the Early- Stage Endometrial Carcinoma
symptoms of menopause. The role of adjuvant radiation therapy following
surgery in patients with early stage early endometrial
Ureter Hydro-nephrosis
cancer a subject of debate.
Following pelvic irradiatio'n, radiation induced pelvic
fibrosis could lead to hydro-nephrosis. However, The indications for adjuvant radiation therapy
progression of primary cervical cancer may be the depend on prognostic factor{45);
CAUSE, o Depth of myometrial invasion
. Tumorgrade
Vagina o Histologicalsubtype
Occlusive vaginal Stenosis (41): this may occur in o lnvolvement of the cervix
sexually inactive women and may make assessment . Lymphovascular sPace invasion
of primary site difficult. Dilators should be provided . Tumor extension (lymph node involvement,
for all patients. extra uterine i nvolvement)
. Age of patient
Skin Subcutaneous Fibrosis ln general, adjuvant radiation is recommended for
More common with Tele cobalt therapy in large size patients with
patients. . deep myometrial invasion
Multiple field arrangements are recommended. . age >60Years
. grade 2 or 3 disease
o lymPhovascularinvasion.
SurvivalRates . serous or clear cell histology
5 year disease free survival (DFS) in patients with
s28
--------:---
Low risk not requiring radiotherapy radiotherapy and adjuvant platinum and taxane
Grade 1-2 tun,crs combinations (52).
Less than 50% myometrial invasion, orforthose with leiomyosarcoma - Doxoru bici n
only Taxane pl us gemcitabi nd53).
Those with a single riskfacto(46). Endometrial stromal sarcomas responds
lntermediate risk tohormonal therap(54).
Patients with at least two of the above factors,
Vaginal brachytherapy alone is preferable to EBRT Radiation Dose and Technique
providing excellent vaginal control without impacting The operative pelvic radiation dose is 45Gy in 25
on quality of lifd47) for intermediate risk patients. fractions, com bi ned with i ntravagi na I brachythera py
High risk or 50.4Gy when pelvic radiation is used alond44).
However for patients with positive pelvic nodes and
other high risk, pelvic radiation therapy is preferred. The role combination external beam and
brachytherapy is currently limited to cases with
cervical involvement and still a matter of debatd55).
Advanced Endometrial Carcinoma The radiation fields used are similar to those
Stage lll - Complete surgical resection of all visible described for cancer of the cervix.
disease, followed by postoperative EBRT andlor
chemotherapy (eight cycles of doxorubicin and The side effects here are similar to those seen in the
a cisplati n, or carboplati n and paclitaxelX43). management of cervical cancer.
Stage lV-Patients with intraperitoneal spread may VULVAR CANCER

benefit from cytoreductive surgery only if there is no Vulvar cancer is rare but an important disease entity
residual tumor. Adjuvant platinum-based because management includes consideration for
chemotherapy is recommended(48). quality of life issues pertaining to sexuality.
Complications of managing this disease could result
For unresectable disease, chemotherapy or hormonal in debilitating functional deformities and high
i
L
therapy for low grade or hormone receptor positive is patient d issatisfaction
I
I recommended. The combinations of doxorubicin,
a
I cisplatin, and paclitaxel (more toxic) or carboplatin The work up should include examination under
I
I and paclitaxel or doxorubicin and cisplatin have been anesthesia, pap smear of the cervix and colposcopy
i shown to be mosteffectivd49). of the cervix and vagina to rule out synchronous
r
I
I
lesions, cystoscopy and prostoscopy when
Hormonal agents include medroxyprogesterone, indicated ( history and examination findings), CT
t'
i megestrol acetate a nd occasiona I ly Tamoxifen( 50). scan of the pelvis as well as hematological, renal and
I
Serous and Clear Cell Histology- this variant tends liver function tes(44).
:
to have a high propensity to spread to the upper
f
abdomen and warrants the inclusion of Staging is by FIGO oTAJCC criteria.
chemotherapy in the treatment plan(43).
lnvasive Vulvar Cancer
It is highly recommended that even with early stage The management of patients with cancer of the vulva
disease, these groups of patients are managed with should be individualized.
intravaginal radiotherapy with concurrent carboplatin
followed by adjuvant platinum and taxane Currently, emphasis is placed on performing the
combinations. most conservative operation consistent with cure of
the diseasd56). lt is very important to consider the
ENDOMETRlAL SARCOMA most appropriate management for the primary lesion
i
Pelvic radiotherapy only controls local disease and the inguinal lymph nodes in the context of
without an impact on survival(51 ). optimizing the overall management of the patient,
l wh i le m i n i m izi ng treatment-related morbid it(57).
Malignant mixed mullerian tumours (MMMT)
limited to the uterus are managed with pelvic Surgical Management
529
En bloc radical vulvectomy with bilateral is less than 1%, thus

negative ipsilateral nodes
inguinofemoral and or pelvic lymphadenectomy has unilateral groin dissection is considered
for several decades been the standard of care. adequatd44).
However, the current management of vulvar caneef
continues to evolve with radiation therapy playing a However, a bilateral groin dissection must be
less significant role in early disease but an important performed for patients with midline tumors, large
role in locally advanced disease with impressive cure lateral tumors and patients with positive ipsilateral
rates(56). groin node{60).
Sentlnel node biopsy may obviate the need for groin Sentinel node biopsy results from breast cancer and
node dissection in node negative disease with results melanoma have been translated into the
translated from trials in breast cancer and management of early stage vulva cancer to obviate
melanomd5S). the need forgroin node dissection.
I ndications for adjuvant rad iotherapy i ncl ude
I ndications for adjuvant radiotherapy incl udd59) . Clinically or pathologically positive lymph
. Clinically or pathologically positive lymph nodes
nodes o Extracapsularextension
o Extracapsularextension . Surgical margins of less than 8mm
. Surgical margins of less than 8mm o LVSI
. Lympho-vascularinvasion.
LOCALY ADVANCED VU LVAR CANCER
Managementof groin lymph nodes- Multidisciplinary treatment approach is
Patients with FIGO stage 1B orstage Il lesionsshould recommended for locally advanced disease. As
have an ipsilateral groin node (inguinofemoral) stated earlier, the groin nodes and primary disease
dissection(60). Routine bilateral groin dissection is should be considered independently for surgically
unnecessary because in patients with small resectable disease via a three incision approach(61).
lateralized lesions and negative ipsilateral nodes, Many patient will however require adjuvant
contralateral node involvement is lessthan 1%,(44). radiotherapy or chemo radiation with cisplatin(59).
Bilateral groin dissection is indicated for midline
tumors, large lateral tumors and positive ipsilateral Management of the primary tumor
groin node{60). Neoadjuvant chemo radiation with cisplatin +/- 5-
fluorouracil, to downstage the tumor followed by
Microinvasive vulvai cancer (Stage !A) surgery can preserve the anall urethral sphincter in
management is by radical local excision without advanced vu lvar cance(62).
groin dissection to minimize the psychosexual
morbidity associated with more extensive Management of groin lymph nodes. - lt is necessary
surgerie{60). to determine the status of the groin nodes prior to
i nitiating any treatment i ntervention.
Early Vulvar Cancer (FIGO stage 1B or stage ll) Unresectable ulcerated or fixed groin nodes should
Management of the primary lesion- treated with primary radiation, with or without
A radical local excision rather than radical chemotherap(63). Additional surgery is of benefit
vulvectomy is the surgical option of choice. for who respond poorly to the chemo
radiotherap(64).
Managementof groin lymph nodes-
Patients with FIGO stage 1 B or stage ll lesions should RADIATION DOSE/ TECHN IQU E
have at least an ipsilateral groin node (inguino- The radiation target region should include the
femoral) dissection(60). Routine bilateral groin inguinofemoral, external iliac, and internal iliac
dissection is not necessary because studies have lymph nodes. lnclusion of the primary tumor is not
shown that the incidence of positive contralateral recom me nd ed fol lowi n g co m p ete loca I excis io r,{,4
I
q .
nodes in patients with small lateralized lesions and Three-dimensional planning using high-quality CT
530
r
+
I
i Principles of Radiotherapy and Chemotherapy in Gynaecology Cancers
i
il
l scan images or preferably intensity modulated omentectomy, and maximal attempt at optimal
i radiotherapy i: recommended for treatment using a cytoreduction (no residual disease) followed by
{
f
It
mixture of low energy electrons and high energy adjuvant chemotherapy in medically fit
photons to improve dose homogeneity(65). Two
l\- dimensional treatment techniques is still being
patient{68),(69).
I
rl
I( used in less developed countries with difficulty in lnterval debulking
attaining homogenous dose distribu-tibn and lnterval debulking surgery can be considered for a
i maintaining a low dose to the femoral heads. selected group of patients with cytologically proven
I
Stage lllC and lV disease(68). Three cycles of
; neoadjuvant chemotherapy, followed by interval
1
The radiation treatment techniques aims at reducing
the acute radiation effects in skin and soft tissue, surgical cytoreduction and additional cisplatin based
I
whiles maximizing dose to the tumor bed. This can be adjuvant chemotherapy to complete 6 cycles.
i very complex and requires using multiple beam
I energies and fields using a shrinking field Following suboptimal cytoreductive surgery, an
!
techniqud65). interval debulking surgery can be considered after

2-3 cycles of systemic chemotherap(70).
I
Adjuvant radiotherapy dose
1 . Lym ph node negative with poor prognostic featu res Chemotherapy
)
45- 50 Gy in 1.8-2.0 Gyfractions is adequatd66). Chemotherapy plays a very important role in the
l-.
2. M u lti pl e positive nodes or extraca psu la r extension, adjuvant management of ovarian cancers.
54- 60 Gy(44). lndications are for stage one grade 2 all 1C, clear
3. Gross residual disease and serous cell types and all other stage{71).
60-7OGyG4).
I
I
The response and survival rates are highly correlated
SIDE EFFECTOFTHERAPY to residual disease aftersurgery.
Prevention and management of sequelae from the
radiation therapy is a major factor affecting patient The gold standard chemotherapy protocol is a
com plia nce to treatment, resu lting in overa ll combination of platinum and paclitaxel in optimally
l
prolonged treatment times. Common side effects surgically debulked patients(71). However, the
I include grade three wet desquamations, neutropenia, choice of chemotherapy depends on many factors
perineal pain and skin infections. Management such as age, stage, performance status, availability
includes necessary treatment breaks, pain and cost.
't
management, improved nourishment, and early
recognition of symptoms and rehydration. Chronic Chemotherapy for early stage cancer -
side effects include soft tissue necrosis, stiff hip joints Stage lA and Stage lB grade 1-2 epithelial cancers of
and f racture of the femoral head/neck. the ovary have very good prognosis and t derive
little benefitfrom adjuvant chemotherap$7 Z.
OVARIAN CANCER
Surgery is the primary treatment for ovarian cancer. Some authors recommend that Higher-grade tumors
The prognosis of epithelial ovarian is dependent and Stage lC disease should receive, adjuvant
onstage at diagnosis, histological subtype, grade and platinum-based chemotherapy even though debated
most importantly the a size of residual disease OZ,
fol lowi ng cytored uctive su rger(67).
All patients with siage lldisease should receive
Staging adjuvant chemotherapy with 3-6 cycles of cisplatin/
A staging laparotomy is an essential part of early paclitaxel as for early stage 1 and 6 for all others(73).
a
management.
Chemotherapy for advanced stage ovarian cancer
Cytoreductive surgery for advanced stage disease Patients who have had primary cytoreduction must
Primary laparotomy with total abdominal receive adjuvant 6 cycles of platinum-based
I combination chemotherapy, with a platinum
hysterectomy, bilateral salpingo-oophorectomy,
531
(carboplatin or cisplatin) and a taxane (paclitaxel or

docetaxel) chemotherapy(7 4). The role of
maintenance chemotherapy is currently under Low risk disease
investigation. Maintenance chemotherapy did not Actinomycin D has higher response rates compared
make statistical difference but a trend to improve to methotrexaldT9).
DFS(75),
High-risk disease
Second LineTherapy Etoposide, Methotrexate, Actinomycin D,
Fifty percent of ovarian cancer patients will relapse Cyclophosphomide, Vi ncristi ne EMACOXT g)
(
within 5 yrs. even after achieving complete response.

Treatment relapse at least 6 months after the last Recurrent disease
Second line chemotherapy agents include with
chemotherapy is considered platinum sensitive and
Taxane, vincristine, ifosfamide, platinums,
allows for re-challenge with a platinum agent,
etoposiddT9).
otherwise it is considered platinum resistant and
non-platinum combinations should be explored(76).
Radiotherapy
The choice is influenced by performance status of the
patient, prior toxicity patterns, bulk of disease as well
Radiotherapy is recommended for managing
palliative symptoms which include bleeding, brain
as comorbid factors.
metastases, hemoptysis or pain(35).
Recommended salvage chemotherapy drugs;

Side effect profile for Common Chemotherapy used
cisplatin or carboplatin, docetaxel, liposomal i n Gynecological ca ncer-
doxorubicin, topotecan and gemcitabine. Others are Cisplatin / carboplatin-
oral etoposide, vinorelbine, oxaliplatin, altretamine, Hydration and urine output, Neuropathy,
capecitabi ne, Ad riamyci n (76). Nausea& Vomiting, cytopenia, otoxicity,
hypomagnesia, low potassium, alopecia
TARGETEDTHERAPY
Cyclophosphomide - hydration, Nausea
&Vomitng, Hematuria, cytopenia,
Targeted agents used in the management of
encephalopathy
advanced or recurrent ovarian cancers include
Taxanes- myalgia, malaise, anaphylaxis,
. VEGF - BEVACICUMAB
. EGRF - ERLOTINIB
neuropathy, alopecia, deranged liver enzymes
. CA125-ORGOVOMAB
Adriamycin- Nausea & Vomiting, alopecia,
. EGRF/HER2 - PERTUZUMAB
. DNA- YONDELIS
These agents are very expensive and not readily Summary of side effect profile for pelvic radiotherapy
available in the developing countries
ACU'T ctt&dtffi
TROPHOBLASTIC TUMORS . Malasorbtlon
" Fatigue
, &haemla ' Borme} Obstrurtion
Choriocarcinoma . Strktures
' Diahorrsa
.
An international scoring system endorsed by FIGO ' l{ausEa & Vomltlfig Fistuke
should be used to stratify patients into risk . Dysllrla, Hematurh ' Thinins Qf Skin
. . C€rvical He{rark
group{77).Choices of chemotherapy protocols are Hemorrhoids
' Prordtli . {ironic Proctitis
dependent on risk factors, tolerance and toxicity .
. V:ginitk Prematur€ Menopaure
profile. Baseline tumor markers - bHCG, should be . SklF DesquanEthn ' lnfertility
obtained and repeated after each cycle of
chemotherapy. Treatments should be continued more
2 cycles beyond time of achieving undetectable
levels. Treatment breaks and dose reductions should
be avoided at all cost and may require granulocyte
cell stimu lating factor su ppor(78).
s32
t
I
I
I
f
f
I DISCUSSION OF MANAGEMENT versus concomitant radiotherapy and chemotherapy
t CONTROVERS!ES in FIGO stage l82, llA > 4cm or llB cervical cancer is
ongoing and hope will answer burning questions
r- Cervical cancer
Surserv versus radiotherapy as
,., i .j.
inl*ff*l*ffi
.
for
about the role of neoadjuvant chemotherapy in
rI cervical cancer especially in places where
t
early stage disease. rad iotherapy faci lities are available.
( The recurrence rate for locally advartced: dervical
l
t cancer (stage lB2 to IVA) is high and negatively Adiuvant Chemotherapv for cervical Cancer
( affects survival. Level 1 evidence from randomized Standard treatment for patients with locally
I trials comparing radical hysterectomy to definitive advanced stage cervical cancer is concurrent
r radiotherapy for early stage cervical cancer showed cisplatin based chemoradiation therapy. Limited
I equivalence in outcomes. Newton et al Studies have data from only two retrospective trials did not find
i reported equivalent survival and pelvic recurrence enough evidence to support the use of adjuvant
I rates in Stage lB and llA cervical cancer patients chemotherapy after concurrent
I treated with either radical hysterectomy or definitive chemoradiatio(84)except in the presence of pelvic
t radiation alone(17),(80). Persistent disease and and para-aortic lymph node involvemen(8S). lts use
recurrence rates are exacerbated when patients with is cu rrently therefore experi mental.
advanced disease undergo upfront surgery,
(
r warranting adjuvant radiotherapy following Role of adjuvant radiotherapy for poor prognostic
r hysterectomy. cervical cancer following TAH/BSO with poor
I prosnostic features
a
(- Neoadiuvant chemotherapv for advanced cervical Major lndications for adjuvant therapy following
I
I cancer radical hysterectomy are positive or close margins,

Neoadjuvant chemotherapy followed by surgery does
1
microscopic parametrial invasion and lymph node

{
l
not improve survival compared to surgery alone. A metastasis. Other indications include tumor >4cm,
r randomized phase lll trial by Gynecologic Oncology deep stromal invasion or lymphovascular invasion.
t' Group(GOG) failed to demonstrate a survival benefit ln the GOG 92 trial(86), post operative pelvic
J
in patients who had neoadjuvant chemotherapy prior irradiation compared to observation after surgery,
I to radical surgery compared to those who had surgery showed there was a relative risk reduction of
I alone for bulky stage l82 diseasd8l). Howeversome recurrence following pelvic radiation by 46Y" and an
t other trials have noted advantages. Takashi et al approximately lO% trend towards improved overall
I
I published data fr.om China on neoadjuvant survival.
i' chemotherapy for locally advanced cervical cancer
i and noted that some advantages were reduction in Concurrent chemoradiation for cervical Cancer
I
{ risk factors of lymph node metastasis, vascular Green et al
demonstrated that stage lB2 to IVA
,, invasion , improvement in the radical cure rate, safety tumours treated with concurrent chemoradiation
:
and improvement in downstaging of tumours well as resulted in improved tumour control, overall survival
suppression of remote metastasi{82). A Cochrane (RR: 0.71; p.0001) and progression -free survival
analysis by Rydzewska et al on Neoadjuvant (RR:0.61; p< .0001) compared to radiotherapy
chemotherapy plus surgery versus surgery in early or alond3l). Significant benefit was recorded in early
locally advanced cervical cancer showed that both stage versus advanced cervical cancer patients (l
: overall and disease free survival were improved with and ll).
neoadjuvant chemotherap(83). This evidence was A meta analysis on five randomized trials on
based on few trials (six trials). Another meta- concurrent chemoradiation for cervical cancer by
analysis involving nine phase 3 trials also confirmed Kantardzic concluded that combined therapy for
the positive outcomes of neoadjuvant chemotherapy cervical cancer is safd87). An overall survival (OS)
fol lowed by surgery for stage 7Br-28. of 817", disease free survival (DFS) of 55.9%for 28
months median survival (MS) was observed in
t A randomized phase lll study (EORTC 55994), of patients with advanced disease and OS of 90%, DFS
neoadjuvant chemotherapy followed by surgery 78.8% observed in early disease patients.
533
Comprehensiv. Gynaecology in the Topics
Endometrial cancer and doxorubicin (19% vrs 8%) and a longer

The role of lymphadenectomv and irTrpact on progression-free survival (median 5.7 vrs 3.8
survival monthsX93).
Lymph node involvement is a significantlQ@t
of treatment outcome and survivat nq@$q A GOG 177 phase lll trial comparing doxorubicin and
d@1..@
patients with stage I and Occult stage lI cisplatin alone with doxorubicin, cisplatin plus
pelvic and 57" of para aortic lymph node paclitaxel, clearlyshowed an increased response rate
involvement in the same group. Over 30% Of prsnts of 57% over 34"/" in the triplet group. There were
with pelvic lymph node involvement invariably have improvements in Progression-free survival and
para- aortic disease. Controversies have arisen overallsurvival(94).
regarding the role of lymphadenectomy. There js no
benefit to pelvic lymphadenectomy in the AS-TEC tr.ial Role of Progesterone theraoy
in terms of overall survival and recurrence free Progesterone is a very important hormone in the
survival for low risk diseasdSS) . A review on the endometrium that opposes estrogen stimulated
Current evidence of the Role of pelvic and para-aortic growth. lnadequate progesterone levels lead to
lymphadenectomy in endometrial cancer by Giorgio unopposed estrogen function, which r',,ru1elu
et al states thatfrom a purely diagnostic perspective, results in endometrial hyperplasia or endometr
lymphadenectomy is important in identifying cancer (95). The use of hormonal therapy in
patients with extrauterine diseasd89) and improves advanced or endometrial cancer has been well
survival intermediate and high risk group{90). known for years. Agents that have been used include
megesterol acetate, medroxyprogesterone acetate
Whole pelvic radiotheraov versus whole pelvic and tamoxifen.
radiotherapy plus vaginal brachytherapv
Recommendations for vault brachytherapy alone as published on past, present
ln a trial by Carlson et al
adjuvant therapy is indicated in intermediate risk and future of hormonal therapy in recurrent
endometrial trial with less toxicity and improved endometrial cancel stated that even though not
quality of life compared to vault brachytherapy in curable, hormonal treatment is a suggested option
addition to whole pelvic irradiation(91). which provides good control of diseasd96). Patients
should however as a matter of importance be
Adjuvant pelvic radiotherapy and vaginal carefully selected and limited to advanced low-grade
brachytherapy is indicated for endometrial cancers disease or progesterone receptor positive disease.
that invade the cervical stroma and for stage lll
disease. Adam et al investigated the lmpact of a Choriocarcinoma
vaginal brachytherapy boost to pelvic radiation in Actinomvcin D versus methotrexate for early stage
stage lll Endometrial cancer. Most patients had disease
excellent pelvic and vaginal control(92).
According to the European Society of Medical
Oncology clinical practice guidelines for gestational
Role of adiuvant chemotherapv trophoblastic diseases published in September 2073
There are several randomized trials on the role of by Seckl et al, recommendation was that nearly all
adjuvant chemotherapy in advanced endometrial Iow-risk gestationa I trophoblastic neoplasia patients
cancer. Adjuvant chemotherapy is recommended in can be managed with single -agent chemotherapy
Stages lB, grade 3 and stage ll, grade 3 diseases as comprising of either methotrexate or Actinomycin
well as stage lll and lV endometrial cancer. ry.97).
Phase ll trials have demonstrated that anthracycline- Lurain et al published a study indicating
based chemotherapy like doxorubicin, taxanes methotrexate- failed low risk gestational
(paclitaxel) and platinum agents (Cisplatin and trophoblastic neoplasia and clearly showed the
carboplatin) are active in the management of superior efficacy of actinomycin D used as secondary
patients with advanced, persistent or recurrent treatmen(98). There was 7 5"/"' complete response
endometrial cancer. The GOG 107 trial showed rate and 100% cure with subsequent chemotherapy
doubling of the complete response rate with Cisplatin with or without surgery.
534
A randomized phase lll trial by Gynecologic Oncology with CA 125 after primary therapy of advanced
group on Dactinomycin and methotrexate in treating ovarian cancer and recommended that CA 125
patients with low-risk gestational tr-e$ohtastic monitoring after treatment will enable patients with
neoplasia to determine how well *ett",@ryorks recurrent disease to be diagnosed early and
co m pa red to dacti nomyci n concl uded-@f$fueekly appropriate interventions taken(105). On the other
dactinomycin had a superior complete fi$i6tr-3e rate hand, guidelines currently do not recommended
to weekly methotrexatd99). routine CAi25 monitoring as it is associated with
anxiety and emotional disorder for the care givers
Ovary and patients.(106)
lmpact of size of residuum on survival
Surgery is the initial treatment for advanced tumours Taxanes versus Cyclophosphamide/ Cisolatin
with adequate cytoreduction. Volume of residual versus Cyclophosphamide/ Adriamvcin/ Platinum
disease left behind after surgery is an important in the adiuvant setting
prognostic factor and significantly impacts survival. Results of two randomized European trials ICON 1
ln a study be Chi et al , removal of all macroscopic (lnternational collaborative Ovarian neoplasm trial)
disease was significantly associated with improved and ACTION (Adjuvant chemotherapy in Ovarian
survival, and was therefore the main objective of neoplasm trial) suggested that in high risk, early
E cytoreductive surger(100). Another study by Suk- stage ovarian cancer, adjuvant chemotherapy
t- Joon Chang et al on the role of aggressive surgical improves progression-free survival and overall
cytoreduction in advanced ovarian cancer, suggested survival.(107),(108). Overall survival was superior
that, if it is not possible to achieve near optimal for platinum-based therapy.
cytoreduction, radical procedures should be avoided
except for palliative reasons(i01). Aggressive Two phaselll randomized trials GOG lll and OV 10
surgical cytoreduction with no residual disease compared a Cisplatin/ Paclitaxel combination to a
provides the utmost opportunity for improved Cisplatin and CyclophosPhamide
i survival in advanced ovarian cancer. regimen.(109),(1 10)The paclitaxel containing
t
i chemotherapy arm experienced a statistically
i Neoadiuvant chemotherapy versus upfront surgery significant response rale (73% vrs 60%; p<0.01),
i
II
in advanced ca Ovarv median Progression- free survival (18 vrs 13
t
I Many of patients presenting in Africa are often months; p< 0.001) and median overallsurvival (38
present with inoperable, bulky advanced stage vrs24 months;p< 0.001)
t
I ovarian cancer. Upfront surgery is likely to end up
i
f
r.-
with large residual disease, limiting their chance of Other trials have compared a non-paclitaxel
I
!'
improved survival. Many of these patients we require platinum-based regimen and combinations of
diagnosis prior to chemotherap( 1 02). cisplatin, doxorubicin and cyclophosphamide.
i
I
;
An EORTC trial 55971 by Vergote et al showed that GOG 158 compared a Carboplatin/pacliatxel
neoadjuvant chemotherapy with three cycles of combination and a Cisplatin/paclitaxel combination.
taxane based chemotherapy followed by interval The PFS and OS were equivalent. The carboplatin-
debulking resulted in equivalent survival as primary based regimen however had a more favorable
debulking surger(103). The complications were toxicity profile hence, the preferred choicd111).
noted to be fewer in the neoadjuvant chemotherapy Vulva
group. Another significant UK-based trial CHORUS
: by Sean Kehoe et al demonstrated that survival after
Chemoradiation versus surgerv and adiuvant
primary chemotherapy is non-inferior to primary chemotherapyfor locally advanced cancer
rl Concurrent chemoradiation is considered the
surgery.(104)
standard of care for locally advanced cancer of the
Role of CA 125 foi follow-up cervix. Bellati et al 2005,.looked at single agent
h
I CA 125 antigen is a high molecular weight cisplatin after radical surgery for advanced vulvar
glycoprotein, which is expressed by most epithelial cancer and 3 year PFS of 7 !"/" and Overall survival of
ovarian cancers. Pignata et al
looked at follow-up 86% was reported.(112)
535
Comprehensiv,' Gynaecology in the Topics
Hans et al 2000 compared chemoradiation or Down-staging of locally advanced disease

radiation alone as primary treatment or in the Chemoradiation has been shown to decrease the
adjuvant setting. The results showed that survival need for exenterative surgery(115). A phase ll study
rates were higher in the chemoradiation arm but not of 73 patients who had unresectable vulvar cancer
statistically significant(1 13). Comparing received concurrent cisplatin and 5FU
chemoradiation in the primary or neoadjuvant Setting chemotherapy, 97% of the patients achieved
and primary surgery, there is no difference in overall adequate cytoreduction and were amenable to
su rvival or treatment-related event{ 1 1 4). surgery.
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h ttp : / /www. n c b i . n I m. n i h. gov / p u b m ed I 1 062 37 0 http I /www. redj ou rn a l. org/a rti c I e I 503 60 30 1 60
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111. Cristea M, Han E, Salmon L, Morgan RJ. L14. Shylasree IS, Bryant A, Howells RE.
Practical considerations in ovarian cancer Chemoradiation for advanced primary vulval
chemotherapy. Ther Adv Med Oncol ilnternetl. cancer. Cochrane database Syst Rev.
20 1 0; 2(3) : 1 7 5-87. Ava i la ble f rom : 2011;(4):CD003752.
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. f cgi ? a rt i d : 3 1 2 60 1 6 &too I : p m ce ntrez&re n d e r for advanced vulvar cancer: a phase ll study o;
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Muzii L, Plotti E et al. Single agent cisplatin 2017 Jan 131;42(1):79-85. Available from:
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542
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cr.,APrER
44
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t f--
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I
I
Premalignant Lesions of the
Female Genital Tract
i
f
T. O. Konney, E. K. Srofenyoh, EY Kwawukume
-*
{ INTRODUCTION Papillomavirus (HPV) genome is functionally divided
into 3 regions''' : the Long Control region (LCR), the
Pre-malignant lesions are precursor lesions, which Early Region (ll,E2, E3, E4, E5, E6, E7, and E8)
I have a significant potential to become an invasive and Late Region (Li and L2) genes. The early genes
fl malignant lesion. Portions of the female genital tract are responsible for DNA replication, transcriptional
of importance as far as pre-malignant lesions are regulation and transformation whilst the late genes
concerned are the vulva, the vagina, the cervix and control the formation of the capsid coat. Early gene
the endometrium. Most of these pre-malignant products, E6 and E7, encode for the major
lesions are usually asymptomatic (especially those of transforming proteins, which are capable of inducing
the vagina and the cervix) and are of clinical cell proliferation and immortalization principally by
importance only in as much as they may progress to binding to the tumour suppressor gene products p53
invasive malignancies. On the other hand and pRBou.
premalignant lesions of the vulva may produce
significant symptoms including burning sensation, HPVs are epitheliotrophic viruses and are
itching and hypopigmented areas, while endometrial responsible for several mucous and skin lesions.
hyperplasia may present as irregular bleeding per lnfection is initiated when the virus gains entry into
vaginam. Since Human Papillomavirus infection is the basal cells of the epithelium. lnitially the viral
implicated in some of these pre-malignant lesions the particles remain dormant in the cells but they may
next few paragraphs will be spent to describe this later become integrated into the host genome. The
virus before proceeding with the discussions on the infection involves co-ordinated expression of early
pre-mal ignant lesions. viral proteins in the lower epithelial layers with a
switch to late gene expression as viral replication
A. HUMAN PAPILLOMAVIRUS INFECTION OFTHE takes place leading to the various histological
FEMALE GENITAL TRACT manifestations of HPV infections which include
koilocytosis (in which the host cellular nucleus is
The Papillomaviruses are members of a large family
displaced to the side with a hollow appearance of the
of viruses known as Papovaviridae'. They are small cytoplasm), perinuclear cavitation, nuclear
double-stranded DNA viruses, approximately 55nm enlargement, multinucleation, dyskeratosis and, in
in diameter consisting of a non-enveloped some cases squamous intraepithel ial neoplasia.
icosahedral outer protein coat, which surround a
I
circular genome of double stranded DNA with The majority of the infective processes are of short
approximately 8000 base pairs. The Human duration. By 72 and 24 months, 70% and 97% of
543
women respectively were no longer infected, having the cervical epithelium gets infected with HPV the
been cleared by the host immune mechanismsu. The host immune system tackles it by cancer immune
remaining persists either in the latent stage cr go on editing", resulting in elimination, equilibrium, or
to develop lesions. Risk factors for persis*nt |tPV escape phases.
infection and neoplastic change include ffi@
dysplastic lesions, oncogenic HPV subtyps, Classification
immunosuppression, cigarette smoking, older age To date over 100 types of HPVs have been identified
with further isolates awaiting complete
characterization. The types are numbered according
Mode of Transmission to their discovery and a new type is identified if it has
The Human papillomavirus infection is a sexually at least 10% of the gene sequence at E6, E7 and L1
transmitted infection and is predominantly different from any previously known.
transmitted by micro trauma to the genital mucosa
that occurs as part of normal sexual behavior. Unlike HPV subtypes and Association with Mucosal
most other sexually transmitted infections which are Neoplasia
transmitted by body fluids, HPVs are transmitted by Low Risk
direct genital contact commonly by penetration. 6, 11: cause papillomas of the upper airwa
Transmission occurs from male to female, female to and external genital condyloma
male, male-to-male, and female-to-female. PCR 42, 43,44: closely related in their nucleotide
sequenceto 6, 11
studies suggest all coital contacts are infected with
one exposure. The incubation period is long, and can
lntermediate Risk
be difficult to accurately assess because of sub- 31, 33, 35, 51, 52: associated with dysplasia
clinical infections and the effect of host immunity.
While condoms are thought to be slightly protective High Risk
for cervical infections by HPV they are not protective A. 16: Present in 50% of high-grade squamous
against transmission from contact between external intraepithelial lesions of the cervix and invasive
genital skins. Human papillomavirus can also be CdnC€r; present in 75% lo 40% of low-grade lesions
transmitted vertically during childbirth. Juvenile in the cervix; present in 85% of high-grade lesions in
laryngeal papillomatosis is a rare sequellum of other areas of the anogenital tract; present in 40% of
vaginal delivery. Other potential modes of subclinical lesions of the vulva and 7O% of
transmission have not been well documented. Non reca lcitra nt condyloma acum inatum.
sexual transmission by fomites can also occur by
prolonged exposure to shared contaminated B. 18: Very rarely found in low-grade lesions.
clothingt'. Co-factors for transmission, persistence, lnvolved in faster transit time to invasive cancer in
and neoplastic change in HPV infections include squamous and glandular lesions and closely linked to
tobacco use immunosuppression and prolonged use glandular dysplasia and adenocarcinoma of the
of ora I contraceptives'o'". cervix.
Viral persistence c. 45, 58,35, 59, 56,39,69, 73,92

The prevalence of HPV infection peaks at the age of
78-28 years and declines thereafter". Approximately Clinical Manifestations of HPV lnfection
90% of lesions regress spontaneously within 12.36 Benign Lesions
months". Persistent infections and premaiignant A vulvar condyloma can show a wide range of
appearances, Small raised crusted lesions can
Iesions are established, typically within 5-1Oyrs.
appear on the vulvar or perianal region. Bigger
Several studies suggest that majority of women clear
condyloma can appear confluent, rising above the
the HPV infection probably through a competent
skin level. ln immuno-compromised patients, the
immune system. Evidence for increasedrtumour
condyloma can extend up to the mons and back to
incidence in T-celt immunosuppressed patients
the buttocks. Small popular changes can either be
suggests that CD4 andlor CD8 T-cell responses also
play a vital role in controlling HPV infection. When
completely asymptomatic or can sometimes be
544
Premalignant Lesions of the Female Genital Tract
attributed to HPV infection. These visual changes can HPV DNA detection methods
either be completely asymptomatic or.can be Non-amplification methods eg, lSH, Southern
associated with vulvar pruritis ar*d bU*ning. methods
Exophytic condyloma can also ocqlr Hybrid Capture systems (HCS) 1st and 2nd
pattern in the vagina. Condyloma on generation
the cervix. The majority of cervicd{ are PCR
f at a lthou gh ra ised eu koplakic lesiofis cdf+&:t6en.
I I
:
B. VULVAR INTRAEPITHELIAL NEOPLASIA _
Premalignant Lesions VIN ('DYSPLASIA')
lntraepithelial neoplasia of the lower genital tract can
be categorized by site as vulvar intraeplthelial VIN represents a spectrum of neoplastic changes in
neoplasia (VlN), vaginal intraepithelial n@{asia the vulvar epithelium that range from mild cellular
(VAIN) and cervical intraepithelial neoplasia (ClN). dysplasia to the most severe cellular changes that fall
There is now no doubt that persistent HPV infection is short of invasive carcinoma. lt is a precursor lesion of
a pivotal step in the development of premalignant and vulvar squamous cel I carcinoma.
malignant lesions of the cervix especially, and also of
Epidemiology
the some pre-malignant and malignant lesions of the
The lesion occurs in elderly women, but is becoming
vagina and the vulva. Indeed, the lnternational
increasingly common in young women between 20
Agency for Research on Cancer (IARC) has recently
: and 35 years old. Most cases (about 9OY") are
classified high risk types 16 and 18 as definite
associated with HPV especially types 16, 18 and
carcinogens in humans'5, with HFV type 16
other high-risktypes.
recognized as the most common high risk HPV type in
most countries'u. The contribution of risk factors such Clinical presentation and Evaluation
as multiple sexual partners, early age at first Patients with VIN are often symptomatic and
intercourse, and a sexual consort with multiple complain of vulva itching, irritation and burning
partners, should be viewed as an association with usually for months. As often as is the case such a
sexual transmission of H PV"'". patient may have been treated for ClN, ClS, invasive
cervical cancer or VAIN, a manifestation of the so-
Malignant lesions
called field carcinogenesis phenomenon. lt has been
lnvasive cancers of the lower genital tract, which
reported that up lo 44% of patients with VIN had an
include anal, vulvar, vaginal, and cervical cancers,
associated pre-invasive or invasive cancer of the
have all been associated with human papillomavirus
female genital tract".
infections.
The usual presenting symptoms are also the
Diagnosis
symptoms of non-neoplastic vulvar diseases such as
Diagnosis of H PV infection and its clinical
vulvo-vaginal infections and vulvar dystrophies and
manifestations can be made by clinical examination,
therefore a clinician faced with such condition must
HPV DNA detection methods, cytology, andlor
take advantage to examine the whole vulvar in good
with biopsy. Most basic and clinical
colposcopy
light with the view of ruling any Vl N lesions.
investigations use one or more of three nucleic acid-
based tests to detect and type HPV. These tests
VIN presents as a white, red, leukoplakic, velvety,
include non-amplification methods such as in situ
erythematous, u lcerated, or hyperpigmented
hybridization (lSH) and southern blot methods,
indistinct macular lesion or well-defined raised
hybrid capture systems (HCS), and polymerase chain plaque, which may be single or multiple. lt is
reaction (PCR). The PCR test is the most sensitive
frequently multifocal with associated lesions in the
and enables identification of HPV subtypes but they
cervix (more often) or the vagina. Most lesions occur
are very expensive. Currently the second generation
on the labia minora and extensive lesions may
hybrid capture system (hybrid capture Il) assay is involve the labia majora. Up to 40% of the time,
ir used commercially for clinical HPV testing with perianal involvement is noted'o.
sensitivity and specificity that approaches PCR.
545
As part of the evaluation, obviously abnormal leHons VIN 3: Severe, carcinoma-in-situ; dysplastic cells
must be biopsied using Keyes dermal panch. For extend into the upper third of the epithelium.
equivocal lesions, acetic acid may be:
'for Carcinoma-in-situ may be used when dysplastic cells
approximately 5 min: any acetowhite.:5ffii6gg*n occupy the full thickness of the epithelium and the
requires biopsy. The evaluation of the:ifit@..,& underlyingstroma has not been invaded.
includes Pap smear of the cervix or the vdffiE fid Based on their morphologic features, VIN 3 lesions
colposcopy (using 3-5% acetic acid) of the.-vutva, are subdivided into three types: warty
vagina, and cervix and colposcopical ffiiected (condylomatous), basaloid (undifferentiated) and
biopsies of abnormal sites. Colposcopyof ftevuffais differentiated (sim plex).
difficult because the characteristic changes in
vascular appearance and tissue patterns seen in the The warty type of VIN 3 is characterized by
cervix are absent. lts usefulness is limitedto being a undulating or spiked surface; large cell with nuclear
magnifying system that allows discrete lesions to be
pleomorphysm; numerous mitosis, surface
seen and biopsied. keratinocytes with koilocytosis, binucleation and
multinucleation.
Histology
Both architectural and cytologic abnormalities are The basaloid type of VIN has a relatively flat surface
present. The normal progression of cell maturation and is composed of atypical immature parabasal
within the vulvar squamous epithelium from basal type cells with numerous mitotic figures. Koilocytes
layer to surface is lost (loss of polarity). Cytologic are seen less frequently.
abnormalities are in the form of dysplastic cells with
The differentiated type is characterized by presence
nuclear hyperchromasia and showing variation in
shape and size (cellular pleomorphism). Some may
of basal or parabasal cells withincreased
eosinophilic cytoplasm, large nuclei and prominent
have appearances of undifferentiated, basaloid cells,
while others may show evidence of single cell nucleoli. The superficial layer shows normal
maturation and keratin pearls may be present.
keratinization (dyskeratosis). There is an increase in
the number of mitotic figures with mitosis present
The warty and basaloid types of lesion are found in
above the basal layer. Abnormal mitoses may also be
HPV associated cancers of younger women; but
seen. Although the lesion is associated with HPV
women with warty lesion are likely to be younger,
i nfection koi locytes are rarely present.
more frequently demonstrate koilocytosis and are
more likely to be HPV-positive compared with those
Grading
The number and distribution of dysplastic cells vary with the basaloid lesions". The differentiated type of
considerably within the thickness of the squamous VIN is often found adjacent to the typical keratinizing
epithelium reflecting the varying severity of the squamous cell carcinoma in older women. This
condition. A conventional way to grade the severity of
grading system is being changed to unify the
VIN has therefore been developed. This is based on nomenclature of HPV-associated squamous lesions
the proportion of the total thickness of the epithelium of the lower genital tract. The ISSVD recommends
replaced by dysplastic cells and is done in thirds of the terms low-grade squamous intraepithelial lesion
the total th ickness of the epithel i um i nvolved. of the vulva (vulvar LSIL) and high-grade squamous
intraepithelial lesion of the vulva (vulvar HSIL) for
VIN 1 : M ild; dysplastic cells are confined to the lower histopathologic diagnoses of productive HPV
third of the epithelium. infections, which includes external genital warts and
preca ncer, respectively.
VIN 2: Moderate; dysplastic cells occupy up to the
lowertwothirds of the epithelium
545
t
i
I
( Premalignant Lesions of the Female GenitalTract
I
I
I
f Table I
I 2015 lnternational Society for the rydf,of Vulvovaginal Disease Terminology of Vulvar Squamous
Y
I
I ntraepithelial Lesions and 2004 Termi@t
t
r 2015 Terminology 5 ':r: ,-,::.,,::'*; 2OO4Terminolosv
il
Low-grade sq ua mous ntraepffi6T,if

{
* i the Condyloma, HPV effect
( Vulva (vulvar LSIL, flat condHtffi, €r't#y effect)
T
I
i H gh -g ra d e sq u a m o u s i ntraeliitlie$fif tE€ion,of th e vu va
i I Usual type VIN (subdivided):
(vulvar HSIL, VIN usual type) a VlN, warty type
iI b VlN, basaloid type
{ c. VIN mixed (warty or basaloid) type
I Differentiated tvpe Vl N Differentiated tvoe VIN
r
I
i Clinical behavior Generally the treatment of choice is wide local

t The lesion may regress spontaneously; recur after excision and if only intraepithelial neoplasia is
local excision, or progress to invasive squamous cell present it is curative in75% of cases'4. Treatment is
{ carcinoma if untreated (10% of cases). The risk of recommended for all women with vulvar HSIL (VlN
progression to invasive carcinoma increases with
I
usual type). Because of the potential for occult
age, in immunosuppressed women, women who invasion, wide local excision should be performed if
I
r smoke and those who have raised lesions with cancer is suspected, even if biopsies show vulvar
i rregu la r su rface patterns. HSIL. When occult invasion is not a concern, vulvar
r
1 HSIL (VlN usual type) can be treated with excision,
I
There is a controversy regarding whether all invasive laser ablation, or topical lmiquimod.
squamous cell cancers begin with an in-situ phase.
)
Whilst most invasive cancers are unilateral, well- The excision should include gross margins of 0.5-1
circumscribed lesions, are not often associated with cm around tissue with visible disease, but may be
HPV, and arise in older women; VIN tends to be altered to avoid injury to the clitoris, urethra, anus, or
multifocal, is often associated with HPV and arises in other critical structures. Women with lesions in
younger women'o. lndeed there may be two types of critical areas should be referred to a specialist to
vulva cancer, HPV associated and non-HPV avoid impaired psycho-sexual function. Women with
+
f associated". The HPV associated cancers tend to be clear margins in the excised tissue specimens have a
associated with VIN and constitute less than one lower, although still significant, risk of recurrence
I third of vulvar carcinomas. Vulvar carcinoma has no compared with women with involved margins'u.
single precursor lesion and can arise from normal However in cases of extensive or multiple lesions one
: squamous epithelium, lichen sclerosus, squamous of various types of vulvectomy as may be found
hyperplasia or in VlN". adequate may be applied. Skinning vulvectomy was
introduced to avoid the cosmetic drawback of simple
Management vulvectomy and also to enhance sexual function. An
Since current techniques do not allow precise important advantage of the excision therapies (wide
prediction of which lesions of VIN will progress to
local excision, skinning vulvectomy and simple
invasive disease it is advisable to eradicate lesions
vulvectomy) is the fact that tissues can be obtained
:
with VIN especially VIN ll and lll. The various for histology io confirm completeness of the excision
treatments modalities are outlined below
I
and rule out any unsuspected invasion.
Wide localexcision
Skinning vulvectomy and split-thickness skin ln one series," (18.8%) unsuspected cases of
graft
invasion were found out of 69 patients who were
Simple vulvectomy (complete or partial)
i diagnosed with VIN treated.with excision'u. ln this
f C0, laser Topical agents eg. lnterferon gel,
series the median age of those without invasion was
Reti nyl acetate gel, 5-Fluro-uracil.
36 years as against 58 years for those with invasion,
547
thus confirming the increased risk of invasion in older invasive or invasive diseases of the vagina, cervix or
patients. For young patients less than 40 yea,rs old in perianalarea.
whom invasion had been adequately excluded the
treatment of choice is laser therapy, if the freility Simple inspection of the vulva with white light is
exists. The laser allows the vulva to be fieM fo a often sufficient to detect all cases of invasive cancer
depth of about 3-4mm, leading to little or no scaning and most cases of VIN'0. For equivocal lesions acetic
during the healing. Laser ablation is also acceptable acid may be applied for approximately 5 minutes and
for the treatment of vulvar HSIL UIN usual,type). lt the area examined by a colposcope or a hand-held
can be used for single, multifocal, or confluent magnifying glass. Any aceto-white lesion is biopsied.
lesions, although the risk of recurrence may be higher All women can be encouraged to carry out periodic
than with excision"'". The disadvantage of laser vulva self-examination and report any abnormal area
treatment is that there is no tissue for histological to a physician.
studies to confirm pure intraepithelial neoplasia.
Because of this, patients likely to be harbouring Prevention
lmmunization with the quadrivalent or 9-valent HPV
underlying invasive disease such as the older patients
vaccine, which is effective against HPV genotypes 6,
with raised lesions should have local excision
performed and have the entire tissue submitted for
11, 16, and 18, and 6, 11, 16, 18,31,33,45,52,
and 58, respectively, has been shown to decrease
histology. Laser is also more difficult to use )
the risk of vulvar HSIL UIN usual type) and should be
successfully in hair bearing areas due to the :
recommended for girls aged 1 1-12 years with catch-
involvement of hair follicles and thus deeper extent of
up through age 26 years if not vaccinated in the
disease.
target age'n''.. The bivalent HPV vaccine (subtype
Post treatment follow-ups 16, 18) has not been studied for vulvar HSIL (VlN
The main problem with the treatment of VIN is the usual type) prevention. Cigarette smoking is strongly
significant risk of recurrence. The risk of recurrence is associated with vulvar HSIL UIN usual type), and
higher if neoplastic epithelium is found at the cessation should be encouraged.
resection margin. lt was noted that the risk of
recurrence is about 70% rt the surgical margins are C. CERVICAL INTRAEPITHELIAL NEOPLASIA
(CI N) (SQUAMOUS DYSPLASIA)
free of disease compared with a 50% risk of
recurrence if there are neoplastic epithelium at the
Definition of terms CIN represents a spectrum of
resection margin'u. Therefore whether resection
intraepithelial changes (dysplasia) with indistinct
margins are free or not'of disease it is crucial to
boundaries that begins with mild atypia and
arrange long-term follow-ups for patients treated for
progresses through stages of more marked
VIN. Periodic examination (say on yearly basis) of the
intraepithelial abnormalities to carcinoma in situ.
vulva using a colposcope or a hand held magnifying
The various categories form points on a disease
lens after application of 5% acetic acid is sufficient.
spectrum rather than separate disease entities. They
SceeningforVlN are precursor lesions to invasive squamous cell
Unlike ClN, VIN has a low incidence in the general carcinoma.
population and less than one-third of the cases of Dysplasia is a potentially reversible change
invasive vulvar cancer arise from VlN. As a result it is
characterized by an increase in mitotic rate, atypical
not worthwhile to screen for VIN in the general cytologic features (size, shape, nuclear features) and
popu lation. H owever, beca use treatment of adva nced
abnormal organization (cellularity, differentiation,
cases is associated with high morbidity and mortality
polarity) that fall short of invasive carcinoma
(premalignant change). Dysplasia may progress to
some form of screening of a defined high-risk group
may be cost effective. A suitable high-risk group cancer and dysplastic changes may be found
adjacent to foci of cancer.
includes those women who harbour cancer-causing
Squamo-columnar junction (SCJ) is the point of
HPV those who currently smoke cigarette, immuno-
intersection between the columnar and the native
compromised individuals, those treated previously
squamous epithelium. lt is an important landmark
for VIN and those who had been treated for pre-
548
where neoplastic change develops in the cervix. ln atypia characterize ClN. Nuclear abnormality is the
young adults the SCJ is usually located on the hallmark of CIN and includes hyperchromasia,
exocervix just distal to the external m, during pleomorphism, irregular borders, and abnormal
pregnancy and after childbirth it more chromatin distribution. These nuclear abnormalities
distally located on the portio of the c
,dffifyfrom persist throughout the epithelium irrespective of
the os. After menopause it is lscatefl in the cytoplasmic maturation towards the surface. Mitotic
endocervical canal. Transformation Zone ffFD. rate is increased and abnormal mitotic figures may
Throughout the reproductive live of a woman part of be seen.
the columnar epithelium undergoes metaplasia. The
area of columnar epithelium and squamous Grading
metaplasia constitute the transformation zone. There are 3 grading systems: Histologic grading of
Greaterthan 95% otall CIN lesions arise in the TFZ of CIN based on the proportion of the epithelium
occupied by dysplastic cells; Cytologic grading based
the cervix.
on the severity of dysplasia and the Bethesda system
Epidemiology (TBS).
The population distribution of cervical intraepithelial
neoplasia/dysplasia resembles the epidemiolory of CIN 1 (mild dysplasia): Dysplastic cells occupy the
an infectious disease that is sexually transmitted. lowerthird of the epithelium.
M ultiple male sexual partners, early age at first sexual
CIN 2 (moderate dysplasia): Dysplastic cells occupy
intercourse, early marriage, low socio-economic
uptothe middlethird of the epithelium.
status and male partner with multiple previous
female sexual partners are very important risk 3 (severe dysplasia, carcinoma in situ):
CIN
factors. Other factors are cigarette smoking and oral
Dysplastic cells extend into the upper third and may
contraceptive use. The putative sexually transmitted
occupy the full thickness of the epithelium.
infection (STl) is HPV and this causal relationship
satisfies all the criteria of epidemiologic research: The histologic and cytologic grading systems of CIN
strength, consistency, specificity of association, dose use a three-tier system. However, the Bethesda
response, temporal relationship and biologic System for cytological diagnosis divides precursors
plausibility". lt seems that though HPV is a of cervical squamous cell carcinoma into low-grade
necessary factor it is insufficient and that other squamous intraepithelial lesion and high-grade
cofactors are necessary. intra-epithelial lesion. This system also recognizes
two other cytologic descriptions namely Atypical
Clinical aBpearances
Squamous Cell of Undetermined Significance
CIN lesions are characterized by the appearance of (ASCUS) and Atypical Glandular Cell of Undermined
white patches on the cervix following application of
Significance (AGUS). The philosophy underlying the
acetic acid. Under colposcopic examination a CIN
Bethesda classification is that it is difficult to
lesion may be marked by a white area with red
distinguish between CIN 1 lesions and HPV effect on
stippling (punctation), sharp-bordered lesions with
Pap smear and as such the two are classified
vessels in a mosaic pattern (mosaicism), white
together as low-grade intraepithelial lesions.
tissues with sharp borders (aceto-white epithelium)
Similarly CIN 2 and 3 lesions are combined together
or atypical vessels. Lesions occur on the anterior lip
as high-grade intraepithelial lesions.
twice as commonly as the posterior lip. They are
found in the transformation zone and areas of Clinical behavior
squamous metaplasia in the endocervix and stop CIN may regress spontaneously, especially CIN 1, it
abruptly at the junction with the native portio may persist or progress into a higher grade CIN
squamous epithelium but can extend along the entire lesions or into an invasive lesion.
endocervicalcanal.
t Histology
Abnormal cellular proliferation, maturation and
549
Table 2
Natural history of CtN lesions
Lesion Regress Persist Progress to invasive

Cancer
CIN 1 60% 30% 10-15"6 1%
CIN 2 43% 35% 22% to CIS or invasive

CIN 3 32% 56"/" 14%
Screening for CIN screening was published by Wilson and Junger in

ln preventive medicine screening is defined as the 1968
systematic application of a test to asymptomatic . The condition targeted should be an important
persons in orderto detect a pre-clinical phase or
early health problem
stages of a disease for the purpose of identifying . There should be an acceptable treatment for
those Iikely or unlikely to have a disease. Applied to patients with screened condition
gynaecologic canceI . Facilities for diagnosis and treatment should
be available
. A screening program comprises the . Screening should classify individuals as to the
following: probability of disease with optimal validity and
. Scheduling and administration of screening predictiveness
test. . There should be a recognizable latent phase or
. Diagnostic evaluation of patients with ea rly symptomatic stage
positive test and . The test should be acceptable to the
. Appropriate treatment of confirmed cases. population both emotionally, physically and
Potential benefits of screening financially
. Detection of a
. The natural history of the condition should be
disease at its pre_invasive
state adequately understood
. lmproved prognosis fortreated cases
. There should be an agreed policy on whom to
. Reduced morbidity after treatment of screen treat as patients
detected cases
. The cost of the programme should be
. Reassuranceofthosewith negativetests economically balanced with the expenditure of
. Cost-effective use of health care resources the medical care as a whole
. Case finding should be a continuous process
Potential limitations of screening and not a once and for all project
. False reassurance of those with false
negatives Pap test
. Unnecessary morbidity for those with false Till date cancer of the cervix is the only gynaecologic
positives cancer that ids amenable to extensive screening and
. Uncertainty regarding appropriate treatment for which a well-established mass-screening
of early lesions of uncertain long term programme is in place in many advanced countries
prognosis leading to reduction in the incidence of cervical
. . Competing priorities of screening activities in cancer deaths by about 7O%. This is because the
use of limited health care resources organ involved is easily accessible, exfoliative cells
can easily be obtained from it and the disease passes
Criteria for appropriate use of screening through a well-defined pre-clini'ial stage (ClN),
methodology
which can be detected by a simple and cheap
The best known list or prerequisites for successful
screening test-tne Pap smear test. The other
s50
I
i
advantages of the Pap smeartest includethefactthat or worse lesions, it resulted in more positive finding
itis fairly well tolerated by patients, it is easy to thus leading to lower positive predictive value.
administer and has reasonable smifWity and However they found fewer unsatisfactory smears
specificity. The sensitivity of Pap sriffi. W from with LBC compared with conventional Pap".
55%to80%andthespecificityestimde _ %". Another added advantage of LBC is that the residual
specimens are available for additional testing such
Specimen Cotlection .. .:. l 'reflex HPV testing ln cases of low-grade or equivocal
The basic idea of cervical cytologr is,lo.sample the cytology results'n'oo. The 2001 Bethesda system for
transformation zone of the cervix, whieh 1s the likely reporting Pap smear results (abridged)
area of premalignant lesions. The standardtEChnique
for Pap smear collection is to sample the Specimen adequacy
portiovaginalis of the cervix and the e.Mocervical .
Satisfactory for evaluation
canal using a special spatula and endocervical brush. . Unsatisfactoryforevaluation
The collected sample is smeared on a slide and fixed . Specimen rejected or not processed (specify
immediately with cytology fixative. The staining is reason)
done using using Papanicolaou stain which gives
. Specimen processed and examined but
differential staining to parabaSal, intermediate and unsatisfactory for evaluation of epithelial
superficial squamous cells and also helps in a bnorma I ity (specify reason)
assessment of nuclear abnormalities. The
General categorization (optional)
conventional smear procedure has several . Negative for intraepithelial lesion or
drawbacks, namely the manual procedure of
malignancy
7
t
applying the cells to the glass slide is impossible to . Epithelialcellabnormality
standardize; cells are distributed unevenly; often . Otherlnterpretation/result
I
( there are thick areas of overlapping; cells can be . Negative for intraepithelial Lesion or
I
obscured by blood and mucous;fixation can be non- Malignancy
t
uniform giving rise to false positive rates of 15-20%
I and false negative rates of 21-50o/o"''0. Furthermore Organisms
t
the inter-observer variation in assessment of .
Trichomonasvaginalis
I
, cytologica Ia bnormal ity com pou nds the problems. .
Fungal organisms morphologicallyconsistent
i with Candida specres
/ Liquid based cytology .
Shift in flora suggestive of bacterialvaginosis
I
t
The liquid based cytology (LBC) collection is directed . Bacteria morphologically consistent with
r\- at improving cytology sampling and specimen Actinomyces species
I
I
t quality'u. The sample from the cervix is collected in . Cellular changes consistent with herpes
r the same manner as in Pap test. The sampling device simplexvirus
I
I
is vigorously rinsed or stirred in a vial of Iiquid
. Reactive cellular changes associated with
I
..
preservative, producing a suspension of cells that are lnflammation, radiation, intrauterine
filtered before a slide is made. The LBC technique contraceptive device, atrophy
i
i gives better cell harvest and ensures more of the
Epithelial Cell Abnormalities
collected cells to be captured in the suspension, and . Squamous cell
transfers most of the collected cellular material into . Atypical squamous cells (ASC)- 0f
the collection media for further processinglu'". The
undetermined' significance (ASC-US), -
LBC solution has special formulation that allows for
Cannot exclude HSI L (ASC-H)
i
i
removal of extraneous material such as blood, Low-grade squamous intraepithelial (LSl L)
I
ensuring the slides are composed of a uniform Encompassing HPV, mild dysplasia, CIN 1)
monolayer of cells. Few randomized controlled trails High-grade squamous intraepithelial lesion
have compared LBC to conventional c$ology. Results (HSIL) encompassing: moderate and severe
t of randomized clinical trial conducted in ltaly, dysplasia, carcinoma"in situ, CIN 2, CIN 3
t
I showed that while LBC had comparable sensitivity Squamous cell carcinoma
compared to conventional Pap for detection of ClN2
551
Glandular Cell every 3 years for women between the ages

r . Atypical glandular cells (AGC),:.Gpecify of 21 years and 29 years.
endocervical, endometrial, or not ot+S.wise . For women aged 30-65 years, co-testing
specified ,:,:,,i .i,.. with cervical cytology screening and HpV
. Atypical glandular cells, favouF:@.*e@ testing is preferred and should be
(specify endocervical or not eBetxdg performed every 5 years.
specified) , i . For women aged 30-65 years, screening
. Endocervical adenocarcinoma in situ (AlS) with cytology alone every 3 years is
. Adenocarcinoma
acceptable.
MANAGEMENT OF SCREEN POSITVE

. Both liquid-based and conventional
methods of Pap cytology are acceptable for
There is currently consensus agreement that cytology
screening.
indicative of high-grade lesions (CIN 2-3 or moderate
and severe dysplasia plus carcinoma in situ or HSIL
. ln women who have had a total
hysterectomy and have never had ClN2 or
in the Bethesda system) should engender immediate
higher, routine cytology screening and HpV
referral for colposcopyo'-o'. Women with ASCUS may
testing should be discontinued and not
be managed by cytology or HpV triage. Low-grade
restarted for any reason.
cytology (LSIL or ASCUS) under circumstances . Women who have a history of cervical
where women can be followed with regular cytology
cancer, have HIV infection, are immuno-
should also be so managedoo.
compromised, or were exposed to
diethylstilbestrol in utero should not follow
When cytology reveals an abnormality colposcopy
routine screening gu idel ines.
and spot biopsy and endocervical curettage (ECC) are
used to confirm diagnosis and rule out more
. Screening by any modality should be
discontinued after age 65 years in women
advanced diseases. Glandular cell abnormalities
with evidence of adequate negative prior
reported on Pap smear may require colposcopy, ECC
screening results and no history of ClN2 or
and endometrial curettage. Endometrial curettage is
higher.
usually reserved for post-menopausal women, but
can also be done for pre-menopausal women. lf these
Visual lnspection of the cervix with Acetic Acid
procedures do not explain the pap smear UIA)
abnormality, then conization is indicated. ln many developing countries the lack of resources
(both human and financial) make it impossible at
!ndications for diagnosticbone biopsy
. least for now to establish an organized mass
Evidence of micro-invasive cancer on pap
screening programme based on the pap smear test.
-:
smeaI cervical biopsy or colposcopy
. Evidence of adenocarcinoma in situ
Another approach to screening for pre-malignant
. Unsatisfactory colposcopy (incomplete lesions of the cervix is by using Visual lnspection of
visualization of the lesion orthe SCJ).
the cervix with Acetic acid (VlA). lt involves naked
. Grade of lesion on pap smear worse than on eye inspection of the cervix, using a bright touch light
biopsy specimen ora halogen focus lamp, 1 minute afterapplication of
. Patient not compliant with follow-up visits 3-5% acetic acid using a cotton swab or a sprayou. A
. Multifocal lesions of severe dysplasia positive test is characterized by well-defined aceto-
. Suggestion of invasive cancer on pap smear white areas in regions where there are abnormal
or biopsy implying the need for definitive cells.
diagnosis.
. As an integral part of VIA suspected pre-invasive
The frequency of Pap smear varies slighfly from one lesions are treated on the spot using cryotherapy. VIA
programme region to another. technique is simple, easy to perform, cheap and
ACOG recommendations acceptable to the clients. Nurses, midwives and even
. Cervical cancer screening should begin at paramedical can be taught to do it. Also there is no
age 27 years.
need for histopathological confirmation of the pre-
Pap cytology screening is recommended
552
------------t
Premalignant Leslons of the Female Genital Tract
malignant lesion before treatment. ln addition the on naked eye examination of the cervix to identify
the spot provision of treatment minirnizes the mustard-yellow lesions after application of Lugol's
problem of several visits to the hs&lth, facility iodine. The results are reported immediately after
associated with standard screening. 'i*,&t..fuor is application of iodine. A positive result is based on the
especially useful in developing count$e urtrere appearance of definite mustard-yellow area on the
majority of people live in remote ateas. Ftmbulant cervixou. The sensitivity of VlLl varies between 44-
services for example can be taken to these remote 92% and specificity between 75-85% in cross-
areas on a once a while basis. sectional studies in lndia, Africa, and Latin
Americao'-u'.
An additional benefit of VIA is that it provides the
opportunity for earlier detection of invasive lesions HPV DNATESTING
thus enabling the patients to benefit from early
treatment and better prognosis. The detection of a Moleculartests can detect DNAfrom cancer- causing
disease in an earlier stage when it is still curable is types in vaginal or cervical smears collected using a
ca I led' Down-stagi ng'. small swab or brush. Molecular testing techniques
employed are the polymerase chain reaction method
Extensive comparative studiesou*t have been done and Hybrid capture assay. HPV testing has been
I which show similar or slightly better sensitivity of VIA shown to be more sensitive and more reproducible
but with worse specificity (64% lo 79%) compared than Pap test for primary screening in controlled
with conventional cytology. The implication of the low observationa I and ra ndom ized control led tria lsu''uo'
specificity is that the false positive rate will be high
i meaning that a high proportion of normal people will A review of studies concluded that HPV DNA testing
i
I
be treated and will suffer unnecessary psychological is valuable in detecting high-grade premalignant
and treatment associated morbidities. Another lesions in women older than 30. HPV infections in
disadvantage aside low specificity with attendant women younger than 30 are likely to be transient, so
I
high false positive rate is the fact that it is not suitable testing young women can lead to unnecessary
i
L
for postmenopausal women because the referrals for treatment of lesions that would regress
I
transformation zone recedes in to endocervical canal spontaneously.
I
and therefore difficult to visualize. The overall cost-
HPV DNA testing not only identifies women with
I
benefit analysis of VIA with on the spot treatment
cervical disease but also those at risk for developing
however, demonstrates its usefulness in resource
I
CIN within the next 3 to 10 years. This is particularly

t poor countries where'the population is at high risk for
r*
I
cervical carcinoma.
important for developing countries that might not
have the resources to screen all women at 5-10-year
t
i Visual Inspection with magnification UIAM) intervals, but might have the resources to screen a
i
!
I Studies are ongoing to find out if the addition of a small subset of high-risk HPV DNA positive women
I
( hand-held magnifying glass would improve the at more frequent intervals. A new test, careHPV
,,
sensitivity and specificity of the VlA. The Avi Scope, a (Quiagen, lnc) test has been developed as a low cost
I
low-power (x4), hand held visual inspection device rapid test to detect a high-risk HPV DNA. lt is a
with an in-built light system is expected to improve screening test that is accurate, affordable, and
the results of VlA. Even though the manufacturers acceptable in resource constrained regions. This test
have indicated a better sensitivity for the instrument offers a promising approach for screening in remote
the South African study did not show any areas that cannot routinely access laboratories that
improvement". Further randomized control trials of process screening specimen i n large vol umeuu.
its use are awaited before its use can be approved or
t
discouraged. lts cost effectiveness is also yet to be
To triage the difficult area of managing those
classified as having low grade or borderline smears'
ascertained.
I
Those who are positive for high risk HPV subtypes
I
Visual Inspection with Lugol's lodine UlLl) will then be referred for immediate colposcopy. For
Visual inspection with Lugol's iodine (VlLl) involves those who are negative for high risk HPV subtype
:
553
:
both tests (i.e. cytology and HPV testing) can be risk for progression to invasive cancer if the
repeated in six months, thus reducing theru6n@ of area is not removed. Therefore, finding these
unnecessary repeated smears. lf the ttrre'@,are lesions is an indication for treatment after
negative, the woman is returned to routine q**@; confirmation with colposcopy and biopsy.
ln a study on patients with borderline st
*-,@
testing had 86% sensitivity for CIN 2i3 compad r The treatment options for CIN-2 are LEEP
with 60% for a repeat smear, with a,,r$ry*tive cone, Laser, cryotherapy and cold-knife cone
predictive value of 9Oo/ouu. biopsy. The treatment options for CIN-3/ClS
are LEEP cone, laser, cryotherapy, cold-knife
1. To triage the management of ASCUS lesion cone biopsy and hysterectomy.
on cytological report (i.e. to determire:which
category of patients with ASCUS smear . The diagnosis and management of
report are at a risk of CIN-3 lesions and will adenocarcinoma in situ is both challenging
therefore benefit from Colposcopy). ln an and controversial. Adenocarcinomas
analysis of 3488 women from the ALTS originate in glandular cells. They tend to be
group in America addressing the use of HCS more aggressive than the more common
ll in the triage ASCUS/LSIL smears, a high squamous carcinoma in situ. Some evidence
sensitivity ot 96.3% (95% Cl:91.6-98.8) suggests that it develops in numerous sites
is reported for HPV testing to detect CIN-3 rather than in a single location and also it is
but at a risk of a higher colposcopy rate of generally located high in the endocervical
56.1"/".u'. The authors concluded that HPV canal. Hysterectomy is generally
testing is a viable option in the management recommended. ln women who wish to retain
.
of women with ASCUS, with a greater fertility, cone biopsy may be performed
sensitivity to detect CIN 3 compared with although this procedure sometimes reduces
repeat cytology. fertility and does not always remove the
2. HPV testing could also be used to follow up lesions. lndeed the risk of residual
patients treated for CIN lesions. In a adenocarcinoma in situ depends highly
retrospective study of patients treated for upon cone biopsy margin status. With
CIN with LEEP HPV testing at 3 months positive margins the risk is about 58% and
predicted the risk of recurrence with with negative margins it reduces to about
sensitivity of 93% and specificity of 847o as 12"/oun. The risk of developing invasive
against sensitivit! of 49% and specificity of adenocarcinoma after cone biopsy for
87% for follow-up Pap smears and a adenocarcinoma in situ has not yet been
sensitivity of 39o/" and specificity of 78"/" for defined, a concern that makes hysterectomy
positive margin statusu'. Positive HPV test the continuing'gold standard' of its
therefore presents significantly high odds treatment. lf the margins are compromised
ratio for treatment failure independent of after a cone biopsy and future fertility is
cytology and margin status. desired, a second cone can be performed
provided the patient accepts the higher
General management principles chance of infertility and the potential risk of
o The management of CIN depends on the type recurrence.
and the extent of abnormal cellular changes.
Some of the treatment of CIN can also be crNl (LGSTL)
used for micro-invasive diseases. The management options of women with a single
The management of CIN 1 lesions is mild abnormal smear result include the following:
generally expectant although local treatment Follow-up with frequent (4-6 months intervals)
of the cervix is acceptable in patients who cytologic surveillance and either
are likely to be non-compliant with follow-up . Referral for colposcopy if evident dyskariosis
or likelyto haboura highergrade lesion. persists orworsens
Women with ClN2 or ClN3 have a definite . Reversion to routine cervical screening
554
Premalignant Lesrons of the Female Genital Tract
programme if cytology revertsto normal. This in crystallization of the intracellularwater. Thespear-

option is not suitable for patients deemed to like crystals of water pierce the cell membrane and
be at riskfor poorfollow-np. 1 ,:' ,t' cause irreversible damage and cell death (cryo-
a Routine referral for col necrosis). After waiting for 3-5 minutes the freezing
a Selective referral for is repeated for another 3 minutes (the double freeze
is likely to default for or if technique). Tissue destruction to a depth of 8mm is
she is likely to habour hiEffi"'i of achieved when an ice ball extending 5mm beyond
dysplasia than revealed bVc$o, the lesion is created. A randomized controlled trial by
Schantz at al demonstrated that double-freeze
THERAPY technique had lower probability of residual disease
Localablative therapy
after treatment of CIN 7 and 2u'. The side effects of
: o After the presence of invasive cancer has
this procedure include cramping, sometimes pain,
I been ruled put, local therapy is appropriate
for a few hours or days and a heavy watery discharge
: only if the following conditions are met:
for 2-4 weeks. The discharge can be irritating, have a
1 . The lesion is located on tlte exocervix or
bad odor, and may be blood tinged. Symptoms that
portio
indicate serious complications are fever and chills,
I
i
. There is no involvement of the endocervix as
determined by colposcopy or ECC.
heavy clotted bleeding, or extreme pain in the
. The lesion is not multifocal severe dysplasia
abdomen or back.
r
I
or carcinoma in situ.
The patient may experience a temporary change in
I
. Satisfactorycolposcopy.
menstrual periods; they may be heavier or lighter or
i . Biopsy consistent with cytology
. come later or earlier. Tampons, douching, bathing,
r All other indications for cone biopsy absent
I swimming, and intercourse should be avoided for
( The local ablative modalities include Cryotherapy, several weeks after cryosurgery to prevent infection.
i
C0, laser therapy and electrocautery. Whatever Cervical stenosis is an infrequent late sequel of
I
method is used, the depth of ablation should be at cryotherapy that does not have any adverse impact
I
least 5mm, the average depth of a crypt in the on fertility or obstetric outcomeu'. An inherent failure
i
I
transformation zone. Unless the full depth is treated, rate of 8-10% requires selection of patients who will
i residual disease will be left behind. A disadvantage of comply with the required follow-up.
t
the local ablative treatments is that they do not yield
CO, laser ablation
t any tissue for histological studies. Careful selection of
I The CO, laser can be precisely controlled and is used
t patient is therefore m'andatory. A systematic review of
published controlled and randomized trials reported
in conjunction with a colposcope or operating
i
;
microscope to destroy tissue to a depth of 8 mm.
I no significant difference in outcomes with respect to
recurrence of CIN between cryotherapy, laser Electro-cautery
ablation, or LEEB in women with satisfactory Electric cautery may be used for the treatment of the
colposcopyuo. entire transformation zone. Apart from electro-
cautery, a hot wire unit can also achieve cautery.
Cryotherapy
Cryotherapy is not usually suitable for large and Excisional therapy Conization
extensive abnormal areas. The procedure removes Other indications of cone biopsy in addition to those
abnormal, but non-cancerous tissue, by freezing it listed above include desire for maintaining child
using a gas whose boiling point is in the cryogenic bearing function in a person who would have been
range, usually liquid nitrous oxide or CO. better served by hysterectomy and who is willing to
Cryotherapy can be performed in a physician's office adhere to a strict protocol forfollow-up. Conization is
in 15 minutes without medication: The vagina is preferred when the suspected lesion extends higher
opened with a speculum and a probe transmits the up into the cervical canal, or when the lesions are so
I
f,
f
gas, which freezes the surface of the cervix. The gas is extensive that they require i
larger biopsy for their
applied for three minutes or until an adequate 5mm complete removal. The procedure can be
I ice-ball is formed on the targeted tissue. This results
555
accomplished either with the cold knife or with the requiring removal of uterus
laser. A general anaesthesia is usually required. 3. Persistent abnormal smear following
Usually it is advisable to perform ? pfe- @trative excision or ablative treatment
colposcopy to delineate the TFZ on the eltge@iXand 4. Positive endocervical margin after
stain the cervix with iodine to outline the ltr,U,BOf,.Sre conization
resection margin. A post-conization ECC is',ffi 5. Completed child bearing,
out. A few weeks after the procedure it is advts.S+e to
6. Adenocarcinoma in situ
sound the cervix to prevent stenosis. The main
The hysterectomy can be performed either
drawback of the laser conization is the deve[opment
abdominally or vagi nal ly.
of burn artifact making histological interpretation
difficult with regard to the state of the excision Hysterectomy and conization are approximately
margin. equivalent in their effectiveness in treating squamous
cell carcinoma in situ especially if the excision
Loop electrosurgical excision proced ure (LEEP)
margins are free-1 .2-2.3% recurrence risk of
This is also called large loop excision of the
carcinoma in situ and 0.9-2.1% risk of invasive
transformation zone (LLETZ). The indications are
cancer.
virtually the same as cone biopsy. lt uses a high
frequency electrical current for cutting away disease
Follow-up after local treatment for CIN
tissue. A local anaesthetic is applied to the cervix and There is a general agreement about the need for
a wire loop is used for cutting the tissue. The follow-up because of the inherent risk of failures or
procedure requires only one office visit. When used
recurrence. Follow-up has traditionally been done
for dysplasia it appears to be as effective as more with pap smears followed by colposcopy as the need
invasive procedures. After conization procedure or may be. Follow up assessments must not be limited
LEEP the patient should avoid coitus or vaginal to the cervix but should include the vagina and the
tampons for approximately 4 weeks. An advantage of vulva because of the field cancerization
LEEP is that it provides tissues for histopathologic phenomenon. Patients who had hysterectomy
studies. should therefore not be left out of the follow up
protocols.
The main complications of excisional therapy include
intra-operative and post-operative bleeding, cervical Recently HPV testing has been suggested as part of
stenosis, cervical incompetence and cervical the postoperative follow-up managements since it
dystocia in labour. was found that by 6-12 months post treatment HPV
persistence was associated with high rate of
Although loop electrosurgical conization have been
treatmentfailure or recurrence. HPV DNA testing has
associated with lower blood loss, better post-
treatment colposcopic visualization, and shorter
the potential to enhance the detection of
persistenVrecurrent disease. The studies evaluating
operative times than cold-knife conization in some
the role of HPV DNA testing during follow-up
studies, pathologic margins are often more frequently
observed that positive HPVtest, even in the presence
involved and more difficult to interpret than with
of normal cytology, can detect treatment failure more
cold-knife conization". Therefore, a decision as to
qu ickly and adequately"''..
which therapeutic option is best for an individual
patient depends on factors such as the training and
D. VAGINAL TNTRAEPITHELIAL NEOPLASIA _
experience of the clinician, the preferences of the VAIN
patient, the resources available, the expected clinical
value of a given treatment modality for that patient, Epidemioloey
and whethercancer has been excluded. VAIN is much less common than cervical or vulvar
dysplasia. lt may occur as an isolated lesion but more
Simple Extrafascial Hysterectomy commonly 05% of cases) a "pre-or co-existing
The indications for hysterectomy include: squamous carcinoma of cervix or vulva is present.
1. CrN-3/C|S This may be due to a field effect involving the
2. Associated gynaecological conditions
556
T
I
i
f
I
(i
squamous epithelium of the lower genital tract involves more than two-thirds of the epithelium.
i
,, (which arises from a common cloacogenic origin) that Carcinoma in situ, which encompasses the full
V is affected by the same carcinogenfe, 4ent. Risk thickness of the epithelium, is included under VAIN
,l
{*- factors include dysplasia elsewhere in.Smihl tract, 3.

f
i
HPV infection and in utero exposuretom. Distinct
i vascular changes are often lacking, but ptinctation ln 2012, as part of the lower anogenital squamous
and acetowhite changes can be scen during terminology (LASD standardization project for
colposcopy. human papilloma virus (HPV)-associated lesions,
the College of American Pathologists and the
Clinical Presentation and evaluation American Society for Colposcopy and Cervical
The lesion is asymptomatic and often no grossly Pathology have proposed a revised terminology by
identifiable lesion can be seen. Diagnosis is usually which VAIN is reported using a two-tiered
considered because of an abnormal Pap smear result nomenclature: LSIL for low-grade disease (VAIN 1)
in a woman with no demonstrable cervical and HSlLfor high-grade disease (VAIN 2/3)"
abnormality or who has had hysterectomy. This is
confirmed ultimately by colposcopy and biopsy. lntraepithelial vaginal dysplasia of glandular origin,
Occasionally women may complain of postcoital or atypical vaginal adenosis, is a separate entity. This
bleeding or unusual vaginal discharge. lt tends to be lesion has a well-established association with in
multi-focal and most lesions occur in the distal third utero diethylstilbestrol (DES) exposure and may be a
;-
of thevagina, occurringoften in anteriorand posterior precursor to
DES-associated clear cell
vaginal walls the lesion may be hidden by speculum. ln addition, cases have been
adenocarcinomauu.
They may be leukoplakic, velvety, erythematous or reported of atypical adenosis and vaginal
i
ulcerated. adenocarcinomas in non-DES-exposed womenu'.
o VAIN 1- Mild - LSIL
Evaluation consists of a complete history, physical o VAIN 2- Moderate- HSIL
examination, Pap smear of the cervix and the vagina, o VAIN 3-Severe- HSIL
colposcopy of the cervix, vagina and vulva and . Carcinoma in situ- HSIL
colposcopically directed biopsies of abnormal areas.
Clinical behavior
It is important to distend the vagina appropriately
The lesion may regress spontaneously, may recur
because of the many folds and rugae and rotate the
after treatment, or progress to invasive squamous
speculum so that no lesions are missed.
cell carcinoma if left untreated. Evidence regarding
Histology the rate of regression or progression is insufficient. A
i!
As with other intraepithelial neoplasia, there are small study quoted 97" of progression into invasive
architectural abnormalities in the form of loss of canceruu. There is also an uncertainty regarding the
{ time of progression. Great debate exists as to
I
epithelial cell maturation towards the surface (loss of
. polarity). Cytologic abnormalities occur with whether all invasive squamous cell cancers begin
dysplastic cells showing nuclear hyperchromasia and with an in situ phase. Most invasive cancers are
pleomorphism, undifferentiated cells resembling the unilateral, well-circumscribed lesions, are not often
basal cells scattered within the epithelium, and associated with HPV and arise in older women,
cellular crowding. Mitotic figures, some abnormal, whereas VAIN tend to be multifocal, is associated
are increased and may be present above the basal with H PV and arises in younger women.
layer.
Treatment
Grading/classification The treatment modalities include the following:
VAIN is defined by the presence of squamous cell 1. Partialvaginectomy.
a$pia without invasion. The disease is classified 2. Vaginalestrogen.
according to the depth of epithelial involvement:
3. Vaginal 5-fluorouracil (s-FU).
A
VAIN 1 and 2 involve the lower one-third and two-
4. Lasertherapy.
I Partial vaginectomy is the treatment of choice in
thirds of the epithelium, respectively, and VAIN 3 patients older than 45 years and when there is any
557
,-!
suspicion of invasion. lt involves a circumferefltial disadvantages of a policy of routine referral for

incision of the lesion to remove the tissue, followed colposcopy include:
by a circumferential closure of the vaginat tkele. ln o lncreased physical and psychologic
cases where a significant amount of vaginatr fu is morbidity,
removed, a skin graft can be used to doe, . The threshold for treatment may be lowered
order to avoid a foreshortening of the t@@j by such a policy leading to over treatment
diseases that are intraepithelial, cur6.ffi..vfffir with resultant increased in iatrogenic
vagi nectomy a pproa ch 9O%. lt h istob{1i.15o6tt,* morbidity.
invasive lesion further treatment, usually r.adiatbnjs o The colposcopic services may be
necessary. overwhelmed.
The remaining three modalities may be used when A rational approach to the issue (the third option) is
there is no suspicion of invasion. ln postmenopausal not to refer every patient with a single smear report
women a trial of vaginal estrogen cream rnay be a first describing a mild cytologic abnormality routinely for
line of treatment, which may convert surface colposcopy. lnstead a selected minority of women
epithelium and Pap smear to normal. This modality with a single mild cytologic abnormality is referred for
of treatment has never been subjected to clinical colposcopy. The rest are managed according to
trials. ln young patients the therapies of choice are 5- management option 1 above. The basis of immediate
FU or CO, laser ablative therapy using operative referral of the selected minority includes the
microscope with cure rates of 85% and 80% following:
respectivelyu'. o A likelihood of default from follow-up
cytology.
Discussion o A viral typing test indicates an increased risk
There is an inherent false negative rate of lb-40% of of significant dysplasia (i.e. those positive for
traditional Pap smearu'and this is most likely to occur high risk HPVs).
with high grade and invasive lesions. lnformation . Women who are immuno-compromised
from several cross sectional studies show a poor o Women who smoke more than 20 cigarettes
correlation between cytological grading and per day
histology, with approximately one-third of women . A cervicographic suggestion of higher-grade
with mild abnormal smears having underlying CIN- lesions.
3un''0. This poor correlation however improves with
repeated smearsu'. Even. with histological grading ln recent years, new paradigms in genital tract
there is a high level of intra-observer and inter- malignancies have been proposed with the objective
observervariability. ln the National Cancer institute,s to maximize participation of target women in
ASCUS/LSIL study (ALTS) only 43% of the cervicat screening and treatment and improve on cost-
biopsies initially diagnosed as CIN-1 were classified effectiveness and efficiency". These include aiming
as CIN-1 by expect pathology review committee, for a single lifetime screening with a highly sensitive
477" were downgraded to normal and 13% were test; screen and treat approach when screen-positive
upgraded to CIN-2 and CIN-30'. Another issue is that women without evidence of invasive cancer are
a colposcopically directed biopsy represents a limited treated with cryotherapy in the same screening
sampling of the cervix that may be influenced by a
session, without diagnostic procedures such as
number of factors including the skill of the colposcopy and biopsy"'". Screening tests such as
colposcopist. Studies of women with CIN-I, VIA and VlLl provide immediate results making the
diagnosed on a colposcopically directed biopsy, who single visit approach more feasible. A major
undergo LEEB have identified CtN-2 and CtN-3 in disadvantage of this approach is that a certain
23%lo 55% of excised specimenso'. number of women will be over-treated. A randomized
controlled screening in lndia evaluate the
The advantages of routine referral for colposcopy and effectiveness of a single visit approach where trained
biopsy are that it enables a prompt histologic nurses performed colposcopy in ViA positive women
diagnosis and avoid the possibility of default. The and did cryotherapy if CIN was suspected on
558
\----r_
colposcopy and lesions were suitable for ablative negative results can extend the period before re-
treatment'.. Out of the total of 2L66 patients treated testing.
for colposcopically suspected ClN, 203 did not have
any evidence of CIN on biopsy resultftrg in wer- Current concerns about the HPV DNA testing as a
treatment. After a mean follow-up duration of 27 primary screeni ng tool i ncluder

months 80.3% of the CIN patients were c,ied of the
. lt is significantly more expensive than the
Pap test,
disease.
. The Pap test is a safe, effective, well-
The efficacy of the bivalent and quadrivalent vaccines established primary screen that has
in inducing immunogenicity, sero-conversion, prevented cervica I ca ncer successfu I ly.
preventing persistent HPV 16 or 18 infection and in o A positive test for HPV-16 or -18 is directly
preventing CIN 2/3, vulvar and vaginal intraepithelial referred for colposcopy/biopsy even though
I
neoplasia have been investigated in multinational, the HPV test identifies the presence of a
randomized controlled clinical trials involving about virus and not abnormal cells.15
50,000 women'u-". Sero-conversion rate exceeded
. Concern about women who are HPV-
negative but develop cervical cancer.
97%for both vaccines and the immune response is
much stronger in 9-L2 year old young girls as
Experts however agree that while HPV testing
compared to older girls. Trials of both vaccines have
increases the sensitivity of screening, it results in a
shown more than 90% efficacy in preventing CIN 2/3
lower specificity than cervical cytology (Pap test)'
caused by HPV 16 or 18 among HPV naiVe women.
When HPV is used as a screen, some form of triage is
: Vaccination does not protect women who are already
needed to reduce the number of HPV-positive
infected with HPV 16 or 18 at the time of
women with clinically unimportant HPV infections
I vaccination'u'".
f rom u ndergoi ng col poscopy/biopsy.
I
Controversies
I
I
Screening for premalignant lesions of the genital tract

While HPV vaccination provides an important
a emerging avenue for cervical cancer prevention,
has seen many advances, particularly with screening
I
I
several challenges and uncertainties need to be

i
for lesions of the cervix. Since the introduction of Pap
resolved before it can be widely implemented
I
test six decades ago, cervical cancer incidence has
through national immunization programmes,
I
I
declined; it has gone from being one of the most
l particularly in developing countries. These include
common cancers affecting women to 2lst among all
I
unaffordability due to high costs, feasibility,
cancers. The Pap test has several limitations. lt is
I
I
1v acceptability, logistics for vaccine delivery, such as

subjective, has complex diagnostic categories and
I
the need for 3 doses over 6 months, and the need for
t management algorithms, and cannot distinguish
( which abnormalities will resolve and which will improved vaccine platforms to reach out to
adolescent target girls.
progress to invasive cancer. The initial use of the
HPV DNA test as a co-test addresses some
limitations of Pap testing. The HPV test is objective
and can improve the sensitivity of the Pap test, and
I
?
559
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I
,
a
563
564
cHAPTER
45
Carcinoma of the Cervix
R. KwameAryee
{ INTRODUCTION HPV is now considered a sexually transmitted

disease with particulartypes being highly oncogenic.
Cancer of the cervix uteri is the most common female The WHO's lnternational Agency for Research on
cancer in developing countries. Worldwide about Cancer (IARC) has classified the HPV into three
500,000 women acquire the disease annually and groups: "carcinogenic (HPV types 16 and 18);
about 75"/o are from developing countries('). About probably carcinogenic (HPV types 31 and 33) and
300,000 women die of the disease annually. possibly carcinogenic (other HPV types except 6 and
Carcinoma of the cervix is the commonest form of 11) '''. Today over 120 types of the HPV have been
female genital cancer seen at the Korle-Bu Teaching described. The diagnosis of genital HPV infection
Hospital in Accra today. Wertheim's hysterectomy for has been done by indirect means (cytology).
operable carcinoma of the cervix forms 4.7"/" of all Recently highly specific HPV DNA tests (e.g.
hysterectomies done at the Korle-Bu Teaching Polymerase Chain Reaction tests and the Hybrid ll
Hospital. Capture tests) have been developed for the detection
of HPV in cervical lvaginal preparations. These tests
ln Europe and Ameriia the incidence of this disease are also very sensitive and are likely to change the
has fallen considerably due to the screening detection of the virus in the genital tract in the very
procedures adopted in the second half of the last
nearfuture.
(20'n) century.
Screeningfor precursor lesions of the cervix has been

U ntil recently the aetiolory of cancer of the cervix had in use for a long time in the industrially advanced
not been fully understood. Many suggestions were countries. The screening test has led to a marked
made to link cancer of the cervix with certain viral reduction in cervical cancer death rate by about
infections. ln the seventies and early eighties 7O%. fhe main screening test, the Pap smear,
Cytomegalovirus and Herpes Simplex ll were
developed by George Papanicolaou in 1943 has
implicated as their proteins were found in a large been the gold standard for the detection of pre-
number of invasive cervical cancer lesions('). Until malignant and indeed early malignant lesions of the
recently the Human Papilloma Virus (HPV) had not cervix.
been linked with the pathogenesis of cervical cancer.
The Human Papilloma virus has been known since ln developing countries or low resource countries,
antiquity to be associated with wafi growths of the the development of the naked eye visual inspection
t hands, vulva and vagina and other parts of the skin(') of the cervix UIA) is likely tb help reduce the high
but the link with cancer of the cervix has now been morbidity and mortality associated with cancer of
elucidated. the cervix. The VIA has been shown to be sensitive
s55
and specific enough to take the role of a good had normal Pap smears and the fifth had ASCUS.
screening method. lt has also been shown to b'eeasy HPV PCR test could not detect HPV DNA in the
to teach nurses and midwives to perform arid for specimens. (Could the lesions have been due to un-
them to go one-step ahead to treat pa@rt identified types of HPV)?
changes in the cervix by cryotherapy.
It must be emphasised that HPV is the most
With the advances in technology vaccines m bdng prevalent sexually transmitted infection in the world
developed against the HPV with the hq*q# occurring in up to 75% of sexually active women('''o).
achieving primary prevention of the disease. ft iSmy Men and women get infected soon after becoming
fervent hope that it will not take too long for the sexually active but it may take up to 20 years for the
vaccines to be approved for use. Until the vaccines cervical cancer changes to appear on the cervix. Only
become available for mass population use it will still about 10% of infected women would go on to
be prudent to practise safe sex. develop cervical dysplasia and of these, only a few
would develop overt cancer of the cervix. From the
AETIOLOGY AN D EPI DEM IOLOG !CAL FACTORS mechanisms of malignant change (discussed below)
it becomes fairly obvious that other risk factors may
The aetiology of cervical carcinoma in the past was
be involved in the carcinomatous change. The risk
attributed to Cytomegalo Virus and later Herpes
factors listed below have been known for a long time
Simplex Type ll infection as viral elements were found
to be associated with carcinoma of the cervix and
in cancer specimens. After many years of research it
they may also play key roles in the cancerformation.
has now become evident, beyond all reasonable
doubt, that the cancer is closely related to certain a. High risk behaviour is associated with the
highly oncogenic strains of the HPV notably types 16 following: Early coitarche (age at first coitus).
and 18 "'u'. ln a press release in 1996 by the WHO(", Early marriage. Multiple child births (High
after the meeting of 55 experts from 17 countries parity) Frequent change of partners (promiscuity
HPV was declared a major cause of the cancer of the and prostitution)
cervix.
There is low risk of carcinoma of the cervix
There are other strains of the HPV which are also developing among those fundamental religious
oncogenic but by far the commonest strain causing groups - viz. Nuns, Amish, Jews and Muslims.
cervical cancer is the type 16 which can be retrieved The disease is rare among virgins.
in over 80% o'f cervical cancer specimens. Type 18
which may be seen in a few cancer specimens may b. The sexual behaviour of the woman's male
be associated with a rapid onset of disease and it partner may also increase the risk of
usually affects the endocervical glands. To date over exposure"". The high-risk husband is one who
99.7% of cases of cervical cancer and severe CIN is promiscuous or develops carcinoma of the
llllll are associated with previous oncogenic HPV penis or one whose other consort develops
infection(u''). The other types involved in cervical carcinoma of the cervix.
changes include but not limited to the following
types: 31, 33, 51, 53, 35 etc. ln developing c. Familial predisposition may occur and history
countries type 35 may be second to type 16. of cervical carcinoma in close relatives may
also be important(").
Recently, anecdotal reports from a few investigators
have indicated that it may not be all cases of cervical d. Cigarette smoking has also been implicated as
carcinoma that can be traced to HPV infection. a co-factor. The nicotine and other by-products
Morrison et al't' provide evidence for 5 cases of of smoke are concentrated in the cervical
unusual variants of large invasive squamous cell mucous with a resultant reduction in the
carcinoma of the cervix diagnosed during immunity of the Langerhan's (dendritic) cells.
Ylitalo et al 1999("'in a case control study in a
hysterectomy for benign uterine disease (prolapse - population based cohort consisting of women
2, fibroids 1 and WF - 2). Four (4) of the patients
participating in a cytological screening test in a
565
Swedish county between 1965 and i999 vaccine against HPV-16, 18, 6, and 11 and a
confirm the association between'smoking and bivalent vaccine Cervarix (GlaxoSmithKline), against
cervical cancer. HPV 16 and 18. They have been evaluated in clinical
tffi'lEftce the
d. I mmune inhibition. Conditions trials and are now licensed in more than 100
immunity are also associateif:tffi!&ncer countries. The vaccines are generally proven to be
formation"o''u)as they enhance vil# Wce safe, producing only local reactogenicity and
in host cervical cells. The ffuFtS-i::ffi6gxe occasional allergic reactions. Trials of both vaccines
Deficiency Syndrome is therefore a contributor have shown more than 90% efficacy in preventing
to carcinomatous change. The chronic use of CIN 2/3 and AIS caused by HPV 16 and 18 among
corticosteroids such as for unrelenting HPV naiVe women. Vaccination does not protect
asthmatic attacks or systemic lupus women who are already infected with HPV 16 or 18
erythematosus may also play a role in cervical at the time of vaccination.
cancer formation.
The current vaccines may offer some modest degree
pill. Recentlythe role of
e. The oral contraceptive of cross-protection against other high-risk HPV
the combined oral contraceptive pill as a risk 2. types. Currently HPV vaccination has been
Adeno-carcinoma (10 - 15%) factor for recommended for use in young girls and women
cervical carcinoma has also been Typical aged 9-26 years: primary target age group: 9-13
{ clarifi Clear cell
endocervical years, and secondary target population for catch up
"o(16)
vacci nation : 73-26 years.
f. Age. Whelan"''gives the mean age for cervical
cancer as 51.4 years with the number of Both vaccines are administered intramuscularly in
patients fairly evenly divided between the age the upper arm deltoid muscles or in the thigh. The
groups 3039 and 60-69 years. quadrivalent vaccine is administered on days 1, 60
and 180, and the bivalent vaccine on days 1, 30 and
g. Race. The disease is commoner among 180. Every effort should be made to administer the
Africans than in Caucasians. The disease may same vaccine for all the 3 doses as there are no data
show familial tendencies.
on safety and efficacy when used interchangeably.
h. Socioeconomic status. Low socio-economic Vaccination is not recommended for pregnant

status is associated with increased incidence of women. Little information is available on the safety
the disease. and efficacy HPV vaccination in immune-
compromised subjects.
PREVENTION OF CERVICAL CANCER
Cervical screening is recommended in vaccinated
Cervical cancer prevention primarily requires
women, commencing at 30 years of age, with HPV
decreasing the risk of infection with oncogenic strains
testing. Much work has been done in thisfield"&''n''o
of HPV. Having few sexual partners and using
condoms have been reported to be associated with a Secondary prevention
reduced risk for cervical cancer. Avoidance of those
factors that enhance the persistence of HPV This involves effective screening and treatment of
infection, viz. smoking and oral contraceptive (OCP) premalignant lesions and HPV testing for high-risk
use has the potential to reduce the rate of malignant HPV types (i.e. types 16 and 18, and also types 31,
change. OCPs, however, are the most effective means 33,45 and 58).
of centraception, and their avoidance overall is not a
wise public health stratery. PATHOLOGY
Primary prevention HistologicalTypes

Safe and effective vaccines now offer the best option The main histological type5 of carcinoma of the
t for cervical cancer prevention. Two vaccines have cervix are:
been developed, Gardasil (Merck), a quadrivalent 1, Squamous cell carcinoma (85 -90%). Large
567
cell keratinising or non-keratinising Small cell 60 years.

Verrucous Endometroid -ThE-adenosquamous variety consists of both
Adenoid cystic (basaloid cylindroma) :: squamous cells and adenomatous elements.
Adenoma malignum ..:: The glassy cell carcinoma is very virulent and
1 Mixed Adeno -squamous Glassy ceH a p pea rs u n -d iff e re nti ateo fr ilF]a rsaEeil-s Jf u s u a y
I I
2 Othertypes lymphoma melanoma

': has a fatal outcome with early metastases.
sarcoma
Types Of Growth
Squamous cell carcinoma is the commonest form of There are 2 maintypes of growth.
cervical malignancy constituting approximately 85- 1The endophytic or ulcerative growth
90% of cases. Most squamous cell carcinomas are of 2 Exophytic or cauliflower growth.
the large cell non-keratinising type but many are
keratinised with visible squamous pearls on Spread
histology. 1. Direct extension. Local soread.involves,the bodv
of the uterG rpp&sl'!+E@r, r99{t6,
the uJgp-*ftr_.lfgamert. Spreadis
@
About 2-5"/" are of small cell origin and they tend to !ry.rmnd
be more virulent with poorer prognosis. They tend to usually lateral into the cardinal ligament due to the
occur in younger women. Thev may contain neug presence of the fascia surrounding the cervix (rql!gg-
endocrine granule cefv_ieal fascia) and the natural drainage of the cervix
/--*-".- --*-.--
cell carcinoma of the lung with higher recurrence rate is through the lymphatics which are laterally placed.
and more distant spread with ooorer orosnosis. The
2. Lymphatic spread. The spread is along the lines of .
ra re ve rru c o u s
-c4q
in q
41q_?pgqeq qq111llqly€lgvut h
which may be large and bulbous. They rarely the following nodal stations: The cervix is drained by
metastasise but they may be mixed up with the more pre-u rqtera l, po9!-u rg_tera I a nd u!g-1q:s1g3lpg!eq
virulenttypical squamous cell carcinoma. into the followi ng first station nodes:
The adenocarcinomas are of many varieties and they Pggag!_ca t "nod gs / p?Ig-[g!lg l. O btu rator n odes.
may not be associated with the various risk factors for External iliac nodes. lnternal iliac nodes. Common
the squamous cell variety. The typical variant is of iiiaC.noOes anO The Pre-sacral nodes. The para-
e1_do;g_ery1qq!- origin.and may contain i$1q- aortic nodes are second station nodes and are
cytop!A:ryq-.[gq!!_( i n va ryi n g qua ntities). The cel ls considered metastases. The supraclavicular nodes
may, however, contain-little or n_o _q,'!gj! tll;ty iiEttiioel mny"G involved through drainage through
resemble endometrial carcinoma (endometroid the thoracic duct.
pattern). lt may be difficult to differentiate the source
of origin of the garcinoma (endocervical or ,$ X."rrtogenous spread. figg11glqgena-U5
endometrial). The endocervical tumours stain :pre4ls*Igg. lt may occur from lymphatic-venous
posillve Oo_re 19Ad i lv with ca rci no-q.m blren ic a ltigen anastomosis br direct venous invasion. Spread is
main ly to the I ungs, liver and less frequently to bone.
than do endometrial tumours.
a, TRANS COELOMIC SPREAD. This occurs only
The adenoma malienum consists of well when the cervical lesion extends into the pouch of
differentiated mucinous glands that vary in size and Douglas.
shape and deeply infiltrate the stroma with early
Pathophysiology
metastasis.
The disease typically arises at the active :gg3qg
The clear cell carcinoma of the cervix is uncommon cggrn-oar--tg.ngtlonfrom a pr.-.Ii.tlrre_--dysoi;if
lesion. There is usually an orderly progression
.
and may be associated @ Fh-rough full thickness dysplasia (ClN lll) before
sti I boestrol ( D ES) exposu rq-
invasion occurs except in 2 conditions: ln
Th.r@srareand may be very feratini.ine dyrplffidy occur before CIN
aggressive and tends to develop in the wornen over llldeveloos.
k-P+
-----..-
568
a Carcinoma of the Cervix
I
t
I
I
e With malignant transformation of the

I
I basal increased frequency and urinary incontinence

I
t cells or reserve cells invasion may:ffie place in from vesico-vaginal fistu la formation.
I
I the absence of dysplasia iii. Rectalsymptoms such as pain.

Ii-' Schiller). tPvlvgl l8 irj!! iv. Pain is usuallya latesymptom and may
?
tumour. occur at the following sites: Low backache.
I
I
I
Deep pelvic ache. Sciatica. Ureteric colic.
a
Direct invasion may result i, t .',ffiing v. Pedal oedema.
I
I complications shown below.

PhysicalSigns
I
L Complications 1. Early cases - may be seen as an erosigl or
I 1
Pyometra as a result of endocervical ctlgiiccelygitjs.
J
I obstruction. 2. Cervical lesion seen on speculum
r 2 Vesicovaginal fistula.may occur in exa m i nati o n m ay be qlgg.a"liVe"gllVlggLlls
I ad@s--dle!o-!14,4 il! an.
r 3 Rectoraginatlislqle (rare) from rectal Diagnosis
1. The final diagnosis depends on.cervical
invasion.
I
4Ureteric-ob_strusJ_ig]{11!ll_Ugp}Igter, Fiopsy. Histolosical ex_amination of the
hydropelvis, hydronephrosis and punch biopsy specimen reveals the cell
pyonephrosis. types q{ t[e.-m a I gna ncy.
i
I
I 5 gBeuk, 2. ln early cases abnormglEap-{1{q9
tyrttler
6 Eaemsrybeee
inv.esjrgatSgl-- !J*-c.gp.o-!9_opy any and
i
t 7 Cachexia suspici.qus_ areas are biopsied under
colposcopiCguiOlnCe.
Causes of death
L Ha,em_orrhage. This is usuqllapfulggs. PROGNOSTIC FACTORS
2 Uilaeffiia Th'6 patient is renEred-
( unconscious and dies later. 1. Clinicalvarieties
I 3 Cachexia associated with recutrent a. Age - in young patientsthe dlsegse tg!!!s !q De lo\ry
I
I haemorrhage. a ggressive as it is usu a I ly srass ly .dircn!.ated"
I
I
:
i CLINICAL FEATURES b. Stage-this is related to distantspread.
I
I The disease is either symptomatic orasymptomatic. c. Tumoursize orvolume. Large tumours have poorer
+.:@
I
1. Asymptomatic The disease is discovered prognosis than smal I tumours.
f-
i accidentally through screening procedures or at
I
Family Planning clinics. The Papanicolaou d.
$g:qJU n'!,-o"ul"c_ex"f!gg1?19!:r - B u ky exo h c o r
I
Ip yt i
r
I smear mav reveal invasive carcinoma or severe endophytic growth or barre_l-s1?p.9-t:11:- ?1.
i
dysplasia
---,--€G.++/ for which colposcopy anq_.rujEgd assojigted with gggr pr9g19iis.
{ biopsres may prove positive for carcinoma of tllg
I
cervix.
--'------ 2. Histopathology
i
f
r
I 2. Symptomatic a. Tumour grade. This does not affect the clinical
staging. Well differentiated (Grade 1 lesions) have
. - Bleeding
; a. Symptoms arise when the cervix ulcerates.
I
i
may be irregular and recur on the best 5-year survival rates and the lowest
( contact including post-coital bleeding. incidence of regional node involvement'"'.
. Vaginal discharge which may be purulent
i . and malodorous due to secondary infection. b. Lymph or vascular space involvement. Roman et
. ln advanced cases systemic effects are also alt")have shown that the degree of lymph-vascular
seen. space involvement correlates significantly with the
I risk of nodal metastases in women with early stage
I i. Cachexia.
r cervical cancer.
a
I
ii. Micturiction symptoms include dysuria,
l'
I'
s69
i
I
t
c. Depth of tumour invasion. Deeper tumours have structures and has been useful in stagingthe disease
poorer prognosis. an o-p1ffi illra gtg=t1g-n- g.q:!
rygyler m n ffi effi
.j.
only changes in the sizgpllheno#*And onla!'rg1e
d. Histologic cell type. Sgdlsell ceg:g$t*E&H+he detected to be 1 cm or more in diameter are
cervix is uncommon but is associated't$tH peor considered positive. False results are obtained from
prognosis'"' normal sized nodes with microscopic cancer
deposits and enlargement from inflammatory and
3. Lymph node involvement. Lymph node hyperplastic cha nges('o).
metastases, either regional (pelvic) or to higher level
(common iliac or para-aortic) lymph nodes, have Abdominopelvic ultrasound examination may detect
proved to be one of the most reliable prognostic large ce_r_,yj-qA-L_-m-AS-S, hyQJq, reter and
factors for patients with cervical cancer. The regional hydronephfoses, lymph node involG?fri6-nt and
node (pelvic) metastases occurs at the following adnexal disease. Ultrasound is unable to differentiate
rates''o': between benign and malignant enlargement of
Stg€q14l9.0.5% lA2 -!-2o/o Stage
Stage lymph nodes. lt, however, has the advantage of being
rc_:!z-zot)% -sgge*2B -16;6% SEEe3 * inexpensive, less time-consuming and avoiding
,1sw stre; +lbo* ::* exposure to
""(31)
4. Newer markers
GSL C&L radiation
Magnetic Resonance I maging.

Level. Pre-treatment serum levels of This is the best imaging method and the details can
sq ua mous-
-cg! ! caIglTT1aNggI correl ates be improved with the use of an g"ndqyqg]IlAtggq!]trr
well with theflGO gl?_gj; tqmoUrsze; q9i-1"'. This may deJ_e.gl_Try9*19{e. and metastases
stroma| invasion and tympll1ggl to the lungs and liver. lt can detect tumor size, degree
mgtlstases'"'. In node-negative patients the of slpgg]-gr1gg1g1, vaginal extension and nodal
risk of recurrence was 3 times-ffi-elif-ple- involvement. Small metastatic lymph nodes c,4gl,rot,
@HPVgenotype however, be detected.
yq]T)fiFV type 18 is associated with increased risk
{+\ '\t- of recurrence and death in surgically treated . lntravenous urography. This enables the renal
G patients("'"). Tumours containing HPV type

18 may progress to frank invasion without a
phase.'"' 0 ,b*\.fJ ^
function to be assessed. The rate of dye
excretion from the kidneys is observed. Thus
prolonged pre-invasive hydronephroses and hydro-ureters can be
diagnosed to place the stage of the tumour as
vr"l<^t"{o\{'l'
-c.Microvessetdensity
High microvessel density is associqted with
stage lllB or higher. Non-functioning kidney
(failure of dye excretion from one kidney) can
t._ur-
(29)reducedsurvival *F €.-&6' also be diagnosed. lt may not be necessary for
^rroiC-
PRETREATMENT EVALUATIO; &..TTTTSd
early disease.
r . Positron emission tomography

L Full Blood Count
2 The Sickling status .,
This is a new imaging technique using
3 Renalfunction tests /
radionuclides which decay with the emission
Blood urea and elegtrqlytes SergtrJrealinine of positively charged particles (positrons). lt is
Serum uric acid of value in delineating more accurately the
I Chest radiograph extent of disease at the primary site and in
2 Electro cardiogram lymph nodes(tt).
3 Noninvasive diagnostic imaging studies Fine Needle aspiration cytology.
This procedure may be performed under
CT Scan sonographic or CT scan guidance for pelvic or
Pelvic and abdominal CT scan examination is used to abdominal masses or enlarged lymph nodes
evaluate the liver, urinary tract and the bony detected during physical examination or
570
imaging studies. The procedure is

usually Findings of optional examinations such as
performed under local anaesthesia. lt is free of lymphangiography, arteriography, venography,
major complications. Accuracy for abdornino- laparoscopy, ultrasound scan, CT scan and MRI are
pe lvic nod es ra nge betwe en 7 47o-95e/"6!''u\ of value for planning treatment. The results of these
studies should not be the basis for changing the
. Barium enema and lymphangit[rCphy may stage of the disease. Fine needle aspiration of scan-
also be indicated. Lymphangiography is detected lymph nodes may be helpful in treatment
particularly helpful in detecting enlarged lymph planning.
nodes due to the carcinoma. Due to its low
specificity the procedure has largely been b. Surgical staging and postsurgical treatment and
abandoned in most centres. pathologic staging
ln surgically treated patients the operative findings
. Examination under Anaesthesia. This is used and the pathological report on the surgically-
to find whether the parametria or uterosacrals removed specimen help immensely in accurately
are involved. Vaginal and recto-vaginal describing the extent of the disease. The findings
examinations are helpful when EUA is being should be accurately recorded but should not be
done to assess the extent of the disease. At the used to change the clinical stage. The TNM system
same examination cystoscopy and proctoscopy can be used in the recording of such findings and it is
with or without biopsy may be done to allow very important for comparing treatment modalities
visualisation of vesical or rectal mucosa. This at different clinics.
helps in stagjngthe disease clinically.
Due to the inability of the diagnostic tests to detect
FIGO STAGING(..) small lymph node metastasis especially to the para-
aortic nodes staging laparotomy was introduced in
Cervical carcinoma is staged clinically as most the 1970's. Due to the later bowel complications of
patients worldwide are treated with radiotherapy. radiotherapy{37'38) the extra-peritoneal approach was
introduced("'. ln the extra-peritoneal approach a
a.Clinical- diagnostic staging
sub-umbilical midline incision is made to explore the
As surgical carcinoma is clinically staged it is very
abdomen. The incision can be extended cephalad
important that careful clinical evaluation be
around the umbilicus if the need arises. The
performed in all cases, preferably by an experienced
peritoneum is opened and the abdominal cavity is
examiner under anaesthesia. The clinical staging
inspected, The peritoneum is then stripped off the
must not be changed because of subsequent findings.
abdominal wall to gain access to the pelvis and
Whenever there is doubt about allocation of the
pelvic side wall. The round ligaments are transected
cancer to a particular stage the earlier stage must be
extraperitoneally to improve exposure. Vascular and
used.
ureteric damage may complicate the surgery but in
The following examinq[ions are perffied: experienced hands complications are low.
In pgctlorf] palpati6flir colposcffi endocervica|
curettage, hysteroscopy, cystoscopy, proctoscopy,
ln the 1990's some investigators''o) introduced
intravenous urography and x-ray examination of the
laparoscopic staging techniques. To day
laparoscopic radical hysterectomy and pelvic and
lungs and skeleton. Suspected bladder or rectal
para-aortic lymphadenectomy are in use in many
involvement must be confirmed by biopsy and
centres worldwide.
h sto ogi ca I exa m i n ati o n . Cgn$rp_n_{ !h g-qgy1l.i s
i I
regarded as clinical examination.
:
t
57L
FIGO EXPLANATION TNM

STAGES
Primary tumour cannot be assesced. TX
No evidence of orimarv tumow" TO
0 Carcinoma in situ (oreinvasive e&dfi&i+a) Tis
I Cervical carcinoma confined to'ffta'E€iflfo. (extension to the corpus should be dis - T1
regarded)
IA lnvasive carcinoma diagnosed only by riticroscopy. All macroscopically visible lesions Tla
even with superficial invasion are stage 18 / Tib.
. lAl Stromal invasion no greaterthan 3mm in depth and 7mm or less in horizontal spread. . Tlal
. lA2 Stromal invasion more than 3mm in depth and not more than 5mm with a horizontal . Tla2
spread 7mm or lessa.
IB Clinically visible lesion confined to the cervix or microscopic lesion greater than 1A2 / T1b
Tla2.
. lBl Clinically visible lesion 4cm or less in greater dimension. . T1b1
.lB2 Clinicallv visible lesion more than 4cm in sreater dimension. . Tlb2
lt Tumour invades beyond the uterus but not to pelvic wall or to Iower third of vagina. T2
. llA Without parametrial invasion. . T2a
. llB With parametrial invasion. . T2b
lll Tumour extends to pelvic wall and / or involves lower third of vagina. T3
a iltA Tumour involves lower.third of vagina. No extension to pelvic wall. T3a
a IIIB T3b
Tumour extends{o ffi[*L*rrr and or causes hydronephrosis or non -functioning kidne y.
. lVA. Tumour invades mucosa of bladder or rectum and I or extends beyond the true pelvis b.
IVB distant metastasis.
T4 Ml
'note: the depth of invasion should not be more than 5mm taken from the base of the epithelium, either
surface or glandular, from which it originates. The depth of invasion is defined as the measurement of the
tumour from the epithelial-stromal junction of the adjacent most superficial epithelial papilla to the deepest
point of invasion. Vascular space involvement, venous or lymphatic, does not affect classification. bnote: the
presence of bullous oedema is not sufficient to classify a tumour as T4.
In 2009, the FIGO Cancer Committee modified the staging. The main changes from the 1994 FIGO
staging were the removal of stage 0, and the division of stage llA into IIAL (tumour <4cm) and llA2
(tumour >4 cm).
Carcinoma of the Cervix Uteri: FIGO Nomenclature (Capetown,2OO9)

Stage I The carcinoma is strictly confined to the cervix (extension to the corpus would
be disregarded)
IA lnvasive carcinoma that can be diagnosed only by microscopy, with deepest
invasion :5 mm and lareest extension :7 mm
tA1 Measured stromal invasion of :3mm in depth and extension of :7
mm
tA2 Measured st j5mm with an extension of
not >7 mm
IB Clinically visible lesions limited to the cervix uteri or preclinical cancers greater
than stage lAu
tBi Clinically visible lesion =4 cm in greatest dimension
tBz Clinically visible lesion >4 cm in greatest dimension
Stage ll Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to
the lower third of the vaeina
ilA Without oarametrial invasion
ilA1 Clinically visible lesion :4
cm in greatest dimension
572
IA2 Clinicallv visible lesion >4 cm in sreatest dimension

ilB With obvious pararnetrial invasion
Stage lll The tumour extends to the pelvic wall and/or involves lower third of the vagina
andlor causes hydronephrosis or non-functioning kidneyP
iltA tuqqqr invplygg lo\rygllljlq ef t[e vaglna, with no extension to !!9 pelvic wall
iltB Extension to the pelvic wall and/or hydronephrosis or nopfunctioning kidney
Stage lV The carcinoma has extended beyond the true pelvis or has involved (biopsy
proven) the mucosa of the bladder or rectum. A bullous edema, as such, does
not permit a case to be allotted to Stage lV.
IVA Spread of the growth to adiacent organs
IVB Spre4 !q !l!!q!t organs
"All macroscopically visible lesions-even with super?cial invasion-are allotted to stage lB

carcinomas. lnvasion is limited to a measured stromal invasion with a maximal depth of 5 mm
and a horizontal extension of not >7 mm. Depth of invasion should not be >5 mm taken from
the base of the epithelium of the original tissue-squamous or glandular. The depth of invasion
should always be reported in mm, even in those cases with "early (minimal) stromal invasion"
(-1 mm). The involvement of vascular/lymphatic spaces should not change the stage
allotment.
bOn rectal examination, there is no cancer-free space between the tumour and the pelvic wall.
All cases with hydronephrosis or non-functioning kidney are included, unless they are known to
be due to another cause. FIGO Committee on Gynaecologic Oncology.
Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. lnt J Gynecol
Obstet. 2OO9;1 05: 1 03-1 04.
TREATMENT Many acceptable treatment modalities are available

The treatment aims at treating both the primary for the treatment of this stage of disease, which
tumour and the potential metastatic areas. The effectively remove the lesion and maintain adequate
treatment modalities for carcinoma of the cervix are: reproductive function in young women. The
a. Primary surgery procedures available include the following:
b. Primary radiotherapy or cIgUgISgv, ql"9q!1o-9-a 1!9rv' [aqe 1 va porlsalio ;r,
c. A combination of both. celyjea] excision by laser, large loop_ dialnegy
%*!,__.:--*+_
d. Adjuvant chemotherapy may be added.
excision of the transformation zone (LLETZ) and
needle diathermy excision of the transformation zone
The choice of treatment may depend on the presence
or absence of the following patientfactors'"':
( N ETZ)'o"a nO cg
{:Ifigcgne biopsy.
a. The stage ofthe disease. . Adnexal mass
b. The facilities available including a qualified
[yometra . fibroids
oncological surgeon. ln much of the developing world uterus
. prolapse of . cervical stump
the facilities may be poor or lacking and there may be . PID . Stenotic vagina
. prior surgery . Advanced age
no trained oncological surgeons.
. prior radiation . bleeding
b. The presence of other patient factors that might . prior chemotherapy . bilateral ureteral obstruction
mod ify the treatment moda I ity(o'). . pelvic kidney . inanition
:
a
1. Cervical intraepithelial neoplasia (ClN) / 2. Stage 1A1
carcinoma in situ. ln micro-invasive lesions with less than 3mm
s73
invasion from the basement membrane cervical Fertility conserving surgery can also be considered in
conisation may be sufficient treatment. This may early stage 1B1 disease using the radical
help preserve fertility in affected..lg$.lgn. trachelectomy procedure(51'52). In this procedure a
Hysterectomy (vaginal or abdominal) m radical excision of the cervix (80% of the cervix) and
Performed' upper vaginal and proximal cardinal ligaments are
., ,.1 carried out with placement of cervical stitch at the
The incidence of nodal involvement i" *@*l isthmus(52). Pelvic lymphadenectomy is
disease is about 0.5% with a S-year survival of 97%- accomplished laparoscopically. Though experience
,oo*(43,44,45) ".(46) is limited live births have been obtained after the
procedure'u".
The Graz studiindicate that a cone biopsy or simple
hysterectomy is just as effective as a radical vaginal 4. Barrel shaped lesions
hysterectomy if stromal invasion is less than 3 mm. A For this type of lesion full external and intracavitary
radical hysterectomy for this stage may be pelvic radiation followed after 6 weeks by extra-
considered overtreatment(o'. fascial abdominal hysterectomy with para-aortic
node biopsy is advantageous.
3. Stages lA2, 1Bl and llA
ln stage 142 disease the stromal invasion is between 5. Stage lB2,2B,3A,38,4Aand 48.
3 and 5 mm. The optimal management of this group For these stages of the diseasefull external and intra-
has not been clearly defined. The options of cavitary pelvic irradiation must be carried out. Vide
treatment are cone biopsy,simple (extrafascial) infra for modifications in radiation therapy.
hysterectomy and radical hysterectomy with pelvic
lymphadenectomy'oa. ln the past the Extended Class HYSTERECTOMY
ll abdominal hysterectomy with bilateral pelvic node
dissection has been used for stage 1A2 lesions(o'). lf The hysterectomies done for cervical cancer is
child bearing is an issue cone biopsy with extra- divided into 5 different classes, according to the
peritoneal and or laparoscopic lymphadenectomy Pivers- Rutledge(u')classif ication shown below.
may be considered. lf vascular channel invasion has
1. Class I
occurred radical trachelectomy with pelvic node
dissection may be a safer option'o'). ln medically unfit
6 Class t hysterectomy is termed extrafascial
hysterectomy.
patients intracavitary radiation may be used.
6 The entire uterus and cervix are removed
For stages 181 and 2A extended (Class lll) without disturbing the ureters in their beds.
abdominal hysterectomy with bilateral pelvic The uterus is removed without dissection into
lymphadenectomy (Meig's-Wertheims) is performed the cervix.
(vide infra). A few high-risk patients may have pelvic 6 The main indication is for the treatment of
stage 1A1 cervical carcinoma or after pre-
radiation in addition to surgery.
operative irradiation e.g. for barrel shaped
With the development and improvement in carcinoma.
laparoscopic pelvic lymphadenectomy the vaginal
radical hysterectomy introduced by Schauta in 1901
2. Class ll
6 This is termed modified radical hysterectomy
has been revived as an alternative therapy to the
or Te Linde's hysterectomy.
traditional abdominal procedure for operable cervical
d This is useful for a small invasive carcinoma of
carcinoma(o''. The procedure involves the radical
the cervix, stage142, and for small central
excision of the uterus and the cervix, parametria, and
recu rrence after radiothera py.
proximal ligaments (Piver's / Rutledge class 2). This
e The operation involves pelvic
has the main advantage of reduced morbidity over lymphadenectomy, hysterectomy with
the abdominal procedure. The five-year survival in removal of half of the uterosacral ligament
both abdominal and vaginal procedures are similar in and removal of para-cervical tissues; the
early stage 1 b disease'o''uo), ureters are retracted laterally but are not
574
dissected from their attachments distal to the Epidural anaesthesia

uterine artery. This is started before the induction of general
anaesthesia. lt is very useful in reducing blood loss
3. Class lll and constricting the bowel so it does not interfere
d This is Meigs - Wertheim's operation. with the surgery, Post-operatively it is very useful for
d lt involves-pelvic lymphadenectomy, total analgesia.
abdominal hysterectomy, bilateral salpingo-
oophorectomy (not done for young patients), Complications of surgery
removal of the upper one-third to half of 1 Anaesthetic complications.
vagina; ligation of the uterine arteries at their 2 Local.
origin and excision of the utero-sacral a. Bleeding.
ligaments close to their origin. b. Damage to the bladder, ureters, rectum and blood
6 This is usually done for stages 18 or 24 vessels.
disease.
3. Bladder. Fistula formation. Neurogenic
4. Classes lV and V. dysfunction. The bladder may be atonic for varying
These are ultra-radical surgical procedures. ln class periods of time.
lV the ureters are completely dissected from their
t
beds and the Superior Vesical Artery is sacrificed. 4. Ureters. Hydroureter and hydronephrosis which
Class V involves resection of the distal ureter, or may
portions of the bladderor both. When the distal ureter
resolve in 6 weeks. Stenosis. Fistula. Sheath
2
is resected re-implantation into the bladder is done.
damage.
These classes of surgery are done for small central
recurrence after radiotherapy to avoid exenteration.
3. Retroperitoneal space.
5. By fa r the commonest mode of su rgery for operable

a. Haematoma.
b. Lymphocystformation.
carcinoma of the cervix (stages 18 and 2A) is the c. lnfection.
class lll hysterectomy (MeigsWertheim's d. Thrombosis. Deepveinthrombosis.
a hysterectomy). Pulmonary embolism.
,.
i
e. Bleeding. intra-operative. postoperative.
I
PREOPERATIVE PREPARATION f. Neuronal damage and neuropathies.
I
Bowel preparation Femoral nerve. Obturator nerve. Peroneal
I
Rigorous bowel pre6iaration is not really necessary nerve. The sciatic nerve.
av
:
but the use of a mild aperient or small enema ensures g. Rectum.
that the pelvis is not filled with distended loops of
bowel during surgery. The first few post-operative h. Partial denervation with acute or chronic
rectal dysfunction
days are more comfortable to the patient.
I Postoperative care
Miniheparin prophylaxis
Started 8-24 hours before the start of surgery the use
1. lntravenous fluids are given for 1-2 days.
of mini-heparin is very important for those at risk of
2. Analgesics Pethidine imi 100-150mg 4
hourly. Morphine imi 10-1Smg 4-6hourly.
deep vein thrombosis e.g. obese and elderly patients.
Patient Determined Analgesia (using morphine
This must be combined with the use of appropriate
in a drip).
stockings.
3. Antibiotic cover. Broad-spectrum antibiotic
prophylaxis is very important.
Prophylactic a ntibiotics
The use of prophylactic antibiotics is also very 4. Maintain catheter drainage (supra pubic or
urethral) for 10-14 days. The bladder must be
important in reducing post-operative sepsis. Blood
retrained till sensation occurs. Culture the
taken for grouping and cross-matching against 2-4
I urine when the catheter is removed.
units of blood is very important as it may be needed
for rapid transfusion.
575
Follow Up have been conducted yet.

1 Patient is first seen 2 weeks after discharge from 3 Post-radiation fistula formation is not
hospital. She can then make monthly,V$e&fu..l- experienced with su rgery.
2 years then 3-4 monthly visits fsr ffi----------------r@,ffi
4th years. Thereafter, visits can be aagq$&,i*i& RADIAT!ON THERAPY
every 6-L2 months. .: ,i,',.ii.r Radiation therapy is indicated for all stages of
At each visit examine for scalene node disease especially for stages llB and above and for
enlargement. Examine the legs and abdomen those with contraindication to radical surgery.
also for palpable lymph nodes or the oceunence
This involves the application of caecium 137 to treat
of lymphocyst or lymphoedema.
Do a speculum examination and at tlre same the local disease (brachytherapy) and external beam
time take a Pap smear from the vaginal vault for radiation (teletherapy) to the pelvic sidewall and
cytologic examination after the vaginal vault has occasionally the para-aortic area. The use of radium
healed, for brachytherapy has largely been abandoned due to
lf there is suspicion of recurrence do a CT Scan, itsvery long half-life of 7620 years.
sigmoidoscopy or cystoscopy as the case may
be.
ln cervical radiation therapy 2 important points are
Recurrence after surgery may be treated by considered: points A & B. Point A refers to a point 2 \---
radiotherapy.
FIGO STAGE SURVIAL RATE / %
Advantages of Primary surgical treatment over STAGE IA1 95.1
primary radiation treatment. STAGE IM 94.9
1 lt is possible to conserve the ovaries in young STAGE B 80.1
patients. Radiation would mean immediate STAGE IA 66.3
menopause. STAGE IB 63.5
It is also possible
to preserve fertility in young STAGE ilA 33,3
women with early disease using the radical STAGE IIIB 38,7
trachelectomy with pelvic lymphadenectomy STAGE IVA 17.1
procedure. STAGE IVB 9.4
Surgery involves the removal of the entire
tumour. Psychologically the patient knows that
ADAPTED FROM: Benedet J et al. carcinoma of the
the whole disease has been removed and she is,
cervix uteri. Annual report on the results of treatment
therefore, happy. in gynecological cancer. J Epidimiol Biostat 1998;
When radiation is used as primary treatment the 3:5-34.
patient may feel that her tissues have been
'cooked'and that can be disturbing
psychologically. SPECIALCASES
1. PREGNANCY
lf there is recurrence after primary surgery It is possible to diagnose these patients if routine Pap
radiotherapy can be used effectively. smears are taken with the addition of colposcopy and
The vagina maintains its capacity for coitus but directed biopsy for suspicious cases. Cone biopsies
in the case of primary radiation therapy the can also be done during pregnancy (only if strictly
indicated) with the attendant complications such as
vagina becomes stenotic with severe
severe haemorrhage, abortion or premature labour.
dyspareunia or apareunia. lt has, however, been
On the other hand it is easy to miss the diagnosis as
noted recentlyuothat surgery may be associated
bleeding due to the cancer may be thought to be a
with an increased risk of insufficient vaginal complication of the pregnancy - threatened abortion
lubrication, vaginal shortness and reduced and antepa rtum haemorrhage.
vaginal elasticity causing considerable coital
distress. Further studies in this area are needed Treatment
to clarify the situation as no randomised studies Before 20 weeks and after 30 weeks the treatment
576
\--------r
plan is easier. lt is more difficult between 20 and 30 be important for young good risk patients who would
weeks. ls is very important to discuss the treatment desire ovarian conservation. Alternatively,
with the patient and preferablythe huster*dmwd. laparoscopic ovarian transposition may be carried
Before 24 weeks termination of the pre with out prior to radiotherapy.
treatment is effected. For stage lB'= ffi,@ree
radical hysterectomy with pelvic { my
with the fetus in situ is performed. For staBeSB - IVB 4. RECURRENCE OF CERVICAL CARCINOMA
disease use external beam radiatior and uelgli,m 30 After radiotherapy
days the fetus aborts. Follow this with brachytherapy. lf r
tu mou recu rs af ter rad iothera py rad ica I
lf the fetus is not aborted-hysterotomy must be hysterectomy with possible pelvic exenteration can
performed. be carried out.
After 24 weeks allow fetal maturity to occur. When After surgery

the fetus is mature perform Classical Caesarean lf tumour recurs after radical surgery radiotherapy
Section and treat according to the stage using either using external beam followed by interstitial radiation
radical surgery or pelvic irradiation therapy. can be carried out.
2
2. CERVICALSTUMP Pelvic Exenteration
Pelvic exenteration is performed for centrally
l When carcinoma of the cervix occurs in the cervical recurring carcinoma of the cervix with the hope of
stump after sub-total hysterectomy radical curing the disease. lt must be emphasised that it is
trachelectomy and upper vaginectomy with pelvic not used for palliation.
lymphadenectomy is performed for operable cases.
Radiation therapy can also be used but may be the The procedure is quite mutilating and involves
sole modality of treatment for advanced cancer. removal of the uterus (and cervix) and bladder
Brachytherapy is compromised if the cervix is shorter (anterior exenteration) or the rectum (posterior
than 2 cm. exenteration) or both bladder and rectum total
exenteration).
Sub-total hysterectomy is being performed more
I
I
L
I
frequently these days and cervical stump carcinoma ln anterior exenteration the ureters are diverted.
I
is likely to be seen more often than in the past. They may be implanted through an ileal loop which
I
i isthen exteriorised atthe right iliacfossa. The ureters
I
I
3. INVASIVE CANCER FOUND AFTER SIMPLE may, however, be implanted in a Koch pouch using
I
I HYSTERECTOMY the caecum with the appendix exteriorised for
repeated catheterisation to emptythe pouch.
I
t
I
lf micro-invasive cancer of the cervix is discovered in
( the hysterectomy specimen (hysterectomy done for ln posterior exenteration a colostomy is performed in
I
I
r apparent benign disease) no further treatment is the left iliac fossa. ln total exenteration it is important
(
required. not to perform a wet colostomy in which the ureters
r are implanted into the colon before the colostomy is
I
1 lf frankly invasive carcinoma of the cervix is done.
I discovered in the hysterectomy specimen 2

I
I alternative treatment modalities exist. Full pelvic 5. CERVICAL BLEEDING
irradiation can be carried out with the expected
, ln a few situations severe or life-threatening cervical
radiation menopause in young patients. This would
bleeding occurs before the patient is ready for full
be very important for patients with extensive residual
1
I treatment. Bedrest, vaginal packing and the

disease or poor-risk surgical patients. Further surgery application of Monsel solution to the lesion can be
I
can also be carried out if no gross residual disease used to control the haemorrhage. lf this fails then
t*
I
exists and the patient is well suited for surgery. embolisation of the hypogastric or uterine arteries
(
Radical parametrectomy, upper vaginectomy and can be carried out if the expertise and equipment are
I
available.
: bilateral pelvic lymphadenectomy may be carried out
:
if the stage of the disease would allow. Surgery would
:
577
The use of external beam radiotherapy (haemostatic also very few, And the very equipment also suffer
dose) should be able to control the bleeding within a frequent breakdown due to the lack of constant
few days. The patient can then be prepared, for. full electrical power supply. Where the power supply is
treatment with adequate blood transfusiql to fairly constant fluctuations in the current may cause
enhance the radiation therapy. damage to the very sensitive equipment. lt is,
therefore, heart-warmingto learn of the development
CONTROVERSI ES AND PROBLEMS of the semi-automatic after-loading system for
developing countries. This equipment is supposed to
be more power-fa i I ure f riend ly.
By and large oncological services in the West African
Sub-region is rudimentary. Recently a number of
hospitals in the area have been equipped with With the knowledge that cancer of the cervix is
radiotherapy centres. Training in gynaecological caused by HPV it would be prudent by all to practice
oncology and for that matter other sub-specialties is safersex. The use ofthe condom may help reduce the
lacking in the sub-region where large numbers of transmission of HPV but will not eliminate it
patients with cancer of the cervix live. There are also completely. Life-style changes especially in
no proper screening programmes to help pick up pre- developing countries should be able to reduce the
cancerous lesions for simpler treatment. Screening is incidence of the problem.
at best opportunistic. Colposcopic services are also
lacking. With the absence of colposcopy early lesions The justification for the routine removal of the cervix
such as stage 1A1 and 742 are not likely to be at hysterectomy has often been the future risk of
diagnosed except in cone biopsy or hysterectomy cervical carcinoma'uu). ln women with previous
specimens. negative smear test results the incidence of cancer is
minimal (0.3%)(u'Dwith the higher risk groups being
Visual inspection with acetic acid, as a screening those who have not been screened. The resurgence
procedure, is likely to gain popularity for mass of the practice of sub-total hysterectomy in well-
screening. Butthe problem still exists with the lack of resourced parts of the world brings about the issue of
enough trained personnel to use it. lt has been well-planned and prolonged cervical pre-cancer
suggested that nurses and midwives can easily learn screening post-operatively. Cancer in the cervical
it and go one-step forward in treating patients with stump may be more difficult to handle, as spread is
pre-cancer. lt is likely many patients with false usually faster. As mentioned above screening in the
positive diagnosis would be treated by cryotherapy. third world countries is at best opportunistic but
Cases that would need colposcopic evaluation are again the bulk of the pathology requiring sub-total
not likely to get attention within the earliest possible hysterectomy really occurs in these same third world
time. countries. Problems with very large uterine fibroids
with massive pelvic adhesions; ruptured uterus from
It is therefore not surprising that most of the lesions obstructed labour and perforated uterus from un-safe
seen are advanced and radiotherapy offers the best abortion demanding subtotal hysterectomy still exist
in large numbers in the third world countries.
chances of survival. Radiotherapy has its own
problems. There are few radiation oncologists around
and the workload is so high. The radiation centres are
578
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11. Schiffman MH, Brinton LA. The epidemiology of Burnett A E, and Qian D et al. lnfluence Of
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37. Sommer FG, Walsh JW, Schwartz PE et al. neoplasia than targe loop excision? Lancet. 353:
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Emission Tomography for evaluating para-aortic Scoiland. Br J Obstet Gynaecol. L997; 84: 67- l
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45. 1980-1987. Br J Obstet Gynaecol. 1994; 101: --
34. McDonald TW, Morley GW, Choo Y et al. Fine 615-620.

Needle aspiration of paraaortic and pelvic nodes 46. Burghardt E, Giradi F, Lahousen M et al.
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'
580
(lnternational Federation of Studd.Churchill Livingstone. Edinburgh. Pages

Obstefrics stage 1A) 317-331.
1045.
47. Nunns David, Symonds 48. Dargent D, Brun JL, Roy M, Remy l. Pregnancies
Prognosis in cervical following radical trachelectomy for invasive
Obstetrics and cervical cancer. Gynecol Ancol L994;
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582
cHAPTER
46
Endometria I Hyperplasia
Baafuor K. Opoku, E. Y Kwawukume
Introduction The view has been expressed that these hyperplastic

lesions are precursors of endometrial cancer (1).
Endometrial hyperplasia is a general term that This belief was based on frequent co-existence of
encompasses a spectrum of proliferative endometrial hyperplastic lesions with invasive cancer. Often there
patterns. Thespectrum of changes affects both the is imperceptible transition from one to the other on
glandular and stromal elements of the endometrium hisiological examination. Endometrial hyperplasia
and is associated with periods of long-term however, has never been proved to be premalignant
unopposed estrogen stimulation of the endometrium. though they appear to evolve into frank cancer.
Typical causes include corpus luteum
insufficiency/anovulatory cycles (premenopause), Classification
polycystic ovary syndrome and obesity with There have been a lot of controversies surrounding
metabolic syndrome (aromatase conversion of the classification of endometrial hyperplasia. Two
ovarian androgens in adipose tissue), inappropriate commonly used terminologies were proposed by
post-menopausal h.ormone therapy (insufficient Vellios (2) and Kurman& Norris (3) and adopted by
r\- gestagens) or an estrogen/ androgen-producing the lnternational Society of Gynecologic

I
tumour. Hyperplasia often manifests as abnormal Pathologists. Both are presented in Table 1.
i
t
patterns of uterine bleeding.
r
I
i
t Ta ble I
!
I Vel lios classification Kurman& Norris classification
i
1. Cystic Hyperplasia 1. Simple hyperplasia
! 2. Adenomatous hyperplasia 2. Complex hyperplasia (adenomatous
3. Atypical adenomatous hyperplasia hyperplasia without cytologic atypia)
!
t
. Architectural atypia (mild, moderate, 3. Atypical hyperplasia (adenomatous
severe) hyperplasia with cytologic atypia)
I Cytologic atyPia (mild, moderate,
t '
l.
severe)
: 583
a
ln 1994, the WHO adopted the classification of 1. benign hyperplasia

Kurman & Norris and classified endometrial 2. endometrial intraepithelial neoplasia (ElN)
hyperplasia into 4 categories.
1. simple hyperplasia without atypia The existence of several classifications has
2. complex hyperplasia without atypia confused clinicians over the years, ln 2Ol4,Ihe
3. simple atypical hyperplasia WHO clarified issues and has come up with only 2
4. complex atypical hyperplasia categories (5):
Categories 7 and2 are considered benign and regress

1. hyperplasia without atypia
with treatment, while categories 3 and 4 are 2. alypical hyperplasia/ endometrioid
associated with progression to invasive endometrial i ntraepithel ial neoplasia
cancers within a few years, or co-exist with
endometrial cancers. This new classification reflects a better
understanding of molecular genetic changes. Table
Other authorities(4) classified endometrial 2 shows how this new classification correlates with
hyperplasias into older terminology.
Table 2: New WHO Classification

wHo 2014 Older terms/Synonyms Genetic changes Co-existent Progression
classification invasive to invasive
endometrial carcinoma
carcinoma
Hyperplasia . Benign endometrial Low level of somatic <7% RR: 1.01-
without atypia hyperplasia mutations in scattered 1.03
. Simple non-atypical glands with
hyperplasia morphology on HE
. Complex non- staining showing no
atypical hyperplasia changes
. Simple hyperplasia
without atypia
. Complex
hlperplasia without
atyoia
Atypical Complex atypical Many of the genetic 25-59% (5,6) RR: 14-45
hyperplasia/ hyperplasia changes typical for
Endometrioid Simple atypical endometrioid
intraepithelial hyperplasia endometrial cancer are
neoplasia Endometrial present, including:
intraepithelial micro satellite
neoplasia (ElN) instability; PAX2
inactivation; mutation
of PTEN, KRAS and
cTNNBI (p-catenin)
584
{ Endometri a I Hy perpl asi a
t
t
r is
Genetic changes and Potential for devetopment characterized by "skip and delays". Marked
I
t into carcinoma increase in the quantity of menstrual flow or more
F
I
Hyperplasias without atypia exhibit: r*9. relevant frequent bleeding may announce the presence of
ft* genetic changes. They are benign al@.$rffis after endometrial hyperplasia.
the endocrine milieu (physiologica{, fusvels)
has normalized. ln a few cases (1-3%), For the teenager with hyperplasia symptoms usually
t
to invasive disease may occur if ffie Eitdocrine manifest as periods of oligomenorrhoea followed by
i disorder persists over the long term. prolonged periods of bleeding per vaginam.
r
Endometrial curetting shows "Swiss Cheese"
I Atypical endometrial hyperplasias exhibit many of endometrium.
r the mutations typical for invasive endometrioid
r endometrial cancer (7). ln up to 60 % of cases, Differential diagnoses include endometrial
rt carcinoma, endometrial polyps, endometritis,
patients have coexisting invasive cancer or are at
( bleeding cervical, vaginal and vulval lesions.
I extremely high risk of developing invasive cancer.
r It is also recognized that endometrial hyperplasias Diagnosis of endometrial hyperplasia requires
r are not a single spectrum but fall into two functional histological examination of the endometrial tissue.
categories namely (8) i. Endometrial surveillance should include
a. Normal polyclonal endometria responding endometrial sampling by outpatient
r*
r diffusely to an abnormal hormonal endometrial biopsy.
r environment (endometrial hyperplasia 2. Diagnostic hysteroscopy should be
I occu rring af ter long term estrogen considered to facilitate or obtain an
?
r sti mu lation leadi ng to carcinoma) endometrial sample, especiallywhere
b. lntrinsically proliferative monoclonal outpatient sampling fails or is non-
t
t
r lesionsthat arise focally conferring an diagnostic.
I
t
increased risk for development of carcinoma, 3. Transvaginal ultrasound may have a role in
i i.e. endometrial adenocarcinoma developing diagnosing endometrial hyperplasia in pre-
without prior endometrial hyperplasia. lt andpostmenopausal women.
I
{
tends to be less well differentiated and have a 4. Direct visualisation and biopsy of the uterine
{ poorer prognosis cavity using hysteroscopy should be
t undertaken whereendometrial hyperplasia
I
? Causes has been diagnosed within a polyp or other

I
I Endometrial hyperplasia occurs during periods of discrete focal lesion.
r\- long-term unopposed estrogen stimulation such as 5. There is insufficient evidence evaluating CT
I
I anovulation, particularly around the time of sca n, d if f u s io n -we igh ted
i
f menopause. magneticresonance imaging (MRl) or
I
Typical causes include biomarkers as aids in the management of
I
t: . anovulatorycycles (pre-menopause) endometrial hyperplasia andtheir use is not
r corpus luteum insufficiency routinely recommended.
. polycystic ovary syndrome
a
. obesity with metabolic syndrome Treatment
(aromatase conversion of ovarian Treatment depends on the degree of atypicality of the
androgens in adipose tissue) hyperplasia and the age of the patient. The risk of
. inappropriate hormone therapy post carcinoma development without cytologic atypia
menopause from the studies of Kurman is about 2% (6). There
I
i . oestrogen-producing tumours are two modal ities of treatment:
( a. Conservative therapy (i.e. hormonal)
Diasnosis b. Surgical treatment (i.e. hysterectomy)
Abnormal uterine bleeding is the most frequent
: symptom of endometrial hyperplasia. lt can occur at Conservative Therapy
If any time during the reproductive years but is most This is directed towards preservation of child bearing
a common during the climacteric period. The bleeding function. Younger women with hyperplasia without
r
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:
oa
585
atypia are ideal candidates for conservative therapy. progestogens or the LNG-l US.
Treatment with oral progestogens or the
A) For the teenager with anovulatory cycles LNG-IUS should be for a minimum of 6
i. Medroxyprogesterone acetate tabtets 10mg months in order to induce histological
daily for a period of 10 to 14 days repeated regression.
for about 3 to 6 cycles provide a regular lf adverse effects are tolerable and fertility is
withdrawal bleeding. This prevents the not desired, women should be encouraged to
development of hyperplastic endometrium. retain the LNG-lUS for up to 5 years as this
ln most cases after the treatment period of relapse, especially if it
reduces the risk
regular ovulatory cycles resume followed by alleviates abnormal uterine bleeding
regu lar menstrual periods. symptoms.
ii. Six cycles of low dose combined oral
contraceptives is also a reasonable choice of iii) Combined oral contraceptives can also be
treatment. The presence of ovulatory cycles used in these patients. This will induce
is assessed in the usual way. monthly withdrawal bleeding. Patients are
iii. Should anovulatory cycles continue, followed up with endometrial sampling in 6
ovulation induction with drugs may be months.
undertaken.
Hyperplasia with atypia
B) Women in the reproductive age group (20's Although about half can regress spontaneously,
and 30's) given the risk of transition to carcinoma these
Hyperplasia without atvpia patients require treatment.
i. The patient with hyperplasia without atypia . Total hysterectomy is recommended.A
can be managed by long-term follow-up if no laparoscopic approach, if available, is
further symptoms develop afterendometrial preferable to an abdominal approach as it
evacuation. Endometrial sampling should be isassociated with a shorter hospital stay, less
repeated if abnormal bleeding occurs. postoperative pain and quicker
Otherwise endometrial sampling should be recovery.There is no benefit from
performed after 6 months. Kurman's studies intraoperative frozen section analysis of the
(10) show that most endometrial endometrium or routine lymphadenectomy.
hyperplasias without cytological atypia . Postmenopausal women should be offered
regress. Such.hyperplasias are also total hysterectomy and bilateral salpingo-
frequently removed by the dilatation and oophorectomy (BSO).For premenopausal
curettage alone, if done. women, the decision to remove the ovaries
ii, Both oral progestogens and levonorgestrel- should be individualized.
releasing intrauterine systems ILNG-lUS] are . Endometrial ablation is not recommended
eff ective in ach ieving regression of because complete and persistent
endometrial hyperplasia without atypia.The endometrial destructioncannot be ensured.
LNG-IUS should be the first-line medical Moreover, intrauterine adhesion formation
treatment because compared with oral may make endometrial
progestogens it has a higher disease h istologicalsu rvei I la nce d ifficu lt.
regression rate with a more favourable
bleeding profile and is associated with fewer Patients who wish to retain their fertility should be
adverse effects. counselled about the risks of underlying
Continuous progestogens should be used malignancyand subsequent progression to
(medroxyprogesterone 10-20 mg/day or endometrial cancer.
norethisteronel0-l5 mg/day) for women . Pretreatment investigations should aim to
who decline the LNG-l US. rule out invasive endometrial cancer or co-
Cyclical progestogens are not recommended existing ovariancancer-
because they are less effective in inducing
. First-line treatment with the LNG-lUS
regression compared with continuous oral should be recommended, with oral
586
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r Endometri a I Hy pe rp I asi a
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progestogens as a second-best alternative. Other treatment options

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,l Those with mild atypia can be treated with a . Danazol has also been reported to be
progestin such as medroxy-progesterone 10 effective in reversing endometrial
t
hyperplasia in doses of 400 mg daily for 3
I
{r- mg twice daily continuously or for 10 to 14

days monthly. The combined low dce oral months.
I contraceptive tablet is an alternate treatment . The use of Gonadotrophin-releasing
regimen if contraception is also desired. hormone analogues has been shown to be
. Once fertility is no longer required, effective and well tolerated. Problems
hysterectomy should be offered in view of the include the cost of the drugs and associated
; high risk of diseaserelapse. Hysterectomy osteoporosis.
should also be offered those with moderate
to severe atypia. ln the work of Ferenczy et al Discussions and Controversies
(1 1), patients with cytologic atypia who were ln the management of women with endometrial
treated with high dose progestin had 75% hyperplasia the principal concern is the risk of the
persistence or recurrence while 25% patient having concomitant carcinoma of the
developed cancer within 2 to 7 years of the endometrium or developing carcinoma in the future.
?. The aims of treatment for endometrial hyperplasia
initiation of hormonal therapy.
are therefore to control symptoms such as heavy
Follow-up for women noi undergoing hysterectomy bleeding and also to detect concomitant invasive
. Endometrial surveillance should include cancer and to prevent the subsequent development
I
repeated endometria I biopsy for h istology of invasive cancer.

L
. Review intervals should be every 3 months

until two consecutive negative biopsies are Endometrial hyperplasia has been linked to the
i
obtai ned. development of endometrial cancer. There is still the
I
. ln asymptomatic women with a uterus and need to develop more precise and reproducible
evidence of histological disease regression, criteria for determining the malignant potential for
based upon a minimum of two consecutive various forms of hyperplasia.
negative endometrial biopsies, long-term
follow-up with endometrial biopsy every Cellular atypia is the single most important indicator
of the possible presence of invasive cancer in
6-72 months is recommended until a
hysterectomy is performed. association with hyperplasia and the likelihood of
l
i
persistence, recurrence and progression to frank
Older Patients ma I igna ncy after conservative thera py.
The risk of carcinoma increases in older patients.
Older patients with moderate to severe cytologic There is still the need to determine the optimal dose
atypical hyperplasia generally require hysterectomy. and duration of progestin therapy for use in
lf hysterectomy is medically unadvisable, long term conservative therapy. Although there is no generally
high dose progestin therapy can be used. accepted classification criteria two groups of
hyperplasia emerge. The first termed hyperplasia
Depo-medroxy progesterone acetate 300mg and with little malignant potential. The second
intramuscularly initially, followed by 150mg i.m termed endometrial intraepithelial neoplasia. This
monthly for 6 months. The patient will remain represents a truly premalignant condition. lt is
amenorrheic after the therapy. Sampling of the distinguished by cellular alypia and a reduced
endometrium should be performed at 6 - monthly stromalvolume.
intervals.
The correlation between histopathology and clinical
High dose progestins are generally well tolerated. The behavior is not as good as one might hope for. ln all
main side effects being weight gain, edema, an experienced gynecological pathologist is essential
I headaches, thromboph lebitis. to help in precise diagnosis and therefore

management.
:
587
REFERENCES
1 Cullen f S. cancer o the uterus; Kandoth C, Schultz N, Cherniack A D. et al,

Appleton and Co 19A0. Cancer Genome Atlas Research Network .
2 Vellios F. Endometrial
lntegrated genomic characterization of
of endometria I ca rci noma.
1972; 7: 201-229 ''' -':'=' endometrial carci noma. Natu re.
Kurman R J and Norris H J. EydfuffiS#-'rl.'' 2013;497:67-73
criteria for distinguishing atypicat emdeffi# Mutter G L, Boynton K A et al Allelotype
m a p p i n g of u n sta b Ie m i crosate I I i tes estab/rshes
hyperp\asia from weII differentiated-
ii
Cancer1982;49:2547-2559. ' "r ,:':: direct lineage continuig between endometrial
t pre cancers and cancer, Cancer Research
Owings R A, Quick C M. Endometrlaf: ;'::: .
1996; 56: 4483-4486

i n t r a e p i th e I i a I n eop I a s i a. A rc h Pa th el.trbE-ffii*
Meck H, Luttges J et al. Treatment of
20 1 4; 1 38: 484-49 1. [PubMed : 2467867&] precursors sf endometria I hyperplasia.
Zaino R, Carinelli S G, E//enson L H, Lyon: Gynecalogic Oncology L 994; 52: 37 3-37 8.
WHO Press; 2014. Tumours of the uterine 10 Kurman R J, Kaminski P F. Behavior of
Corp u s : e p i th e I i a I Tu mo u rs a nd Precu rsars;' Fg. endometrial hyperplasia, a long term study of
125-126 "untreated" hyperplasia in 170 patients, Cancer
1985;56:403.
Antonsen S L, Ulriih t- Hogdatl C. Patients
11 Ferenczy A, Gelfand M. The Biologic
with atypical hyperplasia of the endometrium in progestogen
Significance of cytologic atypia
should be treated in oncological centers. treated endometrial hyperplasia. Am J.
GynecolOncol. 20L2; 1 25: 124-128. ObstetGynecol 1989; 1 60: 1 26.
588
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cHAPTER
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47
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1
Endometria! Cancer
i
t Henry Laryea, A A Odukogbe and B Audu, EY Kwawukume
INCIDENCE younger agesu Large weight gain during adult life is a

I
;'* strong predictor of risku'u.
;I Endometrial cancer (EC) forms over 95% of cancers
of the uterus while the remaining five percent are Due to aromatisation of androstenedione in adipose
those of the uterine mesenchyme. lt is the
I
I tissue, post-menopausal obese women are known to
i
- commonest gynaecologic cancer in developed have higher endogenous oestrogens than lean
I countries where rates are highest in White women women'. Obesity is also associated with reduced
compared to Blacks, Hispanics and Asians'. ln sub- levels of sex hormone-binding globulin8. This further
Saharan Africa (SSA), carcinoma of the cervix is the increases the amount of bioavailable oestrogens.
I
) commonest female genital malignancy followed by

choriocarcinoma, ovarian and endometrial cancers Treatment planning for obese women is made
+
respectively'. ln some parts of Africa, EC occurs ten difficult due to the association of obesity with
; times less commonly compared to developed world'. diabetes mellitus, hypertension and arteriosclerotic
l
Endometrial cancer affects women primarily in the disease. Obesity also serves as a poor prognostlc
peri-menopausal and post-menopausal years, with factor because of operative risk.
l
i over 90% of the cases occurring in those between 50
r* and 65 yearst.
2. Metabolic syndrome.
Diabetes mellitus and hypertension, components of
CAUSESAND RISK FACTORS the metabolic syndrome are markers of obesity and
have been associated with a relative risk of 1.81n
The causes of endometrial cancer are not known but and odds ratio of 2.1'o respectively. The association
current evidence implicates factors that lead to between diabetes mellitus and endometrial cancer
unopposed oestrogenic stimulation of the may be explained by the elevated oestrogen levels,
endometrium either directly or indirectly. Thus the hyperinsulinaemia or lnsulin-like Growth Factor-l
following risk factors are thought to predispose to the (lGF-1) in diabetic women".
development of EC:
lf not aetiological, the association of these conditions
1. Obesity with EC has important screening implications and is
High body mass indices of overweight (25 - 30kg/m') important in the pre - operative and post - operative
bnd obesity (> 30kg/m') constitute the major risk care of these patients.
factor associated with endometrial carcinoma. The
relative risks of overweight and obesity are L.32 and 3. Excessive oestrogen sti m u lation
:
f, 2.54 respectively'. Weight closer to the time of Syndromes of increased ehdogenous oestrogenic
diagnosis appears to be more relevant than weight at stimulation are associated with the production of
endogenous oestrogens in excess of progestins.
589
There is a higher relative risk of endometrial cancer raised by about two fold for 5 or more years after
because there is a longer stimulation of the discontinuation of use". This stimulatory effect of
endometriu m by estrogens as is seen in: ,,. ,,, .r.
oestrogen is seen to occur irrespective of the route of
:.: administration.
a. Obese post menopausalwomen.
b. Early age at menarche and late age at b. When women use prophylactic or therapeutic
Early age at menarche (defined as before l-2-'geals)is
tamoxifen for breast cancer, the relative risk of
associated wilh 2.4 - fold increased" ri* en developing EC is 2.53 times higher compared to age
compared with less than 15 years". matched controls. Premenopausal women using it
for treatment have no risk while postmenopausal
With late age of menopause, a menstruation span
women have an increased risk of 4.0". This risk, as
longer than 39 years was associated with 4.2 times
with hormone replacement therapy depends on dose
the risk of one shorter than 25 years". The
and length of use.
menstruation span indicates years between
menarche and menopause excluding pregnancy 5. Heredity
related-time. There is a small number of sporadic occurrences of
endometrial carcinoma not preceded by risk factors
c. ln patients with polycystic ovarian syndrome, the
of unopposed oestrogen stimulation. These tumours
risk of endometrial cancer is increased in younger
tend to be less well differentiated and to have a
women. The diagnosis of the syndrome has been poorer prognosis. They are the inherited forms of
made in up to 30% of cases with endometrial cancer
endometrial carcinoma. This appears to be of more
in selected groups of premenopausalwomen".
importance in EC in younger patients'o. The majority
of familial clustering of endometrial cancers is in
d. lnfertility and low parity. Nulligravid women have a
five times greater incidence of endometrial cancer
association with colorectal cancer as part of
hered ita ry non-polyposis colorecta I ca ncer
than women of higher parity (5 or more children).
(HNPCC),,.
Obesity and polycystic ovarian syndrome may be
confou nding factors'0.
HNPCC is an autosomal dominant condition
characterized by colorectal cancer occurring at a
e. Oestrogen secreting granulosa cell and theca cell
younger age than is found in the general population.
tumours of the ovary.
The extra-colonic malignancies include those of the
These have been associated with endometrial ovary, endometrium, stomach, small intestine, renal
carcinoma with incidences ranging from 3.S% to and biliarytracts.
277"'u
Errors during replication of DNA within dividing cells
4. Exogenous oestrogens are recognized and repaired by gene products also
known as mismatch repair genes. The loss of
a. Hormone replacement therapy. Nearly all function of a mismatch repair gene by its mutations
case-control and cohort studies that have examined may then result in the accumulation of mutations in
the issue found use of unopposed oestrogen the insertion and deletion loops. When mutations
replacement therapy to be predictive of endometrial occur in MLH1, MSH2, MSH6 or PMS2, women
cancer'u' ", with use of oestrogen therapy for 5 or have up to 40 - 60% lifetime risk of developing both
more years increasing the risk of endometrial cancer endometrial and colorectal cancers, and 9 12% -
by 10-30folds'u. lifetime risk of having ovarian cancef'.
The risk of endometrial cancer escalates with Therefore a family history of endometrial cancer
increasing dose of conjugated oestrogens, although appears to be associated with a greater risk of
large risks have been seen in women taking low-dose disease in a young woman (age less than 50 years).
oestrogen preparations. The risk persists fur many Also young women with a family liistory of colorectal
years after use. lt has been suggested that it remains cancer appear to be at increased risk of endometrial
cancer.
590
Ndometrial Cancer
6. Socioeconomic status. Good history, appropriate clinical investigation of

Hicks and colleagues in reviewing entries in the irregular withdrawal bleeding and aggressive use of
National Cancer Data Base in the United States of endometrial sampling would increase early
America (USA) observed that black wornen a e,often diagnosis of an existing endometrial cancer.
diagnosed with less favourable hist6l@iifs, rnore
advanced stages of disease and poorly differentiated 2.Oral contraceptives
tumours than white women. They thus have more EC The use of the low dose combined oral contraceptive
pills reduces the risk of endometrial cancer and long
deaths".
- term use appears to reduce the risk further' The
FACTORS THAT LOWER THE RISK OF protective effect lasts for 20 or more years after
ENDOMETRIAL CARC!NOMA discontinuation'u. Stages of disease Percentage I 80%
il 60% ilr30% rv5%
Through reducing the risk factors and adjusting
lifestyles, the risk of having EC may be lowered, 3. Life-stylefactors
although most cases cannot be prevented". The association between smoking and endometrial
cancer is unclear. There is a known reduction in
1. Progesterone protection circulating oestrogens among smokers, which might
Administration of cyclic progesterone (for at least 10 lower the risk of endometrial cancer. The deadly
days of each treatment cycle) appears to mitigate the consequences of smoking clearly outweigh this
continuous mitotic stimulation of the endometrium apparent advantage.
.
by unopposed oestrogen therapy and its incomplete
shedding". Progesterone inhibits the effect of An active life style may be protective against
I
oestrogen by decreasing oestrogen receptors and endometrial cancer". Greater consumption of
increasing the activity of enzymes (estradiol-17b vegetables and certain dairy products were
dehydrogenase) that metabolise oestradiol to less associated with a statistically significant decreased
potent metabolites. lt also inhibits the synthesis of risk.
oestrogen receptors. The most popular regimen is
I
0.62Smg of conjugated oestrogens for 25 days in a There appears to be no correlation between alcohol
i
f month, with 1Omg of medroxy-progesterone acetate consumption and the development of EC.
r on days 15 to 25. For women who do not tolerate the
( monthly withdrawal bleeding from the cyclic On account of the foregoing, women should be
I
t regimen, daily progesterone such as 2.5mg of educated about the risk factors and symptoms of
medroxyprogesterone along with uninterrupted endometrial cancer in a bid to prevent or present in
oestrogen provides good hormonal replacement as early stages.
well as suppression of the stimulatory effects of
WPES OF ENDOMETRIAL CANCER
I
oestrogen. Long-terma menorrhoea usua ly resu lts.
I
Analysis of many studies suggests that progesterone

Based on clinico - pathological and molecular
characteristics, two types of endometrial carcinomas
augmentation of exogenous oestrogen will not
have now been identified as shown in Table 1'*.
prevent endometrial carcinoma from occurring',.
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591
Characteristics Tvpe,l Type ll

Age (years) 55-65 65-75
Clinical features U no p posed oestrogen ;''obesity, Atrophy, thin physique
hypertension, d iabetes mel litus
Histology Endometrioid adenocarcinoma Non - endometrioid [serous, clear
cell, carcinosarcoma / Malignant
Mixed Mullerian Tumour (MMMT),
u nd ifferentiated carci nomasl
Precursor Hyperplasia Endometrial intraepithelial carcinoma
Genetic alterations PTEN, KRAS, CTNNB1, PIK3CA. TP53, aneuploidy, PIK3CA
M LH I promoter hypermethylation
Behaviour lndolent, spread via lymphatics Aggressive, i ntraperitoneal and
lymphatic spread
Percentage B0-90 lo-20
SURVIVAL ln the study of patients with endometrioid

EC is generally perceived as having a favourable endometrial cancer by Gottwald et al, reported in
prognosis because in most instances, it is confined to
2010, both the disease - free survival (DFS) and the
the uterus and can be treated successfully. overall S-year survival figures were shown to be
Adenocarcinoma of the endometrium that develops
dependent on age of patient in years at the time of
after prolonged unopposed oestrogen use for most diagnosis, family history
parts results in well-differentiated tumours. They are
of cancer, number of
pregnancies, menopausal status, age at menopause,
with minimal myometrial invasion. When these presence of medical illness, myometrial infiltration,
cancers are diagnosed at the first irregular tumour grade, extent of surgery and use of adjuvant
postmenopausal bleeding or during routine
treatment2s. The figures obtained are displayed in
surveillance, immediate treatment is effective and
Iable2, which compares their rates with more recent
the prognosis is excellent.
statistics of endometrial tumours g enerally,, .
Stage Disease-free 5 year survival: 5 year survival: EC o/o27 \-/-\

survival (DFS): Endometrioid EC o/o26
Endometrioid EC
o/
/o
93.8 94.8 88.0 flA), 75.0 0B)
il 72.2 72.2 69.0
ilt 50.0 53.8 58.0 flilA), 50.0 0il8), 47.0 UilC)
IV 0.0 0.0 17.0 flVA), 15.0 0VB)
HISTOLOGICAL TYPES . Clearcellcarcinoma

The several histologic varieties of EC include: . Mucinous carcinoma
. Endometrioidadenocarcinoma . Squamous carcinoma
. Villoglandularcarcinoma . Mixed types of carcinoma
. Secretoryadenocarcinoma . Undifferentiatedcarcinoma
. Ciliatedcellcarcinoma Almost all endometrial carcinomas are
Endometrioid adenocarcinoma with adenocarcinomas. About 70 to 7b"/o are pure
sq uamous d ifferentiation endometrioid histological types while 20 to 25%
Serous carcinoma
I have mixed squamous elements. The rest are rare. ln
592
I Ndometrial Cancer
I
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r the endometrioid type, squamous epithelium vein drains into the left renal vein, distant
I
i commonly coexists with the glandular elements of metastasis can occur directly into the upper
t,
I'
endometrial carcinoma. lf the squamous element abdomen.
I i.- comprises at least 70% of the tumour and appears b. The broad ligament lymphatics (paracervical and
l
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benign as in squamous metaplasia, the term parametrial lymphatics). They drain directly to
t adenoacanthoma is used. The prognosisiis similar to the pelvic nodes (internal iliac nodes).
?
rI that for adenocarcinoma of comparable c. The round ligament lymphatics. A small lymphatic
I
differentiation. lf the squamous component appears branch along the round ligament explains the
I uncommon occurrence of tumour involvement of
r malignant, the term adenosquamous carcinoma is
t the external iliac and inguinal lymph nodes.
r used. They tend to be less well differentiated and
I
( have a poorer prognosis than typical
The frequency of nodal involvement becomes much
adenocarcinomas or adenoacanthomas. With
I
greater with higher-grade tumours and with greater

papillary endometrial carcinoma, the tumour takes
1
r a
depth of myometrial invasion. The risk of lymph node
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papillaryform.
I
involvement appears to be negligible for endometrial
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l Clear cell adenocarcinoma, serous carcinoma and carcinoma involving only the endometrium. With
primary squamous cell carcinoma are very rare, invasion of the inner third of the myometrium, there
occurring usually in the postmenopausal years. They is negligible risk of node involvement for grade 1 and
I
are virulent with poor prognosis. Secretory grade2 cases. lf the outer third of the myometrium is
I
carcinomas are extremely rare occurring primarily in involved, the risk of nodal metastasis is greatly
I
I premenopausal patients. They are mostly diagnosed increased. The pelvic nodes provide a valid indicator
in the presence of progestational stimulation. The of the risk.
!
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prognosis is good. Mucinous carcinomas are also
2. Transperitoneal spread
extremely rare and appear to have good prognosis.
{ Direct peritonealspread of tumourcan occur.
: They usually occur in postmenopausal women.
;.,
3. Haematogenous spread
PATTERN OF SPREAD OF ENDOMETRIAL
i
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CARCINOMA
Liver metastases occu r more d irectly by
: haematogenous extension.
:
Endometrial carcinoma spreads through the
( following mechanisms:
STAGING OF ENDOMETRIAL CARCINOMA
I
t
The two methods of staging endometrial cancer are
basically the same and utilize the three factors: the
1. Lymphatic spread
:
This occurs through the following lymphatic extent of the tumour, involvement of lymph nodes
I
pathways. and distant metastases. The FIGO (lnternational

a. Branches from the tubal and ovarian pedicles Federation of Gynecology and Obstetrics) and the
(i nfundi bu lo-pelvic ligaments). American Joint Committee on Cancer TNM staging
These are large lymphatics that drain into the systems are shown in Table 3 below".
paraaortic lymph nodes. Because the left ovarian
II
593
Table 3: Surgical staeins of endometrial cancer
Stage TNM Classification FIGO Staging

0 Tis, N0, M0 Carcinamain - situ. This is not included in FIGO staging.
T1, NO, MO Tumou,r confined to the corpus uteri.
IA T1a, N0, M0 Tumour'invofues the endometrium and less than half of the depth of
the myometrium.
IB T1b, NO, MO Tumour involves the endometrium and more than half of the depth
of the myometrium.
il T2, NO, MO Tumour invades cervical stroma, but does not extend beyond the
uterus. Endocervical glandular involvement only should be regarded
as Stage l.
ilt T3, NO, MO Local and / or regional spread of the tumour. Tumour involves the
body of the uterus including the serosa, fallopian tubes, ovaries,
vagina, parametrium and pelvic I peri- aortic lymph nodes.
iltA T3a, N0, M0 Tumour involves the body of the uterus including the serosa and I or
fallopian tubes / ovaries.
iltB T3b, NO, MO Tumour involves the body of the uterus including the serosa and I or
fallopian tubes / ovaries I vagina and I or parametrium. Report
positive cytology separately without changing stage.
iltc1 T1 to T3, N1, MO Tumour involves the body of the uterus including the serosa and I or
fallopian tubes / ovaries I vagina and paametrium. The pelvic
lymph nodes are involved.
lrcz T1 to T3, N2, M0 Tumour involves the body of the uterus including the serosa and I or
fallopian tubes / ovaries I vagina and parametrium. The peri- aortic
lymph nodes with or without pelvic lymph nodesare involved.
IV Tumour involves the mucosa of the urinary bladder and / or the
rectum, the inguinal lymph nodes, and I or distant organs, such as
the bones, omentum or lungs.
IVA 14, any N, MO Tumour involves the mucosa of the rectum or bladder.
IVB Any t, any N, M1 Tumour has spread to distant lymph nodes, the upper abdomen,
the omentum, or to distant organs such as the lungs or bones.
L. Histological staging 2. Clinicalstaging

Clinical staging is done under the following
Histopathologically, cases of endometrial carcinoma conditions:
should be grouped with regards to the degree of
d ifferentiation of the adenoca rci noma as fol lows: 1. When patients are inoperable or
2. When completion of the entire surgical staging is
G1 = 5% or less of a nonsquamous or nonmorular not possible.
solid growth pattern.
The FIGO classification of the clinical stages of the
G2 :6"/" to 50% of a nonsquamous or nonmorular disease is based on a standard cavity length and
solid growth pattern. extension of the disease beyond the uterus and
pelvis.
G3 : more than 50% of a non-squamous or
non moru lar sol id growth pattern. Stage 0. Carcinoma in situ. Histological findings are
594
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t suspicious of mal ignancy. Approximately 80% of all endometrial carcinomas

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t Stage l.
Carcinoma is confined to the corpus, fall into the favourable category.
r
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includingthe isthmus.
[ ".. Stage la. The length of the uterine cavity is:8cm or Poor prognostic histological types are papillary
rt carcinomas, clear cell carcinomas and
I Stage lb. The length of the uterine cavity is rnore than adenosquamous carcinomas.
i
{. 8cm.
I
l Stage ll. Carcinoma involves the corpus and eervix c. Uterine size. The size of the uterus determines the
but not extend i ng outside the uterus. clinical staging in stage l. Uterine size has also
f
I Stage Ill. Carcinoma extends outside the uterus but been correlated with prognosis.
1 not outside the true pelvis. d. Depth of myometrial invasion. The degree of
I
Stage lV. Carcinoma extends outside true pelvis or myometrial invasion does correlate with the risk of
i'
l obviously involves the mucosa of the spread outside the uterus. The higher grade and
r bladder or rectum. higher stage tumours in general have the deepest
L Stage lVa. Spread to the bladderor intestines. myometrial penetration. The depth of myometrial
i
,- Stage lVb. Spread to distant organs.

invasion is the most reliable indicator of tumour
volume and tumour size is prognostic.
PROGNOSTIC FACTORS
Many variables affect the behaviour of endometrial
1,
3. Other prognostic variables.
adenocarcinoma. The main ones are as follow:
These are less important in making treatment
r
{ decisions but their addition to the dominant
1. Clinicalfactors
* a. The patient's age at diagnosis. Younger women
prognostic variables may alter the final surgical
I stage.
I with endometrial carcinoma have an improved
prognosis while older patients have tumours of
a. lncreasing age of the patient. The mean age at
diagnosis tends to rise and the other prognostic
I higher stages and grades and therefore have
factors tend to accelerate as age increases. The
poorer prognosis,
b. Race. White patients have higher survival rates five - year net survival ranges from 87% in 15 -
i
than their black counterparts. This is partially -
39 year-olds to 57% in 80 99 year-olds for
explained by the higher-grade tumours among
patients diagnosed with uterine cancer in
:
England during 2009 -2013'0.
blackwomen.
( c. Tumour stage. The higher the stage at diagnosis, b. Steroid hormone receptors. The endometrium is
I
I the poorer is the prognosis. ln developed sensitive to oestrogen a nd progesterone
I.
countries, most cases (80%) are diagnosed in stimulation. The steroid receptors occupy almost
all nuclear locations. The steroid receptor level in
I
stage lwhich
accounts for a favourable
i.
prognosis", while in developing countries, less endometrial carcinoma is lower than in normal
endometrium.
than 20% present without lymph node
involvement".
The highest level of oestrogen and progesterone
receptors in tumours have been found in the well
2. Pathologicfactors
a. Histological grade. This is a major determinant of differentiated (grade 1) tumours and the lowest
prognosis. A decrease in tumour differentiation is in grade 3 tumours. Survival rates within each
accompanied by a decrease in survival. stage have been noted to be better for women
Histological differentiation is also related to lymph with receptor-rich tumours than for those with
node metastasis. The poorly differentiated a receptor-negative tu mou rs.
tumour is, the higher the risk of lymph node
metastasis. The higher grade carries an increased
Progesterone receptor status is the most
sign ificant prognostic factor after clinical stage.
risk of recurrence of the tumour.
b. Histological type. The best prognosis is associated
Receptor status appears to
influence tumour
with the typical adenocarcinomas, response to progestational therapy. Steroid
adenoacanthomas and secretory carcinomas.
receptor measurement of the tissues of primary
s95
endometrial adenocarcinomas is obtained at the greater than or equal to 50 years (90% of patients),
time of intraoperative specimen evaluation. early menarche, late menopause, nulliparity,
infertility, hypertension, diabetes mellitus, obesity
c. Peritoneal cytology. Results of peritonea,[@y (metabolic disease syndrome), anovulation,
as a prognostic factor have been @flg unopposed oestrogen exposure and tamoxifen use.
Patients with positive cytology are at,higfur risk
for recurrent disease. The presence of malignant Signs
cells is predictive of other poor prognostic f;actors ln the early stages of the disease the patient usually
including advanced histological grade, depth of looks clinically well. The only physical finding may be
myometrial invasion and lymph node metastasis. the bleeding from the uterine cavity. However, in
d. Cervical invasion, lymph-vascular space advanced stages of the disease the patient is
invasion, adnexal spread and presence of generally anaemic and there may be evidence of loss
intraperitoneal disease. These are clear of weight. Fever and offensive vaginal discharge may
indicators of aggressive disease. All correlate well occur with superimposition of infection of the uterine
with other poor prognostic factors. Any of these contents. The uterus may be enlarged and
factors indicate a higher risk for lymph node occasionally enlarged inguinalfemoral nodes may be
metastasis. palpated.
DlAGNOSIS 0nce a clinical suspicion of endometrial carcinoma is

entertained, the definitive diagnosis is hinged on
The definitive diagnosis of endometrial cancer is histological examination. Therefore, an endometrial
based on histological examination. This is preceded
biopsy is mandatory to diagnose or exclude
by a clinical suspicion from the history and physical malignancy.
examination findings. The relatively high survival
rates for early-stage disease emphasize the The principal diagnostic tools used in the evaluation
importance of early diagnosis and treatment. of suspected endometrial carcinoma are:
Symptoms 1. Transvaginal ultrasound scan (TVS)

lrregular or post-menopausal vaginal bleeding is the This is the primary tool for evaluating a suspected
commonest symptom of endometrial cancer. case of endometrial cancer. lt identifies the presence
Although it may present as a symptom of other of the tumour as well as myometrial invasion. With
malignancies, especially cervical cancer, there TVS, the thickness of the endometrium is measured
should be a high index oT suspicion for endometrial as well as imaging of focal abnormalities within the
cancer. Particularly since about 75"/" of cases of endometrial cavity and adnexal pathology. The
endometrial cancer occurs in postmenopausal thickness of endometrium used as cut-off may need
women. ln this age group, the reported incidence of to be varied according to age, ethnic group, use of
endometrial carcinoma in patients with uterine hormone replacement therapy and perhaps body
bleeding ranges from 4 to 247"3'. The bleeding may mass. Generally, a cut-off point of 3-4mm
be associated with offensive vaginal discharge, emdometrial thickness is advocated. Transvaginal
especially in the presence of a draining pyometra. ultrasound scan also excludes ovarian disease. 2.
Abdominal pain and distension may occur late in the Hysteroscopy
disease.
The role of hysteroscopy is controversial. The
Other differential diagnoses in the context of increased sensitivity of endometrial biopsy when
abnormal vaginal bleeding include cervical cancer, accompanied by hysteroscopy has made this the
endometrial polyps, endometritis, degenerating sub- gold standard for the investigation of women with
mucous uterine fibroids, vaginal and vulval lesions possible symptoms of endometrial cancer.
and ovarian tumours (especially granulosa cell Approximately 50% of women with abnormal uterine
tumour). The presence of the risk / epidemiological bleeding will have evidence of uierine pathology at
factors outlined above further increases the suspicion hysteroscopy. ln premenopausal women the
of a diagnosis of endometrial cancer. These are age commonest findings are uterine fibroids, endometrial
596
I
t
r Ndometrial Cancer
I
J
t polyps and simple hyperplasia. The incidence of SUMMARY OF PREOPERATIVE ASSESSMENT

il
l complex hyperplasia or cancer is generally less than STUDI ES I N ENDOMETRIAL CANCER
r
t.
7%.ln postmenopausal women atrophie changes are
[*
ti
the commonest findings. There ls #,'g$+ificant l. Detailed history. This will include family history of
t increase in the incidence of complexftypffiia and cancer, which may provide clues to the risk of
ti
concomitant cancers. lt may suggest that additional
r{ evaluation studies be performed such as
t 3. Other radiological investigations colonoscopy. The presence of pelvic pain or referred
These help with staging of the disease. They include leg pain, leg oedema or swelling, disturbances in
rI chest X-ray (CXR), intravenous urography (lVU), bowel functions, abnormal abdominal swelling,
I computerized tomography scan (CTS) and magnetic pelvic pressure, excesgive flatulence and early
resonance imaging (MRl). CXR is needed to identify satiety may indicate more advanced disease than
r
l
chest secondaries and pleural effusion, while suspected.

r
t obstructive uropathy from compression effect and
i' also the course of the ureters are evaluated with an 2. Complete general physical examination.
I
lVU. MRI is optimal in evaluating myometrial and Attention should be paid to careful palpation of
cervical invasion, but CT scan is superior in axillary, supraclavicular and inguinal lymph nodes.
identifying lymph node involvement. Abdominal CTS
I
t' should be carried outto assess extrapelvic spread. 3. Pelvic examination. This includes the following:
rt lnspection of vulva, palpation of Bartholin's glands,
t
4. Histological examination of endometrial tissue speculum examination of the vagina, Papanicolaou
The diagnosis of endometrial cancer is established by smear, bimanual examination of the uterus to
r histological examination of the endometrium. This determine uterine size, adnexal masses, or other
I
I
follows a clinical suspicion and differential diagnosis. pelvic extension of the tumour. Rectovaginal
r It is necessary to obtain an adequate biopsy examination should also be done to determine
.. specimen using dilatation endometrial curettage or possible extension to the parametrium or spread into
I
any of the modern devices such as the Manual the uterosacral ligaments. Endocervical curettage
{
t Vacuum Aspirator, Pipelle, Tis-U-Trap and Vabra and sounding of the endometrial cavity should also
aspirator. Histological examination will distinguish be performed to help in clinicalstaging.
I benign from malignant disease, and severe atypia
I
from invasive lesion. lt will also identify the 4. Blood tests. The laboratory tests that are useful
r histological type and grade of the disease. Both include: complete haematological profile, liver and
I
histiotype and degree of differentiation are vital in kidney function tests, serum electrolyte
t
I
i planning the management of the disease. determinations and urinalysis. The ovarian cancer
antigen, CA-125 levels appear to have a useful
I
{
lf endometrial carcinoma is found, endocervical predictive value in the preoperative assessment of
curettage is performed to rule out invasion of the patients. A higher than normal value should alert the
a endocervix. A fractional curettage should be surgeon to search for signs of extra uterine tumour.
I
performed, in which the endocervix is first sampled
: with a curette to rule out spread to the cervix. A sound 5. lmaging studies. These have been outlined
i is then used to determine the uterine depth and a above. CTS, MRI and positron emission tomography
complete uterine curettage is then performed. Blind (PET) scan promise to provide the surgeon with
r curettage samples less than half of the uterine cavity greater resolution of depth of myometrial invasion,
i
in most cases and has a false-negative rate for lymph node involvement and distant metastases.
I
I
endometrial carcinoma of up to 2Oo/o3'. Although
( serious complications with this procedure are Othertests are:
I
I'v Lrncommon, they include the risk of perforation and

6. Proctosigmoidoscopy. lt is employed when
I
indicated to assess rectal/bowel involvement in stage
1 bleed i ng wh ich may necessitate hysterectomy.
I
I
lva.
i
i
597
"-!
7. Cystoscopy. This is done to determine bladder Hysterectomy

The intestines are then packed away and the pelvis
exposed. Grasping each side of the uterine fundus
8. Fine needle aspiration is performed on with hysterectomy clamps closes the fallopian tubes
nodes or palpable cutaneous mass6;: and also serves as elevators. After ligation and
provide documentation of distant met '*ld division of the round ligaments, the retroperitoneal
greatly alter surgical plans. spaces are exposed. The paravesical and pararectal
spaces are opened before initiating hysterectomy.
SURGICAL STAGING OF ENDOMETRIAL CA]'ICER
This allows discovery of obviously positive lymph
FlG0 has recommended surgical staging of nodes, allows identification of the ureters down to its
endometrial cancel which involves hyste-rectomy
entry into vesicouterine tunnels, where it may be
with systematic pelvic and parE-aortic necessary to ligate the uterine artery. The
lymphadenectomy. GOG-33 shows that in the
infundibulopelvic ligaments and ovarian vessels are
absence of myometrial invasion or when only
divided and ligated with direct visualization of the
superficial invasion is present, the probability of
ureters.
lymphatic spread is extremely low". ln addition,
those with less than 2cm endometrioid tumour grade Appropriate dissection of the uterine vessels is
I or 2 disease and superficial myometrial invasion performed. The uterine vessels are cross-clamped at
have a 0% lymph node involvement'4. Therefore, the internal os. The bladder is sharply dissected
lymph node dissection is not warranted in this group away from the lower uterine segment and upper .
of patients, especially with the associated increased vagina. Dissection is continued along the upper
morbidity. Such intra-operative selection requires vagina. Paravaginal bites are taken at least 1cm
f rozen section d u ri ng su rgery. below the fornix to allow a full-cuff vaginal specimen.
It is not necessary to remove the upper third of the
Surgical staging technique
vagina as is appropriate for radical hysterectomy. The
The patient is brought to the operating theatre after
vaginal cuff is closed with interrupted sutures. The
appropriate bowel preparation. To prevent the risk of
peritoneal cavity is thoroughly irrigated before and
venous thrombosis, overweight / obese patients are
after closure of the vaginal cuff. This procedure
given prophylactic low molecular weight heparin or
completes total abdominal hysterectomy and
fitted with elastic stockings. The use of pre-operative
bi latera I sa I pi ngo-oophorectomy.
broad-spectrum antibiotics with good anaerobic
coverage is indicated.
More radical hysterectomy may be necessary in the
fol lowi ng ci rcu msta nces:
A midline suprapubic incision is made on the anterior
a. When there is occult invasion outside the lower
abdominal wall after adequate skin preparation and
segment.
draping. Peritoneal washings are obtained by b. Where operative discovery of indurations of the
injecting 50 to 100 ml of warm normal saline parametrium occurs or
solution into the abdominal cavity and patient rocked c. lf gross disease is evident on the uterosacral
from side to side (if there is no ascites). The ligaments.
peritoneal fluid is then aspirated and placed in a
sterile container with dilute heparin and sent for lndividualized wider margins are taken according to
cytologicalstudies. anatomic abnormality. After hysterectomy, the uterus
is opened and evaluated intraoperatively. Gross
The peritoneal cavity is thoroughly explored by inspection is combined with frozen sections (where
pal,pating and inspecting the following (and available). This offers reliable evaluation of the
documenting these intraoperatively): the uterus, operative specimen for myometrial invasion and
Fallopian tubes, ovaries, bladder, retroperitoneal grade of disease. The surgeon must then decide
spaces and the paraaortic areas up to the level of the whether or not to proceed with lyqph node sampling
renal vessels. Others are the hemi diaphragms, to complete the surgical staging.
omentum, stomach, liver, spleen, kidneys, intestines,
colon, rectum, ureters and peritoneal gutters. The role of surgical debulking in endometrial cancer
598
Ndometrial Cancer
is not well established. Omentectomy, resection of b. Stage 1 , grades 2 and 3 . There is a defin ite risk of
visible tumour and appropriate biopsies should tumour spread. Operative approach often includes
accompany the standard surgical proced@- sampling of the paraaortic and pelvic nodes. Use of
postoperative irrad iation depends on the
Post operative treatment pathologica I fi nd i ngs, for exam ple positive peritoneal
After the operative procedure and cytology and deep myometrial invasion. For patients
recovery, the surgicopathologic findings used to who cannot medically tolerate an operation,
assign the patient a surgical stage, and @tment irradiation alone can be used.
plans are formulated. With this approach it is
estimated that 50% lo 60"/o of patients will need no 2. Clinical Stage ll. ln this stage, tumour involves the
further therapy (depending on the proportion cervix as well as the endometrium.
between early and advanced diseases), For patients Three therapeutic options have been employed for
who are thought to need additional therapy after treatment:
definitive surgery, three basic modalities are
available: radiation therapy, chemotherapy and a. Primary surger!: This involves radical'
hormonal therapy. hysterectomy and pelvic node dissection. External
irradiation is usually added if the pelvic nodes are
The use of irradiation in endometrial cancershould be involved with tumour. Removal of the uterus
considered part of therapeutic plan, not merely improves prognosis and survival.
adjunctive treatment. There is a role for primary or
preoperative radiation. Chemotherapy and hormonal b. Primary irradiation, followed by surgery. This
therapy are primarily used for advanced disease or involves intrauterine and vaginal implants and
pal liative situations. external irradiation followed by extra fascial total
abdominal hysterectomy 4 to 6 weeks later.
Treatment by stage of disease Additionally, bilateral salpingo-oophorectomy and
1. Clinical stage l. For the patients in satisfactory para aortic node sampling are performed. This
physical condition, surgery is the primary treatment approach is recommended where there are technical
modality. Most patients undergo hysterectomy. difficulties such as extreme ballooning of the cervix,
Sometimes preoperative irradiation is used to which suggests the benefit of preoperative irradiation
increase the likelihood of eliminating microscopic to reduce the overall size.
tumour deposits outside the uterus and reduce the
risk of tumour dissemination resulting from surgical c. lrradiation as the sole method of management:
manipulation. This involves combined uterine and vaginal local
irradiation and external therapy. Most patients with
The operation performed depends on tumour grade, stage ll adenocarcinoma of the endometrium are
which defines the relative risk of spread of disease elderly and obese and thus not good candidates for
I
f, outsidethe uterus: radical hysterectomy.
a. Stage 1, grade 1. The risk of spread of tumour to 3. Clinical stage lll. Here the disease has spread
pelvic nodes is extremely small. An extra-fascial total outside the uterus but remains confined to the pelvis.
I abdominal hysterectomy with bilateral salpingo- These tumours do not involve the mucosa of the
t oophorectomy is performed. Routine sampling of rectum or bladder. They account for only 7% of all
i retroperitoneal nodes is not performed but any endometrial carcinomas. They occur in patients who
clinically enlarged pelvic or para-aortic lymph nodes are older than those with lower stage tumours and
I are removed for histological evaluation. often patients are medically less able to undergo
surgery.
lf there is evidence of deep myometrial penetration
.r
I
t
f
( after opening the specimen, lymph node dissection is The optimal therapy when possible is total
l.r
lf
indicated. peritoneal cytolory sampling shows abdominal hysterectomy and bilateral salpingo-
tumour cells then radiation therapy is considered. oophorectomy. This is followed by external
I irradiation. lf there is vaginal extension of cervical
I
599
disease, subsequent brachytherapy is given.' For replication. Progestins effect a reduction in available
patients who cannot undergo surgery brachytherapy oestrogen receptors thereby decreasing the response
followed by external irradiation therapy is led. ln of tumours to circulating oestrogens. They also
patients with poor medical conditions r.@
rymly stimulate the production of oestrodiol-178
irradiation therapy is possible. :- !:
dehydrogenase. This enzyme converts the active
form of oestradiol to a weaker estrogen, oestrone.
4. Clinical stage lV. Approximatel.y .32 -nt Both of these physiologic events have an anti-
endometrial carcinomas present in stage lV. Manyof oestrogenic effect on the tumour.
these patients have tumour metastases outside the
pelvis. lndividualisation of therapy is necessary. lf Carefully performed studies in the past two decades
feasible, the uterus, tubes and ovaries are removed to on the use of progestins in metastases and advanced
achieve local control. lrradiation therapy is endometrial carcinoma have reported response rates
administered as an adjunct or if necessary as the sole mostly lower than 30"/ouu''u. Patients with well to
therapy for palliation to achieve pelvic control of moderately differentiated progesterone receptor-
disease. Progestational agents are particularly useful positive tumours are more likely to respond to such
in the case of well-differentiated tumours. hormonal therapy. Unfortunately, the poorly
differentiated tumours are more likely to recur. These
FOLLOW UP AND RECURRENCE tumours are usually progesterone receptor-negative
After definitive treatment, patients should be and refractory to progestins.
followed up for recurrent disease and also screened
for other cancers or health problems as detailed Depot medroxy progesterone acetate has been tried
below. in doses of 400 to 800 mg three times a week for a
month, then once a week for a second month and
History, examination and tests then once a month for maintenance. They have been
1. History and physical examination should include
used in the primary therapy of young women with
pelvic examination, cuff Pap smear and rectal
well-differentiated adenocarcinomas. Such women
examination.
usually have the clinical stigmata of chronic
2. Chest radiography.
3. Mammography.
anovulation, obesity and polycystic ovarian
4. Ultrasonography, computed tomography scan, syndrome. Meticu lous fol low-up is mandatory.
magnetic resonance imaging and positron
A schedule entails consultation every 3 months for 2
emission tomography depending on available
years, then every 6 months for 3 years and then
and affordable resources.
yearly for life. Or every 6 months for 5 years and then
yearlyfor life.
5. Screening for colon ca ncer.
Progestins have also been used in an adjuvant setting

Systemic treatment of recurrent disease
The treatment of recurrent disease depends on the as treatment following definitive surgery for
primary treatment. endometrial cancers. At present there appears to be
no indication for post-operative progestins following
1. Radiation therapy. lf the primarytreatmentdid not surgery for early endometrial cancer. A number of
involve radiotherapy, particularly in diseases relatively large randomised trials have failed to
confined to the pelvis, radiotherapy may be used for demonstrate a benefit for such treatment.
recurrences outside the pelvis. This is still possible
even with prior radiotherapy though it is less b. Tamoxifen: lt is a non-specific anti-oestrogenic
effective. Alternatively hormonal therapy or cytotoxic agent that blocks the oestrogen receptor. Modest
chemotherapy may be used. activity of tamoxifen was found against recurrent :
disease similar to progestins. Patients refractory to
2. HormonalTherapy. progestins are usually also unresponsive to
a. Progestins: Progestins appear
to work at the tamoxifen. Theoretically tamoxif'en may enhance
cellular level by slowing both DNA and RNA progesterone receptor expression and increase the
600
I
(
t,
Ndometrial Cancer
{
{
r response rate to progestins.
I Evidence of positive association between tamoxifen
t
E and endometrial cancer remains inconclusive.
c. Gonadotrophin releasing horrn@,ffialogues
[* (GnRH): Data regarding use of CnR#' *m
in 4. An inherited form of endometrial carcinoma is
advanced or metastatic endometr#lffi.rare considered when the disease occurs in a young
r conflicting. woman or where there is a family history of early-
r onset malignancies. ln spite of this, much more work
t 2. Cytotoxic chemotherapy. l is needed to understand the genetic mechanisms at
t Various chemotherapeutic agents have been used in play and to translate these into use within the clinical
rI limited trials in patients with advanced disase or and therapeutic fields.
i recurrent disease. No effective salvage therapy has
r
i. emerged. 5. Current practice acknowledges that dilatation and
I
t curettage without hysteroscopy should no longer be
r
I
Multi-agent regimens including combinations of used as first line investigation for endometrial.
r cyclophosphamide, 5 - fluorouracil, doxorubin and
I carcinoma. Due to lack of hysteroscopes and
cisplatin were usually employed. Cisplatin and ancillary equipment / instruments and the trained
t
carboplatin have been used as first line personnel to use them (even in tertiary institutions in
chemotherapy. The toxicity of these regimens have developing countries), dilatation and curettage alone
{
! been significant and the duration of response is sti I I the meth od most wid e ly em ployed .
I
disappointing. Newer agents such as oxaliplatin,
+
I
liposomal doxorubin and pyrazoloacridine are being 6. The thickness of endometrium used as a cutoff
i studied. point during transvaginal ultrasonography needs to
r
Il be varied according to age, ethnic group and perhaps
t. It is recommended that cytotoxic chemotherapy body mass. Results of studies from developed
I
should be reserved for patients with less favourable nations may not be applicable to women in resource
I
prognosis and then only after failed trials with poor countries. There is need therefore to conduct
progestin.
.t studies among women in the latter nations.
DISCUSSIONS AND CONTROVERSIES

r
7. lt is debatable whether to perform lymph node
I
dissection in all cases, or limit only to selected
1. lncreased risk has been seen consistently with
r patients at higher risk of lymphatic metastasis
I obesity, diabetes mellitus and hypertension.
I especially considering the increased surgical
Decreased risk is as:sociated with smoking, low-fat
morbidity. There is a low rate of positive lymph nodes
t
diets and physical exercise. Given the (9%) when lymphadenectomy is performed in all'
I
f, interrelationship of many of these, their independent
cases'u, compared lo22% when performed onlyfor
: effects are not clear'0. Prospective studies are still on
patients at risktn. Thus, intraoperative selection
I
t - going to clarify the life-style elements in association significantly avoids unnecessary surgery in low risk
with endometrial cancer.
I patientsoo.
I
: 2. Screening for endometrial cancer. Unlike in the

t 8. The decision to recommend adjuvant radiation
case of cervical cancer, most cases of endometrial
I
j therapy for patients with endometrial cancer is
cancer cannot be easily screened for and prevented
ultimately dependent on assessment of the patient's
I but the risk of developing the disease can be lowered
risk and prognosis. There is a large proportion of
by I ifestyle changes'..
endometrial cancer patients who have favourable
i prognosis and for whom no adjuvant therapy is
3 . The controversies su rrou nd ing the increased risk of
endometrial cancer in women using estrogen needed. Concerns have been raised that adjuvant
replacement therapy was resolved when it was found radiotherapy may improve quality of life without
a
that the increased risk persisted for several years after influencing overall survival. The variability with
i
I which different investigators characterize overall
cessation of therapy beyond any possible duration of
patient prognosis contributes to the controversy over
detection bias".
601
-
the role of adjuvant radiation therapy. practitioners, fear of surgery and poor health
Standardization of nomenclature of the overall risk infrastructure are issues requiring exploration in most
profile in a given patient (into low risk, medium risk developing countries as they contribute to the
and high risk - overall risk profile affects outcome and aetiopathogenesis, progression and prognosis of
treatment) would aid continued research to ffine endometrial cancer.
the role of adjuvant radiation therapy.
10. With the advances in artificial fertility
9. High parity, low life expectancy, poor use of techniques, fertility sparing methods are increasingly
combined oral contraceptive pills, poverty, late needed especially when younger patients are
presentation due to patronage of alternative health affected.
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18. Grady D, Gebretsadik T et al. Hormone replacement ( 1 April 2015, date last accessed).
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metaanalysis. Obstetrics and Gynaecology 1995; 29. Anton C, Favero G, Kohler C, Carvalho FM, Baracat
EC, Carvalho JP Surgical treatment of endometrial
85:304-313.
cancer in developing countries: reasons to consider
19. Fisher B, Costantino JB Wickerham DL, et al. systematic two-step surgical treatment. Clinics.
Tamoxifen for prevention of breast c?[cel: report of 2075;70(7):470-47 4.
the National Surgical Adjuvant Breast and Bowel
Project P-1 Study. J Natl Cancer 30. Office for National Statistics. Cancer survival in
lnst. 1 998;90: 137 1Y13BB. England: adults diagnosed in 2009 to 2013.
20. Olson - JE, Sellers TA et al. Does family history of followed up to 2014 (link is external). Newport:
cancer increase the risk for postmenopausal ONS;2015.
endometrial cancer? A prospective cohort study and
a nested case control family study of older women. 31. Gredmark I Krint S et al. Histopathological
Cancer 1 995; 85: 2444-2449. findings in women with postmenopausal bleeding.
21. LancasterJM, PowellCB, Chen LM, Richardson DL. British Journal of Obstetrics and Gynaecology
Society of Gynecologic Oncology statement on risk 1995; 102: 133-136.
assessment for inherited gynecologic cancer
predispositions. Gynecol Oncol. 2015;136:3Y7. 32. Stock RJ & Kanbur A. Prehysterectomy curettage.
Obstetric Gynecology 797 5; 45 : 537 -547 .
22.Hicks ML, PhillipsJL, Parham G, Andrews N, Jones

WB, Shingleton HM, Menck HR. The National 33. Prodratz KC, Mariani A. Uterine papillary serous
t carcinomas: the exigency bf clinical trials. Gynecol
Cancer Data Base report on endometrial carcinoma
in African - American women Cancer. 1998 Oncol2003; 9l:46L
15;83(72):2629-37 .
603
34. Slomovitz BM, Burke TW et al. Uterine papillary adenocarcinoma of the endometrium. New England
serous carcinomas (USC): a single Journalof Medicine. 1980; 303: 485-4g9.
ot 129 cases. Gynecol Oncol 2OO3;
38. Bristow RE, Duska LR, Montz FJ. The role of
35. Thigpen JI
Brady Mf, Atvarez RD cytoreductive surgery in the management of stage lV
medroxyprogesterone acetate in the uterine papillary serous carcinoma. Gynecol Oncol
advanced or recurrent endometrial 2OO1;81:92.
dose-response study by the
Gynecologic Oncology Group. J Clin 39. Moller KA, Gehrig PA et al. The role of optional
1999;77:1736Y1744. ,, debulking in advanced stage serous carcinoma of
. ..:: the uterus. Gynecol Oncol 2004; 94:170.
36. Decruze SB, Green JA. Hormone therapy iri "'
advanced and recurrent endometrial cartger: a 40. Thomas MB, Mariani A et al. Role of cytoreduction
systematic review lnt J Gynecol Cancer. in stage ll and lV uterine papillary serous carcinoma.
2OO7;17:964Y978. Gynecol Oncol 2007; 107:190.
37. Shapiro S, Kaufman DW et al. Recent and past use
of conjugated estrogens in relation to
604
cHAPTER
4g
Epithelial Ovarian Carcinoma
CAKlufioandTOKonney
Epithelial ovarian cancer has the highest fatalityto- stroma, which resembles a sarcoma. ln
case ratio of all the gynecologic malignancies, postmenopausal women, the stroma is not so
because more than two-thirds of patients have cellular.
advanced disease at diagnosis ".
Significance of ovarian cancer
Cancer of the ovary may be primary or secondary. The Worldwide, ovarian cancer is the 3rd commonest
ovary is a common site for metastatic tumour. gynaecological cancer after cancer of the cervix and
Approximately 10% of ovarian tumours are of cancer of the endometrium. ln Western countries,
secondary origin'. Metastases are usually from the ovarian cancer is the fourth most common cause of
uterus, the breast or the gastro-intestinal (Gl) tract cancer deatho. A woman's risk at birth of having
and pancreas. The endometrium is the commonest ovarian cancer some time in her lifetime is nearly
primary site. Adenocarcinoma of the stomach or 7.4"/", and the risk of dying from ovarian cancer is
colon is the commonest Gl tumour that affects the almost l"/"'. fhe incidence of ovarian cancer varies
ovary. The secondaries from these organs reach the in different geographic locations throughout the
ovaries by trans-peritoneal (trans-coelomic) spread world. Western countries, including the United
and sometimes present the characteristic features of States and the United Kingdom, have an incidence of
lhe Krukenberg tumour. Microscopically, the ovarian cancer that is three to seven times greater
Krukenberg tumour shows mucin-containing cells in than in Japan, where epithelial ovarian tumors are
u.
which the mucin seems to have pushed the nucleus considered rare
to the edge of the cell, giving the cell a "signet-ring"
appearance. ln premenopausal women, the signet- The incidence of epithelial tumors is about 1.5 times
greater in whites than in blacks'.
ring cells are scattered in an extremely cellularfibrous
Table 1. Relative frequencies of Cancers at the Korle-Bu Teaching

Gynaecological Hospital.
Type of Cancer Number (7")
Cervix 288 (57.8)
Ovary 126 ess)
Endometrium 37 Q.4)
Choriocarcinoma 34 (6.8)
Vulva 1 | (2.2)
Vagina L (O.2)
I
Leimyosarcoma 1 (0.2)
Total 498 (100)
605
ln a study of 498 gynaecological cancers at the . Age

Korle-Bu Teaching Hospital, in the periods January o HRT with oestrogen-only pill
1991 to iune i993 and March 1995 to December . Hereditaryfactors
1996, ovarian cancer was more common than . Dysgeneticgonads
endometrial carcinoma (Table 1 )u . lncessant ovulation
o Peutz-Jegher'ssyndrome
Because the symptoms in ovarian cancerare vague in o Tubal ligation
nature and there are as yet no adequate screening o Race
methods, patients with ovarian cancer typically o Environmentalfactors
present late and the survival rate is poor. Most
patients (66%-75%) have Stage lll or Stage lV A. Age
disease at diagnosis with a five-year survival of 24% Age is the single most important risk factor for
and 127", respectively'''. Goff et al. developed an ovarian cancer. lncidence of ovarian cancer increases
ovarian cancersymptom index that included'0: with age. ln the USA, the median age at diagnosis is
o Abdominalpain 6lyrs" and deaths are highest in people aged 75 to
. Pelvic pain 84 years (median age 7l years)'. However,
o Urinaryfrequency andlor urgency worldwide, the highest incidence is in the 40-49 age
o lncreasedabdominalsize/bloating. group, with 68% of the cases older than 40yrs; the
. Decreased appetite/earlysatiety. percentage of women younger than 50yrs is 56"/o12.
Approximately 30% of ovarian neoplasms in
The index had a sensitivity of 56.7 %for early ovarian postmenopausal women are malignant, whereas
cancer and 79.5 Y" for advanced stage ovarian only about 7% of ovarian epithelial tumors in
cancer. Despite the above, over 75 % of patients will premenopausal patients are frankly malignantu.
be diagnosed with advanced stage disease at
presentation. B. Hereditaryfactors
Most cases (90-95%) of ovarian carcinoma arise
Cervical and endometrial cancers present earlier sporadically, i.e. they arise by chance. Between 5%
because unlike the ovaries which are relatively and lO% of cases are attributable to hereditary
inaccessible: factors. Next to age, a positive family history of a
. Cervical and endometrial cancers bleed early first-degree relative is the most important risk factor.
and externally. The cervix can be direcily Women who carry germ-line mutations of the BRCAl
visualised and can easily be sampled and BRCA2 genes have a range of 76%-40%
cytologically. estimated risk of developing ovarian cancer by 70yrs
. The endometrium can easily be screened by of age, compared with a lifetime risk of 7.7% in the
vaginal sonography or ultrasound contrast general population"''0. Approximately 75% of
sa pi ngogra phy (sonohysterosa pi ngogra phy
I I invasive epithelial ovarian cancers are estimated to
or saline infusion sonohysterography). lt can be the result of autosomal dominant genetic factors
be examined relatively easily by with high disease penetrance, predominantly germ-
hysteroscopy. lt can be sampled relatively line mutations in the BRCAl or BRCA2 genes (65%
easi ly by vacuu m aspiration or curettage. to 85%), or in MMR genes (10% to 15%)'u. The
. Cervical and endometrial cancers start with BRCA genes are inherited in an autosomal dominant
detectable pre-invasive lesions that over fashion, which means that every first-degree relative
many years progress through lower stages of of a mutation carrier has a 50% chance of carrying a
invasion to higher stages. Adequate mutation.
treatment of preinvasive lesions prevents
frank cancer. Ovarian cancer has no known C. lncessant Ovulation
precursor lesions. Next to age and a positive family history, incessant
Epidemiology ovulation is the single most consistent riskfactor. The
Aetiological risk factors higher the number of ovulatory cycles, the higher the
These are:
505
Epithe Iia I Ova ri a n Ca rci noma
lifetime risk of ovarian cancer. The mechanism is after age 35 is more protective against ovarian
thought to be as follows: Each ovulation produces a cancer than a pregnancy in a woman 25 years or
tear in the ovarian capsule which is r,qpAif,@. During younger ".
the repair bits of surface epitheliwn.,@E@9me
incorporated into the substance of t10.i44ry}l. ffre Note: One paper raised concerns about increased
repeated regeneration of the eptt'l@-i.s+n may incidence of ovarian cancer in ovulation induction
ultimately result in loss of control of thece+.division with clomifene citrate (CC). lt was therefore advised
process and result in cancer'u. that CC should not normally be used for more than 6
months (6 continuous cycles). However, it has now
Re prod uctive ch a racteri stics that i ncrease riskt been concluded that CC is not associated with any
Evidence in support of incessant ovulation as a risk increased incidence when used for less than 72
factor: cycles, and since the cumulative pregnancy rate
1 Domestic hen: The domestic hen ("layer") increases up to 12 cycles, it is now recommended
ovulates 10 days out of 12 days. The layer's lifetime that CC induction be continued up to 12 cycles'o-'u'
risk of ovarian cancer is almost LOO%
D. HRT with oestrogenonlY Pill
2 Nulliparity: The risk of ovarian cancer is Menopausal women who have one or both ovaries in
approximately 2 times the risk of parous women". situ and who take oestrogen-only hormone
Compared with nulliparae, Para 1 women have a replacement therapy are at significantly greater risk
relative risk of 0.6 -0.8. Each additional birth lowers of developing ovarian cancer than women who had
the riskof ovarian cancerby 10to 75"/o" never taken the oestrogen-only pill. This risk
,-
increases with increasing duration of use. The
i
3 Ovutation induction with HMG increases risk'n. relative risk increases by 7% (95% confidence
I
lf the risk is real at all, it must be very small. interval 2%73%) for every year of use, and is 60%
I
Compared with parous women, nulliparity doubles greater after 10 or more years of use. The relative risk
I
t the risk of ovarian cancer. Nulliparity is therefore a is 1.8 (95% Cl 1.1-3.0) for 10-19 years of use and
r confounding factor in any studies that try to establish 3.2 Q5% Cl 7.7'5.7) for 20 or more years. No such
I
i an association between infertility from anovulation association was found with oestrogen-progestin
I treatment with drugs and ovarian cancer. Ovarian replacement therapy". Currently, the primary
t cancer has been associated with low parity and indications for the prescription of HRT are severe
I
I infertility'zo. Although there has been a variety of postmenopausal symptoms and osteoporosis'
Severa I prospective cohort stud ies"-'n exa m i ned how
t
I epidemiologic varia'bles correlated with ovarian
t
cancer-such as increased risk with talc use, postmenopa usa I estrogen or estrogen/progesti n H RT
t
t galactose consumption, and decreased risk with relates to the risk of developing ovarian cancer. Using
I tubal ligation and the oral contraceptive pill usage, data from the Breast Cancer Detection
i none has been so strongly correlated as prior Demonstration Project, which is a cohort study of
I
reproductive history and duration of the reproductive over 44,000 postmenopausal women, Lacey and
:
I career'o-". colleagues found that use of estrogen-only HRT
: increased ovarian cancer RR by 1.6 (Cl, 7.2-2),
; 4 Early menarche and late menopause; Early while the RR for women using an estrogen/progestin
i menarche'and late menopause increase the risk of combination was not significantly increased (RR,
: ovarian cancer ". These factors and the relationship L.7;O.64-7.7)".
t,
of parity and infertility to the risk of ovarian cancer
I
have led to the hypothesis that suppression of E. Race
t
7 bvulation may be an importantfactor. Ovarian cancer rates are highest among white
t^-: Caucasian women in Western Europe and North
t*
r 5 Late childbearing: A number of case-control America. ln these regions, the incidence rangesfrom
t studies have shown that pregnancy lowers ovarian 80 to 150 per million and the lifetime risk of
I
cancer risk and that the risk reduction is higher with developing the disease is 1 in 70. Women of
each additional pregnancy. lnterestingly, a pregnancy Ashkenazi-Jewish descent have one of the highest
607
rates of ovarian cancer in the world, and this is chiefly women who had at least 5 episodes of PlD. Such
due to a high rate of mutation of the BRCA1 and indications of a dose-response effect always add
BRCA2 genes, which is 1 in 50 compared to 1 in 800 credibility to epidemiologic findings ". Chlamydia
in non-Jewish women'.. trachomatis may be a risk factorfor ovarian cancet''
F. Dysgenetic gonads Protective factors

Dysgenetic gonads with Y components have a high Re p rodu ct i ve c h a ra cte r i stics assocra te d wit h f ew e r
risk (30%) of gonadal tumours (dysgerminoma and ovulatory cycles decrease risk
gonadoblastoma) before 2Oyrs of age. Examples are
Turner mosaic 45XO146XY and pure gonadal 1 Combined oral contraceptive pills (COCP):
dysgenesis in which the gonad is present as a streak COCPs decrease pituitary gonadotropin levels and
but unlike Turner's syndrome, a fragment of the y thereby reduce the incidence of ovarian cysts and
chromosome is present. Such dysgenetic gonads cancer. Depending on the duration of use, combined
must therefore be removed. oral contraceptive pills reduce the risk of ovarian
cancer by 30% lo 60o/"'0. This is the single most
G. PeutzJegher's syndrome practical preventive intervention we have at the
This is associated with an increased incidence of present time
germ cell and sex cord tumours and endometrial
cancer. 2 Breastfeeding
ln general, breast-feeding reduces the risk of ovarian
H. Environmental factors czrfcer: Women who breast-feed for longer lhan 12
1 Diet a) lncreased saturated fat intake b) months have a substantial reduction in the risk of
lncreased coffee intake c) Diets which are poor in ovarian cancel which is in addition to the risk
vegetables and fruits reduction derived from childbirth35. Breast-feeding
probably reduces ovarian cancer incidence through
2 Residence in industrialised country several mechanisms, including suppression of
3 Smoking: Smoking is not generally considered a ovulation, reduced serum concentrations of estradiol
risk factor for ovarian cancer t'. However, current and LH, and elevated FSH levels.
smoking seems to be associated with an increased
risk of developing a mucinous ovarian cancer (OR, 3 Pregnancy at an early age:
7.78; 7.01-3.15) ". Smoking cessation reduces this A number of case-control studies have shown that
risk back to baseline oier 20 years. This may be pregnancy lowers ovarian cancer risk and that the
explained by the antioestrogenic effect of smoking, risk reduction is higher with each additional
resulting in high gonadotropin levels pregnancy. lnterestingly, a pregnancy after age 35 is
more protective against ovarian cancer than a
4. Exposure to granuloma-inducers and carcinogens pregnancy in a woman 2Syearsoryoungertu.
. Talcum from perineum 4 Late menarche
. b) Asbestos
Tuballigation
5. Pelvic lnflammatory disease: Several small case- Bilateral tubal ligation is protective, Comparative
control studies had suggested that PID is associated studies have shown that the lower incidence is not
with ovarian cancer. However, this association only because bilateral tubal ligation affords the
gained wide acceptance with the publication of a opportunity to observe the ovaries and remove those
t'
large study comparing the ovarian cancer incidence with abnormal appearances before they progress to
of 68,000 women who had experienced PID versus frank carcinoma. A large prospective cohort study,
136,000 who had not. ln this well-designed study, the Nurses' Health study t', confirmed smaller case-
the hazard ratio for ovarian cancer in patients with a control studies and showed a RR of 0.33 (Cl,
history of PID (adjusted appropriately for 0.16-0.64) of developing ovarian cancer in women
confounding factors) was twice as high (HR 1.92) as who had a tubal ligation compared to those who did
that of controls, and was even higher (HR 2.46) in not. Possible explanations for the protective effect of
608
c
rt
I
r Epithel ial Ovarian Carcinoma

r
I
;I tubal interruption against ovarian cancer include an carcinoembryonic antigen (CEA) is positive in
t
impaired blood supply to the ovaries/distal tubes only 20% of serous tu mou rs.
f through the superior branch of the uterine artery 2. Endometriod Q5%)
I
{r- leading in most women to earlier menopauee (and 25% of ovarian cancers are endometriod. 15%
i
,l
fewer lifetime ovulations) and the possibitity that of endometriod cancers are bilateral. 15-30%
I
occluding the tube blocks the upward flow of are synchronous with primary endometrial
r carcinogens from the uterus and reduces pelvic cancer. The tumour marker is CA125.
I
infection rates. 3. Mucinous (15%)
70-75% of ovarian cancers are mucinous
Nomenclature cancers. !5o/o are bilateral. The tumour
I
e Terms used in describing ovarian tumours: markers for mucinous ovarian cancer are CEA
i A. Embryological Origin of Cell Type: Epithelial, and CA19-9. CEA is a high molecular weight
germ cell, sex cord-stromal glycoprotein which is positive in 100% of colon
r B. Gross features: Growth extends from surface cancers and in 70-80% of mucinous cancers."
of ovary (exophytic, cystic, papillary) Almost all mucinous tumours whose epithelia
C. Histological (microscopic) predominant cell are of the intestinal-type express CEA.
I
type in epithelial tumours: Serous, 4. Clearcell(mesonephroid)(5%)
Mucinous, Endometriod, Clear cell, Brenner 5% of ovarian cancers are clear cell cancers.
r (SMEC-B) 75-20% are bilateral. The peak age incidence
D. Tumours in which >70"/" of the epithelium is 52yrs. Two thirds of affected women are
I
resembles a second cell type are called nulliparous. Pelvic endometriosis occurs in 50-
t mixed tumours 70% of cases, and 25% arise from the lining of
I
I
i E. lf it has a large amount of fibrous (stromal endometriotic cysts. They are considered to be
connective tissue) component, it is called a variants of endometrioid and serous
i
fibroma (except Brenner, which is mainly carcinomas. They can be associated with
stromal) paraneoplastic hypercalcaemia, but this is
F. Benign tumours are adenomas or uncommon.
:
cystadenomas; clearly malignant tumours
are carcinomas, adenocarcinomas, or 5. Undifferentiated
: cystadenocarcinomas; tumours that are 6. Brenner - Malignant Brenner extremely rare <1"/o
t neither clearly benign nor clearly malignant 7. Mixed
I
are tumours of "low malignant potential" or

"borderline" tumours. B. Germ Cell
G. Degree of Malignancy: Benign, borderline or 1 Dysgerminoma Forms 90%of all germ cell
low malignant potential, malignant tumours
2 Endodermal sinus tumour
H. Functional if tumour is steroid-producing: 3 Embryonalcarcinoma
. Feminising, if it secretes oestrogens 4 Non-gestationalchoriocarcinoma
o Virilising, if it secretes androgens 5 lmmature teratoma
6 Gonadoblastoma
Histopathologic Classification by Cell Type Origin 7 Mixed germ celltumour
A. EpithelialCell C. Sex Cord Stromal

Epithelial cell cancers form approximately 85% to 1 Granulosa cell Forms 70% of all sex-cord
90%of all primary ovarian cancers. tumours: Adult and juvenile types
fv 1. Serous @O%) 2 Thecoma-Fibroma, Almost always benign;
Serous cancers form 4O"/" of all ovarian form 1-1 .5%of all ovarian tumours
L cancers. 337" are bilateral. CA125 is positive in
>80% of serous ovarian tumours (benign and 3. Sertoli-Leydig cell. Less than 0.5% of all
malignant). On the other hand, ovarian tumours"
509
Comprehensive Gynaecology in the Topics -!
Clinical Features of Ovarian Carcinoma tumour: This may be transient and recurrent.
Unfortunately, ovarian cancer has no srgnature 9. Rupture with resulting haemoperitoneum causes
symptom or sign, i.e. it has no early warni@$gns or abdominal pain. Because of adhesion to
symptoms. lt
is typically asymptoma-frb"'.-Wfl it surroundi ng organs, torsion is uncommon.
becomes advanced. Symptoms are often v#ffi trfid 10. lmpaction of the tumour in the pouch of Douglas
non-specific. Up to 50% are referred 'te:ltiffrer (POD) can cause retention of urine.
specialists, e.g. physicians, with ascites. 11. lmpaction of the tumour in the POD can cause
obstructed labour.
Symptoms 12. Pressure of the mass on pelvic veins and
The majority of women with epithelial ovarian cancer lymphatics can cause edema and varicosities of
have vague and nonspecific pelvic, abdominal, and the vulva and legs.
menstrual symptoms "'t'. The symptoms are due to
mechanical effects of the tumour on pelvic and Clinical examination
abdominalstructures. Stgrrs
1 Cachexia: This is typical of large andlor advanced
1. Age incidence: The incidence increases with age. growths.
The mean age at diagnosis is 61yrs. However, Enlargement of a supraclavicular node (scalene
according to the 25'oA nnual FIGO Report on the node in the posterior triangle of the neck) may be
Resu/ts of Treatment of Gynecological Cancer, the first sign, but this is not very common.
the highest incidence is now in the 40-49 age The abdomen should be evaluated for the
group; the percentage of women younger than presence of an umbilical hernia. The involvement
50yrs is now 56%, but 68% of the cases are older of the umbilicus by an ovarian cancer is
than 40yrs". ln Ghana, 7 4% of cases were 40yrs colloquially called "Sister Mary Joseph nodule,"
or olderu named after an assistant to Dr. William Mayo,
2. Once the patient is aware of their presence, who identified the lesion as a sign of advanced
ovarian tumours grow rapidly in size, unlike malignancy. The abdomen should also be
fibroids that grow relatively slowly. inspected for surgical scars and visible veins
3. Upper Gl and urinary symptoms: ("caput medusae") caused by impaired central
a) Vague upper abdominal symptoms: venous return from extensive intra-abdominal
abdominal discomfort, heaviness or pain; disease.
dyspepsia, early satiety, nausea, anorexia, and Palpable irregular rT'rasses: lt may or may not be
vomiting. On the othbr hand, fibroids typically possible to get below the
give rise to lower bowel symptoms, e.g. Shifting dullness and fluid thrill for the presence
constipation. of ascites
b) lncreased frequency of micturition. Physiological cysts do not occur in
4. lncreasing abdominal swelling/distension from postmenopausalwomen. The normal ovary is not
ascites and from rapid growth of the tumour palpable in postmenopausal women. lf an ovary
5. lncidental finding of a mass during abdominal or is palpable in a postmenopausalwoman, it must
pelvic examination be considered malignant.
6. Post-menopausal bleeding may occur if the Pelvic examination findings may also include
tumour is an oestrogen-secreting one. involvement of the parametrium by tumor, or
7. Dyspnoea from: a) Restriction of diaphragmatic nodularity of the rectovaginal septum. lt may not
and abdominal wall respiratory excursions by the be possible to differentiate the uterus from the
pressure of the ovarian mass on the diaphragm tumor and the cervix is sometimes dislocated
ahd from increased intra-abdominal pressure anteriorly behind the pubic symphysis. Some
from the mass and ascites ovarian tumors are behind the uterus and can be
b) Pleural effusion as a result of transudation of fluid best palpated with a rectovaginal exam after the
into the pleural cavities or accumulation of fluid in bladder is emptied.
the pleural cavities secondaryto metastases
8. Aching pain in the abdomen and localised to
610
{
t
L
l
t,
Epithel ia I Ova ria n Carci noma

t
I
i,
jf major lymphatic pathway.

I lmaging
I
, Ultrasonographic signs of malignancy include an
r{ adnexal pelvic mass with areas of comptexity such as . b) From the broad ligament and
{ r-- i rregu a r bo rd ers ; m u lti pl e echogen ic gi*tteins with i n
I
parametrium, it drains laterally to the
fl the mass; and dense, multiple, inegutar septae. external and internal iliacs, obturator and
1
t
Bilateral tumors are more likely to''be rnalignant, common iliacs nodes, lateral sacral and
although the individual characteristics of the [esions thence to the para-aortic nodes
{
are of greater significance. Transvaginal o c) From one ovary it drains across the uterine
ultrasonography may have a somewhat better fundus to the opposite tube and ovary.
.
I
d) Rarely, it can spread along the round

1
resolution than transabdominal ultrasonography for

oo-o',
adnexal neoplasms and Doppler color-flow ligament lymphatics to the inguinal nodes.
imaging may enhance the specificityo'-". Lymphatic dissemination to the pelvic and
;
para-aortic lymph nodes is common,
An abdominal and pelvic computed tomographic particu larly in advanced-stage d isease'u'"
(CT) or MRI scan is of limited value in patients with a
uo-ou.
definite pelvic mass Patients with ascites and no 4. Haematologic spread: This is rare in the absence
I
pelvic mass should have a CT or MRI scan to look of intra-abdominal and lymphatic spread.
ou.
pa rticu la rly for I iver or pa ncreatic tu mors Haematological spread results in parenchymal liver,
pulmonary, bony, or central nervous system
Patterns of Spread metastases.
(
1 Direct invasion: Capsular penetration,
i adherence to neighbouring structures, direct Staging Ovarian Cancer
t
invasion ofstructures Staging is surgical-pathological and consists of:

1 Laparotomy
2 Peritoneal (transcoelomic) spread: This is the 2 Cytology of ascitic fluid or peritoneal
most important mode of spread. All parietal and washings
visceral peritoneal surfaces are at risk of 3 Measurement of metastases to determine if
metastases, especially the omentum and right a metastasis is <2cm or >2cm in its greatest
hemi-diaphragm. Cancer cells that are shed into diameter
a
the peritoneal or ascitic fluid, follow the 4 Removal of lymph nodes and tissues for
direction of large bowel peristalsis upwards histopathology
along the ascending colon to the right hemi- 5 Biopsies to determine spread: peritoneum,
diaphragm and infra-hepatic areas, then across omentum, diaphragm
the transverse colon and upper abdomen to the 6 Evaluation of liver parenchyma
left splenic flexure and left hemi-diaphragm, 7 Location of extra-abdominal, extra-pelvic
and down the descending colon back into the disease: Chest X-ray; fine needle aspiration of
pelvis. Therefore, metastases are typically seen en larged cervical nodes
on the posterior cul-de-sac, paracolic gutters,
right hemidiaphragm, liver capsule, the Histological confirmation of the disease is
peritoneal surfaces of the intestines and their mandatory, as is cytological confirmation of
mesenteries, and the omentum. The disease effusions, e.g. ascites and pleural effusion.
seldom invades the intestinal lumen but
progressively agglutinates loops of bowel, The definitive management of ovarian tumour starts
leading to a functional intestinal obstruction. with laparotomy and staging (comprehensive
This condition is known as carcinomatous ileus. staging laparotomy). A frozen section service
should be available.
3. Lymphatic spread
.
a) Para-aortic chain: The chief lymphatic Why Staging of Ovariarn Cancer rs Surgico-
drainage follows the utero-ovarian vascular Pathological
bundle to the para-aortic nodes. This is the Early peritoneal and lymphatic metastases are
611
clinically occult. Tumours that appear to be confined Fou r Reasons for Stagi ng
to the ovary (early disease) may have occult 1 To select management appropriate to the
metastases in abdomen and lymph nodes. \Sflfputa individualcase
systematic evaluation and biopsy of ,,.p@qtial 2 For prognosis
metastatic sites, occult metastases will h m+wd 3 For comparison of treatment regimens
and treatment will not be adequate. Therefore, 4 For comparison of treatment results from
diagnosis of Stage l/ll requires a corr,puehensive different institutions, e.g. FIGO Annual Reports
su rgica I stagi ng lapa rotomy.
Revised FIGO (2014 Staging of Ovarian Cancer
Stage l: Tumor confined to ovaries

otd New
lA Tumour limited to one ovary capsule /A Tumour limited to one ovary, capsule intact, no tumour
intact, no tumour on surface, negative on surface, negative washings/ascites
washings/ ascites
lB Tumour involves both ovaries othenarise lB Tumour involves both ovaries otherwise like lA
like 1A
lC Tumour involves one or both ovaries with lC Tumour limited to one or both ovaries
any of the following: capsule rupture, tumour lCl Surgical spill
on surface, positive washings/ascites lC2 Capsule rupture before surgery or tumour on ovarian
surface
lC3 Malignant cells in the ascites or oeritoneal washinss
Stage ll: Tumour involves one or both ovaries
peritoneal cancer
old New
llA Extension andlor implant on uterus and/or llA Extension andlor implant on uterus andlor Fallopian
Fallopian tubes tubes
llB Extension to other pelvic intraperitoneal llB Extension to other pelvic intraperitoneal tissues
tissues Old stage llC has been eliminated
Stage lll: Tumour involves one or both ovaries wittr c6
the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes
otd New
lllA Microscopic metastasis beyond the lllA (Positive retroperitoneal lymph nodes and/or
pelvis microscopic metastasis beyond the pelvis)
to.'r,r. retroperitoneal tymph nodes onty iltAt(i)
I]_
lllB M acroscopic, extrapelvic, peritoneal lllB Macroscopic, extrapelvic, peritoneal metastasis <2
metastasis <2 cm in greatest dimension grn +
positive retroperitoneal lymph nodes. lncludes
extension to capsule of liver/spleen
lllC Macroscopic, extrapelvic, p eritoneal lllC Macroscopic, extrapelvic, peritoneal metastasis >2
metastasis >2 cm in greatest dimension cm r- positive retroperitoneal lymph nodes. lncludes
and/or regional lymph node metastasis extension to capsule of liver/soleen
Stage lV: Distant metastases excluding peritoneat nretastases
otd New
lV Distant metastasis excluding peritoneal IVA Pleural effusion with positive cytology
metastasis. lncludes hepatic parenchymal
metastasis
1VB Hepatic and/or splenic parenchymal metastasis,

metastasis to extraabdominal organs (including inguinal
lymph nodes and lymph nodes outside of the abdominal
cavity)
6L2
t
tr
i
7 Epithel ial Ovarian Carcinoma
r
t
t
r Other major recommendations are asfollowsl incidence of postoperative faecal impaction and
l
t o Histologic type including grading should be promotes early return of normal bowel function.
r designated at staging. With the colon empty, examination under
[- o Primary site (ovary, Fallopi#:&@, or anaesthesia is more likely to be satisfactory, i,e.
r peritoneum) should be deslgrr# where the examinercan be more certain of hisfindings.
I
I possible. a) Low-residue high-protein dietfor3 days
f
F . Tumours that may othenerise ryffi for plus
t Stage I but involved with dense adhesions b) A regimen to evacuate the colon. One of the
r justify upgrading to Stage ll if tumour cells following regimens may be used.
r
I
are histologically proven to be present in the Three-day regimen:
r
I i. Bisacodyl (Dulcolax) 1Omg oral tablets nocte x
r adhesions.
t
I
2days
t
i Stages l/ll :
"Early" or "localised" disease. Stages ii. Bisacodyl 1Omg suppository early morning of
r
l :
llUlV "Advanced" disease. the day of surgery or preferably:
(I
t
r,- Histological Gnding 24hr regimen:
This is an objective microscopic assessment of how Gut lavage with Klean-Prep'(Norgine) or a similar
r*
I
closely the cells of the tumour resemble normal cells
of the organ. Histological grading is based primarily
preparation. A sachet of the oral powder contains
polyethylene glycol 59g, anhydrous sodium sulphate
r on what proportion of the arrangement is glandular 5.685g, sodium bicarbonate 1.6859, sodium
rf chloride 1.4659, potassium chloride 743mg and
t rather than solid, or, non-morula. Grading is
( secondarily based on appearance of the cells: nuclear aspartate as a sweetener. Four sachets are dissolved
r
I stratification, nuclear anaplasia, nuclear 4
in litres of water to produce an iso-osmotic
I pleomorphism, nuclear size, mitotic index, cellular solution. The patient drinks 250m1 (a glassful) every
i
r atypia, cel lular stratification. 10-15 minutes until the 4litres have been
,|
! consumed or the patient starts passing watery stools

Grade 1 (G1): Thetumour iswelldifferentiated (<5% that are free of solid matter. To facilitate gastric
I
(.
t solid growth). emptying dopamine antagonists which stimulate

Grade 2 (G2): The tumour is moderately gastric emptying may be given 30 minutes before the
i d ifferentiated (6-50% sol id growth). patient starts drinking the solution, €.9.
t 3 (G3): The tumour is poorly differentiated
Grade domperidone (Motilium') or metoclopramide
t (>50% solid growth). (Maxolon').
I
,
f Preopentive Evaluation and Prepantion 10. Antibiotic bowel preparation together with
t
I 1 Careful history and physical examination, mechanical cleansing, antibiotic preparation
f including bimanual and rectovaginal reduces the risk of peritoneal contamination should
t examination
: the colon be entered accidentally or intentionally
f 2 Lab investigations: FBC, Sickling, BUE & during the operation
on.
Colon antisepsis can be
I
t creatinine, LFTs, Urinalysis
achieved by giving erythromycin 19 plus Neomycin
3 Plain X-ray chest for metastases; if pleural
1g orally for 2 days
I
effusion is present, cytological examination of the
,t fluid must be performed 1. Thrombo-embolism prophylaxis:
1
4 ECG a) Pneu matic com pressive stocki ngs
I
1 5 Ultrasound scan of pelvis and abdomen b) Subcutaneous low molecular weight heparin, if
6 CT scan of pelvis and abdomen, if available
indicated: 2,500units 1-2hrs before surgery and
I
7 Barium enema if indicated
then 5,000 units daily x 7days. Alternatively, it can
i
8 Measurement of the appropriate serum tumour
begiven as 5,000 units l2hrlyforT days
iv markers according to clinical indicators, e.g. age
I 1 2. Arrange fo r'trozen section
ofthe patient.
II 9. Mechanical bowel cleansing: Mechanical Com ponents of Com prehen sive Stagrng
cleansing of the large bowel reduces the
L
Comprehensive staging laparotomy for early ovarian

I
I
i
I
613
cancer consists of the following: procedures in and para-aortic nodes are sampled. However, in
operating theatre obviously Stage lllC or lV disease, there is no
1. EUA: Abdominal, bimanual and rectwaginal need to sample them, since, in either case, the
examinations result wil I not change the stage.
2. Prophylactic intravenousantibiotics
3. Adequate exposure: midline incis,ion into Gross features at laparotomy that suggesf
epigastrium to allow inspection of upper malignancy include;
abdomen and diaphragm 1 Bilaterality: Bilateral tumours are the result of
4. lf apparently Stage 1 or ll, take ascitic fluid for metastatic spread to contralateral ovary. 7 57"
cytology. lf there is no ascites, do thorough of malignant tumours are bilateral compared
peritoneal irrigation with 200-400mls saline; with 15% of benign tumours
aspi rate i nto hepa ri n ised conta iner for cfiology. 2 Shape and consistency of tumour: Solid,
5. Meticulous manual and visual peritoneal nodular and irregular
exploration of entire abdominal and pelvic 3 Ovarian capsule: Papillary surface
contents and the diaphragmatic surfaces. This excrescences, or perforation or rupture of
should proceed in a clockwise fashion from the capsule; areas of necrosis
cecum cephalad along the paracolic gutter and 4 Adhesions: Adhesion of tumour to surrounding
the ascending colon to the right kidney, the liver structures
and gallbladder, the right hemidiaphragm, the 5 lmplants on parietal and visceral peritoneal
entrance to the lesser sac at the para-aortic area, surfaces
across the transverse colon to the left 6 Ascites: Presence of ascitic fluid, especially if it
hemidiaphragm, and down the left gutter and is blood-stained
the descending colon to the rectosigmoid colon. 7 Omental metastases: The whole omentum may
The small intestine and its mesentery from the be replaced by tumour, the so-called "omental
ligament of Treitz to the cecum should cake"
be
inspected. 8 Enlarged regional nodes: Palpable pelvic and
6. Measurement of metastases to determine if a para-aortic lymph nodes.
metastasis is <2cm or >Zcm in diameter prior
Exploratory laparotomy for ovarian cancer may show
to tumour debulking.
7. Biopsies of all suspected sites of involvement one of following:
8. lf no suspicious areas are found, random 1. Disease grossly confined to one ovary or to both
peritoneal biopsies from multiple sites are taken, ovaries, with no gross lesions in pelvis or abdomen
(Stage l): This requires comprehensive staging.
particularly from: the hemi-diaphragmatic
surfaces, liver capsule, paracolic gutters, 2. Disease grossly confined to pelvis (Stage ll): This
peritoneal reflection of the bladder, pouch of requires comprehensive staging because it may be
Douglas and pelvic sidewalls. A spatula can be

Stage lll with occult (microscopic) abdominal
metastases.
used to
scrape the under surface of the
3. An obviously disseminated intra-abdominal
diaphragm, as in a Pap smear preparation; a
disease, with tumour on parietal or visceral
second spatula can be used forthe livercapsule.
peritoneum or in omentum:
9. Total abdominal hysterectomy and bilateral
. lf no distant metastasis was found pre-
salpingo-oophorectomy with resection of the
operatively (by chest Xray, CT scan or MRI or
ovarian mass
10. Total infracolic omentectomy for histological
ultrasound scan of organs, including liver,
pleural effusion cytology), this is Stage lll.
examination. However, if the omentum obviously
contains metastases, the entire omentum must
o lf on palpation at laparotomy a lymph node
is involved, the node is removed for histology.
be removed. The omentum is a favourite site for
ovarian metastases.
lf lymph node invasion is histologically
I 1. Diagnostic lymphadenectomy: Enlarged lymph confirmed, it is Stage lllC.
nodes are removed. ln apparent early stage
. lf palpation detects parenchymal liver
disease, it is Stage lV.
disease (Stages I & ll), apparently normal pelvic
614
Ep ithe I ia I Ova ri a n Ca rci noma
Treatmentof Early Stage Drsease $tages I &il) Role of Lymph Node Dissection in Early Ovarian
ln current clinical practice, optimal staging in early Cancer
ova ri a n ca n cer i ncl ud es ca ref u I i nspectie*-galpation, When treating both early and advanced ovarian
and biopsies of peritoneal surface5.r,.@ragm, cancer, a surgeon must decide whether to perform a
paracoIic gutters, bIadder and:':' {€'de-sac lymph node sampling, limited to the removal of
peritoneu m), pelvic and diaphragmdG'--*irastings, enlarged or palpably suspicious lymph nodes or a
removal of the affected ovary, an infracolic or systematic lymph node dissection, removing all
infragastric omentectomy, and a system*tic pelvic visible lymph nodes within defined anatomic borders
u'. Both the pelvic and paraaortic lymph nodes
and paraaortic lymph node dissection 9n: An
appendectomy can, though rarely, change the final should be removed when a systematic lymph node
staging
u'.
Preserving the contralateral ovary and the dissection is performed. However, given the
uterus in young patients desiring fertility is {ymphatic drainage of the ovaries, the removal of
considered acceptable in the treatment of early-stage high paraaortic lymph nodes is the most important
uu.
epithelial ovarian cancer. Because imaging and intraoperative palpation of
lymph node beds have a low sensitivity and
The thorough surgical staging of early-stage ovarian specificiiy for the detection of lymph node
a
cancer is important to establish the correct stage for metastasis, several studies have investigated the role
determining prognosis and choice of therapy of a systematic pelvic and paraaortic lymph node
(chemotherapy vs. observation). A prospective dissection. ln a prospective trial, Maggioni and
randomized trial of patients with FIGO stage l-llA colleagues randomized 310 patients with early,
u''u'
disease (ACTION tria)l: indicated that complete FIGO stage I and ll ovarian cancer who had
surgical staging was statistically significantly undergone optimal surgical debulking to receive
associated with better outcomes. ln this trial, either a systematic lymph node dissection or lymph
patients were randomly assigned to adjuvant node sampling
uu.
Patients with all major histologic
chemotherapy or observation after they had subtypes were represented in the study: serous
t
undergone either complete or incomplete staging (39Y"), endometrioid (21%), mucinous (13%), and
I surgery. Although the trial was not designed to clear cell tumors Q3%). Positive lymph nodes
:
( compare different surgical staging procedures (and (which upstage a patient to stage lllC) were found in
I extent of surgical staging was not randomized), a 9% of patients in the sampling group, and in 22% of
subgroup analysis found that patients with a poorly the systematic lymph node dissection group (p <
differentiated tumor in the optimally surgically staged 0.05), suggesting that 13% were upstaged because
I
group (n:78) had a significantly longer (p < 0.009) of the lymph node dissection. Of all patients in the
r
1O-year cancer-specific survival of 85% compared to study with negative lymph nodes, 66% of the
I
56% in patients who were not completely staged patients in the control arm and 51% in the
(n:78) which is logically attributable to their higher systematic lymphadenectomy arm received
I risk of undetected residual disease. This improved chemotherapy (p < 0.03), suggesting that in an
outcome was independent of age, presumed stage, unstaged patient, physicians tend to err on the side
I
histology and whether or not chemotherapy was of overtreatment.
u'.
given The benefit of adjuvant chemotherapy was
found to be restricted to patients with incomplete ln summary, systematic lymph node dissection
surgical staging, and incompletely staged patients provides important prognostic and staging
with a poorly differentiated grade lll tumor were information for patients with suspected early-stage
found to derive the greatest benefit from adjuvant ovarian cancer, which assists with decisions about
chemotherapy. Predictors of unappreciated residual adj uvant chemotherapy.
disease after primary surgery, which leads to
upstaging, include a high preoperative CA-125 level, At laparotomy, apparent early-stage disease requires
positive cytology, and grade lll disease
u'. comprehensive staging. Standard treatment at the
I staging laparotomy consists of TAH, BSO, and
u''u'.
t infracolic omentectomy and surgical staging lf
histological examination confirmed Stage lA, Grade
515
1 disease, i.e. (Stage lA-1), then the standard cancer should be followed carefully with
treatment is adequate management. However, routine transvaginal ultrasonography and
recently, it has been shown that in all subodt@o-ries determination of serum CAl25 levels.
of early (Stage l-Stage ll) disease affi,ih a{] Generally, the other ovary and the uterus
histological grades of the tumour, ffiFffiste should be removed at the completion of
plati n um-based adj uvant chemotheraplr si childbearing
improves overall survival (82% versus 74y;,hffiffi
ratio 0.67, 95y" Cl=0.50-0.90; p=0.808). lll lV)
Treatmentof Advanced Disease (Stage
I mediate chemothera py a lso significantly i mproves
m Treatment consists of TAH, BSO, complete
recurrence-free survival at 5 years (75o/ovafSus650/o, omentectomy, and removal of anytumourthat can be
rati o 0. 64, 9 5% C I = 0. 50-0. 82 ; p : O. OO 1 )u'' seen or palpated and resection of any metastatic
lru.rut{ lesions from the peritoneal surfaces or from the
Fertility Preservationl Conservative Management in intestines. The pelvic tumor often directly involves
Ea rly- Stage Ova ri a n Ca n ce r the rectosigmoid colon, the terminal ileum, and the
cecum (primary cytoreductive or debulking surgery)
ln special circumstances (see below), unilateral 67'64.
The aim is not to leave behind any tumour
salpingo-oophorectomy may be performed with which is more than 1cm in its largest diameter. The
conservation of the contra-lateral ovary and the primary surgery is immediately followed by
uterus in order to retain fertility. The indications and chemotherapy.
pre- requisite conditions for this dispensation are
listed below. Theoretic Rationale for cytoreductive surgery
The rationale for cytoreductive surgery relates to
Criteria tor Conservafi've Management of Epithelial general theoretic considerations un-", (i) the
Carcinoma physiologic benefits of tumor excision and (ii) the
The patient must satisfy all of the following improved tumor perfusion and increased growth
conditions: fraction, both of which increase the likelihood of
response to chemotherapy or radiation therapy.
. Comprehensive staging laparotomy showed
disease to be Stage lA Physiologic benefits ascites may be sometimes
o Patient willing and able to have close follow- reasonably well controlled after removal of the
up: clinical examination, transvaginal pelvic primary tumor and a large omental cake. Also,
ultrasound and CA125 every 6 months. removal of the omental cake often alleviates the
o HistologicalgradeT-2 nausea and early satiety that many patients
o Patient understands and has given experience. Removal of intestinal metastases may
assurance that she will come for removal of restore adequate intestinal function and lead to an
contra-lateral ovary when childbearing is improvement in the overall nutritional status of the
complete. ln patients who have undergone a patient, thereby facilitating the patient's ability to
thorough staging laparotomy and in whom tolerate su bseq uent chemothera py.
there is no evidence of spread beyond the
ovary, the uterus and contralateral ovary can lf all recognisable tumour was removed, this is
be retained in women who wish to preserve "adj uva nt" chemothera py. See below for def i n itions of
fertility 63-66. In several studies, women with "adj uva nt", "neo-adj uva nt" a nd "adj u nctive".
stages lA-l C have u ndergone ferti I ity-spa ri ng
surgery, and there have been no recurrences Role of Lymph Node Dissection in Advanced Ovarian
in women whose disease was grade I or 2 Cancer Surgery
' 65'66.
Women with grade 3 or higher=stage A prospective randomized ltalian trial of 427
disease have had a significantly higher paiients with advanced ovarian cancer (stages
recurrence rate and lower survival. Women lllB-lV) compared an extensive systematic lymph
who have undergone fertility-sparing surgery node dissection with resection of 'enlarged ("bulky")
for low-stage, low-grade epithelial ovarian lymph nodes and concluded that positive lymph
nodes are a negative prognostic marker but that
616
Epithel ial Ovarian Carcinoma
systematic lymph node dissection did not contribute effort and 3 cycles of
chemotherapy. The neo-
! to the benefit of optimal tumor debulking. Systematic adjuvant therapy is expected to reduce the size of the
?
lymph node dissection improved PFS (median PFS, iumour and make subsequent surgery possible or
22vs.29 months), but not OS (median OS,59 vs. 56 less difficult or less radical. There is conflicting
uu.
months) evidence from 2large prospective, randomized trials
i
whether secondary cytoreductive surgery can

At this time, however, there is no convincing data that improve survival in these patients "'". (see under
lymph node dissection has a therapeutic survival Controversies).
benefit in advanced ovarian cancer. The current
literature suggests that in advanced ovarian cancer, Defi n itions ; Adi uvant, neoadi uvant, a nd adiu nctive
enlarged/suspicious lymph nodes should be removed therapies
as pad of tumor debulking, and that a systematic Adjuvant therapy: This is therapy given after the
pelvic and paraaortic lymph node dissection might primary treatment, and, when the primary treatment
therapeutically benefit patients who previously had is expected to produce a cure but there may be
been optimally debulked to microscopic residual microscopic disease and there is a high chance of
disease. The results of an ongoing large international recurrence. Adjuvant therapy may be chemotherapy,
phase lll trial in patients with advanced ovarian radiotherapy, or a combination of the two.
t cancer who were debulked to microscopic disease
Neoadjuvant therapy: This is therapy given before
I
and randomized to a systematic lymph node

surgery is performed to reduce the size of the lesion
l'
r dissection or sampling, should be able to clarify the
f so as to make surgery less extensive and less radical,
I roleof a lymph nodedissection
r and often to make surgeryfeasible.
t
1 Second looklaparotomy
Second look laparotomy (SLL) is a repeat laparotomy Adjunctive therapy: This is therapy given when the
at some time after primary surgery/chemotherapy in primary treatment was not complete; i.e. when the
order to perform a thorough intra-operative search for primary treatment did not eradicate the disease, and
residual disease to evaluate the remission, the primary treatment is therefore not expected to be
persistence or recurrence of disease since the primary curative. Adjunctive therapy may be chemotherapy,
su rgery/chemothera py. radiotherapy, ora combination of thetwo.
: Chemothen py of Epithel ia I Ova ria n Ca ncer

lndications: SLL was used for the patient who had all
I
I of thefollowing:
Standard first-line chemotherapy of epithelial
. Had advanced intra-abdominal disease ovarian cancer consists of a combination of a
(Stage lll) platinum (cisplatin or carboplatin) and a taxane
i
. Had undergone primarysurgery
(paclitaxel or docetaxel). Combination
. Had finished a prescribed course of chemotherapy has been shown to be superior to
chemotherapy single-agent therapy in most studies of initial
o Now, has no clinical, radiological, ultrasonic, chemotherapy in patients with advanced epithelial
or chemical evidence of disease ovarian cancer 'o'u. Platinums do not have cross-
resistance with taxanes. The chief complications of
Approximately 50% of those with negative SLL will the two drugs are also different. The two drugs are
develop recurrent disease. Serial measurement of therefore ideally suited for combination therapy.
tumour markers is now used to monitor tumour Currently, a combination of carboplatin and
progression or recurrence. As a result, SLL is no paclitaxel is the gold standard; in trials it has
longer performed for this purpose, but is now produced the most favourable outcome as measured
reserved forthe research setting. by the response rate, time to disease progression,
and overall survival"'". However, it is likely that
I nterval Debulking Surgery docetaxel will replace paclitaxel in the doublet in the
The term interval debulking surgery refers to a near future"-", lt is associated with less peripheral
surgical procedure in a patient with persistent neuropathy, and possibly with a slightly higher
abdominal disease after an initial surgical debulking
517
.-!
recurrence rate. For germ cell and sex cord stromal myelotoxicity, especial ly th rom bocytopen i a (nad i r
cancers, another cytotoxic drug may be added, e.g. 1418 days) and leucopenia (nadir 78-25 days).
vincristine, actinomycin D, bleomycin, eto@stde, or Carboplatin is more myelosuppressive than cisplatin
76'42'43.
cyclophosphamide, with bleomycin, etoposir# ad However, nephrotoxicity, neurotoxicity,
cisplatin (BEP) beingthe preferred regimen. ototoxicity, and nausea and emesis are much less
than with cisplatin. Carboplatin is quantitatively
Platinums secreted by the kidney; 70% is excreted in 24hrs.
Platinums (cisplatin and carboplatin), are inorganic Therefore, its effective concentration depends on its
platinum co-ordination compounds with urine clearance. The dose is ZOO- OOmglm2 of
antineoplastic activity. They are non-classical surface area. The actual dose is determined
alkylators. lnside the cell, a platinum loses a chloride according to renal function (clearance) rather than
ion (Cl-). This generates an intracellular positively body surface area, and it is adjusted to achieve an
charged platinum complex that forms bivalent links Area Underthe Curve (AUC) of 5-7 per hour.
with DNA, RNA, and intracellular protein, resulting in
intra-strand DNA cross-links, and DNA-protein cross- Taxanes
links. Because of the cross-links, synthesis of DNA, These are paclitaxel and docetaxel. Paclitaxel:
RNA and protein is inhibited. The drugs are cell cycle Paclitaxel (Taxol) is obtained from the bark of the
non-specific, i.e. they act in all phases of the cell Western yew tree. Paclitaxel promotes and stabilises
cycle. Platinums are highly bound to protein. They cellular microtubule polymer formation. lt thus
are excreted in urine. The toxicities of platinums inhibits both interphase (G,, S, and Grphases of the
include: cell cycle) and mitosis, and it thereby prevents cell
. Nephrotoxicity, especiallywith cisplatin division and tumour growth. lts dose-limiting toxicity
o Anaemia,thrombocytopenia is myelosuppressrbn (nadir 8-11 days), seen as
. Myelotoxicity neutropenia, especially granulocytopenia.
. Peripheral neuropathy: Heavy-metal distal Secondary side effects are peripheral neuropathy
sensory neu ropathy, especia ly with cisplati n
I ( pa rasthesiae), bradyca rd ia, mya lgia, a rth ra lgia, a nd
o Ototoxicity: High frequency hearing loss, nausea and vomiting, mucositis, and severe
especial ly with cisplati n
hypersensitivity reactions (related to vehicle,
. Nausea and vomiting, especially with
Cremophor). lt is metabolised in the liver and 40% is
cisplatin
excreted in bile in 24hrs;10% is excreted unchanged
in urine in 24hrs. The dose is i35-175mg/m'when
The platinum drugs currqntly used for treatment of
combi ned with carboplatin.
ovarian cancer are cisplatin and carboplatin. They
are administered by intravenous infusion.
Docetaxel: Docetaxel is at least as effective as
paclitaxel "-t'. But, unlike paclitaxel, which requires
Cisplatin: Nephrotoxicity is the dose-limiting toxicity
of cisplatin. The nephrotoxicity is cumulative.257" of
3 hours for intravenous delivery, docetaxel is
generally delivered as a 1-hour intravenous infusion.
cisplatin is excreted in the urine in 24hrs. Renal
This makes docetaxel more suitable for outpatient
tubule damage may result in hypomagnesaemia and
administration. Toxicity profiles of these two taxanes
hypocalcaemia. Nephrotoxicity can be ameliorated
by vigorous intravenous hydration before and during
are also different. Myelosuppression is more
therapy to ensure adequate renal perfusion and
common and more severe (grade 4
anaemia/neutropenia and neutropic fever) with
urinary output. lt is usually administered in 3% saline
followed by mannitol infusion to produce diuresis.
docetaxel than with paclitaxel. However, the
myelosuppression associated with docetaxel is
The dose is determined by body surface area and is
usually transient, is not associated with increased
usuaily 7lmglm' (range 50-125mg/m2). Drugs
mortality and can be managed by oral antibiotics and
which may affect renal function, e.g. non-steroidal
by dose reductions without compromising efficacy.
analgesic drugs and aminoglycosides, should be
On the other hand, both short-term neurotoxicity and
avoided during cisplatin therapy, in an effort to
long-term neurotoxicity of up to 14 months after
reduce the possi bi I ity of synergistic renal damage.
Carboplatin: The main side effect of carboplatin is completion of therapy are more common and more
518
------;----!!
severe with paclitaxel than with docetaxel. period of 24hrs. This usually requires
Hypersensitivity reactions are more common with hospitalisation.
docetaxel, but thesecan be prevented o1 cOntrolled
with histamine prophylaxis. As a result, My of life Because of the above reasons, carboplatin can be
improves more with docetaxel than ,i@,@fuxel given on an outpatient basis whilst cisplatin usually
treatment. Therefore, docetaxel is likbly to r,eptace requires hospital isation.
pacl itaxel i n the ca rbopl ati n-paclitaxel,'dorlbkt'e-".
At the present time paclitaxel-carboplatin doublet is
Neurotoxicity is the most important 'rcason for
discontinuing chemotherapy. Another csrnmon'side
the gold standard. However, because of the
advantages of docetaxel over paclitaxel discussed
effect of docetaxel is persistent fluid retention in the
above, docetaxel-carboplatin may be preferred in the
form of legoedema.
future.
Addition of Bevacizu ma b to Prima ry Chemotherapy
Bevacizumab is a humanized monoclonal antibody
Currently, a commonly employed regime is as
follows:
targeting vascular endothelial growth factor UEGF).
Carboplatin dosed to achieve an area underthe curve
Elevated vascular endothelial growth factor (VEGF or
(AUC) of 5-7 in thr plus Paclitaxel 775m{m'as a
VEGF-A) expression occurs in all stages of ovarian
3hr intravenous infusion every 2I to 28 days for 6
cancer and is associated with poor prognosis,
cycles.
including shorter survival. Bevacizumab as a single
Radiotherapy is no longer a therapeutic option in
agent has produced response rates in the range of
most centres". Unlike chemotherapy, radiotherapy
15% to 20%inthe setting of recurrent ovarian cancer
sterilises the ovaries and destroys fertility. lt is also
'o-'u., which are higher than the response rates seen for
associated with leukaemia.
othersolid tumors.
Pre-Chemothera py La boratory tests
Chemotherapy of Ovarian Cancer Before start of treatment and also at nadir:
The sheet anchor of ovarian chemotherapy is a FBC and platelets
platinum-taxane doublet. The treatment schedule LFTs
consists of 6 cycles (courses) of one of the following RFTs: BUE & creatinine
doublets given at 3 to 4-weekly intervals.
o Paclitaxel-cisplatin Chemotherapy Pre-Medication
. Paclitaxel-carboplatin Cytotoxic therapy is associated with symptoms that
o Docetaxel-carboplatin may be acute, delayed or anticipatory. These are
Carboplatin haS the following advantages over chiefly nausea and vomiting and hypersensitivity
cisplatin: reactions. They can cause the patient to refuse
Emesis is less severe further treatment, or lead to medical discontinuation
i
N eph rotoxi city, neu rotoxicity a nd ototoxicity a re
of therapy. Therefore, it is important to prevent and
less frequent and less severe. Although treat them. This is achieved with pre-medication
myelosuppression is more frequent with with a cocktail of multiple drugs, including an
carboplatin, this is not usually severe.
antihistamine or a phenothiazine, a corticosteroid, a
It is better tolerated
serotonin (5HT.) antagonist, a histamine Hr-receptor
It does not require intensive intravenous
antagonist (blocker), and a benzodiazepine. For
hydration before and during administration and
example, the following combination may be used:
it causes less nausea and vomiting.
ln the carboplatin-taxane doublet, paclitaxel is
Dexamethasone sodium phosphate (a
delivered as a 3-hr infusion whilst docetaxel is
corticosteroid) for prevention of acute and delayed
infused as 1-hr. On the other hand, cisplatin with
symptoms: lt is given as a single dose of 20mg lV
shorter-infusion paclitaxel schedules can result
30min before each chemotherapy course. At the end
in a high incidence of severe peripheral
of the course it may be given as 2mg orally three
neuropathy.
times a day for 5 days. The mechanism of action is
Therefore, in the cisplatin-taxane doublet, the taxane
(paclitaxel or docetaxel) must be administered over a
unknown, but probably it inhibits prostaglandin
619
--------:----l
synthesis. lt has an europhoric effect, which is new vessels indicates new growth or an
beneficial. lts side effects include fluid retention and increase in the size of existing metastases.
insomnia. New vessels have lower impedance than
r Prochlorperazine (Stemetil) (a phenothi- mature vessels and this can be demon-
azine): Stemetil is a dopamine blocker and strated with colourflow Doppler.
an antiemetic. The dose is 10-25mg lM ol lV
or by mouth every 6hrs, or as a 25mg Clinical Pathological Prognostic Factors
suppository. . Stage (Table 2)
o Lorazepan (a benzodiazepine): lt is a . Lymph node involvement (Table 2)
sedative and anxiolytic. The dose is 25- o Histological grade: Regardless of histologic
3Omicrograms/kg (average 1-2mg) by slow type, grade is an important determinant of
lV injection over 15min. lt is used to prevent outcome in all stages of the disease but
anticipatory symptoms because of its especially in Stage l/ll (early) disease."
amnesic, sedative and anxiolytic effects. o Amount of residual tumour, i.e. tumour
. Ondansetron (a 5HT. antagonist): Blocks remaining after primar! surger!: Smaller
SHT. receptors. The dose is 8mg. tt is given residual tumours have better prognosis.
by slow lV injection immediately before Patients with no residual disease have the
treatment. lf required, the dose is repeated at best survival. There is a striking difference in
2-4hr intervals for two more doses. An survival between cases with residual disease
alternative regimen is 1mg/hr by continuous <2cm and the ones with residual disease
lV infusion for up Io 24hrs and then 8mg >2cm. For example in Stage lllC, the 5-yr
orally l2hourly for up to 5 days, or 16mg survival is 34% and 20% for residual
rectally daily for up to 5 days. The chief side disease <Zcm and residual disease >2cm,
effects are headache, elevated respectively"
transami nases, constipation and diarrhoea. . Malignant cytology of ascitic fluid/peritoneal
o Cimetidine (a histamine Hr-receptor antago- washings: Positive cytology is highly
nist): 400mg orally twice daily. suggestive of occult peritoneal metastases
. Age of patient: Younger patients have better
Routine premedication with a combination of prognosis
dexamethasone, an antihistamine, and cimetidine is . Cell type: Stage for stage and Grade for
given before paclitaxel to prevent severe hypersensi- Grade, clear cell cancers have a worse
tivity reactions. For oral docetaxel, dexamethasone prognosis than endometrioid and mucinous
for 3 days, starting a day before each course of cancers. But, in practice, serous cancers
docetaxel helps to reduce fluid retention and hyper- have the worst prognosis, because they have
sensitivity reactions. higher stage and grade at diagnosis than the
other cell types
Observation: Assessment of Residual Disease . Capsule status: Rupture (spontaneous and
. Abdominal and pelvic examinations intraoperative), adherence, penetration, and
. Serial levels of tumour markers: Serum excrescences. I ntra-operative ru ptu re resu lts
CAT2S levels can be used during chemother- in a higher FIGO sub-stage, i.e. lC instead of
apy to follow those patients whose level was lAy'lB, and llC instead of llA/llB
elevated at the initiation of treatment "'". . Cellular/Tumour marker prognostic factors
The change in level generally correlates with which are associated with a worse progno-
response sis: -DNA: Aneuploid tumour -P53 expres-
o Computed tomography or ultrasound scan of sion in tumour -C-erbB-2 expression in
' the abdomen and pelvis for masses and tumour-C-myc expression in tumour
lymph nodes
. Colour flow Doppler for neovascularisation:
Angiogenesis is a necessary pre-condition for
cancer growth. Therefore the presence of
620
Ep ithel ia I Ova ri a n Ca rc i noma
Table 2 Lvmoh node Positivitv. Stase and 5 -vr Survival

Stase il ilt IV
,2-5,
Positive Nodes (7e) 50 75
5-vr Survival (%) Gr,.- 60 25 115
Pseudomyxoma Peritonei Pse ud o my@cl{i,.ffiton e i associated with germ-line mutations in BRCAl

Ir is caused by mucinous tumours of the intestinattype. (BReast CancerAntigen 1) or BRCA2 genes. These
I It is most commonly associated with mucinous are autosomal dominant genes. BRCA1 gene is on
I
f tumours of the ovary and appendix. lt is'associated chromosome 17. A woman who inherits a mutated
I
r with well-differentiated adenocarcinomas and those allele of BRCA1 has 50%-80% risk of breast cancer
I
r of low malignant potential (LMP), rather than with and 20%-50% risk of ovarian cancer by age 70
t malignant tumours. The mean age at presentation is years. In contrast, in North American women, the
t
population risks of breast and ovarian cancer are
r 58yrs.
r 7.5% and 1.4"/", respectively. The risks are much
I
Histogenesis lower (27"/o) for carriers of a BRCA2 mutationo.
Clusters of cells implant on the visceral and parietal
I
Although these appear to be responsible for most

peritoneal surfaces and on the omentum and produce hereditary ovarian cancers, it is likely that there are
fY
I thick gelatinous mucin, which eventually fills the other, as yet undiscovered, genes that also
I abdomen. lt has a protracted clinical course with predispose to ovarian or breast cancer or both '0. ln
I multiple recurrences that leads to bowel dysfunction families with two or more cases of early onset breast
t
I
and eventual death from inanition. Repeated tapping cancer and in families with two or more ovarian
I
results in hypoprotei naemia. cancer, BRCAl is almost always implicatede'.
I
i Families with hereditary non-polyposis colorectal
Clinical features
cancer are also at increased risk of ovarian
t
o Symptomatic pelvic or abdominal
carcinoma. The risk is 9%". The risk of endometrial
?
mass
. cancer is higher. The two most frequently mutated
lncreasing abdominal girth
i genes in hereditary non-polyposis colorectal cancer
I o Abdominalpain
t . Anorexia
arethe mismatch repairgenes hMSH2 and HMLH1.
i
!
o Early satiety There are three distinct patterns of familial ovarian
C?OC€T:
r
t
Treatment
Cytoreductive surgery and appendicectomy, even if i. Site-specific, i.e. where only ovarian cancer is seen
t the appendix looks normal. Systemic and intra- in the family. A mutation in BRCA1 or BRCA2 is
pe ritoneaI adj uva nt cytotoxic thera py Hypertherm ic
( always involved in these cases".
I lntraperitoneal Chemotherapy, HIPEC) 'n are under
I
I ii. Ovarian cancer and Breast cancer seen in family:
review. Abdominopelvic radiotherapy is generally not
r beneficial.
BRCAl or BRCA2 always involved. Carriers of the
I
I
t BRCAl gene have the highest risk of ovarian cancer.
rci noma
Hered ita ry ova ria n ca More than 80% of families with 2 or more ovarian
I
I lncidence: Hereditary ovarian cancer is uncommon; cancer cases and premenopausal breast cancer are
only 5% to at most 10% of ovarian cancers are thought to be due to mutations in BRCAl .
I
attributable to an inherited gene or genes. However,
in some ethnic groups such as Ashkenazi Jews, this iii.
Ovarian cancer, endometrial cancer and non-
,
risk is as high as 3O"/oo. Next to age, a positive family ll cancer family
polyposis colorectal cancer (Lynch
:,
history of ovarian cancer is the most important risk syndrome): Hereditary non-polyposis colorectal
I
factor. With one affected first degree relative, odds cancer involves genetic predisposition to
ratios ranging ffom 1.9 (95% Cl 1.1-3.6) to rynaecological malignancies as well as colon cancer.
i L8.2Q5% Cl 4.8-69) have been calculated'.. Next to colon cancer, endomdtrial cancer is the most
frequent cancer seen in female gene carriers. Ovarian
f Almost all (85%) of hereditary ovarian cancer is
i cancer risk is increased seven fold.
i
I
621
t'
Age at presentation: Hereditary ovarian cancer the mesothelium liningof the coelomic cavity.
occurs at an earlier age than sporadic cancer. The Prognosist Stage for stage, the prognosis for
mean age of onset is about 5 years younger than in hereditary ovarian cancer is not different from that of
sporadic ovarian cancer4'e3-e5. Bias may h be sporad ic ova ria n ca ncer"''oo.
partly responsible for this finding. lt is protldib that
because of suspicion and repeated screenirg; the Tumour Markers in Ovarian Cancer
disease is diagnosed earlier in famffies wJth Currently, tumour markers are used in the following
hereditary cancer. Cancer secondary to BRCAl situations:
mutation occurs some 10 years earlierthan cancer in
1 Monitoring primary treatment: Baseline levels
are compared with levels after completion of
carriers of BRCA2 mutation (50.2 years versus 59.9
years as against 61 years in sporadic cancer).
initial treatment to determine whether therapy
has been effective in controlling the disease, or
Histology= Almost all hereditary ovarian cancers are early therapeutic failure is present. lf after
serous tumours; they are rarely of the mucinous type. completion of initial treatment the tumour
Less than 2% of hereditary ovarian cancers are marker levels are still above their values or are
mucinous (7.4% versus 72.7% in sporadic cases sti I I risi ng then thera peutic fa iI u re is present
2 Diagnosis of recurrent disease: Relapse can
Low malignant potentia/: The proportion of low occur months or years after completion of initial
malignant (borderline) tumours among familial treatment. Tumour markers can be measured
ovarian cases is much smallerthan the proportion in longitudinally. lncreasing tumour marker levels .
sporadic ovarian cancer". often precede the clinical diagnosis of recurrent

disease.
Prevention= Use of the combined contraceptive pill 3 Preoperative diagnosis of germ cell and sex cord
and prophylactic bilateral oophorectomy are stromal tumours in premenarchal girls and in
measures that can prevent death from familial women under40yrs
ovarian cancer (see below). We must assess the 4 Differential diagnosis of small adnexal masses
likelihood of hereditary ovarian cancer in any patient ln using tumour markers, note must be taken of the
we see at our clinic. The important questions we following:
must ask include the followinga: ls there a family
history of breast, ovarian, or colorectal carcinoma?
1 Ageand menopausal statusofthe patient
What is the histological type of the ovarian

2 f
he degree of elevation of the tumour marker
3 Change in the tumour marker level over time:
carcinoma? What isthe ethnic origin of the patient? Rapidly rising levels are more likely to reflect the
Bilateral prophylactic oophorectomy: This should be v-
presence of ovarian cancer.
offered only to women with a proven family history of
4 Concurrent medical conditions that may cause
hereditary ovarian cancer". Ovarian cancer rarely elevation in tumour marker levels t-
occurs in women under 45 (about 11 per 100,000) 5 Family history of ovarian cancer
and even in women with a family history of ovarian 6 The presence of an adnexal mass on pelvic
cancer who are not more than 45 years, it is still examination or scan
uncommon; the rate is 33 per 100,000ee.
Prophylactic oophorectomy has been recommended CancerAntigen 725
after completion of childbearing age or after age CA 125, a high molecularweightglycoprotein, isone
35'oo. Peritoneal carcinomatosis that is of many antigens associated with human epithelial
indistinguishable from ovarian carcinoma can ovarian cancers that are defined by monoclonal
develop in some women after prophylactic antibodies. CA 125 is measured using a monoclonal
oophorectomy. This occurred in 3 of 28 $7"/") antibody to epithelial ovarian cancer, the ovarian
women with a family history of breast and ovarian cancer 125 antibody (0c125). The investigators
cancer". This suggests that the risk of cancer is who discovered CA 125, so named it because it was
inherent in the peritbneum. Embryologically, the at the 125'n attempt that they succeeded in
ovarian epithelium and the general peritoneum share producing the monoclonal ovarian cancer antibody
the same origin, which is the primitive epithelium of that is used for measuring CA 125. CA 125 is
522
r
T
I Epithel ial Ovarian Carcinoma

r
I
r elevated in about 80% of all non-mucinous ovarian teratoma. lt is elevated in nearly IOO% of women
rI
F
cancers. Approximately 85% of patients with with the uncommon germ cell tumours of the ovary,
rI epithelial ovarian cancer have CA125'f6els of endodermal sinus tumour (yolk sac tumour),
Ir- greater than 35 kU/L
o'''o',
with elevat#ffi.jound embryonal carcinoma, and the rare polyembryomas.
r in 50% of patients with stage I diseasa'6iqd'fi@-ethan q-FP measurements are useful in the preoperative
l
i 90% of patients with stage ll to lV Oiseased. Cn tZS diagnosis of these rare germ cell tumours.
is also expressed by various other pathologic and Preoperative recognition of these tumours is
t
normal tissues of Mullerian origin. Therefore, CA 125 important in girls and young women because
I is nonspecific. Apart from non-mucinous ovarian removing the contralateral ovary does not influence
cancers, it is also elevated in the following conditions: patient survival.
i
I o 60% of pancreatictumours
o Pancreatitis Human Chorionic Gonadotropin hCG)
. 257" of other solid tumours hCG is elevated in the presence of non-gestational
r . Du ring menses if endometriosis or choriocarcinoma, embryonal cancer and

;
adenomyosis is present polyembryomas.
. Endometrialcancer
o Uterinefibroids Human Placental Alkaline Phosphatase (Human
. PID PUP)
i
. Early pregnancy Human PLAP is a glycoprotein molecule consisting
. Diverticulitis of two units. Human PLAP is almost always
r . 7 O"/" of women with ci rrhosis of the liver. expressed by germ cell tumours. lt is therefore a
t'
sensitive marker for differentiating germ cell tumours
Urinary Gonadotropin Peptides UGP) from other ovarian tumours. However, it is not a
UGP is a peptide with sequence homology to specific marker because it is elevated in other
segments of the B-subunit of hCG. UGP is present in cancers, particularly those that arise in Mullerian
the urine of 7OY" of women with epithelial cancers of structures.
the ovary. Women with adnexal masses and with
.l
elevated CA 725 levels, but who have normal UGP Serum lactic Dehydrogenase (SLDH)
titres are much more likely to have a benign condition SLDH is elevated in the presence of dysgerminoma,
)
G
than a malignancy. The use of both CA 125 and UGP especially in those with diameters >1Ocm. There is
levels in managing adnexal masses is therefore more a good correlation between the volume of tumour
{I
rewarding than the use of either alone. tissue present and the level of SLDH. lf there is an
i
adnexal mass and SLHD is markedly elevated, but
cA 19-9 other hepatic enzymes and the hCG level are within
This is a carbohydrate antigen. lt is an important normal limits or are only slightly elevated, then a
't
tumour marker for gastrointestinal cancers, dysgerminoma is the most likely diagnosis. ln
especially colon and pancreatic cancers. lt is elevated reproductive age women, this biochemical profile
in mucinous ovarian tumours but not in serous helps to distinguish dysgerminoma from other solid
ovarian cancer. lt is therefore useful in distinguishing ovarian tumours such as ovarian fibroma and
between serous and mucinous ovarian cancers. Brenner tumour. This preoperative distinction is
(Cil) clinically important because dysgerminoma
Carci noem bryon i c Antigen
selectively spreads by lymphatic channels.
CEA is a high molecular weight glycoprotein. lt is a
Paraaortic lymph node sampling is therefore
tumour marker for gastrointestinal cancers and is an
mandatory in staging when dysgerminoma is
excellent marker for mucinous ovarian cancers. lt is
present, irrespective of the macroscopic state of
Elevated in 90% of patients with mucinous ovarian
1 these lymph nodes.
cancer.
Alpha-Feto Protein (
-FP) o-FP is an albumin-like
Prevention of Ovarian Cancer/Reduction of
* Mortality
protein normally present in fetal serum. lt is elevated
lntroduction
in germ cell tumours, except dysgerminoma and The ultimate aim of all cancer research, diagnosis
623
and treatment is to prevent people from developing B. lnterventions

the disease, and if that fails, to prevent them dying 1 Combined oral contraceptive use lowers the risk
from the disease. To achieve this aim, we ,adopt by approxim alely 40%. This is the most effective
actions and interventions at 3 levels: pfJmary, intervention we have.
secondary and tertiary. 2 Prophylactic BSO: This can be done when
1 Primary prevention: Consists of actions and performing indicated total hysterectomy in peri-
interventions which reduce the risk of menopausal and postmenopausal women, and
developi ng the disease. in women with a positive family history of
2 Secondary prevention: These are measures to ovarian cancer (see under "Hereditary Ovarian
identify the disease in its early stages when it is Cancer").
curable.
3 Tertiary prevention: Consists of improrrements in Secon dary Preve ntion (Dow n stagi n g)
treatments that increase progression-free The objective of secondary prevention is to halt the
interval, overall survival rates, and a higher progression of a disease that has just become
quality of life. established. Generally, this is achieved by measures
that aim to detect the disease in its earliest stages,
Primary prevention followed by prompt effective treatment. This is the
The objective of primary prevention is to prevent the purpose of screening and this approach is called
onset of the earliest stages of the disease. ln this downstaglng. lt is based on the fact that, generally,
effort, we make use of what we know of the the treatment of cancer is easier and more effective in
epidemiology, i.e. aetiological risk factors, of ovarian its earliest stages.
cancer.
Action on Symptoms and Signs
A. Changes in life-style Screening
B. lnterventions Screening
A. Changes in life-styles: Age, race, family history, As already discussed, as yet we do not have an
age at menarche and at menopause are factors we effective screening method for ovarian cancer.
cannot change; but nutrition, tobacco smoking, and However, women at high risk of developing ovarian
sexual behaviour can be influenced and cancer can be monitored with annual bimanual
manipulated. The associations have however not examination, serum CA 125, abdominal and
been consistent in the studies carried out. transvaginal ultrasound and colour flow Doppler for
1 Nutrition: lncreasing daily consumption of neovascu I a rizalion
o''o'
.
vegetables, fruits, pulses, and vitamins A, C and

E are protective, whilst increased intake of total Prompt action on symptoms and signs
fat, particularly, saturated fat, and red meat are Although ovarian cancer has no signature symptom
associated with increased riskof ovarian cancer or sign, when women develop the vague gastro-
2 Obesity: Avoiding obesity reduces the risk intestinal symptoms and/or recurrent abdominal
3 Smoking: Stoppingtobacco smoking reduces the pains associated with the disease they wait too long
risk to seek medical care. When they do report for
4 Sexual health education: Women should avoid treatment, health workers often do not take their
sexual behaviours that are likely to result in complaints seriously. A high index of suspicion is
acquisition of the HPV e.g. prostitution, multiple required to diagnose the symptomatic disease early.
sexual partners, male partners who have
multiple Tertiary Prevention
sexual partners or are carrying the HPV and non-use The objective of tertiary prevention is to 'ehabilitate
. of the female or male condom people with an established disease to minimise
1 HRT: Avoiding oestrogen-only hormone residual disabilities and complications. This
replacement therapy reduces the risk objective is achieved through:
2 Breastfeeding reduces the risk . lmproved treatment
3 Daily low dose (75mg) aspirin is protective r Physical rehabilitation (physiotherapy)
. Psychosocial support
624
Epithel i al Ova rian Ca rci noma
lmproved treatment disease. Examples of such populations are:

This includes adequate surgery, adequate a. Post-menopausal
chemotherapy (neoadjuvant, adjuvant, and b. Positivefamily historyof ovarian cancer
adjunctive), physical rehabilitation, and c. Positive family history of breast, colon and ovarian
psychological su pport. cancer (Lynch ll syndrome)
d. A patient with one ovary previously removed for
Controversies ovarian cancer
7
I Are the following interventions beneficial?
r, To make a diagnosis of a genetic predisposition to
Ca rci nom a
Screen i n g fo r Ova ri a n cancer, a family history including details of parents,
I
rI Ovarian cancer is more easily and effectively treated grandparents, aunts and uncles must be taken.
r in its early stages. Survival rates drop steeply when Where there are two or more cases of ovarian cancer
r women present with advanced disease. Therefore, to on one side (paternal or maternal) of the family, or
reduce morbidity and mortality from ovarian cancer it where there is ovarian and pre-menopausal breast
I
r
is crucial to detect it early. The objective of screening cancer, the patient should be referred to a genetics
I
is to diagnose the disease early and treat it early so as centre.
r to improve prognosis. This approach is called
l\Fu
!'- downstaging. lt is secondary prevention. The following multi-modal screen was tested in a
pilot ra ndom ised controlled study of
I
F
] All the available screening tests lack specificity when postmenopausalwomen.
applied to unselected populations. That is, the result Step 1: Estimation of serum CAl25level
r may be positive when the disease is absent. ln other Step 2: Transvaginal ultrasound for ovarian volume if
r
r words, they produce too many false positives. The CAl25 was >30 units/mL
t
t available tests can be categorised as follows:
Step 3: Referral for a gynaecological opinion if
A. Family History of Familial Disease: Note that only ovarian volume was > 8.8mL
l 5% of ovarian cancers arefamilial. The protocol produced a positive predictive value of
: B. Pre-symptomatic genetic testing for a familial 21o/o'o', which was much higher than that obtained
t
: predisposition using a single screen.
r C. Clinicalmethods:
. Annual bimanual examinations Conclusion: Although a multi-modal approach,
I
. Annual bimanual examinations plus using a combination of methods, improves the
t
I cu ldocentesis for cytology detection rate, no test or combination of tests, has
tY yet proved to be practical for screening unselected
I D, I nvestigational methods populations.
1
a. Cancer antigen-125 (CA-125) and other tumour
markers Consolidation Chemotherapy in Advanced Ovarian
I
t b. Transvaginal ultrasonography (TVS) for ovarian Cancer

volume and morphology: This is only useful in ln spite of the high (60-70%) response rate of
.
postmenopausal women. The method is not suitable ovarian cancer to platinum-taxane chemotherapy,
for pre-menopausal women because their ovaries the majority of patients ultimately progress and die of
undergo cyclical changes in ovarian volume. Even in complications of the disease. This outcome applies
postmenopausal women, there is considerable to even those who have achieved a clinically
overlap between the appearances of benign and complete response. Clinically complete response is
malignant masses, leading to high false positive rates defined as absence of symptoms, normal physical
for cancer detection findings, normal computed tomographic scans of
abdomen and pelvis, and normal serum cancer
c. Colour-Flow Doppler ultrasonography to detect antigen 125 levels. Seventy percent or more of these
low-i mpedance flow neovascu larization women ultimately experience a recurrence.
I d. CA-125 plus TVS The methods are only useful in
selected populations with increased incidence of the After complete response has been attained, would
625
continuation of chemotherapy for a period of time can deliver similar concentrations to the tumour
prevent, or at least significanfly delay, , ultimate through the tumour's capillary circulation would
tumour progression? ln other words, would produce intolerable side effects.
consolidation (maintenance) chemotheffiffiove
progression-free survival or overall survivat?'tn an Randomised controlled trials have attempted to
effort to answer this question, a trial was u
Edken determine the role of intraperitoneal chemotherapy
in which patients who had achieved a comptete in the initial chemotherapeutic management of
response to platinum-paclitaxel chemotherapy were small-volume residual advanced ovarian cancer; i.e.
randomised to maintenance single-agent paclitaxel in cases in which initial cytoreduction (debulking)
weekly for either 3 months or 12 months'oo. At the did not leave any tumour which was 1cm or more in
start of the study, the dose was 175mg/m'infused its maximum diameter. The patients were
over 3hrs, but early in the study, because of randomised to receive either intravenous paclitaxel-
neuropathy toxicity, the dose was reduced to cisplatin chemotherapy (control arm) or to receive
13Smg/m'. lnterim analysis demonstrated a median intravenous paclitaxelcisplatin chemotherapy plus
progression-free survival of 2l months in the 3- intraperitoneal paclitaxel or cisplatin (experimental
month arm and 28 months in the 12-month arm of arm). The intraperitoneal drug was administered
the study. through an indwelling intraperitoneal catheter. Toxic
effects, mainly myelogenous (neutropenia,
The hazard ratio was 2.31 (99% Cl 1.08-4.94). The thrombocytopenia), neurologocical, renal, and
difference was significant. Unfortunately, because of gastrointestinal were significantly more common in
this demonstrated difference, the study was the experimental (intraperitoneal) arm. ln addition,
terminated prematurely. At the time of termination, intraperitoneal catheter placement and drug
there was no difference in overall survival between administration was associated with potential
the two arms. Afterthe termination, patients in the 3- morbidity from chemical and bacterial peritonitis.
month arm were allowed to cross over to the 12- Overall, addition of intraperitoneal administration to
month arm. As a result, we will never have survival standard intravenous platinum-taxane therapy
data to determine overall survival rates. euality of life resulted in a 20% to 25% relative reduction in both
assessment was not considered in the study. This the risk of initial disease progression and ultimate
omission is particularly relevant because it is well death from ovarian cancer'ou.
known that in the absence of symptoms patients
perceive the side effects of therapy as detrimental to Following completion of 2 randomized phase lll
the quality of life. Furthermore, there is no evidence intergroup trials comparing lV to lV + lP therapy that
that the advantage in recurrence-free survival is showed positive results, the Gynecologic Oncology
sustained for any appreciable time after completion Group, GOG opened protocol 172 ,whichcompared
of treatment. lV paclitaxel (135 mglm Z ) over 24 h with tV
cisplatin (75 mglm 2 ) on day 2, versus lV paclitaxel
Conclusion: The place of maintenance (135 mg/m 2 ) over 24 h, followed by lP cisplatin
in the management of advanced
chemotherapy (100 mg/m 2) on day 2 and lP paclitaxet (60 mg/m
ovarian cancer remains uncertain. 2) on day 8 106-108. All patients had optimally resected
disease with residual tumor limited to less than or
I ntn pe ritonea I Chemothera py equal to 1 cm in size. The median survival for the lV
To maximise the local cytotoxic effects of only and lV + lP arms were 49.5 and 66.9 months,
chemotherapy while minimising systemic toxicity,
respectively. The RR of death was 0.71 in the lp
cytotoxic drugs have been administered direcfly into
group ( P :0.0076) and tolerability for lP chemo
the peritoneal cavity. This allows very high was a concern as grade 3 and 4 hematologic,
concentrations of the drug to be delivered locally to
metabolic, and gastrointestinal toxicities were
the tumour, and since advanced ovarian cancer is
significantly more common in the lP arm. Only 42"/o
basically a peritoneal disease, such drug delivery
of patients allocated to the lP arm completed 6
would be expected to improve progression-free cycles of chemotherapy. The results of the above
survival and overall survival. lntravenous doses that
study, in combination with previous positive studies
626
rf
l
tI
r exploring lP chemotherapy, resulted in a National ovarian cancer, investigators added an anthracycline
I Cancer lnstitute (NCl) clinical ar+noflncement (doxorubicin or epirubicin) to the standard taxane-
r
B
recommending that women with .qtimally platinum doublet in the first-line treatment of the
Ita n'- cytoreduced Stage lll ovarian caneerr-*@ed disease. By simultaneously exposing the cancer cells
F for lV + lP therapy. to 3 different drugs instead of 2, triple therapy should
I theoretically reduce the chances of emergence of
I
NeoadiuvantChemotherapy .,i,... drug-resistant clones. The 3 drugs may also be
I ln an attempt to make unresectable advaEcedeancer synergistic. ln studies that tested a triplet consisting
operable, patients have been given up front of paclitaxel, carboplatin, and epirubicin against a
{
J
t chemotherapy. Three or four cycles of chemotherapy doublet of paclitaxel and carboplatin, preliminary
i
are used. Surgery can then be performed in those analysis showed marginally significantly increased
I
a
who respond, followed by two orthree more cycles of complete responses with the triple therapy. However,
I chemotherapy. The question is: ls it possible that toxicity was markedly increased with triple therapy:
cases that respond to neoadjuvant therapy and cases myelotoxicity (febrile neutropenia), haematologic
I that do not respond are inherently different, and that toxicity, and gastrointestinal toxicity especially and
f without the neonadjuvant therapy those that undergo emesis were more frequent and more severe. Overall
I satisfactory surgery would have had the same survival was not significantly different in the 2
I
surgical result without the neoadjuvant therapy? arms"''"'. Because of the greater toxicity associated
rI
There may be a role for neoadjuvant chemotherapy in with it, triple therapy may require reductions in the
I
selected patients with stage lllC or stage lV ovarian doses of the 2 more active drugs, or may result in
cancer with large-volume disease with extensive
I
t
i treatment delays and interruptions, thus
? ascites and large pleural effusions as well as in compromising a favourable outcome. Myelotoxicity
I
I
patients who have a poor performance status and are and haematotoxiciy may produce increased demand
therefore at high operative risk because of medical in supportive care.
co-morbidities 'on.
! Currently there are no data that addition of any third
I lnterval Debulking ln Advanced Ovarian Disease cytotoxic agent to front-line chemotherapy of ovarian
It was suggested that women with advanced ovarian cancer improves outcomes, despite an immense
i cancer whose initial surgery did not produce optimal
: amount of investigation of this strategy. Multiple
cytoreduction, i.e. who at the completion of initial randomized phase lll trials testing the addition of
',
surgery had persistent large-volume (> 1cm) residual doxorubicin, epirubicin, gemcitabine, and topotecan
{
f, disease, could undergo 3 courses of chemotherapy to to a platinum/taxane backbone either sequentially or
'melt' the persistent tumour, and another attempt at all at the same time have all been negative. ln
i surgical tumour removal (interval cytoreductive addition, an international multiarm randomized
surgery) undertaken, followed by further study was led by the GOG (GOG #182-|CON5) to
:
chemotherapy. This strategy was reported to produce definitively answer whether triplet cytotoxic
; an improvement in survival"o. A randomised study chemotherapy improves survival "t.
was undertaken to confirm or refute this claim. The
subjects were patients whose initial subopitmal Second look l-apa rotomy
cytoreductive surgery was performed by a Now that we have tumour markers, e.g. CA-125 and
gynaecologic oncologist. The subjects were given high quality imaging techniques such as MRI and CT
chemotherapy for 3
months. They were then scan, is second-look laparotomy still necessary? The
randomised to continue with 3 additional courses or consensus is that there is now no place for second-
to undergo another attempt at tumour resection, look laparotomy.
which was followed by 3 more courses of the same
( chemotherapy. The study did not find any significant Major Surgical Palliative Procedures
difference between the two groups in median Do major surgical palliative procedures, e.g.
duration of survival". resection and anastomosis for intestinal obstruction,
+
Ad d i n g a Th i rd D ru g to th e P I atin u m -Taxane Do u b I et improve the quality of life or prolong life? ln a
ln an attempt to improve the efficacy of therapy of selected population, the answer is "yes".
627
---!
Surgery for Re/apse Drsease favourable response to the same therapyt'u. Patients
ls surgery for relapse disease worthwhile, i.e. does whose disease progresses whilst on first-line
surgery for new disease appearing more .than 6 platinum-taxane therapy are described as having
months after primary surgery prolong life or irtrpve platinum-refractory disease,' those who relapse
the quality of life? ln a selected populati6n;. ttre within 6 months of completion of therapy are said to
answer is "yes". have platinum-resistant disease; those who have a
relapse-free interval for 6 months or longer before the
Second-LineTherapy relapse are said to have potentially platinum-
Although first-line therapy in advanced ovarian
sensitive disease.
cancer produces high response rates of over 7OY", up
to 80% of patients will have recurrence"o. Therefore, For the last group, the first-line treatment can be
in the management of ovarian cancer, second-line repeated with a high chance of another favourable
therapy is usually needed. ln the choice of the drug response.
regimen, first, it should be remembered that the goal
of second-line therapy for recurrence is palliation; For those with platinum-refractory or platinum-
cure is not possible. Therefore, the selected drug resistant disease, single-agent pegylated liposomal
regimen should not compromise the patient's quality doxorubicin is the agent of choice. The dosage is
of life. Second, the drug regimen will depend upon 50mg/m'by intravenous infusion over thr every 4
the time interval between completion of the weeks.
platinum-taxane first-line therapy and the relapse.
The longer the interval is, the higher the chance of a
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634
cHAprE"49
Germ Cell T'uffiffiils

AA Odukogbe and T A O Oluwasota
INTRODUCTION relatively low frequency of advanced-stage disease

but high chemo-sensitivity to contemporary
Primary tumours of the ovary can be broadly platinum-based chemotherapy with concomitant
characterized into three main groups: Epithelial excellent cure rates, and small incidence of severe
tumours - derived from the surface epithelium and o.
late effects Malignant ovarian germ cell tumours
constituting two-thirds of all ovarian tumours and (MOGCTs) have good prognosis with conservative
approximately 85% of malignant ovarian neoplasms; surgery and platinum-based chemotherapy.
ovarian germ cell tumours - derived from the germ Prognostic factors for M0GCTS include the
cells and sex cord - stromal tumours which are lnternational Federation of Gynecology and
derived from ovarian stromal and sex cord elements'. Obstetrics (FIGO) stage, presence of residual disease
Ovarian germ celltumours (OGCTs) are derived from postoperatively, histologic type, and level of serum
the primitive germ cells of the embryonic gonad'''. tumour markers.
They have a common histogenesis and exhibit the
distinctive characteristic of frequently having Presenting symptoms and signs include abdominal
histologically different neoplastic e{ements within the pain and apalpable pelvic-abdominal mass in
same tumour mass, Histological{y, similar neoplasia approximately 85% of patients. Approximately 10%
often occurs in extragonadal locations along the line of patients will present with acute abdominal pain
of migration of the primitive germ cells from the wall mimicking appendicitis, usually caused by rupture,
of the yol k sac to the gonadal ridge'. haemorrhage, or torsion of the ovarian tumour. Less
common signs and symptoms include abdominal
OGCTs are rare tumours which occur predominantly distension, fever, and vaginal bleeding in 35%, lO%
during adolescent or early adult life '. Even though and 10% respectively while a small proportion of
infrequent, their importance lies in their malignant patients exhibit isosexual precocity related to human
potential and threat to the loss of reproductive chorionic gonadotropin (hCG) productiono.
potential and life. Furthermore their production of Compared with unilateral tumors, bilateral OGCTs
tumour markers, most notably alpha fetoprotein are more often associated with advanced-stage
(AFP), lactate dehydrogenase (LDl-l) and beta human disease, high-risk histology, and poor survivalu.
chorionic gonadotrophin (B-hCG), and association of Recently, there have been advances in the
their malignant varieties (especially dysgerminoma) management of ovarian germ-cell tumours. Precise
with intersex states are also of interesf . ln addition, surgical staging, improved imaging procedures,
they have a clear convergence of multiple tumour and more sophisticated laboratory techniques and
host specific characteristics that lead to optimal effective chemotherapy regimens are available
t outcomes in most patients. These characteristics although the standard chemotherapy regimen for
include: unilaterality in location which allows the selected patients vary across the tumour types.
potential for fertility-sparing su{gery, having a
635
- ,-_-\
The histology of GCTs is similar in both males and F. Mixed germ cell tumor, specify
females, whether occurring in the testis, ovary or components
extragonadal sites, implying origin from a c.omrflon I l. Biphasic or triphasic teratoma
precursor cell. However, there are gome A. lmmature teratoma

epidemiologic differences in the incidence of dffiesEmt B. Matureteratoma
types of GCT.U ln humans, GCTs occur in infurts, 1. Solid
children and young adults and are believed to 2. Cystic, dermoid cyst
3. Fetiform teratoma, homunculus
originate from Primordial Germ Cells (PGCs) and
owing to the pluripotent nature of these cells, GCTs
lll.Monodermal teratoma and somatic-type
tumours associated with biphasic or triphasic
can take on a variety of different histologic fates.
teratoma
GCTs in which the PGCs retain pluripotency and do
A. Thyroid tumourgroup (such as stroma
not differentiate are the dysgerminomas while GCTs ovarii)
in which the cells take on a variety of differentiation B. Carcinoid group
states are designated non-dysgerminomas, of which C. Neuroectodermal tumour group
embryonal carcinoma is thought to represent the D. Carcinoma group
stem cell component. GCTs which differentiate into E. Melanocyticgroup
somatic cell lineages (endoderm, mesoderm, and F. Sarcoma group
ectoderm) are known as teratomas while other GCTs G. Sebaceous tumour group
may take on extraembryonic differentiation H. Pituitary-type tumour group
l. Retinal anlage tumourgroup
resembling the fetal yolk sac (yolk sac tumours) or
J. Others
the placenta (choriocarcinoma)u.
CLASSIFICATION
Clinical and Pathologic Features of Malignant
Ovarian Germ Cell Tumours.
The most clinically practical approach would be to
subdivide MOGCTs into the dysgerminomatous
Germ cell tumours constitute the second largest
tumour, which is the most common type and the
group of ovarian neoplasms after the tumours of
counterpart of the male seminoma, and the non-
ovarian surface epitheliumo'u-'0. They are
dysgerminomatous tumours'. The most common
encountered at all age groups and even during fetal
types of non-dysgerminomatous tumours are yolk-
Iife, but occurrence in children and adolescents
sac tumour, immature teratoma, and mixed germ-
account for over 60% of ovarian tumours in these
cell tumours. The embryonal carcinomas, non- groups. One third of ovarian germ cell tumours in
gestational choriocarcinomas, and polyembryomas
children and adolescents are malignant while in
are much less common varieties. However, for
adults, the great majority of germ cel I tu mours (95%)
simplicity, a number of classifications of germ cell
are benign and consist of mature cystic teratomas
tumours of the ovary have been proposed over the (dermoid cysts).
years, each one becoming more detailed than
previous ones and encompassing newly established The malignant tumours arising from constituents of
entities. The current classification of malignant dermoid cysts, most commonly squamous-cell
ovarian germ cell tumours is presented in Table 1. carci nomas, accou nt for 2 % to 3% of ova ria n ca ncers
and have an age-incidence curve similar to that of
Table 1. Classification of Malignant Ovarian Germ
carcinomas derived from the surface epithelium. The
CellTumoursn''
primitive germ cell tumours, which also account for
L Primitive germ celltumours
2"/"to3"/" of ovarian cancers, almost always occur in
A. Dysgerminoma
young women, reaching their peak age incidence in
B. Yolksactumour
1. Polyvesicular vitelline tumour the early thirties'z. Development of MOGCT may
2. Glandularvariant involve the combined effect of genetic alterations or
3. Hepdtoid variant predisposition and disadvantageous environmental
C. Embryonalcarcinoma factors such as exposure to maternal hormones,
D. Polyembryoma external endocrine disruptors, or adverse lifestyle-
. E. Non-gestationalchoriocarcinoma related factors that disturb the cells' normal
636
r
1
I
Germ Cell Tumours

t
I
rl biochemistry although the hazardous involvement of germ cel I tumours respectively'u.

,
tt' environmental compounds in the pathogenesis of
r OGCT remains a hypothesis'. DYSGERMINOMAS
l*
r lnitial evaluation of patient with 4 g@eted
a Dysgerminoma, a term coined by Robert Meyer in
t MOGCL based on history and physiealeffi,lt*lation, 1930n, is the most common malignant germ cell
r tumour accounting for 3"/" of all ovarian cancers and
L should include routine blood studiesr sertlm tumor
t
markers, chest X-ray, and imaging studies-pelvic 45% of a I I ma ligna nt germ cell tu mou rs. The average
)
sonography and computed tomography (CD of the age at diagnosis is 20 years wilh 20% of cases
|. abdomen and pelvis. lf dysgenetic gonads are occurring in prepubertal girls and less than 5% in
I
suspected based on physical findings and a history of women aged over forty years. Most often, patients
primary amenorrhea, then karyotyping is indicated. present with an abdomino-pelvic mass, abdominal
Due to the low incidence of MOGCTs, few survivors enlargement andlor abdominal pain. ln more than
( have been followed long-term, but some studies of two-thirds of patients, the tumour is confined to one .
.
follow up of survivors have reported restoration of ovary at presentation (stage lA) although about 10-
regular menstrual cycles and the ability to conceive in 15% have either bilateral tumours or microscopic
80% or more of those who had fertility-sparing involvement of the apparently normal contralateral
surgery'. ovary'.
The surgical strategy, either via laparotomy or Grossly, dysgerminoma appears as a solid pink to
preferably laparoscopically (including robotic cream coloured lobulated mass with an average
r
1
d ia meter of 1 5cm at d iagnosis. Areas of

surgery)," could be primary (staging, fertility-
I
i sparing, restaging and cytoreductive) or secondary haemorrhage or necrosis are uncommon and the
surgery (second-look, secondary cytoreductive)
a. tumour tends to retain the configuration of a normal
i
l
Minimally invasive surgery in gynecologic ovary. Microscopically the tumour cells resemble the
malignancies has become more common based on primordial germ cells of the embryo. Lymphocytic
well-proven benefits such as lower morbidity, faster infiltrates, non-caseating granulomata and
recovery, and earlier administration of adjuvant syncytiotrophoblastic cells may also be present.
: therapy than traditional open procedures. ln addition, Serum lactate dehydrogenase (LDH) isoenzymes 1,
several studies have shown that laparoscopic surgery 2 and 3 are commonly elevated and are useful for
( monitori ng. Human Chorionic Gonadotrophin (HCG)
I in early-stage gynecologic malignancies is
I
comparable with tr'aditional open procedures in production, estrogenic changes such as precocious
oncologic outcome. For these reasons, the proportion puberty and less commonly, androgenic
I
of early-stage gynecologic malignancies managed manifestations are occasionally seen with
with minimally invasive surgery has increased from dysgerminomas. Early lymphatic spread and
7"/oto9O"/". radiation sensitivity are additional common features.
Bilateral MOGCTs are rare, accounting for only 4.3% Behaviour, Prognosis and Treatment:
of all germ cell ovarian tumours according to data Occasionally, dysgerminomas are present bilaterally
I from the Surveillance, Epidemiology and End Results and when it appears unilateral, visible spread and
(SEER) program'o'"-'u. With respect to individual occult metastases to the contralateral ovary have
histologic types, the S-year survival for bilateral been distinctively reported. Staging is performed
dysgerminomas, immature teratoma, and mixed is dependent on the
surgically and prognosis
germ cell tumors with pure non-dysgerminoma cell histologic diagnosis and surgical stage at
presentation. Unilateral adnexectomy, peritoneal
tumour was 96o/",94o/", and 87"/o, respectively while
bilaterality was not found to be an independent cytology and biopsy of the contralateral ovary will
prognostic predictor of survival'0. Spalt-Like suffice for early stage disease with the 5-year
; survival of patients ranging trom 96Y" for stage lA to
Transcription Factor 4 (SALL4) and Karyopherin 2
+
(KPNA2) are two important biomarkers among as low as 60% for tumours with extra-ovarian
several for diagnostic and prognostic evaluation of extension.
637
Elevated LDH levels, primary tumour greater than membrane materials, which often provide the
1Ocm in diameter, presence of areas of necrosis, and diagnostic clue in tumours exhibiting complex
incompletely staged patients are indicatioas for histologic profiles n. Pure patterns, such as the
dissection of ipsilateral pelvic and aortic nodes. The polyvesicular type, hepatic, and intestinal variants
presence of metastases in these areas is an indication are extremely rare and often mimic other neoplasms
for adjuvant postoperative chemotherapy with such as hepatoid and endometrioid carcinoma.
Cisplatin and Etoposide plus or minus Bleomycin (EP Rarely, the mature intestinal component of yolk sac
or BEP). Dysgerminomas are highly radiosensitive tumour may give rise to a mucinous carcinoid. Yolk
with excellent outcomes but cause subsequent sac tumours can originate from malignant stem cells
i nferti I ity seconda ry to post-rad iation ovarian fa i I ure. present in somatic tumours of the ovary and uterus,
With the introduction of platinum-based regimens, usually endometrioid adenocarcinoma and
chemotherapy essentially replaced radiotherapy as carcinosarcinomao''-'. The histology of these unusual
standard treatment for patients with metastatic YSTs is identical to that of tumours of germ cell origin
dysgerminoma especially in young patients with and their characteristic immunophenotype helps to
lesions larger than stage 1A and who desire to differentiate them from the somatic tumours from
preserve fertility. However, current trend is towards which they arise.
active surveillance of patients before
chemothera py4'7's'13't7-1s . Post-operative management Behaviour, Prognosis and Treatment:
should also include studies to exclude an inter-sex YSTs are highly malignant and mostly affect patients
state if the history and examination findings are younger than age 40 years', They often present with
suggestive. sudden onset of clinical symptoms such as
abdominal pain and associated large abdominal
YOLK SAC (ENDODERMAL SINUS) TUMOURS mass (as seen in over 757" of patients), There is a
preponderance of apparent stage lA disease even
Yolk sac or endodermal sinus tumours (YSTs or ESTs) though some have occult contralateral ovarian
account for approxim alely 20% of primitive ovarian metastases.
germ-cell tumours with less than 57" of them
occurring bilaterally. Grossly, they are solid masses Treatment consists of surgery followed by adjuvant
that are more yellow and friable than is seen wiih chemotherapy - Cisplatin, Vinblastine and
dysgerminoma and in addition have areas of Bleomycin (PVB), or Bleomycin, Etoposide and
necrosis, haemorrhage, cystic degeneration and Cisplatin (BEP)'''^, Although BEP is preferred due to
rupture. its low toxicity, there are no randomized controlled
The most common microscopic pattern of this trials to evaluate thisto''0. The overall survival of
tumour (Reticular) reflects extraembryonic women treated with platinum-based chemotherapy
differentiation. Other microscopic patterns include currently ranges from 87% to 98"/"'. Reasonable
the endodermal sinus pattern with papillae lined survival rates and even occasional successful
tumour cells (Schiller-Duval bodies), the pregnancy have been reported after unilateral
polyvesicular vitelline pattern, glandular yolk sac salpingo-oophorectomy and adjuvant combination
tumour and hepatoid yolk sac tumours describing chemotherapy in young patients with stage lA
respectively primitive yolk sac, gut and liver disease but the prognosis is worse with advanced
neoplastic changes. Classic histologic features in disease'0.
these tumours almost always include reticular
microcystic areas with hyaline globules and DERMOID CYSTS
amorphous acel lu lar basement membrane material'.
Other features of yolk sac tumours include positive The dermoid cyst, which accounts for one-quarter to
staining for alpha-fetoprotein (AFP) and presence of one-third of all ovarian tumours is often benign and
Periodic Acid-Schiff (PAS) positive hyaline bodies. commonly seen in women of reproductive age but is
Classic histologic features in these tumours almost also seen in children and occasionally in elderly
always include reticular microcystic areas with women''o'''n. Dermoid cysts (mature cystic
hyaline globules and amorphous acellular basement teratomas) are teratomatous cysts lined
538
Germ Cell Tumours
predominantly by epidermis with skin appendages. predisposed to somatic (embryonic) differentiation

They are bilateral in about lO% of casm with most and recapitulate tissues from all three primitive germ
tumours measuring less than 15cm in"@Fr' The cell layers: ectoderm, endoderm, and mesoderm and
tumour is usually unilocular with ths-'ffi-.:ftsrlen contain a variable amount of immature, embryonal-
co nta i n in g se ba ceo us m ate ri a l and tra*i;.tf'W#irds type (generally immature neuroectodermal) tissue".
of cases, mature elements reflectirg' These tumours are typically unilateral, large,
into tissues normally derived from allthrassir$ryonic variegated (6-35 cm; average, 18.5cm),
germ layers (ectoderm, mesoderm and endoderm) predominantly solid, fleshy, grey-tan in appearance
are present. These include brain tissue, glia, bone, or occasionally cystic with haemorrhage and
thyroid tissue and hair. Any of these constituents has necrosis, less than 5% being bilateral. They account
the potential for undergoing benign or malignant for about a quarter of all MOGCTs in patients younger
tra nsformation to form a seconda ry tumour especial ly than age 15 years although a benign neoplasm,
squamous cel I ca rci noma, Endocri ne-type secondary usually a dermoid cyst, occupies the contralateral
tumours include struma ovarii and carcinoid tumours ovary in 10% of cases. lmmature teratomas are
causing hyperthyroidism and carcinoid syndrome typically predominantly solid with the cut surface
respectively. Although curable, the most common displaying soft solid areas corresponding to nervous
complications include torsion (especially during system components; cartilage, bone and cysts filled
pregnancy and the puerperium), rupture, infection, with serous or mucinous fluid. Sebaceous material
and development of malignancy. ln the absence of and hair are also evident. lmmature teratoma is
complications that may give rise to symptoms such composed of variable amounts of immature
as abdominal pain, abdominal mass or swelling, embryonal-type tissues, mostly in the form of
mature cystic teratoma are often asymptomatic and neuroectodermal rosettes and tubules, admixed with
are usually discovered as an incidental finding on mature tissue. Microscopically, a disorderly mixture
physical examination (as an adnexal mass), by of tissues derived from all three germ layers is seen
imaging Iplain abdominopelvic X-ray, with some of the components having an immature
abdominopelvic ultrasound, computerized axial embryonic appearance. Neuroectodermal tubules
tomographic (CAT) scan, magnetic resonance and sheets of glia producing malignant cells
imaging, MRI and positron emission tomography constitute most of the immature elements and about
(PET) scanl, or at laparotomy for other indications. one-third of immature teratomas produce AFP".
Preoperative diagnosis of these tumours is possible
by imaging techniques because of the presence of Grading: Based on the quantity of the immature
teeth and bone. Torsion, the most frequent neuroepithelial component, primary and metastatic
complication, presents with severe acute abdominal ovarian immature teratomas (including peritoneal
I
L pain and is treated by emergency laparotomy and implants and lymph nodes metastases) are
excision of the affected ovarY. separately graded from 1 to 3. More recently the
I
i possibility of uslng a two-tiered (low grade and high
: Laparotomy or therapeutic laparoscopic surgeries are grade) grading system was suggested. The grade can
!
i performed for tumour excision and peritoneal be correlated with prognosis and occasionally the
tumour is complicated by peritoneal glial implants
i
a toileting as the treatment of choice with favourable
; prognosis. Though uncommon, infection of the cyst which neither increase the stage nor worsen the
i by coliform organisms has been reported'. ln young prognosis".
I patients with small tumours, conservation of healthy
ipsilateral ovarian tissue and surveillance is the Behaviour, Prognosis and Treatment:
lmmaturity in a teratoma reflects the degree to which
recommended approach of treatment as local
a
the neoplastic tissue resembles embryonic tissue

recurrences on the contralateral ovaries are
and the potential for malignancy and recurrence is a
uncommonu's'13'11'21 .
direct reflection of the amount of immature tissue
I
IMMATURETERATOMAS: present. About three quarterg of immature teratomas
t
t present in stage 1A, usually as abdominal/pelvic
lmmature teratomas are derived from cells mass and/or abdominal pain of short duration in
I
639
onset2. Early spread occurs by direct extension and by in prepubertal girls, secondary amenorrhoea or
peritoneal implantation while lymphatic invasion and abnormalvaginal bleeding in women of reproductive
extra-abdominal metastases are rare. The,st4e and age, elevated serum human chorionic gonadotrophin
grade of the primary tumour and the
ffir&:dits (hCG) levels with positive pregnancytests results and
metastases are important predictive fa
_#V.ier to alpha fetoprotein (AFP) production are other
the chemotherapy era, the overall survilmil,:t#s of common presenting features. These tumour markers
patients with grade l, 2 and 3 neoplasms !Lere EZ%, may aid in diagnosis and monitoring of treatment.
63% and 30%, respectively". A recent report from
the Pediatric Oncology Group concludes that surgery The tumour is often large with mean diameter of
alone is curative in children and adolescents with 15cm, soft with greyish yellow cut surface which is
immature teratoma of any grade, reserving variegated with extensive haemorrhage and necrosis.
chemotherapy for cases with relapse. Microscopically solid sheets of large primitive
Surgery followed by triple agent adjuvant pleomorphic cells with occasional
chemotherapy has recently improved prognosis for syncytiotrophoblast giant cells are seen.
patients with immature teratomas even those with
advanced stage high grade disease. patients with Embryonal carcinoma may coexist with other
stage lA, grade 1 disease are treated by unilater,al neoplastic germ cell elements and differentiation
sa I pi ngo-oophorectomy on ly fol lowed by su rvei I Ia nce from dysgerminoma with which it may occasionally
and reservation of chemotherapy for recurrences. be confused is very important because of a totally
Patients with higher-grade stage I neoplasms and all different prognosis and response to treatment.
those whose capsules have ruptured require maximal Histologic features of malignancy like cellular and
surgical resection for therapy and for accurate nuclear pleomorphism are more frequent with
grading. lf the metastases are all grade 0 and the embryonal carcinoma. Single nucleoli, stromal
primary tumour is no worse than grade 1, no further lymphocytic infiltrate and granulomatous reactions
treatment is necessary. Patients with higher grade are prominent features of dysgerminoma but rare in
metastatic tumours (i.e. grade 1,2, or 3) and those embryonal carcinoma. Cells of embryonal carcinoma
whose primary tumours are grade 2 or 3 require stain positive for AFP and cytokeratin whereas the
adjuvant chemotherapy. great majority of dysgerminoma cells are invariably
negative, providing a useful method for
EMBRYONALCARCINOMA differentiating between the two neoplasms.
Ovarian embryonal carcinoma, unlike its testicular Behaviour, Treatment and Prognosis
counterpart, is a rare tumour composed of epithelial Ovarian embryonal carcinoma is a highly malignant
cells resembling those of the embryonic disc and neoplasm with local aggressiveness, extensive
growing in one or more of several patterns: glandular; peritoneal spread and early metastases, initially by
tubular, papillary and solid while polyembryoma is a lymphatics and later by the haematogenous route.
rare tumour composed predominanfly of embryoid The primary treatment of embryonal carcinoma is
bodies resembling early embryos". They represent surgery (excision of all visible tumour), and
only 4% of all malignant ovarian germ cell tumorsrr, postoperative adjuvant chemotherapy. Since occult
with mean age at presentation of 15 years. The age metastasis to the contralateral ovary rarely occurs
incidence, clinical presentation, and findings are with stage lA tumours they can be treated with
similar to those observed in patients with other unilateral salpingooophorectomy as a fertility sparing
malignant germ cell tumours, the disease occurring measure. Although the tumour is radio-insensitive,
more commonly in children and young adults. Asian S-year survival rates are improved by postoperative
and Black ethnic groups are affected by malignant adjuvant chemotherapy.
germ cell tumours three times as frequenfly as
Caucasian women. CHORIOCARCINOMA
Most affected patients present with recent-onset
abdominal or pelvic mass with about half of them Pure non-gestational ovarian chcjriocarcinoma is an
having abdominal pain. lsosexual precocious puberty exceptionally rare germ cell tumour composed of
640
:--!
Germ Cell Tumours
I
cytotrophob ast, syncytiotro phoblast a nd extravi I lous
I teratoma; haemorrhagic and necrotic areas reflect
I
I trophoblast''" with most of them occurring admixed endodermal sinus tumour or choriocarcinoma. All
I with one or other germ cell component ard are best components of a mixed germ cell tumour and their
I
placed in the mixed germ cell category 'lh pure approximate proportions should be mentioned in the
i
I
forms are usually gestational an$.+ih.@nreal diagnosis.
r
I diagnosis of pure choriocarcinoma of geim*dl'origin
I
can be made only in a prepubertalehitd'. The age Behaviour, Treatment and Prognosis
i
Two thirds of patients present with stage lA disease.
r
I
range of ovarian germ cell choriocarcinoma is from
Poor prognostic features include advanced disease,
infancy to the mid-thirties with a mean of 12 years.
I
i
Abdominal enlargement and pain occur in half of of tumour, histologic composition
increased size
r (more than one third yolk sac tumour,
I patients and one half of the pre-menarcheal gids have
signs ofprecocious puberty due to hCG being choriocarcinoma or grade 3 immature teratoma).
r
I produced by the tumour. Grossly, choriocarcinoma is Patients with tumours composed exclusively of
combinations of dysgerminomas, embryonal
r soft and characteristically haemorrhagic with
carcinoma, grade 1 or 2 teratoma and less than one
I
additions, at times from other germ cell elements.
I Microscopically, syncytiotrophoblast and third yolk sac tumour, choriocarcinoma or grade 3
r teratoma have a more favourable prognosis. Therapy
cytotrophoblast are seen, both being necessary for
histological diagnosis. Viable tumour is usually consists of surgical excision of the tumour and post-
I
F operative adjuvant multiagent chemotherapy if poor

I scanty because of extensive haemorrhage and
t
I
necrosis. Treatment is by surgical excision and

prognostic factors are present or disease is
r
t
multiagent chemotherapy employing an approach advanced.
I
a similar to that for yolk sac tu mours. Vascular invasion

I Hepatoid Carcinoma
t is frequent and the immunophenotype is This is a primary ovarian neoplasm that
t cha racteristic f or each type of proliferating
histologically resembles hepatocellular carcinoma
trophoblastic cell such as cytokeratins, human
t and is positive for alpha-fetoprotein". lt is an
placental lactogen and p-hCG. Non-gestational
I extremely rare tumour which mainly occurs in
choriocarcinoma has a less favourable prognosis and
i
I postmenopausal women with a mean age of 59.6
requires more aggressive chemotherapeutic years (range, 35-78 years). The symptoms are not
I treatment regimens than its gestational counterpart.
I
specific but related to an ovarian mass with
!
characteristically associated elevation of serum AFP
I MIXED PRIMITIVE GERM CELL TUMOURS
I
I
and CA 725in most cases. Tumours vary from 4-20
Mixed germ cell tumours are composed of at least two cm in maximum dimension with no distinctive
I
different germ cell elements of which, at least, one is macroscopic features. Metastatic hepatocellular
a
r primitive and constitutes about i0% of malignant carcinoma and hepatoid yolk sac tumour must be
I ovarian germ cell tumours. Patients with such excluded as prognosis remains poor.
i
f neoplasms are aged between 5 and 30 years with a

GENERAL NOTES ON THE MANAGEMENT OF
t median age of 15 years. Onethird of the children with
OVARIAN GERM CELL TUMOURS
a these tumours present with signs of precocious
puberty, and 40% of non-pregnant patients of
Malignant germ cell tumours of the ovary occur
I reproductive age have positive pregnancytest results.
( principally in girls and young women with a median
Grossly, mixed germ celltumours are large neoplasms
age of 15 to 20 years. They are also known to be
with a mean diameter of about 15cm. The
associated with pregnancy in a small percentage of
appearance of the cut surface depends on the type
.and amount of the various elements present. cases. This includes presentation during the
postpartum period. Symptoms and signs in affected
Histologically, the most common combination of
patients are rather consistent. The commonest
neoplastic germ cell elements found in ovarian mixed
presentation is abdominal.pain associated with a
germ cell tumours consists of dysgerminoma and yolk
f. palpable abdominal mass in 4 out of 5 patients.
sac tumour. Solid, fleshy, tan areas correspond to
Acute abdominal pain with peritonism of varying
dysgerminoma, mucoid cystic areas represent
I
64L
degrees of severity caused by cyst accidents occurs torsion of its pedicles are other common operative
infrequently among the patients. This finding is findings. Benign cystic teratoma is associated with
somewhat more common with endoder,rml,,,s[srrs 5% to 70% of malignant germ cell tumours,
(yolk sac) tumour or mixed germ cell tumeruB and is occurring in the ipsilateral or contralateral ovary, or
frequently misdiagnosed as acute appendieitb- * bilaterally. Peritoneal surface spread and lymphatic
common presentations include abdominal spread are the two principal methods of metastasis
distension, fever and vaginal bleeding. Rarely of ovarian germ cell tumours. Haematogenous
isosexual precocious puberty, presumably, due b spread is less common but when present, affects the
hCG production by the tumour may be a presenting liver orthe lungs.
feature.
The type of primary operative procedure depends
Biologic tumour marker production is seen with ger.m upon the surgical findings but stage I disease is found
cell tumours. These include hCG (dysgerminoma, in about 60 to 70% of patients intraoperatively.
mixed germ cell tumours, choriocarcinoma, Bilateral ovarian involvement with tumour is
embryonal carcinoma and polyembryoma); AFp uncommon and therefore, unilateral salpingo-
(endodermal sinus tumour, mixed germ cell tumour, oophorectomy with preservation of the contralateral
embryonal carcinoma, and polyembryoma); LDH ovary and the uterus followed by surveillance
(dysgerminoma); CA 125 (mixed germ celltumours, remains the main stay of treatment. Biopsy of the
dysgerminoma, immature teratoma) and neuron- contralateral ovary is not indicated as adhesions and
specific enolase (dysgerminoma). Their usefulness in ovarian failure can occasionally complicate ovarian
diagnosis and follow up of patients is limited by their biopsy. Surgical staging should be meticulously
i nconsistent sensitivity a nd specif icity.
approached and cytoreductive surgery for metastatic
disease encountered at initial surgery should be
All prepubertal girls and women in the childbearing undertaken applying the same principles used in
age with abdominal symptoms, andlor an adnexal
managing advanced epithelial ovarian cancer with
mass should be evaluated clinically to exclude an
resection of as much tumouras istechnicallyfeasible
ovarian tumour. Dermoid cysts, most of which occur
and safe. Adjuvant chemotherapy consists of
in women of child bearing age can be diagnosed by
cisplatin-based regimens of either BEp (cisplatin,
radiologic evidence of calcification (teeth andlor
etoposide and bleomycin) or PVB (cisplatin,
bone). Only histology excludes a diagnosis of etoposide, and bleomycin). Virtually all patients with
malignancy, hence the need for laparotomy. This also
early-stage, completely resected disease will survive
allows forstaging of the turnour if malignant.
after careful surgical staging/debulking and cisplatin-
based adjuvant chemotherapy. ln addition, a good
The initial treatment approach for a patient
proportion of patients with disseminated disease will
suspected of having an ovarian germ cell tumour is
also survive their disease. Patients who do not
surgery for both diagnosis and therapy. Laparotomy
respond to BEP may still attain a durable remission
should be carried out using an adequate vertical
midline incision, although laparoscopy including
with cisplatin/vinblastine/ifosfamide (Vlp)
combination as salvage therapy. Newer potential
robotic surgery is increasingly used especially in early
treatments include an ifosfamide combination or
stage disease. A thorough determination of disease
high-dose chemotherapy and autologous marrow
extent by inspection and palpation, followed by
rescue. Second look laparotomy is an outdated
staging biopsies (if necessary) should be undertaken.
practice with no proven advantage.
Malignant germ cell tumours of the ovary tend to be
quite large. Bilateral ovarian involvement by tumours
For dysgerminomas, most patients have stage I
is not common except with dysgerminomas which
disease at diagnosis and can therefore be treated by
can also have contralateral occult metastases. The :
unilateral salpingo-oophorectomy with fertility-
latter finding is exceedingly rare in the non- preservation surgery as indicated. Adjuvant
dysgerminomatous tumours except in the case of
treatment, usually chemotherapy, is given to patients
mixed tumours containing dysgerminoma. Ascites,
with advanced but resected disease who wish to
rupture/and or haemorrhage of the tumour; and
preserve fertility, patients with incompletely resected
642
rI
Germ Cell Tumours
t'
I
I
r
r tumour, and those with recurrences after previous ifosfamide, and cisplatin as salvage regimens. A
{
i radiation treatment. All patients treated with recent randomized trial of conventional dose
f chemotherapy should be followed up with medical chemotherapy with or without high dose
l*
r history, physical examination and appropriate chemotherapy plus stem cell rescue as first line
r tumour markers every 1 - 2 months for 1 year, every thera py for patients with poor prognosis
1 3 months for year 2; ever\ 4 months for years 3 and metastatic germ cell tumors did not demonstrate
{
4; 6-monthly for year 5 and yearly subsequently. any improvement in outcome for patients who
i Patients who did not receive chemotherapy should be received high dose chemotherapy with stem cell
:
followed up more closely. Relapses in patients usually rescueo.
r occur within the first two years after diagnosis. The
role of radiotherapy is yet to be fully established as 6. There are many constraints to managing germ cell
a
most of the tumours are chemo-sensitive. tumours in low and middle income countries'
DISCUSSION AND CONTROVERSIES a. There is poor availability of sophisticated imaging

)
techniques including CT scan, MRI and PET
1. Four reports have documented that at least 80% scan. This, and several cultural and
of patients with MOGCT who were treated with socioeconomic factors lead to late diagnosis and
fertility-sparing surgery and platinum-based poor survival of patients. ln a prospective study
chemotherapy had normal menstrual function, of all ovarian cancers in lbadan, Nigeria, Table2
and there are several documented normal shows the stages at staging laparotomy.
pregnancies. However, a proportion of women
:
may experience premature menopause following Table 2: Stages of disease during staging
chemotherapy. laparotomt'o.
2. A recently completed Gynaecologic Oncology Stage Percentase %

Group prospective questionnaire study of t4
survivors of MOGCT and controls focusing on il 5
physical, sexual, psychosocial, and reproduciive ilt 10
functioning is currently being analyzed. IV 7L
3. ln genera l, second look su rgery is not

i recommended fgr patients with MOGCT'.
i b. The sparsely available laboratory facilities often
lack capacity for assays of tumour markers and
4. A major area of concern with regard to late effects
other immunocytochemical analyses.
of chemotherapy for patients with MOGCT is
Ka ryotypi ng faci ities
I a re a lso severely I i m ited.
secondary malignancy related to etoposide and c. Fertility sparing strategies are little practiced in
acute myelogenous leukaemia appears to be these countries because of the above plus
related to cumulative dose". This is an additional inadequately staffed and equipped tertiary
, reason for pursuing surveillance rather than centres for managing oncology cases.
aggressive chemotherapy immediately post- Nevertheless, artificial reproductive techniques
surgery though the evidence is inconclusiveo'". are becoming increasingly available for oocyte
storage and future use.
5. Most patients with MOGCT are cured, but a small 7. Compared with epithelial ovarian tumours, germ
percentage does develop recurrenceo. Most
cell tumours are less associated with genetic
recurrences occur within 24 months of primary predisposition.
diagnosis. Unfortunately, there is no standard 8. On account of their rarity, screening for germ cell
approach to treatment but strategies extrapolated tumours is not presently cost effective.
from clinical experience with testicular cancer
I patients have been adopted with use of
vinblastine, ifosfamide, and cisplatin; etoposide,
ifosfamide, and cisplatin; or paclitaxel,
543
Comprehensive Gynaecology in the Topics -r
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etal. Molecularcharacterstics of malignant 12. ParkJ-Y Kim D-Y Suh D-S, et al. Outcomesof :
ovarian germ cell tumors and comparison with Surgery Alone and Surveillance Strategy in l
testicular counterparts: lmplications for Young Women With Stage / Malignant Ovarian
pathogenesis. Endocr Rev. 2013;34(3):339- Germ Cell Tumors. lnt J Gynecol Cancer.
376. doi:10.1210/er.2012-1045. 2016;0@):1-6.
2. Okpani AO, Seleye-Fubara D. Ovarian Germ Cell doi:10.1097/1GC.0000000000000702.
and Sex-Cord StromalTumours. ln: Kwawukume 13. Dark BGG, Bower M, Newlands ES, Paradinas E -
E\ Emuveyan EE, eds. Comprehensive Rustin GJS. Surveillance Policy for Stage I
Gynaecology in the Tropics. lst ed. Accra, Ovarian Germ Cell Tumors. J Clin Oncol
Ghana; 2005:472-486. 1997;15(2):620-624.
3. ffaqos N, Taleb A, Bouchbika Z, et al. Ovarian 14. Abdut Razak AR, Li L, Bryant A, Diaz-Padilta l. -
Germ Cell Tumours: Clinicopathological Features Chemotherapy for malignant germ cell ovarian
and Treatment Outcomes. /OSR J Dent Med Sci. cancer in adult patients with early stage, "
2016;15(10):62-65. doi:10.9790/0853- advanced and recurrent drsease. Cochrane

1510036265. database Syst Reu. 2011;(3):CD007584.
4. Gershenson DM. Management of ovarian germ doi:10.1002/14651858.CD007584.pub2.
2007;25(20):2938- 15. Kondagunta G V., Motzer RJ. Chemotherapy
celltumors. J Clin Oncol. for
2943. doi:10.12001JCO.2007.10.8738. Advanced Germ CellTumors. J Clin Oncol
5. Prognostic 2006;24GO:5493-5502
Mahdi H, Kumar S, Seward S, et a/.
germ
impact of laterality in malignant ovarian
doi:10.1200/JCO.2006.08.7882.
Cancer.
cell tumors. lnt J Gynecol 16. He L, Ding H, Wang J-H, et al. Overexpression
2011;21(2):257-262. of karyopherin 2 in human ovarian malignant
doi:10.109711GC.0b013e31820581e5. germ cell tumor correlates with poor prognosis.
6. Sanchez A, Amatruda JF. Zebrafish Germ Cell PLoS One. 2012;7(9):e42992.
2016;9L6:479-494. doi:10.1371/journal.pone.0042992.
Tumors. Adv Exp Med Biol.
doi:10.10071978-3-319-30654-4. 17. Billmire DF, Cullen JW, Rescorla FJ, et al.
7. Low JJH, llancheran,4, Ng JS. Malignant ovarian Surveillance after initial surgery for pediatric
germ-cell tumours. Best Pract Obstet
Res Clin and adolescent girls with stage I ovarian germ
Gynaecol. 2012;26(3):347-355. cell tumors: report from the Children's Oncology - ..
doi:10.1016/j.bpobgyn.2012.01.002. Group. J Clin Oncol. 2014;32(5):465-70.
8. Guillem V, Poveda A. Germ cell tumours of the doi:10.1200/JCO.2013.51.1006.
ovary. 2007;9(4):237-243. Available at: L8. Turkmen O, Karalok A, Basaran D, et al.
http:llwww.scopus.comlscopus/inwardlrecord.url Fertility-Sparing Surgery Should Be the
?eid:2-s2.0- Standard Treatment in Patients with Matignant
34447108864&partnerlD:40&rel:R7.0.0. Ovarian Germ Cell Tumors. J Adolesc Young
9. ffoga/es FF, Dulcey l, Preda O. Germ cell tumors Adult Oncol. 20L7:jayao.2016.0086.
of the ovary: an update. Arch Pathol Lab Med. doi:10.1089/jayao.2016.0086.
2014;1388):351-62. doi:10.58581arpa.2012- 19. Gershenson DM, Morris M, Cangir A, et al.
0547-RA. Treatment of malignant germ cell tumors of the
10. Sigismondi C, Scollo E Ferrandina G, et al. ovary with Bleomycin, Etoposide ans Cisplatin. J
Management of Bilateral Malignant Ovarian Ctin Oncot. 1990;8:715-720. :
Germ Cell Tumors. lnt J Gynecol Cancer. 20. Guillem V, Poveda A. Germ cell tumours of the
2015;25(2):203-207. ovary. Clin Transl Oncol. 2007;9(4):237-243.
doi:10.109711GC.0000000000000358. doi:10.10a7b12094-007-0045-0.
11. Shim S-H, Kim D-\ Lee S-W, et al. 2L. Liao ZW, Rodrigues MC, Poynter JN, Amatruda
Laparoscopic Management of Early-Stage JF, Rodriguez-Galindo C, Frazier AL. Risk of
' Malignant Nonepithelial Ovarian Tumors. lnt J second gonadal cancers in women and children
Gynecol Cancer. 2013;23(2):249-255. with germ cell tumors. Cancer.
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Germ Cell Tumours
20 16; 1 22( 1 3):207 6-2082. Component. J Pediatr Adolesc Gynecol.

doi : 10. 1002lcncr. 300 1 4. 2011;24(1):e1.-e3.
t 22. Tavassoli FA, Devilee P WHO doi 0. 1 0381 nbt. 3 1 2 1. Ch I P- nexus.
:1
classification of tumours of 24. Odukogbe AA, Adebamowo CA, Ola B, Olayemi

Health Organization O, Oladokun A, Adewole lE Omigbodun AO, ''j
,
Pathology and Genetics of Aimakhu CO, Okunlola MA, Fakuluio O and ,!'i
and Female Genital Organs.; Oluyemi FA. Ovarian cancer in lbadan:

Available at: characteristics and management- Journal of
http:llwww.iarc. Obstetrics and Gynecology 2004; 24 (9: 294 - :
.,i
onlinelpat 297. q
23. Moniaga NC, Randall LM. I
Ovarian Germ CellTumor with
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646
CHAPTER
50
Sex Cord-Stromal Tumours
of the Ovary
A.O.U. Okpani and Daye Se/eye Fubara
INTRODUCTION presentation are common. Excessive estrogen

production, whether from increased tumour
The Sex cord - Stromal tumours are tumours derived synthesis or peripheral conversion of androgens,
from the sex cord of the ovary and the specialized influences end-organ responses which are usually
stroma of the developing gonad' Granulosa cells and age dependent and can range from isosexual
sertoli cells are of sex cord cell origin while the precocious puberty through menometrorrhagia to
pluripotential mesenchymal cells are the theca cells, postmenopausal bleeding. ln addition, affected
leydig-cells and fibroblasts from which other patients are at increased risk for endometrial
connmtive-tissue elements and fat cells originate. carcinoma and possibly breast cancer. On the other
Neoplastic transformation of these cellular hand, defeminization followed by frank virilization
constituents either singly or in various combinations suggests a hyperandrogenic state. Whenever female
is collectively termed Sex Cord-Stromal Tumours. The patients present with elevated circulating levels of
term Gonadal StromalTumours is also used forthem. testosterone and or androstenedione, a sex cord-
Sex cord-stromal tumours account for 6"/"1o7% of all stromaltumourof the ovary must be excluded. While
ovarian tumours. About 90% of them are granulosa granulosa cell, thecacell and sertoli cell tumours are
tumours or thecomas. Overall, most sex cord-stromal generally considered estrogenic and Sertoli-Leydig
tumours are of low malignant potential and are cell and Steroid-cell tumours are predominantly
associated with a very favourable long-term androgenic, the functional endocrinologic effects of
prognosis. ln addition, a significant proportion of these tumours are impossible to predict based on
them occur before age 40 Years'. their morphologic features. The clinical presentation
depends not only on what predominant steroid is
All sex-cord-stromal tumours have potential for produced by the tumour but also on the extent of
steroid hormone production; they account for 85% to peripheral conversion of androgen to estrogen'.
90% of functioning ovarian tumours. Each sex cord-
stromal cell may produce multiple steroids GRANULOSATUMOURS
concomitantly especially in the neoplastic state. With
the exception of fibromas, the clinical presentation of Granulosa tumours are relatively uncommon,
patients with Sex Cord-Stromal Tumours is frequently accounting for 7o/o to 3% of all ovarian neoplasms'
governed by the clinical manifestation resulting from Their aetiopathogenesis is relatively ill-defined. They
the endocrinology abnormalities' Although each occur over a wide age range from early infancy to
tumour type is associated with a specific endocrine postmenopausal years. More than half occur in
effect, deviations from the typical clinical women of child bearing age'
647
Clinically they usually present with symptoms of a advanced disease. Long term clinical follow-up is
functional ovarian tumour, abdominal mqss, or both. required.
Less common presentations inclu@:'"+ab4ominal
distension, caused by the tumour ardffilg* " iated SERTOLI TUMOURS:
ascites, and acute abdomen due &'&i,Bffiystic Sertoli tumours are relatively rare accounting for
haemorrhage or rupture of a cystie @asm. about 0.7% of ovarian tumours. Affected patients
Estrogens produced by the tumour can cause range in age from 7 years to 70 years with a mean
isosexual precocious puberty, rrFea$-trual age in the mid-thirties. The common presenting
irregularities, anovulation, endometrial hyperplasia symptom is a pelvic or abdominal mass. More than
:
and endometrial carcinoma. Climacteric and 60% of affected patients produce hormones
postmenopausal women are the most prone to including estrogens, and less commonly androgen
endometrial hyperplasia and endometrial carcinoma. and progestogens. lsosexual precocious puberty,
Such endometrial carcinomas are usually well varying degrees of masculinization and endometrial
differentiated with low metastatic potential. hyperplasia are known functional hormonal effects.
Grossly, granulosa tumours are well circumscribed Grossly, sertoli tumours are unilateral, well
yellow solid masses with a smooth or lobulated circumscribed, solitary, yellow and fleshy.
external surface and areas of haemorrhage and Microscopically, multiple distinct growth patterns
necrosis. Focal cystic areas are often seen and occur (simple tubular, complex tubular, with massive
occasionally the whole tumour is cystic. lipid accumulations) as mixed or single pattern.
Peutz
Microscopically, granulosa cells show small roundish
or polygonal cells with round nuclei. Variable - Jegher's syndrome (PJS) is often a positive
association.
amounts of theca cells may be present, probably a
stromal response since the theca cells are usually not
found in granulosa tumour metastatic deposits.
Behaviour Prognosis and Treatment
Most sertoli tumours are benign but malignant
a\
potential (with a stage 1A predominant presentation) -r{,
Variants include the juvenile granulosa tumours in
is occasionally seen especially with the comple4 .',:'
children and the cystic granulosa tumour presenting
tubular histologic pattern. Stromal infiltration and
with androgenic effects in children and young
anaplasia are other bad prognostic features but 1
woment.
increased mitotic activity without unfavourable
prognosis has been observed in tumours occurring in
Behaviou r, Prognosis.a nd Treatment
Granulosa tumours have a low potential for children and adolescents.
malignant behaviour. The most important prognostic
Basic treatment considerations are the same as for
factor is the stage of the tumour. Almost 90% of
granulosa tumours. Advanced or recurrent disease is
patients present with stage 1A disease. No single
rareo.
histologic feature reliably identifies neoplasms with a
high risk of recurrence: Age greater than 40 years,
SERTOLILEYDIG TUMOURS
large tumour size, bilaterality, rupture of the tumour,
and advanced disease are unfavourable prognostic Sertoli-Leydig tumours are relatively rare, accounting
factors. for less than 0.2% of a I I ova ria n tu mou rs. Most occu r
in young women of reproductive age with a mean of
Hysterectomy and bilateral salpingo-oophorotomy
25 years at presentation. Less than 10% occur in
are the standard treatment. Unilateral salpingo- prepubertalgirls. About 10% occur in women above
oophorectomy is justifiable in young women who
age 45 years.
wish to preserve their fertility if the tumour is
confined to one ovary. Recurrences which can occur Androgen production and virilization complicates
in the pelvis long after initial diagnosis and treatment 50% to 75% of patients mostly women of
can be managed by surgical resection and irradiation. reproductive age. Oligomenorrhoea develops
Chemotherapy has been used in patients with initially, followed by amenorrhoea, deepening of the
648
T
deepening of the voice and hypertrophy of the clitoris Sertoli-cell tumour

usually persist. Leydig- Cell tumours
Sertol i-Leydig cell tumour
Grossly, steroid cell tumours are typicdly solid, well -welldifferentiated
bed a nd occasiona I ly lobulated tumou rs of
ci rcu mscri -of i ntermed iate d ifferentiation
diameter 5 centimetres to 10 centimetres and -Poorly d ifferentiated with
variable colour (especially yellow or brown). Areas of heterologous elements
haemorrhage, necrosis and cystic degeneration are -Retiform
present.
-Mixed. Sex -Cord Tumour with annular tubules
Unclassified Gynandroblastoma Steroid-cell
Microscopically, two cell types are present in various tumours
proportions. The Leydig or hilar cell containing Stromalluteoma
Leydig-cell tumour
lipochrome pigment or Reinke crystals, and the
Hilus-cell tumour
adrenal-cortical-like cell. Both cells contain
Leydig cell tumour nonhilartype
intracytoplasmic lipid. Cytologic atypia is seen in ten
to fifteen percent of tumours. Steroid celltumour not otherwise specified.
Other sex-cord stromal tumours of the ovary worthy
Behaviour Prognosis and Treatment
of mention include tumours in the Thecoma-Fibroma
Steroid-cell tumours are generally benign, but group; Ovarian sex cord tumours with Annular
metastases and recurrence aftertreatment may occur
Tubules; Sex cord stromal tumours, unclassified; and
in up to 75% of cases. Tumours composed Gynandroblastomas.
predominantly of the Leydig cell type are rarely
malignant. Adverse prognostic features include extra Tumours in the ThecomaFibroma Group.
ovarian spread at the time of primary surgery, tumour These include the Thecomas, Fibroma-
size greater than 8 centimetres in diameter, nuclear Fibrosarcomas, and Sclerosing stromal-cell
atypia, and a high level of mitotic activity. Tumours.
U n i lateral sa I pi ngo-oophorectomy usual ly is cu rative Thecomas are composed of lipid laden stromal cells,
and is the treatment of choice for young women with occasionally demonstrating luteinization but
stage 14 neoplasms. Older women, those who have invariably clinically benign. They account for
completed theirfamily and those who have advanced approximately 1o/" of ovarian neoplasms and affect
disease are treated by hysterectomy, bilateral patients in the sixth and seventh decades of life at the
salpingo-oophorectomy and excision of all extra time of diagnosis. They present primarily with
ovarian tumour'. abnormal genital bleeding andlor an abdominal
mass. The presentations, including ascites and
OTH ER SEX CORDSTROMAL TUMOURS
occasionally large tumour size promote early
As scientific knowledge increases more complex but
d iagnosis and treatment.
rational classifications of sex-cord stromal tumours of
the ovary are inevitable (Table ll)'. Thecomas are hormonally active. Excessive estrogen
production is associated with endometrial
TABLE II
Classification of Sex Cordstromal Tumours of the
hyperplasias, increased size of uterine fibroids,
endometrial polyps and well differentiated
Ovary.
Granulosa
endometrial carcinomas. Luteinized thecomas
- Stromal Cell tumours
Granulosa constituting less than one-third of thecomas, are
- Cell Tumour
Adult type either non-functional or androgenic with
Juvenile Type masculinizatione.
Tumours in the thecoma -fibroma Group
Thecoma Fibroma - Fibrosarcoma.
Fibroma-fibrosarcoma Ovarian fibromas represent the most commonly
Sclerosing stromal tumour Sertoli-stromal cell encountered sex-cord-stromal tumour, accounting
tumours for approximately 4% of all ovarian neoplasms. They
650
Sex Cord-Stromal Tumours of the Ovary
are usually unilateral and endocrine-inert. Their size malignancy, spread is usually by lymphatics and
varies from microscopic to extremely large and they remains ipsilateral. The tumour's indolent growth
can occur at any age though infrequent prior to age pattern and ease of resectability afford affected
30 years. Tumour oedema is,qmlr*on as the size patients extended pal liation.
increases and ascites occt#s in 10% to 15% of
sf l. O:centimetres. Sex CordStromal Tumours Unclassified.
tu mou rs exceed i ng a d ia meter
Furthermore 1% of patientsdevdop a hydrothorax in
This ill-defined group of tumours which accounts for
less than 1O% of sex cord-stromal tumours comprise
addition to the hydroperitoneurn both resulting from
excessive fluid loss from the ovarian fibroma (Meigs'
those neoplasms in which a predominant pattern of
Syndrome)'0. Ovarian fibromas are generally testicular or ovarian differentiation is not clearly
considered benign lesions. ln contrast, fibrosarcomas
recognizable. lncluded in this group are sex-
cordstromal tumours which cannot be subclassified
are highly malignant. They are commonly large,
unilateral, highly vascular turnours with evidence of when they occur in pregnant patients because of
haemorrhage and necrosist'. alterations in their usual clinical and pathologic
features'0.
Sclerosing StromalCell Tumours account for less than
5% of sex cord-stromal ovarian tumours and are a Gynandroblastoma
Gynandroblastoma is an extremely rare sex-
histologically clinically distinct subgroup to be
cordstromal tumour. The microscopic criteria for
distinguished from both thecomas and fibromas.
diagnosis include the intermingling of readily
They are benign, contain prominent areas of sclerosis
in size up to 20 identifiable granulosa-cells and tubules of sertoli-
histologically, and are variable
cells. The corresponding stromal cells, namely theca
centimetres in diameter. Ascites is seldom
and/or Leydig cells, may also be present in varying
encountered and steroidogenic activity is usually
degrees.
absent.
The clinical presentation includes a hyperandrogenic

Ovarian Sex Cord Tumour with Annular Tubules.
These are ovarian tumours characterized by either clinical profile, signs or symptoms of excessive
estrogen or rarely no endocrine manifestations. The
simple or complex ring shaped tubules and
histologically represent an intermediate between tumours are typically small, unilateral and
sertoli and granulosa-tumours. About one-third of characterized by well-differentiated ovarian and
such tumours which occur in association with Peutz- testicular elements. They are generally of low
15.
ma lignant potential
Jeghers Syndrome (PJS) are typically small (many
microscopic), multifocal, calcified and bilateral with
GENERAL NOTES ON THE MANAGEMENT OF SEX
an average age of presentation in the fourth decade of
CORD STROMALTUMOURS OF THE OVARY.
life". The non - PJS group constituting about two- Malignant potential and surgical stage are important
thirds of these tumours are larger, seldom multifocal
determinants of the definitive management of sex
or calcified and invariably unilateral. Presentation is
cord-stromal tumours of the ovary. Other
on average in the third decade of life".
determinants include histologic subtype, patient's
is the commonest
Abnormal vaginal bleeding
age and desire for procreation, and various
prognostic factors.
presenting symptom. Abdominal pain and
discomfort, symptoms and signs of intususception
Surgery alone is sufficient for several sex cord
secondary to the colonic polyps in the PJS group, and
stromal tumours lacking malignant potential while
isosexual precocious puberty are other presentations. postoperative adjuvant therapy should generally be
Elevated estrogen levels are seen in most patients
considered for patients with advanced disease and
with this type of tumour. ln a few normal
sertoli leydig cell tumours with poor differentiation or
progesterone levels are Present.
heterologous elements.
The behavioural pattern of this tumour is benign in The principles of operative management are similar
80% of cases. ln the remaining 20% exhibiting to those for ovarian tumours in general. Excision for
651
histologic examination can be readily accomplished

by oophorectomy only in women desiring A thorough endometrial curettage must be performed
preservation of reproductive potential or by in all patients with estrogen producing tumours
hysterectomy and bilateral salpingo-oophorectomy whether they are considered benign or potentially
in women who have completed child bearingor are malignant, when electing conservative fertility-
climacteric. sparing treatment. lf fertility is not an issue or
extroovarian spread of disease is documented, a
This will constitute adequate treatmentforthe benign hysterectomy and residual salpingooophorectomy,
neoplasms including thecomas, fibromas, should be performed. An aggressive maximum effort
gynandroblastomas, stromal luteomas and Leydig- at primary surgery should be undertaken if
cell, sclerosing-stromal, sertoli-cell, and well metastatic disease is encountered. Secondary
differentiated sertoli-Leydig cell tumours. tumour reduction aimed at extended palliation in
Furthermore, sex cord tumours with annular tubules patients with the more indolent tumour types such as
associated with Peutz-Jeghers, Syndrome are also granulosa cell tumours should be seriously
considered benign and can be similarly managed, but considered.
it is imperative that the endocervix, be evaluated and
subsequently observed closely to exclude later The management of patients with recurrent disease,
development of a malignant cervical adenoma. and postoperative adjuvant therapy for patients with
Conversely, histologic confirmation of a granulosa- stage 1A disease must be individualized. Surgical
cell tumour, intermediate or poorly differentiated resection in disease recurrence followed by close
sertoli-Leydig cell tumour, sex-cord stromal tumours observation is justified in select patients. Depending
with annular tubules (independent of peutz-Jeghe/s on the site of disease recurrence, radiation therapy
Syndrome), and steroid-cell tumours not otherwise represents another option.
specified will require definitive surgical staging. This
includes multiple biopsies from high-yield sites, Other approaches include consideration of
omentectomy, and pelvic and para-aortic lymph node medroxyprogesterone acetate'u or gonadotrophin
sampling/dissection. Conservation of the uterus and releasing hormone agonists or antagonist'7
contralateral ovary is reasonable in patients wishing administration to patients with steroid hormone
preservation of fertility following careful surgical receptor containing granulosa cell tumours, radio
staging and exclusion of extra ovarian disease. therapy", andlor chemotherapy" for advanced
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652
Sex Cord-Stromal Tumours of the Ovary
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Surg Pathol 1987; 11:835. with PeutzJeghels Syndrome and four with
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Hartmann LC, Young RH, Evans M E fudratz Cetl, Sertoli-Leydig Cell, and unclassified
t KC. Ovarian Sex Cord-Stromal tumaurs. ln: sex-cord stromal tumours associated with
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10. Samanth K K, Black W C, Benign Ovarian
stromal tumours assoclated with free 17. Martikainen H, Penttinen J, Huhtaniemi, et
i peritoneal fluid. Am J Obstet Gynecol 1970; al. Gonadotropin releasing hormone agonist
107:538. analog therapy effective in ovarian
t
11. Prat J, Scully RE. Cellular fibromas and granulosacel I malignancy. Gynecol Oncol
fibrosarcomas of the ovdtf: a comparative 1989; 35:406.
t clinicopathologic analysis of 17 cases. 18. Plura B, Nemet D, Yanai-lnbar l, et al.
Cancer, 1981; 47:2663. Granulosa cell tumour of the ovdr!: a study
12. Srivafsa PJ, Keeney GL, Podratz KC. of l8 cases. J Surg Oncol 1994; 55:71.
I 19. Gershenson DM, Morris M, Burke TO, Wilson
Dissemi nated Cervical adenoma mal ignum
I
and bilateral ovarian sex cord tumours with MD. Treatment of poor prognosis sex cord
I
annular tubules assocrated with Peutz- stromal tumours of the ovary with the
Jeghels Syndrome. Gynecol Oncol 1994; combination of bleomycin etoposide and
53:256. cisplatin (BEP) (Abstract) Proc ASCO 1994;
13. Young RH, Welch WR, Dickersin GR et al. 13:262.
Ovarian Sex cord tumour with annular
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654
CHAPTE-51
Vulvar Cancer
C. A. Klufio/ Jerry Coleman
lncidence of Primary Vulvar Cancer Aetiological Risk Factors

Primary vulvar cancer forms 3-5% of all Broadly, these are factors that are associated with an
gynaecologica I cancers worldwide'. increased risk of HPV infection and a weakened
immunological competence.
It has been reported that vulvar cancer accounted for
2.7% of all gynaecologic malignancies at the Korle . Other genital csttcelS: Occurs in 15% of all
Bu Teaching Hospital, Accra.' cervical malignancies
o History of genital wartsr HPV oncogenic
It occurs in elderly women, with a peak incidence in sub-types (especially 16 and to a lesser
the 7'ndecade and73%" occurring in patients in their extent 18) cause transformation to vulvar
7'n decade or latert'^. However, the mean age of intra-epithelial neoplasia UIN) mostly in
women with squamous carcinoma in-situ is52.4yrs2. younger patients
Vulvar cancer has shown an increasing incidence r VIN: 5-80% will eventually become cancer,
with concurrently decreasing median age of 55-60 at although 5-10% is more realisticu'. Loss of
onset over the past few decades.A recent large chromosome 17 is frequently found in the
retrospective study reported that older women had a cancer tissue and in coniiguous normal skin
greater mortality risk compared with younger in these cases'
womenu. . Chronic vulvar inflammatory disorders,
particularly the granulomatous transmitted
Because cancer incidence increases with age, the infections'o sexually
increasing elderly demographics will probably result o Multiple sexual partners
in dramatic increases in the number of cancers . lmmuno-suppression, e,g. transplant
diagnosed. patients and H|V-infection: Compared with
women without HIV infection, HIV-infected
Site: 65% occur on the labia majora and minora, and women are approximately four times more
25"/" involve the clitoris. Other cancers, especially likely to have HPV infection". The strong
cancer of the breast can metastasize to the vulva. association between the HIV and VIN is a
They must not be confused with primary vulvar powerf ul i ndication for vol u ntary cou nsel I i ng
cancer. A carcinoma of the vulva that extends into the and testingfor HIV in allwomen with VlN"
vagina should be considered as a carcinoma of the . Maturation disorders (vulvar including
vulva. lichen sclerosis"''0. The lifetime risk of
cancer in lichen sclerosis is 3-5%'u. An extra
Multiple studies have shown that central lesions have chromosome 17 is frequently found in the
a significantly worse prognosis compared to lateral cancer tissue and in contiguous normal skin
lesions. in these cases'
655
. Tobacco smoking i. Paget disease
. Coffee drinking ii. Bartholin's gland
. Extra-mammary Paget's disease iii. Sweatgland
. Vitamin A deficiency
r Achlorhydria ll. Mesenchymal
. Diabetes Soft tissue sarcomas
. Poor perineal hygiene
lll. Other Non- Epithelial
Precursor Lesions a. Lymphomas
Vulvar intra-epithelial neoplasia (VlN) is defined as b. Extra-gonadal endodermal sinus tumou r
any vulvar epithelial condition in which, histological c. Arising in ectopic breast tissue in milk line: I
examination shows nuclear atypia and disordered The presence of normal breast tissue or
maturation, i.e. basal and parabasal cells are found ductal in situ carcinoma differentiates from
in superficial strata of the epithelium, where they do metastatic breast ca ncer
not belong. The transformation to VIN can start only
in the cells that are capable of active division. These lll. Metastatic
are the basal and parabasal cells. ln the mildest Shou ld not be considered as primary vu lvar cancer
grade (VlN 1), the dysplasia involves only the lower - -{
third of the epithelium. ln VIN 2, the lowertwo-thirds Clinical Features of Vulvar Cancer ;
Symptoms and Signs
of the epithelium is involved. The highest grade (VlN :
3) involves the full thickness of the epithelium and in
o
Persistent vulvar pruritus/irritation, or, mass
in >50%
addition to the nuclear atypia and disordered .
Vulvar bleeding -exclude vaginal, cervical
maturation of the cells, it shows an excess of mitotic
and endometrialcauses
figures. VIN 3 is a risk factor for invasive vulvar o Vulvar pain, soreness, or burning
cancer. The incidence of VIN parallels that of HPV . lncidental finding: no symptoms in 2Oo/",
infection and that of invasive cancer. ln women who
found at a medical check-up or during
have been previously treated for VIN 3, the long-term
exami nation for some other complai nt
risk of invasive cancer is 2.5-7"/"'u. ln women with . Appearance: diffuse white lesion or papules,
VIN 3 who were not treated, the incidence of cancer polypoid/granulomatous; ulcer/sore, which
is much higher. With the increasing incidence of does not heal; hyperpigmented lesion;
HPV-infection in recent decades, there has been a chronic vulvitis. Biopsy mandatory if they
dramatic increase in the incidence of high-grade VIN a re present. Su perficia I ly i nvasive ca rci noma
and of vulvar cancer in women aged 50 years and may present as an ulcer, or a red macule, or a
less". red papule, or, as a white hyperkeratotic
plaque
Pathological Classification of Vulvar Cancer
May arise from skin, subcutaneous tissues, glandular
. Vulvar warts are rare in menopausal women:
any warty lesion should be biopsied
elements (Bartholin's, sebaceous and sweat glands),
. Any vulvar symptom in a post-menopausal
smooth and skeletal muscles.
woman demands prompt and thorough
l. Epithelial
examination and biopsy of any abnormal
a. Typical Squamous cell (epidermoid) areas. The same applies to the pre-
carcinoma (90% of al I vu lvar cancers) menopausal woman if there is no response
b. Sub-types of squamous cancer: The risk of to first-l i ne treatment
lymph node metastasis is low in these sub- . Peak age incidence is after 60yrs; but 15%
types occur in women who are <40yrs
i. Verrucous (warty; rare type of squamous) o Diabetes in 10%
ii. Basal cell carcinoma (rodent ulcer) 2Y" - . Hypertension and/orobesity in >30%
labia majora
. Malignancy-associated hypercalcaemia may
c. Melanoma (5% of all vulvar cancers) be present. Usirally there are no bony
d, Adenocarcinoma(1%) metastases. Calcium levels return to normal
after excisison of pri mary tumou r
656
Younger-age and older-age types performed. The gold standard for definitive diagnosis
There are 2 characleristically separate groups of is biopsy of the lesion and obtaining multiple
vulvar cancer. ln older women, vuJvar squamous representative samples and underlying stroma. This
cancer tends to be unifocal, but in yotifr,f! wrnen, is easily done with local anesthesia and a punch
lesions are multifocal and often assodf*ffid' Vtttt biopsy'n.
and HPV infections'u.
Additionally, evaluation for potential inguinal
A. Younger-age group: lymphadenopathy should be performed as well as a
.
Younger (mean age 55yrs) chest x-ray. For larger lesions, CT scan (or PET) could
. Commonly associated with highgrade be utilized to evaluate for nodal involvement, and
VIN cystoscopy and/or proctoscopy are performed if
. Com mon ly associated with h igh bladder or rectal involvement is suspected. Lastly,
oncogenic types(16, and to a lesser
biopsy of any suspected metastatic lesion should be
extent, 18) of HPV performed.
. Heavy cigarette smokers
. Tumour is commonly exophytic and . Adequate biopsy is essential for diagnosis: lf
a
multi-focal there is no macroscopic lesion and
symptoms are diffuse, it is mandatory to take
B. Older-age group
multiple punch biopsies. Keyes biopsy
. Olderagegroup(mean ageTTyrs)
. Not associated with VIN
forceps are ideal for this. To define the sites
. HPV is rarely present in tumour for biopsy, colposcopy (vulvoscopy) is the
. Non-smokers gold standard. lf colposcopy is not available,
the vulva can be painted with Schiller's
t Tumour type is well-differentiated squamous iodine or Toluidine blue, or a roll of gauze
cell cancer and is usually uni-focaL soaked in 5% acetic acid can be applied to
the vulva for a few minutes. The biopsy is
Lichen sclerosis et atrophicus and squamous performed under local anaesthesia. The
cell hyperplasia are often present biopsy should be taken perpendicular to the
Granulomatous disease: Granuloma skin surface so as to avoid confusion induced
inguinale (Donovanosis) is a riskfactor by tangential sectioni ng
. Examine for cancer elsewhere in lower
Diagnosis genital tract. A Pap smear is mandatory.
. Early and accurate diagnosis is crucial for . lf the lesion is small (<2cm), and it is
successful management. Histological possible to remove the lesion together with
confirmation is mandatory. all areas of atypical epithelium, and with
Unfortunately, a delay between first >2cm of normal surrounding epithelium
symptoms and diagnosis is common. around it, a wide local excision can be
Both the patient and the primary health performed. No further local treatment is
caregiver may be responsible for this required if histology confirms that there is
delay. Diagnosis must not be delayed by >1cm tumour-free margin around the
ineffective topical treatments for tumour and stromal invasion is not more
candidiasis etc. However, recent than 1mm.
worldwide statistics indicate a marked
a,
improvement, with the majority of FIGO Staging for Vulva Cancer
patients treated in the triennium 1996- Reasons for staging
98 being diagnosed in Stages lA, lB and 1 To select treatment for Patient -
|' i ndividua isation of treatment
I
A thorough histoiy and physical with evaluation of 2 For prognosis

F adjacent organs (especially vagina, cervix, and anus) 3 To compare results of different treatment
; for field effect and possible involvement must be regimens
To compare results from different
657
-.---r!
institutions in suspected cases of bladder or rectal invasion.

Definitions of the stages are shown in Table 1. Pelvic computed tomography (CT), magnetic
resonance imaging (MRl), and intravenous
STAGING
urography can be used to evaluate the possibility of
Principles of staging
metastatic disease in pelvic lymph nodes or surgical
Cancer of the vulva can spread from the original,sfte
planning''.
by the following: local invasion of adjacent tissues;
embolization to regional lymph nodes, usually to the
superficial and deep inguinal ones and eventually to The staging system of cancer of the vulva has
the pelvic ones (Figure 6); and via blood, rarely changed in recent years and since 1988 has become
reaching the lungs, liver, and bones. Lymph node surgical. The final diagnosis and therefore the stage
involvement is the most important prognostic factol
classification depends on the histopathological
and lymphatic embolization is the major route of evaluation of the surgical specimen (vulva and lymph
spread.
nodes). The classification of the lnternational
Federation of Gynecology and Obstetrics (FIGO) was
The evaluation of patients with vulvar cancer begins
Iast changed in 2009 by the FIGO Committee on
with the physical examination, palpation of inguinal
Gynecologic Oncology and provides a good
and supraclavicular lymph nodes, vaginal
discrimination between prognosis and stages t15l
examination, and digital rectal examination.
The lnternational Union for Cancer Control (UICC)
Oncologic cervical cytology, colposcopy of the cervix
provides a classification for tumor (T), lymph nodes
and vagina (because of the association with (N), and metastasis (M) (TNM classification), which
squamous intraepithelial lesions),
is shown in the following text compared to the FIGO
hematological/biochemical tests, and chest X-ray are
classification2l
routine. Cystoscopy and sigmoidoscopy are indicated
FIGO Stage Description
1 Tumor confined to the vulva
1A :2 cm in size, confined the vulva or perineum and with stromal invasion

Lesions
:1.Omma, no nodal metastasis
1B Lesions >2 cm in size or with stromal invasion >1.0mma, confined to the vulva or
perineum, with negative lymph nodes
il Tumor o-f anysizEwith-eTtens-ion1o acljaccRt perinealstruTtures flowerthird of urethrr

lowerthird of vagina, anus) with negative nodes
ilt Tumor of any size with or without extension to adjacent perineal structures (ower third
of urethra, lower third of vagina, anus) with positive ingulnofemoral lymph nodes
lltA (i) with i lymph node metastasis ( =5 mm), or (ii) with 1-2 lymph node
metastasis(es) (<5 mm)
lilB (i) with 2 lyrnph node metastasis (:5 mm), or (ii) with 3 lymph node metastasis(es)
(<5 mm)
iltc With positive nodes with extracapsular spread
IV tumor invaies olher regional (upper 213 urethra, upper 213 vagina), or distant
structures
Turnor invades any of the following:
658
(i) upper urethral anilor vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to
pelvic bone
(ii) fixed or lymph nodes
FIGO classification of cancer of the vulvar
TNM DESCRIPTION
T1 Tumor confined to vulva and/or perineum
T1a <2 cm with stromal invasion <1.0mm
T1b >2 cm with stromal invasion >1.0 mm

T2 Tumor with invasion of the lower part of urethra/vagina/anus
T3 lnvasion oJ the upper+art of urethralagina, bladder, rectal mucos4, bong,
fixation in pelvic
Staging of cancer of the vulva (FIGO and UICC (TNM)
TNM DESCRIPTION
N1a One or two nodules <Smm
N1b One nodule >Smm

N2b Two or more nodules >5mm
N2c Extracapsular invasion
N3 Fixed, ulcerated
MO Apsence of distant metastases
M1 Distant metastases
FIGO TNM
FIGO TlNOMO
FIGO IA T1a N0 M0
FIGO 1B T1b NO MO
FIGO il T2 NO MO
FIGO ilt A rt,Ttrtta, N1b Mo
FIGO ilrB T1, T2N2a, N2b, M0
FIGO iltc TI,T2 N3 MO
FIGO IVA T7,T2 N3 MO, T3 any N M0
659
Treatment Options for Vulvar Cancer metastases, but is simply the first node draining the
Objectives of Treatme nt site of a tumour. Therefore, a tumour free sentinel
The objective is to achieve safe, effective tr,mtment
lymph node implies the absence of lymph node
with minimum morbidity and maximum p@ly*tton
metastases in the entire draining lymphatic basin,,.
of f u nctio n. Treatm e nt i nvo|ves treatmentd-'4&@[
tumour and treatment of lymph node spreadi.. ,.,, .., Preo pe rative Wor ku p I Pre pa rati on
Treatment Plan
A. Evaluation of Patient's
Physical & Mental
State Because of old age, incidental disease
The treatment plan consists of the following;
Counselling patient to understand management is common, especially diabetes,
options and prognosis and for her co-operation hypertension and dementia. Meticulous
Pre-o pe rative work-u p/prepa ration preoperative assessment for systemic
Definitive treatment disease is therefore essential.
*Definitive treatment is primarily Cervical (Pap) smear
surgical
*The Sentinel Node in Full blood examination
early disease
BUE & Creatinine
Fasting and postprandial blood glucose, or
Place of Chemotherapy and Radiotherapy
*Neoadjuvant, adjuvant fullOGTT
and adjunctive
Follow-up ChestXray and ECG
Urinalysis and renal function tests
Treatment is primarily surgical: Surgery is the
IVU if indicated
primary modality for treating vulvar cancer. Vulvar
skin is prone to radiation dermatitis, fibrosis and B. Assessmentto Determine Metastatic Disease
ulceration. Therefore, radiation is not used as . lmaging of inguinal regions and pelvis for
primary curative treatment for the primary (local) enlarged nodes
tumour. Radiotherapy is used before (neoadjuvant),
or after surgery (4,500 centi-Gray). ln advanced * Ultrasound scan
disease, concurrent combined chemotherapy and x CTscan
radiotherapy is used. Combined chemotherapy and * MRI
radiotherapy is also used primarilyto avoid morbidity.
For example, if surgical treatment of the total lesion
. Fine needle aspiration of enlarged glands and
would involve the anal sphincter, chemotherapy plus other suspected metastatic lesions: This may
radiotherapy can first be given to avoid having to be directed by ultrasound scan.
excise the sphincter.

C. M easu res to Prevent Post-Operative I nfection
Role of Nodal Lymph Node Biopsy
. Local cleansing of vulvar tumour: Eusol or
hydrogen peroxide followed by metronidazole
The sentinel lymph node is the node to which the application
tumour first drains. For women with early disease,
. Mechanical evacuation of the bowel before
only 20% will have lymph node metastases. The Surg€r!: This is to avoid stool running out during
majority of these patients are, therefore, undergoing the operation: lt can be achieved by giving an
an unnecessary lymph node resection and the enema the night before the operation.
associated complications. lf the sentinel lymph node
. Prophylactic antibiotics: Lesions are usually
is isolated and resected, it can be examined by frozen
infected. A first or second generation
cephalosporin can be used.
section pathology. Sentinel node mapping and biopsy
concept was first described by Cabanas in 197 6.
Characteristics of Tumour and Lymphatic Spread
that I nf I uen ce Treatment Option s
The uhderlying principle states that the first lymph
These characteristics have prognostic importance
node/s to receive lymphatic drainage from the site of
and therefore influence which treatment option
a tumour should be the first site of malignant
should be chosen. They allow individualisation of
lymphatic spread. This first node is defined as the
treatment.
sentinel lymph node. lt does not necessarily contain
660
rt
I
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i
{-
t
i
ri
I A. Tu mour characteristics ii. lf tumour does not cross midline
i . Stage and Size of tumour: There is a clitoris, urethra, perineum or anus, spread to
ir
r
't
significant risk of inguinal-fernoral node contralateral nodes can only occur after
; involvement in all stages, except in ipsilateral nodes are involved
I
{ superficially invasive (Stage lA disease, i.e.
!t
i
<2cm wide and < 1mm deep). ln Stage lA, 3. Urethra, outer vagina, perineum drain
t the risk of node metastasis is negligible'ozu bilaterally through internal pudendal to internal
- .
I
Site of tumour: Lateral or rnidline and iliac
i relationship to urethra, anus and perineal
f body (see below) 4' Following are determinants of noda I metastases:
(
I . State of groin nodes: The presence of lymph
/ node metastasis is the most important i. Tumour stage, reflected in following: Tumour
size (diameter) and depth of invasion'''u'"'"'"
I
prognostic factor in vulvar cancer'u''u.
ii. Palpable inguinal nodes
Evaluation of groin nodes is therefore crucial
iii. Tumourgrade
in management
iv. Capillary-lymphatic space involvement
.
I
r Previous excision and whether excision

v. Perineuralinvasion
i margins contained tumour: Positive lateral vi. Olderageof patient
margins contribute significantly to
? morbidity" 5. Spread to lymph nodes is by embolisation, not by
I
. Histology: Celltype permeation. Therefore, recurrence does not
I
I
* Verrucous and basal-cell cancers do not occur in skin bridges when separate incisions are
':
metastasise to nodes. However, risk of used for local excision of tumour and for the
I local recurrence after adequate removal of the inguino-femoral nodes (triple
i
excision is high (about2O%)
I
* Melanoma: Depth of invasion is so
incision technique)
t crucially an important prognostic Prognostic features of positive nodes

factor in survival that the state of the ln patients with nodal metastases, the following
I
I
I nodes is of secondary importance ind icate poor su rviva 122'3234
r i. Presence of extra-capsu lar growth

B. Lymphatic drainage characteristics ii. Numberof positive nodes
t
iii. Morethan 50%of thenodereplaced bytumour
r
I
1. Lymphatic chain always involved in sequence. tissue
The femoral and inguinal nodes are sifes of regional
I
spread. Jst stop; Superficial inguinal nodes 2nd Surgical Treatment

a
stop; Deep inguinal/femoral (Cloquet's node) 3rd Vulval cancer should be managed by a
stop; Pelvic (iliacs, obturator): These are considered multidisciplinary team in a cancer centre. Surgery
i
distant metastases. remains the gold standard of treatment for vulval
I
r cancer.
i
Deeper nodes are never involved unless superficial
i nodes are positive: Deep inguinal/femoral node and Treatment has evolved over time from a radical
a
pelvic (iliacs and obturator) node metastases do not dissection (radical vulvectomy with en bloc bilateral
occur if superficial inguinal nodes are negative"-to inguinofemoral lymphadenectomy) with its
concomitant morbidity to tailored levels of excision
2. Lymphatic pathway is essentra/ly ipsilateral in based on risk factors. Early stage disease is now
vulvar cancer: A unilateral tumour drains to treated by a radical local excision with or without
.ipsilateral groin. lt does not metastasise to the inguinofemoral lymphadenectomy based on the
contralateral inguinal/femoral nodes if the ipsilateral stage of disease. For advanced disease, radical
nodes are free of metastatic disease'o'"-'o vulvectomy is often still necessary, but the morbidity
t has been limited by the uSe of the triple incision
i. Only midline structures (clitoris and perineum) technique. Currently, multimodality therapy using
drain bilaterally
661
chemoradiation is often offered as a way to further nodes are negative for microscopic
limit morbidity. metastatic disease, the ipsilateral pelvic
nodes and the contralateral inguino-femoral
ln Ghana as in many other low to mffi;iitwne
and pelvic nodes are not dissected
countries where patients present witn mrffie
diseasechemoradiation is thetreatmentdetffi_' These modifications reduce the mutilation,
disfigurement, and loss of function that may occur
The National Centre for Radiotherapy and t&*clear with lesions close to the clitoris, urethra, and anus.
Medicine, Korle Bu Teaching Hospital houses a
Cobalt-60 teletherapy machine, a convefitional Surgical Treatment Options according to Stage and
simulator and a conformal treatment planning Situation of Cancer Stage lA. Superficially invasive
system for the treatment of Vulval cancer patients. disease (2cm wide, 1. mm stromal invasion)
Seventy vulval cases were referred to the centre Local excision with a >2cm macroscopically
between January 2000 and December 2014. tumourfree margin; this can be guided by
vulvoscopy, acetic acid application, Schiller's test
En bloc radical vulvectomywith bilateral inguinal and (iodine staining) or toluidine blue staining. No further
bilateral pelvic lymphadenectomy was the standard treatment is necessary if microscopy of the specimen
procedure for the treatment of all stages of vulvar
shows > 1cm margins (frozen section) or 8mm in the
cancer. With this procedure, the overall S-year fixed specimen, to be free of tumour. Taking into
survival rate is roughly 7O%; in Stage l, the S-year account the shrinkage that occurs during preparation
survival rate is over 90%. Postperative mortality, and fixation of the specimen, 2cm is the minimum
even in modern times is high, ranging between 1% width of normal skin that will give a >8mm
and 57o". Lymphoedema can still be significant: microscopically cancer-free margin in the fresh
approximately lO% have significant oedema. specimen.
Morbidity is also high3.
l-ateral lesions (notwithin 2cm of midline)
Because of present knowledge of the characteristic Sfage IB. (2cm wide, > 7mm stromal invasion)
behaviour and lymphatic spread of the tumour, it is Wide local excision with >2cm macroscopically
now accepted that such extensive surgery is not normal margins (wide radical local excision) is
usually necessary in Stages land il disease. performed. Again, vulvoscopy or a stain is used to
Treatment is now customised for the individual define normal skin. lpsilateral superficial inguinal
patient. The most important modifications are: node dissection is performed through separate groin
incision. The specimens are subjected to frozen
. I nstead of the sta nda rd butterf ly incision, section examination.
separate groin incisions are used for the
dissection of the inguinal/femoral nodes. lf negative, no furthertreatment
This decreases the risk of wound breakdown lf only one positive inguinal node and no evidence of
and the prolonged hospitalisation that extranodal growth, immediate deeper node
follows. Recurrences in the skin bridges are dissection is performed, and contralateral groin
rare if the margins of the radically excised dissected.
tu mou r a re free of ca ncer
. lnstead of radical vulvectomy, radical local lf 2 or more positive nodes and/orthere is extranodal
excision is used for patients in whom the growth, radiotherapy is given.
tumour is not more than 3cm in diameter,
and it can be excised together with >2cm of Sfage // (confined to vulva, maximum diameter
' macroscopically normal surrounding skin. >2cm, no node metasfases)
This gives a >8mm histologicalty cancer- Hemivulvectomy and ipsilateral superficial inguinal
free margin in'the fixed specimen. lt has node dissection through separate groin incision.
been shown that 8mm is the most powerful Frozen section perfomed. lf a node is positive:
predictor of local recurrencetu

.. ln unilateral lesions, if the ipsilateral inguinal
lmmediate deeper node dissection and contralateral
662
7
r
I
i
i
I
i groin dissection followed by adjuvant radiotherapy, or should be performed. Depending on the type of
t Contralateral groin dissection followed by radiother- lesion, this dissection is either unilateral or
apy to the deeper nodes is performed.
I
rt bilateral. Studies of vulvar lymphatic drainage

ir- demonstrate that the direction of flow is
r lll
/
I
Stage primarily ipsilateral. When the lesion is > 1 cm
i
I
Radical vulvectomy and bilateral lymphadenectomy from the midline and there are no positive
?
I
followed by radiotherapy: However, a completely ipsilateral nodes, a unilateral
t
resectable TrNoMotumour may not need radiotherapy. lymphadenectomy is acceptable, since the rate
r
I
It has been shown that the incision for the of node metastasis is <1%. The Gynaecology
r lymphadenectomy need not extend to the anterior Oncology Group 36 supported this finding,
r
i
superior iliac spine. The most lateral superficial noting only 2.5% of lateral lesions with
I inguinal node does not arise above the medial margin negative ipsilateral nodes had a positive
I
I
,
of the sartorius muscle, nor far lateral to the point contralateral node. lf the lesion does not meet
I
r where the superficial circumflex iliac vessels cross these criteria, a bilateral dissection is recom-
i the inguinal ligament". mended.
I
r
r Stage IV Com p I ication s of Vu lvectomy
Radiation (4,000cGray) to tumour and (4,5000cGy) A. Early Complications
to regional and pelvic nodes; surgery 5 weeks later. Anaesthetic com pl ications
|. IVote: 1 centi-Gray (1cGy) :lrad; Haemorrhage: primary, reactionary, and
I
lGraY:100rads secondary; retroperitoneal haematoma after
I
i pelvic node dissection. Arteriosclerosis in
a Midline lesions
I these elderly patients predisposes to haemor-
I Anterior, posterior, or complete radical vulvectomy
I rhage. Sartorius muscle cover prevents
and bilateral superficial node dissection through
infection of vein and haemorrhage from vein
i separate groin incisions. Frozen section. lf positive,
lnfection
immediate deeper node dissection or later radiother-
Necrosis and infection of skin flaps Wound
apyto nodes.
! breakdown occurs in up to 85% of cases.
It is the result of:
Positive nodes require adjuvant treatment, and groin * lnfection
recurrence is almost universally fatal. The standard * Necrosis and infection of skin flaps
procedure is a bilateral inguinofemoral With the use of separate incisions (Triple
lymphadenectomy, which includes both the superfi- lncision) for the primary tumour and for the
cial inguinal nodes and the deep femoral nodes.
inguino-femoral node dissection, wound
However, lymph node dissection is associated with breakdown is now less common.
wound complications and lymphedema, and there
have been efforts to decrease morbidity by carefully Deep vein thrombosis and pulmonary
tailoring who receives a full dissection and evaluating embolism
sentinel nodes. Pressure sores
There are two clinical scenarios that obviate the need

B. Late Complications
for bilateral lymph node dissection: Lymphocyst -prevented by Haemovac suction
1. Stage lA: When the depth of stromal invasion is Chronic lymphoedema of the lower limbs occurs in
< 1 mm, there is a negligible rate of lymph node
30-70%. ln 10% it is significant, i.e. it adversely
involvement (< 7%). ln this case, the affects quality of life
inguinofemoral lymph node dissection may be
omitted entirely. Hernia: inguinal and femoral may occur, but this is
unusual
2. Lateralized Stage lB tumors: When the depth of Genital prolapse or relaxation
i invasion is > 1 mm, the risk of nodal metastasis Urinary and faecal incontinence
rises to > 8% and a lymph node dissection I ntroital stenosis and dyspareunia
653
.
Psychological and psychosexual problems: ultrastaging, and it makes possible diagnosis of

These are most significant. They d.rop to the nodal involvement which routine histological
lowest percentile for body image '" preparation is likely to miss. The technique also
,,.
helps in deciding where to place the incision for the
Vaginal estrogen after radiotherapy was b lymphadenectomy according to the location of the
have short-term benefit but more robustsffi Er€
SN. l
required in this area. A psychosexualcounefuand
reconstructive plastic surgeon have an importantrole Recently, Near-infrared fluorescence (NlR) optical
is managing sexual issues and should be'part of the imaging for Sentinel Lymph node (SLN) detection
multidisciplinary team caring for women with vulvar has been introduced. This technique uses the
cancer. clinically available Near-infrared fluorescent tracer
lndocyanine Green (lCG) ".
The Sentinel Node Concept and Ultrastaging in hrty
Disease The use of Near- infrared light (700-900 nm) has
As stated earlier, the presence of lymph node several characteristics that can be advantageous in
metastases is the most important prognostic factor in
SLN biopsy because it offers relatively high tissue
vulvar cancer. Local recurrences can often be penetration (several millimetres) compared with blue
salvaged with re-excision, but groin recurrences are
dye, and detection of low concentrations of traceru'.
invariablyfatal. Determination of node involvement is
therefore crucial in primary management. In 25-30% NIR fluorescence is of added value during SLN
of cases, clinical evaluation of groin lymph nodes is detection, because all SLNs detected could be
inaccurate. The sentinel node (SN) is the first node in identified by the direct optical guidance of NIR
the lymphatic system that drains the primary fluorescence, but only 77% by blue dye staining.
tumoufu. ln vulvar cance[ it belongs to the inguino- Moreover, the NIR fluorescence signal in the SLN
femoral basin. The status of the SN is predictive of could be detected before patent blue in all cases.
the whole groin node pathologic status. Spread of the Blue dye stain ing and N IR fluorescence both provide
tumour does not skip the SN to nodes farther down in real-time optical guidance, however tissue penetra-
the chain. ln other words, there can be no nodal tion of NIR fluorescent light is significantly higher
metastases if the SN is disease-free. This affirmation than penetration of visible light, which enables
used to be made of Cloquet's node. lt is now realised deeper and earlier visualisation of signal by NIR
that this node can be difficult to identify at surgical fluorescence. This can help to determine the location
exploration. On the other hand, the SN can be of the incision and provide improved optical guid-
identified by lymphatic mapping. The most tried ance during SLN localisation. Furthermore, since ICG
method is lymphscintigraphy using radioactiven' is diluted to levels invisible to the human eye after
Technetium sulfur colloid and a gamma-detection injection, no discoloration of the surgical field occurs.
probe to localise the radio-labelled colloid in the
node. A vital blue dye (isosulfan blue) has also been Lymphangiography using the vital blue dye, isosulfan
used, but it is not as accurate. The technique is as blue, can also be used to visualise the sentinel node.
follows. Pre-operatively, an anaesthetic cream is The blue dye technique is performed intraoperatively
applied around the tumour. An hour later, the under general anaesthesia, but the blue dye method
radioactive tracer is injected superficially around the is far less accurate than the radioactive method.
tumour'u. Radioactive SNs are identified by However, when the site of the tumour is close to the
lymphscintigraphy in 5-30 minutes after the injec- inguinal region, a combination of the blue dye and
tion. The procedure ensures removal and examina- radioactive techniques can be used. I r such cases,
tion of the node that is most likely to contain disease; the use of the radiotracer alone can be compromised
it thus defines the extent of the lymphadenectomy. by proximity (shine-through) of the primary tumour
The SN can be subjected to serial stepwise sectioning and the bladdertothe regional lymph node basin.
through the node and application of specific
immunohistochemical staining for tumour antigens For squamous cell cancer, this technique is still
in order to identify micrometastases. This is called experimental, but it is now the standard of care for
vulva carcinoma.
664
r
l
Prognosis and SYear Survival Rates and T3 tumours having 76%, 52% and 27%
S-Year Survival Rates Overall: 7 5% asagainst 90% in survivalrates'
I Number of nodes with metastases: Nodal status
Itr;", -li is extremely important. Survival drops from 69%
7 W
Research has consistently found noOe for patients with negative nodes lo 74% for
r involvement was the most intpq tic patients with 3-4 positive nodes (Table 2)
factor with regard to survival. Accuraklssd@on of
the nodal status is therefore imper.ative b,mking Age over 65yrs carries a reduced survival'
treatment decisions. Nodal invslvenent:a{se posi- lnadequate excision of margins (on histological
tively correlates with depth of invasion of the primary examination, cancer free margins <1cm wide)
tumour. Lymph-vascu lar space i nvolvement
tt
Factors affecti ng prognosis Adjuvant radiotherapy: ln patients with positive
r . Stage is a strong predictor for survival. There is a nodes, adjuvant radiotherapy improves survival
Y
strong association between stage and nodal status but has no effect when the nodes are negative
(Table 2). Five-year survival rates are 77"/",557o,
and37%forStages l, lland lll, respectively lnfiltrative growth pattern For each stage, age
>65yrs, positive lymph nodes and treatment
. Lesion size (largest diameter): Tumour size is a modal ity are i ndependently significant prognostic
very important prognostic factor, with lesions factors in squamous cell cancer of the vulva'.
<2cm having a70% 5-yr survival, and T1, T2,
Table 2. lncidence of Positive Nodes bv Staee

7 Stage il ill IV
I
I Percentage with positive nodes 20 5 60 100
r
r World-wide 5-yr survival by stage (% survival) 80 60 50 20
t World-wide 5-yr Survival Rates by Number of Positive Nodes
?:
r Number of Positive Nodes 0 1 2 >3
f
t <15
r Percentaqe survival 95 90 80
r
Adjuvant radiation . Close or positive margins may benefit from
t There are certain high risk clinical features that local adjuvant rad iation.
c.
r should prompt consideration of adjuvant therapy in o A single microscopic node does not require
fI advanced stage vulvar cancer. For example, in adj uvant rad iation therapy
rt women with positive surgical margins, radiation has

macroscopic nodal disease, extra-capsular
{
demonstrated a survival benefit. Some authors also
f recommend adjuvant radiation for patients with a spread, or stage IVA disease should get
rI groin and pelvic radiation therapy.
high risk of local recurrence, which includes those
I
t
I
with stage IVA disease, LVSI, and deep invasion.
I Chemondiation
t
I
r ln patients with positive groin nodes, adjuvant
therapy has not been shown to improve outcomes Chemoradiation has been used as primary therapy
i
a
.with a single microscopically positive node. Benefit and as neoadjuvant therapy to shrink tumors that are
t-
Fry
from adjuvant radiation has been shown in those with either inoperable or would require surgery with
subsequent colostomy and urostomy to achieve
clinically appreciable nodes, >2 positive nodes, or
h adequate surgical margins. ln most cases, this would
evidence of extracapsular spread. Therefore, in
tt sumffi?l!: involve locally advanced tumors. The use of
{' chemoradiation in vulvar cancer is based on the
I
I
f
655
I
:
;-
experience gained in the treatment of cervical and It is brown, black, or bluish-brown in colour or non-
anal cancer. Most trials have focused on 5- pigmented. lt is most often situated on labia minora
fluorouracil with ciplatin and mitomycin.B w*th a or clitoris. Commonly, it is a superficial (flat)
va riety of rad iation regimens. spreading melanoma; occasionally it may be nodular
a
or ulcerative. Malignant melanoma is classified using
Place of AdjuvantlAdjunctive Raafu: & modified Clark's levels or Breslow's tumour thickness
Chemotherapy (Tables 3 and 4). Treatment: Wide excision with a 1-
3cm tumour-free margin, depending on thickness of
. Adjuvant radiotherapy: To pelvic nodes,after
tumour. Overall 5year survival is less than for
local excision and removal of inguinal-
squamous carcinoma; it is only 50%. The depth of
invasion tt'" and tumour thicknessu''t''oo have
femoral nodes. No difference in survival
rates between surgical removal of pelvic
prognostic significance. Both factors are related to
nodes and radiotherapy to pelvic nodes if tt-ot.
nodal status
radiotherapy is properly delivered to csrrect
depth with electron beam Vulvar melanoma
. Adjunctive local radiotherapy: lf primary Vulvar melanoma is the second most common type of
tumour not adequately excised vulvar cancer (8-10%) and appears unrelated to
. Neo-adjuvant (pre-operative) therapy: ultraviolet radiation exposure. Common symptoms
,r|
uti
1
Radiotherapy with, or without concurrent include a pigmented lesion, pruritis, bleeding, and
chemotherapytoshrink I a rge tu mou rs
:
less often, ulceration. Tissue biopsy is crucial in
before surgery. Can make surgery less making the diagnosis. lmmunohistochemical
extensive, or, it can make a seemingly staining with S100 and melanoma specific antigen
i m possi ble su rgery possi ble can also be helpful in differentiating melanomas from
. Adjunctive therapy: Post-operative radio- other pathologic vulvar lesions.
therapy to nodes, if on surgical removal of
pelvic nodes: Melanoma has three histologic types:
. Two or more nodes are positive . Superficial spreading: most common type,
. A node is completelyfilled with tumour with primarily radial growth and latervertical
. A node shows a breach in its capsule
spread.
Verrucous Carcinoma of the Vulvar

. Nodular: second most common type, with
only a verticalgrowth phase.
This is a rare variant of squamous cell carcinoma. As
its name implies, macroScopically, it is a papillary
. Acral Lentiginous: least common type, with
radial and vertical growth.
(warty) exophytic growth that looks like a large
condylomatous mass, but with a broad base. lt is a Lesions typically originate on the labia minora, labia
highly differentiated squamous carcinoma. Micro- majora, or clitoris. Multiple studies have shown that
scopically, acanthosis is prominent. There are mature central lesions have a significantly worse prognosis
squamous cells with extensive keratinization with compared to lateral lesions. A central primary lesion
pearl nests that invade the underlying vulva tissues.
is associated with a higher rate of recurrence. Other
The invasion appears as bulbous pegs of tumour important risk factors include positive lymph nodes,
pushing into the dermis. The interface between tumor depth of invasion, stage of disease, histologic
tumour and normal dermis is quite distinct. Treat- type (nodular has worse prognosis), and LVSI. Risk
ment: Wide excision. Radiation causes anaplastic factors that only apply to local disease are ulceration
changes in tumour and is therefore contraindicated. and clinical amelanosis.
It recurs only locally and seldom metastasises.
Staging of vulvar melanomas is complicated by
Metanoma of Vulvar
Has a wide age incidence with a median of 50yrs. lt is
multiple systems which include the FIGO staging for v'.
vulvar carcinomas and the fuCC (American Joint
the mostfrequent non-squamous cell carcinom of the
Commission for Cancer) system, as well as three
vulvar. lt forms 5% of all primary vulvar cancers. microstaging systems (Clark, Chung, and Breslow).
Mela noma rises from ju nctiona I or compound naevi.
a
Phillips et al. concluded in a prospective
556
Gynaecology Oncology Group that vulvar melanomas Studies have concluded that AJCC staging was the
have similar behaviors to cutaneous rnelanomas and preferred system for vulvar melanomas and, if
that the AJCC stage was the best predictor of unavailable, use of the Breslow microstaging system
o'.
recurrence free survival was the next most prognostic.
Depth of lnvasion (Modified Clark's Ley9!]!9!1)

Level Level I Level ll Level lll Level lV Level V
Depth of lntri-epithelial 1 Superf'rcial Full thickness of Reticular Subcutaneous

(in situ) papillary dermis papillary dermis dermis (fat) or deeper
invasion
(<1mm invasion) (1-2mm) (>2mm) tissues
MelanomabyBreslow'sTumourThickness(32'33)
M6 I O.Z0-!.S 1.51-3.0 >3.0
5yr-survival (%) 100 72 89 22

.Tumour thtckness as measured from the deep layer of the granular layer of the
overlying epithelium to the deepest point of tumour invasion.
Ditferential Diagnosis of Vulvar Ulcer
Iltrgr*.wi ll,&'firtrsffis r of $trortt*tfnwsi'or
H*ar;rt, no* m$*rft*lrl

dcrmal papilh
Tkr drptil cf:la*rthru (*romd i*vtrbn! li d;fancd rc lkr

rrcwumn*rt ofttc tulior flam lh; rptthclbi stromd$aetbn of
tht rdJrc*at mo$rupcrlicid dcrmrl prplll* to lht dccpa* polnt of
thr trmoff.
Frora thc b*rffiicnt nramb***c. thc lrytr* of tho tpid*nk ar*:
r Bm*lhvrr &elr!i&* Etngl; lrlcr of eulollsl edls with d*rk
*ntntng aucttt *lld mitoth 8gur*" Ttls k thc a*rmhd hyer.
Tkcy dli,id* to r*ph*c lort etllr ou lht mrhsc
, frli&$ttr&Is:
htrl1y kgcrl ofrrktix&lY l8rg.,
r
n Orrnd*r.,krsrflntularumk
i L{sfi!m.'
cartcrol&trxk
667
Primary herpes simplex virus infection Syphilitic prevent and manage the condition. lnadequate
chancre Lymphogranuloma inguinale surgical excision has always been thought to be the
main reason attributed to the development of LVR,
Local Recurence After Treatment but this belief has been challenged by new evidence .
Recurrent disease is common following ptrnary Based on current evidence its thought that local
treatment in Vulvar Cancer with more than half gftte recurrence arise within a field of molecularly altered
cases recurring locally within the vulvoperine*l area. epithelium that is generated as a result of chronic
The rate of local vulval recurrence (LVR) has not inflammation or infection with oncogenic HpV
changed over time and affects at least 1 in 4 patients strains. Recurrence therefore develop in pre-existing
fol lowing primary treatment o'. field of molecularly altered epithelium that have
acquired the necessary mutations to undergo
Disappointingly, we still lack an understanding of malignant transformation.
how recurrences develop and the best approach to
Sites of Local rmurrences
IffitRelryre G.Bl
Sieof kimaryTunxrur
SewdBt*dTrrmr{Sm}
S"*td#r1rttmmrrSFf)
ftuc2:XkpoUfi{ihr h{,tidrlfffi mncrlocrltf in&."ulrr

tlSntg qa*m o( grillrf uaour.
568
r I
I
(
r
i
i
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3I
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670
cHAPrERS2
Gestationa I Trophoblastic Disease

K Nkyekyer and Ol Akinola
The term "gestational trophoblastic disease" (GTD) non-villous GTD includes both benign and malignant
covers a cytogenetically and clinically heterogeneous disease as well as lesions which progress from
group of clinical conditions characterized by benign to malignant such as persistent postmolar
disordered differentiation and/or the proliferation of gestationa I trophoblastic d isease(''
(')
trophoblastic epithelium
Classificationof gestational trophoblastic disease
(GTD) according to clinical and patho-biological
Classification:
criteria based on the classification of the World
Gestational Trophoblastic Diseases are differentiated
Health Organization is shown below in Figure 1.
into villous and non-villous according to the
presence or absence of chorionic villi . Villous and
Figure l: Classification of Gestational Trophoblastic Disease
671
Epidemiology ln women with a past pregnancy affected by

The incidence of gestational trophoblastic disease complete or partial hydatidiform mole, the overall
varies considerably in different regions of the world. risk of recurrent hydatidiform mole is reported to be
For example, the incidence of molar pr@ry@ in
7.8y", a rate that is 20 times higher than that seen in
Japan (2 per 1000 pregnancies) is repo+W g Ue women without a history of molar pregnancy. With
about three times higher than the incitBrrce in regards to recurrence type, the repeat mole is usually
Europe or North America (0.6 to 1.1 per l0OO the same as the initial mole. For women who have
pregnancies). ln West Africa, incidence rates of
experienced two molar pregnancies in the past, the
between 0.87 and 4.88 per 1000 deliveries have risk of a third is about 10%(").
been reported from Nigeria and a rate of 0.g0 per
1000 deliveries reported from Ghana. ln Tunisia an Hydatidiform Mole (Molar Pregnancy)
incidence rate of 7.26 per 1000 pregnancies has H. Mole consists of two distinct entities, Complete
(3'4'5'6)
been reported and Partial Mole, which have been cytogenetically
validated as different '''
Variations in the incidence rates of molar pregnancy
partly result from differences between reporting Complete Mole
hospital-based versus population-based data. ln Cytogenetic studies have revealed that complete
general areas with high incidence of molar mole is the result of proliferation of a purely paternal
pregnancies have proportionately greater incidence conceptus. About 90% of complete moles have I
of chorioca rci noma a risi ng f rom hydatid iform mole. 46/rX diploid chromosome pattern. This is believed
The risk of having a complete molar pregnancy to result from fertilization of an egg by a single sperm
increases with advanced maternal age. The risk for bearing a 23X complement, consequent loss or
complete mole has been reported to be increased inactivation of maternal chromosomes and
two-fold for women over 35 and 7.S-fold for women duplication of paternal nuclear material to a 46)fi
over 40 ''1. There is also increased risk of complete homozygous complement, The remaining 10% have
mole in the under-16-year group. partial mole, in a 46XY chromosomal pattern, probably arising from
contrast to complete mole, does not show any fertilization of an anuclear egg by two sperms ,r,.
significant association with age. lt is difficult to These processes have been referred to as
distinguish the effect of gravidity from the effect of androgenesrs. The androgenetic origin of complete
age. moles has been confirmed by molecular. genetic
Socio-economic and nutritional factors have been studies '''. ln complete moles, therefore, maternal
cited as contributing to the high incidence of molar DNA can only be found in the mitochondria. The
pregnancy in some populations. Studies from ltaly embryo dies early and so complete moles have no
and the United States suggest that the risk for fetal parts, and usually, no amniotic cavity. The
complete molar pregnancy progressively increased genetic abnormalities give rise to excessive
with decreasing levels of consumption of dietary trophoblastic proliferation around diffusely
carotene (vitamin A precursor) and animal fat ,r,'). oedematous chorionic villi, resulting in the typical
Regions with a high incidence of vitamin A deficiency bunch of grapes appearance of the classic complete
correspond to areas with a high frequency of molar mole. lt must be mentioned that a complete mole
pregnancy 'n'. Dietary factors such as carotene may coexist with a normal fetus as a twin pregnancy
therefore partly explain the regional variations in the (T)ay
incidence of molar pregnancy. On histological examination the complete mole

The risk of complete or partial mole appears to be shows hydropic swelling of chorionic villi, often
increased in women with spontaneous abortion. completely surrounded by hyperplastic trophoblast
After.one spontaneous abortion the risk of complete (both cytotrophoblast and syncitiotrophoblast) and
or partial mole is three and two times higher, with nuclear pleomorphism more intense than in
respectively, than the risk in the absence of a previous normal pregnancy. There have been no significant
abortion "o). lt has been reported that after two morphological differences observed between )fi and
spontaneous abortions the risk of a complete mole is XY complete moles. Ultrasound imaging shows an
increased by a factor of 32(") . enlarged uterus with cystic structures but no fetus.
672
rI
i
i
r Gestationa I Trophob I astic Drsease
i
i
rt I
Serum and urine hCG levels are usually significantly be triploid "o'. Some may have tetraploid karyotype.
I elevated, which can lead hyBeremesis,to The resulting embryo is viable for weeks and thus
r
hyperthyroidism or symptoms of,,sq!@mpsia. embryonic tissues or fetal parts are present (in
r'.- Ovaria n theca I utei n cysts presenf*e.fud addition to hydropic villi), unlike in complete moles.
r a re 3O %
of cases.e' ln fetuses identified with partial moles, there are
r generally stigmata of triploidy, including multiple
f
Approxi mat ely L5-20% of wonren urffi' a:eoniplete congenital anomalies and growth restriction.
f, i
mole develop a trophoblastic malignancy.
ri
Histologically, villous oedema involves only some
t'
Partialmole villi and trophoblastic proliferation is focal and slight.
i Partial moles have a triploid karyotype (69XXY or The chorionic villi have characteristically marked
{ 69XYn. They result from fertilizatlon of an egg scalloping and prominent stromal trophoblastic
I
(which has retained its chromosome complement) by
t,
inclusions, and implantation site trophoblast may
r two sperms, one bearing 23X and the other 23Y. exhibitonly mild focal atypia.
I About 90-93"/" of partial moles have been reported to
r
Table I Clinical and pathological characteristics of partial mole and hydatidiform (complete) mole.
t
I
I
r
{
i
rI
> 25% t may be positive in very
{
( ' may be absent or may not be appreciabte in early hydatidiform mole2
r rare cases
i
I
I
a
m issed abortionembryon icffeta I
1
Symptoms vaginal bleedingabsence of an embrp/fetus
Ir malformations
!
a
(
l Macroscopy individual vesicles, large placenta grossly evident hydropic villi, villous vesicles
I
yes, with/without malformations absent

I
I
t
r
I
Microscopy
Stromal edema pronounced, diffuse
r
viili all/many villil
I
I Trophoblastic
severe, possibly ci rcu mferential
hyperplasia
f
t
I
Trophoblastic atypia
673
i
positivd negative3 i
a
,"'-'-j
usually triploid, diploid (usually 46,XX), for the most part uniparental;
biparental paternally derived
usually normal usually enlarged
occasional placental
Ultrasonography
: -"-.:
9y:l:
!l
,1
Ovarian theca lutein

U nusual
hCG level not usually elevated usual ly significantly elevated

I
lPersistent
L____
GTD lrare (O.02-57")
Both complete and partial moles are therefore Non-villous Gestational Trophoblastic Disease
characterized by an excessive amount of paternal Placental site nodules (PSN)
chromosomes. lt is generally acknowledged that Placental site nodules and placental site plaque
complete moles occur more frequently than partial present as nodular or plaque-like lesions of the
moles in a ratio of 311. However, lower ratios of 1:1 intermediate trophoblast; they are usually found
and 1.2:1 have been reported from Nigeria and incidentally in curettage material or hysterectomy
Tu n isia respectively
(o'u).
specimens. ln around 50 % of cases, PSN are
(')
associated with dysfunctional bleeding
lnvasive mole
This is defined as a cellular mole that penetrates and Exaggerated placenta I site (EPS)
may even perforate the uterine wall. There is invasion ln the older literature, exaggerated placental site is
of the myometrium by well-developed embryonic also referred to as syncytial endometritis. EPS is
villi, accompanied by proliferation of both cyto-and described as a hyperproliferation of the intermediate
syncitiotrophoblast. The tumour is locally destructive trophoblast around the placental implantation site.
and may perforate the uterus and invade parametrial The prevalence of EPS in miscarriages in the 1st
e)
tissues and adjacent organs. Hydropic villi may trimester of pregnancy is reported to be 1.6 % EPS
embolise to distant sites such as the lungs and the is usually found incidentally and can occur after
brain but do not grow in these organs as metastases, birth, miscarriage, abortion or in the context of
and rhay regress. Swellingof thevilli is lessoften seen extrauterine pregnancy
in deeply implanted invasive moles.
Placental Site Trophoblastic Tumour (PSTT)
It is always associated with persistently elevated This is a very rare tumour characterised by the
HCG levels and varying degrees of luteinisation of the
presence of proliferating trophoblastic tissue deeply
ovaries. invading the myometrium and is composed largely of
674
rI
i
I G estati o n a I Trop h ob I a sti c Drsease
rI
I
t
r intermediate (nonvillous) trophoblast. lt may occur Like PSTL ETT responds poorly to chemotherapy.
I anytime after a pregnancy, even years later. lt The goal of treatment must therefore be complete
r produces low levels of HCG relative &'iE mass but surgicalremoval.
r..- a bu nd a nt h u ma n pl acenta I actogen tt'lPEErrTtrough
I
! locally invasive, many are self-limitif@t to Choriocarcinoma

Y
( This is a malignant neoplasm in which differentiation
cure by hysterectomy. Malignant lmri*ri$'fmrc been
r towards villous cytotrophoblast and
reported a nd these a re ch a racterised' by.*r E$s, tt$totic
r index, extreme cel|ularity, extensive necrosis., stong syncitiotrophoblast occurs. lt does not contain
I HCG reactivity and distant spread. Histologlcalty, it is chorionic villi but is composed of sheets of both
characterised by sheets of intermediate trophoblast anaplastic cytotrophoblasts and
i cells that insinuate between myometrial muscle syncytiotrophoblasts. While it is most commonly
r preceded by a molar pregnancy, it may develop after
r
i
bundles, splitting them. There are no chorionic villi.
any gestational event: normal pregnancy, stillbirth,
I Absence of cytotrophoblasts, and low production of
HCG distinguish it from choriocarcinoma. Most cases abortion, ectopic pregnancy. lncidence after molar
pregnancy is about a thousand times greater thari
i
appear after miscarriage or unremarkable pregnancy.
r Only 5-8 % of patients with PSTT have a history of after a normal pregnancy. The immediate antecedent
hydatidiform mole, in sharp contrast to pregnancy may not necessarily be the origin of the
choriocarcinoma which, in more than 50 % of cases, tumour. Choriocarcinoma metastasises readily, and
rI is preceded by hydatidiform mole. The mean interval may spread locally to the cervix and vagina. Distant
(' between PSTT and antecedent pregnancy is 3 years metastases occur to the lungsr liver and brain.
I
!
but can be as much as 18 years '') Lymph nodes are rarely involved. "o'.
I
i
i Epitheloid trophoblastic tumor (ETT) .
Molecular pathogenesis
ETT accounts for only 7.4% o't all GTD, it is a rare but Several studies have been conducted to examine the
distinct gestational trophoblastic entity derived from role of various growth factors and oncogenes in the
I
I
intermediate trophoblastic cells. lt a neoplasm molecular pathogenesis of gestational trophoblastic
a
r- composed of chorionic-type intermediate tropho- disease. For example, Ki-67, proliferating cell
{
I
blasts . Histologically ETT is a well-circumscribed nuclear antigen (PCNA), and p53 immunoreactivity,
I and silver-staining nucleolar organizer regions have
lesion with a pushing border and presents as a
!
I monomorphic population of mononuclear been found to be significantly higher in gestational
f
I
trophoblastic cells with abundant eosinophilic trophoblastic disease than in spontaneous abortion
ti with hydropic changes, though none of the three
cytoplasm and geographic necrosis with eosinophilic
i* parameters could reliably discriminate between
I hyalinized material. ETT usually occurs in women of ('u''u).
i
reproductive age. The antecedent pregnancy is gestationa I trophoblastic d isease su bgrou ps
t unremarkable in 67 % of patients, and the interval to
a Expression of c-erbB-2 and p53 gene products has
j the antecedent pregnancy ranged from 1 to 18 years.
been found to be significantly increased and expres-
1: Common symptoms include dysfunctional bleeding
sion of nm23 and c-ras products remarkably
with indications of tumorgrowth and enlarged uterus.
-. decreased in complete hydatidiform moles that
Serum hCG levels are almost always slightly elevated
progressed into postmolar tumor compared with
(< 2500 lU/l). Based on their analysis of the litera-
those that remitted spontaneously after evacuation.
ture, Zhang et al. found that in 26158 cases ETT was
There was no significant difference in the expression
located in the lower uterine segment or endocervix .
ln 6 cases reported in the literature, ETT was initially
of the f ou r genes in invasive mole a nd in
choriocarcinoma. The altered expression of c-ras, c-
misdiagnosed as a squamous cell carcinoma. Up to
erbB-2, nm23, and p53 gene products may be
40% of patients with ETT present with extrauterine
important in the pathogenesis of gestational
spread at diagnosis. These cases generally have a
trophoblastic tumor. lndeed, decreased expression of
malignant course with a high mortality rate and the
nm23 protein and increased expression of c-erbB-2
lungs are the most common site of metastasis from
protein are strong predictors for the malignant
ETT )
transformation of complete mole "". The presence of
675
telomerase activity in complete hydatidiform moles is Patients with complete mole and excessive uterine
associated with the development of persistent enlargement and high hCG values are at increased
gestational trophoblastic tumors, such as- invasive risk for the complications of hyperemesis, theca-
(18).
moles and choriocarcinoma lutein cysts, pre-eclampsia, hyperthyroidism, and
respiratory insufficiency. The cause of respiratory
Genomic imprinting is believed to play a piuohl rote insufficiency, which may occur in about 2"/o ot
in the pathogenesis of hydatidiform moles, afthough patients, is usually multifactorial, including
its precise role and mechanism remain poorly trophoblastic embolization as well as the
u nderstood. Ma I igna nt tra nsformation i n gestationa I cardiopulmonary effects of pre-eclampsia,
trophoblastic tumours, as in other human cancers, is hyperthyroidism, and vigorous intravenous fluid
likely to be a multistep process that involves multiple thera py. With appropriate ca rd iorespi ratory su pport
genetic alterations including activation of oncogenes
respiratory insufficiency usually resolves within
and inactivation of tumour suppressor genes. ln aboutT2 hours.
addition to the expression of telomerase activity,
altered expression of cell-cell adhesion molecules ln recent times, especially in developed countries,
and abnormal expression of matrix through the use of sensitive and accurate tests for
metalloproteinases have also been reported in GTD. HCG and routine ultrasound scanning performed in
These represent disruption of the delicate balance early pregnancy, most complete moles are diagnosed
and regulation of cellular processes including much earlier (during the first trimester) before the
proliferation, differentiation, apoptosis and invasion. classical presentation occurs. The incidences of
(19)
hyperemesis, excessive uterine enlargement,
anaemia and pre-eclampsia in molar pregnancy have
Presentation, diagnosis and management of molar a I I fa I len considera bly i n such ci rcu msta nces.
pregnancy
Complete Mole hrtialmole
ln the classical presentation of complete molar Women with partiat molar pregnancy do not have the
pregnancy intermittent vaginal bleeding (bright red or dramatic clinicalfeatures seen with complete moles.
brownish) is the most common presentingsymptom, They usually present with signs and symptoms of
occurring in 97% of patients. Vesicles may be missed or incomplete abortion. Excessive uterine
passed. Excessive vomiting (hyperemesis enlargement has been reported in only 4-LlT" ot
gravidarum) is reported to occur in 20-26"/" of cases. patients, while pre-eclampsia occurs in l-4"/o Qot.
Variable degrees of anaemia may be found, depend- Hyperemesis, hyperthyroidism, large theca-lutein
ing on the extent of blood loss. Pre-eclampsia may ovarian cysts and respiratory insufficiency are
occur in about 10%, though eclampsia is uncom- uncommon and pre-eclampsia has been reported in
mon. Signs of hyperthyroidism - tachycardia, only about 3%. While the ultrasound diagnosis of a
tremors, warm skin, occur in about 7"/" of cases. complete mole is often reliable, the diagnosis of a
Thyroid storm may develop at the time of evacuation partial molar pregnancy is more complex. Thefinding
of molar pregnancy in patients in whom of multiple cystic spaces in the placenta is suggestive
hyperthyroidism has not been treated. The uterus of a partial molar pregnsrc!; s combination of this
may be larger than expected for gestational age in up with an increase in the transverse diameter of the
to 50% of cases; in others it may be of appropriate gestational sac has a positive predictive value in
size or even small for gestational age. The uterus has diagnosing a partial mole of about 90 percent ''o'. The
a doughy feel. Theca lutein ovarian cysts are present diagnosis is confirmed usually after histological
in about 20-46"/" of cases. Patients may complain of review of curettage specimens. lt must be mentioned
pressure or pelvic pain. Because of the increased that a substantial number of cases of molar preg-
ovarian size, there is a risk of torsion. The cysts nancy (complete and partial) may present as missed
spontaneously regress afterthe mole is evacuated. misc arriagel anembryonic pregnancy
Ultrasound scan shows the typical snow-storm sonographically, highlighting the importance of
appearance of complete mole and the theca-lutein histological examination to diagnose gestational
cysts ofthe ovaries. (").
trophoblastic d isease
676
r
t
Gestati on a I Trophob I a sti c Dlsease
i
r
I
{
I
I
When a molar pregnancy is diagnosed, the patient pregnancies needing chemotherapy is low (0'5%)
r' (€4)-.
I should be evaluated for possible medical complica-
r tions such as anemia, pre-eclampsia'''electtt;yt' ln situations in which the patient wishes surgical
rlr- i m ba la nce a nd hyperthyroid ism. I nvestlg$*oms
that sterilisation, hysterectomy has been performed as
r primary treatment for the mole, with conservation of
may be performed include:
;'t . Quantitative serum beta-HCG the ovaries. Hysterectomy does not guarantee
i
I . Full blood count, including plateletsount removal of all trophoblastic elements and neither
r . Coagulation studies to exclude the danelop does it prevent metastases, although it does reduce
t ment of a coaguloPathY the risk of persistence. lf hysterectomy is indicated
i
( . Liverfunction tests for a woman who has completed childbearing, it is
. Blood urea and electrolytes and creatinine probably best performed after the mole has been
i
. Blood group, rhesusfactorand crossmatching evacuated by other means.
. Thyroid function tests
. Chest x-ra!: oflc€ a
molar pregnancy is Because trophoblastic cells express the Rh D factor'
diagnosed, a baseline chest film should be patients who are RhD-negative should receive'
taken. appropriate doses of anti-Rh D immunoglobulin after
evacuation.
Medical complications, if present, must be dealt with
I and the patient stabilised before definitive treatment, Hydatidiform mole coexisting with a normal twin
which is evacuation of the uterus, is carried out. The felus
r goal of treatment for hydatidiform mole is complete The phenomenon of a twin pregnancy consisting of a
evacuation of all trophoblastic material from the mole and a viable fetus is very well recognised'
i
: uterine cavity. Where the mole is a partial one the pregnancy should
I
be allowed to proceed. ln situations of a complete
Suction curettage under ultrasound guidance is the mole co-existing with a fetus the presenting symp-
method of choice of evacuation for complete molar toms are similar to those in patients with a singleton
pregnancies. Because of the lack of fetal parts a t'u'. The former, however, are at
complete mole
suction catheter, up to a maximum of 12mm, is increased risk for hemorrhage and medical compli-
adequate for the evacuation of all complete molar cations, as well as the development of persistent
pregnancies.However , there is no consensus on the gestational trophoblastic tumor. The risk of malig-
effect of using oxytocics on the prognosis and risk of nancy, and hence the need for chemotherapy, is the
developing gestationat trophoblastic neoplasia. same whether the pregnancy is terminated (sponta-
Whilst some authors found no increased risk using neously or therapeutically), or allowed to go to term
prostaglandins for cervical priming, others found an t26'27'2at.
Therefore the pregnancy may be allowed to
association between medical induction using proceed after appropriate counselling provided that
oxytocin and increased risk of subsequent GTN and severe maternal complications are controlled and
chemotherapy use.(2)lt is advisable to avoid as much fetal karyotype and development are normal' lt must
as possible medical termination of complete molar be mentioned that these pregnancies are associated
pregnancies, including cervical preparation prior to
tzz'ze).
with a reduced live birth rateof 25-4Oo1t3'26'ztt'
suction evacuation 1y6"n suction evacuation is
thought to be complete, careful sharp curettage is Follow-up after molar Pregnancy
performed to remove any residual tissue. Sharp ln view of the risk of persistent trophoblastic tumour
curettage is also indicated after spontaneous evacua- (PTT) following the termination of a molar pregnancy
tion of the mole to ensure that the uterus is empty and it is imperative to follow these patients up with
to obtain tissue for histological examination quantitative determinations of human chorionic
ln partial molar pregnancies where the size of the gonadotrophin (hCG) levels. This may be done on
fetal parts deters the use of suction curettage, serum or urine. One follow-up scheme involves
medical termination can be used' ln such situations Weekly monitoring of hCG levels after curettage to
l
the women may be at increased risk for requiring treat hydatidiform mole. Once hCG levels are found
treatment for persistent trophoblastic disease to be negative (i.e., at least two consecutive hCG
although the risk for women with partial molar
677
measurements are under the detection level of the 40-57% ''o'. Older patients and those with repeated
respective assay), monthly monitoring of hCG levels molar pregnancies also have increased risk. pTT has
should be continued for at least 6 morEhs after been reported in 33% and 37% of patients over 40
curettage.. However in resource limitnrcFfrlfrmrs, years of age 'to't"and in b6% of those over 50 years
serum hCG level estimation can be Oorgffits (32),
until hCG becomes undetectable (Etgrrsgrr,

5mlU/ml). This usually occurs within 9.:I1,iWt$e; The indications for intervention with chemotherapy
post-evacuation. Subsequenfly, monthly r#ine hgc include:
assays are performed tillthey have remained norrmal . High levels of hCG (serum>2O,0OO
for six months. Another scheme involves urine hCG iullitre,urine >30,000iu/24 hours) more
assay fortnightly until it is normal. Subsequenily, than 4 weeks post-evacuation
urine hCG titres are determined every month tillthey . Persisting uterine haemorrhage
have been normal for six months. lt should be . Progressively increasing hCG values at any
recognised that urine hCG assays are less sensitive time post-evacuation
and have a lower level of detection of 25 mlU/ml as
. Any detectable level of hCG not showing a
against 5 ml U/ml for serum. trend towards extinction 4 to 6 months post_
evacuation
Patients must be advised to use effective contracep_ . Choriocarcinoma on histdlogy
tion during the whole of the follow-up period Oral . At any level of hCG, evidence of metastases.
contraceptives should be used during this period. lf
The issue of the use of prophylactic chemotherapy at
hCG levels of up to 1S0O lU/l persist, re-curettage of
the time of evacuation of a complete mole is contro-
trophoblastic tissue which has remained in utero may
versial. There have been several reports indicating
be indicated and could avoid the necessity for
that prophylactic chemotherapy reduces the inci_
chemotherapy in some patients. An IUCD is best
dence of PTT. ln patients with high risk complete
avoided till the hCG levels are normal, in view of the
moles the incidence of PTT has been reduced from
risk of uterine perforation if an invasive mole is
present.
40-47%to 77-14% with chemoprophylaxis (33,34). lt
must be noted, however, that there can be serious
With the completion of follow-up the patient may side effects with the use of the chemotherapeutic
decide to conceive at any time. ln view of the agents and that persistent disease, should it develop,
increased risk of a repeat molar pregnancy efforts may be chemoresistant. Moreover, most moles will
must be made, when the woman becomes pregnant, be cured by suction curettage, and patients requiring
to establish as early as possible whether the chemotherapy for PTT will be identified by follow_up
preg_
nancy is normal or not by USS. Afterthe conclusion of hCG determinations. Routine chemoprophylaxis may
any future pregnancy, whatever the gestation, hCG therefore not be justified. lt has been suggested,
assays should be determined at three weeks and however, that chemoprophylaxis may be considered
three months, since a few patients may present with in patients with high risk complete moles particularly
ch o rioca rci no ma fol lowi n g f u rther pregna ncies.
if hormonal testing is unavailable or follow-up is
unreliable'0.
About 75-20% of patients followed up will develop
persistent trophoblastic tumour (pTT) and will Persistent Trophoblastic Tumour (pTT)
therefore require chemotherapy. The risk of requiring Persistent trophoblastic tumour may follow molar
pregnancy or much less commonly a non_molar
chemotherapy, however, is much greater for com_
plete (15-29%) as compared with partial moles (0.5_
pregnancy. The diagnosis is based on symptoms of
4%).The risk is also increased in patients with signs irregular vaginal bleeding, uterine subinvolution
(sometimes with irregular contour), ovarian theca
indicative of markedly excessive trophoblastic groMh
lutein cysts, rising hCG levels or a plateau in the level
- very high hCG levels, excessive uterine enlarge- persisting for more than three weeks, and other
ment, and the presence"of ovarian theca lutein cysts.
Such patients are considered to have high-risk moles,
clinical and radiological findings, depending on the
extent of involvement of various organs in metastatic
with incidence of persistent trophoblastic disease of
disease. Often it is not possible to obtain tissue for a
678
Gestati o n a I Tro p ho b I a sti c Drsease
precise histopathological diagnosis but this should metastases there may be asymptomatic lesions on
not hamper diagnosis and treatment on clinical and chest x-ray, pleuritic chest pain (due to pleural
other grounds. involvement or to pulmonary infarction by tumour
r emboli), cough, dyspnoea, haemoptysis or signs of
I -ii:..;:J:l :li pul monary hypertension.
lnvasive mole
This is usually seen in the early me"rths fuflowing Headaches may arise as resu a of raised lt
evacuation of a hydatidiform mole. T'he.lesion is intracranial pressure or cerebral haemorrhage. Loss
characterized by molar chorionic'villi within the of consciousness or other neurological deficits may
myometrium or its vascular spaces. Except under occur from cerebral haemorrhage or infarction.
unusual circumstances when curettings contain Gastrointestinal haemorrhage, haematuria,
- myometrium with invasive molar villi, the diagnosis hepatomegaly and hepatic rupture may all be
of an invasive mole can only be made on a'hysterec- presenting features. Lymph node involvement,
tomy specimen. ln some situations invasive mole however, is very rare.
may penetrate through the myometrium and cause
intraperitoneal haemorrhage and/or extension to Choriocarcinoma may mimic other diseases'
; Patients with extensive extragenital involvement may
adjacent organs.
have minimal or no gynaecological symptoms. Thus,
Choriocarcinoma the diagnosis should be considered in any woman of
This tumour can occur after normal pregnancy, reproductive age with unexplained systemic symp-
stillbirth, abortion, ectopic pregnancy, complete or toms.
partial mole, or possibly arise "de novo" as a germ cell
tumour. The tumor is characterized by masses and P I acenta I site tro phoblasti c tu mo u r ( P STf).
sheets of cells that invade surrounding tissue and This tumour may present with amenorrhoea or
permeate vascular spaces. lt tends to grow in an irregular vaginal bleeding months or even years after
expansive, centrifugal fashion, often accompanied by a normal pregnancy, an abortion or, rarely, a
marked central hemorrhage and necrosis, with viable hydatidiform mole. The uterus is enlarged and
tumor limited to the interface with surrounding although HCG levels may be raised they are low
normal tissues. Bulky necrotic tumour may become relative to their mass and are seldom as high as may
the focus for uterine infection, leading to pelvic pain occur in choriocarcinom.a. Human placental
and purulent discharge. The tumour may erode into lactogen (HPL) levels may be raised; indeed HPL is a
uterine vessels, leadjng to vaginal haemorrhage, or useful immunohistochemical marker for the tumour.
may perforate through the myometrium, causing Curettage may yield decidua or myometrium
I intraperitoneal haemorrhage. Choriocarcinoma is infiltrated by trophoblastic cells with dense
i highly vascular and easily tends to bleed heavily; eosinophilic cytoplasm and pleomorphic nuclei'
r
, biopsy of lesions must therefore be avoided as much PSTT has very much less tendency towards vascular
(.
as possible. invasion and very low potential for metatstases;
however, distant metastases can occur to the
t,
ln addition to the gynaecological symptoms men- peritoneum, liver, pancreas, lungs and brain. ln
tioned above, other symptoms and signs may be some cases the tumour has been associated with
present depending on sites of metastases. The most nephrotic syndrome which has resolved after
common sites of metastases, in decreasing order of eradication of the tumour. Placental site
incidence, are the lungs, vagina, pelvis, liver and the trophoblastic tumour is relatively insensitive to
brain. Liver or brain involvement occurs more chemotherapy and therefore treatment of patients
commonly in patients with preceding non-molar with disease confined to the uterus is mainly surgical
pregnancies that have a prolonged delay in diagnosis. -hysterectomy. For those with unresectable tumors,
Almost all patients with hepatic or cerebral involve- combination chemotherapy produces variable
ment have in addition pulmonary andlor vaginal clinical outcomes, with only a few achieving com-
involvement. Abnormal vaginal bleeding may arise plete response. ln a report on a series of thirty-four
from vaginal or cervical metastases. With lung cases treated over a period of twenty-five years in
679
England, risk factors for death included lung meta- Stage !: Disease confined to the uterus
static involvement (50%) and an antecedent preg- lA: With no riskfactors IB: With one riskfactor
nancy interval of four years or more (100%). On the lC: With two riskfactors
other hand, those with no extrapelvic disease or a Stage !l: GTT extends outside of the uterus but is
pregnancy interval of less than four years had LOO"/. limited to the genital structures (ovar5 tube,
survival. Surgery alone was curative in two-thirds of vagina, broad ligament)
patients with disease limited tothe uterus(3u). llA: With no risk factors llB: With one risk
factorllC: With two riskfactors
Management of Persistent Trophoblastic Tumour Stage lll: GTT extends to the lungs, with or without
ln addition to the investigations mentioned under known genita I tract involvement
management of molar
pregnancy, other tests are IllA: With no risk factors lllB: With one risk
necessary to determine the extent of the disease. factor lllC: With two riskfactors
Ultrasound scan of the pelvis and abdomen are Stage lV: Disease involving all other metastatic
essential; CT scan of the chest and the head are sites
helpful. Measurement of HCG levels in cerebrospinal IVA: With no risk factors IVB: With one risk
fluid, in appropriate cases, may be useful in the factor IVC: With two riskfactors
detection of asym ptomatic cerebra I i nvolvement.
Risk factors affecting staging include the following:
For the purposes of effective treatment
it is essential t hCG > 100,000lUll4hoururine
to stage the disease as well as determine the 2 The detection of disease more than 6 months
woman's risk status. Staging is done according to the from termination of the antecedent pregnancy.
FIGO system (Table 2); the prognostic risk scoring
The following factors should be considered and
system was proposed by the World Health Organisa-
noted in reporting:
tion and reliably assesses the potential for resistance
to chemotherapy in the particular patient
1 Prior chemotherapy for known gestational
trophoblastic tumor.
Table 2: FIGO Staging of Gestationa! Trophoblastic
2 Placental site tumors should be reported
separately
Tumours
Table 3:
scoring system for Assessing Resistance to chemotherapy
LET US USE THE TABLE FROM LAST EDITION OF THE TEXTBOOK, BECAUSE THIS
ONE IS BADLY
FORMATTED ESPECIALLY THE MATERIALS IN THE COLUMNS!
Prognostic factor Score

0 I 2 4
Age (yrs)
Antecedent pregnancy
lnterval (months)
HCG (IU/L)
ABO group (female, <39 >39 Abortion 45 >12
103104 O, A or Term7l2104105 B,
male) Largest tumour, Mole <4 AB >5 Gastrointestinal >105
including uterine tumour, A, O 35 Spleen, Brain >8
<103 tract, Liver 48 I drug
(cm) Metastases: Kidneys 13 >2 drugs
Site
Number identified
Prior chemotheraov
580
r
t
I
i.
r
I
Gestati on a I Trop h o b Ia sti c Drsease
i-
f
rI The "lnterval" is the time between the end of the antecedent pregnancy and the commencement of
t
chemotherapy.
r
( The total score is calculated by adding the individual scores for the prognostic factors. A total of
,-
r
rI Table 4: Single Agent Treatment negiffrdns
{
r A. Methotrexate Treatments
I 1 . Methotrexate-Folinic acid (MTX-FA)
1
{ MTX 1.0 mg/kg lM on days 1, 3, 5, andT FA 0.1 mdkg lM or PO on days 2,4,6, and 8
2. S-day Methotrexate MTX 0.4 m{kgld lV or lM daily for 5 days
I
-
r B. Actinomycin D Treatment
\
Actinomycin-D 12 pgkgld lV for 5 days

I
i
i
!'
Other regimens include "pulse" Methotrexate (MTX treated with combi nation chemotherapy.
t 50 mg/m' lM weekly) and "pulse" Actinomycin-D
I (Actinomycin-D 1.25 mg/m'lV every two weeks) Regimens includea combination of methotrexate,
:
,l- actinomycin-D and cyclophosphamide (MAC) or
I
( Courses of treatment may be separated by an interval etoposide, methotrexate, actinomycin-D,
of 6 to 7 days. After HCG levels have fallen to normal cyclophosphamide and oncovin (vincristine) (EMA-
r 2-3 more courses of treatment are given. About 5% CO) Oable 5). lf the disease is resistant to both
I
r
("
need to change regimen for problems of toxicity and single-agent and combination chemotherapy local
t
I
up lo 20% may become resistant and require further uterine resection may be considered, in which case
: treatment. lt is important, during treatment, to look appropriate imaging techniques must be used to
f for evidence of developing resistance, usually identify the site of resistant tumour in the uterus.
I
I suggested by plateauing of HCG levels. Patients with Survival in stage 1 disease is almost 7OO%.
i-
I resistance to single-agent chemotherapy must be
i
:
ldble 5: lhe LMA-CO me
t
Day Etoposide tOOmglm2 by lV infusion in 200 mL of saline over 30 min ActinomycinD 0.5 mg IV
1 stat MethotrexatelO0 mglmZlV stat Methotrexate 200 mg/m2 by lV infusion over 12 hours
r
Day Etoposide 100 mg/m2 by lV infusion in 200 mL of saline over 30 min ActinomycinD 0.5 mg lV
2 stat Folinic acid 15 mg lM or orally every 12 h for 4 doses beginning24 hours after starting
: methotrexate
;
Day Cyclophosphamide 600 m{m2lV in saline Oncovin (Vincristine)7.O mglm2lV stat
8
Treatment in such cases depends on the WHO risk Patients with WHO risk score 8 and above (high-risk
i score. Patients with low or moderate risk (score 7 or metastatic disease) are managed with primary
I less) stage ll and stage lll (low-risk metastatic) combination chemotherapy using EMA-CO.
a
i
disease are treated with primary single-agent
chemotherapy, using either methotrexate or ln situations of resistance to EMA-CO, patients may
actinomycin-D. Complete remission has been be treated by a modification of the regimen in which
reported in 85%-90% of patients so treated eo). cisplatin and etoposide are substituted for oncovin
I Disease resistant to single-agent chemotherapy is and cyclophosphamide on'day 8, and the dose of
treated with EMA-CO (Table 5). methotrexate infusion increased to 1 gm/m'(EMA-
CE) as shown in Table 6 below.
581
Comprehenst:ie Gynaecology in the Topics
Table 6: The EMA-CE Regime
Day Etoposide IOO mglm2 by lV infusion in 200 ml of saline over 30 min Act-D 0.5 mg lV stat
1 Methotrexate 100 mglm2lV stat !flh*fllotrexate 1,000 m{m2 by lV infusion over 12 h
Day Etoposide7oom{m2bylVinfusionin200mIofsaline@stat
2 Folinic acid 30 mg lM or orally every 12 h for 6 dmes beginning32 h after starting
methotrexate
Day Cisplatin60mglm2lVwithprehydrationEtoposide100
8 30 min
saline over
Other forms of surgical intervention may be Follow-up

necessary in the management of stdge ll and lll Patients with stage l, ll or lll disease have weekly
disease. For example, hysterectomy may be beta-HCG measu rements u nti I u ndetecta ble for three
necessary to control uterine sepsis or haemorrhage, weeks, followed by monthly measurements until
or to reduce the tumour burden and thereby reduce levels have been undetectable for twelve months. As
the need for chemotherapy. Ligation of the far as patients with stage lV disease are concerned,
hypogastric arteries may be necessary to control monthly measurements continue till levels have been
profuse bleeding from vaginal metastases and undetectable for twenty-four months, due to the
thoracotomy may be needed to excise resistant greater risk of late relapse. lt is essential that during
tumour. the entire period of follow-up patients are
encouraged to use effective contraception.
Stage !V
Patients with this stage of disease are treated with
Sequelae
primary combination chemotherapy with EMA-CO. ln general, fertility seems to be well preserved in
Where there are cerebral metastases the dosage of women after chemotherapy for trophoblastic
the methotrexate infusion is increased to 1 gm/m'zand tumours. About 86% of those who wished to become
may be alternated weekly with intrathecal pregnant were reported to have had one or more
methotrexate 10-12.5 mg. Patients with disease (tu).
births There is no increased risk of spontaneous
resistant to EMA-CO can be treated with EMA-CE. abortion, congenital anomalies or the need for
caesarean section. Those who receive three or more
Radiation therapy and surgery may be used as
drugs are less likely to conceive than those who
required. Whole-brain irradiation may be receive only methotrexate.
administered simultaneously with the initiation of
systemic chemotherapy to patients with cerebral There is increased risk of secondary cancers, such as
metastases. This may reduce the risk of cerebral leukaemia, colon cancer, melanoma and breast
haemorrhage since it has both a haemostatic and cancer in women who have been treated with
tumouricidal effect. Surgery is performed to either chemothera py for gestationa I trophoblastic d isease.
treat complications of the disease or excise sites of This has been attributed to the inclusion of etoposide
resistant tumour. Hepatic resection may be required in the therapeutic regimen. €o)
to manage hepatic rupture; craniotomy may be

necessary for acute decompression or to control DISCUSSIONS AN D CONTROVERSI ES
haemorrhage. Pulmonary lobectomy or partial lobe
resections may be performed. Ultrasound, CI MRI l. Definition and Classification
and radioisotope-labeled antibody (to HCG) scan all This is a subject that has undergone multiple
have a place in the search for residual disease. modifications. The term Gestational Trophoblastic
Neoplasia was adopted to replace older
The outcome for women presenting with hepatic terminologies such as chorioadenoma destruens,
metastases from GTD is poor with an even worse metastasizing mole and choriocarcinoma which
prognosis if cerebral metastases are also present. were pathologic diagnosis which did not capture the
spectrum of the disease entity. However this tended
682
-------- .------t
G e stati on a I Tro p h o b I a st i c Drsease
to define only hydatidiform mole as gestational commercial assay kits do not measure these portions
trophoblastic disease and did not clarify the , false low values may result in inappropriate
confusion therein '"' The classification adopted in management. lt is also necessary to recognize the
this chapter mirrors the clinical and rnorphological possibility of Phantom hCG which gives a false
characteristics as proposed in the DGGG, OEGGG positive hCG even when there is no GTD. Thisoccurs
(''
and SGGG guidelines because the serum of these patients contains
heterophillic antibodies which react with the
ll.lncidence antibodies in certain assay kits(t')
One of the authors has observed a significant
reduction in the incidence of gestational lV. Prophylactic Chemotherapy and molar
trophoblastic neoplasia in the sub-region over the pregnancy
past 30-40 years. Whether this can be attributed an The place of prophylactic chemotherapy has been
improved management of molar pregnancies or some highlighted in the section on treatment of complete
other intrinsic factors is yetto be researched. mole. Much as it might sound attractive, to prevent
disease persistence and progression with
!ll. Tumour marker and management outcomes prophylactic chemotherapy, the complications
A reliable assay for total hCG is central to the attributable to the drugs and more especially the
management of GTD. Such an assay must measure evolution of drug resistant disease recommend that
all portions of the hCG molecule particularly free beta routine prophylactic chemotherapy should be
subunit, hyperglycosylated hCG (hCG-H), nicked avoided except in areas where post treatment
hCG and hCG missing the terminal carboxyl segment monitoring with hCG cannot be assured.
which are commoner in neoplasia.Since several
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26. Evans A C Jr, Soper J \
Hammond C B. Ctinical
features of molar pregnancies and gestational
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2002;23: 20-31 in hydatidiform mole. Chin Med J (EnSl) 1980;
24. Berkowitz R.S, Goldstein D.P Chorionic tumours. 93: 605-612
New England Journal of Medicine L996; 31. Tow W.S.H. The influence of ihe primary
335:1740-1748 treatment of hydatidiform mole on its subsequent
21. Sebire NJ, Rees H, Paradinas E Seckl M, course J Obstet Gynaecol Br Commonw 1966;
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f Gestation a I Trophob I asti c Disease
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73:545-552. l, Paradinas FJ, Rees H, Newlands ES. Twenly-
t
t. 32. Tsukamoto N, lwasaka T five years' clinical experience with placental site
r trophoblastic tumors. J Reprod Med 2002; 47:
I Kashimura M, Matsuyama T.
?
i trophobl asti c drseases in 460-464.
71
more. Gynecol Oncol L985; 36. Rustln G.J.S, Booth M, Dent J et al. Pregnancy
i,
i
33. Kim D.S, Moon H, Kim K.t after cytotoxic chemotherapy for gestational
I Effects of prophyl actic trophoblastic tumours. Br Med J L984;
k
persrstent trophobl astic 288:103-105
complete hydatidiform mole 37. Benedet JL, Pecorelli$ Ngan HYS, Hacker NF.
f
1986; 67: 690-694. Sfaging Cl assi f i cati ons a n d C I i n i ca I P ra cti ce
( 34. Goldstein D.E Berkowitz R Guidelines for Gynaecological Cancers. A
r chemotherapy of complete collaboration between FIGO and IGCS Nov. 2006
:
i
a 35. Papadopoulos AJ, Foskett M, See*l'ft ':jffi#sfl
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686
CHAPTER
t-
l.
a
i
53
t Reprod uctive Tract Ca ncers
a
in Pregnancy
a A O Omigbodun and O A Ayinde
I
I
r'
I
lntroduction The objective of this chapter is to highlight the

Cancers are rure occurrences in pregnancy, with the peculiarities of the specific reproductive tract
incidence ranging from 1 in 1000 to 1 in 10000 cancers seen in pregnancy and their principles of
pregnancies ''t. The most common cancers encoun- management.
tered in pregnancy are those that are more frequently
seen in the reproductive age group. These include CERVICAL CANCER I N PREGNANCY
cervical cancer, breast cancer, Hodgkin's lymphoma,
Cancer of the cervix is the most common gynaeco-
leukaemias and melanoma. Of all these, genital
logical malignancy globally. This is due to the
cancers are the most commonly seen in pregnancy'.
contribution of developing countries, where it is the
The gynaecological malignancy that is most prevalent
most prevalent genital cancer. Eighty percent of the
in pregnancy is cervical cancer. The frequencies of
nearly half a million new cases diagnosed annually
occurrence of the various malignant genital tumours
o: occur in these countries. ln contrast, in the devel-
associated with pregnancy are as fol lows
oped world, the tumour has now been relegated to
Cervical cancer - 85% the third position among cancers of the reproductive
Ovarian cancer - 97" tract. However, among the genital malignancies co-
Vulval cancer - 3% existing with pregnancy, cervical cancer is the most
Endometrial cancer - 7Y" common in most parts of the world. The reported
Others - 1% incidence of the tumours in pregnancy varies widely
from 1 in 2000 to 1 in 5000 pregnancies' Appraised
Genital cancers co-existing with pregnancy constitute
from another angle, 0.1 to 7.6% of all cervical
a considerable challenge to the Obstetri- cancer patients are pregnant at the time of diagnosis
cian/Gynaecologist for obvious reasons. Diagnostic 4-6.
ln many reports from the developed world,
delay is common because of confusion between cervical intraepithelial neoplasia is also prevalent
symptomatology of the lesions and the physiological among pregnant women. The cited incidence ranges
changes of pregnancy. Also, investigative options 16 and 25 per thousand pregnancies. There is
.available to the clinician are often limited when faced paucity of data on this issue from the developing
with this difficult situation. Apart from these, serious countries.
ethical, moral and religious issues are raised when-
ever the treatment of these tumours is incompatible Histological Types
I u.
with continuation of pregnancY The relative frequencies of the histological types of
cancer of the cervix diagnosed in pregnancy are
687
i-t
similar to the picture outside pregnancy. ln a study and magnetic resonance imaging (MRl) are therefor:e
conducted by Takushi et al (2OO2), 96.4% of the desirable adjuncts for accurate staging of the disease
tumours were squamous cell carcinomas while the '0. Their high resolution helps in the detection of
rema i nders were adenoca rci nomas pelvic and intra-abdominal spread. They also
evaluate the retroperitonial lymph nodes areas. MRI
Diagnosis The clinicaI presentation of cerv{ed is preferred because it is not associated with fetal
in pregnancy is basically similar to what Obtairrs in " ,':
exposure to radiation but it is not as effective at
the non-pregnant state. This largely dep€sr$r:gt.@ lymph node evaluation. ln developing countries, the
stage of the disease. However, in centres where prohibitive costs of the investigations have put them
routine speculum examination of the cervix and Pap beyond the realm of routine use. Alternatively,
smear are done at booking, presence of asymptom- abdomino-pelvic ultrasonography may be able to
atic cervical lesions and abnormal cytologr may detect liver metastasis and ureteral obstruction. lt is
arouse the suspicion of invasive cancer. There is a noteworthy that ureteric dilatation detected through
need to confirm this by colposcopy and directed abdominal ultrasound and intravenous urogram can
biopsy. But endocervical curettage is best avoided. be easily confused with the normal physiological
An obvious lesion can be biopsied without invoking change associated with pregnancy. Cystoscopy and
colposcopy. Diagnostic conisation is indicated when sigmoidoscopy may be necessary to rule out bladder
biopsy suggests microinvasive cancer in order to and rectal mucosa. Other distant metastases such as
assess the depth of invasion. This is best delayed till pulmonary and brain deposits can be excluded by
the early second trimester, when the risks to the fetus chest and skull radiographs or computerised tomog-
are lower. Cold knife conisation at this time has not raphy.
been associated with increased risks of adverse
pregnancy outcomes.t But may be associated Treatment
significant blood loss reported as high as 8.9%. As a result of relatively limited experience with
cervical cancer and other genital malignancies in
Pregnancy represents an ideal time for cervical pregnancy, universally acceptable management
cancer screening because it brings the population of algorithms are not available u. ln general, the
pregnant women into contact with health care management of a patient with genital cancer
providers and it is recommended all pregnant women discovered in pregnancy depends on its type, stage
presenting for antenatal care should have speculum and gestational age at diagnosis ". ldeally such
examination and cervical cytology at booking. Such a management should be multidisciplinary, with
practice will enable the tqmour to be diagnosed at an inputs from the gynaecological oncologists, radiation
early stage in most cases '. Takushi et al QOO2) oncologist obstetricians and the neonatologists.
reported that79% of patients with cervical cancer in Proper counselling of the patient must be done
pregnancy were diagnosed in stage I '. This is in because her wishes must be taken into consider-
contrast with the findings from South Africa, where ation.
54.8% of the cases seen in pregnancy were diag-
o
nosed at stages llB-lv but conforms to the well- Definitive therapy may be immediate or delayed,
known pattern of patients with cervical malignancies depending on the aforementioned factors. lmmedi-
in the developing world reporting late for treatment. ate treatment is favoured when diagnosis is made in
the first half of pregnancy (before 20 weeks gesta-
Further Evaluation tion) with the stage 1A1or after fetal maturity (
ln confirmed cases of cervical cancer in pregnancy, it usually 3032 weeks). This approach to management
is important to stage the tumour at examination is also when the disease is relatively advanced (Stage
under anaesthesia in order to determine the most ll and above) irrespective of the gestational age.
suitable modality of treatment. The likelihood of
clinical under-staging is high because induration of The immediate treatment approach involves termi-
the base of the broad ligament, which usually nation of pregnancy followed by definitive therapy
suggests spread beyond the cervix, is less prominent appropriate for the stage of the disease. ln cases
in pregnancy. Computerlsed tomography (CT) scan whereby the fetus is already mature, the baby is
588
t
T
Reproductive Tract Cancers in Pregnancy
i
tf
{ usually delivered by classical caesarealt section, may be allowed in patients with microinvasive (stage
r
T
although, recent evidence suggeSts, no significant
difference in the outcome between
lA,) disease. A delay as long as 25 weeks has been
reported for this stage without progression. ln this
F have vaginal delivery and those situation, after delivery of the fetus at maturity,
Y
r nally. If the disease is stage llA- simple hysterectomy or therapeutic conisation is
V
*
hysterectomy with pelvic tymp+r is adequate as treatment.
usually performed at caesarean sectisl or,at +-0
r"
? weeks postpartum. However, with rnse, advanced By and large, every case should be treated on its own
ft
I disease, delivery is followed by extenral beam merit in the absence of experimental evidence
Ii irradiation (teletherapy), which should ideally governing the management of this condition. Further
commence about a week postpartum. This should be research is needed on how to optimise the outcome
followed by brachytherapy. ln such cases, comblna- of treatment for both the mother and the baby.
I
I tion of radiotherapy with platinum-based chemother- Routine cervical cancer screening will help reduce
apy has12 been documented to improve survival the problem
I
I
With stages lA,-llA tumours diagnosed in the first half Prognosis

of pregnancy, immediate radical hysterectomy is the The five-year survival for all stages of cervical cancer
preferred mode of treatment. The procedure is diagnosed in pregnancy is not significantly different
r usually performed with the fetus rn sifu. When the from that found in non-pregnant women and is
I
F stage is higher than llA and radiotherapy has been dependent on the stage at diagnosis.
chosen as the preferred treatment modality, initial
teletherapy often induces abortion, though uterine OVARIAN CANCER !N PREGNANCYStudy
evacuation may be necessary if this fails to occur. ln
r 11%ln the first trimester of pregnancy, most ovarian
the early mid-trimester, pregnancy is preferably
masses are functional cysts and over 50 percent of
r terminated by hysterotomy. Abortion should be
them disappear with observation. Only a few are
f followed by brachytherapy.
pathological tumours '0. Most of these are benign
t. cystic tumours, mainly benign cystic teratomas
Delayed treatment is acceptable in stage lA, disease
r (dermoid cysts) and cystadenomas 'u''u. The inci-
even when diagnosed in the early first trimester or
t dence of ovarian tumours in pregnancy is 0.17-
stages IAr-18, diagnosed between 20 weeks gesta-
r
tion and fetal maturity. Fetal salvage rate is increased 0.19"/" 'u-". Malignant ovarian tumours arevery rare
r in pregnancy. Though, the accurate incidence is not
to above 80% throulh this. However, it should be
known, it is in the range of I in 5000 to 20,000
f
i
done with caution and with the patient,s full aware-
ness of the risk of progression of the disease", though pregnancies'u'"'". This represents 4-5% of ovarian
i the risk appears theoretical. ln the seriesof Japanese tumours in pregnancy compared to 75-20% in non-
pregnant women 15' 18' 20. Epithelial cancers are the
: patients with stages lAr-lBrwho had therapy delayed
7
I by 6-15 weeks, no disease progression was most frequently seen malignant ovarian tumours
; documented'. After the delivery of the fetus, appro- associated with pregnancy. Their frequencies in
i priate management for stage should be instituted. lt pregnancy are as shown in Table 1. Germ cell and
should be noted that much longer periods of delay stromal malignancies have also been reported
r
relatively often.
i
a Epithelial
Study
f Dgani et al,
Serous/
Mucinous
Borderline
35%
Undifferentiated Dysgerminomas
Granulosa
cell
5% 77%
7999 zt 30% 73%
/ Sayedur ef af
t 2OO2 ts 67% t1% 17o/"
I 71%
r
589
Diagnosis confinement at 32 weeks. There were no neonatdl

Ovarian cancers constitute a great diagnostic sequelae ". delivery should ideally be timed to avoid
challenge in pregnancy. This is because most the nadir blood counts.
pregnant women, like their non-.p@nmt
counterparts, are asymptomatic. Takaucfii ef a/ Advanced tumours require prompt and aggressive
QO02) reported that 62% of patients were management irrespective of gestational age. l
asym ptomatic wh ile 3 1 % had non-specif ic However extensive counselling of the patient is
abdominal pain. They are usually detected as important particularly in light of the relatively low
adnexal masses during clinical or ultrasound pelvic chance of long term survival for the mother.
examination particularly in early pregnancy. Termination of pregnancy at the time of surgical
Otherwise, they are incidental findings at caesarean staging and cytoreduction is usually inevitable. This
section. Ultrasonography is useful in differentiating should be followed by the appropriate cytotoxic
functional and benign cysts from likely malignant regimen. Alternatively, chemotherapy may be
ones. Multiseptate and partly solid cysts are more instituted with thefetus in situ afterthe initialstaging
likely to be malignant. Three-quarters of ovarian laparotomy and minimal cytoreduction while
cancers in pregnancy are diagnosed as stage 1", awaiting fetal viability. This is followed by
which is in contrast to the non-pregnant state where hysterectomy and further cytoreduction at caesarean
75% present as advanced stage disease. section. Additional courses of chemotherapy are
often administered after surgery. Sood et al (2001)
Treatment managed a patient with stage lllC serous
As in the case of carcinoma of the cervix, treatment of
cyadenocarcinoma diagnosed at 27 weeks gestation
ovarian cancer in pregnancy should be with exploratory laparotomy and initial debulking,
multidisciplinary. The definitive management would followed by 3 cycles of cisplatin and paclitaxel. At 37
be determined by the type, stage, gestational age at
weeks, she underwent caesarean delivery,
diagnosis and the patient's wish. A woman with abdominal hysterectomy and debulking. Several
suspected ovarian cancer in pregnancy requires additional cycles of chemotherapy were given. She
exploratory laparotomy for tissue diagnosis and was able to survive for 29 months after diagnosis
proper surgical staging of the tumour. This is while her baby's development and growth were
preferably done in the early second trimester when
normal ". Tumour markers may be more difficult to
the placenta would have taken over the function of interpret during pregnancy but they can be used for
support of the pregnancy from the corpus luteum and
follow-up (aFB LDH, BHCG).
yet the uterus is not so la'rge as to interfere with the
exploration. ldeally, intraoperative frozen section Prognosis
should be for preliminary confirmation of diagnosis Prognosis is similar to that of non-pregnant women
and determination of theextentof thesurgery. when the various ovarian tumours are considered
stage-for-stage. However, since the vast majority of
Since most ovarian cancers diagnosed in pregnancy the cancers in pregnant women are diagnosed in
are stage I disease and of low malignant potential, stage l, outcome is generally better overall than in
conservative procedures, particularly unilateral non-pregnant women.
salpingo-oophorectomy, are appropriate. This is only
a temporary measure to allow pregnancy continue till VULVAL CANCER IN PREGNANCY
after fetal viability. Caesarean delivery and optimal Vulval cancer is predominantly a disease of the
staging surgery should be performed afterwards. elderly. Although, it sometimes occurs in women
There is a progressively increasing body of evidence below the age of 40 years, it is rarely diagnosed in
in support of safety of platinum-based chemotherapy pregnancy'0. Therefore, only a few cases have been
22,23. and paclitaxel in pregnancy Otton and reported in literature. When vulval malignancy
colleagues (2001) reported a case of early-stage occurs in young women, it is frequently linked with
epithelial ovarian cancer which was treated with human papilloma virus (HPV) infection and ,,24,25.
conservative surgery at 16 weeks of gestation and immunosuppressi
subsequently had four courses of cisplatin prior to
590
Various histological types of the tumour have been colleagues (1998) reviewed 12 cases previously
reported in pregnancy. As with non-pregnant women reported in literature and described an additional
most cancers are squamous cell carcinomas, case. Most of them were well-differentiated
although rare types, including leiomyosarcoma, adenocarcinomas with minimal invasion of the
a
rhabdomyosarcoma, epitheloid sff anO myometrium. ln five of the patients, pregnancy
r
malignant myxoid sarcoma of the Bdt gland occurred in women known to have had conservative
F
have been diagnosed in pregnancy'"t0. treatment for endometrial carcinoma
: l
preconceptionally, with high doses of progestogens.

i Diagnosis The remaining cases were diagnosed for the first
I
7 The diagnosis can only be made by histological pregnancy

t'.
time in
f'
I
examination of suspicious vulval lesions. Therefore,
I
a biopsy of such lesions is mandatory irrespective The common trend is to delay management of the
r
I
pregnancyt'. tumour until after the delivery of a mature fetus 34
i
particularly asit is unlikely that an endometrial
Treatment biopsywill be done on the gravid uterus. Standard'
I
I Treatment depends on the stage of the disease. The treatment is instituted as in the non-pregnant
gestational age at diagnosis is only taken into women. One would predict the outcome is similar to
t-
consideration occasionally. The surgical treatment that in the non-gravid woman and is stage and grade
r offered rarely interferes with pregnancy. Commonly, dependent.
the tumour is treated promptly as in the non-pregnant
I
women. However, if term is close, treatment may be CONCLUS!ON
I
I delayed until the puerperium in early cases. Diagnosis of genital cancer during pregnancy is
I
I distressing for the future parents and causes serious

I Currently, mutilating surgical procedures are no dilemmas for the Obstetrician and the
I longer advocated. The inclination of most Gynaecological Oncologist. Many diagnostic and
(
I
t
gynaecological oncologists is now towards partial therapeutic approaches used outside pregnancy are
( radical vulvectomy and unilateral or bilateral groin not safe because they are known to cause fetal loss or
dissection. Wide local excision may be performed for severe birth defects, yet any delay in treatment may
diseases less than 1mm deep and also less than 2cm unacceptably worsen the maternal prognosis.
( in the maximum dimension. These have been
I
Moreover, in the absence of large randomised
t.
associated with good survival and better quality of life controlled studies, it is difficult to determine the best
I
in many cases. Extensive lesions may require a mode of management for these patients. However,
radical vulvectomy'and bilateral groin dissection.
I
the obstetrician, in close collaboration with the

Nodal positivity is an indication for radiotherapy after oncologist and the paediatrician has a major role to
t delivery of the baby ideally at maturity ". Vaginal play in deciding the most appropriate management
t
delivery may be allowed, provided the vulval wound plan for each patient, with the couple being kept fully
I
I is well healed. ln very advanced disease where informed throughout the process.
F
r prompt radiation is indicated, termination of

pregnancy may be inevitable. ln general, the management usually depends on the
i
r
type of the tumour, the stage and the gestational age.
(
ENDOMETRIAL CANCER IN PREGNANCY ln most cases, a conservative management of the
I
I cancer could be offered given that accumulated
Endometrial cancer is characteristically a disease of
I experiences suggest that this does not cause a
postmenopausal women. Some cases, however, still
f significant setback to the optimal treatment of the
r occur during the reproductive years. The tumour is
tumour or worsening of outcome for the mother but
i
.extremely rare in pregnancy. Victoriano and
may im prove the outcome of the ch ild .
t-
i
I
I
691
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Radcliffe KW. Vulvar carcinoma presenting during
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25. Messing MJ, Gallup DG. Carci nqlva Gynecol 1 990 Jan; 1 62(l)t164-6
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26. Olayemi O, Aimakhu CO, pregnancy: a case report and literature
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Ogunbiyi JO, Udoh lJ. Vulval review.Am J Perinatol 1993 Jul;10(4):334-5.
pregnancy. J Obstet Gynaecol 2gfi2'.=:,: .1 32. Gitsch G, van Eijkeren M, Hacker NF. Surgical
i Jul;22(4):441-2. therapy of vulvar cancer in pregnancy.Gynecol
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Vulvar epithelioid sarcoma in pregnancy. Gynecol 33. Victoriano MJ. Endometrial adenocarcinoma
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MR. A successful pregnancy outcome in treated Deci22(4)1135-46.
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Sep;54(3):371-3. Endometrial carcinoma remaining after term
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Smilari T. Malignant myxoid sarcoma of the medroxyprogesterone acetate. Gynecol Oncol
Bartholin gland in pregnancy. Am J Obstet 2000 Oct;79(7):129-32.
F
I
,
t
f
f
a
rt
693
ALPHABETIC INDEX
A Adhesion formation, 739,I79-BO, 186, 2I4, 428,

464-68
Abdominal CT scan examination, 570
Abdominal gestation, 102 Advanced Ovarian Cancer Surgery, 616
Abdominal girth, 430, 621 Advanced Ovarian Disease, 627
Abdominal hand,79
Abdominal hand palpates, 79 AFP, 635, 639-40, 642,690
Abdominal hysterectomy, 219, 233, 4gO, 57 4, 690
extra-fascial, 574 AIDS, 1 76-77, 1 19, 135, 31 1, 359
extra-fascial total, 599 AIH (Artificial Insemination Husband), 473-7 6
tolal, 292, 467 , 500,531, 575, 598-99, 614,
649 Androgen insensitivity, 340
Abdominal myomectomy, 177, 180, 184-86 Appendicitis, 99, l4l-42, 27 3, 449
performing, 178 acute abdominal pain mimicking, 635
Abdominal pain, ARTIFICIAL INSEMINATION, 473
cyclical lower,342 ART in Developing Countries, 487
lower, 69-70, 90, 98, 138-39, 396 ATFP (arcus tendinous fasciae pelvis),
severe acute, 639 Atypical squamous cells (ASC), 551
severe lower, 138 Autosomal abnormalities, 30
Abdominal Pregnancy, 102-3, 106 Autosomal
advanced,106 Hypothalamo-pituitary-ovarian, 51, 392, 4Oz
Abdominal Sacropexy, 195
Abdominal scacro-hysteropery, 1 95 Ayre spatula ,76-77
abdominal scaro-colpopexy, 1 95 Azoospermia, 312, 447-48, 450-Sl, 454
abdominal swelling, lower, 344
abdominal swelling/distension, 61 0
abdominal symptoms, 642 B
upper,610
abdominaltap, 103 Babieri RL, 184-85
ABHR (Alcohol based hand rub),322 Bacterial infections, 332-33
ABNORMAL CYSTS, 168 associated mixed, 299
Abortion Law of Ghana, 143 secondary, 708, I29
Abortion rates, 369 severe, 1 16
Abscesses, Bacterial Sexually Transmitted Diseases, 135
pelvic, 137, 74O, l43,2gB bacterial vaginosis, 77, 92, 95, i07-13, 136, 138,
small pelvic, 143 551
tuboovarian, L42,2O8
Bartholin gland cysts and abscesses, 159
Acceptability of Cryothera py, 562 Bartholin's abscess, l2O, 157 -59, 16l
ACCP (Alliance for Cervical Cancer prevention), Basal Body Temperature Method, 305
562-63 BBT chart and hormonal assays, 453
Acetic Acid for cervical cancer screening, 562
Acetowhite changes, 367 -68, 557 Bechget's disease, 108
Acupuncture,226, 248 beta HCG level, 101
Acute abdominal pain, 641 Bilateral tubal ectopic, 104
694
>
I
Biopsy forceps, 367 preventing, 559, 567
square-jawed cervical, 374 treatment of, 554-55
Bladder cancer, 201 Clinical breast examination (CBE), 254-55, 496

Bladder Care and Urinary Tract Problems, 292 Cochrane Review, 81, 91, 94, 181 ,785,196, 428,
Bladder control, 197 477,487
Blood clots and Breast cancer, 499 Colposcopy examination, 365
Bloodless Myomectomy, 77 8 Condyloma, 365, 544-45, 547
BLOOD-OVARY BARRIER, 3 Contraception, 101, 118, 143, 212, 238, 246,
Bloody nipple discharge, 257 305-7, 309-16, 442, 577, 567, 587
BMI (body mass index), 72,332, 4O8,425,427, Contraceptive methods, 305-7, 31 1, 313-1 4, 684
431, 436, 449,602 Corpus Iuteum, 3, 51, 55,57,60,62-63,91, L02,
151, 208, 254,397-99, 423-24, 442, 505-6
Bowe! dysfunction, 621 Counseling
BRCAI, 606, 621, 629 post-treatment, 89
t) mutations in,62]- pre-operative, 302
BRCA1 and BRCA2 genesr 606, 608 Counselling patient, 660
Is C-reactive protein (CRP), I4O, 263, 285
, Breast milk, 312 Cysts,
Breast Milk Production, 520 benign, 165-66, 690
BTC (basal temperature chart), 425 chocolate,214
BV/trichomoniasis/desquamative vaginitis, 110 complex,215
corpus luteal, 102
dermoid, 636, 638-39, 642, 689
c
cytobrush, 76-77 , 362, 366-67
cA L25, 535, 622-23, 641-42
Cabergoline treatment, 5 1 6 Cytological diagnosis, 549
long-term, 519 Cytological endocervical sampling, 367
Cytology screening, 363
Candidiasis, 108, 110, 113, 162-63,165,657 cervical, 552, 563
associated vulvar, 108 implemented, 362
recurrent vulvova[inal, 1 14 cytopenia, 532
vaginal, 107-8, 111 cytoplasm, l-2,7 , 19, 22, 478,543
vulvovaginosis, 111 cytoreduction, 604, 632, 690
Carboplatin/pacliatxel combination, 535 initial, 626
CB E (clinical breast exami nation), 254-55, 496 minimal, 690
CC (clomifene citrate), 427 -28, 607 optimal, 531,535,627
cD4,176-17,544 primary, 531
Cervical cancer brachytherapy, 524
Cervical Factor lnfertility, 461 Cytotoxic therapy, 619
Cervical screening plogramme, 561 intraperitoneal adjuvant, 62 1
Chemotherapy, 258-59, 521-23, 525-39, 541, cytotrophoblast, 6-7, 10, 641 ,672,675
615-77 , 679-20, 626-27 , 632-33,638, 640,
642-43, 648-49, 660, 675, 677-82
D
Chiasma, 511-13
optic, 512-13 Dactinomycin, 535
Chlamydia, 175,721-23, 138, 143, 311,443,
f 63i, 633
I 456,463,469, 608 Debulking surgery, 616,
CIN primary, 535
management of, 554 term interval, 617
695
Deep vein thrombosis F
post-operative, 294
risk of, 287, 294, 496, 575 Female circumcision, 208, 347, 350-51, 358-59,
442
Depomedrory progesterone acetate, 308 5g7
Dermatitis Female Sexua! Arousal Disorder (FSAD),244
atopic, 162,17l Female Sexual Dysfunction (FSD), 243,246-49,
seborrheic, 162 257,352,494
Fibroids and infertility, 176, 457

Dysmenorrhea, 215, 225, 230-31, 377 Fibroids and reproductive outcome, 17 6
primary, 223,23O Fistula formation, 575
Dysmenorrhoea,69, I42, 17 S, 220-21, 223-27, Fistula repair surgery, 238
229-31,425,466
cures, 230 Follicle Stimulating Hormone, 435-36
intrinsic, 223 Follicle stimulating hormone and luteinizing
organic,224 hormone, 392
primary, 223-27,23O Follicle stimulation, 468 t-"\
secondary, 2I5, 224-Zb, 230 Follicle tracking, 47 4-77
Dyspareunia 247-48 Frozen section, 598, 613, 662-63,690
I
FSAD (Female Sexual Arousal Disorder), 244
E Gardnerella vaginalis, 108-9, 128
Ectopic gestation GnRH, 51-55, 59, 64, I7B, 217, 3gZ, 396,
ruptured, 98, 103, 208 402-3, 423, 425, 428, 436, 445, 475_77 ,
unruptured early, 98 482-83
EGF (epidermal growth factor), 55, 58, 173,253, GnRH agonist administration, 483
504 GnRH agonist in precocious puberty, 406
ELISA technique, 131 GnRH agonist protocol, 483
Embryo Freezing,473 GnRH agonist regimens, 482
Embryo transfer, 439-40, 454, 4Sg, 464-65, 469,
476,479-Br,4B4 GnRH antagonists in lVF, 483
Endometrial biopsy,lI2, I40, 176, 269, 37g, Gonococcal lnfection, I20,I27, 166, 463
380-81, 397, 425, 437, 45r_53, 597, 596, Granuloma inguinale, lI5, l2g, 657, 669
691 Grave's disease, 413
Endometrial growth factors, 183
Endometrial Pipelle, 381 H

Endometriotic cysts, 2I5, 47 0, 609
Endometriotic deposits, 2lB, 449 HAART (H igh ly Active Anti- Retrovi ral Treatment),
Equipment for Iaparoscopic surgery, 273 117
EUA (Examination under anaesthesia), 361, Haematocolpos, 343-44, 351, 377
373-75, 390, 523, 571, 613_14, 6g8 HCG, 60-62 ,66,94,99, 429,430_31 , 477, 492,
EUA and biopsy, 373-74 623, 635, 637 , 640_42, 675_78, 6B0,
Examination cystoscopy, 57 1 682-83
Excision procedure, 349
loop electroc autery, 37 2 H ighly Active Anti- Retrovira I Treatment (HAART),
loop electrosurgical, 368, 37 2, 556 177
695
?
t
f
t"
r
f HIV disease progression, 118 o
$ HPV infections, 133, 363, 543-45, 557,,559,
! 566-67 ,655-57 oHss 432, 433, 450, 451, 488, 489, 502, 503
persistent, 544-45 Oligomenorrhoea 168, 169, 358, 359, 396, 397,
{t productive, 546 426-429, 440, 447, 444-449, 524, 525, 530-
r :
Hyperprolactinemia, 55, 151, 415, 435;'445, 535, 538, 539,604,605, 668, 669
I 504-5, 507-9, 516, 519-19 Oligozoospermia 468, 469
t
diagnosis and treatment of, 519 Olisospermia 474,475
I regular menses, 415 Oogenesis 20, 21, 24, 25, 4lO, 471, 508, 509
Hypothalamus-pituitary-axis (HPA), 507 Oogonia 22, 23,34, 35, 54, 55, 508, 509
I Hysteroscope, 269-70, 272, 3lL, 376, 452, 60l Oophorectomy 238, 239, 248, 249, 278, 279,
512, 513, 516, 577, 642, 643, 652, 653,
I
I
I
672,673
I Oral-Genital 132, 133
I Osteopenia 524, 525, 530-535, 538, 539
a
ICSI 238, 239, 470, 471,474,475,499,499, Osteoporosis 7I2, ll3, 2O2, 2O3, 236, 237 , 248,
492-495,498-501, 504, 505, 509, 509 249, 448, 449, 5L2-521, 524, 525, 530-535,
a, IGF-1 78,79,608,609 606,607,626,627
LgG 146,147,524-527 Ovary 18, 79, 22-25,30, 31, 34, 35, 54-59, 66-
I
LgM 146, I47, I52, L53 77 , 80-83, 86, 87 , 92, 93, 110, 111, 118,
I
I
1
lnhibin-A 82, 83 lI9, 122, 123, 77 0, L7 l, 226-229, 232-235,
/ lnhibin-B 82, 83 240,247,326,327, 410-473, 416, 417, 422-
t 427, 432-435, 438-441, 446-463, 468, 469,
II
Klinefelte/s 47O,471 484-489, 510, 51 L, 524-529, 548-551, 554,
/ Laparascopy 458,459 555, 558, 559, 600-605, 610, 611,624-637,
t
I 640-645, 648, 649, 654-67 3, 7 00, 7 01
I LNG.IUD 2O2,2O3 Ovulation 18, 19, 22-25,54, 55, 60, 61 ,72-87,
tI
I
LNG-IUS 236, 237 , 242, 243, 516, 5L7,606, 607 138, 139, 168-175, 228, 229, 234, 235, 242-
/ 249, 324-331, 470-42I, 432, 433, 436, 437 ,
i 440-453, 458-473, 476, 477, 4gg-491, 494,
M 495, 504-507, 5lO, 577, 524-527, 536-539,
r
I
606, 607 , 626-629, 649, 649
I
Methotrexate-Folinic. 700, 70 1 Paclitaxel 548-551, 554, 555, 558-563, 636-641,
{ 4 646, 647, 650-653, 662, 663, 7 lO-7 13
Minilaparato my 286, 287 Paclitaxel-Based 652, 653
I
Paclitaxel-Carboplatin 638, 639, 650, 651
I Mirena L62, 763, 202, 203, 244, 245, 332, 333, Pacl itaxelcis platin 646, 647
I
I
458,459 Paclitaxel-Cisplatin 638, 639, 646, 647,650, 651
a
I
Pan-Hypopituitarism 538, 539
I N Papanicolaou 96, 97 , 150, 151, 380-385, 394,
1 395, 570, 57I,582-585, 588, 589,6L6,617
Necrobiosis 194, 195
Neisseria 138, 139, 154, 155, 776, 177, 464, PAPPILOMATA 190, 191
465,474,475 Parkinson's 536, 537
NET.EN 328,329 Parkinsonism 182, 183
a
Neurotransmission 524, 525 PCOS 1 l2-II5,284,285, 426,427, 432, 433,

Nevirapine 138, 139 446-461, 468, 469, 526-529
Norplant 328, 329,334, 335 PCR 136, 137 , 146-151, 564, 565, 596, 597
F PCR-based 144, L45
Perihepatitis 156, 157, 160, 161
Peri-menarcheal 444, 445
697
Perimenopausal24B,249, 4OO,401, 408, 409, pubovaginalis 60, 61
444-447 Pubo-vesico-cervical 312, 313
Punctate 128, 129, 146, 747
Peutz-Jeghels 626, 627, 67 2, 673 Pyosalpinx 146-749, 160, 161, 226-229
Phagocytosis 234,235
Physiotherapy 316, 377, 644, 645
Platinum-Paclitaxel 646, 647 R
Pneumoperitoneum 28O, 287 , 284-289 , 292-2gs
Pneumothorax 234, 235, 28O, 28I Radiation 4, 5, 10-13, 18, 19, 30, 31, BB, 89,
Podophyllin 190, 191 220-223, 254-259, 314, 31 5, 318-321, 349,
349, 388, 3Bg, 400, 407, 406, 407 , 429,
Polycystic 18, 19, 48, 49,92,93, 112,I13, 170, 429, 448, 449, 466, 467,530-535, 538-561,
771,226-229,426-429, 432, 433, 439-441, 570,577,579,579,590-599, 6tg_623,636,
444-447, 452-461, 469, 469, 4gg-497,526- 637,656,657,662,663,672,673,6g0-6g7,
531, 602-605, 610, 6ll, 620, 62L 702,703,708-771
Polyps 96,97 , 168, 169, 774, L75,244,245, Radiotherapy 4, b,10, 11 ,278,279,348, 349,
288-291, 396, 397 , 402, 403, 406-409, 464- 362, 363, 392, 393, 424, 425,430, 431, _
467,514,515,604,605,616, 677,670,67L 444,445,474,475,49g,499,534,535, -l-
538-561,590-599,620,62t,636-641,659, \
Pomeroy 330, 331 659, 662,663, 690-697 ,708-711
Precocious 422-427 , 656, 657 ,660-663, 666-67I Rathke's72,73,530, 531
Pregnenolone 7 6, 77, 432-435 Rectocele 98, 99,208-215,266,267
Premalignant 18, 19, 152, 153,I7O,171,788, Rectovaginal 68,69, 1OO, 101 ,208-213,2L6,
I t Bg, 276, 277 , 3go,3g1, 3g6, 3g7, 400, 2!7 , z3o, 231, 234, 235, zs4-257 , 47o, 47r,
401, 562-593, 596, 597 , 602,603, 606, 607, 546, 547 ,59g, 5gg, 616, 677 ,630-635
690,691 Resectoscope 290-293, 398, 399
Premarin 76,77,188, 189, 518, 519 Reticulo-Endothelial 320, 321
Reynolds 556, 557, 688-691
Premenstrual 18, 19, 74,75, 162, 163, 166, 167, Rhabdomyosarcoma llO-713
r92, 193, 242-251, 27 4, 27 5 RhD-negative 724, 125, 696, 697
PREZYGOTIC 20, 2L
Rheumatoid 266,267
Prolactin 72-75, 234, 235, 268, 269, 274, 275, Rhinorrhea 342, 343
306, 307, 360, 361 , 428-431, 434-437, 446- Rubella 112, 113
449, 452, 453, 456-459, 470-475,522-539 Zlb
Sacro-Colpopexy 2I4,
Prolactinomas 18, 19, 436,437, 44O, 441,526- Sacro-Hysteropexy 2t4,zls
529, 532, 533
Promontory 254,255 Sacrospinous 212-215
Salpingectomies 496, 497
Pseudocapsule 194, 195 Salpingectomy 120, 121, 284, 285, 464, 465,
Pseudocyesis 428, 429, 434, 435, 530, 53 I 484,495,490,49r
Pseudohermaphroditism 426,427,430, 431 Salpingitis 68, 69, gg, g9, l4o-143,156-16i,
Pseudomyxoma 640, 641 164, 165, 402, 403, 464, 465, 472, 473,
480-483
Psychosexual322, 323,384,385, 434, 435, 550, salpingography 402, 4o3, 472, 473, 4go, 4gl,
551, 684, 695 626,627
Salpingolysis 284, 285, 474, 475
Pubocervica, 64-67, 208, 2O9 Salpingo-Oophorectomy 238, 239, 486, 487 , 55O,
Pubococcygeus 206-209, 222, 223 551, 594, 595, 606, 607,61.9,619,634-637,
. Puborectalis 206,207 658-663, 668-673, 7 IO, 7 Ii
Pubovaginal 222-225 Sarcomas 194, 195, 278, 279, 548, 549, 558,
Pubo-Vaginal222, 223 559, 676, 677,770,711
698
Second-Look 49O, 49L, 646, 647 ,652, 653, 656, w
657
Seropositive 152, 153, 464,465 l
Warfarin 772,173
Warts 96, 97 , 566, 567 , 584,585, 588, 589,
Serosanguinous 320, 32 1 676,677,686,687
Sex-Determining-Region-Y 34, 35 Wernicke's 532, 533
Spermatogenesis 20-23 , 44, 45,78,79,82, 83, Wertheim 156, I57 ,312, 373, 392, 393, 584,
V
86,87,332, 333, 336, 337, 466,467,470, 585, 594, 595
ri 471 whiff 96, 97, 130., 131
Spinnbarkheat 472,473, 494, 495
f
Squamo-Columnar 96,97,386, 387 568, 569, x
r 588, 589
STDs 16, 17, 100, 101, 128, 129, L58, l59, 476, X-Linked Disease 486
{ 477 X-Linked Disorders 485, 486
i-
+ X-Linked Dominance lnheritance 29
Teratoma 80,81, 228, 229, 530, 531, 628, 629, X-Linked Dominant Disorders 26,29
642,643,656-663 XO Gonadal Dysgenesis 411
X-Rays, Plain 514, 523,613
Thrombo-Embolism 300, 301, 326,327, 632,633 XY Gonadal dysgenesis and Female
TORCHS 112, 113 Pseudohermaphroditism 340, 341
Torsion 194, 195, 238,239,292,293,450, 451,
630, 631, 654, 655, 658, 659, 662,663,
( 696,697 Y
I Trichomoniasis 126-135, t46, 147, 756, 157
* 96,97,386,387 YolkSac 7,13,61, 1OO, 102,635, 638,642
t Yolk Sac Tumours 623,636,638,641
f
I U
I z
?; Utero-Vaginal 212-275, 3 12, 3 13, 328, 329
Utero-Vesical 58, 59, 66, 67, 230, 231 ZIFT (zygote intra-fallopian transfer) 454,47O, 473,
479
Zona Pellucida 5, 394
t V Zygote 5,27,98,479
Vaginectomy 57 6-57 9, 596, 597

i
Vaginismus 264-269
i Vaginoplasty 362-365
t
Von-Willebrand 304, 305
i
Vulvoscopy 676, 677 ,682, 683
Vulvo-Vaginal L7 8, 779, 362, 363, 564, 565
a Vulvo-Vaginoplasty 362, 363
699

Comprehensive Gynaecology

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Comprehensive Gynaecology

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r-

Enyonam Yao Kwawukume

All rigbffi No part of this book orpotiono'nray

Prof BA Ekele Prof KA Danso Prof EE Emuveyan

Consultant Obstetrician-Gynaecolggist;rKqmfo Anokye Teach,ing'Hospital, Kumasi, Ghana

Consultant Obstetrician-Gynaecologist, University of Lagos Teaching Hospital, Lagos, Nigeria

Abiodun PeterAboyeji, MBBS, FWACS, FIGS.

Aisha Nana Adamu, MBBS, M Sc, FWACS.

E Teddy Agida, MBBS, FWACS, FICS

Christopher Odianosen Aimakhu, MBBS , FWACS, FMCOG , FICS.

Godwin O. Akaba, MBBS, FWACS

Oluwarotimi lretiAkinola, MBBS, FWACS, FICS

Hannah N.G. Ayettey Ani. MB.CHB ,MGCP

Eric I. Archibong, MBBS, FMCOG, FWACS, FRCOG.

;- Ayodele O. Arowojolu, MBBS, FMCOG, FWACS, FRCOG.

Visiting Professor, University of Gambia Medical School, Banjul, The Gambia

Edward Ejiro Emuveyan, MBBS, FMCOG, FWACS, FICS.

Saturday Job Etuk, MBBS, FMCOG, FWACS, FICS

' Oluwarotimi O. Fakeye, MBBS, FMCOG, FWACS, FACOG.

Osato F. Giwa-Osagie, MA, MBBChir, M Sc, FRCOG, FWACS, FICS.

Hadiza S. Galadanei, MBBS, MSc, FWACS, FRCOG

' Audu ldrisa, MBBS, FWACS, FICS

. Joseph L lkechebelu, MBBS, FWACS, FICS

. John E. lkimalo, MBBS, FWACS, FICS.

Aliyu Yabagi lsah, MBBS, FMCOG

Celestine Theophilus John, MBBS, FMCOG, FWACS, FRCOG, FICS, KSM.

CecilAdjei Klufio, MBChB, FRCOG, FRCSE, FWACS, FGCS

Thomas O. Konney MD, FWACS, FCGS

lsaac Koranteng, MB ChB, FWACS, FGCS

Robert A. Kwame-Aryee, MBChB, FWACS, FGCS

Henry Laryea, MB CHB, FWACS, FGCS

AnyeteiTornyeli Lassey, MBChB, FRCOG, FWACS, FGCS

Kareem Mumuni, BSc. MB, CHB, FWACS, MPH, FGCS

Kobby Nkyekyer, MBChB, FRCOG, FWACS, FGCS

Micheal Ntumy, MB ChB, FWACS, FGCS

SamuelA. Obed, MBCHB, FWACS, FGCS

Alexander Tawiah Odoi, BSc, MBChB, FWACS, FGCS

i ,_ Examiner, West African College of Surgeons

; Akintude A. Odukogbe, MBBS, M. Sc, FMCOG, FWACS

Richard A. Offiong, BM BCh, FWACS, FICS

. Anthony Amanfo Ofori; BSc, MB ChB, FGCS, MBA

;--* Olasurubomi K. Ogedengbe, BMBCh, MA, FMCOG, FWACS, FRCOG.

Former Head of Department, University of Lagos, Nigeria

Olayinka O. Ogunbode, MBBS, FWACS, FMCOG, FICS.

Temidayo O. Ogundiran, MBBS, FRCS, FWACS

Joseph A. Olamijulo, MBBS, FMCOG, FWACS, FRCOG

Timothy O. A. Oluwasola, MBBS, M Sc, FWACS.

Raymond Ugochukwu Okolo, MBBS, M Sc, Ph D

Jude Okohue, MBBS, FWACS, FMCOG, FICS,

Anthony O.U. Okpani, MBBS, FWACS, FICS

Akinyinka O. Omigbodun, MBBS, FMCOG, FWACS, FICS.

Lawrence A. Omo-Aghoia, MBBS, FMCOG, FWACS

Olatunde Onafowokan, MBBS, FMCOG, FWACS.

Henry Sakyi Opare-Addo, BSc, MBChB, FWACS, FGCS

School of Medical Sciences, Kumasi. :

Consultant Obstetrician-Gynaecologist, Komfo Anokye Teaching Hospital, Kumasi.

Baafuor KofiOpoku, BSc, MB Chts, FWACS, FGCS

Roderick Emil Larsen-Reindorf, BSc, MBChB, MSc BioMedED, FWACS

AliSamba, MB, CHB, FWACS, FGCS

PearlAba Anoa Scott, MB,ChB ,MGCPS

Joseph D. Seffah, MBBCh, FWACS, FGCS

Daye Seleye-Fubara, MBBS, FWACB FMCPath

Sunday Oladapo Shittu, MBBS, FWACS, FICS