Gynecology PDF

Gynecology
A CREOG and Board Exam Review

Sherif Shazly
Shannon K. Laughlin-Tommaso
123
Gynecology
Sherif Shazly
Shannon K. Laughlin-Tommaso
Gynecology
A CREOG and Board
Exam Review
Sherif Shazly Shannon K. Laughlin-Tommaso
Obstetrics and Gynecology Department of Obstetrics &
Mayo Clinic Gynecology
Rochester, MN Mayo Clinic
USA Rochester, MN
USA
ISBN 978-3-030-41127-5 ISBN 978-3-030-41128-2 (eBook)

https://doi.org/10.1007/978-3-030-41128-2
© Springer Nature Switzerland AG 2020

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Contents
Part I General Gynecology

1 Basic Gynecology�� 3
Anatomy�� 3
The External Genital Organs (The Vulva) . . . . . . 3
Pelvic Outlet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Pelvic Organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
The Pelvic Floor . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Pelvic Avascular Spaces . . . . . . . . . . . . . . . . . . . . . 21
Pelvi-Abdominal Vasculature . . . . . . . . . . . . . . . . . 24
Anatomy of Anterior Abdominal Wall . . . . . . . . . 27
Physiology�� 30
Puberty �� 34
Physiologic Changes with Puberty . . . . . . . . . . . . . 34
Precocious Puberty . . . . . . . . . . . . . . . . . . . . . . . . . 35
Embryology�� 40
Further Reading�� 42
2 Menstrual Disorders�� 45
Abnormal Uterine Bleeding�� 45
Postmenopausal Bleeding�� 59
Amenorrhea�� 63
Amenorrhea-Related Disorders�� 73
Polycystic Ovary Syndrome . . . . . . . . . . . . . . . . . . 73
Gonadal Dysgenesis . . . . . . . . . . . . . . . . . . . . . . . . 84
Outflow Tract Obstruction . . . . . . . . . . . . . . . . . . . 89
Sheehan syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Hyperprolactinemia�� 92
Dysmenorrhea �� 98
Premenstrual Syndrome �� 99
vi Contents
3 Genital Infection�� 105

Lower Genital Infections �� 105
Bacterial Vaginosis . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Trichomoniasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Vulvovaginal Candidiasis . . . . . . . . . . . . . . . . . . . . 113
Atrophic Vaginitis . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Desquamative Inflammatory Vaginitis . . . . . . . . . 119
Genital Herpes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Chancroid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Granuloma Inguinale (Donovanosis) . . . . . . . . . . 132
Lymphogranuloma Venereum (LGV) . . . . . . . . . . 133
External Genital Warts
(Condyloma Acuminata) . . . . . . . . . . . . . . . . . 134
Molluscum Contagiosum . . . . . . . . . . . . . . . . . . . . 137
4 Contraception�� 151
Barrier Methods�� 153
Combined Hormonal Contraception�� 156
Combined Oral Contraceptive (COC) Pills . . . . . 156
Transdermal Patches . . . . . . . . . . . . . . . . . . . . . . . . 157
Vaginal Ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Progestin-Only Contraception�� 170
Non-hormonal Intrauterine Devices�� 185
Missing IUD Strings . . . . . . . . . . . . . . . . . . . . . . . . 194
Postpartum Contraception �� 196
Emergency Contraception �� 197
Natural Contraception�� 201
Female Sterilization�� 205
Male Sterilization�� 209
5 Uterine Leiomyomas�� 211
6 Chronic Pelvic Pain �� 233
Endometriosis�� 241
Adenomyosis �� 257
Contents vii
7 Menopause �� 261

Osteopenia and Osteoporosis�� 266
Vulvar Pruritus�� 269
Part II Urogynecology
8 Urinary Incontinence�� 275
9 Pelvic Organ Prolapse�� 293
10 Genital Fistulas�� 315
Genitourinary Fistuae�� 315
Rectovaginal Fistula�� 326
Female Genital Mutilation�� 330
11 Urodynamic Study�� 335
Part III Reproductive Endocrinology and Infertility
12 Infertility�� 343
Male Factor Infertility�� 347
Female Factor Infertility�� 351
Tubal Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
Ovarian Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
Uterine Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Asherman syndrome . . . . . . . . . . . . . . . . . . . . . . . . 375
Unexplained Infertility�� 377
13 Recurrent Pregnancy Loss �� 381
14 Fertility Preservation�� 389
viii Contents
15 Anomalies of Female Genital Tract�� 393

Disorders of Sex Development (DSD)�� 393
Congenital Anomalies of the Vulva�� 396
Hymeneal Anomalies �� 397
Congenital Anomalies of the Vagina�� 397
Müllerian Duct Anomalies�� 398
Vaginal Agenesis (Blind Vagina)�� 401
Cervical Anomalies�� 404
Fallopian Tube Anomalies�� 404
Ovarian Anomalies �� 404
Part IV Gynecologic Oncology
16 Lower Genital Tract Cancers �� 409
Vulval Neoplasia �� 409
Vulval Intraepithelial Neoplasia (VIN) 409
Invasive Vulval Carcinoma 412
Vaginal Neoplasia�� 417
Vaginal Intraepithelial Neoplasia (VAIN) 417
Invasive Vaginal Carcinoma 419
Cervical Intra-Epithelial Neoplasia-CIN �� 422
Cervical Carcinoma�� 435
17 Uterine Corpus Cancers �� 453
Endometrial Hyperplasia�� 453
Endometrial Carcinoma �� 461
Uterine Sarcoma �� 474
Gestational Trophoblastic Neoplasia�� 479
18 Ovarian Tumors �� 489
Ovarian Torsion�� 517
19 Perioperative Care�� 521
Surgical Recovery�� 521
Venous Thromboembolism Surgical Prophylaxis�� 524
Antibiotic Prophylaxis�� 527
Index�� 531
Part I
General Gynecology
Chapter 1
Basic Gynecology
Anatomy
The External Genital Organs (The Vulva)
• Superficial structures:
–– The clitoris (homologue of the penis):
The clitoris is a sensory organ that consists of two
parts (the body and the crura):
Body: it is the midline shaft. It is attached to the sym-
physis pubis by a suspensory ligament.
Crura: two crura are present underneath the shaft
and are attached to the pubic bones.
–– Vestibule:
It is the region between the labia minora and the
hymen, which creates a triangular area that is bounded
by the labia minora laterally and the clitoris at the apex.
The external urethral meatus, the vagina, and
Bartholin ducts open into the vestibule.
–– Subcutaneous tissues of the vulva:
The mons pubis: a mass of adipose tissue covered by
the skin and hair and lies on the symphysis pubis.
© Springer Nature Switzerland AG 2020 3

S. Shazly, S. K. Laughlin-Tommaso, Gynecology,
https://doi.org/10.1007/978-3-030-41128-2_1
4 Chapter 1. Basic Gynecology
The labia majora: two folds of the skin (hair bearing)

and adipose tissue:
• Anteriorly: they unite with the mons pubis.
• Posteriorly: they unite to form the posterior
commissure.
• Contents:
➊ Sebaceous glands
➋ Sweat glands
➌ Termination of round ligaments
➍ Obliterated processus vaginalis (canal of Nuck)
The labia minora:
• Two thin flaps of nonkeratinized hairless skin
medial to the labia majora.
• Anteriorly: they divide into:
–– The upper flaps unite above the clitoris to form
the prepuce.
–– The lower flaps unite under the clitoris to form
the frenulum.
• Posteriorly: they unite to form a fold of the skin
called the fourchette.
• Contents: they contain loose connective tissue
devoid of fat.
Minor vestibular glands (Skene glands):
• They are located around the lower end of the
urethra.
Subcutaneous glands:
• Sebaceous glands: they are present in the labia
majora and minora.
• Sweat glands:
–– Apocrine sweat glands: they may give rise to
hidradenitis suppurativa (chronic infection)
and hidradenomas (benign neoplasm).
Anatomy 5
–– Eccrine sweat glands: they may give rise to syr-

ingomas (benign neoplasm).
Camper’s fascia: it is the superficial fascia of the
vulva. Fat is predominant.
Colle’s fascia: it is in the deeper fascia of the vulva.
Fat is less predominant compared to Camper’s
fascia.
• Deep structures (muscles and glands):
–– Perineal muscles:
Origin Insertion
Ischiocavernosus The ischial On the upper
muscles tuberosities and crura and body of
the free surfaces the clitoris
of the crura
Superficial The ischial The perineal body

transverse tuberosity
perineal muscles
Bulbocavernosus The perineal body Insert into the
muscles and lie over their body of the clitoris
lateral surfaces and act to pull it
downward
–– Vestibular bulbs (erectile tissue):

Lie immediately under the vestibular skin.
They are covered by the bulbocavernosus muscles.
–– Major (greater) vestibular glands (Bartholin glands):
They are located in the posterior lateral areas of the
vestibule.
The openings of their ducts are present 3–4 mm out-
side the hymenal ring.
• Vascular and nerve supply:

Blood supply Branches from the internal and external
pudendal arteries
Lymphatic • Areas external to the hymenal ring: drain to

drainage superficial inguinal lymph nodes
• The clitoris: directly drains to deep pelvic
lymph nodes
Nerve supply • The pudendal nerve
• The ilioinguinal nerve
• Genital branch of the genitofemoral nerve
• The posterior cutaneous nerve of the thigh
Prepuce of
the clitoris The clitoris
Labia
majora
Vestibule
Urethral
orifice Labia minora
Vaginal
orifice
Anatomy of the vulva

Anatomy 7
Pelvic Outlet
• The bony pelvic outlet:

–– Boundaries:
The ischiopubic rami anteriorly
The coccyx and sacrotuberous ligaments posteriorly
–– Divisions:
The pelvic outlet is divided by a line extending
between the ischial tuberosities into anterior and poste-
rior triangles.
The anterior triangle (urogenital triangle):
Layers of the anterior triangle from external to
internal are:
➊ Skin
➋ Subcutaneous tissue: Camper’s fascia–Colle’s
fascia
➌ Superficial perineal pouch:
• Clitoris and its crura
• Ischiocavernosus muscle
• Vestibular bulb
• Bulbocavernosus muscle
• Greater vestibular gland
• Superficial transverse perineal muscle
• Labial arteries, artery to the vestibule
• Posterior labial nerves
➍ Deep perineal pouch (superior to perineal
membrane):
• Deep transverse perineal muscles
• Compressor urethrae
• Urethrovaginal sphincter
• Proximal portion of the urethra
• Vagina
• Posterior triangle (anal triangle):

➊ Ischiorectal fossa:
This area is bounded by the following
structures:
–– Medially: the anal canal and external anal
sphincter
–– Anterolaterally: obturator internus mus-
cle and pudendal canal
–– Superiorly and medially: levator ani
muscle
–– Inferiorly: skin and subcutaneous tissue
➋ Anal sphincters:
① The external anal sphincter:
–– The subcutaneous portion: this part is

attached to the perianal skin resulting in
radially directed folds around the anus.
–– The superficial part:
• Anteriorly: it is connected to the peri-
neal body.
• Posteriorly: it is attached to the coccyx.
–– The deep portion: it forms a circle around
the rectum and merges with the
puborectalis.
② The internal anal sphincter:
It is present inside the external sphinc-
ter. It is a thickened layer of circular
smooth muscle.
Anatomy 9
Pelvic Organs
• Vagina:
–– Shape:
The vagina is a flattened fibromuscular tubal struc-
ture. The lumen is a transverse slit due to fascial
attachment to the lateral edges of the vagina.
The vagina is angled at 120 degrees by the traction
effect of the levator ani muscle.
–– Length:
The anterior vaginal wall is 7–9 cm. The posterior
vaginal wall is about 3 cm longer.
–– Anatomical landmarks:
Anterior and posterior fornices: the recesses anterior
and posterior to the cervix
Lateral fornices: the recesses lateral to the cervix
Lateral vaginal sulci: lateral creases on each side,
which present the junction between the anterior and
posterior walls
–– Anatomical relations:
The • Anteriorly: this part is fused with the urethra
lower • Posteriorly: it is fused with the perineal body
third •L aterally: it is fused with the levator ani muscle
The • Anteriorly: this part is adjacent to the vesical neck

middle and trigone
third • Posteriorly: it is adjacent to the rectum
• Laterally: it is fused to with the levator ani
The • Anteriorly: it is adjacent to the bladder and ureters
upper • Posteriorly: the cul-de-sac
third • Laterally: the cardinal ligaments
–– Structure:
The wall of the vagina consists of:
Mucosa: nonkeratinized stratified squamous epithelium.
Submucosa: a dense layer underneath the mucosa.
Vaginal muscularis: a bihelical muscular area that fuses
with the submucosa.
Adventitia: the vaginal muscularis and adventitia are
adherent to each other. Therefore, they are both called the
fibromuscular layer of the vagina (endopelvic fascia).
Serosa: the vagina is not covered by serosa except at the
upper posterior wall where the cul-de-sac is.
–– Vascular and lymphatic connections:
Blood supply • Vaginal artery
•B ranches of uterine, internal pudendal,
middle, and inferior rectal arteries
Lymphatic • The upper two-thirds of the vagina follow the
drainage lymphatic drainage of the cervix
• The lower third of the vagina follows the
lymphatic drainage of the vulva
Uterus
Bladder Rectum
Symphysis
pubis Posterior
Anterior fornix
fornix
Anatomical relations of the vagina and the uterus

–– Uterus:
The uterus is a hollow pear-shaped fibromuscular
organ, which consists of the upper muscular corpus and
Anatomy 11
lower fibrous cervix. The fundus is the upper portion of the

corpus (above the level of insertion of the Fallopian tubes):
Corpus uteri:
• Endometrium: the corpus is lined with the endome-
trium (columnar epithelium with endometrial
glands).
• Myometrium: it consists of three layers, outer lon-
gitudinal, inner circular, and middle interlacing
fibers (which create figures of 8 around blood ves-
sels to control bleeding when they contract).
• Serosa: it is the peritoneal coverage of the uterus.
The cervix:
The cervix is primarily formed of dense fibrous
tissue. The smooth muscle presents 10% of the whole
structure of the cervix:
• The portio supravaginalis is the upper part of the
cervix which lies above the vagina.
• The portio vaginalis is the part that protrudes into
the vagina.
The internal part of the cervix (the cervical canal)
is lined with columnar epithelium. The portio vagina-
lis part of the cervix is covered primarily with squa-
mous epithelium.
The uterus is centrally located in the pelvis. The exter-
nal os is at the level of the ischial spines. The uterus is usu-
ally anteverted (the cervix is bent forward on the vagina)
and anteflexed (the body is bent forward on the cervix).
Anteriorly The uterus is adjacent to the urinary bladder and
uterovesical pouch
Posteriorly It is adjacent to the cul-de-sac and loops of the

intestine
Laterally It is adjacent to the broad ligament and its
contents, e.g., ureters and uterine arteries
–– Size:
The corpus: on average, a normal uterine corpus is
2.5 cm in thickness, 5 cm in width, and 7.5 cm in
length.
The cervix: the cervix is 2–4 cm in length.
–– Ligamentous and fascial attachments of the uterus:
Uterine • Round ligaments: one on each side:
corpus • Origin: they are attached to the cornua of the
attachments uterus on each side (anterior to the Fallopian
tubes)
• Course: they extend laterally through the broad
ligament and enter the internal inguinal ring to
travel through the inguinal canal
• Insertion: they are inserted in the labia majora
•U tero-ovarian ligaments (ovarian ligaments):
one on each side:
• Origin: the lower pole of the ovary
• Insertion: the cornu of the uterus (posterior to
the Fallopian tubes)
• Broad ligaments: they consist of a fold of the
peritoneum on each side of the uterus:
• Origin: from the side wall of the uterus
• End: lateral pelvic walls
The upper outer part of the broad ligament
is called the infundibulopelvic ligament,
which connects the upper pole of ovary and
infundibulum of the Fallopian tube to the lateral
pelvic wall
• Contents:
- The Fallopian tubes
- The round ligament
- The ovarian ligament
- The mesovarium
- The mesosalpinx
- Remnants of the Wolffian system
- Ureters (in the base of the broad ligament)
- Blood vessels (uterine and ovarian)
- Lymphatics, nerves
- Pelvic connective tissue (parametrium)
Anatomy 13
Cervical •T he transverse cervical (Mackenrodt or cardinal)

attachments ligaments:
• Origin: the lateral side of supravaginal cervix
and vaginal vault
• Insertion: to the lateral pelvic wall (obturator
fascia)
• Uterosacral ligaments:
• Origin: from the supravaginal cervix and
vaginal vault
• Insertion: in the rectum and the third vertebra
of the sacrum (S3)
• Pubocervical ligaments:
• Origin: from the supravaginal cervix and
vaginal vault
• Insertion: the back of the symphysis pubis

Blood supply • Uterine arteries
• Branches of ovarian arteries
Lymphatic • The uterine corpus:

drainage • The upper third of the corpus: drains to
interiliac and then common iliac lymph nodes
• The middle and lower third of the corpus: drain
mainly to obturator lymph nodes (lateral) and
then into the internal iliac lymph nodes
• The cornua of the uterus: it may drain along
the round ligaments into inguinal lymph
nodes
• The cervix:
• The paracervical lymph nodes
• The obturator lymph nodes
• The external iliac lymph nodes
• The common iliac lymph nodes
• The sacral lymph nodes
Nerve supply • The sympathetic fibers: from the presacral nerve
(autonomic plexus (stimulation produces uterine muscle
nervous relaxation and vasoconstriction)
system) • The parasympathetic fibers: from the second,
third, and fourth sacral nerves (stimulation
produces the opposite effects)
• The Fallopian tubes:

–– Length: 7–12 cm in length
–– Parts:
Interstitial portion: the most proximal part of the
tube which traverses the uterine cornu.
Isthmic portion: it is approximately 2–3 cm in length.
It is characterized by a narrow lumen and thick mus-
cular wall.
Ampulla: it is lateral to the isthmus and is the widest
part. It is approximately 5 cm in length.
The fimbriated end (infundibulum): has many frond-
like projections (fimbriae) which facilitates ovum
pickup at the time of ovulation.
Blood supply Ovarian and uterine arteries (double
blood supply)
Lymphatic drainage Along the ovarian lymphatics to para-

aortic lymph nodes
Nerve supply From the ovarian plexus of nerves
(sympathetic)
• The ovaries:
–– Size: ovarian size is 2.5–5 cm long, 1.5–3 cm thick, and
0.7–1.5 cm wide
–– Structure:
The tunica albuginea: a dense layer of connective tis-
sue covering the ovary.
Germinal epithelium: a single layer of cubical to
columnar epithelium that covers the tunica.
The cortex: contains ovarian follicles within special-
ized stroma. At birth, each ovary contains 400,000
primordial follicles.
The medulla: it consists of highly vascular connective
tissue.
Anatomy 15
–– Ovarian attachment:
The ovary lies over a shallow depression on the lat-
eral pelvic wall called the ovarian fossa. The ovary is not
covered by the peritoneum.
Lateral pole: it is attached to the pelvic wall by the
infundibulopelvic ligament, which contains the ovar-
ian artery and vein.
Medial pole: it is connected to the uterus through the
utero-ovarian ligament.
The ovary is attached to the broad ligament through
the mesovarium.
Blood supply Ovarian and uterine arteries
Lymphatic drainage Para-aortic lymph nodes

Nerve supply (ovarian • Sympathetic supply: ovarian plexus,
plexus of nerves) which originates from the renal
plexus and celiac ganglia
• Parasympathetic supply: from the
second, third, and fourth sacral nerves
• The pelvic ureter:

–– Length: the pelvic portion of the ureter is 12–15 cm long
and is 3 mm in diameter
–– Course:
It enters the pelvis by crossing the end of the com-
mon iliac artery and passes anterior to the internal
iliac artery behind the ovarian fossa.
At the level of the ischial spine, it turns anteriorly
and medially.
The ureter then runs at the base of the broad liga-
ment where it crosses below the uterine artery
(water under the bridge).
The ureter is located 2 cm lateral to the cervix and
2 cm above the vaginal vault.
–– Blood supply:
The pelvic ureter is supplied mainly by a branch from
the internal iliac artery or lower aorta.
It is supplied also by branches from the uterine, vagi-
nal, middle rectal, and superior vesical arteries.
• Urinary bladder:
–– Structure:
The dome of the bladder: this part is thin, distends
during bladder filling, and contracts during bladder
emptying.
The base of the bladder: this part is thick, less dis-
tended with bladder filling. Contraction of this part
prevents urinary incontinence. It consists of:
• The trigone: it consists of a smooth muscle. It is an
inverted triangular area. Ureteric orifices are
present at the upper angles. The lower angle is
continuous with the bladder neck and urethra.
• Detrusor loop: it is a U-shaped thickening of the
detrusor muscle.
Anteriorly: the bladder is adjacent to the lower
abdominal wall.
Laterally and inferiorly: it is adjacent to the pubic
bones, the obturator internus, and the levator ani.
Posteriorly: it is adjacent to the vagina and cervix.
–– Blood supply:
Superior vesical artery: a branch from the obliterated
umbilical artery
Inferior vesical artery: a branch from the internal
pudendal artery or the vaginal artery
Anatomy 17
• Urethra:
–– Course:
The urethral lumen begins at the internal urinary
meatus. The part of the urethra that traverses the
bladder base is called the bladder neck.
The urethra runs anterior to the vagina; the distal
two-thirds of the urethra are fused with the vagina.
–– Structure:
Urethral mucosa: is formed of nonkeratinized squa-
mous epithelium.
The submucosa: is vascular. It contains paraurethral
or Skene glands which open into the lumen of the
urethra.
The muscular layer: consists an outer layer, circular
skeletal muscle layer (urogenital sphincter), and
inner longitudinal layer of smooth muscle.
–– Blood supply: from vesical and pudendal vessels
• Sigmoid colon and rectum:
–– The sigmoid colon:
It begins at the pelvic brim. It enters the pelvis where
it straightens and becomes the rectum at the level of
the third sacral vertebra (total length is 35–40 cm).
The sigmoid colon is not retroperitoneal. It has its
own mesentery (sigmoid mesocolon).
The wall of the sigmoid colon contains circular
smooth muscle layer covered by its three tenia coli
(bands of longitudinal muscles).
Blood supply: sigmoid arteries (terminal branches of
inferior mesenteric artery).
–– The rectum:
The rectum starts as a continuation of the sigmoid
colon. It ends at the anorectal junction where it
becomes the anal canal (12 cm).
Anorectal junction is angled at 90 degrees by the

pulling action of:
• Puborectalis attachment to the pubic bone (ante-
rior traction).
• External anal sphincter attachment to the coccyx
(posterior traction).
The rectum is adjacent to the vagina anteriorly and
to the sacrum and levator ani muscles posteriorly.
The rectum is covered with two bands of smooth
muscle (anterior and posterior).
Blood supply of the anorectum:
• The superior rectal (hemorrhoidal) branch of the
inferior mesenteric artery
• A direct branch from the internal iliac artery
• The inferior rectal (hemorrhoidal) branch of the
internal pudendal artery (supplies the anus and
external sphincter)
The Pelvic Floor

The floor consists of the levator ani muscles and perineal
membrane:
• Perineal membrane (urogenital diaphragm):
It is a triangular, dense, fibromuscular sheet, which creates
the inferior portion of the anterior part of the pelvic floor.
–– Origin: the inner aspect of the inferior ischiopubic rami
above the ischiocavernosus muscles
–– Insertion: the medial attachments to the urethra, walls
of the vagina, and perineal body
• Levator ani muscle:
Muscle parts
The pubococcygeus The iliococcygeus The puborectalis
Origin From the posterior aspect From the arcus tendineus From the inner surface of
of the body of the pubic levator ani (a thickening of the pubic bones
bone on both sides. Fibers the pelvic fascia covering
meet in the middle line obturator internus muscle)
where they are pierced by
the urethra, vagina, and
rectum
The anococcygeal raphe The anococcygeal raphe They are inserted into
Insertion
and superior aspect of the and coccyx the rectum and form a
coccyx sling around the posterior
aspect of the rectum
Function
• Supportive action: of pelvic organs including the bladder and uterus
• Sphincter action: for the urethra, vagina, and rectum

• Obstetric action: it is responsible for internal rotation of the head during labor
Anatomy
19
• The coccygeus muscle:

–– Origin: the ischial spine
–– Insertion: the lowest area of the sacrum and the coccyx
(cephalad to the sacrospinous ligament)
–– Nerve supply:
Puborectal and pubococcygeal muscles: by pudendal
nerve
Iliococcygeal and coccygeal muscles: by the anterior
branch of the ventral ramus of the third and fourth
sacral nerves
Urogenital
diaphrgm
Ischiocavernosus
Transversus
perinei Bulbospongiosus
superficialis Perineal body
External anal Levator ani
sphincter
Coccygeus
Pelvic floor muscles

Pelvic Avascular Spaces
Space Boundaries Contents Surgical importance

Prevesical space (space • Anteriorly: symphysis pubis • The dorsal clitoral This is the space used
of Retzius) • Posteriorly: urinary bladder vessels to perform Burch
•S uperiorly: anterior abdominal wall • The obturator nerve colposuspension
•L aterally: arcus tendinous fascia and vessels
pelvis, pelvic wall muscles, and • Venous plexus of
ischial spines the Santorini
•N erves of the lower
urinary tract
Vesicovaginal •S uperiorly: anterior cul-de-sac Areolar connective This is the space used
(vesicocervical) space • I nferiorly: the junction of the tissue to form a bladder flap
proximal one-third and distal two-
thirds of the urethra
• Anteriorly: bladder and proximal
urethra
•P osteriorly: uterus, cervix, and vagina
•L aterally: pelvic side wall, bladder
pillars (vesicouterine/vesicocervical
Anatomy
ligaments)
(continued)
21
22
Space Boundaries Contents Surgical importance
Paravesical space • Anteriorly: superior pubic ramus The ureters are During radical
•P osteriorly: by the cardinal ligament present between hysterectomy, the
•M edially: the bladder and the paravesical and parametrium, which
obliterated umbilical artery vesicovaginal spaces is present between
• Laterally: obturator internus paravesical and
•S uperiorly: lateral umbilical folds pararectal spaces, is
(peritoneal folds covering inferior removed
epigastric vessels)
• Inferiorly: levator ani
Rectovaginal space • Anteriorly: the vagina - This space is developed

• Posteriorly: the rectum by incising the posterior
Chapter 1. Basic Gynecology
• Superiorly: the cul-de-sac cul-de-sac peritoneum

• I nferiorly: the apex of the perineal between the two
body (2–3 cm above the hymenal uterosacral ligaments,
ring) e.g., during vaginal
•L aterally: uterosacral ligaments, hysterectomy
ureter, and rectal pillars
Pararectal spaces • Anteriorly: cardinal ligament Lateral sacral and The sacrospinous
• Posteriorly: the sacrum hemorrhoidal vessels ligaments are accessed
•M edially: the ureter, uterosacral through this space
ligament, and rectum
•L aterally: internal iliac vessels and
pelvic wall
• Inferiorly: the coccygeus
Retrorectal and Retrorectal space: •P
resacral nerve This space is entered
presacral spaces • Anteriorly: the rectum (superior during sacrocolpopexy
• Posteriorly: the sacrum hypogastric plexus)
•L aterally: the uterosacral ligaments •M
iddle sacral artery
The presacral space: and vein
• Anteriorly: the colon •L
ateral sacral
• Posteriorly: the sacrum vessels
•L aterally: internal iliac arteries
•S uperiorly: the bifurcation of the
aorta
Anatomy
23
Pelvi-Abdominal Vasculature
• Abdominal aorta:
–– Origin: it is a continuation of the thoracic aorta. It starts
as it crosses the aortic hiatus, of the diaphragm, at the
level of T12.
–– Branches: from above downward:
➊ Inferior phrenic arteries (T12)
➋ Celiac trunk (T12)
➌ Suprarenal arteries (L1)
➍ Superior mesenteric artery (L1)
➎ Renal arteries (L1–L2)
➏ Ovarian artery (L2)
➐ Inferior mesenteric artery (L3)
➑ Middle sacral artery (L4)
➒ Lumbar arteries originate between the levels of
L1–L4.
–– Termination: it bifurcates into the common iliac arteries
at the level of L4. Each common iliac artery bifurcates
into the external and internal (hypogastric) arteries.
• Celiac trunk:
–– Origin: it originates directly from the aorta at the level
of T12.
–– Branches:
➊ Left gastric artery
➋ Splenic artery
➌ Common hepatic arteries
• The superior mesenteric artery:
–– Origin: it originates from the abdominal aorta, at the
level of T1, approximately 2–3 cm below the celiac trunk.
–– Branches:
➊ Jejunal and ileal artery branches
➋ The ileocolic artery
➌ The right colic artery
➍ The middle colic artery
Anatomy 25
• The inferior mesenteric artery:

–– Origin: it originates from the abdominal aorta at the
level of T3.
–– Branches:
➊ The left colic artery
➋ The sigmoid branches
➌ The superior rectal artery
• External iliac artery:
–– Origin: it originates from bifurcation of the common
iliac artery.
–– Branches:
➊ The deep epigastric arteries
➋ The deep circumflex iliac arteries
–– Termination:
It ends by becoming the femoral artery as it runs
under the inguinal ligament into the femoral canal.
• Internal iliac (hypogastric) artery:
–– Origin: it originates from bifurcation of the common
iliac artery.
–– Branches:
The internal iliac artery divides, 3–4 cm distal to its
origin, into:
Anterior division of the hypogastric artery:
➊ Obliterated umbilical artery
➋ Uterine artery
➌ Superior vesical artery
➍ Vaginal artery
➎ Obturator artery
➏ Middle rectal artery
➐ Internal pudendal artery
➑ Inferior gluteal artery
Posterior division of the hypogastric artery:
➊ The iliolumbar arteries
➋ Lateral sacral arteries

➌ Superior gluteal arteries
• Ovarian artery:
–– Origin: from the side of abdominal aorta at the level of
L2
–– Branches: to the ovary, the Fallopian tube and the uter-
ine cornu
The right ovarian vein passes into the inferior vena
cava. The left ovarian vein passes into the left renal vein.
• Uterine artery:
–– Origin: it arises from the anterior division of the hypo-
gastric (internal iliac) artery.
–– Branches:
➊ Ascending branch: it runs alongside the uterus
between the two layers of the broad ligament and
ends by anastomosing with the ovarian artery at the
uterine cornu.
➋ Descending branch: to the cervix and vagina.
➌ Branches: to the ureter and urinary bladder.
Cervical and vaginal branches anastomose with
vaginal arteries and create the azygos arteries of the
vagina.
• Pudendal bundle (nerve and vessels):

–– Origin:
Pudendal nerve: from the sacral plexus (S2–S4)
Pudendal artery: from the anterior division of the
internal iliac artery
–– Course:
They bend around the ischial spine and sacrospinous
ligament to exit the pelvis.
They enter through the lesser sciatic foramen where
they run into the pudendal (Alcock’s) canal.
Anatomy 27
–– Branches (nerve and vessels):

The clitoral branch
Perineal branch, which supplies:
• Bulbospongiosus muscle
• Ischiocavernosus muscle
• Transverse perineal muscle
• The inner skin of the labia majora, labia minora,
and vestibule
Inferior hemorrhoidal branch, which supplies exter-
nal anal sphincter and perianal skin
Anatomy of Anterior Abdominal Wall
• Skin and subcutaneous layer:

–– Camper’s fascia: it presents the superficial portion of the
subcutaneous layer, which predominantly consists of fat.
–– Scarpa’s fascia: it is the deeper layer, in which the
fibrous tissue is dominant.
• Muscle layer:
Muscle Origin Insertion
External External surface of Iliac crest, linea alba
oblique lower eight ribs
Internal Lumbosacral Costal cartilages of the

oblique fascia, iliac crest, last three ribs, linea alba
inguinal ligament
Transversus Internal surfaces of Linea alba

abdominis the lower six costal
cartilages
Rectus Pubic symphysis Anterior surface of the

abdominis and pubic crest xiphoid process and five
to seven costal cartilages
Pyramidal The pubic bones The linea alba above the
muscles (may symphysis pubis
be absent)
–– Rectus sheath:
It is formed by fusion of the aponeuroses of all
abdominal wall muscles lateral to the rectus muscles.
Above the costal margin:
• Anteriorly: tendons of the external obliques.
• Posteriorly: the rectus sheath is deficient.
Above the arcuate line:
• Anteriorly: the aponeurosis of the external oblique
blends with the anterior lamella of the dividing
aponeurosis of the internal oblique.
• Posteriorly: the aponeurosis of the transversus
abdominis blends with the posterior half of the
internal oblique aponeurosis.
Below the arcuate line:
• Anteriorly: the aponeuroses of all three muscles
• Posteriorly: deficient
–– Conjoint tendon:
The conjoint tendon is formed of the lower part of
the combined aponeurosis of the internal oblique
muscle and the transversus abdominis muscles.
It is inserted into the pubic crest and pectineal line.
It forms the medial part of the posterior wall of the
inguinal canal.
• Transversalis fascia:
This is a fibrous layer that lies inside the muscular layers
and outside the peritoneum.
• Peritoneum:
The peritoneum is a single layer of serosa. The following
peritoneal folds are formed by underlying ligaments:
–– The median umbilical fold: it is formed by the median
umbilical ligament or obliterated urachus.
Anatomy 29
–– The medial umbilical folds: they are lateral to the

median umbilical fold and are formed by the obliter-
ated umbilical arteries.
–– The lateral umbilical folds: they are lateral to the medial
umbilical folds. They are formed by the inferior epigas-
tric vessels.
• Vascular supply of the abdominal wall:
–– Superficial epigastric artery:
A branch from the femoral vessels.
It runs medially toward the umbilicus.
–– External pudendal artery:
A branch from the femoral artery.
The artery runs medially to supply the area of the
mons pubis.
–– The superficial circumflex iliac artery:
A branch from the femoral artery.
It runs laterally toward the flank.
–– The deep circumflex iliac artery:
A branch from the external iliac artery.
It lies between the internal oblique and transverse
abdominal muscles.
–– Inferior epigastric artery:
A branch from the external iliac artery.
It runs medially deep to the transversalis fascia. It
intersects the lateral border of the rectus muscle
midway between the pubis and umbilicus where it
runs under the muscle and anterior to the posterior
rectus sheath.
Physiology
The menstrual cycle refers to the cyclical changes that occur
in the female reproductive system, which involve interaction
among the hypothalamus, pituitary, ovaries, and uterus.
The ovarian cycle:

Gonadotropin-releasing hormone (GnRH), secreted in a pulsa-
tile manner (60–90 minutes), stimulates the production of
gonadotropins (follicle-stimulating hormone [FSH] and lutein-
izing hormone [LH]) from the basophil cells of the anterior
pituitary. This initiates the following cyclic changes in the ovary:
Phase Events Follicular phases

Follicular •P ituitary FSH •P rimordial follicle
phase stimulates the (50 μm): it is a primary
growth of 100–1000 oocyte which is covered
primordial follicles with a single layer of
into preantral flat cells. The oocyte is
follicles in both arrested at prophase of
ovaries meiosis I
• Typically, only one •P reantral follicle
follicle continues (200 μm): a primary
to grow and forms oocyte covered with
a Graafian follicle. multiple layers of
The Graafian rounded granulosa cells
follicle secretes an • Antral follicle (500 μm):
increasing amount a primary oocyte,
of estradiol granulosa cells, theca
cells, and antral cavity
•G raafian follicle
(18–24 mm): it is
a primary oocyte
surrounded by
perivitelline space, zona
pellucida, corona radiata,
cumulus oophorus, cavity
filled with liquor folliculi,
granulosa cells, theca
interna cells, and theca
externa cells
Physiology 31
Phase Events Follicular phases
Ovulation •E
strogen level • With ovulation,
peaks 48 hours Graafian follicle
before ovulation ruptures and the
•E
strogen stimulates oocyte is released. The
increasing secretion remaining part of the
of LH which Graafian follicle forms
subsequently peaks the corpus luteum
36 hours before • After ovulation, meiosis
ovulation. LH surge I is completed with the
leads to ovulation formation of the first
and corpus luteum polar body, and the
formation primary oocyte becomes
secondary oocyte
and is arrested at the
metaphase of meiosis II,
awaiting fertilization
Luteal phase • The corpus luteum The corpus luteum
is formed after consists of luteinized
ovulation. Under granulosa cells (lutein
LH stimulation, it cells) and luteinized theca
secretes estrogen interna cells secreting
and progesterone progesterone
•H igh level of
progesterone
subsequently
inhibits the
secretion of LH
(negative feedback)
• I f fertilization
does not occur,
the corpus
luteum starts
to degenerate,
with subsequent
drop in the level
of estrogen and
progesterone
Granulosa cells
Ovum
Antrum
Corona radiata
Zone pellucida
Graafian follicle
The endometrial cycle:

Phase Duration Characters
Menstrual 2–7 days • The superficial endometrium: sloughs
phase off following degeneration of the
corpus luteum, which secretes estrogen
and progesterone (hormonal support
of the endometrium). This results
in shrinkage of the endometrium,
increasing coiling of the spiral
arterioles, ischemia, and necrosis of the
superficial endometrium, endometrial
separation, and bleeding (menses)
• PGF2α causes vasoconstriction
and myometrial contraction,
and thromboxane A2 causes
vasoconstriction and aggregation of
platelets. These mechanisms facilitate
cession of bleeding
•T he basal endometrium: is not involved
because it is supplied by the basal
arterioles which anastomose freely. The
basal layer and the basal parts of the
glands are responsible for regeneration
of the endometrium
Physiology 33
Phase Duration Characters
Proliferative 9–10 days • The principal hormone: estrogen

phase (starts after produced by the growing Graafian
the end of follicle
menstruation • Thickness of the endometrium: 3–4 mm
to the time of • Endometrial glands: increase in
ovulation – number and length, tubular
variable • Endometrial lining: become low
duration) columnar
• Stroma cells: increase in size and
become globular
• Vascularity: is increased
Secretory 14 ± 2 days • The principal hormone in this stage:
phase (it begins at estrogen and progesterone from the
ovulation corpus luteum
and ends at • Thickness of the endometrium: 6–8 mm
the onset of on average
menstruation – • Endometrial glands: continue to grow
fixed duration) and become tortuous. The lumen is
distended with secretions (glycogen
and mucin)
• Endometrial cells: become high
columnar. Secretory granules appear
initially as subnuclear vacuoles and
then supranuclear vacuoles
• Stroma cells: increase in size, become
polygonal, closely packed together,
and become differentiated into three
layers:
• Superficial compact layer: around the
necks of the glands
• Middle spongy layer: around the
distended lumens of the glands
• Deep compact layer: around the
basal parts of the glands
• Vascularity: markedly increases:
• Basal arterioles: anastomose freely
and supply the basal part of the
endometrium
• Spiral arterioles: they are end arteries
and do not anastomose with each
other. They supply the superficial
layer of the endometrium
Puberty
Physiologic Changes with Puberty
• Definition of puberty: puberty is a series of normal physi-

ologic process that present the transition from childhood
to sexual and reproductive maturity.
• Pubertal changes: pubertal changes occur between the age
of 8 and 13 years in the following sequence:
–– Thelarche: it refers to pubertal breast development. At
the age of approximately 10–12, thelarche manifests by
the development of breast budding, which is the first
physical sign of puberty in 90% of girls.
–– Pubarche: it refers to pubic hair growth.
–– Growth spurt: this refers to accelerated increase in
height, which typically occurs between the ages of 10.5
and 13.5.
–– Menarche: it is the age of the first menstrual period.
• Diagnosis of normal puberty: Signs of puberty are assessed
using Tanner staging:
Staging Breast development Pubic hair development
Tanner 1 Prepubertal appearance Prepubertal appearance
Tanner 2 Elevation of the breast Sparse long, slightly

and papilla (breast bud), pigmented hair, along
enlargement of the areola the labia
Tanner 3 More enlargement of the Dark, coarse, and curled

breast and areola hair, spreading sparsely
over the mons pubis
Tanner 4 Elevation of the areola Hair adult in type,

and papilla above the but not spread to the
level of breast contour medial surface of the
(secondary mound) thighs
Tanner 5 Recession of the areola to Adult in type and
breast contour quantity, with
horizontal distribution
(“feminine”)
Puberty 35
According to this, the following is the normal sequence of

pubertal growth:
Stage of
development Breast stage Pubic hair stage Age
Initial growth 1 1 9
acceleration
Thelarche 2 1 10
Adrenarche 2 2 10
Peak growth 3 3 12
Menarche 4 4 13
Adulthood 5 5 15
Precocious Puberty
• Definition: Precocious puberty is the onset of pubertal

changes at an age that is less than 2–2.5 standard deviation
earlier than mean of the population (corresponds approxi-
mately to the age of 8 in girls)
• Incidence: Precocious puberty is more common among
girls than boys (23:1). The overall incidence is 1:5000 to
1:10000 children.
• Types of precocious puberty:
1. True (central – GnRH-dependent) precocious puberty:
Early activation of the hypothalamic–pituitary–ovarian
axis initiates GnRH secretion, which stimulates gonad-
otropin production, and synthesis of gonadal
hormones.
2. False (peripheral – GnRH-independent) precocious
puberty:
This refers to the production of sex hormones (estrogen
or androgen) without hypothalamic–pituitary stimula-
tion, e.g., estrogenic or androgenic ovarian tumors.
Subtypes:
➊ Isosexual precocious puberty: a girl who feminizes
early
➋ Heterosexual precocious puberty: a girl who virilizes
early
3. Incomplete precocious puberty:
A single pubertal change (e.g., breast development)
occurs before the age of 8 in the absence of increased
estrogen production.
Subtypes:
➊ Premature thelarche: premature development of the
breast (unilateral or bilateral). Approximately 60%
of cases are diagnosed between the ages of 6 and 24
months.
➋ Premature adrenarche: premature development of
pubic and axillary hair.
• Etiology:
I. Central (GnRH-dependent)
➊ Idiopathic or constitutional (90%): it refers to hypo-

thalamic–pituitary activation with no identified
etiology.
➋ Central nervous system (CNS) tumors: e.g., hamartomas,
astrocytomas, adenomas, gliomas, and germinomas.
➌C NS infection: meningitis, encephalitis, and brain
abscess.
➍ Head trauma
➎ Iatrogenic: e.g., radiation, chemotherapy, or surgical
trauma.
➏Malformations of the CNS: e.g., hydrocephalus and
empty sella syndrome.
Puberty 37
II. Peripheral (pseudo-precocious puberty)
➊ Gonadotropin-secreting neoplasms:
➀ HCG-secreting tumors: e.g., choriocarcinomas and
hepatoblastomas
➁ LH-secreting tumors: pituitary adenomas
➋ Gonadal neoplasms:
➀ Estrogen-secreting tumors: e.g., granulosa-theca cell
tumors
➁ Androgen-secreting tumors
➌ Adrenal neoplasms: e.g., adenomas and carcinomas
➍ Congenital adrenal hyperplasia
➎ Autonomous gonadal hypersecretion:
➀ Benign follicular ovarian cysts: the most common
estrogen-secreting mass in children.
➁ McCune–Albright syndrome:
• The syndrome comprises precocious puberty, cys-
tic changes in bones, and cafe au lait skin.
• It is caused by autonomous production of estrogen
by the ovaries.
➏ Iatrogenic ingestion/absorption: of estrogens or
androgens
III. Heterosexual puberty
➊ Nonclassic forms of congenital adrenal hyperplasia

➋ Idiopathic hirsutism
➌ Mixed gonadal dysgenesis
➍Rare forms of male pseudohermaphroditism
(5α-reductase deficiency)
➎ Cushing syndrome (rare)

➏ Androgen-secreting neoplasms (rare)
• Diagnosis of precocious puberty:
–– History:
To rule out iatrogenic sources of estrogen or
androgen
To differentiate isosexual from heterosexual preco-
cious puberty
To identify any CNS symptoms that may be caused
by an underlying cause, e.g., mental state changes
and headache
–– Physical examination:
To identify signs of McCune–Albright syndrome.
Neurologic and ophthalmologic exam may help to
identify underlying lesions of the brain.
–– Work-up:
Work-up is guided by history and physical findings:
Hormonal profile: e.g., FSH, LH, estradiol, testoster-
one, and 17α-hydroxyprogesterone.
Ultrasonography: pelvic and abdominal ultrasound is
performed to detect ovarian or adrenal tumors.
CT head and MRI of the brain: to rule CNS lesions.
X-ray examination: of the hand and wrist to deter-
mine bone age:
• Estrogen: stimulates growth of bone and causes
early fusion of the epiphysis
• Hypothyroidism: is the only etiology that is associ-
ated with retarded bone age
Idiopathic precocious puberty is diagnosed after excluding all
other pauses.
Puberty 39
Basal LH level or GnRH stimulated level
Pubertal Prepubertal
Central Peripheral
MRI (brain) Serum estradiol
Negative Positive Low Pubertal
Idiopathic CNS related Premature thelarche Pelvic US
Abnormal
Negative ovaries
McCune-Albright Café au lait
Adrenal or exogenous Ovarian cyst
syndrome spots
Work-up algorithm for precocious puberty
• Treatment:
I. Central (GnRH-dependent)
• Aim of treatment: to prevent reduced final adult height

(epiphyseal fusion is estrogen-dependent) and limit the
psychological impact of early pubertal development
• Lines of treatment: GnRH agonists to downregulate
pituitary gonadotrophs
II. Peripheral (GnRH-independent): isosexual
• Treatment of the cause: e.g., thyroxine for hypothyroid-

ism, removal of ovarian and adrenal tumors, and elimi-
nation of the external estrogen source.
• Treatment of McCune–Albright syndrome: recom-
mended treatment is with aromatase inhibitors, e.g.,
letrozole.
III. Peripheral (GnRH-independent): heterosexual
• Treatment is by correction of underlying etiology.

Embryology
Embryology of internal reproductive organs:

The organ Development sequence
The ovaries •P rimordial germ cells migrate from the yolk sac
through the mesentery of the hindgut to the
posterior body wall mesenchyme (the site of the
future ovary)
• Once germ cells reach this area, they induce
proliferation of cells which form a pair of “genital
ridges” medial to the mesonephros. Proliferating
cells form a supporting aggregate of cells (the
primitive sex cords) which invest germ cells
•G erm cells differentiate into oogonia and enter
the first meiotic division where they become
primary oocytes. Their development is arrested
until puberty
Germ cells
Mesonephric duct
Coelomic Genital ridge

epithelium
Gut
Embryology 41
The uterus • Absence of anti-Müllerian hormone in female

and the embryos allows for Müllerian growth (anti-
Fallopian Müllerian hormone is normally secreted by
tubes Sertoli cells of the testes; they cause regression
of the paramesonephric duct system in male
embryos)
•M üllerian (paramesonephric) ducts grow
caudally and then medially and fuse in the
midline. They connect to the urogenital sinus at
a slight thickening known as the sinus tubercle
(Müllerian eminence):
• The inferior fused portion: becomes the
uterovaginal canal, which forms the lining and
glands of the uterus and the upper vagina
• The cranial unfused portions: open into the
coelomic cavity (future peritoneal cavity) and
become the Fallopian tubes
Paramesonephric
duct
Urogenital sinus
The vagina • The most inferior portion of the uterovaginal

canal forms the upper 80% of the vagina
• A pair of sinovaginal bulbs: is formed by
proliferation of sinus tubercle. Sinovaginal bulbs
form the inferior 20% of the vagina
• The vaginal plate is the inferior end of the
uterovaginal canal which canalizes by central
desquamation to connect the upper and the
lower portions of the vagina
Accessory •P
araurethral or Skene glands: they develop as
genital outgrowths from the urethra
glands •G
reater vestibular or Bartholin glands: they
develop as outgrowths from the urogenital sinus
The mesonephric duct system degenerates, and remnants may be
found in the mesovarium (epoophoron, paroophoron) or along the
lateral wall of the uterus or vagina (Gartner duct cyst). Hydatids of
Morgagni are pedunculated small cysts found near the fimbriae of
the tube. They are remnants of the Müllerian ducts.
Embryology of external genitalia:

• The genital tubercle: (a mass of tissue at the caudal end of
the abdominal wall) forms the clitoris
• The two genital folds around the tubercle: forms the mons
pubis
• The two genital folds on either side of the urogenital sinus:
form the labia majora
• The membrane covering the urogenital sinus: breaks down
and forms the labia minora
Further Reading
Baggish MS. Intra-abdominal pelvic anatomy. In: Baggish MS,
Karram MM, editors. Atlas of pelvic anatomy and gynecologic
surgery. 3rd ed. St. Louis: Saunders Elsevier; 2011. p. 179.

Carel JC, Leger J. Precocious puberty. N Engl J Med.
2008;358(22):2366–77.
Further Reading 43
Horii M, Boyd TK, Quade BJ, Crum CP, Parast MM. Female genital
tract development and disorders. In: Diagnostic gynecologic and
obstetric pathology e-book, vol. 13. Netherlands: Elsevier Health
Sciences, Amsterdam; 2017. p. 1.
Leffler KS, Thompson JR, Cundiff GW, et al. Attachment of the rec-
tovaginal septum to the pelvic sidewall. Am J Obstet Gynecol.
2001;185(1):41–3.
Ramanah R, Berger MB, Parratte BM, DeLancey JO. Anatomy and
histology of apical support: a literature review concerning cardi-
nal and uterosacral ligaments. Int Urogynecol J. 2012;23:1483.
Reed BG, Carr BR. The normal menstrual cycle and the control of
ovulation. InEndotext [Internet] 2018. MDText. com, Inc..
Saber AA, Meslemani AM, Davis R, et al. Safety zones for anterior
abdominal wall entry during laparoscopy: a CT scan mapping of
epigastric vessels. Ann Surg. 2004;239(2):182–5.
Chapter 2
Menstrual Disorders
Abnormal Uterine Bleeding

Definition:
Abnormal uterine bleeding (AUB) refers to deviation from
the normal menstrual pattern, which is considered one of the
most common gynecologic complaints.
Clinical types of AUB:

AUB is classified based on frequency, regularity, duration,
amount, and etiology:

https://doi.org/10.1007/978-3-030-41128-2_2
46 Chapter 2. Menstrual Disorders
Terminology Classification
In terms of • Acute AUB: which is generally less than 6
acuity months
• Chronic AUB: when patient concern is
consistent for 6 months or more
In terms of • Absent bleeding (amenorrhea): this topic will be
frequency discussed separately
• Infrequent AUB: menstrual cycle is longer
than 38 days (equal to the previous term:
oligomenorrhea)
• Frequent AUB: menstrual cycle is shorter
than 24 days (equal to the previous term:
polymenorrhea)
In terms of • Irregular AUB: the difference between the
regularity longest and the shortest cycles is more than 7–9
days (depending on age)
In terms of • Prolonged menstrual bleeding: menstrual
duration bleeding that lasts for more than 8 days
In terms of • Heavy menstrual bleeding: menstrual bleeding
volume that is significant enough to interfere with
patient’s quality of life (equal to the previous
term: menorrhagia)
In terms of • Intermenstrual bleeding (IMB): uterine bleeding
relation to in between cyclic menses
cycle • Cyclic IMB:
– Cyclic midcycle IMB: this is caused by
midcyclic estrogen drop at the time of
ovulation
– Cyclic premenstrual or postmenstrual IMB:
this is most likely related to luteal phase
defect or structural causes
• Acyclic IMB: it is most likely due to structural
etiology, e.g., uterine polyps
• Postmenopausal bleeding: vaginal bleeding that
occurs 12 months or more after cessation of
menstruation (menopause)
Abnormal Uterine Bleeding 47
Terminology Classification
In terms of • AUB-P: polyp (uterine or cervical polyps)
etiology • AUB-A: adenomyosis
(PALM– • AUB-L: leiomyoma
COEIN) • AUB-M: malignancy/hyperplasia
• Cervical intraepithelial neoplasia, cervical
cancer
• Endometrial hyperplasia and uterine
cancers
• Estrogen-secreting (granulosa cell) ovarian
tumors
• AUB-C: coagulopathy
• von Willebrand Disease
• Coagulation factor deficiencies, e.g.,
hypofibrinogenemia, hemophilia A and B
carriers
• Thrombocytopenia
• AUB-O: ovulation dysfunction
• Hepatic failure (AUB is present in 60%
of these patients): AUB is caused by
ovulation dysfunction (abnormal estrogen
metabolism), coagulation factor deficiency
(secondary to diminished synthesis), and
thrombocytopenia (secondary to portal
hypertension)
• Chronic renal failure (80% of patients
requiring dialysis): ovulatory dysfunction
is due to disturbance of pulsatile GnRH
secretion
• Endocrinopathies, e.g., hypothyroidism,
adrenal disorders, polycystic ovary
syndrome, hyperprolactinemia, obesity
• AUB-E: endometrial dysfunction
• Atrophic endometritis, e.g., postmenopausal
• AUB-I: iatrogenic
• Exogenous hormones, e.g., hormonal
contraceptives, steroids
• Intrauterine devices
• AUB-N: not otherwise specified
• Müllerian anomalies, e.g., uterus didelphys,
septate and bicornuate uterus
• Arteriovenous malformation (congenital or
acquired)
• Cesarean scar defect
Assessment of AUB:
First step: exclusion of extragenital source of bleeding should
be made, e.g., rectal or urethral bleeding.
Second step: exclusion of pregnancy (serum β-HCG).
Third step: evaluation of the cause and management of AUB.
I. History taking
• Personal history:
–– Age of the patient:
Patient age may be a clue to possible diagnosis. The
most common causes in relation to age are:
Newborn: withdrawal bleeding may occur in the first
week (due to withdrawal of maternal hormones).
Childhood: vulvovaginitis is the most common cause.
Adolescence: ovulatory dysfunction is the most com-
mon cause.
Reproductive age: pregnancy-related bleeding is the
most common cause.
Perimenopausal: ovulatory dysfunction is the most
common cause.
Menopause: atrophic endometritis/vaginitis is the
most common cause.
–– Risk factors: risk factors may be identified e.g., sexual
transmitted infections/HPV are risk factors for cervical
cancer; obesity is a risk factor for endometrial cancer.
• History of present illness (HPI):
–– Type of bleeding: detailed history is warranted to define
the clinical type of bleeding (see under: Clinical types
of AUB).
–– Severity of bleeding:
Assessment of volume of bleeding is challenging. The
following methods can be used:
Subjective assessment: patient’s own perception of

blood loss may not correlate with anemia or iron
deficiency. However, new onset of anemic symptoms
and diminished quality of life should be considered.
Objective assessment: the technique involves extrac-
tion of hemoglobin from sanitary pads using NaOH
to be measured spectrophotometrically. The tech-
nique is sophisticated and is not used in clinical
setting.
Pictorial blood assessment chart (Warner and col-
leagues 2004):
• Scoring system:
–– Each cycle is scored based on number of pads/
tampons and how far they are stained or
soaked. In addition, blood clots are also scored
based on their number and size.
–– The score is calculated daily during menses. The
total score presents the summated score per
each cycle.
• Total result: total >100 points per cycle indicates
>80 mL objective blood loss (heavy menstrual
bleeding).
–– Presence of pelvic pain: severe dysmenorrhea may
indicate uterine pathology, e.g., adenomyosis. Similarly,
pelvic pressure may be associated with uterine
leiomyomas.
–– Menopausal symptoms: the presence of hot flushes and
night sweats may be concerning for premature ovarian
failure among women younger than 40 years.
• Gynecologic history:
–– Known history of uterine leiomyomas
–– History of abnormal PAP testing
• Obstetric history:
–– History of recent delivery or miscarriage
–– History of infertility particularly due to chronic
anovulation
• Contraceptive history:
–– E
strogen–progestin contraceptives: may be associated
with IMB
–– Progestin-only contraceptives: may be associated with
acyclic IMB
–– Copper IUD: may cause heavy menstrual bleeding
–– Levonorgestrel IUDs: may cause initial acyclic IMB
• Medical history:
–– History of medical disorders, e.g., bleeding disorders,
thyroid diseases
–– Medications, e.g., anticoagulants, steroids
• Surgical history:
–– Prior myomectomy
–– History of Cesarean delivery (Cesarean scar defect may
present with postmenstrual bleeding)
• Family history: of gynecologic cancers (e.g., endometrial,
breast, ovarian, and colon cancers)
II. Physical examination
• General examination: assessment of physical signs of

medical disorders that may cause AUB, e.g., enlarged thy-
roid, jaundice, purpura, ecchymosis
• Pelvic examination:
–– Inspection: for ongoing vaginal bleeding, external geni-
tal pathology, e.g., ulcers, masses
–– Speculum exam: to rule out any visible pathology
related to the vagina or the cervix
–– Bimanual examination:
For palpable lower genital pathology or contact
bleeding
For uterine enlargement due to leiomyomas or
adenomyosis
For uterine tenderness due to adenomyosis
III. Work-up
• Laboratory work-up:
Test Significance
Complete blood count • Hemoglobin/hematocrit: it is an
indicator of severity of bleeding and
patient general status
•P latelets: to rule out
thrombocytopenia
Hormonal profile • TSH and prolactin: warranted if
bleeding pattern is consistent with
ovulatory dysfunction anticipated
• Androgen profile: testosterone and
17-hydroxyprogesterone are indicated
in patients with ovulatory dysfunction
and hyperandrogenism
• Serum FSH: if premature ovarian
failure is a concern, e.g., menopausal
symptoms in women younger than 40
years
Coagulation profile • Indications:
The American College of
Obstetricians and Gynecologists
recommends testing for bleeding
disorders for any of the following
indications:
❶ I n adolescents with severe heavy
menstrual bleeding
❷ I n women with significant heavy
menstrual bleeding when other
causes are excluded
❸P rior to hysterectomy indicated for
severe bleeding
• Tests:
Coagulation profile includes partial
thromboplastin time, prothrombin
time, bleeding time, platelet count ±
von Willebrand factor assay, platelet
function, factor VII and IX
• Pathological tests:
➀ Cervical screening:
• Pap smear is indicated for cervical cancer screening if
pap smear is due or if the patient has history of
abnormal pap testing.
• Colposcopy is indicated based on pap testing results
or if the cervix is visually suspicious.
➁ Endometrial sampling:
• Indications:
Age 45 years to Patients younger than
menopause 45 years
Endometrial sampling • Women with persistent AUB
is indicated in any despite medical management
woman with AUB • AUB with a personal history of
at or above this age, unopposed estrogen exposure,
e.g., IMB, frequent e.g., obesity, chronic ovulatory
bleeding, heavy dysfunction
menstrual bleeding • AUB in women at high risk
of endometrial cancer (e.g.,
tamoxifen therapy, Lynch or
Cowden syndrome)
• Techniques:
❶ Office sampling ❷ Dilation and
(e.g., pipelle biopsy) curettage
Indication It is the standard It can be performed
sampling technique if office sampling is
in most patients (less inadequate, technically
cost, shorter time, less difficult, or intolerable
surgical risks)
Anesthesia No anesthesia/local Regional or general
anesthesia is required anesthesia
Procedure Rarely, dilation is Cervical dilation is
required required
Complications Risk of uterine Risk of uterine
perforation is 0.1–0.2% perforation is 1–2%
• Microbiological tests:
Chlamydia/gonorrhea testing: is indicated in women at
high risk of sexually transmitted infection, women with fri-
able cervix on examination, or in the presence of sugges-
tive pattern of bleeding, i.e., contact bleeding
• Sonography:
–– Transvaginal sonography:
Transvaginal sonography is the gold standard imag-
ing technique in women with AUB. Sonography may
provide information on:
❶M yometrial pathology: e.g., leiomyomas or
adenomyosis
❷ Endometrial thickness:
In postmenopausal women In premenopausal women
− 4 mm or less: endometrial −U
nlike postmenopausal
cancer/hyperplasia can be women, there is no
reasonably excluded cutoff for endometrial
− ≥5 mm: further evaluation biopsy
is indicated to rule out
endometrial pathology
(e.g., hysteroscopy,
endometrial biopsy)
❸ Endometrial appearance:
• Endometrial polyps: polyps may appear as punc-
tate cystic areas within thick endometrium.
• Submucous leiomyomas: they appear as solid
masses that distort endometrial lining.
• Endometrial cancer: no specific findings but may be:
–– Significant fluid collection within the uterine
cavity
–– Heterogenous areas within the endometrium
–– Irregular endometrial–myometrial junction or
thickened endometrium
❹ Uterine vascularity (color Doppler sonography):
–– It may help to assess intracavitary lesions and
differentiate submucous leiomyomas (supplied by
several vessels arising from the inner myometrium)
and endometrial polyps (only single feeding

vessel).
–– It can be used to rule out arteriovenous malformation.
–– Saline infusion sonography:
This technique may be used to visualize suspected
intracavitary masses (endometrial polyps and submuco-
sal leiomyomas).
• Hysteroscopy:
It is the gold standard method for evaluation of intra-
cavitary uterine pathology. This technique uses a small
scope to visualize and differentiate between submucosal
leoimyomas and polyps.
Treatment:
Treatment plan is made according to anticipated etiology and
acuity. Correction of anemia should be considered. Transfusion
of blood products may be indicated if hemoglobin is less than
7 g/dl or if patient’s anemia is symptomatic.
I. Patients with acute uterine bleeding
• If the patient is unstable:

After stabilization of patient status through IV fluids
with or without transfusion, the following treatment
options can be performed if bleeding continues:
–– Uterine curettage: it is a temporary treatment option
for women who are hemodynamically unstable. Bleeding
usually responds within 1 hour.
–– IV estrogen (given with an antiemetic):
Treatment is initiated by IV injection of Premarin
25 mg in 5 mL isotonic saline over 2 minutes. The dose
can be repeated after 4 hours if bleeding continues:
After 8 hours: if bleeding does not respond, treat-
ment is considered failed. Uterine curettage is indi-
cated in these patients.
If, within 8 hours, bleeding responds, switch to oral
estrogen, e.g., oral contraceptive pills (OCPs with
high-dose estrogen), two pills per day for 5 days and

then once daily for 20 days.
• If the patient is stable:
–– High-dose OCPs (with an antiemetic):
2–4 times daily or the following regimen:
5 pills on day 1
4 pills on day 2
3 pills on day 3
2 pills on day 4
1 pill on day 5 and for at least 1 week and then stop
for 3–5 days
–– High-dose progestins:
It is an appropriate option in patients with anovula-
tion. It should continue for 5 to 10 days, e.g.:
Medroxyprogesterone acetate “MPA” (20 mg three
times daily)
Norethindrone (5 mg once or twice daily)
–– Tranexamic acid: 1–1.5 gram 3–4 times/day

–– Gonadotropin-releasing hormone (GnRH) agonist
–– Endometrial ablation
II. Patients with chronic uterine bleeding
I. If AUB is structural
Treat according to the cause. Examples include:
• AUB-P: hysteroscopic polypectomy.

• AUB-A:
Hysterectomy is the only definitive treatment. However,
hormonal treatment may be very effective, e.g., levonorg-
estrel-releasing IUD (for details, see under: Pelvic pain and
endometriosis).
• AUB-L:
Medical treatment (see below), minimally invasive pro-
cedures to shrink the leiomyomas, myomectomy, or hyster-
ectomy (for details, see under: Uterine leiomyomas).
• AUB-M:
Surgery versus hormonal treatment (for details, see
under: Uterine corpus cancers).
II. If AUB is functional - UAB-O
• Medical treatment:
Long-term treatment may follow the next algorithm:
Treatment according to patient preference
If the patient has infertility If the patient does not have infertility issues
Induction of ovulation
Contraception desired Contraception is not desired
a
• OCPs: 21/7 regimen may • Non-hormonal treatment: see below
reduce bleeding by 40–70% • Oral progestins: 10mg of MPA, given
• Levonorgestrel- from day 16–25 of the cycle especially
releasing USD: it provides for ovarian dysfunction
long term contraception and • OCPs: may be used for short-term till
bleeding control pregnancy is desired
If these options fail to control bleeding

• Surgical treatment: hysterectomy or endometrial
ablation
• GnRH agonist or androgens: may be used as a
temporary method to control bleeding prior to
surgery or ablation

Non-hormonal treatment
Mechanism Regimen Advantages Disadvantages
Nonsteroidal They increase Examples include •O nly taken during Risk of stroke and
anti- thromboxane A2 ibuprofen 600 mg menses heart failure with long-
inflammatory over PGE2 and favor daily or mefenamic • Improves term use
drugs thrombosis and acid 500 mg 3 times dysmenorrhea if
hemostasis daily present
Tranexamic Antifibrinolytic 1300 mg (650 mg • Taken only during Risk of systemic
acid action (preventing tablets times two) menses thrombosis
conversion of three times daily • I t reduces bleeding Side effects include
plasminogen into in 50% of cases nausea, dizziness, and
plasmin) diarrhea
Etamsylate It activates 250 mg or 500 mg • Taken only during Gastralgia, nausea,
thromboplastin and 2–3 times daily menses headache, and rash
facilitates platelet
aggregation
Abnormal Uterine Bleeding
57
• Surgical treatment:
❶ Endometrial ablation:
• Definition: it is a hysteroscopic procedure that
involves destruction or resection of the endometrium.
It is a less invasive alternative to hysterectomy.
• Rationale: the procedure aims at removing/destroy-
ing superficial endometrium and basal endometrium
down to approximately 3 mm of myometrial depth to
prevent endometrial regeneration.
• Indications:
–– Heavy menstrual bleeding in premenopausal
women.
–– Uterine cavity should not be distorted (or mini-
mally for some of the options).
–– Patient should not be interested in future fertility.
• Methods:
First-generation methods (under vision)
• The neodymium-doped-yttrium-aluminum-garnet
(Nd-YAG) laser
• Rollerball ablation
Second-generation methods (blind procedure)
• Hot liquid balloons • Cryoablation
• ThermAblator (heated free • Microwave
fluid) endometrial ablation
• Radiofrequency ablationa
The current most popular option
a
• Contraindications:
➀ Genital tract malignancy
➁ Women wishing to preserve their fertility
➂ Pregnancy
➃ Acute or recent pelvic infection
➄ Transmural surgery: because thinning of the myo-
metrium may increase the risk of thermal injury to
adjacent bowel or bladder, e.g., classical Cesarean
delivery, transmural myomectomy
Postmenopausal Bleeding 59
• Complications:
➀ Fluid overload and electrolyte disturbance.
➁ Uterine bleeding.
➂ Uterine perforation and damage to surrounding
structures.
➃ I njury of the cervix and vagina.
➄ Post-procedure infection, the risk is approximately
1%.
➅ Postablation tubal ligation syndrome, in women with
prior or concomitant tubal ligation. The patient expe-
riences cyclic pelvic pain with no or minimal menses
due to retained blood at uterine fundus or cornua
caused by residual functioning endometrium.
❷ Hysterectomy:
• Advantages:
➀ Removal of the uterus is the only definitive treat-
ment for bleeding.
➁ Surgery may improve dysmenorrhea and some
premenstrual symptoms.
• Disadvantages:
Intraoperative and postoperative complications,
hospitalization, recovery time, and costs
Postmenopausal Bleeding
Definition:
Postmenopausal bleeding (BMP) refers to bleeding from the
genital tract that occurs 12 months or more after cessation of
menstruation (menopause) in a woman above the age of 40.
Etiology:
❶ Hormonal therapy (HT):
• Women on HT may experience breakthrough
bleeding.
• Withdrawal bleeding occurs if hormonal therapy is
given cyclically.
❷ Malignant and precancerous lesions:

• Endometrial carcinoma and endometrial hyperplasia
(15–20% of patients with PMB)
• Sarcomas of the uterus (3–5%)
• Cervical carcinoma and cervical intraepithelial neo-
plasia (5–10%)
• Ovarian carcinoma (rare): estrogen-secreting ovarian
tumors or tumors spreading to the tubes and the uterus
• Vaginal, vulvar, and tubal cancers (rare)
• Uterine polyps
• Postradiation therapy:
Radiation may cause vaginal bleeding secondary to
vaginitis, hemorrhagic cystitis, proctitis, or vaginal vault
necrosis.
❸ Genitourinary syndrome of menopause (vulvovaginal atro-
phy): it may present with slight bleeding or blood-stained
discharge.
❹ Traumatic lesions: e.g., trophic ulcers of genital prolapse,
neglected pessary, or direct trauma.
Diagnosis:
In all patients with postmenopausal bleeding, extragenital
sources of bleeding should be excluded, e.g., urethral or blad-
der carcinoma and hemorrhoids. Assessment of women with
postmenopausal bleeding includes:
• History:
–– History of present illness:
Characteristics of bleeding (e.g., amount, duration)
The presence of associated symptoms, e.g., pain and
foul discharge
The presence of urinary or bowel symptoms
Recent fever, loss of weight, respiratory symptoms
–– Obstetric history: nulliparity is a risk factor for endo-
metrial carcinoma.
–– Medical history: hormonal therapy and tamoxifen
therapy.
Postmenopausal Bleeding 61
–– Gynecologic history: history of prolapse, use of pessary,

and mesh-related surgeries.
–– Family history: of breast, ovarian, colon, and endome-
trial cancer.
• Physical examination:
–– General examination (suggesting malignancy):
The presence of lymph node enlargement
The presence of lower limb edema
–– Pelvic examination:
Inspection and speculum examination:
• To determine the source of bleeding
• To identify vulvovaginal atrophy (the vagina is
pale and dry, with loss of most rugae)
• To identify any suspicious lesions, erosions, lacer-
ations, or foreign bodies
Bimanual examination:
• To assess uterine size and mobility
• To assess adnexal masses
• Work-up:
I. Noninvasive diagnostic procedures
❶ Office endometrial biopsy:

Endometrial sampling may be done during office visit if
available and well tolerated by the patient.
❷ Transvaginal sonography:
• Normal finding: thin (≤4 mm), homogeneous endome-
trium, with no adnexal masses
• Endometrial biopsy is recommended if:
➀ The endometrial lining is >4 mm
➁ Endometrial heterogeneity
➂ The endometrium is not adequately visualized

➃ The woman has persistent bleeding (remember: type
2 endometrial cancer may not be associated with
increased endometrial thickness)
❸ Cervical cancer screening:
Pap testing can be performed if the patient is due for
screening. Colposcopy and biopsy are warranted if the
cervix looks suspicious.
II. Invasive diagnostic procedures
❶ Dilation and curettage (D&C): it should be done if:

➀ Office endometrial biopsy is not tolerated.
➁ Nondiagnostic office biopsy.
➂ Persistent bleeding.
➃ Incomplete office biopsy due to cervical stenosis.
➄ When a concomitant operative procedure, such as lapa-
roscopy, is indicated.
❷ Biopsy from suspected lesions: in the vulva, vagina or cervix.
Treatment:
• Patients who are on HT:
–– Vaginal bleeding within 6 months of initiation of con-
tinuous combined therapy: expectant management if
appropriate. Endometrial biopsy is indicated if bleeding
persists beyond 6 months.
–– Abnormal bleeding in patients on cyclic progestins:
transvaginal sonography may be performed early in
cycle to assess endometrial thickness when it should be
the thinnest. If findings are suspicious or if bleeding is
persistent, endometrial biopsy is indicated.
–– Bleeding after a period of cession of bleeding: endome-
trial biopsy indicated.
–– Women with bleeding refractory to hormonal manipu-
lation: endometrial biopsy indicated.
Treatment is determined by endometrial biopsy results.
Amenorrhea 63
• Patients on tamoxifen:
–– Patients on tamoxifen typically have thickened endo-
metrial stripes.
–– Biopsy is indicated in the presence of abnormal bleed-
ing due to increased risk of endometrial cancer (1/1000).
• Patients who are not on HT:
Treatment should be established according to the D&C
findings.
Amenorrhea
Definitions:
• Primary amenorrhea: is the absence of menstruation:
–– By the age of 13: in absence of secondary sexual charac-
teristics OR
–– By the age of 15: in the presence of secondary sexual
characteristics OR
–– 3 years after thelarche
• Secondary amenorrhea: is cessation of menstruation for:
–– A period equivalent to three cycles if the patient has
regular cycles OR
–– A period of 6 months if the patient has irregular cycles
Etiology:
I. Physiological amenorrhea
• Before puberty: due to the low secretion of GnRH

• After menopause: due to depletion of ovarian follicles
• During pregnancy: due to continuous estrogen and proges-
terone production without withdrawal
• During lactation: because prolactin suppresses GnRH,

diminishes ovarian response to gonadotrophins, and inhib-
its ovarian steroidogenesis
• Perimenarche: due to hypothalamic–pituitary–ovarian
axis immaturity
• Perimenopause: due to diminished ovarian follicle count
and increased resistance to gonadotrophins
II. Pathological amenorrhea
A. Primary amenorrhea:
I. Patients with well-developed secondary sexual characteristics
With present uterus With absent uterus

Uterovaginal origin Ovarian Uterovaginal Ovarian
origin origin origin
Outflow tract Polycystic Müllerian Androgen
obstruction ovary agenesis insensitivity
syndrome syndrome
II. Patients with poorly developed secondary sexual

characteristics
Ovarian origin Pituitary Hypothalamic origin
origin
Gonadal Levi–Lorain Kallmann syndrome
dysgenesisa syndrome Idiopathic
Resistant ovary Empty sella hypogonadotropic
syndrome syndrome hypogonadism
Gigantism Fröhlich syndrome
(acidophil Laurence–Moon–Biedl
adenoma) syndrome
III. Patients with male characteristics (virilization)

Ovarian causes Adrenal causes
Virilizing ovarian Congenital adrenal hyperplasia
tumors Androgen-secreting tumors
a
The most common cause of primary amenorrhea (43%)
Amenorrhea 65
B. Secondary amenorrhea
I. Hypothalamic origin
Functional causes Organic causes
• I ntense exercise (jogger’s/ •B rain tumors (e.g.,
athletic amenorrhea) craniopharyngioma)
• Stress • Post-traumatic brain injury
• Malnutrition
• Anorexia nervosa
• Pseudocyesis (false pregnancy)
II. Pituitary origin
Functional causes Organic causes
• Medication-induced • Pituitary tumors, e.g.:
hyperprolactinemia, e.g., • Prolactin-secreting
some antipsychotic drugs, tumors (prolactinoma)
antidepressants, and • ACTH-secreting
antihypertensive agents adenomas (Cushing’s
•P ituitary deficiency: Sheehan disease)
syndrome and Simmonds’ • Growth hormone-
disease secreting adenoma
(acromegaly)
III. Ovarian origin
Functional causes Structural causes
• Polycystic ovary syndrome •S urgical removal (bilateral
•P remature ovarian failure oophorectomy)
(POF) •E xposure to radiotherapy,
chemotherapy
• Androgen-secreting tumors
IV. Uterovaginal origin
Functional causes Structural causes
• Pregnancy a • Asherman syndrome
(intrauterine adhesions)
• Hysterectomy
General causes
• Thyroid disease
• Chronic kidney disease
• Chronic liver disease
• Adrenal diseases (e.g., Cushing’s syndrome, Addison’s disease)
• Bronchogenic carcinoma
a
The most common cause of secondary amenorrhea
Evaluation of a case of amenorrhea – diagnosis:
I. History
• History of present illness: the following symptoms may

provide a clue for diagnosis of the underlying cause:
Symptom Related diagnosis
• Headache/visual changes • Pituitary/CNS tumors
• Anosmia • Kallmann syndrome
•H
eat or cold intolerance, • Thyroid disease
hair loss, bowel symptoms,
weight changes
•S
pontaneous bilateral • Hyperprolactinemia
breast discharge
•H
ot flushes and vaginal • Premature ovarian failure
dryness prior to the age of
40 years
• Hirsutism and acne •P
olycystic ovary syndrome or
late-onset congenital adrenal
hyperplasia
•C
yclic pelvic pain, • Cryptomenorrhea
abdominal distension
•E
xercise, weight loss, • Hypothalamic amenorrhea
eating disorder, chronic
illness
•U
nprotected intercourse, • Pregnancy
failed contraception use
Amenorrhea 67
Headache
Anosmia
Hot flushes
Hirsutisum
Thyroid
symptoms
Breast
discharge
Cyclic
pelvic pain
• Pubertal history: including age at onset and sequence of

pubertal changes
• Menstrual history: including history of previous regular
menstrual cycles and their characters
• Contraceptive history: a period of amenorrhea may persist
after discontinuation of contraceptive injections
• Medical history:
–– History of thyroid, chronic renal, or hepatic diseases,
radiotherapy, or chemotherapy
–– Autoimmune disease (e.g., thyroid or adrenal), which
may be associated with premature ovarian failure
–– List of current medications: e.g., medications causing
hyperprolactinemia
• Surgical history: history of intrauterine surgery, e.g., dila-
tion and curettage (possibility of Asherman syndrome)
• Family history:
–– Family history of polycystic ovary syndrome
–– Family history of congenital adrenal hyperplasia (or
sudden neonatal death)
–– Family history of premature ovarian failure or autoim-
mune disease which may be associated with premature
ovarian failure
II. Examination
• General examination: a thorough physical examination

includes:
–– General assessment:
The following physical signs may give a clue for
diagnosis:
Physical sign Related diagnosis
•L
ow body mass index, loss of • Eating disorder
tooth enamel
• Webbed neck, short stature • Turner syndrome
• Acanthosis nigricans, hirsutism, • PCOS
or acne
•S
upraclavicular fat, abdominal • Cushing’s syndrome
striae, hypertension
• Enlarged thyroid, heart rate • Thyroid disease
changes, altered neurologic reflexes
• Bilateral galactorrhea • Hyperprolactinemia
Amenorrhea 69
–– Assessment of secondary sexual characteristic develop-

ment (Tanner staging):
Staging Breast development Pubic hair development
Tanner 1 Prepubertal Prepubertal appearance
appearance
Tanner 2 Elevation of breast and Sparse long, slightly
papilla (breast bud), pigmented hair, along labia
enlargement of areola
Tanner 3 More enlargement of Dark, coarse and curled
breast and areola hair, spreading sparsely
over mons pubis
Tanner 4 Elevation of the areola Hair adult in type, but no
and papilla above the spread to medial surface of
level of breast contour thighs
(secondary mound)
Tanner 5 Recession of areola to Adult in type and quantity,
breast contour with horizontal distribution
(“feminine”)
According to this, the following is the normal sequence for

pubertal growth:
Breast Pubic hair

Stage of development stage stage Age
Initial growth 1 1 9
acceleration
Thelarche 2 1 10
Adrenarche 2 2 10
Peak growth 3 3 12
Menarche 4 4 13
Adulthood 5 5 15
–– Local examination:
Examination of the genitalia may reveal the follow-
ing clues:
Physical sign Related diagnosis

• Sparse/absent pubic hair • Androgen insensitivity syndrome
• Clitoromegaly • Virilization
• Atrophic vagina • Premature ovarian failure
• Bulging hymen • Imperforate hymen
• Vaginal dimple • Androgen insensitivity syndrome
or Müllerian agenesis
III. Investigations
❶ Laboratory testing:
➀ Urinary or serum β-hCG: should be the first step to rule
out pregnancy for all sexually active women (regardless
of whether they are currently using contraception or not)
➁ Serum hormone levels:
• Indications: any patient with amenorrhea and nor-
mal pelvic examination
• Tests:
Primary laboratory tests Secondary laboratory tests
• Follicle-stimulating hormone • Serum testosterone:
(FSH): − Slightly high (≤200 ng/dL):
− High (2 FSH levels >40 mIU/mL likely chronic anovulation
at least 1 month apart): indicates (PCOS)
ovarian etiology (menopause, − Significantly high (>200 ng/
premature ovarian failure, gonadal dL): androgen-secreting
dysgenesis) tumor is suspected
− Low: indicates hypothalamic– • Serum DHEAS (N= 250–300
pituitary etiology ng/dL):
• Prolactin: high level indicates − Slightly high (≤700 ng/dL):
hyperprolactinemia (e.g., pituitary chronic anovulation
adenoma) − Significantly high (>700 ng/
• TSH: abnormalities indicate thyroid dL): adrenal/ovarian tumor
dysfunction is suspected
• Serum 17-OH progesterone:
− High: indicative of
congenital adrenal
hyperplasia
Amenorrhea 71
➂ Hormonal withdrawal tests:

Estrogen and
Progesterone progesterone
withdrawal test withdrawal test
Test method 10 mg of Combined oral
medroxyprogesterone contraceptives are
acetate is given daily for given for 21 days
5 days
Positive testa Consider anovulation Functioning uterus
and patent outflow
Negative test Estrogen progesterone Consider
withdrawal is uterovaginal cause,
recommended e.g., Asherman
syndrome
a
Positive test is indicated by withdrawal bleeding within 7–10 days of
cessation of exogenous hormone(s)
❷ Imaging tests:
➀ Pelvic sonography:
• It may be performed as a part of work-up of PCOS.
• It helps to determine the presence or absence of the
uterus.
➁ CT and MRI:
• Indications:
–– Patients with hypogonadotropic hypogonadism
(brain imaging)
–– Patients with elevated androgens concerning of
ovarian or adrenal tumors (abdominal/pelvic
imaging)
❸ Chromosomal analysis: indicated in:
• Patients with gonadal dysgenesis (up to age 35 years) to
identify Y chromosome requiring bilateral
oophorectomy
• Patients with absent uterus for differentiation between
AIS and Müllerian agenesis
• Patient with family history of premature ovarian
failure
Primary amenorrhea
Assessment of secondary sexual characteristics

Absent Present
Assessment of serum FSH Pelvic exam/pelvic sonography/MRI
Low FSH (<5 IU/L) High FSH Uterus absent Uterus present
(hypogonadotropic (hypergonadotropic
hypogonadism) hypogonadism)
Karyotyping Outflow obstruction
Karyotyping
CT and MRI for 46 XX 46 XY Yes No
hypothalamic
and pituitary evaluation 46 XX 45 XO Crypto Check TSH,
Müllerian Androgen
Premature Turner agenesis insensitivity menorrhea prolactin,
ovarian failure syndrome syndrome and HCG
(see below)
Secondary amenorrhea
β-HCG to
If negative
Check TSH and prolactin
Both are normal Abnormal TSH Normal TSH, high prolactin
Assessment of Thyroid MRI to evaluate for

FSH level disease prolactinoma
Low FSH High FSH Normal FSH

(hypogonadotrophic (hypergonadotropic
hypogonadism) hypogonadism)
Assessment of 17-hydroxy
progesterone, DHEAS, and
CT and MRI for Premature ovarian testosterone
hypothalamic and failure
pituitary
evaluation/consider
hypothalamic All normal High testosterone High DHEAS level High 17-hydroxy-
causes, e.g., eating progesterone
disorders
Progesterone Polycystic ovary syndrome
challenge test Congenital
adrenal
hyperplasia
Consider pelvic Consider adrenal
sonography for MRI if significantly
ovarian assessment high
Withdrawal bleeding No withdrawal bleeding
Anovulation Estrogen/progesterone
challenge test
Withdrawal bleeding No withdrawal bleeding
Hypothalamic-pituitary- Uterine cause (e.g.,

ovarian axis dysfunction Asherman syndrome)
Amenorrhea-Related Disorders 73
Treatment:
Example
• Anatomic abnormalities: surgical correction, if possible
• Hypothyroidism: thyroid replacement
• Late-onset CAH: low-dose corticosteroids to block ACTH stimulation
Management according to patient concern
Absence of menstruation only Infertility
If treatment of the cause fails or if underlying cause Fertility usually regains after treatment of underlying
cannot be corrected, hormonal therapy should be cause. POF can be offered third-party options
offered to all women with hypo-estrogenic disorders Induction of ovulation is given according to WHO
If no cause is identified, COCs, given for three classification of causes of anovulation
successive cycles, may restore normal rhythm
Hypogonadotropic Normogonadotrophic Hypergonadotropic Hyperprolactinemic

hypogonadism normoestrogenic, hypoestrogenic anovulation
(Hypothalamic/pituitary) e.g., PCOS (POF)
Induction of ovulation Induction of ovulation Third-party Dopamine agonists,

using pulsatile GnRH using letrozole, reproduction options, e.g., cabergoline
or gonadotrophins clomiphene citrate, or e.g., IVF and egg
gonadotrophins donation
Amenorrhea-Related Disorders
Polycystic Ovary Syndrome
Definition:
ESHRE/ASRM Rotterdam conference criteria (2003)
To include two out of three of the following:
• Oligo- or anovulation
• Clinical and/or biochemical signs of hyperandrogenism
• Polycystic ovaries
The diagnosis should be made after exclusion of other causes of
these features
Incidence: polycystic ovary syndrome (PCOS) is the most

common cause of chronic anovulation (4–12%).
Etiology and pathogenesis:
The underlying cause of PCOS is unknown and is likely mul-
tifactorial and polygenic. However, PCOS pathology seems
to be initiated by alteration in GnRH pulsatility which leads
to increased production of LH. Processes associated with

PCOS are shown in this figure:
Hypothalamus
↓
Alteration of GnRH release
↓
Pituitary gland Abnormal
feedback
↓
↑ LH:FSH ratio
Adrenal ↓
gland Ovary (theca cells)
↓ Converted in adipose tissue
Abnormal
lipid profile ↑ Androgen production ↑ Estrone
Uterus
Skin Insulin Follicular
resistance atresia Endometrial
Acne, Hirusutism, acanthosis hyperplasia
negricans Anovulation/
amenorrhea
Diagnosis:
• Clinical features:
❶ Menstrual irregularities:
• Type of menstrual irregularities:
–– The most common are infrequent uterine bleeding
(previously known as oligomenorrhea) and
amenorrhea.
–– Women with PCOS may present with postmenar-
chal menstrual irregularities that persist for more
than 2 years after the age of menarche.
• Etiology of menstrual irregularities:
–– Anovulatory cycles
–– Endometrial hyperplasia associated with chronic
anovulation
–– Endometrial atrophy secondary to the effect of
excess androgens
• Other possibilities to rule out: within 2 years of men-
arche, menstrual irregularities are common due to hypo-
thalamic–pituitary–ovarian axis immaturity (50%).
❷ Hyperandrogenism:
➀ Hirsutism:
• Definition:
Hirsutism refers to the presence of thick, dark,
terminal hair that has a male pattern distribution.
• Clinical assessment:
Ferriman–Gallwey score refers to a scoring sys-
tem that assesses nine regions of the body (upper
lip, chin, chest, upper back, lower back, upper
abdomen, lower abdomen, arm, and thigh). Each
region is given a score of 0 to 4 depending on the
distribution of terminal hair.
A score of 8 or more is consistent with hirsutism.
Advantage: standardized clinical method for
quantitative assessment of hirsutism
Disadvantage: racial variation in non-patholog-
ical hair growth
• Other possibilities to rule out: hypertrichosis,
which refers to generalized increase in soft, lightly
pigmented body hair.
➁ Acne:
PCOS may be associated with persistent or late-
onset acne
➂ Alopecia:
PCOS association with androgenic or male pat-
tern alopecia is less common.
❸ Acanthosis nigricans:
• Definition:
Acanthosis nigricans refers to thickened, grayish
or brownish plaques that are most noted at body flex-
ures, e.g., nape and axillae. It is more common among
obese compared to nonobese women with PCOS.
• Etiology: these lesions are likely caused by abnormal
stimulation of keratinocytes by excess insulin sec-
ondary to insulin resistance.
❹ Infertility:
• Infertility related to PCOS is most commonly caused
by anovulation.
• However, not all women with PCOS present with
infertility.
Complications associated with PCOS:

Short-term complications Long-term complications
• Pregnancy-related risks: • Diabetes mellitus:
❶ Early pregnancy loss The risk increases in the
❷ Gestational diabetes presence of obesity and family
❸ Gestational hypertension history of diabetes
❹ Preterm birth • Cardiovascular disease:
❺ Perinatal mortality Risk of coronary artery
• Obesity: disease in women with PCOS
• PCOS is associated with may be attributed to insulin
central obesity resistance, impaired glucose
• Obesity is present in 80% tolerance/diabetes, and obesity
of cases • Endometrial cancer:
• Sleep apnea • Increased risk of
• Abnormal lipid profile: endometrial cancer is
Insulin resistance results in attributed to endometrial
dyslipidemia stimulation with estrogen
• Metabolic syndrome: unopposed sufficiently
Approximately 45% of women with progesterone due to
with PCOS meet the criteria of anovulation
metabolic syndrome • Obesity and insulin
• Impaired glucose tolerance: resistance also
It is reported in 35% of PCOS contributes to the
patients by the age of 40 increased risk
• Nonalcoholic fatty liver
disease
• Anxiety and depression
• Work-up:
Testing for PCOS consists of testing for diagnosis and
testing for complications:
I. Work-up to establish diagnosis

❶ Hormonal profile:
The aim of hormonal testing is to rule out other
causes of hyperandrogenism and anovulation to con-
firm the diagnosis of PCOS.
Test Significance
I. Tests to rule out other similar diagnoses (tested in all patients
with possible PCOS)
Serum TSH • The test is used to rule out thyroid disease
Serum prolactin • The test is to rule out hyperprolactinemia
• A slight increase in serum prolactin can be
seen in up to 25% of PCOS patients
17-Hydroxypro- • It is used to rule out adult onset congenital
gesterone adrenal hyperplasia (CAH)
Serum FSH • Anovulation due to hypogonadotropic
hypogonadism (hypothalamic/pituitary origin)
is associated with significantly low FSH
• Anovulation due to hypergonadotropic
hypogonadism (premature ovarian failure) is
associated with significantly high FSH
II. Androgen profile (not tested in all patients, only as indicated)
Serum total • It is indicated in:
testosterone ➀ Women with severe virilization.
Significant rise may indicate androgen-
secreting ovarian neoplasms and ovarian
hyperthecosis
➁ Possible PCOS with no clinical
hyperandrogenism (to rule out
hyperandrogenemia as a criterion of
diagnosis)
• The test is may be performed to access
hyperandrogenemia if clinical signs of
hyperandrogenism are not clear. Otherwise,
clinical signs should be sufficient as a criterion
for diagnosis of PCOS
• Total testosterone testing is superior to
free testosterone. Free testosterone is less
standardized and reliable compared to total
testosterone
Test Significance
Serum • Increases in PCOS patients
androstenedione
Serum DHEAS • It is indicated in women with severe
virilization. Significant rise may indicate
androgen-secreting adrenal neoplasms
• Increased in 50% of women with PCOS
Among women with PCOS who receive oral contraceptives,

androgen profile is not informative and should not be tested.
❷ Pelvic sonography:
• Diagnostic features:
Sonographic criteria for polycystic ovaries (Rotterdam

conference)
❶ The presence of ≥12 small cysts (2 to 9 mm in diameter) or
❷ An increased ovarian volume (>10 mL)
• Other possibilities to rule out:

A subjectively similar sonographic appearance of PCOS
may be noted in women with CAH and Cushing’s syn-
drome (pearl necklace appearance of ovarian follicles).
II. Work-up to assess complications
❶ Diagnosis of diabetes:
• A 2-hour glucose tolerance test (2-hr GTT) and HgbA1C
are recommended at initial diagnosis of PCOS.
• Follow-up should be performed every 2 years in absence of
impaired glucose tolerance or 1 year in the presence of
impaired glucose tolerance for early diagnosis of diabetes.
❷ Diagnosis of dyslipidemia:
Fasting lipid profile should be evaluated at initial diag-
nosis of PCOS.
❸ Diagnosis of endometrial hyperplasia/carcinoma:

Although endometrial biopsy is indicated in women >45
years old with abnormal uterine bleeding, women with
PCOS are at higher risk, and therefore, endometrial biopsy
is indicated in women younger than 45 years in the pres-
ence of abnormal uterine bleeding.
Differential diagnosis of PCOS:
Other causes of oligo- or Other causes of

anovulation hyperandrogenism
• Hyperthyroidism • Late-onset CAH
• Hypothyroidism • Cushing’s syndrome
• Hyperprolactinemia • Androgen-secreting ovarian
• Hypogonadotropic tumor
hypogonadism (hypothalamic/ • Androgen-secreting adrenal
pituitary origin) tumor
• Hypergonadotropic • Ovarian hyperthecosis
hypogonadism (premature • HAIR-AN syndrome
ovarian failure) (hyperandrogenism–insulin
resistance–acanthosis
nigricans)
Treatment:
I. General recommendations
Lifestyle changes including well-balanced hypocaloric diet

and exercise. Weight reduction may restore normal ovulatory
cycles.
II. Treatment according to patient concern
A. Patients who present with menstrual disorders

❶ Combined oral contraceptive pills (OCPs):

OCPs present the first-line treatment for menstrual
disorders in patients with PCOS. Exclusion of pregnancy
should be documented before starting treatment.
• Advantages:
–– Restoration of regular menstrual cycles
–– Reduction of androgen levels (through suppression
of pituitary gonadotropins)
–– Reduction of circulating testosterone (estrogen
increases level of sex hormone-binding globulin
which binds to free androgens)
–– Endometrial protection (progestin antagonizes pro-
liferative effect of unopposed estrogen on the
endometrium)
–– Contraception method in women who are not willing
to become pregnant
• Disadvantages:
Side effects and complications associated with OCPs.
Attention should be paid to venous thromboembolism
given the high BMI of this population. PCOS itself is
not a risk factor for venous thromboembolism.
• Options:
–– Contraceptive pills containing at least 20 mcg ethinyl
estradiol should be given. High-dose ethinyl estra-
diol may be required to improve symptoms (30–35
mcg).
–– Norethindrone is an appropriate progestin option as
it has moderate androgenic activity and similar
venous thromboembolism risk compared to
levonorgestrel.
❷ Progestins:
• Indication: it is indicated if estrogen component of
OCPs is medically contraindicated.
• Options:
Endometrial
Option Regimen protection Contraception
Medroxy- 5–10 mg orally Yes No
progesterone daily for 12
acetate (MPA) days
Norethindrone 0.35 mg Yes Yes
orally daily
(continuously)
Levonorgestrel- Once every 5 Yes Yes
releasing IUD years
❸ Metformin:
Metformin may restore ovulatory function in 30–50%
of PCOS patients. Nevertheless, the medication does not
provide contraception. Evidence on endometrial protec-
tion is limited.
B. Patients present with hirsutism
Treatments may require 6 to 12 months before clinical

improvement is apparent.
Options Treatment
OCPs • First-line therapy
• If the cosmetic results are suboptimal after
6 months, spironolactone can be added
Androgen • Spironolactone: 50 to 100 mg twice daily
receptor • The medication should be given in
antagonists combination with a contraceptive because
of the risk of pseudohermaphroditism to
exposed male fetuses in early pregnancy
Options Treatment
GnRH agonists • The medication is expensive and is
associated with significant side effects.
“Add-back” therapy should be added
Antimetabolite • Eflornithine hydrochloride inhibits hair
creams growth
• It is applied twice daily to areas of facial
hirsutism and should be used indefinitely
5α-Reductase • Finasteride is modestly effective in the
inhibitors treatment of hirsutism
Hair removal • Hirsutism can be treated mechanically
(depilation and epilation)
C. Patients who present with acne
❶ OCPs: it improves acne within 3 months

❷ Topical retinoids: with or without antimicrobial agents
❸ Antiandrogens: such as spironolactone
• Three to six months of therapy is necessary before
treatment success is assessed.
• In pregnant women, safe alternatives include oral or
topical erythromycin and topical clindamycin.
D. Patients complaining of infertility
❶ Induction of ovulation:
• Letrozole: it is the first-line medication for women with
BMI >30.
• Clomiphene citrate: it is used for nonobese patients

(BMI <30).
• Gonadotrophins: if medications fail to achieve ovula-
tion induction.
• Insulin-sensitizing agents: e.g., metformin 250–500 mg
three times daily.
Metformin does not increase probability of ovulation
or pregnancy. However, it may reduce the risk of ovar-
ian hyperstimulation during in vitro fertilization (IVF)
cycles.
For more details, please read under: Infertility.
❷ Surgical treatment:
• Laparoscopic ovarian drilling is comparable in efficacy
to ovulation induction with gonadotrophins.
• Although it is not associated with risk of ovarian hyper-
stimulation, medical induction is the preferred approach
because of associated surgical risks.
❸ Assisted reproductive technology: if above options are not
successful
E. Patients with associated metabolic abnormalities
❶ Obesity:
Management is similar to obese patients without PCOS
(lifestyle modification, medications, possible bariatric
surgery)
❷ Glucose intolerance/diabetes:
Among women with PCOS, metformin is recommended
for the following benefits:
➀ It may prevent or delay the development of diabetes.
➁ It restores menstrual cycle regularity in 30–50% of
patients.
➂ It reduces the risk of ovarian hyperstimulation associ-
ated with IVF cycles.
❸ Dyslipidemia:
As with patients without PCOS, statins can be used to
manage dyslipidemia.
Gonadal Dysgenesis
onadal Dysgenesis with Abnormal Karyotype

G
(Turner Syndrome)
Definition:
Turner syndrome is a sex chromosome abnormality that
results in in utero accelerated atresia of fetal oocytes. Ovaries
eventually appear as fibrous streaks with no or reduced num-
ber of oocytes.
Incidence:
Turner syndrome represents about two-thirds of gonadal dys-
genesis. It occurs in 1:2000–2500 live female births.
Types:
• 45-XO karyotype: which refers to complete absence of one
X chromosome (monosomy)
• Chromosomal mosaicism:
–– The most common form of mosaicism is 45 XO/46 XX
karyotype.
–– Patients can be at risk of malignant germ cell tumor if
chromosomal mosaicism includes a Y chromosome, e.g.,
45X/46 XY (risk is 25%).
• 46 XX karyotype: in this case, partial deletion of X chro-
mosome results in Turner syndrome (abnormal X
chromosome).
Diagnosis:
I. Clinical presentation
I. Classic presentation (45 XO karyotype – monosomy)
• Symptoms:
Primary amenorrhea, delayed puberty, and primary
infertility
• Physical features:
–– Short stature
–– Webbing of the neck
–– Shielding of the chest
–– Underdeveloped breasts
–– Cardiac (aortic coarctation) and renal anomalies
–– Bilateral cubitus valgus (wide carrying angle)
–– Ears, fingers, and toes deformities
–– Infantile genital organs
II. Presentation in patients with mosaic Turner syndrome
Compared to classic 45 XO features, mosaic Turner syndrome

may have:
• Taller stature (but likely still shorter than average for their
age).
• Fewer somatic abnormalities.
• Few oocytes; 20% of these women may undergo spontane-
ous menstruation that eventually ends in premature meno-
pause (premature ovarian failure).
III. Presentation in patients with abnormal X

chromosome
86
Patients with
Patients with terminal Patients with deletions on isochromosome Xq (2
deletions on long arm of X short arm of X chromosome copies of long arm of X Patients with ring
chromosome (Xq) (Xp) chromosome) chromosome X (rX)
• Normal stature • Typical physical features Autoimmune disorders • Clinical features are
• No somatic abnormalities of Turner syndrome such as thyroiditis similar to women with Xp
Chapter 2. Menstrual Disorders
• Primary amenorrhea and • Ovarian insufficiency deletion

infertility (streak gonads) • Some patients may have
atypical features, e.g.,
facial dysmorphisms and
syndactyly
II. Work-up
• Indications for work-up:

–– Unexplained primary amenorrhea or delayed puberty
–– Infertility particularly with elevated FSH
–– Females with physical features of Turner syndrome
–– Unexplained short stature
–– Obstructive left-sided cardiac defects, e.g., aortic coarc-
tation, bicuspid aortic valve
• Testing:
–– Karyotype analysis:
Tests cells are mononuclear cells from peripheral
blood.
If it is negative despite high suspicion of Turner syn-
drome, it may be repeated using skin fibroblasts, buc-
cal mucosa, or urine sample.
Fluorescence in situ hybridization (FISH) and
reverse transcriptase polymerase chain reaction
(PCR) increase the chance of detection of chromo-
somal mosaicism (specially if a Y chromosome is
suspected).
–– Imaging:
Once the diagnosis of Turner syndrome is made,
appropriate imaging should be performed to detect
possible associated anomalies, e.g., cardiac and renal
anomalies.
Management:
• General management:
–– Associated structural abnormalities should be thor-
oughly evaluated and should be managed as indicated
by specialists.
–– Genetic counseling should be considered.
• Hormonal treatment:
–– Growth hormone therapy:
The aim of treatment is to achieve adequate final
adult height.
Treatment starts before initiation of estrogen
therapy.
–– Estrogen therapy:
Oral estrogen and estrogen patches can be used.
Goal of treatment: it promotes sexual maturation
and initiates menstruation. The treatment also
reduces the risk of mortality related to estrogen defi-
ciency, e.g., cardiovascular diseases and osteoporosis.
Initiation of treatment: it starts at 11–12 years old
when growth hormone therapy is completed, to
avoid premature closure of bone epiphyses.
Treatment regimen: micronized estrogen starts at
0.25 mg and is increased gradually to 2 mg or estro-
gen patch 25 mcg that is increased gradually to 100
mcg by the age of 15.
–– Progestin therapy:
Goal of treatment: it is given for endometrial
protection.
Initiation of treatment: it starts at 12.5–13.5 years.
Treatment regimen: MPA is given 5–10 mg (or
200 mg of micronized progesterone) daily for 10–14
days each month.
• Surgical treatment: if patient’s karyotype is mosaic with Y
chromosome involved, streak gonads should be removed
to avoid the risk of malignant transformation (25%).
• Fertility management:
–– Preconception counseling: prior to conception, medical
assessment of associated cardiac abnormalities should
be considered. A transesophageal echocardiogram
should be obtained within 2 years of fertility
management.
–– IVF using oocyte cryopreservation: is an option among

women with some initial ovarian function. Success rate
is overall low.
–– IVF using donor oocytes: success rate is more favorable
compared to oocyte cryopreservation.
onadal Dysgenesis with Normal Karyotype

G
(Pure Gonadal Dysgenesis)
Etiology:
• Genetic causes, likely due to single gene defects
• In utero gonadal tissue damage, likely secondary to infec-
tion, radiation, or toxins
Features:
• Karyotype: normal karyotype either 46XX or 46XY
(Swyer syndrome).
• Phenotype: Regardless of karyotype, patients are pheno-
typically female.
Treatment: treatment is similar to management lines of

Turner syndrome.
Outflow Tract Obstruction
Causes:
Inherited Acquired
• Labial agglutination or • Cervical stenosis secondary
fusion, e.g., fetal congenital to conization, electrosurgery,
adrenal hyperplasia (CAH) or or cryosurgery
luteoma of pregnancy • Cervical obstruction, e.g., by
• Imperforate hymen a cervical fibroid
• Transverse vaginal septum
• Isolated atresia of the vagina
or cervix
Pathology:
• Due to the presence of outflow obstruction, blood accu-
mulates above the level of obstruction and becomes thick
and dark-colored.
• Accumulated blood expands the vagina (hematocolpos),
the uterus (hematometra), and the tubes (hematosalpinx)
and eventually accumulates in the pelvis (pelvic
hematocele).
Diagnosis:
Symptoms
• Primary amenorrhea
• Cyclic lower abdominal pain
• Abdominal swelling which may be caused by hematocol-
pos or a full bladder secondary to urinary retention
• Pressure symptoms, e.g., urinary frequency, dysuria, and
urinary retention
• Fever and malaise
Signs
• General examination: well-developed secondary sexual

characteristics
• Abdominal examination: tense, cystic pelvi-abdominal
mass of limited mobility
–– Vaginal examination:
Imperforate hymen: it appears as a bulging bluish
closed hymen.
Vaginal aplasia: it is noted as a vaginal dimple with
absent vagina.
–– Rectal examination: cystic swelling may be palpated

compressing anterior rectal wall.
Work-up
• Pelvic MRI: for assessment of presence of the uterus and

of site of obstruction and possibly to identify associated
urological abnormalities
• Laparoscopy: is typically not indicated in diagnosis
Treatment:
• Identification of the cause
• Surgical treatment of the cause including:
–– Imperforate hymen:
Elliptical incision (along diagonal diameters) or cru-
ciate incision of the hymen is done to create or
enlarge hymenal orifice.
Retained blood is allowed to drain slowly (a suction
cannula may be used to help evacuating a large
hematocolpos).
Edges of the hymen are sutured to the vaginal
mucosa using interrupted sutures to ensure good
hemostasis.
–– Transverse vaginal septum:
If the septum is thick: it can be managed by excision
and skin grafting.
If the septum is thin: it can be managed by excision
and end-to-end anastomosis or Z-plasty.
Sheehan syndrome
Definition:
It is a syndrome of anterior pituitary necrosis (postpartum
hypopituitarism) due to severe postpartum hemorrhage or
extreme hypotension during or after labor.
Diagnosis:
Sheehan syndrome presents with varying degree of anterior
pituitary gland hormonal deficiency, e.g.:
Defect Clinical feature Work-up

Deficient Failure of lactation Assess serum
prolactin (1st symptom) – breast hormonal levels,
atrophy hormone stimulation
tests
Deficient Secondary amenorrhea,
gonadotrophins genital atrophy, loss of
libido
Deficient ACTH Hypoglycemia,
hypotension, increased
susceptibility to
infection, anemia,
thrombocytopenia
Deficient TSH Mental dullness, recent
cold intolerance, hair
falling
Treatment:
• Hormonal replacement: this includes levothyroxine, corti-
costeroids, estrogen and progesterone (up to the average
age of menopause), and growth hormone (to maintain
bone density, muscle bulk, and cholesterol levels).
• Infertility treatment: these patients may receive gonado-
trophins for ovulation induction.
Hyperprolactinemia
Definition:
Hyperprolactinemia refers to abnormal elevation of serum
prolactin (which is derived from lactotrophs of the anterior
pituitary gland). Prolactin level above 15–20 nanograms/ml is
considered abnormal:
Hyperprolactinemia 93
• Mild hyperprolactinemia: 20–50 nanograms/ml

• Moderate hyperprolactinemia: 50–100 nanograms/ml
• Severe hyperprolactinemia: >100 nanograms/ml
–– Function of prolactin hormone: the main function of
prolactin is production of milk from the mammary
glands.
–– Regulation of prolactin hormone:
Inhibition of prolactin secretion: prolactin-inhibiting
factor (dopamine)
Stimulation of prolactin secretion: estrogen, sero-
tonin, and thyrotropin-releasing hormone (TRH)
Causes:
• Physiological causes:
–– Pregnancy: due to high estrogen level during
pregnancy.
–– Lactation: breast stimulation causes reflex suppression
of dopamine.
–– Stress: both physical and psychological.
–– Sexual intercourse
–– Sleep: the highest prolactin secretion occurs between 5
and 7 am.
–– Hypoglycemia
• Pathological causes:
–– Hypothalamic disorders:
Infiltrative pathology (e.g., sarcoidosis): interferes
with dopamine secretion
Destructive pathology (e.g., craniopharyngiomas,
metastatic cancer): interferes with dopamine
secretion
Traumatic pathology (e.g., head trauma): may injure
hypothalamic–pituitary stalk and interferes with
dopamine transport
–– Pituitary disorders:
Idiopathic hyperprolactinemia: no cause is
identified.
Prolactinomas (lactotroph adenomas): these adeno-
mas present 30–40% of pituitary adenoma. They are
associated with increased secretion of prolactin.
Other pituitary adenomas: due to interference with
secretion and transport of dopamine.
–– Thyroid disorders:
Primary hypothyroidism may be associated with
hyperprolactinemia due to increased production and
pituitary responsiveness to TRH.
–– Chest wall disease or injury (e.g., chest burn, herpes
zoster, breast diseases, and mastectomy): may stimulate
prolactin secretion.
–– Chronic renal disease: due to increased prolactin pro-
duction and decreased urinary secretion.
–– Polycystic ovary syndrome: it may be associated with
slight hyperprolactinemia that may be attributed to
increased estrogen level.
–– Drug-induced hyperprolactinemia, e.g.:
Antipsychotics (most common drug-related cause):
e.g., risperidone, phenothiazines, and haloperidol (D2
receptor antagonists)
Antihypertensives: as methyldopa inhibits dopamine
synthesis
Antiemetics: e.g., metoclopramide (D2 receptor
antagonists)
Diagnosis:
I. Clinical features
Short Mild • Infertility: with or without

term hyperprolactinemia menstrual disorders due to:
– Anovulation
– Short luteal phase
Moderate • Infertility
hyperprolactinemia • Amenorrhea (20% of
patients with secondary
amenorrhea) because
prolactin causes:
– Inhibition of GnRH
secretion
– Refractoriness of the
ovary to pituitary
gonadotrophins
– Inhibition of ovarian
steroidogenesis
• Oligomenorrhea
Severe • Infertility
hyperprolactinemia • Amenorrhea
• Menopausal symptoms: hot
flushes, vaginal dryness,
loss of libido (due to
hypoestrogenism)
• Hirsutism: prolactin
decreases sex hormone-
binding globulin level.
Therefore, free testosterone
level increases
Long term • Osteoporosis
• Galactorrhea:
–– Definition: persistent secretion of non-bloody non-
purulent discharge from the breast in absence of
breastfeeding.
–– Etiology: it may be caused by hyperprolactinemia or
hypersensitivity to prolactin action.
–– Assessment:
Each quadrant of the breast should be squeezed

from the periphery toward the nipple.
Galactorrhea can be confirmed by the presence of
fat globules (microscopic assessment using fat stains).
–– Clinical significance:
66% of women with hyperprolactinemia do not have
galactorrhea, and 50% of women with galactorrhea do
not have hyperprolactinemia. Therefore, this sign is nei-
ther conclusive nor essential for diagnosis.
II. Work-up
For diagnosis For etiology

Rule out drug
induced
Assessment of serum prolactin hyperprolactinemia
• Patients with amenorrhea
Indication
• Patients with galactorrhea

• Infertility with anovulation
Assessment of Assessment of
• Hirsutism with irregular cycles
renal function thyroid function
• 5–20 ng/ml = normal
Results
• 20–50 = mild elevation

• 50–100 = moderate elevation
• > 100 = severe elevation Serum Serum thyroid
• Borderline elevation may be due creatinine cascade
to physiologic causes and it If both are negative
should be repeated
Precautions
• Hook effect: very high elevation

Pituitary MRI with contrast
may test as slight elevation. This
can be solved by sample dilution
• Macroprolactin: it causes false
positive results. This can be Pituitary mass Negative
resolved by treating the sample
with polyethylene glycol
Check insulin-like growth factor 1 Idiopathic
and ACTH hyperprolactinemia
Treatment:
Symptomatic patients secondary to hyperprolactinemia

Symptomatic patients secondary to pituitary adenoma (visual changes, headache)
Patients seeking fertility treatment
Initiation of treatment
Treatment of the cause, e.g., thyroid replacement
Idiopathic hyperprolactinemia Prolactinomas
Dopamine agonists
Microadenoma Macroadenoma
Regimen Advantages Side effects
(< 1 cm) (> 1 cm)
0.5 mg once Prolonged Risk of vulvar heart
Cabergoline
weekly action, less disease if the dose is

(maximum is side effects higher than 2
Cabergoline or Start Cabergoline
2 mg/ week) mg/week
Bromocriptine for 4
weeks
1.25 mg Cheaper Nausea, vomiting, Follow up
Bromocriptine
twice daily postural hypotension,

dizziness and • Serum prolactin: every 1–3
constipation months to titer medication
Check serum
prolactin level dose.
• MRI: every 6–12 months to
Up to 300 µg Non-ergot Not available in the
follow-up adenoma size
Quinagolide
daily medication (not USA

associated with • Vision assessment: monthly
cardiac
complications) if visual field changes are
present at baseline
Inadequate Adequate response

response (normal prolactin,
Complete response Partial response (serum No response or resolution of
(Normal prolactin) prolactin improves, but treatment intolerance symptoms, significant
still high)
shrinkage in
Continue treatment for 12- • Titer medication to adenoma size)
months, check prolactin maximum dose
Increase medication dose
yearly
and continue prolactin level
follow-up • Shift to cabergoline if After 1 year of adequate
initially on bromocriptine response: dose can be
If prolactin is normal, decreased

dose can be decreased. No response After 2 years: treatment
Treatment may be
stopped after 24 months may be stopped if MRI is
Trans sphenoidal negative
surgery
Dysmenorrhea
Definition: cyclic abdominal cramping pain during menstruation
Types:
Primary Secondary dysmenorrhea
dysmenorrhea
Definition Cyclic menstrual pain Cyclic menstrual pain
with no identifiable secondary to underlying
underlying pathology pathology
Etiology Pain is likely caused Examples of

by prostag landin underlying causes
release during include endometriosis,
menstruation, which adenomyosis, leiomyomas,
stimulates uterine pelvic inflammatory
muscle contractions. disease, endometrial polyps,
Some of these or outlet obstruction
contractions may
intermittently occlude
myometrial arterial
supply resulting in
ischemic pain
Clinical Age at 6 to 24 months after It usually starts after the

featuresa onset menarche age of 30
Parity More common among It may be more common

nulliparous women among parous women
Pain onset It may start It may start few days

immediately before or before the first menstrual
on the first menstrual day
day
Associated Nausea, vomiting, Additional symptoms
symptoms diarrhea, low back may be present due to the
pain primary cause, e.g., heavy
menstrual bleeding
a
Differences between primary and secondary dysmenorrhea may not be necessar-
ily present in all cases
Work-up:
Primary dysmenorrhea is a diagnosis of exclusion. Causes of
secondary dysmenorrhea can be identified based on clinical
features and transvaginal sonography. Chlamydia/gonorrhea
testing may be performed if PID is suspected.
Premenstrual Syndrome 99
Treatment
• Non-hormonal treatment (NSAIDs):
–– Mechanism of action: these medications act by lowering
endometrial prostaglandin level.
–– Regimen: e.g., ibuprofen 400 mg every 6 hours.
• Hormonal treatment:
❶ Oral contraceptive pills: cyclic administration may be
tried first. However, extended or continuous regimen
may be considered if cyclic regimen does not control
pain.
❷ Progestins: e.g., levonorgestrel-releasing intrauterine
device, medroxyprogesterone acetate injections, or sub-
dermal implants.
❸ GnRH agonists: they are associated with significant
side effects.
❹ Androgens (e.g., danazol): they are associated with sig-
nificant side effects.
❶ Surgical treatment of the cause: e.g., laparoscopic resec-
tion of endometriosis.
❷ Presacral neurectomy: it may be indicated if pain is not
responsive to all other measures particularly among
women who want to preserve their fertility. Presacral
neurectomy may improve central (midline) pelvic pain
only, but it has no rule in women with unilateral or bilat-
eral pelvic pain (see under: Endometriosis).
❸ Hysterectomy: it is the last resort among women who
are not responding to all treatment options and who are
not interested in future fertility.
Premenstrual Syndrome
• Definition: premenstrual syndrome (PMS) refers to cyclic
physical and behavioral symptoms that occur in the second
half of the menstrual cycle and interfere with quality of life.
• Diagnosis:
–– Time of symptoms:
Recurrent symptoms are observed for approximately
6 days each cycle. These symptoms are typically most
significant within 4 days prior to menstruation and
through the first 2 days of the cycle.
–– Types of symptoms:
Behavioral symptoms Physical symptoms
• Depression • Headache and dizziness
• Anxiety • Generalized aches
• Irritability • Fatigue
• Mood swings • Appetite changes
• Confusion • Breast tenderness
• Social withdrawal • Bloating and weight gain
• Poor concentration • Abdominal pain
• Insomnia • Gastrointestinal symptoms
• Sleepiness • Swelling of the hands or feet
• Altered sexual desire • Skin problems
These symptoms are not associated with physical

signs. No laboratory testing or imaging is required for
diagnosis.
–– Diagnostic criteria:
Menstrual diary to monitor premenstrual symptoms
can be used to confirm diagnosis:
Symptoms occur within 5 days before the onset of
menstrual cycle and resolve within 4 days after com-
pletion of the cycle for at least three successive cycles.
Diagnosis is made if the patient experiences 1 to 4
physical or behavioral symptoms, or ≥5 symptoms,
that are either physical or behavioral.
Premenstrual Syndrome 101
The diagnosis of premenstrual dysphoric disorder

(severe form of PMS) is made if the patient has ≥5
symptoms including at least 1 affective symptom
(e.g., depression, anxiety, mood disorders, anger).
No physical signs are associated with this syndrome.
No labs are needed for diagnosis.
–– Differential diagnosis:
Other diagnoses that can cause similar symptoms
include depression, anxiety, perimenopause, chronic
fatigue syndrome, irritable bowel syndrome, and thy-
roid disease.
However, symptoms of these diagnoses are not cyclic.
• Treatment:
–– Mild symptoms: mild symptoms may respond to life-
style changes including exercise, diet changes, and relax-
ing techniques.
–– Moderate to severe symptoms:
❶ Selective serotonin uptake inhibitors (SSRIs):
SSRIs are the first line of treatment.
Agents Fluoxetine or sertraline

Dose Starting dose is fluoxetine 10 mg or sertraline
25 mg. The dose can be increased gradually to
achieve satisfactory response in the first cycle
Regimens ➀ Continuous regimen: daily treatment
➁ Luteal phase regimen: treatment starts only on
cycle day 14 and continues till the onset of the
next cycle
– Advantages of luteal phase regimen:
comparable efficacy to continuous regimen
with less cost and fewer side effects
– Disadvantages: a higher dose may be needed
Adverse They are dose-dependent (15%), e.g.:

effects • Nausea:
– It is the most common side effect
– It resolves within 4–5 days of administration
– Low-dose regimens are associated with less
nausea
– Nausea is less likely with luteal phase regimen
• Headache
• Insomnia
• Decreased libido:
– Sexual function usually recovers after
discontinuation
– Decreased libido may be less prominent with
luteal phase regimen
Response to 60–70% of symptomatic women respond to an
therapy SSRI (no predictors), but 30 to 40 percent of
women do not respond. Failure of response is
diagnosed after several menstrual cycles
❷ Oral contraceptives: containing drospirenone (sec-

ond line).
• Regimen: starting with 3 mg drospirenone/20 mcg
ethinyl estradiol OC with a 4-day pill-free interval
(can increase to 3 mg drospirenone/30 mcg EE if
there is breakthrough bleeding).
• Counsel: the patient on higher risk of DVT with
drospirenone (assess individual risks, still low and
less than in pregnancy).
• No response: try continuous regimen (levonorg-
estrel 90 mcg and ethinyl estradiol 20 mcg).
Counsel patient on higher bleeding rate.
❸ Low-dose alprazolam: 0.25 mg 2–3 times daily
(patients with PMDD). Effect is questionable.
❹ GnRH agonist therapy (with add-back): severe
symptoms (if all other lines fail or not tolerated).
• Regimen: start with leuprolide acetate 3.75 mg
depot monthly injection.
Further Reading 103
• Add-back therapy: continuous daily oral estradiol

(1 mg = transdermal estradiol 0.05 mg = conju-
gated estrogen 0.0625 mg) + oral micronized pro-
gesterone (100 mg = MPA 2.5 mg).
❺ Surgery:
• Bilateral oophorectomy, usually with concomitant
hysterectomy
• The last resort as most cases respond to medical
treatment (refractory cases with severe, disabling
symptoms)
Further Reading
Committee on Gynecologic Practice. Committee opinion no. 580: von
Willebrand disease in women. Obstet Gynecol. 2013;122:1368.
Reaffirmed 2018.
Committee on Practice Bulletins—Gynecology. Practice bulletin no.
128: diagnosis of abnormal uterine bleeding in reproductive-aged
women. Obstet Gynecol. 2012;120:197. Reaffirmed 2016.
Kjerulff KH, Erickson BA, Langenberg PW. Chronic gynecological
conditions reported by US women: findings from the National
Health Interview Survey, 1984 to 1992. Am J Public Health.
1996;86:195.
Lethaby A, Duckitt K, Farquhar C. Non-steroidal anti-inflammatory
drugs for heavy menstrual bleeding. Cochrane Database Syst Rev.
2013;(1):CD000400.
Lukes AS, Moore KA, Muse KN, et al. Tranexamic acid treatment for
heavy menstrual bleeding: a randomized controlled trial. Obstet
Gynecol. 2010;116:865.
Mashchak CA, Kletzky OA, Davajan V, et al. Clinical and laboratory
evaluation of patients with primary amenorrhea. Obstet Gynecol.
1981;57:715–21.
Matteson KA, Boardman LA, Munro MG, Clark MA. Abnormal
uterine bleeding: a review of patient-based outcome measures.
Fertil Steril. 2009;92:205.
Milsom I, Andersson K, Andersch B, Rybo G. A comparison of
flurbiprofen, tranexamic acid, and a levonorgestrel-releasing
intrauterine contraceptive device in the treatment of idiopathic

menorrhagia. Am J Obstet Gynecol. 1991;164:879.
Munro MG, Critchley HO, Broder MS, et al. FIGO classification
system (PALM-COEIN) for causes of abnormal uterine bleeding
in nongravid women of reproductive age. Int J Gynaecol Obstet.
2011;113:3.
Practice Committee of the American Society for Reproductive
Medicine. Current evaluation of amenorrhea. Fertil Steril.
2004;82:266–72.
Medicine. Current evaluation of amenorrhea. Fertil Steril.
2006;86:S148.
Speroff L, Fritz MA. Clinical gynecologic endocrinology and infertil-
ity. 7th ed. Philadelphia: Lippincott Williams and Wilkins; 2005.
Sum M, Warren MP. Hypothalamic amenorrhea in young women with
underlying polycystic ovary syndrome. Fertil Steril. 2009;92:2106.
Thorne JG, James PD, Reid RL. Heavy menstrual bleeding: is
tranexamic acid a safe adjunct to combined hormonal contracep-
tion? Contraception. 2018;98:1.
Chapter 3
Genital Infection
Lower Genital Infections
Vulvovaginitis
Bacterial Vaginosis
Definitions:
It is a clinical syndrome characterized by altered growth of
normal vaginal flora and abnormal vaginal discharge in the
absence of inflammation.
Etiology:
• Risk Factors:
Bacterial Vaginosis Risk Factors
• Oral sex • Intrauterine device
• Sex during menses • Early age of sexual intercourse
• Vaginal douching • New/multiple sexual partners
• Cigarette smoking • Women having sex with women

https://doi.org/10.1007/978-3-030-41128-2_3
106 Chapter 3. Genital Infection
• Microorganisms:
Bacterial vaginosis occurs when the composition of nor-
mal vaginal flora shifts from the normal balance where
lactobacillus is predominant to mixed polymicrobial flora
associated with overgrowth of the anaerobes.
Gardnerella vaginalis Anaerobic gram-negative
coccobacilli
Bacteroides species Anaerobic gram-negative bacilli
Mobiluncus species Anaerobic gram-positive cocci
Peptostreptococcus species Anaerobic gram-positive cocci
Mycoplasma hominis Facultative anaerobic gram-
negative organism
Ureaplasma urealyticum Facultative anaerobic gram-
negative organism
Diagnosis:
I. Symptoms
❶ No symptoms: up to 50% are asymptomatic and they

require no treatment.
❷ Vaginal discharge: the primary complaint. Vaginal dis-
charge in bacterial vaginosis is characterized by being:
• Milky: thin and grayish
• Malodorous (fishy odor):
–– Odor is aggravated by alkalinity: therefore, it is
most observed during menses and following
intercourse.
–– It is caused by volatilization of amine by-products
of anaerobic metabolism.
• Nonirritating: the discharge is typically not associ-
ated with vulvar itching.
Lower Genital Infections 107
• The vagina is not erythematous, and the cervix shows no

abnormalities (no signs of inflammation).
• Milky vaginal discharge may be noted during examination.
III. Work-up
I. Office diagnosis
❶ Microscopic examination (wet mount preparation):
• Test: A drop of saline is added to a drop of discharge
on a glass slide. The slide is covered and examined
microscopically without staining (office test).
• Findings:
–– Clue cells (superficial vaginal cells with abun-
dant organisms covering their borders) exceed-
ing 20%
–– Absent or few lactobacilli
–– No increase in white blood cells
❷ Whiff cells: adding 10% potassium hydroxide (KOH)
to a fresh sample of vaginal secretions results in
production of fishy odor due to release of volatile
amines.
❸ Vaginal pH: vaginal pH is above 4.5 and due to
diminished acid production.
These office diagnostic tests are referred to as Amsel diag-
nostic criteria (three out of four are diagnostic).
Amsel diagnostic criteria (1983)
• Abnormal gray discharge
• Microscopic evaluation of a saline “wet prep” of vaginal
secretions
• Determination of the vaginal pH
• Release of volatile amines produced by anaerobic metabolism
II. Laboratory diagnosis

❶ Gram stain (Nugent score):
• Nugent score is gram stain scoring system based on
bacterial morphotypes (standard for diagnosis).
• The score consists of three components: (1)
Lactobacillus (0 to 4), (2) Gardnerella and Bacteroides
(0 to 4), and (3) curved gram-variable rods (0 to 2).
• A total score of 0–3 is normal, 4–6 is intermediate,
and 7–10 is consistent with bacterial vaginosis.
❷ Culture: there is no role for culture in the diagnosis of
bacterial vaginosis because these organisms are pres-
ent as a part of normal vaginal flora.
Complications and associations:
Pregnant women Nonpregnant women
• Premature birth • Pelvic inflammatory disease
• Prelabor rupture of • Post-procedure gynecologic
membranes infection
• Low birthweight • Acquisition of HIV and herpes
simplex type 2
Treatment:
I. If nonpregnant
Agent Dose
Oral metronidazole 500 mg orally twice daily for 7 days
Metronidazole gel 0.75% 5 g intravaginally once daily for
5 days
Clindamycin cream 2% 5 g intravaginally at bedtime for
5 days
Precaution: because of the risk of disulfiram-like effect,

patient should be counseled to avoid alcohol during treat-
ment and for 24 hours after completion of metronidazole
course
II. If pregnant
Both metronidazole and clindamycin can be used in treat-

ment of pregnant women. They do not have any known tera-
togenic effects:
• Low-risk women: routine screening and treatment of
asymptomatic women is not indicated. Only symptomatic
women should be tested and treated.
• High-risk women (e.g., prior preterm labor): the role of
screening and treatment is controversial.
III. Treatment of recurrence
• Incidence: 30% within 3 months of treatment of initial

infection
• Mechanisms:
➀ Bacterial persistence
➁Exogenous reinfection, e.g., sexual intercourse
➂ Failure of normal flora to reestablish
• Treatment:
–– Metronidazole gel: twice weekly for 4–6 months.
–– One course of topical treatment plus vaginal boric acid
for 21 days then 4–6 months of metronidazole gel twice
weekly (limited data)
–– Monthly Diflucan with metronidazole (limited data)
Trichomoniasis
Etiology:
• Causative organism: anaerobic flagellated parasite
(Trichomonas vaginalis)
• Incubation period: 5–28 days
• Vulnerable sites of infection: the vagina, urethra, ectocer-

vix, and the urinary bladder (predilection for squamous
epithelium)
• Mode of transmission:
–– Sexual transmission: the parasite may harbor male
prepuce, urethra, prostate and seminal vesicles.
–– Vertical transmission (during vaginal delivery) is
possible.
Diagnosis:
I. Symptoms
❶ No symptoms: approximately 30% of women with

trichomoniasis are asymptomatic
❷ Symptomatic:
➀ V
aginal discharge: vagina discharge is characterized
by being:
• Foul smelling
• Thin and copious
• Yellowish or greenish
• Frothy (due to carbon dioxide production second-
ary to organism metabolism of glycogen)
➁ Vulvar itching and burning
➂ Postcoital bleeding
➃ Dyspareunia
➄ Dysuria
• Vulva: may be erythematous, edematous, and excoriated.

• Vagina and cervix: vaginal discharge and subepithelial
hemorrhages (strawberry spots) that do not bleed on
touch are seen in the vagina and cervix.
III. Work-up
I. Office diagnosis:
Microscopic identification of parasites in a saline
preparation. Trichomonads are:
• Anteriorly flagellated
• Oval shaped
• Slightly larger than a white blood cell
Test sensitivity is 55–60%.
❷ Vaginal pH: it is often elevated (>4.5). The test is not
diagnostic.
❸ OSOM Trichomonas Rapid Test (point-of-care test):
• This test is a dipstick test (color immunochromato-
graphic test).
• The test uses murine monoclonal antibodies.
• Results are available within 10 minutes.
• Test sensitivity is 88% and specificity is 99%.
Therefore, it is a good alternative to microscopy
or culture if they are not available particularly in
communities where trichomonas prevalence is
significant.
II. Laboratory diagnosis:
❶ Culture:
Culture is indicated if trichomoniasis is suspected
despite negative wet mount preparation test:
➀ History of trichomoniasis with persistent symp-
toms after treatment.
➁ High vaginal pH plus many leukocytes under
microscopy.
➂ Trichomonas is reported incidentally with Pap
test.
➃ Patient concern of possible exposure.
❷ Nucleic acid amplification tests (NAAT):

• The test is FDA-approved.
• The test can be applied to vaginal, endocervical, or
urine specimens.
• It is highly sensitive and specific (>95% for both).
❸ Testing for other STDs:
If the diagnosis of trichomonas is confirmed, the
patient and the partner should be tested for other sexu-
ally transmitted infections referred for evaluation.
Complications:
Pregnant women Nonpregnant women
• Preterm labor • Post-procedure gynecologic
• Prelabor rupture of infection, e.g., cuff cellulitis
membranes • Pelvic inflammatory disease
• Low birth weight • Skene and Bartholin gland
(<5.5 lbs) inflammation
• Vertical transmission to • Acquisition of HIV
the newborn
Treatment:
I. Primary treatment
• Metronidazole: single 1 g dose orally or 500 mg orally

twice daily for 7 days
• Tinidazole: single 2 g dose orally
Both treatments are comparable in efficacy and side effects.
Instructions during treatment:
• Male partner should be treated at the same time.
• Abstinence from intercourse or condom use during
treatment.
• Because of the risk of disulfiram-like effect, patient should
be counseled to avoid alcohol during treatment and for
24 hours and 72 hours after completion of metronidazole
and tinidazole courses, respectively.
II. Treatment of resistant cases
Causes of failure of therapy

• Resistant organism (high-level resistance is rare, low-level
resistance is 5%)
• Poor intestinal absorption
• Poor compliance to treatment
• Reinfection from untreated partner
Management
• Exclude patient/partner noncompliance to treatment
• Exclude possible causes of malabsorption
• Susceptibility testing
• Treatment with tinidazole, 500 mg 4 times daily for 14 days
III. Treatment during pregnancy
• Metronidazole can be used safely during pregnancy.

Information about safety of tinidazole during pregnancy is
limited, and, therefore, metronidazole is preferred.
• Treatment of trichomoniasis during pregnancy may not
prevent associated obstetric complications.
Vulvovaginal Candidiasis
Etiology:
• Causative organism:
–– It is most commonly caused by Candida albicans (a nor-
mal vaginal commensal).
–– Few cases are caused by other non-albicans Candida,
e.g., Candida glabrata and Candida tropicalis.
• Risk factors:
Factors that cause imbalance of normal vaginal flora
contribute to vulvovaginal candidiasis, e.g.:
–– Pregnancy: due to the following pregnancy-related

changes:
Increased vaginal glycogen due to high estrogen level
Vaginal thinning secondary to high progesterone level
Altered immunity status
Renal glucosuria
–– Uncontrolled diabetes mellitus: due to diminished
immunity and glucosuria
–– Recent use of broad-spectrum antibiotics: which alters
natural balance of vaginal flora
–– Immunosuppressive disorders: immunosuppressive
drugs
–– Use of oral contraceptives or hormonal treatment:
which increase vaginal glycogen
–– The use of steroids: which are both diabetogenic and
immunosuppressive
–– Vulvovaginal candidiasis is not a sexually transmitted
disease. Candida albicans is present normally in 25% of
women. However, it could become symptomatic in the
presence of the above risk factors.
–– Some studies report an association with sexual trans-
mission through orogenital sex.
Diagnosis:
I. Symptoms
Symptoms may be most noted premenstrual and may improve

during the time of menstruation (due to change in vaginal
pH):
❶ Vulvovaginal itching and irritation: is the main complaint
❷ Vaginal discharge: whitish, thick, scant (cheesy), and
odorless
❸ Dyspareunia: pain and burning during intercourse

❹ Dysuria: burning sensation with urination
• The vulva: vulvar erythema and edema with excoria-

tions.
• The vagina: it may be red, inflamed, and tender. White
patches may be noted adherent to vaginal wall. Removal
of these patches may result in slight bleeding.
III. Work-up
I. Office diagnosis:
• Test: saline and 10% KOH are added to vaginal
discharge, and the slide is examined microscopically.
• Findings: under microscope, Candida albicans
appears dimorphic; blastospores or pseudohyphae
can be seen.
• Disadvantages:
➀ Test sensitivity is 50%.
➁ Self-treatment reduces sensitivity.
➂ False-positive rates up to 50%.
❷ Vaginal pH: Vaginal pH is normal (less than 4.5).
II. Laboratory diagnosis:
❶ Vaginal culture:
It is the standard test for confirmation of diagnosis.
However, it may not be routinely obtained.
• Indications for culture:
➀ Recurrent vulvovaginal candidiasis
➁ Possible non-albicans candidiasis (microscopy if

only blastospores or persistent vulvovaginal can-
didiasis despite antifungal therapy
➂ Symptomatic women with negative microscopy
• Disadvantages:
➀ Cost.
➁ Delayed diagnosis.
➂ Culture can still be positive in asymptomatic
women.
❷ Assessment of blood glucose: ruling out diabetes
may be warranted particularly among women with
recurrent vaginitis.
Both clinical diagnosis and self-diagnosis (even with prior
diagnosis) are not sufficient for diagnosis. Accuracy of self-
diagnosis is 11% and 35% among women without or with prior
diagnosis, respectively
Definitive diagnosis is made by the presence of one of the
following:
➀ P ositive microscopic examination (wet mount preparation
test)
➁ A positive culture in a symptomatic woman
Treatment:
Treatment depends on vulvovaginal candidiasis classification
(uncomplicated versus complicated):
Uncomplicated Complicated
• Sporadic or infrequent • Recurrent candida infection
• Mild to moderate (4 times or more per year)
• Infection with Candida • Severe infection
albicans • Non-albicans candidiasis
• Immunocompetent (C. tropicalis, C. glabrata, etc.)
woman • Diminished immune status, e.g.,
uncontrolled diabetes, HIV,
pregnancy
I. Treatment of uncomplicated cases
Agent Form Regimen Side effects

Topical agents (all options are comparable)
Clotrimazole 1% vaginal 5 g Burning and
cream intravaginally irritation
7–14 days
Vaginal 100 mg for
tablet 7 days or
200 mg tablet
for 3 days
Miconazole 2% vaginal 5 g
cream intravaginally
for 7 days
Vaginal 100 mg for
suppository 7 days or
200 mg for
3 days
Tioconazole 6.5% 5 g once
ointment intravaginally
Oral agents
Fluconazole Oral tablet 150 mg oral Headache,
tablet once dizziness, GI
upset, and mild
self-limited liver
function test
elevation, drug
interactions
with several oral
medications
Because of side effects and drug interactions, topical treat-

ment is preferred to oral medication for uncomplicated
infections.
II. Treatment of complicated cases
Assessment of underlying cause
Pregnant Diabetic Not diabetic, non-pregnant
Topical treatment for Control of blood glucose Culture

7 days + treatment
(low-dose short-term
fluconazole use is not
Candida albicans Non Candida albicans species
associated with birth
defects compared to
higher doses) Topical treatment (response
Recurrent Severe rate is 50%)
infection infection
If it fails
600-mg vaginal boric acid capsule

Topical azole therapy for Fluconazole
daily for at least 2 weeks
7 to 14 days followed by 150 twice, 3
oral fluconazole weekly days apart
Intolerance? If it fails
for 6 months (90% cure (80% cure rate)
rate, 50% protection rate)
Refer to a specialist
Intermittent
topical therapy
Atrophic Vaginitis
Etiology:
• Most common among postmenopausal women due to
estrogen deficiency.
• It may occur among premenopausal women particularly
with hypoestrogenic states, e.g., postpartum, hypothalamic-
pituitary insufficiency (examples: functional hypothalamic
amenorrhea, hyperprolactinemia).
Diagnosis:
I. Symptoms
Vaginal discharge, vulvar burning and irritation, dyspareunia,

and dysuria
Atrophy of vaginal mucosa and loss of rugae and luster
III. Work-up
❶ Microscopic examination: parabasal or intermediate

cells are noted.
❷ Vaginal pH: elevated vaginal pH is suggestive hypoes-
trogenic state.
❸ Amine test: negative.
Treatment:
• Exclusion of premalignant or malignant pathology: if dis-
charge is associated with vaginal spotting, work-up to rule
out underlying pathology is warranted.
• Estrogen vaginal cream: 1 gm twice to three times weekly
Desquamative Inflammatory Vaginitis
Clinical presentation:
Perimenopausal or postmenopausal women
• Symptoms:
–– Vulvar burning and irritation
–– Dyspareunia
–– Abnormal yellow or green discharge
–– Purulent discharge
–– Vestibular and vaginal erythema
–– Focal or linear erosion
–– Ecchymotic rash
Work-up:
• Vaginal pH is elevated and the amine test result is negative.
• Microscopy: large amounts of leukocytes and parabasal
cells.
Diagnosis criteria
❶ One or more symptoms: vaginal discharge, dyspareunia,
pruritus, burning, irritation
❷ One sign (ecchymotic rash, erythema, erosions)
❸ Vaginal pH > 4.5
❹ Increased numbers of parabasal cells and leukocytes
(leukocyte to epithelial cell ratio >1:1)
Treatment:
14-day course with 2% clindamycin cream often achieves a
cure; relapse is common.
Bartholinitis and Bartholin cyst
Etiology:
• Bartholinitis and Bartholin abscess:
–– Nonsexually transmitted organisms: polymicrobial
infection with E. coli being the most common organism.
MRSA infection is currently increasing.
–– Sexually transmitted organisms: e.g., gonococci.
Sexually transmitted infections present one third of
cases and the incidence is decreasing.
• Bartholin cyst:
Bartholin cyst is not an infection. It results from accu-
mulation of clear fluid due to Bartholin duct obstruction.
However, this fluid may become infected with subsequent
development of Bartholin abscess.
Diagnosis:
I. Symptoms
• Bartholinitis and Bartholin abscess: vulvar pain on walk-

ing or sitting, labial swelling, dyspareunia, and fever.
• Bartholin cyst: Painless labial mass. The mass may be ten-
der, e.g., during intercourse.
• Labial erythema, tenderness, and edema

• Bartholin gland: enlarged, indurated, tender, beneath pos-
terior part of labia majora
III. Work-up
• Bacterial culture:
–– Bacterial culture should be performed on purulent
material drainage of the abscess.
–– Cultures should cover MRSA because of the increasing
incidence and the need for specific antibiotics to cover
these bacteria.
• Nucleic acid amplification test (NAAT) for gonorrhea and
chlamydia:
This test is recommended in patients at risk of sexually
transmitted diseases.
• Biopsy:
Because of the possibility of underlying malignancy in
high-risk patients, biopsy may be recommended in women
at 40 years or older or at any age in the presence of the
following risk factors:
❶ Palpable solid mass within the abscess
❷ Fixation of the lesion to the surrounding tissue
❸ Failure to respond to treatment
Differential diagnosis of Bartholin gland cysts

Epidermal inclusion Benign, mobile, non-tender cyst,
cyst (obstruction of usually noted in labia majora
pilosebaceous ducts)
Vestibular cyst (mucous Single or multiple asymptomatic soft,
cyst of the vestibule) smooth, small, non-tender, and superficial
cyst, located at labia minora or vestibule
Differential diagnosis of Bartholin gland cysts

Hidradenoma Benign, small, sharply circumscribed
papilliferum (apocrine nodule, typically seen between labia
sweat glands) majora and minora
Cyst of the canal of Soft and compressible cyst at the mons
Nuck pubis or labia majora
Skene's duct cyst A cyst of variable size adjacent to
urethral meatus (large ones can cause
urethral obstruction)
Treatment:
• Bartholinitis: treated with analgesics and antibiotics if not
associated with abscess formation.
• Bartholin cyst:
–– Asymptomatic patients younger than 40 years: no inter-
vention is necessary.
–– Asymptomatic women at or above 40 years: incision
and drainage with biopsy to exclude associated
carcinoma.
–– Symptomatic cyst: treatment is similar to treatment of
Bartholin abscess (see below).
• Bartholin abscess:
–– First or second episode of uncomplicated abscess: inci-
sion and drainage with Word catheter placement if
possible
–– Recurrence after Word catheter placement is tried
(once or twice): treatment with marsupialization
Incision and
drainage Word catheter Marsupialization
Procedure • A 3–5 mm • Incision and • A 1.5–2 cm
incision is drainage single or cruciate
made on are initially incision is made
the mucosal performed into the vestibule
surface of • Word catheter outside hymenal
the labia is inserted into ring
minora to cavity, and the • After emptying
drain the catheter bulb the abscess/
abscess is inflated to cyst, the edge
• Abscess fill the cavity is everted with
cavity may • Catheter end is interrupted
be irrigated tucked inside sutures
the vagina
• The catheter
is left inside
the cavity for
approximately
4 weeks
Pros Simple and In treating Marsupialization is
fast, can initial episodes, superior to gland
be done Word catheter excision because:
under local has equivalent • It preserves
anesthesia, efficacy to gland function
outpatient marsupialization • It is associated
procedure and is associated with less
with lower risk bleeding
of complications and better
postoperative
recovery
Cons High Recurrence Compared to
incidence of incidence is other options, this
recurrence 10–20% procedure is done
under anesthesia in
the operative room
–– Antibiotic administration with Bartholin abscess:
Healthy women with uncomplicated abscess: no antibi-

otic therapy is indicated after drainage is performed.
Indications of antibiotic therapy:
❶ Recurrence
❷ Pregnancy
❸ Immunosuppression
❹ MRSA risk
❺ Associated extensive cellulitis
❻Confirmed diagnosis with gonorrhea or chla-
mydia infection
Antibiotic options include ceftriaxone, cipro-
floxacin, doxycycline, and azithromycin
Infectious genital ulcers
Genital Herpes
Etiology:
• Causative organism: herpes simplex type II infection. Type
I can spread through associated oral sex.
• Incubation period: 2–12 days.
• Disease process:
–– With initial infection, the virus travels by retrograde
axonal transport and becomes dormant at the dorsal
root ganglia.
–– On activation, the virus travels again by antegrade axo-
nal transport and causes reinfection.
Types:
• Primary infection: first-time infection with HSV. HSV-2 is
detected in a patient who has no antibodies to either
HSV-1 or HSV-2.
• Non-primary first episode: first-time infection with

HSV-2 in a patient with prior HSV-1 infection. Therefore,
antibodies to HSV-1 are detected.
• Recurrent episodes: recurrent infection with HSV-2 in a
patient with prior HSV-2 infection. Therefore, antibodies
to HSV-2 are detected.
Clinical picture:
I. Patient with no previous exposure
• Site: vulva, vagina, cervix, perineum, and rectum.

• Lesion: the disease appears as multiple vesicles which
break into small, shallow, erythematous, and painful ulcers.
• Lymph nodes: inguinal lymph nodes are often enlarged.
• Healing: complete healing occurs within 10 days.
II. Patients with recurrent infection
Recurrent episodes are similar to primary episode but:

• Symptoms are significantly milder.
• Lesions are less extensive.
• Disease process is shorter with shorter vesicular stage.
III. Patients with non-primary first episode
Clinical presentation is intermediate in severity between pri-

mary and recurrent infection
Work-up:
I. Viral detection tests

Polymerase chain reaction

Tissue culture (PCR)
Specimen • For vesicles: vesicles are Unroofing of herpetic
unroofed and vesicular vesicles is not necessary
fluid is obtained (sensitive test)
• For ulcers: ulcer base
is scrapped
Pros Gold standard test. It Higher sensitivity (3–5
yields high specificity times higher than culture),
commercially available
Cons Low sensitivity Not yet a standard
especially with test because it lacks
recurrent infection and interlaboratory standards,
as the lesions start to and it is not currently
heal. Thus, a negative FDA-approved for this
test does not rule out indication
infection
II. Antibody detection tests
• Indications of antibody detection testing:

➊ Absence of active lesions
➋ Negative culture or PCR results
• Advantages of the test:
➊ High sensitivity (93–100%)
➋ High specificity (93–98%)
➌ FDA-approved
• Disadvantages of the test:
Identification of certain antibodies does not reflect the
site of infection, e.g., oral and genital lesions can be both
caused by HSV-1
Treatment:
• Local care: to avoid secondary bacterial infection and
analgesia for pain relief
• Antiviral treatment:
Primary episode • Acyclovir: 400 mg TID for 7–10 days

• Valacyclovir: 1 gram BID for
Non-primary first
7–10 days
episode
Recurrent episodes • Acyclovir: 400 mg TID for 5 days
• Valacyclovir: 1 gram daily for 5 days
Severe episode Acyclovir IV 5–10 mg/kg TID for
2–7 days then oral treatment for a total
of 10 days
Oral suppression Acyclovir 400 mg BID daily
(if it is recurrent
every 2–3 months)
Syphilis
Incidence:
• The incidence in the United States is 2.3 cases per 100,000
women.
• The increasing incidence of syphilis over the last 5 years
may be attributed to increased illicit drug use especially
methamphetamine use.
Etiology:
• Causative organism: Treponema pallidum (spirochete)
–– Direct contact: with a syphilitic lesion during sexual
intercourse.
–– Transplacental: transmission from the mother to the
fetus.
–– Hematogenous transmission: blood transfusion is not
typically a source of transmission because donors are
screened for syphilis and because Treponema pallidum
cannot survive storage conditions. However, transmis-
sion is increasing among IV users.
• Incubation period: 3 weeks
Clinical presentation:
Syphilis is clinically divided into four stages:
Primary • Onset: 3 weeks after initiation Infectious

syphilis of infection
• Clinical features: syphilitic
chancre (non-tender ulcer,
with raised rounded borders
and clean base)
• Site of lesion: the cervix,
vagina, or vulva
• Outcome: If not treated,
lesions spontaneously heal
within 6 weeks
Secondary • Onset: 6 weeks to 6 months Infectious
syphilis after a chancre appears
–– M
aculopapular rash of
the palms and soles, trunk,
and extremities. They are
diffuse and symmetric
–– Condylomata lata: broad,
pink, or grayish white,
highly infectious plaques
–– Generalized symptoms:
fever, lymphadenopathy,
headache, sore throat,
fatigue, patchy hair loss
Latent syphilis • Early latent syphilis which is May be
(asymptomatic) within the first year following infectious
secondary syphilis without (early),
treatment noninfectious
• Late latent syphilis which (late)
is beyond 1 year following
secondary infection or if the
time of initial infection is
unknown
This stage is not infectious.
However, congenital infection
can still occur for up to 4 years
after maternal initial infection
Tertiary This phase of untreated syphilis Noninfectious

Syphilis may occur up to 20 years after
latency. Complications of this
stage include:
• Gummatous syphilis:
rounded or irregular ulcers
or granulomatous lesions.
They are noninfectious.
They involve internal
organs, bone, or skin
• Cardiovascular syphilis:
it most commonly affects
ascending thoracic aorta. It
can cause aortic dilation and
aortic valve regurgitation
• Neurosyphilis:
manifestations may include
general paresis and tabes
dorsalis. Confirmation of
neurosyphilis warrants
testing of cerebrospinal fluid
Diagnostic work-up:
• Indications for testing:
Symptomatic patients Asymptomatic patients
• Patients with classic features • All pregnant women should
of syphilis, e.g., painless be screened
genital ulcer, maculopapular • Women at higher risk of
rash consistent with acquisition of syphilis, e.g.,
secondary syphilis, general a partner diagnosed with
paresis, or tabes dorsalis infectious stages of syphilis,
• Sexually active patients with HIV-infected individuals,
a genital ulcer or rash of the multiple sexual partners
palms and soles with no clear
etiology
• Patients with unclear
diagnosis of a non-specific
symptom that may be
attributed to tertiary
syphilis, e.g., neurological or
cardiovascular symptoms
• Laboratory tests:
I. Non-treponemal tests (screening tests):
–– Test principle: these are indirect tests. Patient serum
is tested for antibody (IgG and IgM) reactivity to
cardiolipin-cholesterol-lecithin antigens:
➊ Rapid plasma reagin (RPR)
➋ Venereal Disease Research Laboratory (VDRL)
These tests are reported as a titer of antibodies
–– Role of testing:
➊ Initial screening test: these tests are cheap and
easy. A confirmatory test is needed because of
high false-positive rate of these tests.
➋ Quantitative follow-up of treatment response
(follow-up of titer).
II. Treponemal tests (confirmatory tests):
–– Test principle: Treponemal tests are direct tests that
detect antibody to T. pallidum proteins, e.g.:
➊ Fluorescent treponemal antibody absorption
(FTA-ABS)
➋ Microhemagglutination test for antibodies to
T. pallidum (MHA-TP)
➌ T. pallidum particle agglutination assay (TPPA)
➍ T. pallidum enzyme immunoassay (TP-EIA)
–– Role of testing:
These tests are used as confirmatory tests. However,
as these tests have become easier and less com-
plex, their use as initial testing has increased.
Treatment:
Primary, secondary, early latent syphilis
Recommended regimen • Benzathine penicillin G,
Alternative regimens (with 2.4 million units IM once
penicillin allergy) • Doxycycline 100 mg orally
twice daily for 2 weeks
Late latent, tertiary syphilis

Recommended regimen • Benzathine penicillin G,
Alternative regimen (with 2.4 million units IM weekly 3
penicillin allergy) doses
• Doxycycline 100 mg orally
twice daily for 4 weeks
Non-Treponemal tests (screening)
Negative Positive
No symptoms or Treponemal tests

Symptoms or
signs of syphilis (confirmatory test)
signs of syphilis
No further testing FTA-ABS Negative

Positive
(confirmatory test)
False positive test

No prior history of Prior treated (no disease)
syphilis syphilis
New diagnosis of Compare non-

syphilis is made Treponemal test
titer to post-
treatment titer
Persistent low titer 4 -fold increase in Neither persistently low,

(serofast) titer or more nor significantly increased
No action New infection Failure of

required treatment
Chancroid
Etiology:
• Causative organism: Haemophilus ducreyi (gram-negative
bacillus)
• Incubation period: 3–10 days
• Mode of transmission: direct contact through breaks in the
skin or mucous membrane
Diagnosis:
Diagnostic criteria of chancroid
➊O ne or more painful genital ulcers (typical ulcers have
erythematous margins, irregular edges, and red and soft base
and is covered with purulent material)
➋R egional lymphadenopathy (unilateral or bilateral tender
inguinal lymph nodes)
➌ Negative testing of T. pallidum
➍ Negative HSV PCR test or HSV culture on ulcer exudate
Treatment:
Antibiotic Regimen
Azithromycin 1 g orally in a single dose
Ceftriaxone 250 mg IM in a single dose
Ciprofloxacin 500 mg orally twice a day for 3 days
Erythromycin bass 500 mg orally three times a day for 7 days
Granuloma Inguinale (Donovanosis)
Etiology:
• Causative organism: intracellular gram-negative bacteria
(Klebsiella granulomatis)
• Mode of infection: direct contact through open sores
Diagnosis:
• Clinical picture:
–– The lesion: painless inflammatory nodules that progress
to beefy red ulcers that bleed easily on contact and
heals by fibrosis and scarring.
–– Inguinal lymph nodes are usually uninvolved.
• Work-up: Giemsa staining of tissue crusts or biopsy is used
to visualize Donovan bodies
Treatment:
Antibiotic Regimen
Azithromycin 1 g orally weekly for at least 3 weeks
Doxycycline (recommended)
Ciprofloxacin 100 mg orally twice a day for at least 3 weeks
Erythromycin 750 mg orally twice a day for at least 3 weeks
base 500 mg orally four times a day for at least
3 weeks
Lymphogranuloma Venereum (LGV)
Etiology:
• Causative organism: Chlamydia trachomatis, serotypes L1,
L2, and L3
• Incubation period: 2 weeks
• Route of infection: sexually transmitted disease (sexual
contact)
Diagnosis:
• Clinical presentation:
Stage 1 A small ulcer or papule at the site of

inoculation that completely heals without
scarring
Stage 2 • Unilateral painful inguinal or femoral
(Inguinal syndrome) lymphadenopathy
• Enlarged nodes may mat together
“groove sign”
• These lymph nodes may rupture
through the skin, forming chronically
draining sinuses
Stage 3 Proctocolitis (mimicking inflammatory
(anogenitorectal bowel disease) which may present by:
syndrome) • Rectal pruritus, mucoid discharge
from rectal ulcers
• Rectal bleeding
• Fever, crampy abdominal pain, and
abdominal distention
• Work-up:
Diagnosis is made based on clinical features after exclu-
sion of other causes of inguinal lymphadenopathy or proc-
tocolitis. Additional tests that can support diagnosis include:
Direct tests Indirect tests

Specimen Swabs from genital Serology
lesions, rectal specimens,
swabs from inguinal
sinuses or aspiration from
enlarged lymph nodes
Tests • Culture • Complement fixation
• Direct test: titers >1:64 are
immunofluorescence positive or
• Nucleic acid • Micro-
amplification test immunofluorescence:
titers >1:256 are positive
These tests are not
standardized and should
be used in clinical context
Treatment:
Antibiotic Regimen
Doxycycline 100 mg orally twice a day for at least 3 weeks
Erythromycin (recommended)
base 500 mg orally four times a day for at least
3 weeks
Infectious genital masses
External Genital Warts (Condyloma Acuminata)
Etiology:
• Causative organism: human papilloma virus (HPV, double-
stranded DNA), non-oncogenic types, usually types 6 and 11
–– Sexual transmission: via direct contact.

–– Vertical transmission: during labor may cause neonatal
genital and laryngeal papillomatosis.
Diagnosis:
Multiple small papillomata (condyloma acuminata) at
the vulva, vagina, cervix, and around the anus. The lesions
grow extensively in diabetics, pregnant, and immune-
compromised patients.
• Work-up:
Diagnosis is clinical. Biopsy is not recommended as a
routine. However, it may be indicated if warts are not
responsive to treatment or if changes concerning of malig-
nancy are noted, e.g., dark discoloration, increased pigmen-
tation, rapid growth, or fixation to underlying structures.
Treatment:
I. Prophylaxis
Three types of vaccines to HPV are available:

Types of
HPV
protected by Age at
Vaccine this vaccine administration Regimen
Gardasil HPV 6, 11, 16, • Vaccination • Before the age
and 18 should be given of 15: 2 doses
routinely at the 6–12 months
Gardasil 9 HPV 6, 11, 16,
age of 11–12 apart
18 and 31, 33,
• Women between • At and after
54, 52, and 58
13 and 26 years the age of 15: 3
Cervarix HPV-16 and old with no prior doses; 2nd dose
18 (does vaccination is 1–2 months
not prevent after the first
genital warts) dose, 3rd dose is
6 months after
the first dose
II. Treatment
• Patient-applied treatment:
Side
Treatment Action Use effects Precautions
Imiquimod It enhances It is Skin Sexual
(5%) cream immunity applied irritation, contact
response once at induration, should be
to wart bedtime, 3 and avoided when
lesions times/week ulceration the cream is
for up to used
16 weeks. The cream
It should may weaken
be washed condoms and
with soap diaphragms
and water
after
6–10 hours
Podophyllin It causes Up to 4 Skin Maximum
and podofilox wart cycles; irritation, treated area
necrosis each is soreness, is 10 cm2,
(antimitotic 3 days of or pain maximum
drug) application dose is
twice/day 0.5 mL/day
followed It is not
by 4 days recommended
without during
treatment pregnancy
(first It should not
application be applied
may be internally
performed
by the
provider)
Sinecatechins It is Mild side It should be
(15%) applied effects avoided in
ointment three (skin patients with
times daily, redness HIV
maximally and
16 weeks itching)
• Provider-applied treatment:
❶ Trichloroacetic acid (80–90%):
• It acts by direct chemical destruction of the warts. It
may be repeated weekly as indicated.
• It may spread to and destroy surrounding tissues.
❷ Nonmedical treatment:
These options may be used for large lesions, when
medical treatment is ineffective, or to treat pregnant
women to prevent vertical transmission:
• Cryotherapy
• Electrocautery
• Surgical excision
• Laser treatment
Side effects include pain, swelling, and scarring
Molluscum Contagiosum
Etiology: molluscum contagiosum virus is a DNA virus that

is transmitted by intimate contact.
Diagnosis:
• Clinical picture: papular lesions with central umbilication.
It may be single or multiple.
• Investigations: Giemsa staining shows the molluscum
bodies (large intracytoplasmic structures).
Treatment:
• Most lesions spontaneously regress over 6–12 months.
• Medical treatment includes podophyllotoxin cream
(0.5%), iodine, salicylic acid, potassium hydroxide, treti-
noin, and imiquimod.
• Nonmedical options are similar to treatment of genital
warts.
Pelvic Inflammatory Disease
Definition:
Pelvic inflammatory disease (PID) is a spectrum of acute,
subacute, recurrent, or chronic diseases caused by infection of
the upper genital tract organs (endometritis, salpingitis,
oophoritis, and peritonitis).
Etiology:
• Causative organisms:
PID is commonly caused by a mixture of organisms,
they include:
❶ Sexually transmitted organisms: (30–50%)
➀ Chlamydia trachomatis: the most common sexually
transmitted organism
➁ Gonococci: the second most common sexually trans-
mitted organism
❷ Polymicrobial infection (20–30%): including gram-
positive cocci (streptococci, staphylococci) and gram-
negative bacilli (e.g., E. coli)
❸ Anaerobic bacteria: Gardnerella vaginalis, Peptostrepto-
coccus, Ureaplasma urealyticum, and Mycoplasma
genitalium
❹ Actinomyces species: the infection which is almost
exclusively associated with intrauterine device
❺ Viruses: e.g., cytomegalovirus, herpes simplex type 2
❻ Specific infection: Mycobacterium tuberculosis or
Schistosoma species (at certain regions of the world
where these infections are prevalent)
• Risk factors:
❶ Multiple sexual partners
❷ Women younger than 25 years old
❸ History of prior PID or a sexually transmitted infection
❹ History of sexual abuse
❺ Frequent vaginal douching

❻ Gynecologic surgical procedures through the cervix
(ascending infection)
Diagnosis:
I. Identification of patients at risk
• Any sexually active woman is at risk of PID.

• Women at higher risk of PID include young women and
women who have multiple sexual partners, prior PID or
recent gynecologic procedure.
II. Symptoms
• Lower abdominal pain:

–– Bilateral, variable in character.
–– Pain may be aggravated by intercourse or with jarring
movement.
–– Pain may be severe in the presence of peritonitis or
pelvic abscess.
• Abnormal vaginal discharge
• Urinary symptoms, e.g., frequency
• Abnormal uterine bleeding: in approximately one third of
patients
III. Physical signs
• Abdominal examination:
Abdominal tenderness, maximal tenderness is appreci-
ated over the lower quadrant rebound tenderness
–– Speculum exam: purulent endocervical discharge and/
or vaginal discharge. Lateralization is uncommon.
–– Bimanual examination: cervical motion tenderness,
uterine and adnexal tenderness.
IV. Work-up
Tests to confirm PID Test to exclude other causes
• WBC count • B-hCG: this test is done to
• Microscopic examination of rule out ectopic pregnancy
vaginal discharge • Urinalysis: to rule out
• Nucleic acid amplification tests urinary tract infection
(NAATs) of cervical discharge
for C. trachomatis, Neisseria
gonorrhoeae, and Mycoplasma
genitalium
• Transvaginal sonography:
–– Indications:
Clinical assessment is usually enough to make pre-
sumptive diagnosis. Further work-up may be indicated
in the following situations:
➀ Atypical presentation
➁ Severe illness
➂ No improvement despite treatment within 72 hours
➃ Persistent symptoms after completion of treatment
Ultrasound examination helps to:
➀ Rule out tubo-ovarian or pelvic abscesses complicat-
ing PID
➁ Exclude other causes of pelvic pain, e.g., adnexal
torsion
–– Findings:
Cogwheel sign: cogwheel appearance of the tube on
cross-sectional view (tube is fluid filled and tubal
wall is thickened).
Heterogeneous thickening of endometrial line and

fluid/gas within the endometrial cavity.
Tubo-ovarian abscess: it appears as complex thick-
walled, multilocular cystic lesion associated with
internal echoes or multiple fluid levels.
–– Laparoscopy:
Indication:
➀ If imaging studies (sonography/CT scan) are
not conclusive in the context of failure to
response to medical treatment
➁ High suspicion of an alternative diagnosis (e.g.,
appendicitis)
Findings:
–– Minimum criteria of salpingitis (3E): erythema,
edema, and exudates from the fimbrial end
–– Violin string adhesions between the liver and
abdominal wall (Fitz-Hugh-Curtis syndrome)
Have a look by Have a look by

(laparoscopy) (ultrasound)
With diagnosis (bacteriological

Have a sample for study, ESR & CRP)
(laboratory
Exclusion of other possibilites
examination)
(Pregnacy test, Urine analysis)
• Endometrial biopsy:
Although pathology can be confirmatory, it is not
required as a part of work-up.
V. Differential diagnosis
Other gynecologic causes Non-gynecologic causes

• Ruptured ectopic • Acute appendicitis: pain starts
pregnancy: clues include around the umbilicus then
positive pregnancy test/B- moves to the right iliac fossa.
hCG possible missed Tenderness is elicited at the
period and unilateral McBurney’s point. Ultrasound
symptoms and CT studies can support the
• Ovarian torsion: diagnosis
sonographic finding of • Urinary tract infection: clues
ovarian mass/cyst and include symptoms of urinary
impaired blood flow by tract infection, urinalysis, and
Doppler studies urine culture
• Torsion of pedunculated
subserous leiomyoma
• Endometriosis
Diagnostic criteria
The following criteria can be used for diagnosis of PID:
Criteria for diagnosis of PID

Minimal One of the following physical signs:
criteria ❶ Cervical motion tenderness
❷ Uterine tenderness
❸ Adnexal tenderness
Additional These criteria can increase diagnosis specificity:
criteria ❶ Fever: oral temperature >38.3 °C (>101 °F)
❷ M ucopurulent cervical discharge or cervical
friability
❸ Abundant WBCs on saline microscopy of cervical
secretions
❹ Elevated erythrocyte sedimentation rate (ESR)
❺ Elevated C-reactive protein (CRP)
❻ L aboratory confirmation of cervical N.
gonorrhoeae or C. trachomatis
Criteria for diagnosis of PID

Specific These signs are confirmatory for acute PID. This
criteria work-up may be necessary for diagnosis of some
unclear cases:
❶ Evidence of endometritis on endometrial biopsy
❷ Thickened fluid-filled tubes or tubo-ovarian
complex on transvaginal sonography
❸ Tubal hyperemia on Doppler studies
❹ Laparoscopic findings consistent with PID
Complications of PID:
❶ Infertility: the risk of infertility is influenced by the follow-
ing factors:
➀ Severity of inflammatory reactions of the tubes:
• Risk of infertility after a single episode of mild dis-
ease is approximately 6%.
• Risk of infertility after a single episode of severe dis-
ease is approximately 27%.
➁ Number of episodes of salpingitis:
• Risk of infertility after one episode is approximately
15%.
• Risk of infertility after two episodes is approximately
35%.
• Risk of infertility after three or more episodes is
approximately 75%.
❷ Ectopic pregnancy:
• PID is associated with four- to eightfold increase in risk
of ectopic pregnancy.
❸ Pelvic abscess:
• PID is complicated by pelvic abscess in 5–15% of cases.
❹ Recurrence:
• Risk of recurrence following one episode of PID is up
to 20–25% of patients.
❺ Chronicity:
• Chronic PID may be associated with chronic pelvic
pain.
❻ Fitz-Hugh-Curtis syndrome:
• Definition: The term refers to acute perihepatitis and
perihepatic adhesions following acute salpingitis.
• Incidence: 5–10% of PID cases.
• Etiology: the syndrome is most commonly associated
with N. gonorrhoeae and C. trachomatis.
• Diagnosis:
–– Symptoms: right upper quadrant abdominal pain in
association with history of PID. Pain may be aggra-
vated by breathing and coughing, and it may radiate
to right shoulder.
–– Physical signs: right upper quadrant tenderness.
–– CT of the abdomen with IV contrast: it may show
subtle enhancement of the liver capsule.
–– Endocervical swab: to test for chlamydia and
gonorrhea.
–– Diagnostic laparoscopy: it is rarely indicated. It visu-
alizes violin string adhesions between the liver and
the anterior abdominal wall.
• Treatment: antibiotic treatment of causative organ-
isms. Laparoscopic adhesiolysis may be indicated for
refractory pain.
Treatment:
I. Prevention of PID
• Limiting number of sexual partners

• Condom use
• Avoidance of vaginal douching
II. Treatment of PID
A. Inpatient medical management

• Indications for inpatient management
(hospitalization):
–– Pregnancy
–– Lack of response or tolerance to oral medications
–– Noncompliance to therapy
–– Inability to take oral medications: nausea/vomiting
–– Severe clinical illness (high fever, nausea, vomiting,
severe abdominal pain)
–– Pelvic or tubo-ovarian abscess
–– Possible need for surgical intervention or exclusion
of other causes (e.g., appendicitis)
• Treatment regimens:
❶Symptomatic treatment: analgesics, antipyretics,
antiemetics
❷ Antibiotic regimens:
Regimen A Intravenous cefotetan 2 g IV every 12 hours or
cefoxitin 2 g every 6 hours plus doxycycline 100 mg
orally or intravenous every 12 hours
Regimen B Clindamycin 900 mg IV every 8 hours plus
gentamicin loading dose 2 mg/kg followed by a
maintenance dose of 1.5 mg/kg every 8 hours
• Criteria of response to treatment:

–– Lysis of fever
–– Resolution of symptoms (pain, nausea, and
vomiting)
–– Down trending of WBC count
–– Resolution or marked improvement of physical signs
(tenderness)
If the patient continues to express clinical
improvement after 24 hours of parental antibiotics,
she can be transitioned to oral antibiotics, which
consist of a 14-day course of doxycycline (100 mg
twice daily).
B. Outpatient medical management

• Indications of outpatient treatment: In women with a
mild to moderate clinical presentation (not meeting
criteria for hospitalization)
• Treatment regimens:
–– Ceftriaxone (250 mg intramuscularly in a single
dose) plus doxycycline (100 mg orally twice a day
for 14 days) or azithromycin (1 gram once per week
for two weeks)
–– Alternative treatment regimens for women with
penicillin allergy include:
Patients with mild Patients with severe

allergy to penicillin allergy to penicillin
Patients at Ceftriaxone Gentamicin and
high risk of clindamycin
gonorrhea
infection
Patients at Levofloxacin (500 mg orally once daily) or
low risk of ofloxacin (400 mg orally twice daily) with
gonorrhea or without metronidazole for 2 weeks
infection
• Outpatient follow-up:
–– Patient should be seen in the clinic within 48–72 hours
to assess treatment response.
–– Patient should be offered screening of other sexually
transmitted diseases.
–– Partners within the last 2 months should be offered
evaluation and treatment.
III. Treatment of PID with pregnancy
• Although rare, PID can occur in pregnancy specially in the

first trimester.
• Patient should be hospitalized.
• Antibiotic treatment is similar to nonpregnant women.

However, azithromycin is used instead of doxycycline
because the latter is teratogenic.
IV. Management of tubo-ovarian abscess
• Antibiotic treatment:
–– Candidates:
Premenopausal women
Hemodynamically stable patient with no signs of
sepsis or acute abdomen (ruptured tubo-ovarian
abscess)
Small- to moderate-sized abscess (e.g., less than
9 cm)
Patients who show immediate adequate response to
initiation of antibiotics
–– Effectiveness: it may be effective in approximately
60–80% of patients.
–– Treatment regimen:
Cefoxitin, clindamycin, and metronidazole have
good abscess wall penetration. Anaerobic coverage is
important in treatment of tubo-ovarian abscess.
Otherwise, antibiotic regimen is described under
(inpatient medical management).
If adequate response to treatment is observed for
24–48 hours, outpatient treatment should be contin-
ued for at least 2 weeks (or till abscess resolves on
imaging studies).
–– Treatment failure:
Close observation for at least 48–72 hours after ini-
tiation of treatment. Treatment is considered failed if:
Fever is persistent.
Symptoms are persistent or worsening.
WBC count does not decrease.
Abscess size increases.

Signs of sepsis.
• CT or ultrasound guided drainage:
–– Candidates:
Drainage should be offered if available. However,
treatment success depends on abscess location and
accessibility (percutaneous, transvaginal, transrectal,
and transgluteal).
Treatment success is more likely with easily accessi-
ble, smaller, and unilocular abscesses.
–– Effectiveness: success rate ranges from 70% to 100%.
• Surgery:
–– Indications:
Signs of ruptured tubo-ovarian abscess and sepsis,
e.g., hypotension, tachycardia, and tachypnea
Large abscess
Failure of other treatment options
Postmenopausal women (likelihood of underlying
malignancy)
–– Approach:
Laparotomy (Maylard transverse or vertical midline
incision)
Laparoscopy (especially if there is no evidence of
ruptured abscess)
Surgery includes acquisition of fluid sample for
anaerobic and aerobic cultures, irrigation of perito-
neal cavity, and unilateral adnexectomy.
Toxic shock syndrome
Etiology:
This disorder is caused by a toxin (toxic shock syndrome toxin-
1) produced by Staphylococcus aureus or group A streptococci.
Symptoms may start 2 days following surgery or onset of

menstruation (high-absorbency tampon use is a risk
factor).
Diagnosis:
Criteria for diagnosis of toxic shock syndrome
❶ Hypotension
❷ Diffuse macular erythroderma
❸ Fever
❹ Skin desquamation (late sign)
❺ Minor criteria (at least three of the following):
• Gastrointestinal symptoms: diarrhea or vomiting
• Mucous membrane involvement: oral, pharyngeal,
conjunctival, and/or vaginal erythema
• Muscule involvement: myalgia or elevated creatinine
phosphokinase level (greater than twice normal level)
• Renal involvement: creatinine greater than twice normal
• Hematologic involvement: platelet count
<100,000 per mm3
• Hepatic involvement: liver enzymes and/or bilirubin levels
greater than twice normal
• Central nervous system involvement: altered consciousness
or disorientation in absence of focal localizing signs
Probable diagnosis is made if all four out of five criteria

are present.
Confirmed diagnosis is made if all the five criteria are
present
Treatment:
• Hospitalization
• Stabilization: with large volumes of intravenous fluids and
electrolyte replacement to replace massive fluid loss
• Empirical antibiotics: vancomycin and clindamycin
Further Reading
Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal com-
plaints. JAMA. 2004;291:1368.
Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease.
N Engl J Med. 2015;372:2039.
Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines 2006. MMWR 2006;55(No. RR-11).
Farley TM, Rosenberg MJ, Rowe PJ, et al. Intrauterine devices and
pelvic inflammatory disease: an international perspective. Lancet.
1992;339(8796):785–8.
Gaydos CA, Beqaj S, Schwebke JR, et al. Clinical validation of a test
for the diagnosis of vaginitis. Obstet Gynecol. 2017;130:181.
Landers DV, Wiesenfeld HC, Heine RP, et al. Predictive value of the
clinical diagnosis of lower genital tract infection in women. Am J
Obstet Gynecol. 2004;190:1004.
Nygren P, Fu R, Freeman M, et al. Evidence on the benefits and harms
of screening and treating pregnant women who are asymptomatic
for bacterial vaginosis: an update review for the U.S. Preventive
Services Task Force. Ann Intern Med. 2008;148:220.
Sobel JD. Current concepts: vaginitis. N Engl J Med.
1997;337:1896–903.
Sobel JD. Vulvovaginal candidosis. Lancet. 2007;369:1961.
Soper DE. Pelvic inflammatory disease. Obstet Gynecol.
2010;116:419.
Workowski KA, Bolan GA, Centers for Disease Control and
Prevention. Sexually transmitted diseases treatment guidelines.
MMWR Recomm Rep. 2015;64:1.
Chapter 4
Contraception
• Types of contraception:
Hormonal Combined hormonal contraception, progestin-
methods only contraception, and levonorgestrel-
releasing intrauterine device (IUD)
Mechanical Barrier methods, e.g., condoms/non-hormonal
methods IUD
Surgical Female sterilization/male sterilization
methods
Natural methods Breastfeeding (lactational amenorrhea
method), periodic abstinence, coitus
interruptus
Chemical Spermicides
methods
• Effectiveness of contraceptive methods:

Effectiveness of a contraceptive method is defined
using the following terms:
➊ Theoretical effectiveness: this term refers to reliability
of a contraceptive method to prevent pregnancy with
perfect use. It is measured using Pearl index (PI):
No of pregnancies
´ 1200 no of months used by 100 women in 1 year
PI =
Total months of pregnancy exposure


https://doi.org/10.1007/978-3-030-41128-2_4
152 Chapter 4. Contraception
PI presents as number of pregnancies/hundred woman

years (HWY).
➋ Use effectiveness: this term describes reliability of a
contraceptive method when used by general population
(actual use).
➌ Cost-effectiveness: the term describes the effectiveness
of a contraceptive method in relation to its cost.
Therefore, a contraceptive method failure rate can be either:
Perfect-use failure rates Typical-use failure rates
The number of pregnancies The number of pregnancies
during cycles when the during cycles when the method
method is used consistently is used either perfectly or
and correctly imperfectly, e.g., missing her pills
The difference between the two rates reflects how easy

compliance to this method is. Therefore, provider-dependent
methods, e.g., IUD, have no difference between their perfect-
and typical-use failure.
• The WHO Medical Eligibility Criteria Classification
categories:
These categories are used to define how safe the use of a
contraceptive method is in relation to different medical
conditions:
WHO Medical Eligibility Criteria Classification categories
• Category 1: no restriction/contraindication to the use of this
contraceptive method
• Category 2: the benefits of this method outweigh the risks,
favoring its use
• Category 3: the risks outweigh the advantages of using the
method (relative contraindications)
• Category 4: the risk of using this method is unacceptable
(absolute contraindications)
Barrier Methods
Description Mode of action Failure rate Advantages Disadvantages
Male condom Male condoms can be: It is a 2% with Safe, reversible, It interferes
Latex rubber condoms
➊ mechanical perfect use user dependent, with sexual act
Polyurethane condoms
➋ barrier that and 15% with protects against and may impact
(more adherent and prevents sperm typical use STIs sensation
thinner) deposition
Female It is a polyurethane sheath It is a Perfect use: It does not Relatively
condom (15 × 7.5 cm) placed mechanical 5%, typical interfere with difficult to place
to line the vagina. The barrier that use: 21% sexual act. Less
internal ring is placed prevents sperm diminution
over the cervix, and the deposition of sensations
external ring is outside of compared to
the vagina male condoms
Barrier Methods
153
Description Mode of action Effectiveness Advantages Disadvantages
154
Vaginal They can be either: It prevents Perfect use: Safe, easy, It may interfere
diaphragm ➊ Flat spring diaphragm: sperms from 5%, typical effective, with sensation
the standard one reaching use: 21% reversible, and It is relatively
➋ Coil spring diaphragm: the upper user dependent difficult to place
softer, suitable for a genital tract. Does not protect
tight vagina Spermicides against STDs
➌ Arcing diaphragm: are used at the It is not suitable
suitable for lax vagina same time. from prolapse
and early
postpartum users
Chapter 4. Contraception
Cervical cap It is a cup-shaped cap that It prevents Perfect use: Unlike the It is not suitable
is applied directly over sperms from 9%, typical diaphragm, it for short,
the cervix; it comes in reaching the use: 16 % is suitable for damaged cervix
different sizes cervix. A weak pelvic floor or unreachable
spermicide musculature and cervix
is used along is unlikely to It is relatively
with the cap interfere with difficult to use,
sensation and it requires
proper size
selection
Vaginal It consists of a It acts as 9–12% Easy to use Relatively
sponge polyurethane sponge a barrier, Does not require expensive
containing spermicide releases training to place
spermicides,
and is also an
absorbent of
seminal fluid
Spermicides Nonoxynol-9 is a chemical It is a chemical Failure rate It provides extra It increases
compound that is present compound that is 28%. lubrication susceptibility to
in different forms, e.g., alters sperm Therefore, HPV infection
creams and gel permeability it should be Its use may be
resulting used with associated with
in osmotic a barrier unpleasant odor
damage method and irritation
Barrier Methods
155
Combined Hormonal Contraception
Types of Combined Contraception
Combined Oral Contraceptive (COC) Pills
• Components of COCs:
I. Estrogens: estrogen form is ethinyl estradiol (EE) at
different doses.
II. Progestogens: synthetic formulations of progesterone
• 1st-generation progestin: norethindrone
• 2nd-generation progestin: levonorgestrel
• 3rd-generation progestins:
–– Multiple available:
For example, desogestrel (Marvelon®), ges-
todene (Gynera®), and norgestimate (Cilest®)
–– Advantages of 3rd-generation progestins:
➀ Effective suppression of ovulation (high affin-
ity to progesterone receptors)
➁ Less androgenic side effects (lower affinity to
androgen receptors)
–– Disadvantages:
Third and fourth generations are associated with
higher risk of thromboembolism compared to
first and second generations.
• 4th-generation progestins: e.g., drospirenone
(Yasmin®), derived from 17α-spironolactone
Classification Ethinyl estradiol (μg)
Ultralow-dose pills 20 or less
Low-dose pills 30–35
High-dose pills 50
Combined Hormonal Contraception 157
• Types of COCs:
–– Monophasic pills: these pills contain a constant dose of
progestogen and estrogen throughout the 21 days.
–– Biphasic pills: they contain two dose formulations (the
first 7–10 days contain higher estrogen-to- progestin
ratio compared to the rest of pills).
–– Triphasic pills: three different doses of hormones at
approximately every 7 days.
Transdermal Patches
• Composition: the patch delivers 20 μg ethinyl estradiol and

150 μg norelgestromin daily.
• Administration: the patches are applied for 21 consecutive
days (a patch works for 1 week) followed by a 7-day patch-
free interval. The patch can be applied on the upper arm,
lower abdomen, buttocks, or back.
• Advantages: better compliance compared to the pills.
• Disadvantages (side effects): skin irritation, itching, and
soreness at the site of patch application. Risk of falling off
is <2%.
Vaginal Ring
• Preparation: vaginal ring releases 15 μg ethinyl estradiol

and 120 μg etonogestrel.
• Administration: it is used for 3 weeks followed by a 7-day
ring-free interval.
• Advantages: fewer bleeding issues, less systemic side
effects (e.g., nausea, acne, irritability, depression) com-
pared to oral pill.
• Disadvantages: vaginal irritation and discharge.
Mode of action
• Inhibition of ovulation:
–– Estrogens: they inhibit FSH secretion with subsequent
inhibition of follicular growth.
–– Progestins: they inhibit LH with subsequent inhibition
of ovulation.
• Alteration of cervical mucus: hormonal action reduces the
probability of successful transportation of sperms through
cervical mucus into the upper genital tract.
• Alteration of endometrium: endometrial growth is sup-
pressed. Therefore, it remains thin and unfavorable for
implantation.
• Tubal motility alteration: interferes with gamete transfer.
Effectiveness
• Perfect-use failure rates: 0.2–0.3/HWY (0.2–0.3 per 100

women get pregnant in 1 year)
• Typical-use failure rates: 7/HWY
• Contraceptive indications: primary indication
• Non-contraceptive indications:
• Dysmenorrhea • Heavy menstrual bleeding
• Premenstrual syndrome • Acne, hirsutism
• Endometriosis • Functional ovarian cysts
Contraindications
U.S. Medical Eligibility Criteria for Contraception Use

(U.S. MEC) category 4
• Less than 21 days postpartum
moking (≥15 cigarettes/day) in women aged ≥35 years
• S
• Uncontrolled hypertension (systolic ≥160, diastolic ≥100) or
hypertension complicated with vascular disease
• Multiple risk factors of atherosclerotic cardiovascular disease

• History of venous thromboembolism/pulmonary embolism
(not on anticoagulation) at higher risk of recurrence
• Current venous thromboembolism/pulmonary embolism
on anticoagulation for at least 3 months at higher risk of
recurrence
• Major surgery with prolonged immobilization
• History of or current ischemic heart disease
• Known thrombogenic mutations
• Peripartum cardiomyopathy with moderate or severe cardiac
dysfunction or with normal to mild cardiac dysfunction
(within 6 months of diagnosis)
• History of cerebrovascular accident
• Complicated valvular heart disease, e.g., pulmonary
hypertension, atrial fibrillation, or subacute bacterial
endocarditis
• Migraine with aura
• Complicated solid organ transplantation
• Systemic lupus erythematosus with positive or unknown
antiphospholipid antibodies
• Current breast cancer
• Complicated or uncontrolled diabetes (with nephropathy,
neuropathy, retinopathy)
• Viral hepatitis (active or flare)
• Severe (decompensated) cirrhosis
• Hepatocellular adenoma and hepatoma
• Smoking (<15 cigarettes/day) in women aged ≥35 years
• Breastfeeding women between 21 and <30 days postpartum
• Breastfeeding women between 30 and 42 days postpartum

with other risk factors of venous thromboembolism
• Non-breastfeeding women between 21 and 42
days postpartum with other risk factors of venous
thromboembolism
• History of venous thromboembolism/pulmonary embolism
(not on anticoagulation) at lower risk of recurrence
• Current venous thromboembolism/pulmonary embolism
on anticoagulation for at least 3 months at lower risk of
recurrence
• History of or acute superficial venous thrombosis
• Controlled hypertension or mildly elevated blood pressure
(systolic 140–159, diastolic 90–99)
• Multiple sclerosis with prolonged immobility
• Peripartum cardiomyopathy with normal to mild cardiac
dysfunction (>6 months of diagnosis)
• Past breast cancer with no evidence of recurrence for at least
5 years
• History of bariatric surgery (malabsorptive procedures)
• Controlled diabetes
• Current symptomatic or medically treated gallbladder disease
• History of COC-related cholestasis
• Drug interactions, e.g., antiretroviral therapy (fosamprenavir),
lamotrigine, rifampin, and some anticonvulsants (phenytoin,
carbamazepine, topiramate, barbiturates, primidone)
Stroke
Age >35 years

Heavy smoking
Severe hypertension
ischemic heart
disease
Breast feeding
Active hepatitis breast cancer
liver tumors
decompensated Uncontrolled DM
cirrhosis
Pregnancy
gestational
trophoblastic
disease
Unexplained vaginal
bleeding
Venous
thromboembolism
Memorizing diagram: Category 4 Medical Eligibility

Criteria for combined hormonal contraception
Advantages
I. Contraceptive benefits
• A safe method; serious complications are rare.

• Easy to use.
• Highly effective if used correctly.
• Reversible with rapid return to fertility.
• Initiation and discontinuation are controlled by the user.
• It is not teratogenic.
II. Non-contraceptive benefits
• Reducing risk of ovarian cancer and benign ovarian cysts:

Risk reduction of ovarian cancer is duration dependent.
After 5 years of use, the risk is reduced by 50%, and the
protection effect continues for 10 years or more after dis-
continuation of pill use.
• Reducing risk of endometrial cancer:
The use of COCs for 1 year reduces the risk of endome-
trial cancer by 30–50%. Protection effect continues for 10
years after discontinuation.
• Reducing risk of ectopic pregnancy: due to inhibition of
ovulation
• Reducing menstrual irregularities:
–– When used as a 21/7 regimen, COCs regulate menstrual
cycle and reduce menstrual blood loss.
–– When used continuously, they induce amenorrhea. This
may be beneficial to correct anemia in patients with
heavy menstrual bleeding or in women with
dysmenorrhea.
• Reducing symptoms associated with endometriosis and
premenstrual syndrome
• Preventing formation of functional ovarian cysts
• Improving acne and hirsutism

• Protecting against systematic disorders: there is some evi-
dence that COCs are protective against rheumatoid arthri-
tis, thyroid disease, and duodenal ulcer.
• Improve bone mineral density: COCs are associated with
increases in bone mineral density (BMD) especially in
women with hypoestrogenic conditions.
Acne
Thyroid
diseases
Benign breast
disease
Peptic ulcer
Ectopic pregnancy
Ovarian
cancer
Functional cysts
Endometrial
cancer
Menstural
disturbance
Memorizing diagram: non-contraceptive benefits of combined hor-

monal contraception
Disadvantages
• Incorrect use and missed pills are common. Therefore,

typical use is associated with significantly higher failure
rate (7%) compared to perfect-use failure rate
(0.2–0.3%).
• It requires daily pill intake.
• Short-term contraception, resupply is required.
• It offers no protection against sexually transmitted infec-
tions (STIs).
• Side effects are common.
Adverse (major side) effects
• Venous thromboembolism (VTE): the risk is tripled com-

pared to general population. The risk seems to be higher
with third- and fourth-generation COCs.
• Myocardial infarction:
–– The risk of myocardial infarction increases by 2.5 for
current users of COCs.
–– The risk resolves rapidly after discontinuation of COCs.
• Stroke:
–– The risk of ischemic stroke: it is increased among cur-
rent users of the combined pill (relative risk is 2.7).
–– The risk of hemorrhagic stroke: it is not increased.
• Migraine:
Migraine is associated with an increased risk of isch-
emic stroke, and the risk is more with aura.
• Cancer:
–– Breast cancer: an increased risk of breast cancer is sug-
gested (relative risk is 1.24). The increased risk takes 10
years to decline to that of nonusers.
–– Cervical cancer
Women with persistent infection with HPV infection

who use hormonal contraception for >5 years, the
relative risk of cervical cancer is increased up to
fourfold.
Hormonal contraceptive use for longer than 10 years,
even among women who are HPV negative, may
double the relative risk of cervical cancer.
The risk declines after discontinuation.
The risk may reflect either a biological etiology or it
may be because use of barrier methods is less likely
among hormonal contraception users. Thus, these
women may be more likely to acquire HPV.
• Liver cancer: use of the combined pill is associated with
an increased risk of liver cancer but only in populations
with a high rate of hepatitis B infection.
• Increase risk of gall stones
Side effects
• Nausea and vomiting:

Nausea and vomiting are caused by the estrogen com-
ponent. Therefore, this side effect is uncommon with low-
dose preparation.
–– Management:
Change the time of taking of the pill. Take the pill on
a full stomach.
Change the pill to a lower-dose preparation.
If persistent, consider other methods of
contraception.
• Breakthrough bleeding (intermenstrual bleeding related
to COC use):
–– Management: the steps of management are shown in
the next illustration.
Duration of COC use
< 3 months > 3 months
Reassurance Exclusion of Ds
Default: missed pills (commonest).

Disease: examine the cervix for local
cause (ectropion, cervical polyp,
neoplasia, STI "chlamydial").
Disorders of pregnancy: pregnancy test is
indicated.
Drugs: that may alter COCs metabolism.
Diarrhea: and/or vomiting.
Disturbance: of absorption.
Diet: vegetarian food (reduced flora).
No obvious cause
Monophasic pills Bi- or Triphasic
Increase the dose of estrogen Change to

Change progestogen type (LNG is better than norethisterone) monophasic
Combined contraceptive vaginal ring and changing the method of

contraception are the last choices
• Amenorrhea:
–– Management:
Exclude pregnancy especially if there is a history of
missed pills then reassurance.
Shift to triphasic pills.
Post-pill amenorrhea is a hypothalamic amenorrhea
caused by extended suppression which usually
extends for not more than 3 months.
• Chloasma:
–– Definition: a brownish pigment to the skin of the face
particularly with exposure to sunlight.
–– Etiology: it can occur with both estrogen and
progestogen.
–– Management:
Mild chloasma: can be hidden by the use of cosmetics.
Severe chloasma: the only solution is to change to a
non-hormonal method of contraception.
• Breast tenderness:
–– Etiology: it may be due to either estrogen or
progestogen.
–– Management:
Reassurance: it tends to improve with time.
Changing progestogen: the anti- mineralocorticoid
effects of drospirenone may be of benefit.
• Fluid retention:
–– Etiology: thought to be related to progesterone.
–– Management: pills containing drospirenone may be
associated with less fluid retention.
• Weight gain:
–– Etiology: water and salt retention, anabolic effect of
progesterone, increased appetite
–– Management: advise about diet and exercise
• Headache, dizziness, and mood changes
• Excessive vaginal discharge: it may due to increased tran-
sudation from the vagina or cervical ectopy.
• Vaginal candidiasis
Administration
• Clinical evaluation:
I. History
• Medical history: a good medical history that is updated at

annual review
• Sexual history: to assess the risk of sexually transmitted

infection
• Family history: to identify any increased risk of conditions
such as breast cancer
II. Examination
It is not necessary for women to undertake routine physical

examination before they start using hormonal
contraception.
• The measurement of blood pressure is mandatory.
• An assessment of BMI is strongly recommended.
• Counseling: women should be counseled about different
contraceptive options, their side effects, and possible
adverse effects. She should be aware of warning signs of
COCs:
Warning symptoms: suggestive of complications (ACHES)
Abdominal pain
Chest pain
Headache
Eye symptoms
Severe leg pain
• Prescription:
–– Choosing the pill:
The first choice should be a monophasic preparation
containing 30 μg ethinyl estradiol with either norethis-
terone or levonorgestrel as the progestogen.
–– Initiating method use:
–– Method continuation:
Oral contraceptive pills, the contraceptive patch, and
the vaginal ring are used every day for 21 days fol-
lowed by 7 days without medication.
Injectables are given monthly with not more than 3

days early or late.
–– Discontinuation indicated with:
Onset of manifestation of one of the complications,
e.g., jaundice
Sustained blood pressure above 160/100 mmHg
Appearance of a new risk factor
Preoperative, 4 weeks before the operation
Significant immobilization, including that of a limb
When pregnancy is desired or contraception is no
longer needed
–– Management of missed pills:
Woman with missed pills
If one pill is If 2 or more

missed are missed
Take the last pill as soon as she Take the last pill as soon as she
remembers remembers
+ +
Continue taking the pills as Continue taking the pills as usual
usual +
Back up method (or abstinence) for 7
days
+
Further advice according to the time of
taking pills
If the pill is missed in If the pill is missed in the If the pill is missed in the 3rd
the 1st week of the cycle 2nd week of the cycle week of the cycle
Emergency No emergency The next pill free interval is

contraception is needed contraception is needed cancelled
If menstruating • Any day up to the fifth day of the menstrual

cycle
• When a woman starts the pill beyond day
5, she should be advised to use backup
contraception for the first 7 days
If amenorrheic It can be started any day after exclusion of
pregnancy
If postpartum • Lactating: 6 months postpartum
• Non-lactating: 3 weeks postpartum
If post-abortive 1 or 2 days post-abortive
Progestin-Only Contraception
• High-dose progestin-only contraception: progestin-only
injectables
• Low-dose progestin-only contraception: implants
• Very low-dose progestin-only contraception:
–– Progestin-only pills (POPs)
–– Vaginal rings (levonorgestrel rings)
–– Levonorgestrel IUDs
Progestin-Only Pills (POPs)
• Types of POPs:
Progestogen Dose (μg)
Norethisterone (Norethindrone) 350
Levonorgestrel 30
Desogestrel (new POPs) 75
• Mode of action:
–– Cervical mucus modification: cervical mucus becomes
hostile and impenetrable to sperm (the main action of
older pills).
Progestin-Only Contraception 171
–– Endometrial modification: progestins act on the endo-

metrium, so it thins out and becomes unfavorable for
implantation.
–– Tubal modification: affecting motility and secretions.
–– Ovulation inhibition:
Newest POPs: prevent follicular development and
maturation and ovulation in 97% of cycles.
Older-type POPs: their effect on ovulation is variable,
and it is not a reliable mechanism of contraception.
• Efficacy:
–– Older-type POP (norethisterone and levonorgestrel): it
varies from 0.3/HWY in women >35 years old to 4.0/
HWY for younger users.
–– Desogestrel-containing POP: it is 0.17/HWY in non-
lactating women.
• Indications:
It may be particularly useful in the following
situations:
–– Breastfeeding:
The POP does not affect the volume of milk.
The amount of progestogen transferred in the milk
to the baby is extremely small.
–– Contraindication to estrogen: e.g., migraine with aura
–– Serious side effects to estrogen: e.g., cholestatic
jaundice

• Past breast cancer with no evidence of recurrence for at least
5 years
• Severe (decompensated) cirrhosis

• History of bariatric surgery (malabsorptive procedures)
• Current and history of ischemic heart disease
• Hepatocellular adenoma or hepatoma
• Drug interactions, e.g., rifampin and some anticonvulsants
(phenytoin, carbamazepine, topiramate, barbiturates,
primidone)
• Advantages:
–– Contraceptive benefits:
General advantages: effective (failure rate of 0.3–4/
HWY), safe, easy to use (intercourse independent),
and reversible
Advantages over CHCs:
• Can be used during breastfeeding.
• Less drug interactions.
• No effect on metabolic parameters, blood pres-
sure, coagulation factors.
• There is no evidence of increased risks of any
malignancy.
–– Non-contraceptive benefits:
Definite benefit: protection against endometrial
carcinoma
Probable benefit: protection against ascending pelvic
infection and ectopic pregnancy
Unproven benefit: protection against endometriosis,
leiomyoma, benign breast disease, and ovarian
carcinoma
• Disadvantages:
–– Older-type POPs are not highly effective in young non-
breastfeeding women compared to other options
–– Needs continuous daily intake (risk of missing pills)
–– No protection against sexually transmitted diseases

–– Side effects of POPs
• Side effects:
–– Menstrual disorders: this ranges from complete amen-
orrhea to unpredictable bleeding. Bleeding disorders
are the main reason of discontinuation.
–– Functional ovarian cysts: due to the persistent unrup-
tured follicles which then gradually enlarge and become
symptomatic.
–– Progestin-related side effects: headache, dizziness, nau-
sea, weight gain, bloating, acne, and mood.
• Administration:
–– Clinical evaluation:
I. History
A full history should be taken with details.
II. Examination
Blood pressure (BP), weight, height, and body mass index

(BMI) should be recorded as a baseline. Following the initial
assessment, BP should be monitored annually.
• Counseling:
The following should be discussed with the patient:
safety and efficacy, mechanism of action of POPs, their
advantages and disadvantages, potential side effects,
administration regimen, and management of missed pills.
• Prescription:
–– Starting regimens:
–– Continuation regimen (daily pill taking):
–– The POP should be taken every day at the same time of
day continuously without a break (no pill-free intervals).
The pill is taken within 3 hours of the same time of tak-
ing the pills.
–– Missed or late pills:

For older-type POPs (3-hour rule): if a woman is
more than 3 hours late this is a “missed” pill, she
should take the missed POP as soon as possible, take
the next POP at the usual time, and use additional
contraception or abstain for 48 hours.
Desogestrel-containing POP (12-hour rule): it may
be taken up to 12 hours late. If desogestrel-containing
POP is taken >12 hours late, then do as mentioned in
older POPs.
If the woman is breastfeeding (amenorrheic, exclusive
breastfeeder, during the first 6 months postpartum),
there is no need for backup method.
If menstruating • Any day up to the fifth day of the menstrual

cycle
• When a woman starts the pill beyond day
5, she should be advised to use backup
contraception for the first 2 days
pregnancy
If postpartum • Lactating: 3 weeks postpartum
• Not lactation: the same
If post-abortive 1 or 2 days post-abortive. When a woman starts
the pill beyond 7 days, she should be advised
to use backup contraception for the first 2 days
Progestin-Only Injectables
• Types of progestin-only injectables (POI):

–– Depot medroxyprogesterone acetate (DMPA): there is
no limitation to the duration of use (150 mg).
–– Norethisterone enanthate (NET-EN): NET-EN only for
short-term use (200 mg). It is not available in the
United States.
• Mode of action:
–– Main action: inhibition of ovulation through suppres-
sion of the hypothalamic/pituitary/ ovarian axis (sup-
pression of LH and to some extent, FSH)
–– Secondary mechanisms of action: endometrial suppres-
sion and increased cervical mucus thickness
• Efficacy:
–– POIs are highly effective. Perfect-use failure rate is 0.3/
HWY.
–– Typical-use failure rate is 4%.
• Advantages:
• General advantages: easy, effective, safe, and reversible

• Advantages over CHCs: no estrogen side effects, safe
for breastfeeding
• Advantages over POPs: highly effective and long-acting
contraception
• It may improve premenstrual symptoms and

dysmenorrhea.
• It reduces frequency of sickle cell crisis in women with
sickle cell disease.
• It reduces frequency of epileptic seizures.
• It may protect against pelvic inflammatory disease.
• It reduces the risk of extrauterine pregnancies as POIs
inhibit ovulation.
• It is associated with fewer functional ovarian cysts.
• It may relieve endometriosis-related pain and reduce
fibroid formation and growth.
• It reduces the risk of endometrial cancer by fivefold at
least 8 years after cessation.
MASS SHAPED (ovarian cysts,

fibroids, carcinoma) CRESCENT SHAPED (sickle cell
anemia)
A helpful diagram: how
to remember non
contraceptive benefits of
injectables (syringe)* DROPS (heavy
TUBE-LIKE (ectopic pregnancy,
pelvic inflammatory disease) INJECTION PAIN menstrual bleeding)
(dysmenorrhea,
endometriosis-related
pain)
* Injection pain refers to pain-relieving indications, drops refer to bleeding related indications
A helpful diagram: how to remember non-contraceptive

benefits of injectables (syringe) (Injection pain refers
to pain-relieving indications; drops refer to
bleeding-related indications)
• Disadvantages:
–– Given intramuscularly, therefore cannot be removed if
adverse effects occur
–– Side effects of POIs
• Specific side effects and complications:
–– Disturbances in menstrual pattern:
Types:
• Amenorrhea: (most common) 55% within the
first 3 months
• Frequent irregular bleeding: 10% within the first 3
months
• Prolonged bleeding episodes: 30% within the first
3 months
Management:
• If estrogen is not contraindicated: two cycles of
30 μg COCs may restore menstrual pattern.
• If estrogen is contraindicated: NSAIDs may be
used (mefenamic acid).
–– Weight gain: the main mechanism is progestin-related

increase in appetite.
–– Bone mineral density: bone loss is approximately 5–7%
in the hip and spine. Bone loss is reversible, and it usu-
ally returns to normal within 2 years after discontinua-
tion of POIs.
–– Progestogenic side effects, e.g., bloating, mastalgia,
headaches, acne, and low libido.
–– Delay in return of fertility:
Cause: this delay is due to persistence of progestogen
in the circulation.
Duration: 9 months after the last injection.
• Indications:
–– Contraceptive indications: e.g., women who have con-
traindications to estrogen, women with sickle cell dis-
ease, and women with epilepsy
–– Non-contraceptive indications: e.g., endometriosis-
related pain
WHO Medical Eligibility Criteria Category 4 conditions

WHO Medical Eligibility Criteria Category 3 conditions
• History of breast cancer and no evidence of current disease
for at least 5 years
• Severe decompensated cirrhosis
• Diabetes for more than 20 years or diabetes with
nephropathy, retinopathy, or neuropathy
• Uncontrolled hypertension (systolic ≥160, diastolic ≥100) or
hypertension complicated with vascular disease
• Multiple risk factors of atherosclerotic cardiovascular disease

• Unexplained vaginal bleeding before assessment
• Administration:
–– Clinical evaluation and counseling
–– Using the method:
Initiation:
Continuation: DMPA is given every 12 weeks;
NET-EN is administered every 8 weeks.
If menstruating Within the first 5 days of the menstrual

cycle or an additional contraceptive method/
abstinence is required for 7 days
pregnancy
If postpartum Lactating: 6 weeks postpartum (3–6 weeks is
under category 2)
Not lactation: 3 weeks postpartum
If post-abortive 1 or 2 days post-abortive
Progestogen-only implants
• Types of subdermal implants:

–– Etonogestrel implant (Nexplanon, Implanon): it is a
single rod measuring 40 × 2 mm. It contains 68 mg of
etonogestrel. Duration of use is 3 years.
–– Levonorgestrel implants: Norplant (6 capsules, not
manufactured anymore), Jadelle (Norplant II, not avail-
able in the United States)
• Mode of action:
–– Suppression of ovulation: this is the primary mechanism
of contraception of Nexplanon.
–– Alteration of cervical mucus consistency: cervical mucus

becomes thick and inhibits normal sperm penetration.
• Effectiveness:
Failure rate of Nexplanon is 0.1/HWY

• Advantages and disadvantages:

Advantages Disadvantages
• General advantages: e.g., highly • It provides no
effective, long-acting, reversible, protection from STI-
easy (e.g., HIV)
• Advantages over CHCs: no • Insertion and removal
estrogen effect, suitable for require special
breastfeeding training
• Advantages over injectables: rapid • Risks of procedure
return to fertility, no effect on bone • Risks of difficult
density removal
• Non-contraceptive advantages: • Side effects
reduced dysmenorrhea with less • Discontinuation is not
menstrual loss self-controlled
• Side effects and complications:
I. Complications of insertion and removal
• Impalpability of the implant, broken or damaged

implant, and difficult localization.
• Formation of a fibrous capsule can lead to difficult
removals.
• Implant migration is rare.
• Traumatic peripheral neuropathy and other neurovas-
cular injuries have been reported.
II. Menstrual side effects
Abnormal bleeding patterns are common, e.g., prolonged

irregular bleeding. Management includes proper counseling
and reassurance. COCs or NSAIDs may be offered for short-
term management depending on bleeding pattern.
III. Non-menstrual side effects
• Weight gain: gradual increase in body weight has been

observed.
• Ovarian follicles/cysts: they spontaneously regress.
• Metabolic effects: it does not increase risk of diabetes
complications.
• Administration:
–– Clinical evaluation: history and examination
–– Counseling: covering all items
–– Prescription:
Timing of insertion:
• Implants should be inserted from day 1 to day
7 of the menstrual cycle.
• Implants can be inserted at any other time of the

cycle if it is reasonably certain that the client is
not pregnant, but additional contraception is
required for 7 days.
Implant insertion:
Nexplanon is inserted subdermally in the medial
aspect of a subject’s upper non-dominant arm,
6–8 cm above the elbow in the groove between the
biceps and triceps using a specially designed pre-
loaded disposable applicator.
Implant removal
I. If the implant is easily palpable
• Removal, using a “pop-out” technique, through a

2–3 mm incision over the distal tip of the implant(s).
• Gently push the implant(s) toward the incision until the
tip is visible. Grasp the bare implant(s) with forceps and
remove.
II. If the implant is deep
• If the implant is not palpable:

• Exclude pregnancy then start additional contraception.
• Do not attempt to remove the implant. Localize it using
an appropriate technique:
–– Jadelle® rods can be located through X-ray or
ultrasound.
–– Implanon® is localized by linear transducer of
ultrasound.
–– Nexplanon® (radiopaque) is localized by X-ray or
ultrasound.
• Removal of deep implants should be performed in the
operating room.
Intrauterine systems
• Types of intrauterine system (IUS):

The device The hormone Duration
Mirena® T-shaped frame It releases 20 μg At least
with a central levonorgestrel per day 5 years
silastic sleeve (52 mg per device)
Skyla® Similar to It releases 14 μg Acts for
Mirena, smaller levonorgestrel per day 3 years
in size (13.5 mg per device)
Kyleena® Similar to It releases 17.5 μg Acts for
Mirena, smaller levonorgestrel per day 5 years
in size (19.5 mg per device)
Liletta® T-shaped It releases 20 μg Acts for
polyethylene levonorgestrel per day 6 years
frame (52 mg per device)
• Mode of action:
–– These devices work primarily through local hormonal
effect of progestin on the endometrium (severe atrophy
and decidualization of the stroma).
–– Alteration of cervical mucus (inhibits sperm
penetration).
• Advantages:
• General advantages: easy, effective, safe, and rapid

return of fertility on removal
• Advantages over CHCs: no complications of estrogen.
• Advantages over other progestin-only methods: very low
serum hormone levels, and this minimizes side effects.
• Advantages over copper IUD: lower risk of PID. It is not

associated with heavy menstrual bleeding. In fact, levo-
norgestrel-releasing IUD is a treatment option for
heavy menstrual bleeding.
• It is an effective option in management of heavy men-

strual bleeding.
• It may improve dysmenorrhea.
• It may reduce endometriosis-related pain.
• It provides endometrial protection against estrogen
effect.
• Disadvantages and side effects:
–– Bleeding disorders: users may experience several
months of persistent and irregular bleeding. They
should be reassured that bleeding will gradually set-
tle with time and end by cyclic scant menstrual
bleeding or amenorrhea.
–– Progestogenic side effects: compared to other
progestin-containing contraception, IUS delivers sig-
nificantly lower serum hormonal level. Nevertheless,
some progestogenic side effects may occur, e.g.,
breast pain, acne, and mood swings.
–– Emergency contraception: unlike IUD, an IUS
should not be used for emergency contraception.
• Indications:
I. Contraceptive indications
An IUS is ideal for women who are interested in a highly

effective, completely reversible, and long-acting contracep-
tive method. The presence of a concomitant non-contraceptive
indication (e.g., heavy menstrual bleeding) favors their use,
and women should be counseled on other contraceptive ben-
efits of IUS.
II. Non-contraceptive indications
• Treatment of heavy menstrual bleeding

• Treatment of dysmenorrhea
• Treatment of endometriosis-related pain
• Treatment/prevention of endometrial hyperplasia
• As a progestin component of hormonal therapy (endo-
metrial protection)

• Pregnancy
• Current pelvic inflammatory disease
• Current purulent cervicitis or chlamydial/gonorrhea infection
• Gestational trophoblastic disease with persistently elevated
β-hCG, suspected or diagnosed intrauterine malignant disease
• Pelvic tuberculosis
• Immediate post-septic abortion
• Postpartum sepsis
• Cervical cancer awaiting treatment
• Distorted uterine cavity
Non-hormonal Intrauterine Devices 185

• Administration:
–– Insertion procedure:
Progestin-releasing intrauterine device has a special
disposable introducer. It has a wider diameter in its
insertion tube (4.7 mm) than some of the older copper
IUDs.
–– Duration of use:
Contraception: Mirena® and Kyleena® are licensed
for 5 years for contraception, Skyla® for 3 years, and
Liletta® for 6 years.
Gynecological indications: IUS can remain in situ for
as long as it controls patient symptoms.
Endometrial protection: if IUS is used to provide
progestin component of hormonal therapy, duration
of use should be the same as with contraceptive use.
Non-hormonal Intrauterine Devices

• Types of copper IUDs:
Framed copper devices Frameless copper devices
• T-shaped devices: GyneFix:
• Copper T380A: licensed for • It consists of non-
8–10 years of use biodegradable, monofilament
• Nova-T380 and Flexi-T380 thread and six copper beads
are licensed for 5 years with a surface area of 330 mm2
• U-shaped devices: • A knot at the upper end of the
• Multiload 250: licensed for filament serves as an anchor
5 years which is implanted into the
• Multiload 375: are licensed fundal myometrium
for 8 years • The device is licensed for 5
years
The number, e.g., 380, refers to the copper wire surface area
(380 mm2)
• Mechanism of action:
Prevention of fertilization rather than implantation is
the main mode of action.
–– Alteration of the endometrium (aseptic endometritis):
IUDs trigger a foreign body reaction, enhanced by
their copper coat, in the endometrium with subsequent
increase in prostaglandins and leucocyte infiltration.
–– Alteration of tubal motility and uterine contractions:
mediated by prostaglandins.
–– Alteration of uterine and tubal fluid: this impairs the
viability of the gametes.
–– Inhibition of sperm transport: this action is mediated
by copper.
• Effectiveness: typical-use failure rate is 0.5/HWY. Five-
year failure rates is 2%.
• Indications:
➊ Users who are interested in long-term
contraception.
➋ Emergency contraception; it may be inserted within
5 days of unprotected intercourse.
• Pregnancy
• Current pelvic inflammatory disease
• Current purulent cervicitis or chlamydial/gonorrhea infection
• Gestational trophoblastic disease with persistently elevated
β-hCG, suspected or diagnosed intrauterine malignant disease
• Pelvic tuberculosis
• Immediate post-septic abortion
• Postpartum sepsis
• Endometrial cancer
• Cervical cancer awaiting treatment

• Distorted uterine cavity
• Systemic lupus erythematosus with severe thrombocytopenia
TB salpingitis/PID
Endometrial cavity
Gestational Pregnancy
trophoblastic
disease
Puerperal sepsis
Cervical infection
endometrical/cervical
carcinoma
Unexplained vaginal
bleeding
A helpful diagram: how to remember Category 4

indications for copper IUD
• Advantages:
–– Safe and effective.
–– It is not user dependent.
–– Inexpensive.
–– Long acting.
–– Reversibility.
–– No systemic side effects.
• Disadvantages:
I. Side effects
Cause Management
Menstrual It may be • Women should
disorders attributed be reassured
(the most to increased that menstrual
common is fibrinolytic disorders are
heavy menstrual activity of the common in the
bleeding) superficial first 3–6 months of
endometrium IUD placement,
and they will likely
improve over time
• I n the meanwhile,
COCs or
tranexamic acid
may be offered
temporarily to
improve bleeding
pattern
Dysmenorrhea It may be caused • Women should
by uterine be reassured that
irritation by dysmenorrhea is
transverse arms likely to resolve
of the IUD over time
• I n the meanwhile,
analgesics may be
offered to control
pain
Increased vaginal Vaginal discharge • Women should
discharge may increase be reassured that
as a sequence watery or mucoid,
of uterine non-offensive
inflammatory discharge is not
reaction uncommon
•H owever, they
should be warned
to report profuse,
persistent, or
offensive discharge
II. Complications
• During insertion (for both IUD and IUS):

➊ Vasovagal reaction:
–– Incidence: rare.
–– Cause: dilatation of the internal cervical os with the
sound or introducer
–– Clinical presentation: syncope and bradycardia due
to vasovagal attack
–– Management:
It is usually transient and self-limiting, and the
procedure can be completed safely.
If severe, insertion has to be stopped and the
woman resuscitated.
➋ Perforation:
–– Incidence: 1 per 1000 insertions (highest risk between
48 hours and 4 weeks postpartum)
–– Types:
➀ Partial: with part of the IUD piercing the uterine

or cervical wall
➁ Complete: with IUD passing through the uterine
wall into the peritoneal cavity
–– Clinical evidence:
➀ Development of severe pain or abnormal bleeding
at the time of insertion
➁ Persistence of bleeding or pain after insertion
➂ Disappearance or shortening of strings
➃ Development of pelvic infection
➄ Occurrence of pregnancy
–– Outcome: perforations that occur most often heal
quickly without any treatment. However, copper
devices cause an intense inflammatory reaction
within the peritoneal cavity leading to adhesions.
–– Management:
If perforation is recognized prior to insertion (due
to cervical dilation or uterine sound): patient
should be observed for signs of internal bleeding
and IUD should not be placed.
If perforation is recognized during or just after
insertion: the procedure should be stopped and the
device removed. The patient observed for signs of
internal bleeding.
If the perforation is recognized within a few days
or weeks after insertion: the device should be
removed by laparoscopy or laparotomy.
➌ Failure to insert: due to anxiety/pain, poor technique, or
anatomical abnormalities
• After insertion:
➊ Intrauterine pregnancy:
–– Incidence: 0.5 per HWY
–– Management (see the table below):
During 1st Risk of removal equals the risk of leaving the
trimester IUD so if:
• Sac is above the IUD with long strings,
remove
• Sac is below IUD, leave the IUD in place
After 1st trimester IUD is usually left high and is delivered
during labor
➋ Ectopic pregnancy: IUD is more effective in preventing

intrauterine rather than extrauterine pregnancy.
Therefore, if pregnancy occurs, it is more likely to be
extrauterine. IUD itself does not increase the risk of
ectopic pregnancy.
➌ Pelvic infections: (PID and actinomycosis)
–– Incidence:
There is a sixfold increase in the risk of PID in the
20 days following insertion.
Beyond the first 3 weeks, the risk remains very
low.
–– Etiology:
The woman has an undetected infection.
The operator fails to use proper aseptic technique.
–– Management: treatment of PID is initiated per pro-
tocol. IUD does not need to be removed unless
patient is not responsive to treatment.
➍ Extrusion (expulsion): (IUD and IUS)
–– Incidence: cumulative expulsion rate is approxi-
mately 5%, most commonly in the first 3 months.
–– Management (see the table below):
Partial expulsion Complete expulsion
Diagnosis The woman or Misings strings with no IUD by
the doctor feels ultrasound/abdominal X-ray
the bottom of the
IUD
Treatment IUD should be Pregnancy should be ruled out
removed Patient should be counseled.
Another IUD can be inserted,
or another contraceptive option
may be used
➎ Perforation/transmigration: (IUD and IUS)

Perforation occurs during IUD placement.
Transmigration is due to unrecognized partial perfora-
tion. As stated before, copper IUDs should be removed.
➏ Displacement of IUD within the uterine cavity: (IUD
and IUS)
–– Types:
IUD rotation: this may cause pain and bleeding.
Downward displacement may cause cervical
perforation.
–– Management: IUD should be removed; hysteroscopy
may be indicated.
• Administration:
–– Clinical evaluation:
History: this should include details of age, past con-
traception, menstrual history, obstetric, and gyneco-
logical history.
Examination:
• Pelvic examination: to determine the size, shape,
and position of the uterus.
• Speculum examination: the vagina and cervix are
inspected for signs of infection.
–– Counseling: women should know the following data
about IUDs, e.g., mechanism of action, side effects, and
potential complications.
–– Procedure:
I. Insertion
• Timing of insertion: this follows the following table.

Insertion during menses has conventionally been
recommended:
–– Advantages:
Pregnancy is unlikely.
The internal os is slightly open (possibly making
insertion easier).
Post-insertion bleeding is disguised by menses.
–– Disadvantages:
Expulsion rates are slightly higher as uterine con-
tractility is increased.
Some women prefer not to be examined during
menstruation.
• Procedure:
➀ Perform bimanual examination while the woman lies in
a modified lithotomy position.
➁ Grasp the cervix with a tenaculum; apply gentle traction
to straighten the uterocervical canal.
➂ Pass a uterine sound gently to determine the depth and
direction of the uterus.
➃ Load the device into the introducer, and carefully insert
the introducer tube through the cervical canal and
release the IUD.
➄ Trim the IUD strings with long scissors to about 3 cm
from the external os.
➅ Before the woman leaves the clinic, she should be given:
–– A written record of the date and type of IUD
inserted
–– Clear information regarding symptoms which should
make her return for review
II. Follow-up
A follow-up visit after the first menses or 3–6 weeks after

IUD insertion is recommended to exclude perforation, expul-
sion, and infection. There is no need for further routine
reviews.
III. Removal
• Indications of removal:
–– When pregnancy is desired
–– If pregnant and the strings are seen
–– If complications which cannot be controlled occur
–– If the patient reaches the menopause
–– If expired
• Timing of removal:
At any time during menstrual cycle. If the patient does
not wish to become pregnant in the cycle, she should avoid
intercourse for 7 days prior to its removal. Alternatively, it
is removed during menses, and another contraception
method is started immediately.
• Technique:
The cervix is exposed with a speculum to visualize the
strings; grasp them near the external os by a pair of a
straight artery forceps, and then traction is applied.
Category Recommendations
Women with Anytime in the cycle, if certain she is not
regular periods pregnant. Luteal phase should be avoided to
avoid disruption of an early pregnancy
Women who are Anytime at her convenience, if certain she is
amenorrheic not pregnant. A period of 14 days should be
given after last unprotected intercourse to
avoid disruption of a possible early pregnancy
Postpartum Early IUD insertion may be considered after
(including post thorough counseling. Placement within 10
CS) minutes of delivery of the placenta is considered
category 1 by U.S. Medical Eligibility Criteria
for Contraception Use. Otherwise, it may be
placed after 4 weeks postpartum
Post-abortive At the time of surgical termination or as soon
as possible
Switching from Anytime, if reasonably certain she is not
another method pregnant
Missing IUD Strings

• Definition: This means that the IUD strings can be felt by
the client.
• Etiology:
–– Undiagnosed perforation at the time of insertion.
–– Pregnancy on IUD.
–– IUD expulsion.
–– IUD displacement.
–– Strings displaced into a large uterine cavity.
–– Strings are cut short or stuck to cervical canal.
• Management:
Postpartum Contraception
I. Natural methods of postpartum contraception
(Lactational amenorrhea method – LAM)
See under: Natural contraception
II. Medical methods of postpartum contraception
• Combined hormonal contraception:

–– For breastfeeding women: COCs can be used safely
after 6 months postpartum.
–– For non-breastfeeding women: COCs can be used
safely after 3 weeks postpartum.
• Progestogen-only methods:
–– For breastfeeding women: it can be used safely after 3
weeks postpartum. It is considered category 2 if given
earlier.
–– For non-breastfeeding women: it can be started imme-
diately postpartum.
• Intrauterine methods
–– An intrauterine device (IUD): it can be placed within
10 minutes of delivery of the placenta or >4 weeks post-
partum (category 1). Between these points of time, IUD
placement is considered category 2.
–– The levonorgestrel-releasing intrauterine system: it can
also be inserted from 4 weeks postpartum regardless of
Emergency Contraception 197
whether or not a woman is breastfeeding. Use of IUS

in the first 4 weeks postpartum (including immediate
postpartum placement) is under category 2 of U.S.
Medical Eligibility Criteria for Contraceptive Use.
• Barrier methods:
–– They can be generally used safely. The use of dia-
phragms and caps should be postponed until involution
of the uterus is complete at about 6 weeks postpartum.
• Sterilization
Female sterilization can be done within the first 3 days
postpartum by minilaparotomy or at the time of Cesarean
section.
III. Emergency contraception
• Women less than 3 weeks postpartum: no indication for

emergency contraception.
• Women at 3–4 weeks postpartum: progestogen-only emer-
gency contraception.
• If the woman is over 4 weeks postpartum: an IUD may be
considered.
However, if LAM criteria are fulfilled, (see under: natu-
ral contraception), no emergency contraception is needed
during the first 6 months postpartum.
Emergency Contraception
• Definition: the use of certain methods after unprotected
intercourse to avoid pregnancy.
• Indications:
I. When there has been no contraceptive use

• Sex where no contraception is used
• Relying only on withdrawal method
• Following sexual assault
II. Incorrect use of a contraceptive method
Missed COCs Two or more pills missed in the first week PLUS
unprotected intercourse in week 1 or in the pill-
free week
Missed POPs One or more pill is missed or taken >3 hours late
(>12 hours for newer pills) PLUS unprotected
intercourse in the next two days
Late If contraceptive injection is overdue (>14 weeks
progestogen- since the last injection of DMPA or >12 weeks
only for norethisterone enanthate) PLUS unprotected
injectable intercourse during this delay
Intrauterine Complete or partial expulsion or midcycle removal
contraception PLUS unprotected intercourse in the last 7 days
Barrier Following an accident; a broken or displaced
methods condom
• Types of emergency contraception:

–– POPs (levonorgestrel):
Dose: 1.5 mg of levonorgestrel as a single dose (two
tablets, each containing 0.75 mg, taken 12 hours
apart, are an alternative regimen).
Time: within 72 hours of unprotected sex.
Mode of action: it inhibits ovulation (by delaying fol-
licular development) rather than interfering with
implantation.
Advantages:
• If a woman is already pregnant, it will not induce
an abortion.
• It is not associated with an increased risk of fetal
abnormalities.
Emergency Contraception 199
• 1.5 mg regimen does not require a prescription

and is available without age restrictions (0.75 mg
regimen is available over the counter for girls who
are 17 or older).
Effectiveness: 89% with perfect use, 85% with typical
use (95% effective if given within the first 24 hours)
–– Ulipristal acetate:
Dose: 30 mg, single dose.
Time: up to 5 days after unprotected intercourse.
Mode of action: selective progesterone receptor
modulator (antiprogestin) that inhibits ovulation by
preventing follicular rupture. Unlike levonorgestrel,
it is still effective even if LH level starts to rise.
Effectiveness: ulipristal is more effective than levo-
norgestrel. Pregnancy rate after using ulipristal is
1.4% (versus 2.2% for levonorgestrel regimen).
However, levonorgestrel regimen (1.5 mg) is more
accessible as it does not require a prescription.
–– A copper intrauterine device (at least 300 mm2 of
copper):
Indications:
• Obese women: levonorgestrel and ulipristal are
less effective among obese women, while IUD
efficacy is not influenced by body weight.
Therefore, IUD may be the best option for obese
women.
• If the patient presents 72 hours after unprotected
intercourse (ulipristal is another option).
• It may be used to cover multiple exposures.
Time: it is inserted up to 5 days after the first unpro-
tected intercourse or the calculated earliest day of
ovulation.
Mode of action: it acts primarily by preventing fertil-

ization due to the toxic effects of copper on sperm
function and viability. It may affect oocyte and alter
endometrium, so it is not favorable for implantation.
Advantages:
• Copper IUD is not an abortifacient and is highly
effective.
• It is not affected by a woman’s BMI.
• It provides long-term contraceptive option if the
user is interested.
• No hormonal side effects, e.g., headache and
nausea.
Effectiveness: highly effective (> 99%)
• Side effects:
–– Levonorgestrel and ulipristal:
Headache
Nausea (14%)
Vomiting is rare (1%). If a woman vomits within 2
hours, another dose should be given.
Unscheduled bleeding:
• Most women will have a normal menstruation
within 7 days of expected date.
• Irregular bleeding and spotting are common
within 1 week of emergency contraception.
–– Copper intrauterine device:
Risk of uterine perforation (1:1000).
Other side effects are similar to those described in
long-term use, e.g., cramping.
• Counseling and administration:
–– Women should be counseled that emergency contracep-
tion is not an elective abortion, and it prevents rather
than terminates possible pregnancy.
tion can still be administered even in the presence of a
Natural Contraception 201
contraindication to conventional hormonal

contraception.
tion may be used more than once within the same cycle.
However, emergency contraception should not be used
as a long-term contraceptive strategy as it is less effec-
tive than non-emergency contraceptive regimens.
–– Effectiveness of emergency contraception is directly
related to administration time (the earlier, the better).
–– Prior to initiation of emergency contraception, no
physical examination or pregnancy test is required.
–– Long-term contraceptive options should be discussed if
she is interested.
–– According to circumstances, offering sexually transmit-
ted infection screening and well-woman care may be
necessary (sexual assault).
–– If ulipristal is used, hormonal contraceptives should be
initiated no earlier than 5 days after ulipristal is
administrated.
• Follow-up:
–– No follow-up visit is required.
–– Women should be aware of warning signs that they
should report to their providers:
➊ If menses is delayed for 1 week or more beyond
expected day
➋ Lower abdominal pain
➌ Persistent irregular vaginal bleeding
–– In these circumstances, pregnancy should be ruled out
including intrauterine and extrauterine pregnancy
Natural Contraception
Lactational amenorrhea method (LAM)
• Definition:
It is the use of breastfeeding as a temporary natural
method to prevent pregnancy among postpartum women.
• Requirements:
To consider lactation as a contraceptive method, the
following criteria should be fulfilled:
–– Within 6 months postpartum
–– Amenorrhea
–– Exclusive breastfeeding on demand
• Mode of action:
Stimulation of nipples by the act of suckling initiates
nerve impulses transmitted to maternal hypothalamus.
Thereby, prolactin is released. Prolactin disrupts GnRH
release resulting in decreased production of FSH and
LH. This results in arrest of follicular growth and inhibi-
tion of ovulation.
• Advantages:
–– It is universally available to all breastfeeding women.
–– Highly effective (failure rate is 1–2%).
–– Immediate protection after birth.
–– No cost.
–– It promotes breastfeeding, thus providing other benefits
to the mother and the baby.
–– It can be used while a breastfeeding woman decides on
her best contraceptive choice.
• Disadvantages:
–– Exclusive breastfeeding may be challenging.
–– It provides contraception for limited duration.
–– It is only available to breastfeeders.
–– It does not provide protection against STDs and HIV.
Fertility awareness methods (Periodic abstinence)
• Definition:
Natural Contraception 203
A group of methods that promote voluntary avoidance

of intercourse by a couple during the fertile phase of the
menstrual cycle to prevent pregnancy
• Methods of fertility awareness contraception:
1st day of Last day of
Method fertility fertility
Calendar or Cycle length Shortest Longest cycle
rhythm method is recorded cycle minus minus 10
for a 20
minimum of
six cycles
Temperature Daily – After three
method recording of consecutive
temperature temperatures
immediately >0.2°C
after sleep. above the
Temperature six preceding
is plotted on recordings (3
a specially over 6 rule)
designed
chart
Cervical mucus Observation At the first The 4th day
method of dryness, sign of after peak
wetness, mucus (wet mucus (defined
and physical days) as the last day
features of when mucus
mucus seen at is noted to
the introitus be clear and
slippery)
Cervical Observation The first day The end is the
palpation of cervical of cervical fourth day after
method changes softening reversal of these
through the and upward changes
cycle shift of the
cervix
1st day of Last day of

Method fertility fertility
The double- It combines The 1st day The 4th day
check method calendar, of fertile after the peak,
(most efficient) cervical mucus or mucus or the
mucus, and the shortest morning of the
temperature cycle third day after
methods minus 20 the BBT shift
(whatever (the latter of
comes either of them)
earlier)
Multiple index It includes the use of temperature method and
(symptothermal cervical mucus method, in association with
method) observation of other symptoms and signs, e.g.,
breast changes and mood swings
• Advantages of fertility awareness contraception:

–– Natural and safe method
–– User dependent after appropriate teaching
–– It involves both partners in family planning
responsibility
• Disadvantages of fertility awareness contraception:
–– It may require long periods of sexual abstinence.
–– It requires daily monitoring of fertility signs.
–– It may require long learning period (3–6 months).
–– It does not provide protection against STIs.
–– This method is inappropriate in women who experience
irregular cycles, e.g., during breastfeeding.
Coitus interruptus
• Definition:
This method refers to withdrawal of the penis outside
the vagina before ejaculation, to prevent the contact
Female Sterilization 205
between sperms and an oocyte, thus preventing

pregnancy.
• Disadvantages of withdrawal:
–– Correct and consistent use is more difficult compared to
other contraceptive options.
–– Failure rate is 4% with perfect use and 19% with typical
use.
–– It does not protect against STIs/HIV.
Female Sterilization
• Indications:
–– Patient desire is the main indication, but she may take
into account isssues of medical contrindications to preg-
nancy and failure of other contraceptive methods.
Federal funding for sterilization is limited for women
under age 21 and for women without decision-making
capability- restrictions should be reviewed carefully.
• Approaches to female sterilization:
I. Postpartum sterilization
Approximately 9% of vaginal deliveries are followed by

postpartum sterilization. Ideally, counseling and consent-
ing should take place during prenatal visits:
• Minilaparotomy:
This is the standard approach for early postpar-
tum sterilization. Abdominal entry is performed
through an infraumbilical incision (<5 cm, ideally
2–3 cm) under general or regional anesthesia.
• Laparotomy: abdominal entry is performed through
an incision greater than 5 cm. This is rarely used.
Postpartum sterilization is performed either by partial

salpingectomy (via minilaparotomy or at the time of
Cesarean delivery) or complete salpingectomy (at the time
of Cesarean delivery).
Techniques of partial salpingectomy

Pomeroy A loop from the mid portion of the tube is ligated
technique with absorbable suture material at its base. The
loop above the ligature is then excised
Parkland The tube is tied in two places, and a 2 cm segment
technique of tube is excised between the ligatures
Kroener The fimbriated end of the tube is excised
technique
II. Post-abortion sterilization
Safety and outcomes are comparable to interval steriliza-

tion. Laparoscopy or minilaparotomy may be performed
immediately after the first and second trimester uncompli-
cated spontaneous or induced abortion. Abortion and steril-
ization can be performed under the same anesthetic
coverage.
III. Interval sterilization
• Laparoscopic approach:
This is the standard approach of interval sterilization.
Several procedures can be performed through this
approach:
• Minilaparotomy:
This approach is rarely used to perform interval steril-
ization. It may be used if laparoscopic procedure cannot be
safely performed.
• Hysteroscopy:
There is currently no hysteroscopic option to perform
tubal sterilization. Manufacture of Essure has been discon-
Female Sterilization 207
tinued since the beginning of 2019 and Adiana in April

2012.
Method Description
Mechanical devices
Clips Spring-loaded clips or titanium clips are placed at
right angles to the tube, approximately 1–2 cm from
the uterine cornu using a special applicator
Silicone A band is placed over a loop of tube using a special
rubber ring applicator. Therefore, tubes should be sufficiently
mobile to allow safe and efficient placement of the
applicator
Electrocautery
• Electrocoagulation is usually a second option if other
methods are not feasible
• The procedure should include complete coagulation of 3 cm
of ischemic part of fallopian tubes bilaterally
Tubal excision (salpingectomy)
Salpingectomy has increasingly become favorable given the
opportunity to reduce lifetime ovarian cancer risk. In addition,
current evidence shows no difference in length of hospital stay,
postoperative complications, blood transfusion, or readmission with
or without salpingectomy. It can be done laparoscopically or at the
time of Cesarean delivery
• Effectiveness and failure: 5-year failure rate is 13:1,000.

Postpartum sterilization is superior to interval tubal occlu-
sion. Titanium clips are less efficient compared to partial
salpingectomy if used for postpartum sterilization.
• Advantages:
I. Contraceptive advantages:
➊ Highly effective and permanent method
➋ No systemic side effects
II. Non-contraceptive advantages:
➊ Tubal occlusion may protect against pelvic inflamma-

tory disease, probably by preventing spread of
organisms.
➋ Salpingectomy reduces lifelong risk of ovarian can-
cer. In addition, tubal occlusion is associated with
reduction in ovarian cancer risk.
• Disadvantages of female sterilization:
➊ No protection against sexually transmitted diseases
➋ Risk of surgical complications (0.1–3.5%):
• Injury to the bowel, bladder, or blood vessels
• Wound infection
• Hematoma
➌ Risk of regret (13% after 14 years of follow-up) is influ-
enced by:
• Age (20% in women younger than 30 years com-
pared to 6% in women above this age).
• Interval between delivery and sterilization: the
longer the duration, the lesser the regret. This
does not apply to post-abortion sterilization.
• The risk also increases if the patient did not
receive enough information on the procedure and
its alternatives.
➍ Ectopic pregnancy:
• Tubal sterilization does not increase risk of ecto-
pic pregnancy. However, pregnancy following ster-
ilization is likely ectopic.
• Cumulative incidence in 10 years is 7.3:1.000.
• The risk is related to patient age at time of the
procedure (greater if <30 years old).
• The risk does not decrease over time.
➎ Hysterectomy:
Although women who undergo tubal occlusion are
4–5 times likely to have hysterectomy, this seems to be
an association rather than a causal relation.
• Sterilization reversal:
Male Sterilization 209
–– Successful pregnancy following sterilization reversal

occurs in 50–80% of women. Factors that impact this
percentage include:
Patient age.
Type of sterilization (ring/clip sterilization is associ-
ated with higher likelihood of success compared to
other techniques).
Remaining length of the tubes after reversal.
Presence of other causes of infertility; these factors
should be ruled out before a decision is made.
–– 3–8% of pregnancies may be ectopic.
Male Sterilization
• Techniques:
–– The vas is palpated in the upper scrotum and fixed; a
small midline or two lateral incisions are made, and the
vas is ligated and divided.
–– Non-scalpel technique is an alternative technique that
is associated with lower risk of surgical complications
compared to conventional technique.
• Follow-up:
The couple should use another contraceptive method in
the first 3 months after the procedure. Thereafter, semen
analysis should be performed to confirm azoospermia.
• Effectiveness: 0.15/HWY
• Advantages: It is safer, more effective, and less expensive
compared to female sterilization.
• Disadvantages:
–– Partner regret
–– Risk of complications:
Early complications: bruising and hematoma, wound
infection
Late complications: sperm granulomas, post-vasec-

tomy syndrome (chronic interscrotal pain and dis-
comfort), late recanalization, and failure
Further Reading
ACOG practice bulletin. No. 73: Use of hormonal contraception
in women with coexisting medical conditions. Obstet Gynecol.
2006;107:1453.
Buhling KJ, Zite NB, Lotke P, et al. Worldwide use of intrauterine
contraception: a review. Contraception. 2014;89:162.
Dragoman MV, Tepper NK, Fu R, et al. A systematic review and
meta-analysis of venous thrombosis risk among users of com-
bined oral contraception. Int J Gynaecol Obstet. 2018;141:287.
Eisenberg DL, Schreiber CA, Turok DK, et al. Three-year efficacy
and safety of a new 52-mg levonorgestrel-releasing intrauterine
system. Contraception. 2015;92:10.
Finer LB, Jerman J, Kavanaugh ML. Changes in use of long-acting
contraceptive methods in the United States, 2007–2009. Fertil
Steril. 2012;98:893.
Jensen JT, Schlaff W, Gordon K. Use of combined hormonal contra-
ceptives for the treatment of endometriosis-related pain: a sys-
tematic review of the evidence. Fertil Steril. 2018;110:137.
Lethaby A, Wise MR, Weterings MA, et al. Combined hormonal
contraceptives for heavy menstrual bleeding. Cochrane Database
Syst Rev. 2019;2:CD000154.
Mascarenhas L. Insertion and removal of Implanon: practical con-
siderations. Eur J Contracept Reprod Health Care. 2000;5 Suppl
2:29.
Practice Bulletin No. 152: Emergency contraception. Obstet Gynecol
2015; 126:e1. Reaffirmed 2018.
Tepper NK, Whiteman MK, Zapata LB, et al. Safety of hormonal
contraceptives among women with migraine: a systematic review.
Contraception. 2016;94:630.
Wong CL, Farquhar C, Roberts H, Proctor M. Oral contraceptive
pill for primary dysmenorrhoea. Cochrane Database Syst Rev
2009:CD002120.
World Health Organization. WHO Medical Eligibility Criteria for
starting contraceptive methods; 2017.
Chapter 5
Uterine Leiomyomas
Definition:
Uterine leiomyomas (fibroids) are benign neoplasms arising
from the smooth muscle fibers of the uterus.
Incidence:
• Uterine leiomyomas are the most common female

neoplasm.
• Uterine leiomyomas are clinically diagnosed in 25% of
women of reproductive age. However, it may be as preva-
lent as 70% among women during their reproductive years
although many women are asymptomatic.
• Among women with uterine leiomyomas, 25% experience
severe symptoms that require treatment.
Etiology:
• Risk factors:
❶ Age: the risk increases with age during reproductive
years. Leiomyomas arise in the late 20s for African
American women and late 30s for Caucasian women.
❷ Premenstrual state
❸ Parity: nulliparity/low parity is a risk factor.
❹ Time since last birth: the longer the duration, the higher
the risk.
❺ Family history: of uterine leiomyomas.

https://doi.org/10.1007/978-3-030-41128-2_5
212 Chapter 5. Uterine Leiomyomas
❻ Race: more common in black women.

❼ Hypertension: association between hypertension and
uterine fibroids has been reported.
❽ Nutritional factors: while there are many small studies
associating diet with leiomyoma, the most consistent
risk factor for leiomyoma is vitamin D deficiency.
• Protective factors:
❶ Injectable contraceptive use
❷ Parity
❸ Vitamin D
Classification:
• Traditional classification of leiomyomas:

–– Intramural fibroids: the most common, grow in the wall
of the uterus
–– Subserosal fibroids: grow on the outside of the uterus,
covered by serosa
–– Submucosal fibroids: grow into the cavity, covered by
endometrium
Subserous fibroid
Interstitial
fibroid
Submucous
fibroid
Chapter 5. Uterine Leiomyomas 213
• New classification of leiomyomas (FIGO classification):

–– Class 0: pedunculated intracavitary leiomyoma.
–– Class 1: leiomyoma is less than 50% intramural.
–– Class 2: leiomyoma is 50% or more intramural.
–– Class 3: leiomyoma is 100% intramural, contact the
endometrium.
–– Class 4: leiomyoma is 100% intramural, no endometrial
contact.
–– Class 5: leiomyoma is subserosal, 50% or more
intramural.
–– Class 6: leiomyoma is subserosal, less than 50%
intramural.
–– Class 7: leiomyoma is subserosal, pedunculated.
–– Class 8: other types (e.g., cervical, parasitic).
Pathology:
• Site of pathology:
–– From the body of uterus: about 95% of cases (see under:
Classification)
–– From the cervix: about 4% of cases
–– Rare sites (1% of cases): e.g., the round ligament and
broad ligament
• Macroscopic features:
–– Size: it varies from small to large-sized tumors.
–– Shape: spherical in shape.
–– Consistency:
Firm: the usual consistency
Soft: during pregnancy, with hyaline or cystic degen-
eration, or with malignancy
Hard: if calcified
–– Color: whitish (diminished blood supply)
–– Cut surface:
Bulging, whorled appearance: due to interlacing of
muscle and connective tissue fibers. Absence of
whorled appearance is seen with:
• Red degeneration
• Hyaline and cystic degeneration

• Malignancy
• Calcification
A false capsule is formed of compressed uterine
muscles around interstitial fibroids. The capsule con-
tains feeding blood vessels, so it appears darker than
the fibroid
–– Number: corporeal fibroids are usually multiple; cervi-
cal fibroids are typically single.
• Microscopic features:
The tumor is composed of smooth muscle fibers in a
connective tissue stroma. The mitotic figures are less than
5–10 per high-power field (HPF).
• Secondary changes in fibroids:
❶ Atrophy:
• Atrophy and shrinkage of uterine fibroids occur after
menopause, postpartum, and after hormonal therapy
(GnRH agonist).
• Failure of shrinkage/growth of uterine fibroids after
menopause may occur in women on hormonal ther-
apy or in case of malignancy (leiomyosarcoma).
❷ Necrosis:
Necrosis may occur due to complete interruption of
blood supply to the fibroid, e.g., after torsion of a subse-
rous fibroid.
❸ Degeneration:
➀ Hyaline degeneration (the most common):
• It starts at the center of a large fibroid (the least
vascular area).
• The affected area is replaced by hyaline material
and appears structureless, homogenous with loss
of the whorled appearance.
• Patient may be symptomatic (dull aching pain),

and the fibroid becomes softer in consistency.
➁ Cystic degeneration:
• It may occur as a sequence of liquefaction of hya-
line material and formation of cystic spaces.
• The fibroid may have “honeycomb appearance”
by ultrasound. This appearance may be similar to
sonographic features of molar pregnancy
(pregnancy test is negative).
➂ Fatty degeneration (lipoleiomyoma):
• This may occur around or after the menopause,
due to fatty infiltration or metamorphosis.
• Fatty degeneration may be followed by
calcification.
➃ Calcification (calcareous degeneration):
• It most commonly occurs after menopause.
• Clinically, the tumor may become hard in
consistency.
➄ Red degeneration (necrobiosis):
• Definition: it is a status of incomplete necrosis
from which fibroid tissues can recover.
• Etiology:
Red degeneration most commonly occurs during
pregnancy or postpartum. It is thought to be due
to:
–– Alternation of coagulation factors favoring
thrombosis
–– Fibroid enlargement that may cause kinking of
feeding vessels
–– Increased vascularity and vascular dilation that
may cause stasis of blood
Thrombosis leads to ischemia and incomplete necrosis
of the tumor.
• Pathology:
The fibroid becomes soft and salmon pink colored
(hemoglobin stain).
–– Symptoms:
Acute abdomen: pain is localized over the
affected fibroid.
Nausea and vomiting
Mild fever
Sometimes, the condition is subacute, and
the symptoms are mild.
–– Physical signs: abdominal tenderness, localized
over the fibroid
–– Differential diagnosis: other causes of acute
abdomen during pregnancy, e.g., torsion of
ovarian tumor, placental abruption, etc.
• Treatment:
Management of red degeneration during preg-
nancy should be CONSERVATIVE; myomec-
tomy should be always avoided in pregnancy
(high-risk surgery due to increased size and
vascularity).
Diagnosis:
• Symptoms:
I. Asymptomatic
Approximately 30% of patients are asymptomatic, and

fibroids are incidentally found during pelvic-abdominal
imaging.
II. Gynecologic symptoms
❶ Abnormal uterine bleeding (the most common symp-

tom, class 0 and 1 fibroids):
Type Underlying causes
Heavy menstrual Submucous fibroids may cause heavy
bleeding (most common menstrual bleeding due to:
symptom) • Fibroids that may impair uterine
contractility which is necessary to
stop menstrual bleeding
• Increased vascularity of the uterus
• Increased endometrial surface area
due to uterine enlargement
Symptoms of anemia may develop
secondary to blood loss
Intermenstrual bleeding Submucous fibroids may cause
intermenstrual bleeding due to:
• Ulceration of mucosal layer covering
submucous fibroid or fibroid polyp
• Associated endometrial polyps,
hyperplasia, or carcinoma
• Leiomyosarcoma
❷ Pressure symptoms:
Pelvic pressure symptoms (more common with lower
uterine or cervical fibroids) may include:
• Pelvic pressure
• Back pain
• Urinary frequency and urgency
• Incomplete emptying of the bladder/urinary
retention
• Constipation
❸ Pain:
• Colicky pain: fibroids may be associated with sec-
ondary dysmenorrhea.
• Dull aching pain: may be caused by pressure effect of
the mass.
• Dyspareunia: fibroids may be associated with deep
dyspareunia.
• Acute abdominal pain: acute pain may be associated
with fibroid-related complications, e.g., torsion of a
pedunculated subserous fibroid.
❹ Abdominal distension/mass:
This complaint may be reported in women with large
subserous fibroids.
III. Obstetric symptoms/complications
During Early pregnancy:

pregnancy • About 11% of women in early pregnancy
have fibroids
• Prior studies indicated that leiomyoma
could cases miscarriage, but a recent study
has found no association with miscarriage
• Bleeding: it is more common when the
placenta is implanted above or close to the
fibroids
Late pregnancy:
• Preterm labor: but not preterm rupture of
membranes
• Placental abruption: the risk is increased
over baseline by threefold. Risk factors
include submucosal fibroids, retroplacental
fibroids, and larger fibroids. This is possibly
due to diminished blood flow to the fibroid
and surrounding tissues, which may result in
decidual necrosis
• Placenta previa: the risk may increase by
twofold in the presence of fibroids
During labor • Malpresentation

• Prolonged labor (labor dystocia)
• Increased risk of Cesarean delivery
(due to the above causes)
• Postpartum hemorrhage
• Retained placenta
IV. Infertility
Approximately 5%–10% of women with infertility have

fibroids.
Cervical factor Mechanical obstruction by a cervical fibroid

Uterine factor • A submucous fibroid may interfere with
implantation of the fertilized ovum (area
of diminished blood supply)
• Uterine enlargement increases sperm
traveling distance
Tubal factor Uterine fibroids may cause tubal blockade
Vaginal factor Frequent bleeding and dyspareunia
–– General examination: patient may look pale or ane-
mic. Dizziness with ambulation may be noted.
–– Abdominal examination:
Uterus/uterine fibroids may be felt abdominally if
large enough (> 12 weeks). The lower pole of the
mass cannot be reached abdominally.
Inspection: abdominal mass may be noted in thin
women with large subserous fibroid.
Palpation:
• Surface: the surface of the mass is irregular
(fibroids are usually multiple).
• Consistency: firm.
• Mobility: the mass is usually mobile from

side to side but not up and down.
• Tenderness: non-tender if uncomplicated.
Percussion: dull on percussion.
• If the uterus is pelvic-abdominal (>12
weeks): the palpable abdominal mass is con-
tinuous with the uterus; it moves in corre-
spondence to pushing on the cervix.
• If the uterus is pelvic (<12 weeks):
–– Interstitial and subserous fibroids: the
uterus feels asymmetrically enlarged,
firm, and non-tender with irregular con-
tour (multiple fibroids).
–– Subserous pedunculated fibroids: felt as a
separate firm mass that may be mistaken
with an adnexal mass.
–– A broad ligament fibroid: felt at one side
of the uterus that displaces it to the oppo-
site side.
–– A cervical fibroid: felt as fixed firm cervi-
cal mass; the uterus is felt on its top.
• Speculum examination: cervical fibroid polyp
can be visualized during speculum
examination.
• Uterine sound: in the presence of bulging
fibroid polyp, a uterine sound can help to
differentiate uterine fibroid polyp (uterine
sound can be completely rotated within the
cervical canal) from cervical fibroid polyp
(uterine sound cannot be completely rotated
with the cervical canal due to polyp attach-
ment). However, office hysteroscopy can be
used instead.
• Work-up:
–– Laboratory tests:
Pregnancy test: exclusion of pregnancy is indi-
cated in all women with abnormal uterine
bleeding.
Complete blood count: assessment of potential
anemia secondary to blood loss.
–– Imaging tests:
❶ Level I imaging studies
➀ Pelvic ultrasound:
Pelvic ultrasound is the study of choice. Other
imaging tests are only performed if indicated.
• Findings:
–– Well-circumscribed round masses, typi-
cally hypoechoic.
–– Calcification is indicative of
degeneration.
–– If the uterus is less than 10 weeks in size,
diagnostic sensitivity of pelvic ultrasound
is as high as 95–100%.
• Diagnostic challenges:
–– Localization of fibroids is difficult in the
presence of a large uterus or multiple
fibroids.
–– Differentiation between fibroids and ade-
nomyomas or sarcomas is difficult.
➁ Renal ultrasound:
Renal ultrasound may be indicated if urinary
tract obstruction is concerning (rule out
hydronephrosis).
❷ Level II imaging studies (assessment of the uter-
ine cavity):
➀ Saline infusion sonography:

• Saline infusion sonography can be per-
formed as a part of infertility work-up.
• Saline infusion sonography may help to
assess eligibility for hysteroscopic resection
particularly if office hysteroscopy is not
available.
➁ Office hysteroscopy:
• It is the best modality to plan for hystero-
scopic resection.
• It also helps to rule out other intracavitary
causes of abnormal uterine bleeding, e.g.,
uterine polyps.
❸ Level III imaging studies (magnetic resonance
imaging):
Although MRI is the best imaging tool to deter-
mine the size and site of uterine fibroids, this
method is expensive, and it may be limited to the
following indications:
➀ Surgical planning for challenging cases, e.g.,
class 3–6
➁ Differentiating leiomyomas from leiomyosar-
comas if cancer is suspected (however, MRI is
not conclusive, and diagnosis is only made by
histopathology)
➂ Planning for uterine artery embolization to
predict success of treatment
Complications of leiomyomas:
• Anemia: may develop secondary to blood loss
• Compression effect: large fibroids may cause hydrone-
phrosis (due to ureteric compression), lower extremity
DVT (venous compression), and urinary retention (blad-
der compression).
• Torsion: of a pedunculated subserous fibroid.
• Infertility (see under: Symptoms).

• Obstetrics complications (see under: Symptoms).
• Uterine Inversion: may be caused by a large fundal sub-
mucous fibroid or fibroid polyp (rare).
• Ascites/pseudo-Meigs syndrome: large pedunculated sub-
serous fibroids may produce ascites due to mechanical
irritation of the peritoneum.
• Rupture of a vein on the surface of a subserous fibroid:
which results in life-threatening intraperitoneal hemor-
rhage (extremely rare).
Treatment:
• Goal of treatment: relief of symptoms
• Determinants of treatment:
–– Patient age
–– Desire for future fertility
–– Type and severity of symptoms
–– Size and locations of leiomyomas
• Lines of treatment:
I. No treatment
Asymptomatic fibroids are common, and they require no

intervention unless they become symptomatic. Leiomyomas
after menopause do not require treatment unless they are
growing. Women near menopause have high success with
expectant management with or without iron use.
II. Medical treatment
• Treatment depends on symptoms: bleeding-predominant

vs. bleeding and bulk symptoms
• Indications of medical treatment:
–– As a sole treatment:
Perimenopausal women (to control symptoms tem-
porarily till reaching menopause).
Women with bulk symptoms who cannot undergo
surgery or who refuse surgery.
For heavy menstrual bleeding due to leiomyomas, if
medical therapy can control symptoms.
–– As a temporary preoperative treatment:
For immediate correction of severe anemia prior to
surgery
If surgery has to be postponed for any medical
reasons
If reduction of fibroid size would facilitate surgery
(reduction of fibroid size and blood loss)
• Lines of medical treatment for bleeding:
❶ Non-hormonal treatment:
Non-hormonal options including NSAIDs and
tranexamic acid can be offered to improve bleeding
symptoms.
❷ Combined contraceptive pills:
They can improve symptoms through their atrophy-
inducing action on the endometrium.
❸ Progestin-only methods:
• Levonorgestrel-releasing intrauterine system:
although it may significantly reduce bleeding, it
should not be placed in the presence of class 0 and I
fibroids (distorted cavity).
• Progestin implants, injections, and oral pills: other
forms of progestins that can be used to improve
symptoms.
❹ GnRH agonist:
• GnRH agonist (e.g., subcutaneous goserelin 3.6 mg
monthly).
• It is a temporary treatment (typically 3–6 months)
that reduces or stops bleeding and reduces size and
vascularity of the fibroids if needed.
❺ GnRH antagonists:
• The drug is not commonly used in treatment of
fibroid symptoms.
• Compared to GnRH agonist, absence of an initial
flare-up effect may result in more rapid decrease in
fibroid volume.
Ulipristal acetate is increasingly studied as a potential
treatment of uterine fibroids. However, it is not currently
available in the United States for this indication.
III. Surgical treatment
• Indications:
–– Abnormal uterine bleeding or bulk-related symptoms
–– Infertility or recurrent pregnancy loss (after exclusion
of other causes)
• Lines of surgical treatment:
–– Myomectomy:
Candidates:
Myomectomy is offered as a treatment option when
uterine preservation is desired.
Technique:
Conventional route Endoscopic route

Laparoscopic/
Abdominal Vaginal Hysteroscopic robotic
myomectomy myomectomy myomectomy myomectomy
The This Best candidates It may be
traditional approach are women appropriate in
route of may be used with class 0 to women with
myomectomy in women 1 leiomyomas intramural
for large with cervical (less than 50% or serosal
multiple fibroid, intramural) leiomyomas
fibroid polyps or less than 5 cm ≤15 cm or
(type 2 and pedunculated in size. Type 2 ≤3 fibroids
higher) when submucous leiomyomas each <5 cm
laparoscopic polyp (class can also be in diameter
surgery is not 0) that addressed this (depends
feasible protrude way. on surgical
through the Preoperative expertise)
cervix medical
treatment may
be considered
prior to surgery
if a leiomyoma
is larger in size
Before consenting for abdominal and laparoscopic myo-

mectomy, women should be counseled about the risk of uter-
ine rupture in subsequent pregnancies.
• Hysterectomy:
–– Indications:
Hysterectomy is indicated only when other treat-
ment options fail.
If the patient desires definitive treatment and future
fertility is not desired.
If there is associated other indications of
hysterectomy.
–– Technique:
Minimally invasive hysterectomy:
Determination of the best route of hystectomy

depends on:
• Uterine size
• Uterine descent within the vagina (best if the
uterus descends at least half the length of the
vagina when pulled out)
• Prior Cesarean deliveries
Vaginal hysterectomy: vaginal hysterectomy is the
safest approach.
• Laparoscopic/robotic hysterectomy
• Laparoscopic-assisted vaginal hysterectomy
Open hysterectomy (laparotomy): it is indicated if
the patient is not candidate for minimally invasive
approach.
–– Counseling for hysterectomy:
The surgeon should discuss surgical risks associated
with hysterectomy and postoperative recovery.
Premature menopause: oophorectomy is not indi-
cated in hysterectomies for benign indications, and
women should not experience premature meno-
pause. However, there is evidence that they may
become menopausal 1 to 3 years earlier than would
naturally occur. Long-term risks of cardiovascular
disease, anxiety, and depression are associated with
hysterectomy even if ovaries are conserved.
Sexuality: women can typically resume sexual activ-
ity 6 weeks postoperatively (after a postoperative
check visit). Most studies did no show negative
impact of hysterectomy on sexuality.
• Endometrial ablation:
–– Endometrial ablation with hysteroscopic myomectomy
may be an option in women whose primary complaint is
heavy menstrual bleeding, not desiring future fertility.
–– The risk of second surgery is only 8% after 6 years of
follow-up.
• Myolysis/ablation:
–– Approach: through laparoscopic approach, thermal,
radiofrequency, or cryoablation is applied to a leiomy-
oma to shrink it. Intraperitoneal ultrasound may be
used to optimize guidance.
–– Advantages: the approach is minimally invasive, easy,
and safe compared to other surgical options.
–– Disadvantages: adhesion formation, risk of rupture dur-
ing pregnancy.
IV. Interventional Radiology
• Uterine artery/fibroid embolization (UAE/UFE):

–– Principle:
It is a fluoroscopy-guided procedure in which a catheter
passes through the femoral artery to inject embolic
agents to the feeding vessels of the fibroid.
–– Candidates:
This option can be offered to premenopausal symp-
tomatic women who are not actively trying to get
pregnant as an alternative to surgery.
Women with larger uteri (leiomyomas >12 cm) are at
greater risk of failure.
–– Contraindications:
Current or recent pelvic infection.
Uncertain diagnosis.
Pregnancy or desire for fertility.
Hysterectomy is absolutely refused.
–– Advantages:
Compared to surgery, UAE is associated with shorter
hospital stay, quicker recovery, and less post-procedure
pain.
–– Complications:
Puncture site infection
Puncture site hematoma
Uterine infection
Uterine ischemia and necrosis
Thromboembolic complications
Expulsion of fibroid tissue
Chronic vaginal discharge
Ovarian dysfunction (ovarian failure as a complica-
tion of nontarget embolization of the ovaries)
Postembolization syndrome (pelvic pain and cramp-
ing, nausea and vomiting, low-grade fever, and fatigue
and malaise)
Treatment failure
• Magnetic resonance-guided focused ultrasound
(MRgFUS):
–– Principle:
Multiple waves of focused ultrasound energy are
applied under MRI guidance to a small volume of tissue
resulting in thermal destruction (outpatient procedure).
MRI provides excellent visualization of abdominopel-
vic structures and facilitates monitoring of tissue
destruction.
–– Candidates:
This option can be offered to premenopausal symp-
tomatic women as an alternative to surgery.
The maximum size of a fibroid that can be treated by
MRgFUS is not clear. Generally, MRgFUS may not
be used for a fibroid size >10 cm. However, this is not
an absolute contraindication.
–– Relative contraindications:
Five or more fibroids
Nonenhancement with gadolinium
Skin burn
Damage to nearby tissues
Nerve stimulation may cause temporary post-proce-
dure back or leg pain
Deep venous thrombosis
Treatment failure
V. Treatment of fibroid with pregnancy
During No intervention is done during pregnancy.

pregnancy If red degeneration develops, it should be
managed conservatively
During labor •
If the fibroid is obstructing labor:
Cesarean delivery. Myomectomy should
not be done at the time of delivery.
Cesarean incision should not be made
through the fibroid
•
Non-obstructing labor: allow vaginal
delivery. Fibroids can be evaluated
after 3–6 months postpartum if they are
symptomatic (fibroids tend to shrink
significantly after pregnancy)
VI. Treatment of fibroid-related infertility
• Indications for surgery:

–– For treatment of infertility:
Full infertility work-up should be performed before
infertility is attributed to uterine fibroids. Generally,
only cavity distorting myomas are treated.
If other causes of infertility are found, they should be
managed first before myomectomy.
Further Reading 231
–– Prior to in-vitro fertilization:

Myomectomy for submucous fibroids is a reasonable
approach if a patient is planned for in vitro fertiliza-
tion and embryo transfer.
Myomectomy may be indicated if fibroids cause sig-
nificant distortion of pelvic structures that may inter-
fere with oocyte retrieval.
• Patient counseling:
Patients with infertility and uterine fibroids will be moti-
vated to undergo surgery. It is important to discuss expec-
tations with the patient:
–– There is insufficient evidence that subserosal myomec-
tomy improves fertility.
–– There is evidence that hysteroscopic myomectomy
improves clinical pregnancy rate.
–– Myomectomy does not seem to impair reproductive
outcomes of in vitro fertilization.
Further Reading
American College of Obstetricians and Gynecologists. ACOG
Practice Bulletin no. 96. Alternatives to Hysterectomy. Obstet
Gynecol. 2008a;112:201.
American College of Obstetricians and Gynecologists. ACOG prac-
tice bulletin. Alternatives to hysterectomy in the management of
leiomyomas. Obstet Gynecol. 2008b;112(2 Pt 1):387.
Buttram VC Jr, Reiter RC. Uterine leiomyomata: etiology, symp-
tomatology, and management. Fertil Steril. 1981;36:433.
Committee on Practice Bulletins—Gynecology. Practice bulletin no.
128: diagnosis of abnormal uterine bleeding in reproductive-aged
women. Obstet Gynecol. 2012;120:197. Reaffirmed 2016
Fraser IS, Critchley HO, Munro MG, et al. A process designed to lead
to international agreement on terminologies and definitions used
to describe abnormalities of menstrual bleeding. Fertil Steril.
2007;87:466.
Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. Fibroids and
reproductive outcomes: a systematic literature review from con-
ception to delivery. Am J Obstet Gynecol. 2008;198:357.
Marret H, Fritel X, Ouldamer L, et al. Therapeutic management of

uterine fibroid tumors: updated French guidelines. Eur J Obstet
Gynecol Reprod Biol. 2012;165:156.
Munro MG, Critchley HO, Fraser IS. FIGO Menstrual Disorders
Working Group. The FIGO classification of causes of abnor-
mal uterine bleeding in the reproductive years. Fertil Steril.
2011;95:2204.
Pérez-López FR, Ornat L, Ceausu I, et al. EMAS position statement:
management of uterine fibroids. Maturitas. 2014;79:106.
Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated
systematic review of the evidence. Fertil Steril. 2009;91:1215.
Stewart EA. Uterine fibroids. Lancet. 2001;357:293.
Chapter 6
Chronic Pelvic Pain
Definition:
Chronic pelvic pain refers to pain situated below the umbili-
cus, for at least 6 months, that causes functional disability or
requires treatment.
Causes:
Only 20% of chronic pelvic pain cases are attributed to gyne-
cologic causes. Most common causes are musculoskeletal,
gastrointestinal, and urological causes.
❶ Gynecologic origin:
• Endometriosis:
–– Endometriosis is found in 30–70% of women who
undergo laparoscopy.
–– Endometriosis is most commonly diagnosed in
women aged between 25 and 35 years.
• Adenomyosis:
–– Adenomyosis is most commonly diagnosed in women
aged between 40 and 50 years.
–– Women with adenomyosis may present with abnor-
mal uterine bleeding and dysmenorrhea.

https://doi.org/10.1007/978-3-030-41128-2_6
234 Chapter 6. Chronic Pelvic Pain
• Ovarian cysts/masses:
Large ovarian cysts may cause chronic dull aching
pain. Ovarian cysts at risk for torsion may result in
acute pain.
• Pelvic inflammatory disease (PID): Women with acute
PID may develop persistent pelvic pain. Risk factors of
persistent pelvic pain in these patients include:
➀ Tubal damage (e.g., development of hydrosalpinx)
➁ Persistent pelvic pain/tenderness 30 days after diag-
nosis and treatment
➂ Smokers
➃ Two or more episodes of PID
• Ovarian remnant syndrome:
–– Defined as residual ovarian tissue left behind after
oophorectomy.
–– Patients may present with pelvic pain, possibly pelvic
mass, and absence of immediate menopausal symp-
toms despite bilateral oophorectomy.
• Primary dysmenorrhea
• Pelvic adhesive disease: the causative relation with pel-
vic pain is not definitive.
• Post-ablation tubal syndrome: these women have his-
tory of endometrial ablation and tubal ligation. They
complain of cyclic pelvic pain due to fluid/blood trapped
between the scarring in the uterus and the tubal
ligation.
• Uterine leiomyoma: uterine leiomyomas do not typi-
cally present with pain. However, dull pain may be
attributed to large uterine size and pressure symptoms.
❷ Urinary origin:
• Interstitial cystitis/painful bladder syndrome:
These patients present, in addition to pelvic pain,
with bladder irritability and urinary urgency and
frequency.
Chapter 6. Chronic Pelvic Pain 235
• Radiation cystitis: in women with prior pelvic

radiation.
• Bladder cancer: patients are usually above the age of
60; they commonly present with hematuria.
• Recurrent cystitis: patients present with frequency,
urgency, and/or hematuria.
• Recurrent/chronic urolithiasis
❸ Gastrointestinal (GI) origin:
• Irritable bowel syndrome (IBS):
The diagnosis of IBD is made through Rome IV cri-
teria: recurrent abdominal pain at least once/week in
the last 3 months PLUS 2 or more of the following
criteria:
➀ Pain related to defecation
➁ Pain associated with a change in stool frequency
➂ Pain associated with a change in stool form
• Inflammatory bowel disease (IBD):
These patients present with crampy abdominal pain
in association with:
–– GI symptoms: diarrhea with or without rectal bleed-
ing (bleeding is more common with ulcerative
colitis)
–– General symptoms: fatigue, weight loss, and fever
• Colorectal carcinoma: hematochezia or melena,
abdominal pain, and/or bowel change
• Celiac disease: recurrent diarrhea and weight loss and/
or chronic pelvic pain
• Diverticular disease:
–– Patients may complain of cramping abdominal pain
in the left lower quadrant associated with chronic
diarrhea with or without intermittent hematochezia.
–– Diverticular disease has several forms that may
cause pelvic pain.
Diverticular colitis: segmental colitis of interdiver-
ticular mucosa associated with diverticula.
Diverticulitis: inflammation of a diverticulum.

Symptomatic uncomplicated diverticular dis-
ease: patients present with persistent abdominal
pain. Abdominal CT scan shows colonic wall
thickening with no signs of inflammation.
• Chronic constipation:
Chronic constipation may be associated with pelvic dis-
comfort (uncommon).
• Hernias
❹ Musculoskeletal origin:
• Chronic abdominal wall pain:
–– Patients may report history of muscle or nerve injury
or strain.
–– Unlike visceral pain, Carnett’s sign is positive (ten-
derness does not change, or it becomes worse when
abdominal wall muscles are tensed by unsupported
head lifting).
• Myofascial pain syndrome:
–– Patients may report abdominal wall injury, strain, or
scoliosis.
–– Stimulation of myofascial trigger points (hyperirri-
table muscular spots) results in local and visceral
pain and autonomic symptoms, e.g., nausea, vomit-
ing, and vasodilation.
• Pelvic floor tension myalgia:
–– This disorder may be evoked by pelvic floor surgery,
genital trauma, or secondary to other causes of pelvic
pain, e.g., endometriosis.
–– Pain is aggravated by prolonged sitting and improved
by local heat and lying down with flexed hips.
• Fibromyalgia:
–– Patients report pain at multiple spots, including both
upper and lower part, and both sides of the body.
–– To make the diagnosis, pain should present at 11 of
18 separated areas.
• Osteitis pubis:
–– This pain may be evoked by surgical or nonsurgical
trauma, pregnancy and childbirth, or strenuous
activity.
–– Pain is aggravated by walking. Symphysial area is
tender to palpation.
❺ Vascular origin:
• Pelvic congestion syndrome:
Patients are usually multiparous and complain of
aching pain of shifting location. Pain increases after
prolonged standing. Patients may also complain of deep
dyspareunia.
❻ Neurological origin: e.g., somatization and centralized pain
syndrome
Diagnosis:
• History:
–– History of present illness (pain characteristics):
Site of pain: fixed or shifting
Type of pain: aching, colicky, sharp, or pressure like
Duration of pain: pelvic pain more than 6 months
defines chronic pelvic pain
Constant vs. intermittent
Radiation of pain: e.g., to the flanks, upper or lower
back, and thighs
Precipitating factors: e.g., following exercise, surgery,
or vaginal delivery
Factors reducing pain: resting, medications, and
bowel movement
Factors exacerbating pain: activity, standing, sitting,

and intercourse
Pain in other body parts (e.g., fibromyalgia)
–– Gynecologic history:
Menstrual history and relation of pain to menstrual
cycle
History of leiomyomas
History of pelvic inflammatory disease, prior treat-
ment, and number of episodes
History of ovarian cysts
–– Urinary symptoms:
Presence of urinary urgency, frequency, dysuria, or
hematuria
History of renal stones
–– GI symptoms:
Diarrhea/constipation (acute or chronic)
Relation to pain to bowel movement
Straining with bowel movement
Hematochezia
Unintentional loss of weight
Fatigue, intermittent fever
–– Sexual history:
Dyspareunia, superficial versus deep dyspareunia
–– Surgical history:
History of abdominal surgeries (laparotomy)
History of pelvic surgeries
History of endometrial ablation and tubal ligation
–– Obstetric history: parity, recent delivery, and significant
labor events
–– Medical history: history of chronic medical disorders
and medications
–– General examination: including assessment of other
painful spots
–– Back examination:
Assessment of back asymmetry or abnormal

curvature
Assessment of tenderness over sacroiliac joints and
paraspinal muscles
Assessment of tenderness over the sacrum or coccyx
Examination starts by asking the patient to point to the
area of pain. Ask her if she can localize her pain by one
finger.
Inspection: of abdominal swelling and scar sites
Palpation:
• Superficial palpation: using a cotton swab to test
for abdominal wall neuropathy (allodynia)
• Deep palpation: assessment of tender spots, palpi-
tation of symphysis pubis for tenderness, and
assessment of Carnett’s sign
Pelvic examination is performed to assess:
Pelvic floor tenderness
Cervical motion tenderness
Uterine tenderness
Adnexal or post fornix tenderness
Uterine enlargement (adenomyosis, fibroids) or
adnexal masses
Limited uterine mobility
Work-up:
• Laboratory work-up: is guided by clinical suspicion, e.g.,
pregnancy test, urine culture, and endocervical culture
• Imaging work-up:
–– Pelvic ultrasound:
Ultrasound is used to assess the uterus and adnexa.
Pelvic congestion syndrome may be suspected in the
presence of the following findings by pelvic ultrasound
(or CT scan):
➀ Dilated ovarian veins (>4 mm)
➁ Dilated tortuous arcuate veins in the myometrium
➂ Slow blood flow (<3 cm/s)
–– Pelvic abdominal CT scan: it may help to rule out some

other non-gynecologic causes of chronic pelvic pain.
–– Pelvic MRI: this modality is superior to other imaging
techniques in detecting deep infiltrating endometriosis.
• Endoscopic work-up:
–– Colonoscopy: to rule out some GI-related disorders if
clinically suspected
–– Cystoscopy: to rule out some urinary disorders if clini-
cally suspected
–– Laparoscopy: is the modality of choice for diagnosis of
endometriosis and pelvic adhesions
Treatment:
Treatment of chronic pelvic pain is determined by underlying
cause. However, multifactorial causes should always be
addressed. Examples of these causes include:
• Gynecologic causes: e.g.,
–– Endometriosis: NSAIDs, hormonal treatment, or
surgery.
–– Adenomyosis: progestins, progestin-releasing
hysterectomy.
–– Leiomyomas: radiologic procedure to shrink fibroids or
surgery if indicated.
–– Ovarian remnant syndrome: excision of remnant tissue.
–– Primary dysmenorrhea: NSAIDs and hormonal
treatment.
–– Post-tubal ligation pain syndrome: hormonal suppres-
sion might be effective, but hysterectomy is definitive.
–– Ovarian cancer: surgery and chemotherapy.
• GI causes: e.g.,
–– Irritable bowel syndrome: diet changes, increase dietary
fibers, and anticholinergic medications (dicyclomine
and hyoscyamine)
–– Inflammatory bowel disease and celiac disease: GI
referral
–– Chronic constipation: hydration, fibers, and laxatives
–– Colorectal carcinoma: GI surgery referral
Endometriosis 241
• Urinary causes: e.g., interstitial cystitis

–– Urinary analgesics (e.g., phenazopyridine; pyridium)
–– Oral analgesics
–– Intravesical instillation of local analgesic (lidocaine
with heparin and/or sodium bicarbonate)
• Vascular causes (pelvic congestion syndrome): GnRH
analogue, hormones including progestin-releasing IUD
can be effective, embolization.
Endometriosis
Definitions:
Endometriosis is the presence of endometrial glands and
stroma outside the uterus.
Incidence:
• 6–10% of US women
• 20–50% in infertile women
• 71–87% in women with chronic pelvic pain
Etiology:
• Theories for etiology:
Etiology of endometriosis is controversial. The following are
examples of these theories:
Theory Explanation
Retrograde Retrograde menstruation from
menstruation (Sampson the uterus to the peritoneal cavity
theory) through the fallopian tubes results in
dissemination of endometrial tissue
within the pelvis
Lymphatic or vascular Endometriosis may originate from
spread (Halban’s abnormal lymphatic or vascular
theory) spread of endometrial tissue
Theory Explanation
Coelomic metaplasia Endometriosis may result from
(Meyer’s theory) metaplastic transformation and
parietal peritoneum to normal
endometrium
Induction theory Some hormonal or biologic factor(s):
endometriosis may be attributed
to some hormonal or biologic
factors that induce differentiation
of undifferentiated cells into the
endometrium
• Risk factors:
–– Age: most common age of pelvic endometriosis is 25–30
years.
–– Parity: more common in nulliparous women or women
with low parity especially with delayed childbearing.
–– Menstrual rhythm: frequent menstrual cycles, pro-
longed, and heavy menstrual bleeding.
–– Family history: there is evidence of a familial inheri-
tance pattern for endometriosis. There is a tenfold risk
increase if the disease is present in first-degree
relatives.
–– Anatomic defects: reproductive outflow tract obstruc-
tion may predispose to development of endometriosis.
Women younger than 20 years with endometriosis often
have anatomic anomalies.
Pathology:
• Site of endometriosis:
–– Pelvic endometriosis:
Ovaries (44%)
Pelvic peritoneum (34%)
Tubes
Uterosacral and round ligaments
Rectovaginal septum
Urinary bladder and ureters
Endometriosis 243
Rectum and sigmoid colon

Vagina and vulva
–– Extrapelvic endometriosis: e.g.,
Umbilicus
Abdominal scar after Cesarean delivery
Abdominal viscera such as the gallbladder or
appendix
–– Macroscopic features:
Endometriosis of the ovaries: (bilateral in 50% of
cases)
The lesion can be either:
• Small dark brown spots on the surface of the
ovary
• An ovarian endometrioma:
–– Usually small to moderate sized.
–– Irregular surface.
–– May be surrounded by adhesions in advanced
stages.
–– Consists of one or more endometrium-lined
cysts filled with dark brown-altered “chocolate
cysts.”
–– Ovarian tunica albuginea is thickened.
Endometriosis of the pelvic peritoneum: the lesions

are either:
• Typical lesions:
–– Tobacco stains or powder (gunshot) burns
–– Dark brown, black, or bluish nodules
–– Small cysts containing old blood
• Subtle lesions:
–– Red implants
–– Clear vesicles
–– White plaques
Endometriosis of the colon:

Small hemorrhagic nodules are found on the sero-
sal surface of the colon and may involve the wall of
the colon. These lesions may be surrounded by dense
adhesions.
–– Microscopic features:
Endometriosis consists of typical endometrial glands
and stroma containing blood collection. Other features
include local inflammatory reaction and adhesion
formation.
Classification System:
Revised classification of the American Society for
Reproductive Medicine (ASRM) – 1997
This classification is based on laparoscopic findings. Scores
are given to the following findings:
• Peritoneal endometriosis: is scored depending on the size
and depth:
–– Superficial endometriosis is scored 1 if <1 cm, 2 if 1–3
cm, or 4 if >3 cm.
–– Deep endometriosis is scored 2 if <1 cm, 4 if 1–3 cm, or
6 if >3 cm.
• Ovarian endometriosis: is scored depending on the size
and depth (each ovary is calculated separately):
–– Superficial endometriosis is scored 1 if < 1 cm, 2 if 1–3
cm, or 4 if >3 cm.
–– Deep endometriosis is scored 4 if <1 cm, 16 if 1–3 cm, or
20 if >3 cm.
• Posterior cul-de-sac obliteration:
–– If partially obliterated: it is scored 4.
–– If completely obliterated: it is scored 40.
• Ovarian adhesions: they are scored based on density and
enclosure (each ovary is calculated separately):
Endometriosis 245
–– Filmy adhesions are scored 1 if enclosure is <1/3, 2 if

enclosure is 1/3 to 2/3, or 4 if enclosure is >2/3.
–– Dense adhesions are scored 4 if enclosure is <1/3, 8 if
• Tubal adhesions: they are scored based on density and
enclosure (each ovary is calculated separately):
–– Filmy adhesions are scored 1 if enclosure is <1/3, 2 if
–– Dense adhesions are scored 4 if enclosure is <1/3, 8 if
A completely enclosed fimbriated end of the fallopian tube is
scored16.
Staging according to score

Stage I (minimal): 1–5 Stage III (moderate): 16–40
Stage II (mild): 6–15 Stage IV (severe): >40
Diagnosis:
I. Symptoms
Women with endometriosis may be asymptomatic (15%).

Common symptoms of endometriosis include:
❶ Endometriosis-related pain:
➀ Dysmenorrhea:
• Incidence: 60–80% of women with endometriosis
• Description of pain:
–– Cyclic pain typically starts 24–48 hours prior to
menses (congestion of endometrial glands).
–– Pain increases in severity afterward. Worst pain
may be reported at the end of menstruation (dis-
tension of glands with menstrual blood and
inflammatory cytokines).
–– Afterward, pain gradually diminishes (partial

absorption of blood and resolution of inflamma-
tory reaction).
➁ Noncyclical chronic pelvic pain: 40–60% of women
with endometriosis
➂ Dyspareunia:
• Incidence: 5–15% of women with endometriosis
• Etiology: endometriosis-associated dyspareunia may
be caused by stretching of endometriotic lesions
especially if the rectovaginal septum or uterosacral
ligaments are involved.
• Character: endometriosis causes deep dyspareunia.
Pain may be most significant shortly before
menstruation.
➃ Dysuria:
Patients may experience painful urination, cyclic uri-
nary frequency, and urgency despite negative urine
cultures particularly if the bladder is involved.
➄ Defecatory pain:
Patients may experience chronic or cyclic defecatory
pain that may be associated with constipation, diarrhea,
or cyclic hematochezia particularly if rectosigmoid or
uterosacral ligaments are involved.
❷ Endometriosis-related infertility:
• Incidence: the incidence of endometriosis in women
with infertility or subfertility is 20–30%.
• Causes:
–– Ovarian factor:
Ovarian factors may be attributed to elevated
local inflammatory mediators in peritoneal fluid.
Endometriosis 247
Impaired folliculogenesis and embryogenesis

(oocyte quality and number may be diminished in
women with endometriosis).
Early degeneration of the corpus luteum.
–– Tubal factor:
Peritubal adhesions may interfere with ovum pick up.
High concentration of prostaglandins may alter tubal
motility.
–– Uterine factor: endometrial changes causing implan-
tation defects, e.g., deficient v3 integrin expression.
–– Cervical factor: sharp uterine retroversion pulls the
cervix away from the seminal pool in the posterior
fornix.
–– Vaginal factor: dyspareunia interferes with fre-
quency of sexual intercourse.
–– Immune factor: endometriosis is associated with
increased macrophages in the peritoneal fluid and
presence of autoantibodies in 60% of patients of
endometriosis.
In many women with endometriosis, no abnormality is

detected during clinical examination.
• Speculum examination:
–– Speculum examination is usually unremarkable. Women
complaining of dyspareunia are likely to experience
uncomfortable examination.
–– Bluish or brownish tender lesions may occasionally be
noted on the cervix or the posterior fornix.
• Bimanual examination:
–– Posterior fornix: multiple small firm tender nodules may
be felt due to endometriosis of the pelvic peritoneum.
–– Adnexa: enlarged cystic mobile or adherent adnexal

mass(es) may be noted in the presence of ovarian
endometrioma.
–– Uterus: the uterus may be retroverted immobile in
advanced stages due to pelvic adhesions.
• Rectal examination:
Rectal examination may reveal small firm tender nodules
in the region of the uterosacral ligaments or rectovaginal
septum.
III. Differential diagnosis
Endometriosis should be thoroughly differentiated from

other gynecologic or non-gynecologic causes of chronic pel-
vic pain. History and examination are crucial to differential
diagnosis. Further work-up may be indicated based on patient
clinical presentation (see under: Chronic pelvic pain).
IV. Work-up
–– Laboratory tests may be indicated to rule out other
diagnoses suspected by clinical scenario, e.g., urinalysis
and urine cultures (urinary causes), vaginal cultures,
and cervical swabs (pelvic infection).
–– Serum CA125 may be elevated in moderate or severe
cases (>35μ/mL in >80% of cases). The diagnostic value
of this test in patients with suspected endometriosis is
limited because:
It is often normal in early stages.
CA125 is not specific; it may be elevated in several
conditions, e.g., pelvic inflammatory disease, preg-
nancy, and ovarian cancer.
Endometriosis 249
• Diagnostic imaging:
–– Sonography:
Transvaginal sonography (TVUS):
• Value: TVUS is accurate in detecting endometrio-
mas that are 2 cm or more.
• Findings: endometriomas appear as:
–– Cystic structures with low-level internal echoes
–– Thick cystic wall with occasional thick
septations
–– Pericystic flow with color Doppler assessment,
no intracystic flow
• Limitation: TVUS is not adequate in assessment
of superficial, deep endometriosis, or adhesions.
Transrectal sonography:
Transrectal sonography is superior to TVUS in delin-
eating rectal involvement.
–– Magnetic resonance imaging (MRI):
MRI is the imaging modality of choice in women
with endometriosis. The use of T2 weighted and T1
weighted with fat suppression promotes visualization
of deep endometriotic lesions.
High experience in reading endometriosis-indicated
MRI helps preoperative planning for surgery, e.g.,
the presence of rectosigmoid involvement.
• Diagnostic laparoscopy:
Diagnostic laparoscopy is the primary diagnostic tool of
endometriosis. Laparoscopy allows:
• Visual diagnosis of endometriosis (endometriomas, pow-
der burns, nodules, or small cysts, subtle lesions)
• Pathological assessment (biopsy)
• Classification of the disease
• Assessment of degree of anatomical distortion
• Pathologic testing:
Although definite diagnosis of endometriosis is made
through pathological assessment, it is not mandatory in
every case of endometriosis to make the diagnosis unless
clinically doubtful.
Treatment:
Treatment is determined according to patient symptoms.
I. Asymptomatic endometriosis
• If the diagnosis is incidentally made (e.g., during laparo-

scopic surgery) while the patient is otherwise asymptom-
atic, treatment is not necessary. The patient should be
educated about endometriosis.
• Patient should be counseled that the data on disease
course is inadequate; it may progress, regress, or stay stable
over time. However, the disease should regress after
menopause.
II. Treatment of endometriosis-related pain: Desires fertility
I. Medical treatment
• Non-hormonal treatment (NSAIDs):

–– Indication: it may be selected as a first-line therapy in
selected patients with minimal or mild pain symptoms.
–– Mechanism: they act by reducing prostaglandin produc-
tion through COX-2 inhibition (endometriotic tissues
express greater levels of COX-2).
–– Limitation: long-term use of COX-2 inhibitors increases
cardiovascular risks.
Endometriosis 251
• Combined hormonal contraceptives (CHCs):

–– Mechanism: they act:
Centrally by inhibiting release of pituitary
gonadotropin
Peripherally by decidualizing endometriotic tissue
–– Regimen: continuous regimen may be preferable to

cyclic regimen for pain control.
• Progestins:
–– Mechanism of action: progestins act on endometriotic
tissue by antagonizing estrogenic stimulation, with sub-
sequent decidualization and atrophy of endometriotic
lesions.
–– Routes:
➀ Oral progestins: medroxyprogesterone 100 mg orally
daily for 6 months
➁ Parenteral progestins:
–– Intramuscular medroxyprogesterone acetate
150 mg every 3 months.
–– Effectiveness is comparable to GnRH analogue.
–– Less bone loss compared to GnRH analogue.
–– It may be associated with delayed return of
fertility.
➂ The levonorgestrel-releasing intrauterine system
(LNG-IUS): it may be effective in women with
endometriosis-related dysmenorrhea.
➃ Selective progesterone receptor modulators (SPRMs –
mifepristone RU486):
–– It is an emerging new option for treatment of
endometriosis.
–– Suggested dose is 50 mg daily for 6 months.
• Side effects: progestin-related side effects, e.g., head-
ache, weight gain, fluid retention, and depression
• GnRH analogue:
–– Mechanism of action: continuous administration (as
opposed to natural pulsatile GnRH secretion) results in
pituitary desensitization and prevention of gonadotro-
pin secretion and ovarian steroidogenesis (pseudo-
menopause status).
–– Regimen:
Drug Route Regimen

Goserelin S.C 3.6 mg every 4 weeks
Triptorelin IM 3.75 mg every 4 weeks
Nafarelin Intranasal 200 μg twice daily
–– Side effects:
It causes hot flushes, vaginal dryness, mood changes,
and bone loss.
The recurrence rate within 5 years after cessation of
treatment is 53–73%.
–– Add back therapy with GnRH analogue:
Why: it is used primarily to prevent or reduce bone
loss associated with extended use of GnRH.
When:
• Add back therapy may be added if GnRH treat-
ment successfully improves pain and is intended
to be used for more than 6 months.
• Add back therapy may be initiated with initiation
of GnRH administration.
How:
• Norethindrone 5 mg daily with or without conju-
gated estrogens 0.625mg daily.
• Transdermal estradiol 25 mcg with medroxypro-
gesterone 2.5 mg daily.
• Calcium 1000 mg may be added to this regimen.
Endometriosis 253
• GnRH antagonist:
Elagolix is a novel oral GnRH antagonist that can be
used to treat endometriosis-related pain. Elagolix is given
in a dose of 200 mg twice daily.
• Aromatase inhibitors: (anastrozole, letrozole)
–– Administration: it should be used in conjunction with
another medication that suppresses the ovaries (e.g.,
CHC, progestins, GnRH analogue) in premenopausal
women (otherwise, it may stimulate the ovaries and
develops ovarian cysts).
–– Mechanism of action: these agents act by inhibiting aro-
matase, which produce estrogen through aromatization
of circulating androgens. Aromatase is expressed at
high levels in endometriotic tissue.
–– Side effects: hypoestrogenic side effects (mild hot
flushes and decreased libido).
II. Surgical treatment
• Surgical approach:
Surgical treatment provides significant pain relief com-
pared to expectant management (80% vs 30%).
–– Management of endometriomas:
Endometriomas should be removed to improve pain
and exclude malignancy (cysts >3 cm).
Ovarian cystectomy is superior to drainage or cyst
wall ablation (better pain relief).
If endometriomas are recurrent, treatment should be
individualized.
–– Management of endometriotic lesions:
Resection of the implants and adjacent peritoneum
is the primary treatment. Laser energy or electrosurgi-
cal ablation may be used.
–– Adhesiolysis:
Lysis of adhesions including peritubal and periovar-
ian adhesions and correction of anatomical distortion
may improve pain.
–– Neurointervention:
Presacral neurectomy:
–– Indications: it may be used if patient’s primary
complaint is central pain (severe dysmenorrhea).
–– Technique: it is performed by transection of nerve
bundles at the level of S3 (third sacral vertebra).
➀ Injury to the middle sacral artery and vein
➁ Risk of constipation (> 90%)
➂ Risk of urinary retention
Laparoscopic uterine nerve ablation (LUNA): cur-
rent evidence does not show this treatment is
effective.
• Pre and postsurgical medical treatment:
–– Presurgical hormonal treatment: current evidence does
not support the role of hormonal pretreatment prior to
surgery.
–– Postsurgical hormonal treatment:
Postsurgical hormonal treatment may extend pain-
free interval after surgery.
Treatment options:
• CHCs: it should be used for at least 24 months,
either cyclic or continuous.
• GnRH analogue: it may be used for 12–24 months.
• Reintervention:
Risk of reintervention is higher among younger women.
Rate of reintervention is:
Endometriosis 255
–– 20% after 2 years

III. Pain-associated endometriosis: No fertility desire
• Medical treatment:
Medical treatment is still the first option. Even if the
patient is not interested in future fertility, medical treat-
ment should be considered as the first line to avoid short-
and long-term risk of hysterectomy with or without
oophorectomy.
• Total hysterectomy, bilateral salpingo-oophorectomy,
cytoreduction of visible endometriosis, and adhesiolysis:
–– This is the most definitive treatment. However, patient
age should be taken into account prior to surgery.
–– Risk of recurrence of symptoms after surgery is approx-
imately 15%; recurrence may be managed with reopera-
tion (aromatase inhibitors may be used; no rule for
GnRH treatment in these patients).
–– Hormonal therapy can be started immediately after
surgery.
• Hysterectomy and cytoreduction of visible endometriosis:
–– This option is an alternative to radical surgery in
younger women.
–– In these patients, ovarian cystectomy of ovarian endo-
metriomas may be performed.
–– The risk of recurrence in women preserving their ova-
ries is sixfold higher than women undergoing
oophorectomy.
IV. Treatment of endometriosis-related infertility
• Based on disease stage:

Disease stage Treatment options
Minimal to mild •S urgery to women with minimal to mild
disease (stages disease may improve pregnancy rate (rate is
I–II) doubled)
•C lomiphene citrate with intrauterine
insemination may be tried for three cycles.
The probability of successful pregnancy is
10% per cycle in women younger than 40
years
• I f above options are not successful, the next
two options are either:
• P arenteral ovulation induction with
intrauterine insemination
• In vitro fertilization
Moderate to •S urgery is technically more challenging, and
severe disease overall pregnancy rate is still low. However,
(stages III–IV) surgery can still improve pregnancy rate
• I f pregnancy does not occur within 6
to 12 months after surgery, assisted
reproduction, rather than a repeat surgery,
is recommended. A repeat surgery may
adversely impact in vitro fertilization
outcomes
• Based on endometriotic lesions:

–– Endometrioma:
Surgical treatment significantly improves pregnancy
outcome. Treatment of endometriomas larger than
3 cm is recommended prior to assisted reproduction
Excision is superior to incision and drainage (higher
pregnancy and less recurrence).
Removal of endometriomas decreases ovarian reserve.
–– Deeply infiltrative endometriosis:
• Value of excision on infertility is unclear. It may adversely
affect fertility.
Adenomyosis 257
Adenomyosis
Definition:
It is the presence of endometrial glands and stroma within the
myometrium.
Etiology:
• Theories for etiology:
Theory Explanation
Diverticular theory Endometrial glands grow deeply
(Cullen’s theory) into the myometrium in the form
of diverticula. The deep portions
separate forming adenomyosis
Developmental theory Adenomyosis develops from
endometrial tissue that is deposited
within the myometrium during
uterine development in utero
Postpartum inflammation This theory links postpartum
theory endometrial inflammation to
adenomyosis. This inflammation
breaks endometrial-myometrial
interface and allows endometrial
cells to develop within the
myometrium
Stem cell origin theory Bone marrow stem cells may
invade the myometrium and
develop endometrial tissue
• Risk factors:
–– Age: the most common age is between 40 and 50 years
–– Parity: more common among multiparous women
–– Prior uterine surgery: e.g., myomectomy, Cesarean
delivery
Pathology:
Diffuse type Localized type

The uterus is slightly and Adenomyosis is localized and
symmetrically enlarged whorled without a capsule. Small
and firm dark brown spots may be noted
within the lesion. The uterus may
be asymmetrically enlarged
The lesion arises from the basal endometrium which does

not always respond to ovarian hormones due to lack of pro-
gesterone receptors (so it is not always distended with blood).
Ectopic endometrial tissue is present within the normal
myometrium. This area is surrounded by a zone of myome-
trial hypertrophy and hyperplasia.
Diagnosis:
• Types of patients:
–– Age: patients aged 40–50 years
–– Parity: parous women
–– Social and economic state: more common among the
lower classes
• Symptoms:
–– Asymptomatic: 30–40% of patients are asymptomatic.
–– Heavy menstrual bleeding: (the most common symp-
tom, 60% of patients). It may be attributed to increase
surface area of the endometrium and impaired myome-
trial contractions.
–– Dysmenorrhea: (20% of patients)
Dysmenorrhea is a less common symptom compared to
endometriosis. This may be attributed to the fact that
adenomyosis is typically composed of basal endome-
trium which is less responsive to cyclic hormonal
stimulation.
Adenomyosis 259
The uterus is usually slightly symmetrically enlarged
(less than 12 weeks), firm, and tender to palpation.
• Work-up:
–– Transvaginal ultrasound:
Diffuse adenomyosis
• The anterior or posterior uterine wall is thicker
• Myometrial heterogenicity
• Small myometrial hypoechoic cysts
• Linear striated projections into the myometrium
Localized adenomyosis
Differentiation of localized adenomyosis from uterine
leiomyoma may be challenging. Features of adenomyosis
include:
• Poorly defined margins
• Elliptical rather than globular lesion
• No mass effect on the surrounding tissues
• No calcifications
•M ultiple anechoic cysts of varying diameters may be present
–– Magnetic resonance imaging: adenomyosis may appear

as decreased signal intensity.
• Histological examination: of the uterus after hysterec-
tomy is the only definitive method.
Treatment:
• Medical treatment
–– Non-hormonal treatment: NSAIDs may improve both
dysmenorrhea and heavy menstrual bleeding.
–– Hormonal treatment: progestins (oral progestins, pro-
gestin-releasing intrauterine devices) may be used.
Other options include CHCs and GnRH analogues.
• Surgical treatment: hysterectomy is a definitive treatment
but should be used only if other methods fail.
Further Reading
Ayorinde AA, Bhattacharya S, Druce KL, et al. Chronic pelvic pain
in women of reproductive and post-reproductive age: a popula-
tion-based study. Eur J Pain. 2017;21:445.
Bazot M, Bharwani N, Huchon C, et al. European society of urogeni-
tal radiology (ESUR) guidelines: MR imaging of pelvic endome-
triosis. Eur Radiol. 2017;27:2765.
Burney RO, Giudice LC. Pathogenesis and pathophysiology of
endometriosis. Fertil Steril. 2012;98:511.
Cheong YC, Smotra G, Williams AC. Non-surgical interventions for
the management of chronic pelvic pain. Cochrane Database Syst
Rev. 2014;3:CD008797.
Dunselman GA, Vermeulen N, Becker C, et al. ESHRE guide-
line: management of women with endometriosis. Hum Reprod.
2014;29:400.
Gambone JC, Mittman BS, Munro MG, et al. Consensus statement
for the management of chronic pelvic pain and endometriosis:
proceedings of an expert-panel consensus process. Fertil Steril.
2002;78:961.
Howard FM. Chronic pelvic pain. Obstet Gynecol. 2003;101:594.
Lippman SA, Warner M, Samuels S, et al. Uterine fibroids and gyne-
cologic pain symptoms in a population-based study. Fertil Steril.
2003;80:1488.
Nisenblat V, Bossuyt PM, Farquhar C, et al. Imaging modalities for
the non-invasive diagnosis of endometriosis. Cochrane Database
Syst Rev. 2016;2:CD009591.
Practice bulletin no. 114: management of endometriosis. Obstet
Gynecol. 2010;116:223.
Medicine. Treatment of pelvic pain associated with endometrio-
sis: a committee opinion. Fertil Steril. 2014;101:927.
Speer LM, Mushkbar S, Erbele T. Chronic pelvic pain in women. Am
Fam Physician. 2016;93:380.
Zondervan KT, Yudkin PL, Vessey MP, et al. Prevalence and inci-
dence of chronic pelvic pain in primary care: evidence from
a national general practice database. Br J Obstet Gynaecol.
1999;106:1149.
Chapter 7
Menopause
Definitions:
• Menopausal transition (previously known as perimeno-
pause or climacteric): The term refers to a span of approxi-
mately 4–7 years, that start by the onset of menstrual
irregularities at late reproductive years and until 1 year
after cessation of menstruation.
• Menopause: Menopause is defined as a point of time that
starts 1 year after cessation of menses (average age is 51.5
years). Premature menopause refers to menopause diag-
nosed before the age of 40.
Manifestations and Complications of Menopause:

Approximately 30% of women report moderate to severe
symptoms related to menopause:
❶ Vasomotor manifestations:
➀ Hot flushes:
• Incidence: 10% of women during menopausal transi-
tion and 50% after menopause.
• Risk factors: surgical menopause, early menopause,
and smoking are associated with significant hot
flushes.
• Clinical features: Hot flushes present as acute propa-
gation of heat and sweating waves over the face and
upper body. This may be a ssociated with palpitations,

https://doi.org/10.1007/978-3-030-41128-2_7
262 Chapter 7. Menopause
anxiety, and irritability. Each episode usually lasts for

5 minutes or less.
➁ Night sweats
❷ Neuropsychologic symptoms:
• Sleep difficulties
• Cognitive decline and poor concentration
• Depression and mood changes
❸ Somatic symptoms:
• Headache and dizziness
• Joint aches and back pain
❹ Bone changes:
• Osteopenia and osteoporosis: See below under:
Osteoporosis
• Dental manifestations: Oral alveolar bone loss results in
tooth loss
❺ Cardiovascular complications:
• Increased risk of cardiovascular diseases: e.g., hyperten-
sion, coronary heart disease, and atherosclerosis
• Weight gain and central (truncal) adiposity
❻ Urinary symptoms:
Women after menopause are more prone to urinary
incontinence, urgency, and recurrent urinary tract
infection
❼ Sexual symptoms:
Women commonly report vaginal dryness, dyspareunia,
and decreased libido after menopause due to hypoestro-
genic state
Urinary and sexual symptoms of menopause are referred to
as genitourinary syndrome of menopause.
Chapter 7. Menopause 263
Work-up:
Menopause is a clinical diagnosis that is made 12 months
after cessation of last menstrual period. However, in certain
clinical circumstances, clinical diagnosis cannot be made, e.g.,
after hysterectomy or endometrial ablation. If diagnosis of
menopause is crucial, it may be aided by assessment of serum
FSH (elevated) and estradiol (decreased).
Treatment:
I. General measures
• Avoidance of triggers of hot flushes: e.g., stress, caffeine,

alcohol, spicy foods, heat, and smoking
• Healthy lifestyle: including regular exercise, low-fat diet,
and increase calcium intake
II. Medical treatment
• Hormonal therapy:
–– Indications:
❶ Severe menopausal symptoms: e.g., hot flushes and
night sweats.
❷ Premature menopause: hormonal therapy is recom-
mended to the anticipated age of menopause to
provide cardiovascular benefits and prevent
osteoporosis.
❸ Osteopenia/osteoporosis: in women with decreased
bone density, hormonal therapy is beneficial.
–– Initiation:
Hormonal therapy initiated before the age of 60
years or within 10 years of last menstrual period
rovides the best benefits and is not associated with

p
increased risk of cardiovascular disease or mortality.
–– Contraindications:
Seve re active liver disease
History of breast or endometrial cancer
Undiagnosed vaginal bleeding
History of myocardial infarction or cerebrovascular
accident
Thromboembolic disorders
Porphyria
Hypertriglyceridemia
–– Types of hormonal therapy:
Estrogen therapy:
• Systemic estrogen treatment without progestogen
is considered only in women who do not have a
uterus.
• Topical estrogen can be used without progestogen
in all women. Topical estrogen is superior to sys-
temic estrogen in management of vaginal dryness,
burning, or dyspareunia.
• Systemic estrogen may be used in oral form (con-
jugated estrogen) or transdermal patch.
• Transdermal estrogen is associated with lower risk
of thromboembolism compared to oral
preparations.
Estrogen and progesterone therapy:
• If the uterus is present, progesterone must be
added to estrogen regimen.
• When the use of progesterone is necessary, micron-
ized progesterone is a safe option, but medroxy-
progesterone and progestin- releasing IUDs are
used as well.
Chapter 7. Menopause 265
The use of progestins without estrogen, testosterone,

bioidentical hormones, and phytoestrogens is not
supported by current evidence for menopausal
symptoms.
–– Benefits of hormonal therapy:
Symptomatic relief of menopausal symptoms, e.g.,
hot flushes and night sweats.
It may reduce the risk of colon cancer.
It protects against osteoporosis.
–– Side effects and risks of hormonal therapy:
Nausea and bloating
Fluid retention
Mood swings
Breakthrough bleeding
Breast tenderness
–– Complications of hormonal therapy:
Cardiovascular disease: hormonal therapy does not
increase the risk of cardiovascular disease if treat-
ment starts under the age of 60 year. However, initia-
tion of treatment beyond this age is associated with
increased risk of cardiovascular disease and related
mortality. Therefore, it should be avoided.
Breast cancer: hormonal therapy is associated with
slight increase in the risk of breast cancer (1.1–1.3
times), after at least 5 years of continuous use.
Endometrial cancer: cyclic progesterone therapy
with constant estrogen, rather than continuous regi-
men, may be associated with increased risk of endo-
metrial cancer after 5 years of treatment.
Thromboembolism: hormonal therapy is associated
with increased risk of venous thromboembolism. The
risk is lower with transdermal patches compared to
other routes of systemic therapy.
Biliary complications: hormonal therapy is associ-
ated with increased risk of biliary stones and
cholecystitis.
• Non-hormonal treatment:
In patients with vasomotor symptoms, hormonal ther-
apy is the first option. However, if hormonal treatment is
contraindicated or not tolerated, alternative options
include the following:
❶ Selective serotonin reuptake inhibitors:
Paroxetine is an FDA-approved treatment of vaso-
motor symptoms of menopause.
Paroxetine is associated with serious adverse effects, e.g.:
➀ Risk for suicidality
➁ Bleeding risk
➂ Risk for serotonin syndrome
➃ Diminution of effectiveness of tamoxifen in breast
cancer patients
❷ Selective serotonin and norepinephrine reuptake
inhibitors:
Venlafaxine has been increasingly used in manage-
ment of vasomotor symptoms (off-label).
Common side effects include headache, nausea, som-
nolence, nervousness, asthenia, and anorexia.
❸ Clonidine
❹ Gabapentin
Osteopenia and Osteoporosis
Definition:
Osteopenia and osteoporosis refer to systemic skeletal condi-
tion characterized by a progressive reduction in bone mass,
which increases the risk of bone fractures, e.g., spinal, and
femoral fractures.
Risk factors:
Major risk factors:

• Age > 65 years
• Family history of osteoporotic fracture
• Steroid therapy (>3 months)
Osteopenia and Osteoporosis 267
• Malabsorption syndrome
• Primary hyperparathyroidism
• Early menopause
Minor risk factors:

• History of hyperthyroidism
• Low calcium intake
• Smoker
• Alcoholism
• Chronic heparin therapy
Management of osteoporosis:
I. Prevention
Prophylaxis against osteoporosis should start early in life

through regular weight-bearing exercise, cessation of smok-
ing, reduction of alcohol intake, and adequate supplementa-
tion with vitamin D and calcium. Recommended doses are:
Recommended dose of Recommended dose

Age vitamin D of calcium
9–18 600 IU 1,300 mg
19–50 600 IU 1,000 mg
51–70 600 IU 1,200 mg
71 or 800 IU 1,200 mg
more
II. Screening and early detection
• Dual energy X-ray absorptiometry (DEXA) is used to

screen for osteoporosis in all women at the age of 65.
• Screening is indicated at younger age in the presence of

risk factors of osteoporosis, e.g., low body weight <58 kg,
smoking, alcoholism, parental history of hip fracture, who
smoke, and rheumatoid arthritis.
• DEXA scan interpretation is done using T-score. T-score
refers to the standard deviation of bone mineral density of
the patient from bone mineral density of young adult
women:
Normal bone mineral density T-score between +2.5 and –1.0
Osteopenia T-score between –1.0 and –2.5
Osteoporosis T-score lower than –2.5
• Further follow-up depends on T-score results:

–– If DEXA scan is normal or if T-score is -1.5 or greater,
it should be performed every 15 years.
–– If T-score is −1.5 to −1.99, it should be performed every
5 years.
–– If T-score is −2.0 to −2.49, it should be performed
annually.
III. Treatment of osteopenia/osteoporosis
• Indication of treatment:
–– T-score ≤ −2.5 (osteoporosis).
–– T-score between −1.0 and −2.5 and calculated Fracture
Risk Assessment Tool (FRAX), which calculates the
10-year risk of osteoporotic fractures, is 20% or more
for major osteoporotic fracture or 3% or more for hip
fracture.
–– History of low-trauma fracture.
Vulvar Pruritus 269
• Treatment options:
–– Bisphosphonates:
It is the first-line therapy.
The medication is contraindicated in the presence of
esophageal abnormalities or higher-risk aspiration.
–– Raloxifene:
It is a selective estrogen receptor modulator (SERM).
it is preferred in younger postmenopausal women.
It is associated within increased risk of venous
thromboembolism.
–– Denosumab:
It is a RANK ligand inhibitor.
It may be indicated in women at high risk of
fracture.
–– Teriparatide:
It is a recombinant human parathyroid hormone.
It is used to treat women with severe osteoporosis or
with history of osteoporotic fractures.
–– Calcitonin: is not as effective as other options
–– Hormone therapy:
Estrogen therapy may be used in women at higher risk
of osteoporosis and osteoporotic fractures.
• Follow-up:
DEXA scan may be performed initially every 1–2 years
after treatment.
Vulvar Pruritus
Vulvar pruritus is a common gynecologic complaint that may
reflect vulvar skin disorder. Causes of vulvar pruritus include:
Acute vulvar pruritus Chronic vulvar pruritus

• Vulvovaginal candidiasis • Vulvar atrophy
• Trichomonas vaginitis • Lichen sclerosus
•P arasitic infection, e.g., scabies, • Lichen simplex chronicus
pediculosis • Lichen planus
• Contact dermatitis • Psoriasis
• Vulvar intraepithelial
neoplasia
• Vulvar cancer
•P aget disease of the vulva
• Crohn disease
Clinical evaluation:
• History:
History taking should include onset and duration of vulvar
symptoms, associated dermatologic, gastrointestinal symp-
toms, and history of prior vulvar biopsies and autoimmune
diseases.
–– Dermatitis and eczema: they appear as erythematous
poorly demarcated rash. Severe forms may be associ-
ated with erosions and ulcers.
–– Vulvar lichen simplex chronicus: the lesions appear as
scaling and lichenified plaque. It is associated with his-
tory of chronic skin irritation.
–– Lichen sclerosus: the skin appears thinned, porcelain
white (cigarette paper). Disease distribution creates a
“figure of eight” around the vulva and anus. The vagina
is usually spared.
–– Lichen planus: the most common form is erosive type,
which is the most severe type and is associated with
painful, erythematous erosions and extensive scarring.
Other types include papulosquamous (wart-like lesions)
and hypertropic type. Lichen planus of buccal mucosa
has characteristic white reticulate striae (Wickham
striae).
–– Vulvar atrophy: vulvar skin and vaginal mucosa appear
pale, thin, and dry.
Further Reading 271
–– Vulvovaginitis: erythema associated with vaginal

discharge.
–– Paget disease: it may appear as multiple bright red scaly
plaques (eczema-like lesions).
• Work-up:
–– Vulvovaginitis work-up: including microscopy, yeast
culture, PCR for diagnosis of herpes virus. Parabasal or
intermediate cells on microscopy indicate vulvar
atrophy.
–– Vulvar biopsy.
Treatment:
Treatment depends on underlying cause, e.g.:
• Vulvovaginitis: antibiotic treatment (see under: Genital
infection)
• Vulvar atrophy: low-dose topical estradiol is superior to
systemic hormonal therapy
• Lichen sclerosus: high-potency topical steroids (clobetasol
propionate) are the standard treatment. Annual examina-
tion is recommended if the disease is responsive to treat-
ment; lichen sclerosus is associated with <5% risk of
malignancy. Patient should be seen earlier if she develops
new symptoms or worsening of current symptoms.
• Lichen planus: high-potency topical steroids are the first
line of treatment. Second-line options for unresponsive
cases include topical and oral cyclosporine, topical tacroli-
mus, and hydroxychloroquine. Close follow-up is recom-
mended; risk of malignancy is approximately 1%.
• Precancerous and cancerous lesions: see under: Lower
genital tract cancers.
Further Reading
Barnabei VM, Cochrane BB, Aragaki AK, et al. Menopausal symp-
toms and treatment-related effects of estrogen and progestin in
the Women’s Health Initiative. Obstet Gynecol. 2005;105:1063.
McKinlay SM, Brambilla DJ, Posner JG. The normal menopause

transition. Maturitas. 1992;14:103.
National Osteoporosis Foundation. Clinician’s Guide to Prevention
and Treatment of Osteoporosis. Washington, DC: National
Osteoporosis Foundation; 2014.
Practice Bulletin No. 141: Management of Menopausal Symptoms.
Obstet Gynecol. 2014;123:202–16.
Practice bulletin no. 129. Osteoporosis. Obstet Gynecol.
2012;120:718–34.
The NAMS 2017 Hormone Therapy Position Statement Advisory
Panel. The 2017 hormone therapy position statement of The
North American Menopause Society. Menopause. 2017;24:728.
Thurston RC, Joffe H. Vasomotor symptoms and menopause: find-
ings from the Study of Women’s Health across the Nation. Obstet
Gynecol Clin North Am. 2011;38:489.
World Health Organization. WHO scientific group on the assessment
of osteoporosis at the primary health care level: summary meet-
ing report. Brussels, Belgium; May 5–7, 2004. Geneva, Switzerland:
World Health Organization; 2007.
Part II
Urogynecology
Chapter 8
Urinary Incontinence
Definition:
Urinary incontinence is involuntary leakage of urine.
Incidence:
The incidence is 25% among younger women, 50% of
middle-aged women, and 75% of older women.
Types:
• Stress urinary incontinence: involuntary leakage of urine
with events associated with increased intra-abdominal
pressure (e.g., during straining, sneezing, coughing, laugh-
ing) and in absence of full bladder and urgency to
micturate.
• Urge urinary incontinence: involuntary leakage of urine
preceded by sudden urgency.
• Mixed urinary incontinence: both stress and urge inconti-
nence. It can be either mixed urinary incontinence pre-
dominantly stress or predominately urgency incontinence.
• Overflow incontinence: involuntary leakage of urine from
an overdistended urinary bladder in the absence of urge
–– Detrusor failure: can be idiopathic or secondary to neu-
rological disease such as multiple sclerosis
–– Medication side effect: anticholinergic side effects of
certain antipsychotics and antidepressants, alpha-
adrenergic agonists, and calcium channel blockers

https://doi.org/10.1007/978-3-030-41128-2_8
276 Chapter 8. Urinary Incontinence
• Functional incontinence: urine leakage due to physical or/

and mental disease that interferes with mobility or toilet-
ing, e.g., Alzheimer’s disease
• Total incontinence: continuous urine leakage
–– Severe form of other types of incontinence
–– Anatomical cause: genitourinary fistula, congenital
cause (ectopic ureter, epispadias)
Definition and Etiology of Urinary Incontinence
I. Stress urinary incontinence
Definition:
Involuntary leakage of urine with events associated with
increased intra-abdominal pressure (e.g., during straining,
sneezing, coughing, laughing) and in absence of full bladder
and urgency to micturate
Etiology:
• Risk factors:
–– Age: the incidence increases with age secondary to
physical changes associated with aging.
–– Menopause: lack of estrogen results in tissue atrophy.
–– Parity: the number of vaginal deliveries and forceps-
assisted vaginal delivery results in weakness/damage to
the pelvic floor.
–– Obesity: body weight increases the risk of stress incon-
tinence due to increased pressure on abdominal and
pelvic organs (4.2-fold greater risk).
–– Previous pelvic surgeries:
Previous pelvic surgeries can cause weakness/dam-
age to pelvic floor muscles, which precipitate stress
incontinence.
Chapter 8. Urinary Incontinence 277
Pathogenesis:
In patients with stress

Normal physiology incontinence
The urethra is maintained Stress urinary incontinence is
continent through the caused by impaired urethral
following mechanisms: function secondary to
• Mucosa and submucosa: interruption of the continence
the urethra is maintained mechanisms:
by a cushion of submucosal • Mucosa and submucosa:
venous plexus mucosal atrophy, submucosal
• Smooth muscle layer: scarring, and poor submucosal
the urethral tone is also venous plexus
maintained by the circular • Muscle layer: muscle atrophy,
portion of muscular layer denervation, and loss of
• Striated urethral sphincter: connective tissue elasticity
the surrounding mid- secondary to the above risk
urethra (voluntary control) factors
Classification of stress incontinence:
Type I Slightly hypermobile bladder neck and urethra.

The urethra descends less than 2 cm with
increased abdominal pressure
Type II IIA Hypermobile bladder neck and urethra. The
urethra descends more than 2 cm with increased
abdominal pressure. Associated cystocele is mild
(not protruding outside the vagina)
IIB Hypermobile bladder neck and urethra.
The urethra descends more than 2 cm with
increased abdominal pressure. Associated
cystocele is significant (protruding outside the
vagina)
Type III Weak urethral sphincter (intrinsic sphincter
deficiency)
II. Urge urinary incontinence
Definition:
Involuntary leakage of urine preceded by sudden urgency
(overactive bladder)
Etiology:
• Bladder wall irritation: urinary tract infection, bladder
tumors, bladder stones, bladder irritants, e.g., coffee, tea,
and carbonated drinks, even without caffeine, alcohol, car-
bonated drinks, certain acidic fruits, and spicy food
• Neurological diseases: such as multiple sclerosis or
Parkinson’s disease
• Nerve damage: caused by prior surgery or nerve injury
In most cases, no underlying cause is identified,
Evaluation of Urinary Incontinence
History:
Patient • Name, age, menopausal status

demographics
Symptoms • Incontinence with cough, lifting, sneezing,
of stress exercise, laugh, or sex (no preceded by full
incontinence bladder or urgency)
Overactive • Sense of urgency
bladder • Urge incontinence (onset, frequency),
symptoms frequency of urination
• Nighttime frequency (nocturia), nocturnal
enuresis (loss of urine during sleep)
• Amount of water and bladder irritants per day
(coffee, soda, milk, juice, tea)
Voiding • Sense of incomplete emptying

symptoms • Positional voiding or straining with voiding
• Need for perineal splinting (explain) to
complete emptying
• Presence of current urinary tract infection
(UTI)
• History of recurrent UTIs
Prolapse • Sensation of vaginal pressure or bulge
symptoms • Protrusion of tissues/mass through the vagina
Bowel • Frequency per day
symptoms • Presence of constipation, straining, sensation of
stool trapping
• Presence of fecal incontinence
Obstetric • Number of vaginal deliveries
history • History of forceps delivery
Sexual history • Presence of dyspareunia
Medical • Chronic medical conditions
history • Medications that may influence bladder
function, e.g., anticholinergic drugs,
antihistamines, psychotropic drugs, alpha-
adrenergic blockers, alpha-adrenergic agonists,
calcium channel blockers, and diuretics
Surgical • Hysterectomy, prior pelvic or incontinence
history surgery
• Prior abdominal surgeries
Social history • Tobacco smoking (it increases the risk of mesh
erosion “including sling erosion”)
Urinary diary:
Bladder diary should be provided to the patient and be filled
at home over 3–5 days. Urinary diary reports fluid intake,
frequency and amount of urination, urgency, and inconti-
nence accidents. It also includes events associated with
incontinence.
An example is illustrated:
Fluid intake Urine output Activity

prior to
Time Type Amount Times Amount Leak Urge leak
6–7 am Coffee 1 cup 1 200 cc Once No Cough
7–8 am
8–9 am
Examination (office assessment):

• Inspection:
–– Inspection of the urethra:
Urethral diverticulum: urethral diverticulum can
cause postvoid dribbling
Cough stress test:
• How to do it:
–– During pelvic examination, the patient is asked
to cough. If a prolapse is present, it should be
pushed up into normal anatomic position by a
large cotton swab.
–– If the test is negative, it should be repeated in
standing position.
–– If it is still negative despite being reported by
the patient, you may retrograde fill the bladder
with at least 300 mL.
–– If it remains negative despite all these steps,
multichannel urodynamic testing is indicated.
• Interpretation:
–– A test is considered positive if fluid leak from
the urethra is visualized.
–– False-negative test can occur if the bladder is
not full or the urethra is kinked by the presence
of prolapse.
–– False-positive test: urine leak that occurs shortly
but not immediately after cough is a negative
test (cough-induced overactive bladder).
Urethral mobility:
• What is urethral mobility:
Resting angle and displacement angle of urethra-
bladder neck with maximum Valsalva, at least 30°
displacement, are indicative of urethral mobility.
• How to test:
Q-tip test is passed through the urethra during
resting, and the patient is asked to push (Valsalva).
The change in the angle of the cotton swab is
assessed.
• Significance:
–– Urethral mobility is associated with higher success
rate compared to absence of urethral mobility
(1.9-fold increase in midurethral sling failure rate).
–– Patients with lack of urethral mobility may be
candidates for urethral bulking agents.
–– Inspection of the perineum: for extraurethral leakage
“fistula, ectopic ureter,” and vulvar/vaginal atrophy
–– Inspection of the vagina: inspection of the prolapse
(cystocele, rectocele, vault/uterine), inspection of vagi-
nal discharge
• Speculum examination:
Speculum examination is used to assess pelvic organ
prolapse.
• Palpation/bimanual examination (pelvic floor):
–– Pelvic floor tenderness (pelvic floor tension myalgia)
–– Strength of pelvic muscle contraction (Kegel exercise)
• Rectal examination:
–– Assessment of anorectal pathology: e.g., fistula, tumor,
hemorrhoids, or fissure
–– Anal sphincter tone and strength and prior sphincter tears
• Screening neurologic examination:
–– Assessment of mental status
–– Assessment of sensory and motor function of the
perineum and both lower extremities (S2–4)
Postvoid residual urine assessment:

• Patient is asked to void in a measuring hat. The amount of
urine voided is measured. Then, residual volume of urine
in the bladder is assessed either by bladder scan ultra-
sound or via in-and-out catheterization.
• Postvoid residual is considered normal (normal bladder
emptying) if it is less than the volume voided (50% of
total). This volume is typically less than 50–100 cc.
By the end of evaluation, if stress incontinence is the pri-
mary diagnosis, it can be classified to uncomplicated versus
complicated (which needs further evaluation):
Uncomplicated Complicated
History History:
• Isolated stress urinary incontinence • Associated urgency, incomplete
• Absence of recurrent UTI emptying, chronic urinary retention, or
• No prior extensive pelvic surgery continuous leakage
• No prior surgery for incontinence • Recurrent UTI
• Absence of voiding symptoms • Previous extensive or radical pelvic
• Absence of medical condition that surgery
affect urinary function • Prior anti-incontinence or urethral
Examination: surgery
• No vaginal prolapse beyond the
hymen (type I or IIA) • Voiding symptoms
• Urethral mobility • Presence of neurological disease or
Post-void residual urine volume: poorly controlled DM
• <150 ml Examination:
Urine analysis and urine culture: • Vaginal prolapse beyond the hymen,
• Negative result for infection or absent urethral mobility (type IIB, III)
hematuria
Post-void residual volume: >150 ml
Types of stress incontinence
Work-up:
• Urinalysis:
–– UTI should be diagnosed and treated before other
work-up.
–– Clean midstream or catheterized urine sample: if dip-
stick urinalysis is suspicious for infection (nitrites, leu-
kocytes), do urine culture and empiric antibiotic
therapy.
–– If microscopic hematuria is present (3 or more per high

power field in microscopic examination of urine), cys-
toscopy and computed tomography are indicated to
identify the source of bleeding.
• Urodynamic studies:
–– When (indications):
Based on patient demographics:
• Elderly patient with multiple diagnoses
Based on history of present illness/type of
incontinence:
• Unclear diagnosis, e.g., “negative cough stress test
despite clear patient history”
• Significant urge incontinence, acute onset
• Symptoms of urinary retention
• Continuous/total incontinence
Based on medical history:

• Advanced diabetes
• Suspected neurologic disease
Based on surgical history: previous failed inconti-
nence surgery
Based on physical examination:
• Abnormal neurological examination
• High postvoid residual volume
–– How (components):
Cystometry:
This component includes assessment of bladder
(and abdominal) pressure during filling (filling cys-
tometry) and voiding (voiding cystometry) to assess:
1. Bladder sensation
2. Bladder capacity
3. Bladder compliance
4. Presence and magnitude of voluntary and invol-

untary detrusor contractions
Normal values Abnormal
Filling cystometry
• First sensation: volume • Diminished bladder capacity:
at which the patient first overactive bladder
becomes aware of fluid filling • Increased capacity:
(50–200 mL) neurogenic bladder
• Second sensation: volume • Low-compliance bladder
at which the patient reports (rising bladder pressure
urge sensation (200–400 mL) during filling): bladder
• Maximum capacity: patient fibrosis, bladder radiation
is uncomfortable and asks to • Bladder contraction during
stop filling (400–600 mL) filling: contraction amplitude
of 15 cm H2O or more
over baseline is significant
(indicative of overactive
bladder)
Voiding cystometry
• Postvoiding residual volume: • Abnormal if >50–100 mL,
normal if <50–100 mL, <20% >20% of voided volume
of voided volume (retention)
Uroflowmetry:
This component reflects rate and pattern of urine
flow.
• Normal: bell-shaped pattern, maximum flow rate
is at least 15 mL/s.
• Abnormal: flattened prolonged flow due to either
bladder outlet obstruction or decreased detrusor
contractility or intermittent flow.
Urethral pressure profiles:
• Functional urethral length: length of urethra that
has pressure greater than vesical pressure (1–4 cm)
–– Lower urethral pressure indicates poorer conti-
nence outcomes and predicts surgical failure.
• Valsalva leak point pressure: abdominal pressure

at which urinary leak occurs
–– Valsalva leak point pressure less than 60 cm
H2O defines intrinsic sphincteric deficiency.
Electromyography:
This component studies neuromuscular coordina-
tion between pelvic muscles and urethral sphincter
during urination.
• Cystourethroscopy:
–– Indications:
1. Microscopic hematuria
2. Acute onset of urge incontinence
3. Refractory urgency incontinence
4. Recurrent urinary tract infections
5. Suspicion for fistula
Management of Urinary Incontinence
I. Behavioral therapy
• Type of incontinence: it is equally effective in all types

(stress, urgency, or mixed). It can be offered as an initial
noninvasive treatment.
• Effectiveness: It provides 50% reduction in mean inconti-
nence episodes.
Behavioral therapy consists of bladder training, weight
loss, and fluid management:
❶ Bladder training:
• It includes timed voiding to increase the time inter-
val between voiding.
• It is primarily used for treatment of urge incontinence.

However, it can still be used to treat stress urinary
incontinence and mixed urinary incontinence.
• Example of bladder training instructions:
–– Avoid bladder irritants. Drink six to eight glasses
of water daily. When you feel the urge, do three
quick pelvic muscle contractions and set down till
urge resolves.
–– From day 1 to 3, empty your bladder regularly
every 1 hour.
–– From day 4 to 6, empty your bladder every 1.5 hours.
–– From day 7 to 9, empty your bladder every 2 hours.
–– From day 10 to 12, empty your bladder every
2.5 hours.
–– Target interval is 3–3.5 hours.
❷ Weight loss:
• Type of incontinence: stress urinary incontinence.
• Effectiveness: moderate weight loss reduces inconti-
nence episodes by 47% (overweight) and 28%
(obese) within 6 months.
❸ Dietary fluid management:
• Patient is advised to reduce fluid intake (maximum
2 L a day), to reduce caffeine intake, and to reduce
late day drinking.
• Patient is advised to empty bladder frequently when
a restroom is accessible.
II. Physical therapy
Pelvic floor muscle (Kegel) exercise, biofeedback, or elec-

trical stimulation
• Type of incontinence:
It can be effective as a first line for the three types of
incontinence (most effective when initiated under a physi-
cian supervision)
• Effectiveness:
–– Satisfaction rate is 50% after 1 year of treatment.
–– 50% of women eventually end up be undergoing sling
surgery.
III. Pessaries
• Type of incontinence: stress and mixed incontinence

• Effectiveness:
–– Patient satisfaction after 3 months is 63%; when com-
pared to 3-month satisfaction rate of behavioral and
physical therapy (75%), pessary is lower.
–– After 1 year, patient satisfaction rates decreased in both
to 50%.
• Indication:
Patients who wish to avoid surgery, who cannot be
adherent to behavioral physical therapy, or who would
prefer immediate improvement.
IV. Pharmacological therapy
• Type of incontinence: urge incontinence only

Options include antimuscarinic medications, beta-ago-
nists, estrogen therapy, and bladder injection with ona-
botulinumtoxin A.
Side effects and
Drugs Indication Mechanism of action Effectiveness contraindications
288
Antimuscarinic For example, Second line for urge They block bladder Higher continence Dry mouth (most
medications fesoterodine, oxybutynin, incontinence (first M2 and M3 receptors rate – modest effect common cause of
tolterodine, and trospium line after behavioral, causing inhibition of discontinuation), dry
Example: tolterodine physical therapy) involuntary detrusor eyes, constipation,
extended release once contractions delirium in high-risk
daily (4 mg/day) population
Beta-agonists Mirabegron 25–50-mg Second line for urge They stimulate beta-3 Significant symptom This medication is
PO daily incontinence for adrenergic receptors reduction (only short- not recommended
patients who do not in the detrusor muscle term follow-up is among women with
tolerate side effects causing muscle available) severe uncontrolled
of antimuscarinic relaxation hypertension, end-
medications stage renal disease,
and significant liver
impairment
Onabotulinumtoxin A Known as Botox A Third-line treatment Botulinum Similar reduction UTI (33%)
Chapter 8. Urinary Incontinence
Administration is through for urge incontinence toxin inhibits in incontinence Risk of incomplete
cystoscopic injection into presynaptic release episodes to second- emptying requiring
detrusor muscle of acetylcholine line treatment after 6 intermittent
Dose starts with 100 units. at neuromuscular months – higher rate catheterization (5%)
This can increase by 50 junction causing of complete resolution
units up to temporary muscle (27% versus 13%)
paralysis
Estrogen • Systemic estrogen therapy: not effective
• Vaginal estrogen cream: may be associated with some improvement of incontinence
V. Sacral neuromodulation
• Type of incontinence: urge incontinence only

• Indication: third-line treatment in refractory urge inconti-
nence (after failed conservative and pharmacologic
management)
• Procedure: an implanted electric device acts by stimula-
tion of nerves supplying the bladder and pelvic floor. This
stimulation may modulate reflex pathways of bladder to
suppress involuntary bladder contractions.
The procedure is done in two stages:
❶ Step one (trial phase): an electrode is implanted near
the sacral foramen and is connected to an external pulse
generator to determine if symptoms are responsive.
❷ Step two (permanent phase): If patient is satisfied with
outcome (symptoms decrease by at least 50%), the sec-
ond step of the procedure is performed. A permanent
battery is placed and connected to the electrode that is
previously situated close to the sacral nerves.
• Effectiveness: success rate (defined as more than 50% reduc-
tion in incontinence episode) for treating refractory urge
incontinence is 62%. Complete resolution is reported in 26%.
VI. Injection of bulking agents
• Type of incontinence: stress incontinence only.

• Indication: Stress urinary incontinence with:
–– Symptomatic women with no urethral mobility (intrin-
sic sphincter deficiency)
–– If surgery has failed
–– Recurrence after surgery
–– Women who are not candidates for surgery
• Agent: pyrolytic carbon-coated beads and calcium
hydroxylapatite.
• Procedure: the bulking agent is injected transurethrally or

periurethrally around the bladder neck and proximal ure-
thra. Repeated injection may be needed.
• Effectiveness: less effective than surgical procedures;
improvement of symptoms is reported between 63% and
80% after 1 year.
VII. Surgical treatment
• Type of incontinence: stress incontinence only

• Indication:
–– Second line for stress urinary incontinence if conserva-
tive treatment does not improve symptoms.
–– First-line treatment for women declining conservative
treatment.
• Surgical options:
I. Synthetic midurethral mesh slings:
• Indication: standard of care in treatment of stress
urinary incontinence
• Effectiveness:
–– Compared to suburethral fascial slings, it shows
similar effectiveness and less adverse events.
–– Compared to open or laparoscopic colposuspen-
sion, it shows similar effectiveness and less void-
ing dysfunction.
• Approach:
❶ Retropubic sling
❷ Transobturator sling
They are comparable in efficacy and patient
satisfaction. Retropubic sling may be superior to
transobturator sling in repeat sling surgery.
❸ Single-incision mini-slings: this sling does not

pass through the retropubic or obturator spaces.
It may be associated with lower cure rates and
higher rates of reoperation.
• Effectiveness:
Subjective cure rates at 1 and 5 years for retro-
pubic and transobturator slings are comparable
(80–85%).
• Complications:
–– Retropubic sling: is associated with higher risk of
voiding dysfunction, bladder perforation, retro-
pubic vascular injury, and blood loss
–– Transobturator: is associated with higher risk of
postoperative groin pain
–– Both: risk of mesh complications (2%) with both
approaches
II. Autologous fascial bladder neck slings:
• Indications:
–– Severe stress incontinence with absence of ure-
thral mobility because it can be applied under
higher tension compared to synthetic sling (no
risk of erosion).
–– Prior mesh-related complications.
–– Concomitant urethral procedure (e.g., diverticu-
lectomy or fistula repair).
III. Burch colposuspension:
• Principle:
Stitches are placed to attach bladder neck fascia
on each side to the iliopectineal ligaments (Cooper
ligaments).
• Indication: it may be indicated in concomitance
with a primary abdominal surgery, e.g., abdominal
sacrocolpopexy.
• Success rate: 80–90%.
• Management of stress urinary incontinence associated

with pelvic organ prolapse:
Pelvic organ
prolapse with stress
urinary Pelvic organ prolapse without stress urinary
incontinence incontinence
• They coexist in • Patient should be counseled that
80% of cases 40% of women may develop stress
• Management urinary incontinence after pelvic organ
includes prolapse surgery (occult stress urinary
performance of incontinence)
two concomitant • Therefore, women with significant apical
procedures or anterior prolapse should be assessed
for occult stress incontinence. If positive,
consider concomitant incontinence
surgery, e.g., Burch colposuspension, at
the time of abdominal sacrocolpopexy or
retropubic midurethral sling at the time
of vaginal surgery
• This procedure reduces the risk of
postoperative stress incontinence from
49% to 24%
Further Reading
Abrams P, Cardozo L, Fall M, et al. The standardisation of terminol-
ogy of lower urinary tract function: report from the standardi-
sation sub-committee of the International Continence Society.
Neurourol Urodyn. 2002;21:167.
Gormley EA, Lightner DJ, Burgio KL, et al. Diagnosis and treat-
ment of overactive bladder (non-neurogenic) in adults: AUA/
SUFU guideline. J Urol. 2012;188:2455.
Lukacz ES, Santiago-Lastra Y, Albo ME, Brubaker L. Urinary incon-
tinence in women: a review. JAMA. 2017;318:1592.
Nygaard I. Clinical practice. Idiopathic urgency urinary inconti-
nence. N Engl J Med. 2010;363:1156.
Rogers RG. Clinical practice. Urinary stress incontinence in women.
N Engl J Med. 2008;358:1029.
Chapter 9
Pelvic Organ Prolapse
Definitions:
It is the descent of one or more of the genital organs below
their normal position.
Etiology:
• Advancing age:
–– Risk of pelvic organ prolapse increases with age.
–– Menopause increases the risk of pelvic organ prolapse
(atrophy of estrogen-dependent pelvic support).
• Pregnancy and vaginal delivery:
–– Pregnancy: may present a risk factor regardless of the
mode of delivery
–– Young age at the first delivery
–– Increased parity
–– Prolonged second stage of labor
–– Infant birthweight >4,500 g
–– Forceps delivery
–– Unrepaired or poorly repaired perineal tears
• Family history: of pelvic organ prolapse
• Racial predisposition: Hispanic or white race

https://doi.org/10.1007/978-3-030-41128-2_9
294 Chapter 9. Pelvic Organ Prolapse
• Intra-abdominal pressure:
–– Obesity and overweight
–– Chronic constipation
–– Chronic cough
–– Repeated heavy lifting
• Connective tissue disorders: personal and family history
• Prior pelvic surgery
–– Hysterectomy
–– Previous prolapse surgery
Classification:
I. Traditional classificationa
I. Vaginal prolapse
A. Anatomical types of vaginal prolapse
Anterior vaginal wall • Urethrocele: descent of the
prolapse lower third of the vaginal wall
related to the urethra
• Cystocele: descent of the upper
two-thirds of the vaginal wall
related to the bladder base
• Cystourethrocele: complete
anterior vaginal wall prolapse
Posterior vaginal wall • Rectocele: descent of the lower
prolapse third of the vaginal wall related
to the anal canal or descent of
the middle third of the vaginal
wall related to the underlying
rectum
• Enterocele: descent of the
upper third of the vaginal wall
related to the peritoneum of
Douglas pouch and loops of
the intestines
Chapter 9. Pelvic Organ Prolapse 295
Vault prolapse Descent of vaginal vault after

hysterectomy (apical prolapse)
B. Pathophysiological types of vaginal prolapse
Distention (central) cystocele or rectocele
Vaginal wall prolapse caused by attenuation of the vaginal wall
itself
The vaginal wall may appear smooth without rugae
Displacement (paravaginal) cystocele or rectocele
Vaginal wall prolapse caused by loss of the connective tissue
attachment of the lateral vaginal wall to the pelvic side wall
Vaginal rugae are preserved
II. Uterine prolapse (apical prolapse)
First degree Cervical external os descends
below the level of the ischial spine
on straining or standing but not
beyond the hymenal ring
Second degree The cervix (but not the whole
uterus) protrudes beyond the
hymenal ring on straining
“incomplete procidentia”
Third degree The whole uterus protrudes
outside the vulva. The vagina is
completely inverted, and therefore,
enterocele usually present
“complete procidentia”
a
There is no perfect way to completely identify anatomical struc-
tures related to prolapse, e.g., rectocele versus enterocele except
intraoperatively. Therefore, the terms “anterior, posterior, and api-
cal” are broadly used to refer to the anatomical site of prolapse
during physical examination
II. Pelvic Organ Prolapse Quantification (POP-Q)
Prolapse in each segment is measured relative to the

hymen, which is a fixed anatomic landmark. This staging
allows objective description of prolapse for research and
documentation purposes:
Anterior vaginal wall Total vaginal Posterior vaginal wall

points length points
Point Aa An anterior Total vaginal Point Ap A Midline
vaginal wall length posterior
midpoint, (TVL) is vaginal
3 cm the greatest wall, 3 cm
proximal to length of the proximal to
the urethral vagina when the hymenal
meatus prolapse is ring
fully reduced
Point Ba A midpoint Point BP A midpoint
between Aa between
and anterior Ap and
fornix posterior
fornix (cuff)
Apical vaginal points
Point C Edge of the cervix or vaginal cuff
Point D Posterior fornix
Perineal points
gh The genital hiatus (gh): the middle of the urethral
meatus to the posterior hymenal ring
pb The perineal body (pb): the posterior margin of the
genital hiatus to the middle anus
Ba
Bp
Aa
Ap
The Pelvic Organ Prolapse Quantification (POP-Q) Staging

System is made based on these measures:
• Stage 0 Perfect support
• Stage 1 Lowest point is higher than −1 (1 cm above
the hymenal ring)
• Stage 2 Lowest point within 1 cm of the hymenal ring

(between −1 and +1)
• Stage 3 Lowest point >1 cm below the hymenal ring
• Stage 4 Complete prolapse with the lowest point equal
to the total vaginal length
Role of POP-Q examination:
• It provides a validated objective tool to assess anatomical
success of surgery by comparing preoperative and postop-
erative assessment. It is important to realize that anatomi-
cal success may not necessarily reflect symptom
improvement.
• It allows a consistent tool in reporting among gynecologic
providers.
• It allows a consistent tool for reporting follow-up in
women who do not undergo surgery.
Anatomical changes and complications of POP:

• Vagina:
–– Thickening of the vaginal wall due to edema and
congestion.
–– Vaginal mucosa loses its rugae and becomes smooth.
–– Dryness, keratinization, and pigmentation due to exter-
nal exposure.
–– Formation of trophic ulcers: kinking feeding vessels due
to uterine prolapse results in congestion, poor venous
drainage, and ischemia, which chronically results in
ulcer formation. Criteria of trophic ulcer:
Site: the most prolapsing areas of the cervix and the
vagina
Shape: decubitus ulcer of different shapes
Number: single or multiple
Floor: red floor
Size: usually moderate size
Depth: superficial
Base: soft
Edges: clean cut edges
Healing: by reposition, healing starts from
periphery
• The urinary tract:

–– Bladder neck and urethra: a large cystocele may cause
kinking of the urethra and dysuria. In general:
Prolapse and incontinence independently coexist
(80%, pelvic floor and supportive tissue weakness is
a common etiology).
Prolapse may be masked by stress incontinence due
to kinking of urethra (reduction of the prolapse is
needed before cough stress test is performed).
–– The bladder:
The cystocele forms a pouch in which urine may
accumulate and stagnate causing:
Incomplete emptying unless anterior vaginal wall is
splinted
Irritation of the trigone (causing diurnal frequency)
Risk of cystitis (causing diurnal and nocturnal
frequency)
Marked prolapse that may cause retention of urine
–– Ureters:
Kinking of the ureters at the level where it is tra-
versed by the upper part of Mackenrodt’s ligaments in
women with complete procidentia may cause ureteric
obstruction, hydroureter, and hydronephrosis.
Clinical evaluation:
• History:
–– History of present illness:
Assessment of vaginal bulge symptoms: degree of
interference with life quality. Treatment of POP is
guided by patient’s goals.
Assessment of urinary tract dysfunction: inconti-
nence, incomplete emptying.
Assessment of defecatory dysfunction: if there is a his-
tory of straining with bowel movements, laxative use,
fecal incontinence, and incomplete rectal emptying.
Assessment of sexual function: dyspareunia, coital
incontinence, and sexual dysfunction associated with
the onset of prolapse (after exclusion of other possi-
ble causes of dyspareunia).
Symptoms of POP
❶ Bulge symptoms
Bulge symptoms tend to get worse toward the end of the day or
after prolonged standing:
• Pelvic heaviness: which gets worse toward the end of the day
• Vaginal bulge: the patient feels or even sees a bulge outside
the vagina on straining that disappears on lying flat
❷ Urinary symptoms
• Urinary frequency:
– Diurnal frequency: due to residual urine in prolapsing
bladder pouch (incomplete emptying)
– Diurnal and nocturnal: due to bladder irritation and
cystitis
• Sense of incomplete bladder emptying: due to residual
urine. Emptying of the bladder may require positioning
and splinting of the anterior vaginal wall
• Urinary retention: due to urethral kinking
❸ Bowel symptoms
• Incontinence: of flatus, liquid, or solid stool
• Feeling of incomplete emptying: of the rectum. Splinting of
the vagina or perineum may be needed to start or complete
defecation
❹ Sexual symptoms
• Dyspareunia: due to the presence of vaginal mass and
mucosal dryness due to exposure
❺ Pain symptoms
• Chronic pelvic pain: may be caused by pelvic congestion
and anatomical distortion
• Low back pain: due to traction on uterosacral ligaments
• Gynecologic history: history of gynecologic symptoms,

related or unrelated to the prolapse, history of abnormal
pap smear
• Obstetric history: parity, number of vaginal deliveries, and
prior Cesarean deliveries
• Menstrual history: menopausal status and menstrual

symptoms
• Sexual history: sexual activity, history of prior sexual com-
plaints, and their relation to the onset of prolapse
• Medical history: history of chronic medical disorders,
medications including anticoagulants and steroids (inter-
fere with tissue healing specially in mesh-related
procedures)
• Surgical history: history of hysterectomy, salpingo-oopho-
rectomy, prolapse, or incontinence surgery
• Social history: occupation (sedentary or associated with
heavy lifting), alcohol intake, and active smoking (inter-
fere with tissue healing specially in mesh-related
procedures)
Treatment is indicated if prolapse is causing:
❶ Bulge and pressure symptoms
❷ Sexual dysfunction
❸ Lower urinary tract dysfunction
❹ Defecatory dysfunction
However, no intervention is needed unless any of these
symptoms interfere with the patient’s quality of life
–– Inspection:
Inspection of the external genitalia and vaginal epithe-
lium for vaginal atrophy, skin irritation, or ulceration.
Assessment of maximum descent of prolapse in
supine position by spreading the labia while the
patient performs the Valsalva maneuver, repetitive
coughing, or both.
Cough stress test: the patient is asked to cough repeat-
edly to assess associated stress urinary incontinence.
Occult stress urinary incontinence should be excluded
by reducing prolapse while the patient coughs.
Examination may be repeated in standing position if
examination in supine position does not reveal physical
findings consistent with patient symptoms.
–– Palpation:
Assessment of pelvic muscle strength: patient is
asked to “squeeze” her pelvic muscles around exam-
ining fingers. Strength is reported as “absent,”
“weak,” “normal,” or “strong” OR graded between 0
and 5:
• 0 = no contraction
• 1 = flicker with voluntary contractions
• 2 = weak contractions
• 3 = moderate contractions
• 4 = good contractions
• 5 = strong contractions
Assessment of pelvic floor myalgia:
• Upper lateral vaginal wall tenderness (on supine
position): refers to tenderness of the obturator
internus muscle
• Lower lateral vaginal wall tenderness (on supine
position): refers to tenderness of the levator ani
muscle
• Anterior vaginal wall tenderness (on supine posi-
tion): refers to bladder tenderness (e.g., interstitial
cystitis)
–– Bimanual exam:
To rule out adnexal masses
To assess uterine size and mobility
–– Speculum exam:
Examination is done while the patient performs the
Valsalva maneuver, repetitive coughing, or both.
Examination is performed using the whole speculum
first to assess uterine descent. Thereafter, the specu-
lum is split, and one blade is used to examine the
anterior wall by retracting the posterior wall and vice
versa.
Type and stage of prolapse and POP-Q assessment and
staging can be performed during this examination.
• Work-up:
Generally, no additional work-up is necessary prior to
treatment. Additional work-up may be added in the pres-
ence of particular indications:
❶ Postvoid residual urine volume (catheter or ultrasound
scan):
➀ If the lowest point of the prolapse is beyond the
hymen
➁ If the patient reports voiding symptoms
❷ Urinalysis, culture, and microscopy:
➀ If the patient reports lower urinary tract symptoms,
e.g., frequency and urgency
❸ Urodynamic testing:
➀ If there is incontinence associated with stage II to IV
POP
➁ If there is voiding dysfunction
If examination is not consistent with patient symptoms,
consider referral to urogynecology specialist.
• Differential diagnosis (of a mass protruding from the
vagina)
I. Mass from the anterior vaginal wall
❶ Cystocele: the mass appears on standing or strain-
ing. It is central, reducible, and compressible.
❷ Gartner cyst: the mass is anterolateral in the vagina
and incompressible.
❸ Urethral diverticulum: pressure on the mass causes
discharge of urine from the external meatus. The
diagnosis can be confirmed by magnetic resonance
imaging, ultrasound, and cystoscopy.
II. Mass from the posterior vaginal wall
❶ Rectocele: the mass appears on standing or strain-
ing. It is central, reducible, and compressible. During
rectal examination, the examiner’s finger can be felt
within the mass.
❷ Enterocele:
• By vaginal examination: descent of the upper
part of the posterior vaginal wall is suggestive.
An impulse on cough may be seen or felt.
Peristalsis of the intestine may be palpated.
• By rectal examination: the rectum is pushed
backward by the mass.
• By combined vagino-rectal examination: the
small bowel may be felt between the rectum and
the vagina.
❸ Implantation dermoid cyst: it is incompressible.
During rectal examination, the examiner’s finger is
not felt within the mass.
III. Mass from the uterus
❶ Uterine prolapse: the external os is seen in the most
dependent part of the mass.
❷ Congenital elongation of portio-vaginalis of the
cervix: the vaginal vault is at its normal level.
Vaginal fornices are deeper than normal.
❸ Large fibroid polyp: absence of the external os on
the mass. Normal position of the cervix and the
fornices.
❹ Chronic uterine inversion:
• Absence of the external os on the mass.
• The mass is covered by smooth thin endome-
trium. Therefore, it is more reddish and darker
compared to uterine prolapse.
• The uterus cannot be felt per the abdomen.
• Sound can be introduced for a short distance or
not introduced at all.
❺ Vaginal or cervical cancer: the mass is friable,
irregular, and necrotic and bleeds on touch.
Management:
• Conservative management:
–– Reassurance and education:
Data on the progress of POP is limited. However,
patients should be counseled that no or slight prog-
ress may be noted within 1 year.
If the patient is asymptomatic or mildly symptom-
atic, she should be counseled that the objective of
treatment of POP is to improve life quality rather
than to treat a disease or prevent worsening or
complications.
However, education is important, so patients corre-
late any voiding or defecatory dysfunction in the
future to POP and seek medical advice.
–– Lifestyle modification: this may improve some
symptoms:
Defecatory dysfunction: symptoms may improve
with fiber supplementation and osmotic laxatives.
Bulge symptoms:
• Foot elevation while sitting
• Pelvic muscle exercises (Kegel’s exercise) may
improve symptoms or slow POP progression. An
example of Kegel’s exercise is as follows:
–– Exercise is performed three times a day.
–– Each time consists of ten repetitions. Pelvic
floor muscles are tightened, held tight for 5 s,
and then relaxed for 5 s.
–– Local or systemic estrogen: there is limited evidence on
the benefit of estrogen. However, local estrogen may
improve vaginal dryness associated with POP, which
may improve irritation and dyspareunia.
• Vaginal pessary:
–– Indications:
❶ Symptomatic women who want to preserve their fer-
tility or preserve their uteri
❷ Women who decline or who are not a candidate for
surgery
–– Effectiveness: pessary may fit successfully in 92% of

women.
–– Pessary selection: in general, a ring pessary may be
tried first. Gellhorn pessary can be used if a ring pessary
fails. A ring with knob pessary may be used in women
who has associated stress urinary incontinence:
Stage II: ring pessaries are 100% successful.
Stage III: ring pessaries are 71% successful.
Stage IV: Gellhorn pessaries are commonly required
(64%).
–– Pessary care and follow-up:
Women should be taught to remove, clean, and place
their pessary independently. This can be done once
or twice a week. Pessary is cleaned with mild soap
and warm water, and it should be adequately lubri-
cated using water-based lubricants. An annual fol-
low-up visit is recommended by her provider.
If a woman is unable to self-care for her pessary, regu-
lar clinic follow-up is recommended every 3–4 months.
–– Adverse effects:
Local devascularization/erosion (2–9%) due to pres-
sure of the pessary on vaginal walls. It may be treated
by removing the pessary for 2–4 weeks and local
estrogen therapy. A smaller pessary or a different
pessary type may be used thereafter.
Vaginal fistulas are generally rare.
• Surgical management:
–– Indications: women with symptomatic POP whose
symptoms are not relieved by (or who decline) nonsur-
gical treatments
–– Factors affecting surgical option selection:
❶ Presence of urinary, bowel, or sexual dysfunction
❷ Patient’s general health
❸ Patient preference
❹ Surgeon’s expertise
–– Surgical options:
Type of POP Surgical option Indication

Uterine Vaginal hysterectomy, Uterine prolapse
prolapse uterosacral ligament
suspension, and
prophylactic McCall
culdoplasty
Hysteropexy Uterine prolapse (in
women requiring
surgery and declining
hysterectomy)
Vault Abdominal Recurrent cystocele,
prolapse sacrocolpopexy vault prolapse, or
enterocele
Uterosacral ligament Post-hysterectomy vault
suspension prolapse (or at the time
of hysterectomy)
Sacrospinous fixation
Anterior wall Anterior Prolapse of the bladder,
prolapse colporrhaphy urethra, or both
(standard surgery)
Vaginal repair with Because of reported
synthetic mesh mesh-related
or biologic graft complications, these
augmentation procedures are no
longer used
Posterior wall Posterior Rectocele
prolapse colporrhaphy
McCall culdoplasty Enterocele
I. Vaginal approach
• Uterine prolapse:
–– Vaginal hysterectomy with vaginal apex suspension: to
reduce the risk of recurrent POP. This is the standard
vaginal approach for all women interested in preserving
their sexual function, who can tolerate surgery.
–– Obliterative surgeries:
Indication: these surgeries are effective as an alterna-
tive in women with medical comorbidities, who are
not interested in preserving their sexual function.
Effectiveness:
• The procedure is highly effective (objective and
subjective improvement of POP are 98% and
90%, respectively).
• Low incidence of recurrence compared to other
procedures.
Adverse outcomes:
• Low rate of complications compared to other
procedures.
• Regret rate is low (9%) with appropriate patient
selection and counseling.
Types: Le Fort-style partial colpocleisis and total
colpectomy:
Le Fort partial Total colpectomy

colpocleisis
Indication It is performed The procedure is performed
when the uterus is in women who had prior
preserved at the hysterectomy
time of surgery
Procedure A strip of the The entire vaginal epithelium
epithelium from is denuded. Serial sutures are
the anterior and taken to invert the vagina
posterior vaginal
walls is denuded,
and the edges are
sutured together
to create lateral
canals to drain
cervical and
uterine secretions
Le Fort partial Total colpectomy

colpocleisis
Precautions • Normal cervical cytology, HPV testing, and
endometrial biopsy should be reported prior
to surgery (because the uterus is difficult to
access postoperatively)
• Suburethral plication or midurethral sling may
be performed at the time of surgery to reduce
the risk of postoperative stress incontinence
• Perineorrhaphy may be performed at the
time of surgery to reduce the risk of recurrent
posterior vaginal wall prolapse
• Vault prolapse:
Uterosacral ligament Sacrospinous fixation
suspension
Procedure The vaginal apex is The vaginal apex
attached bilaterally is attached to the
to the ipsilateral sacrospinous ligament
uterosacral ligament at one side. The right
or to the plicated ligament is preferred to
uterosacral ligament in avoid dissection around
the midline the sigmoid colon
Outcomes Both procedures are comparable in anatomical
and functional outcomes (approximately 60–65%
success rate after 2 years)
Adverse The risk of serious complications is also
outcomes comparable (approximately 15%)
• Anterior vaginal wall prolapse:

–– Anterior colporrhaphy:
The procedure refers to midline plication of anterior
vaginal wall fibromuscular connective tissue to pre-
vent anterior vaginal wall descent.
This is the standard surgery for anterior vaginal wall
prolapse.
–– Anterior transvaginal mesh repair:
After implementation of synthetic mesh in vaginal
wall repair, FDA, driven by reported complications,
has down-classified vaginal mesh from class II (mod-

erate-risk devices) to class III (high-risk devices) in
2016.
In April 2019, all manufacturers were ordered to stop
producing and marketing transvaginal mesh due to
increasing concerns of safety issues.
• Posterior vaginal wall prolapse:

–– Posterior colporrhaphy: midline plication of the poste-
rior vaginal wall fibromuscular connective tissue.
Tension on the levator ani muscle during repair should
be avoided to minimize postoperative dyspareunia.
–– Perineorrhaphy: in conjugation with posterior colpor-
rhaphy, reattachment of the perineal muscles to the
rectovaginal septum may be performed if perineal
defect is noted.
–– Site-specific repair: as an alternative to posterior col-
porrhaphy, site-specific repair may be performed by
dissecting the vaginal epithelium and exposing the
underlying fibromuscular connective tissue. Repair of
localized defects is performed under guidance by plac-
ing a finger in the rectum to stretch and detect fibro-
muscular connective tissue defects.
II. Abdominal approach
I. Abdominal sacrocolpopexy
• Technique:
–– A synthetic mesh/biologic graft is sutured over the
apex of the vagina anteriorly and posteriorly (lower
ends) and to the anterior longitudinal ligament of
the sacrum (upper end). Therefore, the mesh forms
an inverted Y shape in the sagittal plane.
–– There is no strong evidence on the best surgical
approach:
Open surgery is associated with shorter operative

times compared to minimally invasive surgery.
Minimally invasive surgery is associated with less
blood loss and shorter hospital stay compared to
open surgery.
–– Synthetic mesh is superior to biologic graft (5-year
anatomic cure is 90% versus 60%, respectively). The
FDA warning is limited to transvaginal meshes and
not meshes intended for abdominal sacrocolpopexy
or stress incontinence.
–– However, a biological graft may be considered over
synthetic mesh in patients at high risk of mesh-
related complications, e.g.:
Chronic steroid use
Current smokers
• Indication:
❶ Shortened vaginal length
❷ Intra-abdominal pathology
❸ High risk for recurrent POP. Risk factors include:
–– Age younger than 60 years at diagnosis
–– Advanced POP (stage 3 or 4)
–– BMI > 26
• Complications:
–– Ileus or small bowel obstruction (3%)
–– Thromboembolic phenomena (0.5%)
–– Mesh or suture complications (4%)
–– Significant reoperation rate (10.5%) due to mesh-
related complications (erosion into the vagina, vis-
ceral erosions, and sacral osteitis)
II. Uterus-preserving surgery (hysteropexy)
• Indication: women with advanced uterine prolapse
who want to preserve their uterus
• Technique: a synthetic mesh/biologic graft is sutured to
the cervix (caudal end) and to the anterior longitudinal
ligament (cephalad end). The procedure may be per-

formed through laparoscopy or laparotomy.
• Advantages: hysteropexy is associated with preserva-
tion of the uterus, shorter operative time, and lower
risk of mesh erosion compared to hysterectomy and
sacrocolpopexy.
• Outcomes: data on pregnancy outcome after hystero-
pexy is limited. Similarly, information on efficacy of
this procedure compared to other standard procedures
is scant.
• Intraoperative cystoscopy:
–– Cystoscopy is recommended after completion of the
procedure when surgery is associated with significant
risk of injury to the bladder or ureter to avoid delayed
diagnosis. These procedures include:
❶Suspension of the vaginal apex to the uterosacral
ligaments
❷ Sacrocolpopexy
❸ Anterior colporrhaphy
–– Cystoscopy is performed to survey the bladder and con-
firm urine efflux from ureteral orifices bilaterally.
• Complications of surgery:
–– Native tissue POP surgery:
Bleeding
Urinary tract infection
Voiding dysfunction (usually transient)
Rectovaginal or vesicovaginal fistula
Bladder or ureteral injury
Dyspareunia (15%) due to postoperative vaginal
shortening, narrowing, and change in vaginal anat-
omy and axis. Management includes:
• Vaginal estrogen
• Progressive dilation
• Surgical correction (last option)
Further Reading 313
–– POP surgery with synthetic mesh:

In addition to other complications listed above, patients
are at risk of mesh contracture and erosion into the
vagina, urethra, bladder, and rectum.
• Management of recurrence:
–– Patients should be counseled that postoperative recur-
rence rate is 6–30%.
–– If the patient presents with recurrent POP, she should
be counseled on treatment options:
❶ Conservative and nonsurgical management: may be
recommended in women with minimal symptoms
❷ Anterior/posterior colporrhaphy: may be performed/
repeated if the patient presents with anterior/poste-
rior vaginal wall prolapse, respectively
❸ Abdominal sacrocolpopexy: is an effective option in
women with recurrent apical prolapse
❹ Colpocleisis: may be offered in patients who are not
interested in preserving their sexual function
Further Reading
ACOG Committee on Practice Bulletins—Gynecology. ACOG
Practice Bulletin No. 85: pelvic organ prolapse. Obstet Gynecol.
2007;110:717.
American College of Obstetricians and Gynecologists. Urinary
incontinence in women. Obstet Gynecol. 2005;105:1533.
Bump RC, Mattiasson A, Bø K, et al. The standardization of termi-
nology of female pelvic organ prolapse and pelvic floor dysfunc-
tion. Am J Obstet Gynecol. 1996;175:10.
Burrows LJ, Meyn LA, Walters MD, Weber AM. Pelvic symptoms in
women with pelvic organ prolapse. Obstet Gynecol. 2004;104:982.
Jelovsek JE, Maher C, Barber MD. Pelvic organ prolapse. Lancet.
2007;369:1027.
Maher C, Baessler K. Surgical management of anterior vaginal wall
prolapse: an evidencebased literature review. Int Urogynecol J
Pelvic Floor Dysfunct. 2006;17:195.
Manonai J, Mouritsen L, Palma P, et al. The inter-system associa-

tion between the simplified pelvic organ prolapse quantification
system (S-POP) and the standard pelvic organ prolapse quanti-
fication system (POPQ) in describing pelvic organ prolapse. Int
Urogynecol J. 2011;22:347.
Nygaard IE, McCreery R, Brubaker L, et al. Abdominal
sacrocolpopexy: a comprehensive review. Obstet Gynecol.
2004;104:805.
Chapter 10
Genital Fistulas
Genitourinary Fistuae
A genitourinary fistula is an abnormal connection between
urinary and genital organs:
• Ureteric fistulae: ureterovaginal, ureterouterine, and ure-
terocervical fistulas
• Vesical fistulae: vesicovaginal, vesicouterine, and vesico-
cervical fistulas
• Urethral fistulae: e.g., urethrovaginal fistulas
Vesicovaginal Fistula (VVF)
Definition:
Vesicovaginal fistula is an abnormal connection (fistulous
tract) between the urinary bladder and the vagina
Causes:
• Traumatic fistula: which is either:
–– Obstetric trauma:
Obstetric fistulas are the most common fistulas
among developing countries.

https://doi.org/10.1007/978-3-030-41128-2_10
316 Chapter 10. Genital Fistulas
Obstetric fistulas result from prolonged labor

obstruction (obstructed labor complex), which causes
prolonged tissue compression between fetal head
and pelvic walls, tissue ischemia, and necrosis.
These fistulas become symptomatic 7–10 days after
delivery.
–– Surgical trauma:
These fistulas may occur as a complication of urinary
bladder injury during uterine or vaginal surgery, e.g.,
hysterectomy, anterior colporrhaphy.
–– Direct trauma: a fistulous tract may result from a direct
trauma that involves the bladder and the vagina, e.g.,
falling on sharp objects, fracture of the pelvis.
• Inflammatory fistulas:
These fistulas develop secondary to infectious process
which results in damage to intervening tissues between the
bladder and the vagina, e.g., syphilis, tuberculosis, and lym-
phogranuloma venereum.
• Malignant fistulas:
These fistulas develop due to local spread of a malig-
nant tumor originating from the cervix (most common),
vagina, or the bladder.
• Post-radiation fistulas:
These fistulas develop from local application of radio-
therapy for treatment of cervical or vaginal cancer.
Radiation causes ischemic necrosis and fistulous tract,
which is surrounded by excessive fibrosis. They make take
months to years to present after treatment.
• Congenital fistula: congenital fistulas are very rare.
Genitourinary Fistuae 317
Diagnosis:
I. History
Prior history suggestive of a possible etiology is
suggestive of diagnosis, e.g., recent complicated
delivery, pelvic surgery, irradiation, etc.
II. Symptoms IV. Examination

Incontinence of urine Abdominal examination
Total incontinence: continuous and Evidence of urinary tract infection: suprapubic
complete leakage of urine through the tenderness or renal angle tenderness may warrant
vagina further work-up and treatment
Partial incontinence: when the fistula is Pelvic examination
small or situated high in the bladder, the Inspection:
patient may still be able to retain some The vulva: may appear red, wet, and exfoliated
urine and void voluntarily The vagina: may appear red and wet. Dribbled urine
Patient may describe it as vaginal discharge may be noted
Soreness and itching of the vulva Palpation:
This is secondary to irritation to the vagina If fistula is large: it can be palpated by the
and vulva by continuous urine dribbling examining finger
Suprapubic and flank pain If fistula is small: it may be recognized by the
These symptoms may reflect ascending surrounding fibrosis
lower and upper urinary tract infection Speculum examination:
Pooling of urine at the apex of the vagina may be
III. Differential diagnosis noted
A thorough history should be taken to rule If the fistula is mature, a pin point opening may be
out other causes of urinary incontinence e.g. seen at the vaginal apex, and a tiny metal catheter may
urge incontinence, stress incontinence be passed through the fistulous tract
If the fistula is immature, the involved area appears
as inflamed erythematous vaginal mucosa and
granulation tissue
V. Work-up
Diagnosis of Vesicovaginal fistula
• Double dye test:

–– Value of the test: the test is used to diagnose vesicovagi-
nal or ureterovaginal fistulas.
–– The test: the patient receives oral phenazopyridine
(pyridium) (turns urine orange in the kidneys), and
indigo carmine is instilled into the empty bladder using
a catheter (turns urine blue in bladder). A tampon is
placed inside the vagina and is inspected for staining.
–– Interpretation:
If the tampon becomes blue: vesicovaginal fistula is
suspected.
If the tampon becomes orange: ureterovaginal fistula
is suspected.
• Creatinine in vaginal secretions:
–– If the diagnosis is not clear, pooled fluid/vaginal secre-
tions should be assessed for creatinine level, and serum
creatinine is tested simultaneously.
–– Significantly higher creatinine level in vaginal fluid
(compared to serum creatinine) confirms that collected
fluid is urine.
• Urinalysis and urine culture:
It may be performed to rule out urinary tract infection.
• Urinary imaging:
–– Intravenous pyelography: to rule out ureteric fistula
–– CT cystogram: facilitates visualization of the fistulous
tract
• Cystoscopy:
Cystoscopy helps to visualize the anatomical site of fis-
tulous opening and its relation to ureteric orifices.
Treatment:
I. Preventive management
• Appropriate management of labor: to prevent the scenario

of obstructed labor.
• The bladder should be maintained empty during any pel-
vic surgery.
• Intraoperative diagnosis of bladder injury if suspected (via
retrograde dye filling, cystoscopy).
• Adequate dissection of the bladder from the anterior vagi-
nal wall and vaginal cuff in the correct plane (pubocervico-
vaginal endopelvic fascia) during pelvic surgeries.
• Adequate closure of dead space underneath the anterior

vaginal wall to prevent hematoma formation.
• A Foley catheter should be maintained postoperatively for
7–14 days after repair of any bladder injury.
II. Non-surgical treatment
Spontaneous closure of small fistulae may occur if the

bladder is continuously drained by placing a Foley catheter or
suprapubic catheter. Selection criteria of conservative man-
agement include:
❶ Diagnosis and management are conducted within 7 days
of causative surgery.
❷ Continuous bladder drainage for 4 weeks.
❸ Small fistula (<1 cm).
❹ No associated carcinoma or radiation.
III. Surgical treatment
• Preoperative preparation:
–– Timing of surgery:
Late interval: 8–12 weeks after injury.
Early interval: 4–8 weeks after injury.
This exact timing is controversial. In general, it
should be driven by clinical assessment. Tissue should
be pliable, not infected, and not inflamed before sur-
gery is decided.
One-year interval: this is recommended for radia-
tion-induced fistulas to ensure resolution of tissue
necrosis.
–– Preoperative treatment:
Treatment with local estrogen cream may be consid-
ered, especially in hypoestrogenic conditions (post-
menopausal women, lactating women).
• Surgery:
Treatment is determined by etiology, site, accessibility,
and complexity of VVF.
I. Congenital and traumatic fistulae
Treatment of congenital and traumatic fistulae
Vaginal approach Abdominal approach
It is the standard approach for treatment of single VVF. It

Indications
is associated with minimal blood loss, low rate of
· Inadequate exposure via vaginal
complications, and faster recovery
approach
· The need for concomitant abdominal
surgery
If the fistula is low If high and inaccessible
· Complex VVF (involving other organs,
and accessible (post-hysterectomy) e.g., bowel)
· Ureteric orifices involved by the fistula
Flap splitting Latzko partial Approach
surgery colpocleisis · Transvesical (extraperitoneal) approach
OR
· Intraperitoneal approach
Vaginal cuff excision
Surgery
· O’Conor and Sokol technique
· Vesical autoplasty
· Bladder mucosal autologous grafts
· Flap Splitting surgery: the anterior vaginal wall is incised around the fistula, and the vaginal wall is
dissected from the underlying fascia. Bladder defect is closed in two layers followed by closure of
the vaginal wall
· Latzko partial colpocleisis: The vaginal mucosa is dissected from the fistula in all directions
without excising the fistula. Two layers of sagittal sutures are taken at the raw edges of the fistula
to invert it into the bladder. The vaginal wall is then sutured. The procedure results in shortening
of the vagina (1.5 cm)
· Vaginal cuff excision: The vaginal mucosa is denuded circumferentially around the fistula, and
vaginal cuff scar and the fistulous tract are resected. The bladder is then closed, followed by
pubocervicovaginal fascia, and then the vaginal wall.
· O’onor and Sokol technique: Posterior bladder wall is dissected, and the bladder is bivalved at
the dome, down to the level of the fistula. The fistulous tract is excised. Bladder wall and vaginal
wall are closed in layers
· Vesical autoplasty: A transverse incision is made at the bladder dome. The fistula is excised, and
the vaginal wall is closed. A bladder flap is created to close bladder defect
· Bladder mucosal autologous grafts: Bladder mucosa is denuded at the fistula site and an anterior
bladder mucosal graft is secured to fistula site
II. Post-radiation fistula
Interposition flaps are typically used to insert a viable tis-

sue with intact blood supply between the bladder and vagina
(where blood supply is deficient due to prior radiation):
• Martius (bulbocavernosus muscle) flap
• Full-thickness fasciocutaneous Martius flaps
• Gracilis muscle flap
• Peritoneal flap
III. Malignant fistula
VVF associated with cancer is managed by a diverting

procedure:
• Ileal conduit: implantation of ureters into an isolated loop
of ileum which drains through the abdominal wall
• Ureterocolic implantation: implantation of the ureters into
the sigmoid colon
IV. Inflammatory fistula
Treatment of the underlying infection followed by surgical

closure of the fistula after complete resolution of infected
tissues
• Postoperative care:
–– Bladder drainage:
Low bladder fistula (at trigone or bladder neck): a
large suprapubic catheter may be used for up to 8
weeks.
High bladder fistula (post-hysterectomy):
• Both transurethral and suprapubic catheters may
be inserted.
• Urethral catheter is removed in 1 week.
• Cystogram is performed after 2 weeks to ensure
bladder wall healing.
• Suprapubic catheter can be removed if cystogram
confirm bladder integrity.
–– Postoperative antibiotics:
Prophylactic antibiotics may be given while the
transurethral catheter is in place. Alternatively, anti-
biotics may be given if urinary tract infection is
diagnosed.
Vitamin C may be given to reduce the risk of infec-
tion and formation of bladder stones (through urine
acidification).
–– Postoperative medications:
Estrogen therapy: estrogen therapy enhances tissue
healing in postmenopausal women.
Bladder antispasmodics: medications containing
atropine and hyoscyamine (parasympatholytics) are
recommended to control of postoperative bladder
spasms.
Stool softeners: stool softeners and high-fiber diet
are recommended to avoid straining.
• Causes of recurrence (surgical failure):

Preoperative causes • Preoperative genital or urinary infection
• Preoperative anemia and poor nutritional
status
Intraoperative • Incomplete closure
causes • Excessive trauma to the tissues
• Improper suture material (rapidly
absorbed)
Postoperative • Postoperative hematoma
causes • Blockade of urinary catheter
• Postoperative infection
Vesicouterine fistula (menouria syndrome)
• Definition:
An abnormal connection between the urinary bladder
and the lower uterine segment
• Etiology:
It may be a complication of lower segment Cesarean
delivery (suturing of the bladder to the uterine incision).
• Diagnosis:
–– Clinically, the patient may present with amenorrhea
with cyclic hematuria (menouria).
–– Cystoscopy, hysteroscopy, and hysterography can be
used to visualize the fistula.
• Treatment:
Abdominal closure is performed by dissection of the
uterus from the bladder, primary closure of both organs,
and interposition of an omental flap.
Ureterovaginal Fistula
Definition: It is an abnormal connection between the ureter

and the vagina
Etiology:
• Traumatic:
Less commonly, it may result from as a sequence of
obstructed labor complex with ischemic involvement
of the ureterovesical junction.
More commonly, it results from operative injury dur-
ing Cesarean section or emergency peripartum
hysterectomy.
–– Surgical trauma: e.g., operative injury during abdominal,
vaginal, or radical hysterectomy, anterior colporrhaphy,
or retropubic bladder neck suspension.
–– Direct trauma: e.g., pelvic fracture.
• Post-radiation fistula: e.g., radiotherapy for treatment of
cervical and vaginal carcinoma
• Malignant fistula: e.g., malignant tumor originating from
the cervix, vagina, or bladder
• Congenital fistula: is very rare
Diagnosis:
History of a possible etiology may support diagnosis, e.g.,
recent complicated delivery, pelvic surgery, radiotherapy, etc.
• Clinical diagnosis:
❶ Partial incontinence of urine: total incontinence occurs
when the fistula is bilateral or when the opposite kidney
is non-functioning or absent.
❷ Soreness and itching of the vulva
❸ Symptoms of urinary tract infection
❹ Flank pain, secondary to upper urinary tract infection,

hydroureter, or hydronephrosis (a complication of
fibrosis at the site of the ureteric fistula)
• Work-up:
–– Double dye test: (see before) vaginal tampon turns
orange.
–– Urinalysis and urine culture: it may be performed to
rule out urinary tract infection.
–– Creatinine in vaginal secretions: significantly higher
creatinine level in vaginal fluid compared to serum
creatinine.
–– Intravenous pyelography:
In the presence of ureterovesical fistula, the course
of the ureter is interrupted at the site of the fistula; the
lower end of the ureter is not seen.
–– Cystoscopy:
Ureteric jet is absent from the affected side.
A ureteric catheter stops at the site of the fistula and
cannot reach the renal pelvis.
Treatment:
• Preoperative management: recommendations are similar
to those followed in patients with VVF.
• Surgery:
If the • Ureteroneocystostomy: with the aid of psoas bladder
fistula is hitch. The use of anti-reflux submucosal tunnel is
low controversial
• Reimplantation with Boari flap: reimplantation
of the ureter into a rolled bladder flap is used to
replace the lower ureter if the fistula is higher
If the More complex options are necessary, e.g.,
fistula is transureteroureterostomy, ileo-uretero-cystoplasty
high
• Postoperative management:
Recommendations are similar to those followed in
patients with VVF. Specific recommendations for uretero-
vaginal fistula include:
–– Antibiotics should continue postoperative and while

the stent is in place.
–– Pelvic drain can be removed after 1–2 days (prior to
discharge).
–– Foley catheter is placed for 2 days (to reduce stent-
related reflux).
–– Ureteral stent may be removed after 6 weeks.
–– Urogram may be performed at 3–6 months after stent
removal to rule out ureteric stricture.
Rectovaginal Fistula
Definition: It is an abnormal connection between the rectum
and the vagina.
Etiology:
• Traumatic fistula: due to different types of trauma:
Inadequate repair or incomplete healing of complete
perineal tear
Obstructed labor complex, due to tissue ischemia
and necrosis
–– Surgical trauma: e.g., total hysterectomy or posterior
colporrhaphy
–– Direct trauma: to the perineum and the vagina
• Inflammatory fistula: e.g., syphilis, pelvic abscess, inflam-
matory bowel disease
• Malignant fistula: local spread of malignant tumor of the
cervix, vagina, or rectum
• Post-radiation: radiotherapy for the treatment of cancer of
cervix or vagina
• Congenital fistula: is very rare
Rectovaginal Fistula 327
Diagnosis
History of a possible etiology may support diagnosis, e.g.,
recent complicated delivery, pelvic surgery, radiotherapy, etc.
• Symptoms:
–– Fecal incontinence: loss of voluntary control over the
passage of feces and flatus
Depending on the size of the fistula, patient may
complain of loss of control over flatus, liquid stool or
fecal matter
–– Foul smelling vaginal discharge
–– Vulvar soreness and itching
–– Recurrent urinary tract infection
–– Dyspareunia
–– Site and size of the fistulous tract may be assessed by
digital vaginal and rectal examination. A speculum
examination may be needed to visualize fistulous open-
ing vaginally. Proctoscopy is performed to identify the
level of the fistula. A blunt probe may be passed
through the fistulous opening to delineate the tract if
the fistula is small.
–– During examination, it is important to address any con-
cerning masses or signs of infection that would explain
the etiology specially if history is not clear. A biopsy
may be taken at the time of examination.
• Work-up:
–– Dye test:
It is done by injection of a blue dye, e.g., methylene
blue into the rectum, while a tampon is placed in the
vagina.
Staining on the tampon with blue color is indicative
of a fistula.
–– Contrast study: a vaginogram or a barium enema helps

to delineate the fistulous tract.
–– Abdomen and pelvis CT scan:
It helps to determine the site and size of the fistula.
It helps to identify underlying cause if
undetermined.
–– Pelvic MRI:
It also helps to determine the site of the fistula and
whether other organs are involved.
It helps to determine underlying cause.
–– Anorectal ultrasound:
Anorectal ultrasound helps to determine anal sphinc-
ter structure and integrity if obstetric injury is
suspected.
–– Anorectal manometry:
Anorectal manometry may help to evaluate rectal
sphincter function and facilitate appropriate surgical
plan.
Treatment:
• Preoperative treatment:
–– Antibiotics and local care: are given to control ongoing
infection.
–– Dietary modification: to control symptoms while tis-
sues heal in preparation to surgery or in patients with
radiation-induced fistulas where surgical treatment is
generally challenging.
–– Steroid and antimetabolite therapy: Patients with
inflammatory bowel disease should receive treatment
to control the disease even though this increases the
risk of surgical failure.
–– Mechanical bowel preparation: prior to surgery.
–– Timing of surgery: patient is medically treated for 6–12
weeks to allow tissues to heal. During this period, spon-
taneous healing may occur. Otherwise, surgical treat-
ment should be performed.
Rectovaginal Fistula 329
• Surgery:
Surgical treatment of rectovaginal fistula

According to the location of the fistula
Low fistula High fistula
Transanal/transvaginal repair Transabdominal repair
Inadequate perineal Small fistula with Tissues are Fistula is small and
body intact perineal body unhealthy tissues are healthy
Lawson Tait Bowel resection Division and

operation Low anterior closure of the
Conversion of the
resection and fistula
fistula into a Dissection of the
coloanal
complete perineal rectovaginal septum,
anastomosis
tear which is then division of the fistula,
repaired in layers and closure of rectal
Transanal Vernon-David
and vaginal wall with
advancement flap operation
repair (transvaginal or without omental
A flap is outlined inversion repair) interposition
cephalad to the The fistulous tract is
fistula, the fistula is dissected and inverted
curetted, and the muscle into the rectum. The
layer is closed. The rectal wall and vaginal
flap is used to close wall are closed
the rectal side of the separately
fistula, while the
vaginal opening is left
for drainage
• Postoperative care:
–– Stool softeners: patient should be advised to use stool
softeners with the goal of soft formed bowel move-
ments. Both constipation and diarrhea should be
avoided.
–– Postoperative antibiotic treatment: it may be given for
3–5 days
–– Pelvic rest: sexual and strenuous activity should be
avoided during recovery time.
Female Genital Mutilation
Definition:
Female genital mutilation (FGM) refers to any procedure
that includes partial or total removal of the external female
genitalia without medical indication.
Classification (WHO classification):
Type I Partial or total Type Ia Removal of the

removal of the clitoral hood or
clitoris and/or the prepuce only
prepuce
Type Ib Removal of the
clitoris and the
prepuce
Type II Partial or total Type IIa Removal of the labia
removal of the minora only
clitoris, labia
minora, with or Type IIb Partial or total
without labia removal of the clitoris
majora and the labia minora
Type IIc Partial or total
removal of the
clitoris, the labia
minora, and the labia
majora
Type III The vaginal Type Removal and
orifice is IIIa apposition of the
narrowed by labia minora
cutting and Type Removal and
apposition of the IIIb apposition of the
labia labia majora
Type IV All other procedures performed for nonmedical
purposes, e.g., pricking, piercing, incising, and
cauterization
Female Genital Mutilation 331
Clinical assessment:
• Gynecologic examination:
–– To assess type of FGM
–– To assess if de-infibulation is indicated
–– To assess local complications caused by FGM
• Psychological assessment
• Screening for HIV and hepatitis B and C
Complications:
Immediate complications Long-term complications
• Severe pain • Psychological complications
• Hemorrhage • Recurrent urinary tract infection
• Infection; tetanus or • Epidermal inclusion cysts, e.g.,
sepsis clitoral cysts
• Urine retention • Keloid scar formation
• Injury to nearby • Dyspareunia and sexual
structures dysfunction
Management:
• Gynecologic management:
–– De-infibulation:
Procedure:
• De-infibulation refers to surgical re-opening of
vaginal introitus.
• The procedure may be performed under local
anesthesia in outpatient setting.
Indication: Type III FGM.
Timing: if patient agrees to the procedure after coun-
seling, the procedure should be offered before first
sexual intercourse or before pregnancy.
–– Clitoral reconstruction:
The procedure is not recommended (risk of compli-
cation, no evidence of benefits).
• Obstetric management:
–– Prenatal management:
Pelvic examination to assess if de-infibulation is indi-
cated before delivery
Screening for hepatitis C
–– Intrapartum management:
De-infibulation may be performed during labor
under local anesthesia if indicated or immediately
after a Cesarean delivery.
Any labial lacerations should be managed per rou-
tine standard protocols.
–– Postpartum management:
Postpartum management is similar to management
of all postpartum patients. If indicated de-infibulation is
not performed for any reason, it should be offer to the
patient prior to her next pregnancy.
Further Reading
Birge O, Ozbey EG, Erkan MM, et al. Youssef’s syndrome following
cesarean section. Case Rep Obstet Gynecol. 2015;2015:605325.
Demirci U, Fall M, Göthe S, et al. Urovaginal fistula formation after
gynecological and obstetric surgical procedures: clinical experi-
ences in a Scandinavian series. Scand J Urol. 2013;47:140.
Ezzat M, Ezzat MM, Tran VQ, Aboseif SR. Repair of giant vesico-
vaginal fistulas. J Urol. 2009;181:1184.
Nardos R, Menber B, Browning A. Outcome of obstetric fistula
repair after 10-day versus 14-day Foley catheterization. Int J
Gynaecol Obstet. 2012;118:21.
Saclarides TJ. Rectovaginal fistula. Surg Clin North Am.
2002;82:1261.
Wall LL. Obstetric vesicovaginal fistula as an international public-
health problem. Lancet. 2006;368:1201.
Further Reading 333
Wiskind AK, Thompson JD. Transverse transperineal repair of

rectovaginal fistulas in the lower vagina. Am J Obstet Gynecol.
1992;167:694.
World Health Organization (WHO). Types of female genital muti-
lation. https://www.who.int/sexual-and-reproductive-health/
types-of-female-genital-mutilation
Yip SK, Leung TY. Vesicouterine fistula: an updated review. Int
Urogynecol J Pelvic Floor Dysfunct. 1998;9:252.
Chapter 11
Urodynamic Study
I. Filling and voiding cystometry
• Two pressures should be measured to calculate detrusor

pressure:
–– P ves (vesicle bladder pressure), which is measured by
bladder catheter
–– P abd (abdominal pressure), which is measured by
rectal/vaginal catheter
P det ( detrusor pressure ) = Pves - Pabd

• Filling phase:
–– During filling of the bladder, detrusor pressure should
be zero (detrusor muscle should not show contractions
during filling). Increased detrusor pressure during fill-
ing is indicative of overactive bladder.

https://doi.org/10.1007/978-3-030-41128-2_11
336 Chapter 11. Urodynamic Study
–– During filling, patient is asked to cough. Normally,

abdominal pressure increases, but detrusor pressure
should be zero. Urine flow is observed with coughing to
assess stress incontinence.
Pves
During
filling Pabd
(resting)
Pdet
During Pves
filling
(cough) Pabd
Pdet
• Voiding phase:
During voiding, detrusor pressure is reported. Low detru-
sor pressure is indicative of areflexia, while abnormally
high detrusor pressure is indicative of outflow
obstruction.
• Interpretation of cystometry:
Chapter 11. Urodynamic Study 337
Normal values Abnormal findings

Filling •F
irst sensation: is •L
ow bladder capacity:
cystometry fluid volume at which it may reflect
the patient first is interstitial cystitis,
aware of filling of detrusor overactivity,
the bladder (normal or bladder fibrosis
value = 50–200 mL) •H
igh bladder
•S
econd sensation: capacity: it may
volume at which indicate neurogenic
the patient would bladder, bladder
feel the urge to void outlet obstruction,
(normal value = 200– or abnormal voiding
400 mL) habits
•M
aximum capacity: •L
ow compliance:
fluid volume at which rising bladder pressure
patient experiences during filling is
significant discomfort indicative of chronic
and asks to stop infection or radiation-
filling (normal induced fibrosis
value = 400–600 mL) •B
ladder contraction
•N
ormal compliance: during filling (at least
bladder pressure 15 cm H2O):
does not rise during − I f the patient is
filling asymptomatic
•D
etrusor relaxation: during these
detrusor muscle contractions: their
should not contract clinical value is
during filling uncertain
(amplitude of any − I f contractions
detrusor activity are associated
should not exceed with urgency: they
15 cm H2O) indicate detrusor
overactivity
− If contractions
are associated
with leakage: they
indicate urge urinary
incontinence (UUI)
Voiding Postvoiding residual •P
VR is abnormal if
cystometry volume (PVR) is >50–100 mL (>20%
measured. Normal value of voided volume). It
<50–100 mL (<20% of indicates incomplete
voided volume) emptying
• Example:
The following figure shows a normal cystometry: P ves, P
abd, and P det. Also, no leakage is noticeable with
coughing.
200
Pves
100
0
200
Pabd
100
0
200
Pdet
100
0
Filling phase Cough Voiding
phase
II. Uroflowmetry
• It graphs the pattern of urine flow over time and docu-

ments the rate of urine flow per second:
–– Urine flow rate:
Qmax: refers to maximum flow rate (the maximum
point of the curve). It is normal if >20 cc/s.
Qave: average flow rate (voided volume divided by
the flow time). It should be at least 50% of Qmax.
TQmax: time to maximum flow (time from initiation
of voiding to the point of maximum flow).
–– Flow pattern:
Flow pattern can be one of these shapes:
Continuous smooth: bell-shaped smooth curve is
normal.
Continuous fluctuating: bell-shaped with fluctua-
tions that do not reach baseline.
Intermittent: It is caused by straining or detrusor
sphincter spasm.
Chapter 11. Urodynamic Study 339
• Uroflowmetry is not usually accurate if voided volume is

low (should be >150 mL to validate the test).
Continuous Continuous Intermittent

40 smooth fluctuating
Flow (ml/s)
30
20
10
Q max
0
Uroflowmetry patterns
III. Urethral pressure profile
• Maximum urethral pressure: it is the highest measured

urethral pressure.
• Maximum urethral closure pressure: it is the difference
between maximum urethral pressure and intravesical
pressure.
• Functional urethral length: it represents the length of the
urethra where urethral pressure is higher than intravesical
pressure.
• Leak point pressure: it refers to intravesical pressure at
which urine leakage occurs in the absence of a detrusor
contraction. This pressure is produced by Valsalva or
cough.
IV. Electromyogram
Electromyogram is used to evaluate striated (voluntary)

sphincter contractions during filling and voiding. It may help
to diagnose detrusor–external sphincter dyssynergia.
Sphincter contraction is normally recorded gradually during
filling and at the time of cough/strain to prevent leakage.
Sphincter relaxation should be recorded at the time of

voiding
Further Reading
American College of Obstetricians and Gynecologists. Urinary
incontinence in women. Obstet Gynecol. 2005;105:1533.
Byrne DJ, Stewart PA, Gray BK. The role of urodynamics in female
urinary stress incontinence. Br J Urol. 1987;59:228.
Chaliha C, Digesu GA, Hutchings A, Khullar V. Changes in urethral
function with bladder filling in the presence of urodynamic stress
incontinence and detrusor overactivity. Am J Obstet Gynecol.
2005;192:60.
Glazener CM, Lapitan MC. Urodynamic investigations for manage-
ment of urinary incontinence in children and adults. Cochrane
Database Syst Rev. 2002;3:CD003195.
Part III
Reproductive Endocrinology
and Infertility
Chapter 12
Infertility
Definitions:
• Infertility: failure of conception after 1 year (for women
under 35 years old) or 6 months (for women 35 years and
older) of regular intercourse without use of contraception
–– Primary infertility: infertility with no prior history of
conception
–– Secondary infertility: infertility after one or more previ-
ous pregnancies
• Fecundability: refers to the possibility of a live birth per
single cycle:
–– 50% of couples conceive within 3 months of trying.
Therefore, diagnosis of infertility is typically made after 12
months.
• Subfertility:
–– Subfertility refers to couples who may conceive without
intervention if given enough time beyond 12 months.
–– Subfertility may represent 50% of couples diagnosed
with infertility.
Incidence: 10–15% of couples trying to conceive

https://doi.org/10.1007/978-3-030-41128-2_12
344 Chapter 12. Infertility
Evaluation of an infertile couple:

• When to initiate evaluation of infertile couple:
–– If the patient is younger than 35 years: start evaluation
after 1 year of trying to conceive. However, earlier
evaluation is indicated in:
❶ Women who have anovulatory cycles
❷ Women with a history of severe pelvic inflammatory
disease (PID)
–– If the patient is 35 years or older: offer evaluation after
6 months
• How to evaluate an infertile couple:
I. History
Male partner Female partner

Pubertal History of pubertal History of pubertal
history development and development and pubertal
pubertal abnormalities abnormalities
Menstrual • Regularity and frequency
history of menstrual cycle
• Intermenstrual pain and
bleeding
• Dysmenorrhea and
pelvic pain
Obstetric Prior conception with Events of prior conception
history another partner should be discussed in
women with secondary
infertility
Sexual • History of erectile • History of female
history dysfunction and other sexual dysfunction and
sexual issues dyspareunia
• History of sexually • History of sexually
transmitted diseases transmitted diseases
(obstruction of and pelvic inflammatory
vas deferens may disease (which may result
complicate epididymitis) in tubal factor infertility)
Chapter 12. Infertility 345

Medical • History of chronic • History of chronic
history diseases: hypertension, diseases: e.g.,
diabetes mellitus, and hypertension, diabetes
neurologic disorders mellitus, thyroid, renal,
may be associated and liver diseases
with male sexual (ovulatory dysfunction)
dysfunction • History of gynecologic
• Treatment history: disorders: e.g.,
– Cimetidine, endometriosis, fibroids
erythromycin, • Treatment history:
gentamicin, – Hyperprolactinemia-
tetracycline, and inducing medications
spironolactone – Chemotherapy
– Anabolic steroids – Pelvic radiation
– Chemotherapy therapy
– Radiation therapy
Surgical • Cryptorchidism • History of pelvic and
history • Testicular torsion abdominal surgeries
• Testicular trauma • History of uterine
• Varicocele surgeries
Social History of smoking, History of smoking,
history alcohol, use of illicit alcohol, use of illicit drugs,
drugs, and exposure to and excessive caffeine
environmental toxins intake
Family • Family history of • Family history of
history infertility infertility
• Family history of • Family history of
cystic fibrosis recurrent miscarriage or
fetal anomalies
• Family history of
polycystic ovary
syndrome or
endometriosis
• Family history of
premature ovarian
failure
Physical examination is directed by history taking, and it may

be performed according to positive history findings:

General • Assessment of • Assessment of
examination development of development of
secondary sexual secondary sexual
characteristics characteristics
• Presence of • Assessment of signs of
gynecomastia hyperandrogenism
or eunuchoid • Thyroid examination
habitus in patients
with Klinefelter
syndrome (47
XXY)
Pelvic • Penile urethra: is Difficult/painful
examination assessed to rule out examination is concerning
hypospadias of dyspareunia/infrequent
• Testes: assessment intercourse
of testicular growth • Vagina: dryness and
(normal length is atrophy are concerning
4 cm) for premature ovarian
• Epididymis: it failure
should palpate soft • Uterus: enlarged
and painless uterus/irregular uterine
• Pampiniform contour may present
plexus of veins: it is leiomyomas. Immobile
palpated to rule out uterus may reflect
varicocele pelvic adhesions
• Vas deferens: it is • Tubes and pelvis:
palpated to rule out Douglas pouch
congenital absence nodularity or ovarian
masses may be signs of
endometriosis
Male Factor Infertility 347
III. Work-up
Semen analysis should be included in the initial work-up. It is

a simple test that satisfactorily rules out male factor infertility
prior to assessing female partner. Female infertility assess-
ment is more sophisticated and is directed based on clinical
assessment.
Male Factor Infertility

Incidence: 45% of cases of infertility
Etiology:
Etiology of male factor infertility

Pretesticular causes
• Chromosomal cause:
for example, Klinefelter
syndrome
• Hypothalamic Testicular causes
disorders: for example, • Congenital causes:
isolated GnRH deficiency, for example, anorchidism,
Kallmann syndrome Post-testicular causes
cryptorchidism
• Semen passage defect:
• Pituitary dysfunction: • Infectious causes: Bilateral obstruction of
for example, prolactin for example, mumps virus epididymes, vas deferens,
secreting tumor) • Structural causes: or ejaculatory ducts, which
• Thyroid dysfunction varicocele, hydrocele, can be:
• Chronic liver and renal and testicular torsion.
Congenital
diseases • Environmental factors: Post-Infectious
• Adrenal dysfunction: for example, heat
Iatrogenic, for example, a
for example, exposure, irradiation,
complication of
adrenogenital syndrome illicit drugs
herniorrhaphy
and congenital Adrenal • Immunological factors:
hyperplasia for example, anti-sperm • Semen deposition defect:
antibodies Erectile dysfunction
Hypospadias
Premature ejaculation
Retrograde ejaculation
Diagnosis:
• History and examination: discussed before
• Work-up:
I. Semen analysis
• Test prerequisites:
–– Period of abstinence: 2–3 days prior to sample
collection.
–– Method of collection:
Clean glass container (masturbation)
Silastic condoms without lubricants (intercourse)
–– Collection-to-test time: a sample should be delivered to
the lab within an hour of ejaculation.
• Semen parameters:
Summary of
WHO Criteria
Parameter Normal Abnormal 2010
❶ Physical parameters
Ejaculate 1.5–6 mL Hypospermia: • Ejaculate

volume volume less than volume: lower
1.5 mL limit is 1.5 mL
Aspermia: zero • Semen pH:
volume lower limit
is 7.2
Appearance Opalescent white Other colors
pH 7.2–7.8 (alkaline) Acidic pH
Liquefaction 5–20 min (action of Liquefaction

prostatic enzymes) after 30 min is
called delayed
liquefaction
Male Factor Infertility 349
Summary of
WHO Criteria
❷ Microscopic parameters
Sperm 15–200 million/mL Oligospermia: less • Concentration:

count (total sperm number than 15 million/ 15 million/mL
is 39 million/ mL (<5 million is • Total sperm
ejaculate) considered severe number:
oligospermia) 39 million/
Azoospermia: ejaculate
no sperms per • Total motility:
ejaculate 40% (or 32%
for progressive
motility)
• Sperm vitality:
58% live sperms
• Sperm
morphology: 4%
normal forms
Viability 58% at least are Necrospermia:

living less than 58%
viable sperms
Morphology 4% at least are of Teratospermia:

normal morphology less than 4% of
normal forms
Motility At least 40% are Asthenospermia:

motile within the 1st less than 40% of
hour (Grade A + B) sperms are motile
OR at least 32% The hypoosmotic
are actively motile swelling test:
(grade A) this test can
Motility grades differentiate
Grade A: progressive nonviable from
motility non-motile
Grade B: move sperm. Exposing
forward but in a the sample to
curved or crooked hypoosmotic
motion medium, only
Grade C: non-motile viable
nonprogressive sperms swell
motility, (tail
movement)
Grade D: immotile
Summary of
WHO Criteria
Other WBCs < 1 million/ Leukocytospermia:
elements mL WBCs > 1 million/
Round cells mL
(leukocytes or
immature sperm)
< 5 million/mL
❸ Chemical parameters
Fructose 120–240 mg/mL Low fructose or
low prostaglandin
content of
the seminal
fluid (fructose
is essential
for sperm
metabolism;
prostaglandins
are essential for
sperm motility)
II. Hormonal profile
• Indication: hormonal testing may be indicated if a sperm

concentration is less than 10 million/mL.
• Tests:
Serum FSH and • High FSH and low testosterone: indicated
testosterone testicular failure
• Low FSH and low testosterone: they are
consistent with hypothalamic/pituitary
dysfunction
Prolactin and Elevated prolactin level and abnormal TSH:
TSH hyperlactatemia and thyroid dysfunction may
impact spermatogenesis
Female Factor Infertility 351
III. Imaging
• Scrotal ultrasound: it helps to diagnose structural local

abnormalities.
• Vasography: it helps to diagnose vasal obstruction.
IV. Genetic testing of the male
• Indications: azoospermia and severe oligospermia

• Possible abnormal results:
❶ Klinefelter syndrome (47 XXY)
❷ Microdeletion of the Y chromosome
❸ Mutations in the CFTR (cystic fibrosis) gene: which is asso-
ciated with congenital bilateral absence of the vas deferens
V. Testicular biopsy
• Indication: severe oligospermia or azoospermia.

• Significance: if sperms are retrieved from testicular biopsy
(testicular sperm extraction), they may be used for intracy-
toplasmic sperm injection.
Treatment:
Refer to an andrology specialist for further management and
follow-up.
Female Factor Infertility
Tubal Factor
Incidence: 30–40% of female infertility
Etiology:
• Inflammatory: (PID)
–– Causative organisms:
Sexually transmitted organisms: e.g., chlamydial
infection, gonococcal infection
Non-specific organisms: e.g., staphylococci, strepto-
cocci, E. coli
–– Route of infection:
Sexually transmitted infection
Ascending infection: e.g., post-abortion, postpartum,
or post-uterine procedure infection
Spread from the surrounding structures: e.g., appendi-
citis or diverticulitis
• Surgical/traumatic: e.g., bilateral salpingectomy and post-
operative adhesions
• Neoplastic: tubal distortion or blockade by pelvic masses,
e.g., uterine leiomyomas
• Congenital: e.g., congenital long and narrow tubes and
failure of canalization
Diagnosis:
• History: full infertility history should be taken (see under:
How to evaluate an infertile couple). Tubal factor infertil-
ity should be suspected if:
–– There is history of chronic pelvic pain or severe dys-
menorrhea (endometriosis)
–– History of PID (Fallopian tube damage, pelvic adhesions)
–– History of pelvic or abdominal major surgery (postop-
erative adhesions)
Unknown abdominal scars and signs of pelvic infection
should be investigated.
• Work-up:
Evaluation of tubal patency may be performed using
hysterosalpingography or hysterosalpingo-contrast sonog-
raphy. Tubal patency may be evaluated as a part of laparos-
copy and hysteroscopy performed for other indications:
❶ Hysterosalpingography (HSG)
Definition
It is a contrast X-ray film of the female genital tract (the uterus
and the tubes)
Procedure
The procedure involves injection of a radio opaque dye
(urographin) through the cervix followed by pelvic X-ray to
visualize the uterine cavity and the Fallopian tubes
Timing
The test should ideally be done on cycle day 5–12 (follicular
phase), so it does not disrupt a possible early pregnancy. The
procedure is contraindicated in women with pelvic infection
Findings
• Normal findings:
–– Cervix: smooth or serrated cervical lining, not distorted
–– Uterus: smooth lining, triangular or T-shaped, single
cavity with no filling defect
–– Tubes: 8–13 cm in length, visualized throughout the
whole length, with no abnormal tubal dilation (e.g.,
hydrosalpinx). The dye spills distally through tubal ostia
into the pelvis
–– Pelvis: homogenous spill of the dye in the pelvis
• Abnormal findings:
–– Tubal obstruction either proximal (tubes are not visual-
ized at all) or distal (absence of tubal spillage) with or
without significant tubal dilation (hydrosalpinx)
–– Uterine filling defects (e.g., fibroids, polyps, adhesions)
or abnormal cavity (e.g., uterine anomalies)
–– Localization of pelvic spillage may suggest pelvic
adhesions
Advantages
• Diagnostic:
–– It diagnoses tubal obstruction and determines laterality
and site of tubal block
–– It assesses integrity of uterine cavity at the same time
• Therapeutic: occasionally, HSG may improve tubal patency
and pregnancy may occur following the procedure
➋ Hysterosalpingo-contrast sonography
Procedure
• After transcervical injection of echogenic contrast media
(e.g., saline), transvaginal ultrasound is performed to
visualize the distended uterus and tubes and to assess
Douglas pouch
Findings
• The uterus should distend adequately and without
difficulty. The uterine cavity should appear elliptically
uniform and smooth
• Passage of fluid to Douglas pouch indicates tubal patency.
However, it does not indicate whether patency is bilateral
or unilateral
Advantages
• Quick, easy, safe, and well-tolerated compared to HSG
• Diagnostic performance for diagnosis of tubal occlusion is
comparable to HSG (92% sensitivity and 95% specificity)
➌ Diagnostic laparoscopy and chromopertubation
Indications
Diagnostic laparoscopy may be performed if:
• HSG findings are abnormal
• Suspected endometriosis
Procedure
After laparoscopy is used to evaluate the uterus, tubes, and
pelvis, a dye (diluted indigo carmine solution) is injected into
the uterus and tubes through the cervix. Spillage of the dye
out from the fimbrial ends on both sides is an indication of
structural patency
➍ Hysteroscopy
If hysteroscopy is performed for another indication, visu-
alization of tubal ostia on both sides should be documented.
Treatment:
I. Prevention
➊P revention of infection: e.g., protection against STDs, asep-

tic measures and antibiotic prophylaxis during D&C, and
immediate diagnosis and adequate treatment of PID per
protocol
➋ Minimizing postoperative adhesions:
➀ Surgical technique: to reduce risk of adhesions, surgical
technique should include gentle tissue handling and
proper hemostasis.
➁ Infection control during surgery: sterile technique and
use of prophylactic antibiotics.
➂ Use of tissue barriers: there is no evidence that placing
an inert substance to prevent formation of adhesions
improves pain or fertility outcomes among women
undergoing pelvic surgery.
II. Treatment of tubal factor infertility
➊ Surgical intervention:
➀ Microsurgical or laparoscopic tuboplasty:
Tubal reconstruction is not commonly offered. It is
associated with low success rate and high risk of ectopic
pregnancy. Most common types of tuboplasty are rever-
sal of tubal sterilization, adhesiolysis of peritubal adhe-
sions, and fimbriolysis.
Site of
tubal Prognostic Ectopic Pregnancy
block Surgery factors risk rate
Distal tubal • Fimbrioplasty: • Fimbrial 12% 25–50%
obstruction repair of status (depends on
partially • Severity severity of
occluded of adhesions)
fimbria adhesions
• Fimbriolysis:
lysis of
fimbrial
adhesions
Mid- Resection and • Postop- 1–7% 50–80%
segmental end-to-end erative (depends
(sterilization) anastomosis tubal on proper
(sterilization length patient
reversal) (>3–4 cm) selection)
• Site
(ampul-
lary or
ischemic)
Proximal • Hystero- Extent of 7–12% 55% fol-
obstruction scopic- or obstruction lowing
fluoroscopic- microsurgi-
guided proxi- cal resection
mal tubal and reanas-
cannulation tomosis
• Microsurgical 50–85%
resection and (following
reanastomosis proximal
tubal
cannulation)
➁ Salpingectomy:
• In the presence of hydrosalpinx, women undergoing
IVF should undergo laparoscopic salpingectomy to
improve the outcomes of IVF treatment compared to
no surgical intervention.
• The rationale of this procedure is to prevent proximal

release of tubal fluid into the uterus, thus preventing
embryotoxic substance or washout effect of this fluid
from disrupting implantation.
➂ Excision of endometriosis:
Surgical resection of endometriosis, ovulation induc-
tion plus intrauterine insemination, and assisted repro-
ductive technologies are stepwise approaches for
treatment of endometriosis-related infertility (see
under: Endometriosis).
➋ Assisted reproductive technology (ART):
ART is the conventional management of tubal factor
infertility particularly if tubal block is bilateral or if other
treatment options fail.
Ovarian Factor
Incidence:
30–40% of female infertility
Etiology (causes of anovulation):

➊ Physiological causes:
• Before puberty and few years after
• During pregnancy and lactation
• Peri- and postmenopause
➋ Pathological causes:
➀ General causes:
• Severe anemia, malnutrition, obesity, and vigorous
exercise
• Chronic diseases, e.g., chronic liver disease and
chronic renal disease
• Hyperprolactinemia
• Thyroid dysfunction: hypo- and hyperthyroidism
• Adrenal dysfunction, e.g., Addison’s disease, Cushing’s
syndrome, and adrenogenital syndrome
➁ Hypothalamic causes:
• Head trauma
• Brain tumors (craniopharyngioma)
• Anorexia nervosa
• Kallmann syndrome
➂ Pituitary causes:
• Pituitary tumors, e.g., prolactinoma
• Empty sella syndrome
• Simmonds disease
• Sheehan syndrome
➃ Ovarian causes:
• Polycystic ovary syndrome (PCOS)
• Premature ovarian failure (POF)
• Resistant ovary syndrome
• Gonadal dysgenesis (e.g., Turner syndrome)
• Luteinized unruptured follicle (LUF)
Classification of anovulation – WHO classification:

WHO class 1 Hypogonadotropic hypogonadal anovulation
(hypothalamic-pituitary)
WHO class 2 Normo-gonadotropic normo-estrogenic
anovulation
(e.g., PCOS)
WHO class 3 Hypergonadotropic hypoestrogenic
anovulation
(e.g., POF)
Hyperprolactinemia Anovulation is caused by hyperprolactinemia
Diagnosis of ovarian factor infertility (ovulatory

dysfunction):
• History:
–– Menstrual disorders:
Women with normal ovulatory cycles report regular
menstrual rhythm (every 25–35 days) associated with
premenstrual symptoms. They may also report pri-
mary dysmenorrhea and intermenstrual pain, bleed-
ing, and discharge.
Women with ovulatory dysfunction may present with
amenorrhea, infrequent menstrual cycles, or irregu-
lar uterine bleeding.
–– Infertility: women with anovulation may present with
infertility issues.
–– PCOS-related symptoms: in addition to menstrual dis-
orders, patients may present with symptoms of hyperan-
drogenism, e.g., hirsutism and acne.
–– Menopausal symptoms: amenorrhea and infrequent
cycles along with hot flushes, night sweats, vaginal dry-
ness, mood and concentration concerns, and decreased
sexual desire in women younger than 40 are concerns of
premature ovarian failure
–– Positive medical history: e.g., chronic renal or liver dis-
eases and thyroid disorders.
During physical examination, the following signs may
be suggestive of ovarian factor infertility:
–– High body mass index
–– Acanthosis nigricans, hirsutism, and acne
–– Thyroid enlargement
• Work-up:
I. Work-up for diagnosis of anovulation
➊ Mid-luteal serum progesterone:

• Test: serum progesterone is tested on cycle day number
21 following the first day of menstrual bleeding, or 7
days following anticipated date of ovulation.
• Result:
–– Serum progesterone ≤ 3 ng/mL is associated with
non-ovulatory cycles.
–– Serum progesterone > 3 ng/mL indicates ovulation.
There is no progesterone level that can be used to
make the diagnosis of luteal phase defect.
• Limitations: the test assesses progesterone secretion,
which may be normal despite anovulation in patients
with LUF.
➋ Ovulation predictor kits (LH kits):
Urinary ovulation predictor kits measure the concen-
tration of urinary LH by colorimetric assay. In most
instances, ovulation will occur the day following the uri-
nary LH peak.
• Disadvantages: 5–10% false-positive and false-negative
rates
➌ Ultrasound monitoring:
Ultrasound monitoring is not a screening test of ovula-
tion. It may be used to monitor ovulation during ovulation
induction particularly in unresponsive patients. Monitoring
includes:
➀ Serial follow-up of follicular development: ovulation is
likely to occur if preovulatory follicle(s) exceed l8 mm.
➁ Signs of ovulation: ultrasound signs of ovulation include:
• Reduction in the size of the dominant follicle by >1/3
of its original size
• Free fluid in Douglas pouch

• Formation of corpus luteum (in ultrasound, corpus
luteum is characterized by internal echoes and cren-
ulated inner margin. Using Doppler mode, periph-
eral vascularity around corpus luteum appears as a
“ring of fire”)
➂ Findings associated with ovulation dysfunction, e.g.,
inadequate follicular growth, PCOS, and LUF.
II. Work-up for assessment of ovarian reserve
• Indications:
➊ Women above 35 years
➋ Any woman with a history of ovarian surgery, chemo-
therapy, or irradiation
➌ Poor response to gonadotropins
➍ Family history of early menopause
➎ As a part of evaluation prior to IVF
• Tests:
➊ Anti-Müllerian hormone (AMH):
–– Principle: AMH is secreted continuously by preantral
and early antral follicles. Therefore, it reflects the size
of the primordial follicle pool regardless of cycle day.
–– Advantages:
➀ AMH is an early and direct indicator of ovarian
reserve.
➁ The test can be performed at any day of the cycle.
–– Clinical value:
Diagnosis of diminished ovarian reserve, which
may change management plan.
AMH is an indicator of ovarian response and
number of retrieved oocytes during IVF cycles.
Therefore, it is used to counsel patients before the
decision of IVF is made.
AMH < 1.0 ng/mL: it indicates diminished ovarian
reserve and limited number of retrieved eggs dur-
ing IVF cycle.
AMH > 1.0 ng/mL but <3.5 ng/mL: it presents the
normal range and indicates good response to
ovarian stimulation.
AMH > 3.5 ng/mL: it predicts exaggerated
response to ovarian stimulation. Therefore, atten-
tion should be paid to avoid ovarian hyperstimu-
lation syndrome.
➋ Antral follicle count (AFC):
–– Principle:
Transvaginal ultrasound is performed at cycle day
3 to count the total number of antral follicles
(2–10 mm) in both ovaries.
Diminished ovarian reserve is diagnosed if less
than five to seven follicles are visualized in both
ovaries. This number is associated with poor
response to ovarian stimulation. However, it is a
poor predictor of pregnancy rate.
Women with PCOS may have elevated AFC.
Women using hormonal contraceptives and
women with hypothalamic disorders may have
diminished AFC.
➌ Day 3 FSH concentration:
Day 3 serum FSH > 10 mIU/mL indicates diminished
ovarian reserve.
➍ Day 3 serum estradiol:
–– Day 3 estradiol is not a reliable test of ovarian
reserve. If basal FSH is normal, elevated estradiol
(>60–80 pg/mL) is of limited clinical value.
–– Day 3 estradiol is tested along with serum FSH to
facilitate correct interpretation of FSH results. An
elevated estradiol level may result in decline of an

otherwise elevated FSH to a normal level. Therefore,
measurement of FSH alone may be misleading.
➎ Clomiphene citrate challenge test:
–– Test: 100 mg of clomiphene citrate is given from
cycle day numbers 5–9. Estradiol and FSH are mea-
sured on day 3, and FSH is measured on day 10.
–– Result: elevation of FSH at either day 3 or day 10
indicates diminished ovarian reserve. This test is less
commonly used nowadays given the availability of
simple and reliable tests.
III. Work-up for diagnosis of underlying etiology
➊ Serum FSH:
Serum FSH > 40 mIU/mL indicates ovarian failure.
Premature ovarian failure is defined as ovarian failure prior
to the age of 40. Further work-up is indicated in women with
premature ovarian failure to identify underlying causes:
–– Fragile X carrier screening: to identify FMR1 premutation
–– Karyotyping: Turner syndrome (45XO)
–– Autoimmune disorders, e.g., Addison’s disease and
autoimmune hypothyroidism
➋ Serum prolactin: to rule out hyperprolactinemia
➌ Thyroid function test: to rule out thyroid dysfunction
➍ Serum 17-OH progesterone: increased in adult onset adre-
nal hyperplasia
➎ Serum androgens:
–– Serum total testosterone: it increases in patients with
PCOS. Significant increase may indicate virilizing ovar-
ian tumors.
–– Serum DHEAS: it may be indicated in patients with
acute or severe virilizing symptoms to rule out adrenal
tumors.
Treatment:
I. General treatment
• Weight loss and lifestyle modification in obese patients

• Correction of malnutrition and anemia if present
• Smoking cessation and reduction of alcohol and excess
caffeine intake
• Treatment of the cause:
–– Psychotherapy, e.g., anorexia nervosa
–– Treatment of hyperprolactinemia, e.g., cabergoline
–– Treatment of thyroid dysfunction, e.g., thyroid replace-
ment for hypothyroidism
II. Further management depends on patient presentation/

concern
I. No desire of fertility
• Patients with abnormal uterine bleeding: in addition to

treatment of the cause, hormonal treatment may be con-
sidered, e.g., cyclic progestogens and combined oral con-
traceptives (see under: Menstrual disorders)
• Patients with hirsutism: combined oral contraceptives,
antiandrogen drugs, and dermatological consultation (see
under: Polycystic ovary syndrome)
II. Desire of fertility
• Induction of ovulation:
–– Types of induction:
➊ Ovulation induction:
Ovulation induction refers to stimulation of ovula-
tion in patients with infertility due to ovulatory dys-
function, e.g., PCOS.
➋S uperovulation or controlled ovarian hyperstimula-
tion:
Superovulation refers to medical enhancement of
current ovulation to produce multiple eggs in the same
cycle to increase the likelihood of pregnancy in women
with normal ovulation who have other causes of infer-
tility, women with unexplained infertility, or women
undergoing IVF cycle.
–– Methods of induction: according to WHO classification
Line of
Type Definition management
WHO class 1 Hypogonadotropic Pulsatile GnRH or
hypogonadal gonadotropins
anovulation
(hypothalamic-
pituitary causes)
WHO class 2 Normo-gonadotropic Clomiphene,
normo-estrogenic letrozole or
anovulation (e.g., gonadotropins
PCOS)
WHO class 3 Hypergonadotropic Third-party
hypoestrogenic reproductive
anovulation (e.g., options (egg
POF) donation)
Hyperprolactinemia Anovulation due to Dopamine
high prolactin level agonists (e.g.,
cabergoline)
➊ Clomiphene citrate (CC):

Mechanism of action:
CC is a selective estrogen receptor modulator
(SERM) that acts as a competitive inhibitor of
endogenous estrogen at hypothalamic receptors,
thus decreasing negative feedback on the hypo-
thalamus and increasing GnRH pulsatile
secretion.
Induction regimen:
• CC is given orally, from the third to fifth day
of the cycle (either after spontaneous or pro-
gestin-induced menstruation), beginning with
a single 50 mg tablet daily for five consecu-
tive days.
• Ovulation is monitored (e.g., serum proges-
terone, sonographic monitoring).
• If ovulation does not occur, the dose is
increased by 50 mg in subsequent cycles until
ovulation is induced (100 mg is the maximum
dose approved by the FDA).
• The minimal effective dose is maintained for
six cycles.
Contraindications to CC:
• Pregnancy (CC is classified as category X)
• Ovarian cyst
• Liver disease
• Undiagnosed vaginal bleeding
• Intracranial lesion (e.g., pituitary tumor)
Side effects and complications:
• Ovarian hyperstimulation syndrome
• Multifetal pregnancy (incidence of twin preg-
nancy is 5–12% of all pregnancies; triplet and
higher-order pregnancy occurs in <1% of all
pregnancies)
• Nausea, vomiting, blurring of vision, head-
ache, and breast tenderness
Outcome of CC: Ovulation rate is approximately

75%; pregnancy rate is approximately 50%.
Failure of CC can be either:
• Conception failure: failure to achieve preg-
nancy despite successful induction of ovula-
tion. This may be attributed, in part, to
peripheral antiestrogenic effect of CC on
endometrium (endometrial thinning) and
cervical mucus (thick mucus).
• Ovulation failure: failure to achieve ovula-
tion despite maximal dose of CC.
➋ Aromatase inhibitors:
Regimen: letrozole, starting with 2.5 mg/day on
day 3–5 of the cycle and for 5 days. If ovulation
does not occur, the dose is increased by 2.5 mg/
cycle up to 7.5 mg/day (maximum dose). Its cur-
rent use in ovulation induction is off-label.
Indications:
➀ Induction of ovulation in women with PCOS:
in women with PCOS, letrozole has shown
superiority to CC. Letrozole has less periph-
eral antiestrogen effect on the endometrium
and cervical mucus.
➁ Aromatase inhibitors in combination with
gonadotropins may be used for controlled
ovarian hyperstimulation of IVF cycles in
women with breast cancer.
➌ Gonadotrophins:
Indications:
• Clomiphene-resistant patients
• Hypogonadotropic hypogonadal anovulation
(WHO class 1)
• Controlled ovarian hyperstimulation of IVF
cycles
Members:
➀ FSH and LH preparations (1:1 ratio): human
menopausal gonadotrophin “HMG” injec-
tions (75 or 150 units)
➁ LH-dominant preparation: human chorionic
gonadotrophins “HCG” injection
➂ FSH-dominant preparations: purified FSH,
ultrapure FSH, and recombinant FSH
injections
Regimens:
• Gonadotrophins are injected daily starting on
the second day of the cycle.
• Two regimens may be used:
–– Step-up regimen: starting with 1 ampule
daily
–– Step-down regimen: starting with a higher
dose (2–3 ampules)
• Serum estradiol is measured on cycle day 7,
and gonadotrophin dose is adjusted
accordingly.
• Serum estradiol and follicular growth are
followed up until maximum diameter of
the largest two follicles reach 18–22 mm,
and serum estradiol is 500–2000 pg/
mL. Ovulation is triggered by injection of
5000 IU of HCG.
• If estradiol is >2000 pg/mL or if >4, follicles
are larger than 18 mm, cancellation of the
cycle may be considered to avoid ovarian
hyperstimulation.
Gonadotrophin failure: failure to achieve preg-
nancy after 6 months of treatment
➍ GnRH agonists:
Indication:
➀ GnRH agonist is commonly used as a part of
IVF protocols. It prevents spontaneous ovu-
lation and premature LH surge. Therefore, it
increases the number of retrieved oocytes and
decreases the chance of cycle cancellation.
➁ GnRH agonist trigger: GnRH agonist may be
given to trigger ovulation instead of
HCG. GnRH trigger reduces the risk of ovar-
ian hyperstimulation compared to HCG trig-
ger in cycles not preceded by GnRH agonist
protocol. Luteal phase support is needed in
these cycles.
Regimens:
• Long protocol (luteal protocol):
This regimen starts on day 21 of the previ-
ous cycle. Therefore, it reduces the risk of
flare-up (due to initial stimulatory effect of
GnRH agonist).
• Short protocol (flare protocol):
This regimen starts on the follicular phase
of the same cycle.
➎ GnRH antagonists (cetrorelix and ganirelix):
Indication: a similar rule to GnRH agonist is car-
ried out by GnRH antagonists during IVF cycles.
Regimen:
• Single-dose protocol: a single dose is given at
the seventh to eighth day of the cycle.
• Multiple-dose protocol: multiple daily smaller
doses given from the fifth or sixth day until
ovulation is triggered.
➏ Pulsatile GnRH:
Pulsatile GnRH may be used for induction of
ovulation in patients with hypogonadotropic
anovulation.
• Complications of ovulatory drugs:
➊ Ovarian hyperstimulation syndrome:
–– Definition: it is a clinical syndrome associated with
ovarian enlargement secondary to exogenous stimula-
tion of the ovaries by ovulation-inducing medications.
–– Etiology:
Predisposing factors:
• Multi-follicular ovaries, e.g., PCOS
• Young age
• High estradiol level prior to ovulation trigger
• Pregnancy
Pathophysiology: etiology of OHSS is complex. It
is triggered by HCG, either administered exoge-
nously or produced endogenously by occurrence
of pregnancy in the same cycle:
Gonadotrophin stimulation (ovulation induction)
High estrogen level

HCG administration
Release of biological factors,
e.g., VEGF
Increased capillary permeability
Fluid accumulation in third space Intravascular volume depletion
Ascites Hemoconcentration
Hydrothorax Hypercoagulability
Ovarian Oliguria
enlargement
Pathophysiology of ovarian hyperstimulation syndrome
–– Diagnosis and management:
Degree Presentation Management

Mild • Abdominal distention Conservative management:
and discomfort follow-up, pelvic rest
• Mild symptoms (mild
nausea, vomiting
and diarrhea, mild
dyspnea)
• Enlarged ovaries
Moderate In addition to prior Patients should be strictly
features, the following followed-up using:
is present in moderate • Labs: CBC and serum
OHSS: electrolytes
• Ascites • Ultrasound
(ultrasonographic • Serial weight
diagnosis) measurement
• Hematocrit value >
41%
• WBC count >
15,000 mL
Severe • Severe dyspnea • Hospitalization
• Intractable nausea/ • Serial labs: hematocrit
vomiting value, serum electrolytes,
• Ascites (clinical renal tests
diagnosis) • Fluid replacement: with
• Hydrothorax isotonic solution (saline)
• Oliguria/anuria • Salt-free albumin: may be
• Hematocrit value > considered
55% • Thromboprophylaxis
• WBC count > • Paracentesis: may
25,000 mL be indicated doe
• Elevated liver symptomatic relief of
enzymes massive ascites
• Na < 135 mEq/L, K >
5 mEq/L
• Serum creatinine >
1.6 mg/dL
Degree Presentation Management

Critical • Severe abdominal • Admission to intensive
pain care unit
• Hypotension • Supportive treatment
• Arrhythmia • Management per
• Massive hydrothorax complications
• Pleural effusion
• Pericardial effusion
• Adult respiratory
distress syndrome
• Venous or arterial
thrombosis
• Anuria
• Acute renal failure
• Sepsis
–– Prevention:
The following strategies may be used to prevent
or reduce the risk of ovarian hyperstimulation syn-
drome during ovulation induction:
“Coasting”: it refers to withholding FSH adminis-
tration for one or more days prior to HCG injec-
tion for ovulation trigger.
Use of GnRH agonist instead of HCG trigger in
patients at higher risk of ovarian hyperstimulation.
If estradiol level is >2000 pg/mL or if >4, follicles
are larger than 18 mm, cycle cancellation is
recommended.
Prophylactic treatment with volume expanders.
➋ Multifetal gestation:
–– Ovulation induction with CC: incidence of twin preg-
nancy is 5–12% of all pregnancies; triplet and higher-
order pregnancy occurs in <1% of all pregnancies.
–– Ovulation induction with gonadotrophins: 30% of
pregnancies are multifetal. Of these, 5% are triplets
or higher-order pregnancies.
The risk of multifetal pregnancy correlates with the

magnitude of follicular response as indicated by follicle
number and serum estradiol levels.
–– Laparoscopic ovarian drilling in patients with PCOS is
a method of induction of ovulation. Outcomes of ovar-
ian drilling are comparable to ovulation induction using
oral medications (CC or letrozole).
–– Compared to medical induction of ovulation, advan-
tages and disadvantages of ovarian drilling include:
Advantages: ovarian drilling is not associated with
ovarian hyperstimulation.
Disadvantages: ovarian drilling is associated with
risk of surgery and risk of excessive damage to
the ovaries and subsequent diminished ovarian
reserve.
• Third-party reproduction:
Third-party reproductive options include egg donation
and surrogacy.
Uterine Factor
Incidence:
Uterine factor causes 10–15% of female factor infertility
Etiology:
➊ Müllerian anomalies: uterine aplasia (Müllerian agenesis)
and hypoplasia.
➋ Intrauterine synechiae (Asherman syndrome): it may be
caused by uterine surgery (e.g., D&C) or uterine infection.
➌ Intracavitary lesions: cavity-distorting fibroids or endome-
trial polyps.
Diagnosis:
• History:
During history taking, some clues to uterine factor
infertility include:
–– Amenorrhea, scant menstruation: may indicate uterine
anomalies or intrauterine synechiae
–– Heavy menstrual bleeding or intermenstrual bleeding:
may indicate intracavitary lesions
–– History of uterine surgery: may indicate intrauterine
synechiae
Uterine abnormalities are found in 16% of women
with infertility and 40% of women with abnormal uterine
bleeding.
• Work-up:
➊ Sonohysterography:
–– Sonohysterography is used to diagnose endometrial
polyps, leiomyomas, and intrauterine synechiae.
–– Sensitivity and specificity of sonohysterography in
diagnosing cavitary lesions are high (91% and 84%,
respectively).
➋ Transvaginal ultrasonography:
–– Transvaginal ultrasonography facilitates identifica-
tion of site, size, and location of uterine leiomyomas.
–– 3D ultrasonography may be used to detect Müllerian
anomalies.
➌ Hysteroscopy:
It may be used to confirm diagnosis and treat intra-
cavitary lesions.
➍ Hysterosalpingography:
Hysterosalpingography is less sensitive in diagnos-
ing intracavitary lesions compared to other diagnostic
modalities.
Treatment:
Treatment of the cause may improve fertility after exclusion/
management of other causes of infertility, e.g., hysteroscopic
myomectomy and polypectomy.
Asherman syndrome
Definition:
It is an infrequent acquired uterine disorder characterized by
intrauterine adhesions.
Etiology:
Etiology of Asherman syndrome
Trauma related to conception Trauma not related to conception

• Dilation and curettage/evacuation: as • Myomectomy
a part of management of abortion, • Diagnostic and therapeutic curettage
molar pregnancy, or postpartum
hemorrhage
• Cesarean section
Classification:
American Society for Reproductive Medicine (ASRM)
classification
Scoring system is calculated based on:
➀ The extent of cavity involvement of the uterine cavity (<1/3,
1/3 to 2/3, >2/3)
➁ The type of adhesion at the time of hysteroscopy (filmy, filmy
and dense, dense)
➂P atient’s menstrual pattern (normal, hypomenorrhea,
amenorrhea)
Diagnosis:
• History:
–– Abnormal uterine bleeding: menstrual pattern may cor-
relate to the extent of adhesions. It ranges from amen-
orrhea to normal menses.
–– Infertility: intrauterine adhesions may cause proximal
tubal obstruction (obliteration of tubal ostia) and endo-
metrial cavity obliteration.
–– History suggestive of the cause: e.g., history of amenor-
rhea, scant menses, or infertility following D&C or
other uterine surgeries.
• Work-up:
➊ Sonohysterography:
In Asherman syndrome, sonohysterography may be
associated with:
–– Technical difficulty
–– Limited uterine distension with saline
–– Visualization of adhesion bands
–– Failure of passage of fluid to Douglas pouch (evi-
dence of tubal patency)
➋ Hysteroscopy:
It is the best diagnostic tool. Hysteroscopy deter-
mines extent, type, and location of adhesions.
➌ Hysterosalpingography:
Hysterosalpingography may show intrauterine
defects and provide information on tubal patency.
Treatment:
Step 1: Adhesiolysis
Hysteroscopic adhesiolysis: in patients with moderate or severe
adhesions, the procedure may be performed under laparoscopic
guidance to reduce the risk of perforation and intraperitoneal
injury
Unexplained Infertility 377
Step 2: Prevention of readhesion

➊ I ntrauterine splint, e.g., using intrauterine balloon catheter
for 14 days
➋ Antibiotics: should be added
Step 3: Hormonal therapy
Estrogen is given for 60 days. Medroxyprogesterone acetate is
added for 5 days in each 30 days of estrogen therapy
Step 4: Re-evaluation
2–3 months after surgery, hysterosalpingography or diagnostic
hysteroscopy is done for reassessment of uterine cavity
Unexplained Infertility
Definition:
Unexplained infertility refers to infertility associated with
normal basic infertility work-up.
Incidence:
up to 30% of infertile couples
Diagnosis:
Unexplained infertility is the diagnosis of exclusion. Couples
with at least evidence of ovulation, tubal patency, and
normal semen analysis meet the criteria of unexplained
infertility.
Treatment:
I. Expectant management
• Candidates: young women (<32 years) with normal ovar-

ian reserve.
• Outcome: the chance of pregnancy among these couples is
1–3% per month.
II. Lifestyle modification
Lifestyle modification may improve fertility outcome with

both expectant and active management:
• Smoking cessation: both partners should be counseled on
smoking cessation.
• Weight loss: women should be counseled on impact of
weight reduction on fertility outcomes.
• Caffeine reduction: daily caffeine intake should be
<250 mg (two cups of coffee) a day.
III. Assisted reproduction
If the above approaches are not applicable or if pregnancy

is not achieved, women may be offered one of two options:
Accelerated
Conventional approach approach
• Three cycles of ovulation induction • Three cycles of
with CC with intrauterine CC plus IUI
insemination (IUI) • IVF (up to six
• Three cycles of ovulation induction cycles)
using gonadotrophins (FSH) with IUI
• IVF (up to six cycles)
Further Reading
American College of Obstetricians and Gynecologists. ACOG
Committee opinion no. 738: aromatase inhibitors in gynecologic
practice. Obstet Gynecol. 2018;131:e194.
Further Reading 379
American College of Obstetricians and Gynecologists Committee

on Gynecologic Practice and Practice Committee. Female age-
related fertility decline. Committee opinion no. 589. Fertil Steril.
2014;101:633.
Brosens I, Gordts S, Valkenburg M, et al. Investigation of the infer-
tile couple: when is the appropriate time to explore female infer-
tility? Hum Reprod. 2004;19:1689.
Collins JA, Crosignani PG. Unexplained infertility: a review of
diagnosis, prognosis, treatment efficacy and management. Int J
Gynaecol Obstet. 1992;39:267.
Committee on Gynecologic Practice. Committee opinion no. 618:
ovarian reserve testing. Obstet Gynecol. 2015;125:268. Reaffirmed
2017.
Evers JL. Female subfertility. Lancet. 2002;360:151.
Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomi-
phene for infertility in the polycystic ovary syndrome. N Engl J
Med. 2014;371:119.
Practice Committee of American Society for Reproductive
Medicine. Definitions of infertility and recurrent pregnancy loss.
Fertil Steril. 2008;90:S60.
Practice Committee of American Society for Reproductive Medicine.
Diagnostic evaluation of the infertile female: a committee opin-
ion. Fertil Steril. 2012;98:302.
Medicine. Use of clomiphene citrate in infertile women: a com-
mittee opinion. Fertil Steril. 2013;100:341.
Medicine. Testing and interpreting measures of ovarian reserve:
a committee opinion. Fertil Steril. 2015a;103:e9.
Medicine. Current clinical irrelevance of luteal phase deficiency:
a committee opinion. Fertil Steril. 2015b;103:e27.
Saunders RD, Shwayder JM, Nakajima ST. Current methods of tubal
patency assessment. Fertil Steril. 2011;95:2171.
Soares SR, Barbosa dos Reis MM, Camargos AF. Diagnostic accu-
racy of sonohysterography, transvaginal sonography, and hys-
terosalpingography in patients with uterine cavity diseases. Fertil
Steril. 2000;73:406.
Chapter 13
Recurrent Pregnancy
Loss
Definition:
• Two or more successive spontaneous clinical pregnancy
losses.
• Clinical pregnancy is defined as pregnancy confirmed by
ultrasound or histopathology. Pregnancy test alone is not
sufficient to diagnose clinical pregnancy.
Etiology:
❶ Cytogenetics (2–5% of couples with recurrent preg-
nancy loss):
Recurrent pregnancy loss may be caused by paternal
balanced reciprocal or Robertsonian translocation.
❷ Antiphospholipid antibody syndrome (aPL, 15%)
❸ Anatomical causes (12.6%):
• Müllerian anomalies (e.g., uterine septum, unicornu-
ate, bicornuate, didelphic uterus) may cause second-
trimester miscarriage and preterm labor. However,
their association with first-trimester miscarriage is
debatable.
• The role of other uterine abnormalities, e.g., fibroids,
polyp, and Asherman syndrome, is not supported by
adequate evidence.

https://doi.org/10.1007/978-3-030-41128-2_13
382 Chapter 13. Recurrent Pregnancy Loss
❹ Hormonal causes:
• Thyroid dysfunction
• Uncontrolled diabetes
• Polycystic ovary syndrome (PCOS)
• Hyperprolactinemia
• Luteal phase defect (LPD)
❺ Male factor causes:
• Sperm parameters are not predictive of recurrent
miscarriage.
• The role of sperm DNA fragmentation is
controversial.
❻ Psychological factors:
There is inadequate evidence to support impact of anxi-
ety and stress on pregnancy loss. However, psychologi-
cal support is always recommended.
❼ Alloimmune factors:
The role of alloimmune mechanisms (e.g., include HLA
typing, blocking Abs, anti-paternal leukocyte antibod-
ies) is controversial.
❽ Environmental factors:
• Obesity increases risk of RPL.
• Alcohol intake (as low as 3–5/week) may increase
the risk of miscarriage.
• Excess caffeine intake (>3 cups/day) may increase
the risk of miscarriage.
• Cocaine use increases risk of miscarriage.
❾ Unexplained:
In 50–75% of cases, all possible causes are ruled out,
and there is no clear explanation of RPL.
Chapter 13. Recurrent Pregnancy Loss 383
Diagnosis:
I. History
• Detailed history of previous miscarriages:

–– Method of diagnosis of prior pregnancies (clinical ver-
sus biochemical)
–– Gestational age at miscarriage:
First-trimester miscarriage: which is suggestive of
genetic/endocrine causes
Second-trimester miscarriage: which is suggestive of
immune/anatomical causes
–– Pregnancy characteristics at miscarriage: cardiac pulsa-
tions absent vs. present
–– Documentation of previous pregnancies: e.g., imaging,
pathology, and genetic testing
–– Clinical criteria of APA syndrome:
Vascular thrombosis
1 or more pregnancy losses >10 weeks with normal
fetal morphology
1 or more preterm labor <34 weeks with normal fetal
morphology due to preeclampsia with severe fea-
tures or eclampsia
3 or more pregnancy losses <10
The diagnosis is made after exclusion of other causes.
• Menstrual history: menstrual disorders may suggest endo-
crine causes.
• Medical history: medical history may reveal relevant dis-
eases, e.g., galactorrhea, thyroid dysfunction, and diabetes.
• Family history (suggesting genetic causes):
–– Family history of fetal losses
–– Family history of genetic disorders
–– Family history of consanguinity
–– Family history of loss prior to cardiac activity

–– Personal or family history of venous and/or arterial
thrombosis
II. Examination
• Physical examination: relevant findings include hirsutism

and high body mass index.
• Psychologic assessment: screening for stress and
depression.
III. Work-up
• Laboratory tests:
–– APA syndrome work-up:
Diagnosis of APA requires one clinical criterion (see
under clinical criteria) + 1 laboratory testing:
2 positive lupus anticoagulant results at least
12 weeks apart
2 anticardiolipin IgM and/or IgG antibody titer
above >40 GPL or MPL at least 12 weeks apart
2 anti-β2 glycoprotein-I titer >99% at least 12 weeks
apart
There is inadequate evidence to support an association
between inherited thrombophilias and RPL. Therefore,
routine testing is not recommended. Inherited throm-
bophilias may be tested only if clinically indicated by
the presence of suggestive personal or family history of
venous thromboembolism.
–– Thyroid screening:
Initially, serum TSH level is checked. Further action
depends on TSH results:
Chapter 13. Recurrent Pregnancy Loss 385
If TSH is normal: no further action.

If TSH is abnormal: test for serum T4 to identify type
of thyroid dysfunction.
If TSH is not abnormal but >2.5 mIU/L: test for thy-
roid peroxidase antibodies (TPO). The presence of
TPO may double the risk of miscarriage.
–– Screening for diabetes:
Diabetes can be screened for reproductive purposes
using HgBA1C (cutoff level is 5.6%).
–– Screening for hyperprolactinemia:
Serum prolactin is indicated in women with history sug-
gestive of ovulatory dysfunction.
There is no reliable approach to diagnose LPD.

There is no role for serum progesterone testing or endometrial
biopsy.
• Imaging tests:
–– Imaging studies are used to screen for anatomical
causes of recurrent pregnancy loss, e.g., Müllerian
anomalies.
–– Sonohysterography or hysterosalpingography may be
used as the first imaging test.
–– If indicated, laparoscopy, MRI, or 3D ultrasound may
be used as a second imaging option to verify diagnosis.
• Karyotyping:
Karyotyping of products of conception, rather than paren-
tal peripheral blood, is recommended as a first step:
–– If normal: consider testing for other causes.
–– If products of conception reveal aneuploidy: no need to
test parents.
–– If the fetus has chromosomal rearrangement: this can
be inherited or sporadic. In this case, parents should be
tested for balanced chromosomal translocation (periph-
eral blood karyotyping) to rule out inheritance.
Management:
❶ Life style modification:
–– Caffeine, alcohol, tobacco cessation
–– Weight reduction
❷ Parental karyotype abnormality:
➀ Referral for genetic counseling
➁ Prenatal genetic testing (amniocentesis or CVS) in
future pregnancies for elective termination of preg-
nancy if abnormalities are detected
➂ IVF with preimplantation genetic testing
➃ IVF using third-party reproductive options
❸ Anatomic causes:
–– Hysteroscopic repair of uterine septum.
–– Adhesiolysis for intrauterine adhesions or hystero-
scopic myomectomy for submucosal leiomyoma (type 0
or 1) may be considered if all other causes are ruled out.
❹ Medical/hormonal causes:
–– APA syndrome: low-dose aspirin and low-molecular-
dose heparin during pregnancy.
–– Hypothyroidism or positive HPO antibodies: levothy-
roxine may decrease the risk of miscarriage.
–– Diabetes: initiation of treatment or improvement of
diabetic control is indicated.
–– PCOS: administration of metformin (1000–2000 mg)
has been suggested. However, the role of this approach
has not been proven.
–– Hyperprolactinemia: cabergoline 0.25 mg twice a week
or 0.5 mg once a week.
–– Thrombophilia: anticoagulation is controversial.
❺ Unexplained RPL:
Although there is no treatment that can be offered to
these patients, they should be counseled that unexplained
RPL carries a good prognosis; their likelihood of a success-
ful pregnancy is 50–60%.
Further Reading 387
Further Reading
American College of Obstetricians and Gynecologists. Management
of recurrent early pregnancy loss. ACOG practice bulletin no.
24. Washington, DC: American College of Obstetricians and
Gynecologists; 2001.
Brezina PR, Kutteh WH. Recurrent early pregnancy loss. In: Falcone
T, Hurd WW, editors. Clinical reproductive medicine and surgery.
Cham: Springer; 2017. p. 269–88.
Chetty M, Duncan WC. A clinical approach to recurrent pregnancy
loss. Obstet Gynaecol Reprod Med. 2018;28(6):164–70.
El Hachem H, Crepaux V, May-Panloup P, Descamps P, Legendre G,
Bouet PE. Recurrent pregnancy loss: current perspectives. Int J
Womens Health. 2017;9:331.
ESHRE Guideline Group on RPL, Bender Atik R, Christiansen OB,
Elson J, Kolte AM, Lewis S, Middeldorp S, Nelen W, Peramo B,
Quenby S, Vermeulen N. ESHRE guideline: recurrent pregnancy
loss. Hum Reprod Open. 2018:1–12.
Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-
based guidelines for the investigation and medical treatment of
recurrent miscarriage. Hum Reprod. 2006;21:2216.
Practice Committee of American Society for Reproductive Medicine.
Definitions of infertility and recurrent pregnancy loss: a commit-
tee opinion. Fertil Steril. 2013;99:63.
Chapter 14
Fertility Preservation
Definition:
Fertility preservation refers to interventions that aim at pre-
serving the protentional for biologic parenthood among
women undergoing surgical resection of reproductive organs
or treatment with gonadotoxic chemotherapy or radiother-
apy including treatment of malignancy and some precancer-
ous or benign conditions.
Indications:
❶ Malignant diseases:
➀ Childhood cancers: e.g., Hodgkin and non-Hodgkin
lymphoma, Ewing sarcoma, Wilms tumor
➁ Adult cancers: e.g., breast cancer, gynecologic cancers.
❷ Autoimmune diseases:
• Systemic lupus erythematosus.
• Steroid-resistant glomerulonephritis.
• Rheumatoid arthritis.
• Inflammatory bowel disease.
• Multiple sclerosis.

https://doi.org/10.1007/978-3-030-41128-2_14
390 Chapter 14. Fertility Preservation
❸ Hematologic diseases:
• Sickle cell disease.
• Aplastic anemia.
❹ Patients receiving pelvic radiation: e.g., treatment of rectal
cancer
Methods of Fertility Preservation:

❶ Cryopreservation:
• Methods:
–– Cryopreservation of embryos.
–– Cryopreservation of mature oocytes.
–– Cryopreservation of immature oocytes and ovarian
tissue.
–– Cryopreservation of the whole ovary with an intact
pedicle.
Cryopreservation of embryos and mature oocytes
is a well-established technique. Cryopreservation of
immature oocytes and ovarian tissue is an approach
for prepubertal patients. The technique is experimen-
tal. However, initial results are promising.
Cryopreservation of the whole ovary is also under
investigation.
• Patient selection:
Criteria of patient selection vary among institutes.
Conventionally, Edinburgh criteria can be used for
patient selection:
➀ Women under the age of 35 with no prior children.
➁ Risk of premature ovarian failure is 50% or more
after treatment.
➀ Women with ovarian cancer or at high risk of ovarian
cancer, e.g., BRCA 1 and BRCA 2 germline mutation
carriers
➁ Blood-borne malignancies, e.g., leukemias.
Chapter 14. Fertility Preservation 391
❷ Protection of ovarian function:

• With radiation therapy:
➀ Transposition (oophoropexy):
This is a surgical procedure that aims at moving
ovary to a location that best protects it from radia-
tion effect.
➁ Shielding:
If radiation is distant from the pelvis, the ovaries
can be protected from scatter radiation using exter-
nal shield.
➂ Autotransplantation:
It refers to transplantation of the ovary to the
upper extremity. This approach is suitable for women
who will receive pelvic radiation.
• With chemotherapy:
GnRH agonist treatment may be offered to suppress
ovarian function during chemotherapy if cryopreserva-
tion is not available. However, outcomes are less favor-
able compared to cryopreservation.
❸ Protection of the uterus:
➀ Cervical cancer: Radical trachelectomy for stage IB1 to
preserve the uterus.
➁ Endometrial cancer: use of progestins and Mirena IUD
in stage IA endometrial cancer to preserve the uterus.
➂ Borderline ovarian tumors: unilateral salpingo-oopho-
rectomy with preservation of the uterus and the other
ovary.
See under gynecologic oncology for more details.
Future Management:
Future options for fertility preservation may include:
❶ Uterine transplantation:
It may be future option for women with congenital uter-
ine anomalies or women whose uterus is damaged (e.g.,
following pelvic radiation) or surgically absent.
392 Chapter 14. Fertility Preservation
❷ Stem cell technology:

The aim of this technology is to use germ stem cells in
adults to replenish ovarian oocytes.
Further Reading
Demeestere I, Brice P, Peccatori FA, et al. No evidence for the ben-
efit of gonadotropin-releasing hormone agonist in preserving
ovarian function and fertility in lymphoma survivors treated with
chemotherapy: final long-term report of a prospective random-
ized trial. J Clin Oncol. 2016;34:2568.
Martinez F. Update on fertility preservation from the Barcelona
International Society for Fertility Preservation-ESHRE-ASRM
2015 expert meeting: indications, results and future perspectives.
Hum Reprod. 2017;32:1802.
Oktay K, Harvey BE, Partridge AH, et al. Fertility preservation in
patients with cancer: ASCO clinical practice guideline update. J
Clin Oncol. 2018;36:1994.
Senra JC, Roque M, Talim MCT, et al. Gonadotropin-releasing
hormone agonists for ovarian protection during cancer chemo-
therapy: systematic review and meta-analysis. Ultrasound Obstet
Gynecol. 2018;51:77.
Chapter 15
Anomalies of Female
Genital Tract
Disorders of Sex Development (DSD)
Category I: 46 XX DSD
This category refers to patients with 46 XX karyotype with

male or ambiguous phenotype (previously known as female
pseudohermaphrodite).
• Etiology:
–– Adrenal causes:
21-Hydroxylase deficiency (congenital adrenal
hyperplasia, CAH):
• CAH is an autosomal recessive inherited disorder.
• 21-Hydroxylase deficiency (CYP21A2 gene muta-
tion) results in failure of conversion of 17-hydroxy-
progesterone to 11-deoxycortisol
• The disease has three clinical types: classic salt-
losing, classic non-salt-losing, and non-classic
(late-onset) CAH:
❶ Salt-wasting types: this is the most severe form
of the disease. Complete enzyme deficiency
causes severe deficiency in cortisol and aldoste-

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394 Chapter 15. Anomalies of Female Genital Tract
rone resulting in hyponatremia and

hyperkalemia.
❷ Non-salt-wasting (simple virilizing) type: in this
type, cortisol is deficient. However, aldosterone
production is normal or slightly deficient.
❸ Non-classic CAH: this type is mild, not associ-
ated with salt wasting. Aldosterone and cortisol
levels are normal with mild androgen excess.
11β-Hydroxylase (CYP11B) deficiency:
CAH caused by 11β-hydroxylase deficiency is
associated with androgen excess. This condition is
associated with hypertension due to excessive miner-
alocorticoid activity (accumulation of
deoxycorticosterone)
–– Non-adrenal causes:
Maternal exposure to drugs, e.g., testosterone (nor-
mal 17-OH prog?)
Maternal virilizing ovarian tumors, e.g., virilizing
adrenal tumors.
• Clinic features:
–– Karyotyping: 46 XX.
–– Internal development: ovaries, uterus, cervix, and
upper vagina are present.
–– External development (phenotype): virilized external
genitalia to a varying degree.
In addition to DSD, classic salt-wasting CAH is associated
with hyponatremia, hyperkalemia, and hypotension. The con-
dition is life-threatening if not appropriately treated. Newborns
are screened for CAH using serum 17-hydroxyprogesterone,
which is elevated in these patients. If the diagnosis is doubtful,
ACTH stimulation test may be used to confirm the diagnosis.
• Treatment:
–– Urgent medical management of underlying cause, e.g.,
classic congenital adrenal hyperplasia.
–– Surgical reconstruction of external genitalia.
Disorders of Sex Development (DSD) 395
Category II: 46 XY DSD
This category refers to patients with 46 XY karyotype with

female or ambiguous phenotype (previously known as male
pseudohermaphrodite)
• Etiology:
❶ Testicular enzyme defect: e.g., cholesterol side-chain
cleavage enzyme.
❷ Peripheral enzyme defect: a defect in five α-reductase.
❸ Androgen receptor defect: result in androgen insensitiv-
ity syndrome (AIS)
• Characters:
–– Karyotyping: 46 XY, testes are present .
–– Internal development: the uterus is absent.
–– External development: there may be:
Complete resistance: development of external geni-
talia is consistent with a normal female.
Incomplete form: there is a varying degree of genital
ambiguity.
• Treatment:
❶ Creation of a functional vagina either by:
–– Gradual dilation.
–– Surgical management (vaginoplasty).
See under: Congenital absence of the vagina
❷ Surgical excision of the testes is recommended to
decrease the risk of germ cell tumors. Gonadectomy is
recommended after puberty to allow spontaneous
puberty to occur. Replacement therapy with physiologic
levels of estrogen thereafter.
Category III Disorders of Genetic or Gonadal Development
• Gonadal dysgenesis: e.g., Turner syndrome (see under:

Amenorrhea).
• Ovotesticular DSD (previously known as true hermaphro-
ditism): both ovarian and testicular gonadal tissues are
present.
• Embryonic testicular regression (agonadism):
This condition may affect 46 XY embryos. Müllerian
inhibiting substance (MIS) may or may not be produced.
Therefore, the uterus may or may not be present.
Congenital Anomalies of the Vulva
I. Anomalies of the Clitoris
• Clitoral duplication (bifid clitoris).

• Female phallic urethra (the urethra opens at the tip of the
clitoris).
• Congenital clitoromegaly.
II. Anomalies of the labia
• Labial fusion (labial adhesions): it occurs due to inade-

quate estrogenization of the labia and vagina. Management
includes:
–– Observation: spontaneous resolution is anticipated in
80% of cases within 1 year. Most cases will likely
resolve at the time of puberty (in response to endoge-
nous estrogens).
Congenital Anomalies of the Vagina 397
–– Topical estrogen cream: this may be considered if the

patient is symptomatic or if there is associated blockade
of vaginal secretions.
–– Manual or surgical separation: this is only indicated if
medical treatment fails or in severe cases associated
with urinary retention.
• Labial hypertrophy: this disorder may result in irritation,
discomfort, or a bulge sensation especially during physical
activities and intercourse.
Hymeneal Anomalies
• Types of hymeneal anomalies:
Microperforate, septate, cribriform, imperforate hymen
–– Imperforate hymen: cyclic pain, amenorrhea, urinary
urination.
–– Microperforate, cribriform, or septate hymen: difficulty
with tampon placement or intercourse, menstrual
irregularities.
• Management: see under: Amenorrhea.
Congenital Anomalies of the Vagina

• Vaginal aplasia: the vagina is completely absent; only a
shallow perineal depression is present.
• Vaginal hypoplasia: the vagina is short and narrow.
• Congenital stricture.
• Duplicated vagina: in association with uterus didelphys.
• Congenital ureterovaginal, vesicovaginal, or rectovaginal
fistula.
• Vaginal septum:
–– Transverse vaginal septum: incomplete fusion between
the caudal portion of the Müllerian ducts and the uro-
genital sinus.
–– Longitudinal vaginal septum: failure of fusion of

Müllerian ducts in the midline.
• Gartner duct cysts:
Gartner duct cysts originate from vestigial remnants of
the Wolffian ducts.
Müllerian Duct Anomalies

• Classification of Müllerian anomalies:
Class I Segmental Müllerian hypoplasia or agenesis

(a) Vaginal (failure of urogenital sinus to
develop)
(b) Cervical
(c) Uterine
(d) Tubal
(e) Combined
Class II Unicornuate uterus:
(a) R
udimentary horn with cavity,
communicating to unicornuate uterus
(b) R
udimentary horn with cavity, not
communicating to unicornuate uterus
(c) Rudimentary horn with no cavity
(d) U
nicornuate uterus without a rudimentary
horn
Class III Uterine didelphys (2 tubes, 2 uterine cavities, 2
cervices, and 2 vaginas)
Class IV Bicornuate uterus:
Complete bifurcation (bicollis) = 2 uterine
cavities and 2 cervices
Partial bifurcation (unicollis) = 2 uterine
cavities and a single cervix
Class V Septate uterus:
Complete septation
Partial septation
Class VI Arcuate uterus
Class VII Diet hylstilbestrol-related anomalies
Müllerian Duct Anomalies 399
• Clinical features of Müllerian anomalies:

❶ Gynecologic complications:
➀ Heavy menstrual bleeding: due to increased surface
area of the endometrium and impaired uterine con-
tractility (malarrangement of muscle fibers).
➁ Dyspareunia/difficult use of tampons: if there is
associated vaginal septum.
➂ Failed IUD:
–– Failed IUD placement may occur due to the pres-
ence of a vaginal septum.
–– Pregnancy on top of IUD may occur in the pres-
ence of septate/doubled uterine cavity).
❷ Obstetrical complications:
➀ Recurrent abortion:
• First trimester: septate uterus may be associated
with first trimester recurrent abortion.
• Second trimester: bicornuate or didelphys uterus
may be associated with second trimester recurrent
abortion.
➁ Preterm labor: due to diminution of uterine capacity
and associated congenital cervical weakness (bicor-
nuate or didelphys uterus).
➂ Malpresentation: breech and transverse
presentation.
➃ Prolonged labor (increased incidence of Cesarean
delivery): due to impaired uterine contractility
(malarrangement of muscle fibers).
➄ Retained placenta and placenta accreta: septate
uterus may be associated with retained placenta (if
the placenta is implanted over the underdeveloped
septum).
➅ Postpartum hemorrhage: secondary to the above
causes.
➌ Urologic complications:
• Urologic anomalies are present in 20 to 30% of
women with Müllerian anomalies.
• Urologic anomalies are most frequently associated
with unicornuate and didelphic uterus (approxi-
mately 30% of patients).
• Partial bicornuate, subseptate, and arcuate uterus is
rarely associated with urologic anomalies.
• The most common renal anomaly is unilateral renal
agenesis.
• Work-up:
Work-up is usually initiated by clinical suspicion (per
clinical manifestations as listed above):
❶ Hysterosalpingography (HSG):
• HSG may be performed as a part of infertility
work-up.
• HSG can identify uterine anomalies. However, deter-
mination of the type of uterine anomaly often
requires assessment of uterine external contour,
which cannot be adequate evaluated by HSG.
❷ Ultrasonography:
Sonography may provide the following information:
➀ Presence of hematometra or hematocolpos (obstruc-
tive anomalies).
➁ Presence of female internal organs (patients with
primary amenorrhea).
➂ Associated renal anomalies, e.g., renal agenesis, pelvic
kidney.
➌ Three-dimensional ultrasound (3D-US):
• 3D-US visualizes the uterine cavity, myometrium,
and the external contour of the uterus.
Vaginal Agenesis (Blind Vagina) 401
• It reliably differentiates septate from the bicornuate

uteri; if the fundus is more than 5 mm above the line
drawn between the two cornua, it is likely septate
uterus.
❹ Magnetic resonance imaging:

MRI is a noninvasive method that provides excellent
delineation of uterine cavity and external uterine
contour.
❺ Laparoscopy:
Laparoscopy used to be mandatory to provide accu-
rate diagnosis of suspected uterine anomalies. Currently,
3D ultrasound and MRI provide a reasonable noninva-
sive alternative.
Vaginal Agenesis (Blind Vagina)

• Causes and types:
❶ Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser
syndrome).
❷ Isolated vaginal agenesis: due to failure of the urogeni-
tal sinus to form the caudal end of the vagina.
❸ Androgen insensitivity syndrome:
Androgen insensitivity Müllerian agenesis

syndrome syndrome
Etiology Androgen receptors Failure of development
defect of Müllerian ducts
Karyotype 46 XY 46 XX
Phenotype . .
Internal Testes, NO uterus or Ovaries, NO uterus or
organs vagina vagina
External Female genitalia Female genitalia
organs
Clinical Primary amenorrhea, Primary amenorrhea,
features dyspareunia, and dyspareunia, and
Symptoms infertility infertility
Physical Well-developed Well-developed
exam secondary sexual secondary sexual
characters, blind vagina characters, blind vagina
(vaginal dimple), and (vaginal dimple), and
absent pubic hair normal pubic hair
Work-up Chromosomal analysis, pelvic MRI, rule out
associated urological anomalies if diagnosis of
Müllerian agenesis is made
Treatment •G ender assignment •C reation of
should be with neovagina
consent of the patient. • M
anagement of
Surgical management associated anomalies
should be offered in
concordance with
patient decision, e.g.,
creation of neovagina
•S urgical removal
of the gonads after
puberty
• Hormone therapy
Vaginal Agenesis (Blind Vagina) 403
• Treatment:
I. Creation of a neovagina
• Conservative management:
Nonsurgical management aims at gradual dilation of the
vaginal dimple using graded firm silicon dilators.
• Surgical management:
❶ McIndoe vaginoplasty:
• The principle of the original surgery is to create a
canal within the connective tissue between the blad-
der and rectum. The neovagina is then lined with a
split-thickness skin graft.
• Modifications to the original surgery are performed
using human amnion, peritoneum, and buccal mucosa
as neovaginal linings.
• Recently, stem cell technology has been used to cre-
ate a natural neovaginal lining. The initial results are
promising.
❷ Williams vaginoplasty:
The procedure involves creation of a vaginal pouch
using labial skin flaps.
❸ Vecchietti procedure:
The procedure involves application of an apparatus,
formed of a sphere and two guide wires, to the vaginal
dimple. Daily traction on the sphere using the two guide
wires causes gradual dilation and stretching of the vagi-
nal pouch.
II. Achievement of conception
Women with Müllerian agenesis may conceive via oocyte

retrieval, in vitro fertilization, and embryo transfer to a
surrogate.
Cervical Anomalies
• Cervical agenesis: congenital absence of the cervix and the
upper vagina.
• Cervical stenosis: cervical stenosis likely presents segmen-
tal Müllerian hypoplasia.
Fallopian Tube Anomalies

• Tubal aplasia.
• Tubal hypoplasia (long, narrow and tortuous).
• Accessory ostia.
• Congenital diverticula.
Ovarian Anomalies
• Aplasia or complete absence.
• Gonadal dysgenesis.
• Ovotestis.
Further Reading
ACOG Committee on Adolescent Health Care. ACOG Committee
Opinion No. 355: vaginal agenesis: diagnosis, management, and
routine care. Obstet Gynecol. 2006;108(6):1605.
Chan YY, Jayaprakasan K, Tan A, et al. Reproductive outcomes in
women with congenital uterine anomalies: a systematic review.
Ultrasound Obstet Gynecol. 2011;38:371.
Folch M, Pigem I, Konje JC. Müllerian agenesis: etiology, diagno-
sis, and management. Obstet Gynecol Surv. 2000;55(10):644–9.
Grimbizis GF, Gordts S, Di Spiezio Sardo A, et al. The ESHRE/
ESGE consensus on the classification of female genital tract con-
genital anomalies. Hum Reprod. 2013;28:2032.
Further Reading 405
Hughes IA, Werner R, Bunch T, Hiort O. Androgen insensitivity

syndrome. In Seminars in reproductive medicine 2012 Oct (Vol.
30, No. 05, pp. 432–442). Thieme Medical Publishers.
Mazouni C, Girard G, Deter R, et al. Diagnosis of Mullerian anoma-
lies in adults: evaluation of practice. Fertil Steril. 2008;89:219.
The American Fertility Society classifications of adnexal adhesions,
distal tubal occlusion, tubal occlusion secondary to tubal ligation,
tubal pregnancies, müllerian anomalies and intrauterine adhe-
sions. Fertil Steril. 1988;49:944.
Woodward M, Burns K. Disorders of sex development. Surgery.
(Oxford). November 2019;37(11): 646–52.
Part IV
Gynecologic Oncology
Chapter 16
Lower Genital Tract
Cancers
Vulval Neoplasia
Vulval Intraepithelial Neoplasia (VIN)
Classification:
I. Traditional classification
VIN I The lower third of the vulvar epithelium is replaced

by undifferentiated cells
VIN II The lower two-thirds of the vulvar epithelium is
replaced by undifferentiated cells
VIN III Full thickness of the vaginal epithelium is replaced by
undifferentiated cells
No invasion below the basement membrane is noted
II. ISSVD (The International Society for Study of

Vulvovaginal Disease) classification 2015

https://doi.org/10.1007/978-3-030-41128-2_16
410 Chapter 16. Lower Genital Tract Cancers
Low-grade squamous Flat condyloma or HPV virus effect

intraepithelial lesion of the (previously known as VIN I)
vulva (vulvar LSIL)
High-grade squamous Usual type VIN (previously known
intraepithelial lesion of the as VIN II–III):
vulva (vulvar HSIL) − VIN, warty type
− VIN, basaloid type
− VIN, mixed type
Differentiated-type VIN VIN associated with vulvar
(VIN simplex) dermatoses such as lichen sclerosus
(rather than HPV)
What is vulvar Paget’s disease:

• It is a specific type of intraepithelial neoplasia that is char-
acterized by the presence of Paget cells.
• Paget cells have pale vacuolated cytoplasm and large
round or oval secretory cells with large central and hyper-
chromatic nuclei.
• The cells appear first at the basal layer of the epithelium
but may involve the whole thickness of the epithelium, i.e.,
adenocarcinoma in situ.
Diagnosis:
• Symptoms:
–– 50% of the patients may have no complaints.
–– Symptomatic patients present with vulvar pruritus and
vulvar soreness.
• Physical signs:
Squamous vulvar Nonsquamous intraepithelial
intraepithelial neoplasia (VIN) neoplasia (Paget’s disease)
• The vulva may look normal • The lesion may appear hyperemic,
or may show bright-red, sharply demarcated, and thickened
dark-red, brown, gray, or • There may be foci of induration
white areas and excoriation
• Lesions are multifocal in • The hyperemic area may be
more than two-thirds of covered by white spots (which is
patients known as cake icing appearance)
Vulval Neoplasia 411
• Work-up:
–– If clinical examination is not conclusive, colposcopic
examination of the vulva before and after acetic acid
application and biopsy of abnormal areas
–– Indications of biopsy include:
❶ Visible lesions without definite clinical diagnosis

❷ Visible lesions with preliminary clinical diagnosis not
responding to standard treatment
❸ Visible lesions grossly concerning of malignancy or
visible lesions that change rapidly in size, color, or
appearance
❹ Condylomas not responsive to topical treatment or in
postmenopausal women
Management:
I. Prevention
• HPV vaccination:
–– It decreases the risk of VIN usual type (HSIL).
–– Recommended age at vaccination is 11–12. However,
the vaccine may be given as early as age 9. It can still be
used up to the age of 26. However, three doses may be
given instead of two doses.
–– Vaccination between the age of 27 and 45 years is less
beneficial as many women have likely been exposed to
HPV. However, a woman who has not been vaccinated
before may decide to receive the vaccine after appropri-
ate counseling.
• Smoking cessation: cigarette smoking is a strong risk factor
for VIN usual type.
• There are no screening strategies for the prevention of
vulvar cancer through early detection of vulvar HSIL
(VIN usual type).
II. Treatment
• LSIL VIN (VIN I):

–– Most of these cases resolve spontaneously. Therefore,
regular follow-up is an appropriate option.
• HSIL VIN (usual type [VIN II and III]):
–– If occult cancer is suspected: wide local excision
–– If occult cancer is not a concern: wide local excision,
laser ablation, or topical imiquimod
• Paget’s disease:
–– The disease should be treated with wide local excision.
Frozen section at the time of surgery is recommended
until all margins are negative.
–– Complete vulvectomy with skin graft is rarely indicated
for extensive disease.
III. Follow-up
Because of the high risk of recurrence, follow-up visits should

be scheduled after 6 months, 12 months, and annually
thereafter.
Invasive Vulval Carcinoma
Incidence: approximately 6% of all cancers of the female

genital tract in the United States. Life-long risk of vulvar can-
cer is 1:333.
Risk factors:
• Age: the risk increases with age. The average age at diag-
nosis is 70.
• Human papillomavirus: high-risk types of HPV, e.g., HPV

16 and HPV 18.
• Smoking: the risk is higher if combined with high-risk
HPV infection.
• HIV (human immunodeficiency virus) infection.
• Vulvar intraepithelial neoplasia (VIN).
• Lichen sclerosus.
Pathology:
• Site of origin: any part of the vulva can be affected. The
most common sites, in decreasing order of frequency, are the
labia majora “inner aspects,” labia minora, and clitoris.
Vulvar cancer may appear as a cauliflower mass, malig-
nant ulcer with everted edges and indurated base, nodular
masses, or raised plaques.
• Microscopic types:
–– Squamous cell carcinoma: present in the majority of
cases (90%)
–– Melanocarcinoma: 8%
–– Adenocarcinoma: of Bartholin gland or paraurethral
ducts (2%)
• Modes of cancer spread:
–– Direct spread: to the urethra, bladder, vagina, perineum,
anus, or groin
–– Lymphatic spread:
Anatomical site Draining lymph nodes

Labia majora and They drain into the superficial
minora, fourchette, inguinal and femoral lymph nodes,
perineum, and which drain into deep femoral nodes
prepuce
Glans clitoris It is similar to the rest of the vulva.
However, lymphatics from the
clitoris may drain directly into pelvic
lymph nodes
–– Hematogenous spread: to the liver, lungs, brain, and

bone (late)
• Clinical staging (International Federation of Gynecology

and Obstetrics, FIGO):
Stage 0 Intraepithelial carcinoma (carcinoma in situ)

Stage I IA Tumor confined to the vulva and/or perineum,
2 cm or less maximum diameter with stromal
invasion 1 mm or less. No nodal or distant
metastasis
IB Tumor confined to the vulva and/or perineum
either >2 cm maximum diameter or stromal
invasion >1 mm. No nodal or distant metastasis
Stage II Tumor of any size with spread to any of the
following: lower urethra, vagina, or anus. No
nodal or distant metastasis
Stage III IIIA Tumor of any size with spread to any of the
distant metastasis
PLUS
Spread to a single regional lymph node with the
area of cancer spread 5 mm or more
OR
Spread to one or two regional lymph nodes
with both areas of spread <5 mm
IIIB Tumor of any size with spread to any of the
distant metastasis
PLUS
Spread to two or more regional lymph nodes;
each area of spread to lymph nodes is 5 mm or
more
OR
Spread to 3 or more regional lymph nodes; each
area of spread to lymph nodes<5 mm
IIIC Tumor of any size with spread to any of the
distant metastasis
PLUS
Spread to regional lymph nodes with at least
one lymph node showing extracapsular growth
(through lymph node outer layer)
Stage IV IVA Tumor of any size with spread to any of the

following: upper urethra, bladder mucosa, rectal
mucosa, pelvic bone, or regional lymph node
metastasis with infiltration to surrounding
structures of the lymph nodes (fixed lymph
nodes)
IVB Any distant metastasis including pelvic lymph
nodes
Diagnosis:
The patient is usually postmenopausal, about 60–70 years old.
Less than 20% of patients are diagnosed before the age of 50.
• Symptoms:
–– Patients may be asymptomatic in early stages of the
disease.
–– Vulvar mass or ulcer.
–– Vulvar pain and pruritus.
–– Purulent or bloody discharge.
• Physical signs:
–– The lesion may appear as a cauliflower mass, malignant
ulcer with everted edges and indurated base, nodular
masses or raised plaques, with indurated base.
–– Inguinofemoral lymphadenopathy.
Treatment:
Stage I IA Wide local excision with safety margin (1 cm)
IB Modified radical vulvectomy and inguinal
lymph node dissection (or sentinel lymph node
biopsy). If lymph nodes are positive for cancer,
radiation and chemotherapy may be given
Stage II Modified radical vulvectomy and inguinal lymph node
dissection (or sentinel lymph node biopsy)
PLUS
Postoperative radiation therapy if cancer cells are at or
near surgical margins
Radiation with or without chemotherapy may be
considered for women unfit for surgery
Stage III Surgery (either a radical wide local incision or modified

or complete radical vulvectomy) PLUS inguinal lymph
node dissection PLUS postoperative
radiation therapy (± chemotherapy which may facilitate
radiation effect)
OR
Neoadjuvant therapy (radiation with or without chemo),
followed by surgery to remove residual cancer
This is often done to try to preserve normal structures
such as the vagina, urethra, and anus
OR
Radiation and chemotherapy (without surgery) if the
patient is unfit for surgery
Stage IV IVA Surgery (radical vulvectomy and inguinal
lymph node dissection vs. pelvic exenteration
depending on tumor spread) PLUS radiation
and chemotherapy (before or after surgery)
IVB Palliative treatment
Recurrent Local recurrence: surgery can still be tried for tumor
vulvar resection OR combinations of chemo, radiation therapy,
cancer and surgery
Widespread recurrence: palliative therapy
• Operative complications:
–– Wound breakdown (the most common complication)
–– Bleeding (primary or secondary)
–– Wound infection
–– Venous thrombosis and pulmonary embolism
–– Injury of femoral vessels during lymphadenopathy
–– Lower extremity lymphoedema (30%)
Prognosis:
Stage I and II The 5-year survival rate is 80–90%

Stage III The 5-year survival rate is 40–50%
Stage IV The 5-year survival rate is 20%
Vaginal Neoplasia 417
Vaginal Neoplasia
Vaginal Intraepithelial Neoplasia (VAIN)
Classification:
I. Squamous cell type
LSIL VAIN I The lower third of the vaginal epithelium

is replaced by undifferentiated cells
HSIL VAIN II The lower two-thirds of the
vaginal epithelium is replaced by
undifferentiated cells
VAIN III Full thickness of the vaginal epithelium
is replaced by undifferentiated cells. No
invasion below the basement membrane
is noted
II. Glandular cell type
Intraepithelial vaginal dysplasia of glandular origin (atypical

vaginal adenosis) is typically associated with in utero diethyl-
stilbestrol (DES) exposure.
Diagnosis:
• Symptoms:
In most cases, VAIN is asymptomatic, or it may present
by vaginal discharge, postcoital spotting, or dyspareunia.
–– In most cases, speculum and digital examination reveals
normal vaginal mucosa. Irregular, thickened, or red
areas in the mucosa may be noted.
–– Majority of lesions are located in the upper third of the

vagina, and they are multifocal in more than 50% of
cases.
• Work-up:
Colposcopic examination of the vagina is performed to
identify irregular surface or vascular abnormalities.
Schiller’s or Lugol’s iodine solution is applied to the vagi-
nal mucosa to delineate abnormal area before biopsy is
performed.
Treatment:
• LSIL: it can be managed by close surveillance.
• HSIL:
–– Surgical therapy:
❶ Local excision: it is the standard treatment, whenever
possible.
❷ Partial vaginectomy: it may be indicated when there
is extensive involvement of the vaginal vault.
❸ Total vaginectomy: it is rarely indicated for extensive
and persistent disease
–– Laser ablation:
The procedure is appropriate when the involved
area is well visualized and there is no suspicion of
invasion.
–– Topical therapy:
Topical therapy may be used for patients who are not
candidate for surgery or if the disease is early and mul-
tifocal, e.g., 5% imiquimod cream and fluorouracil.
–– Radiation therapy:
Because of associated complications, intracavitary
radiation therapy is rarely used and is only indicated if
other measurements fail.
Invasive Vaginal Carcinoma
Incidence: 3% of all malignant tumors of the female genital

tract
Pathology
The tumor may appear as a cauliflower mass, a malig-
nant ulcer, or diffuse infiltrative growth.
–– Squamous cell carcinoma in the majority of cases.
–– Adenocarcinoma may arise from vaginal adenosis,
Wolffian remnants, periurethral glands, or vaginal
endometriosis.
–– Melanoma.
• Mode of spread:
–– Direct spread:
Anteriorly to the bladder and urethra, posteriorly to
the rectum, superiorly to the cervix, inferiorly to the
vulva, and laterally into the parametrium
Carcinoma of the upper two-thirds: lymphatic spread
follows drainage of cervix.
Carcinoma of the lower third: lymphatic drainage
follows drainage of the vulva.
–– Hematogenous spread: distant metastases to liver and
other organs (late)
• Clinical staging (FIGO classification):
Stage 0 Carcinoma in situ

Stage I Invasive carcinoma limited to vaginal wall
Stage II Extension to paravaginal tissues, but not to the
pelvic wall
Stage III Extension to the pelvic wall

Stage IV Extension to bladder or rectal mucosa or outside
the true pelvis
IVa: extension to bladder or rectal mucosa
IVb: spread outside the pelvis
Diagnosis
• Symptoms:
–– Vaginal symptoms:
Vaginal bleeding: postcoital, unscheduled, or post-
menopausal bleeding
Watery, bloody malodorous vaginal discharge
Vaginal mass
Dyspareunia
–– Symptoms caused by local extension:
Urinary symptoms (e.g., dysuria), rectal symptoms
(e.g., tenesmus), pelvic pain
• Physical signs:
–– Most lesions occur in the upper third of the posterior
vaginal wall.
–– Speculum and bimanual examination: the lesion is indu-
rated, is necrotic, and usually bleeds on touch.
–– Rectal examination: it is performed to rule out local
extension of the disease to the rectum.
• Work-up:
–– Vaginal cytology: it is obtained at the time of physical
examination
–– Colposcopy: colposcopy is recommended if:
Cytology is abnormal despite normal physical
examination
In the presence of localized visible lesions to evalu-
ate the other parts of the vagina
Vagina is examined after application of acetic acid
and Lugol’s iodine stain
–– Office biopsy: of abnormal, acetowhite, no non-iodine

stained areas
–– Imaging studies:
Pelvic CT and MRI: to determine disease extent and
treatment plan
18-Fluoro-2-deoxyglucose-positron emission tomog-
raphy (FDG-PET): to evaluate lymph node
metastasis
Chest CT: to rule out distant metastasis
Treatment
Stage I Squamous cell carcinoma Adenocarcinoma

• If the tumor is <5 mm thick: • If the tumor is in
radiation therapy may be the upper part of
used alone (intracavitary the vagina: radical
radiation) hysterectomy,
• If the tumor is >5 mm: partial or radical
– If the tumor is in the vaginectomy,
lower or midportion of the pelvic lymph node
vagina: partial or radical dissection ± internal
vaginectomy (depends on and external
tumor size and site) radiation therapy
– If the tumor is in the • If the tumor is in
upper vagina: radical the lower portion of
hysterectomy, bilateral the vagina: external
radical pelvic lymph node and internal
dissection, and/or radical radiation therapy
or partial vaginectomy may be considered
External beam radiation to including radiation
inguinal/pelvic lymph nodes to regional lymph
may be indicated after surgery nodes
Stage II • Primary treatment is radiation (brachytherapy

and external beam radiation) including external
radiation to regional lymph nodes
• Radical surgery (radical vaginectomy or pelvic
exenteration) may be offered to women with a
small tumor in the upper vagina with adjuvant
radiotherapy
• Chemoradiation may be considered
Stage III • Primary treatment is radiation or chemoradiation

• Surgical role is limited in this stage
Stage VIA • Primary treatment is radiation or chemoradiation
• Surgical role is limited in this stage
Stage VIB Palliative radiation therapy to reduce control local
symptoms including bleeding. Chemotherapy may be
considered
Prognosis: The 5-year survival rate for stage I is about 70%;

stage II, 50%; stage III, 30%; and stage IV, 0–20%.
Cervical Intra-Epithelial Neoplasia-CIN

Definition: it refers to the presence of abnormal cells
occupying part or whole thickness of cervical epithelium
without invasion of the basement membrane.
Incidence: the incidence is 3–4% per year. Average age is
30–35.
Pathogenesis
• Site of carcinogenesis: abnormal/cancerous changes in the
cervix start within a physiologic area known as transfor-
mation zone (TZ):
–– Definition: it is a dynamic histological area that is cre-
ated by the process of squamous metaplasia where
columnar epithelium is transitioned to squamous epi-
thelium. The term squamocolumnar junction (SCJ)
describes the junction between cervical ectocervix
(squamous) and endocervix (columnar).
–– Anatomical site: TZ anatomical site changes in response
to various factors, e.g., age and hormonal changes
including:
During childhood: exposed on ectocervix
(ectropion)
In young and middle-aged women: at the external os
In menopausal women: within the cervical canal
Cervical Intra-Epithelial Neoplasia-CIN 423
• Risk factors:
–– HPV: it is the most important risk factor for precancer-
ous and cancerous cervical pathology of both histologi-
cal types:
Squamous cell carcinoma: HPV 16, 18, 58, 33, 45
Adenocarcinoma: HPV 16, 18, 45, 31, 33
–– Immunosuppression: e.g., HIV infection, immunosup-
pressive therapy.
–– Cigarette smoking.
–– Sexually transmitted disease, e.g., herpes simplex virus
and chlamydia. These infections may predispose to per-
sistence of oncogenic HPV.
–– Oral contraceptives: it may increase the risk of precan-
cerous and cancerous cervical pathology among HPV-
positive women.
Classification:
I. Traditional classification
• CIN I: the lower third of the cervical epithelium is replaced

by undifferentiated cells.
• CIN II: the lower two-thirds of the cervical epithelium is
replaced by undifferentiated cells.
• CIN III: the whole thickness of the cervical epithelium is
replaced by undifferentiated cells, but there is no invasion
below basement membrane.
II. The Bethesda system
Squamous cell lesions

Atypical squamous cells of Cells that are suggestive of, but
undetermined significance do not fulfill, the criteria for
(ASC-US) SIL
Atypical squamous cells cannot Cellular changes that do not

exclude HSIL (ASC-H) fulfill criteria for HSIL cytology
Low-grade squamous This includes HPV infection
intraepithelial lesion (LSIL) and CIN 1
High-grade squamous This includes CIN 2 and CIN 3
intraepithelial lesion (HSIL)
Squamous cell carcinoma Invasion of basement
membrane
Glandular cell lesions
Atypical glandular cells Atypical endocervical cells,
(AGC) atypical endometrial cells, or
atypical glandular cells not
otherwise specified (NOS)
Atypical glandular cells, favor More concerning changes of
neoplastic neoplasia
Endocervical adenocarcinoma Neoplastic changes, no invasion
in situ (AIS) of basement membrane
Adenocarcinoma Neoplastic changes, with
invasion of basement
membrane
Diagnosis:
• Symptoms:
–– Most patients are asymptomatic and are diagnosed at
the time of routine cervical cancer screening (pap test).
–– Few patients may present with postcoital bleeding.
• Physical signs:
Physical examination is usually normal in women with
CIN.
• Work-up:
I. For screening
• Whom to screen: all sexually active women should be

screened for CIN and cervical cancer. HPV-vaccinated
women should be screened per age-specific recommenda-
tions as non-vaccinated women
• Screening guidelines:
Initiation of screening At age 21 regardless of age of

initiation of sexual activity
Screening intervals • Age ≤ 30 years: every 3 years
(cytology only) if normal. HPV
reflex is advocated every 3 years
in this age group
• Age >30 years: every 5 years
(co-testing = cytology and HPV
testing). If HPV testing is not
available, cytology every 3 years
(if normal) is acceptable
Discontinuation of • Age 65 in low-risk women with
screening prior adequate screeninga
• At least 20 years after resolution
or adequate treatment of a high-
grade lesion (CIN 2 or more
severe lesion)
a
Adequate prior screening is defined as three consecutive negative
cytology or two consecutive negative HPV results in the last 10
years prior to the age of cessation of screening (with at least one
negative test within the last 5 years)
• How to screen:
I. Pap testing
• Definition: Pap test is a cytological test of the cervix and

vagina. Cytology is the study of morphologic changes in
exfoliated cells.
• Preparation:
–– Regarding the patient:
Pap test should be scheduled to avoid menstruation.
Abstinence from intercourse, douching, tampons,
vaginal medications, or vaginal contraceptives is rec-
ommended for 2 days before a test.
–– Regarding the physician:
No antiseptic solution is used.
Treatment of cervicitis or vaginitis prior to Pap test-
ing if possible.
• Sampling:
–– First: from the ectocervix by the end of the spatula. The
cervix is scraped in a 360° fashion at the squamocolum-
nar junction.
–– Second: from the endocervical canal, the endocervical
brush is inserted and rotated into the cervical canal for
half a circle.
• Test interpretation:
–– Negative Pap test: this reflects normal findings (absence
of malignant or premalignant changes) and the pres-
ence of endocervical component.
–– Positive (abnormal) results: abnormalities are reported
using Bethesda system, e.g., ASC-H.
–– Unsatisfactory: the sample cannot be adequately evalu-
ated. The test can be repeated in 2–4 months.
II. HPV testing
• Co-testing (pap test and HPV test) is considered at 30 years

or more. Cytology alone is less sensitive. Therefore, if co-
testing is not available, cytology should be performed more
often e.g. every 6 months if cotesting is indicated every 12
months, and yearly if co-testing is indicated every 3 years.
• The test reports high-risk HPV genotypes if present. HPV
16 and 18 are responsible for about 70% of cervical cancer.
All positive primary HPV screening tests should have addi-

tional testing performed from the same laboratory specimen
(reflex cytology). These findings may determine whether the
patient qualifies for expedited managment versus colposcopy.
If HPV 16 or 18 testing is positive, and additional testing is
not feasible, the next step should be to proceed with
colposcopy.
II. For diagnosis
I. Colposcopy
• Definition:
It is a stereoscopic system that uses magnification for
examination of vascular patterns of surface epithelium.
• Indications:
–– Abnormal cytology: see under Management – Abnormal
Pap test results
–– Abnormal examination: e.g., cervical warts, cervicitis,
polyps
–– Unexplained vaginal bleeding
There are no absolute contraindications to colposcopy.
However, treatment of cervicitis prior to examination, if
present, is recommended to avoid misinterpretation
• Preparation:
Vaginal douching, tampons, vaginal medications, and
intercourse should be avoided 24 hours prior to the test.
• Procedure:
–– After placement of the speculum, colposcopy is focused on
TZ of the cervix that is first examined with a high-intensity
light. Green filters can be used to enable better visualiza-
tion of cervical vascular pattern (turns red color to black).
–– Examination can be performed using:

Normal saline: to remove cervical mucus and allow
good exposure of cervical surface
Acetic acid (3–5%): acetic acid results in the acetow-
hite changes of abnormal cervical areas including
possible neoplastic lesions.
Lugol’s iodine solution: stains mature squamous cells
mahogany due to high cellular glycogen content in
these cells. Therefore, it helps to define limits of
TZ. Abnormal areas are not stained.
–– Biopsy is taken from abnormal areas (visually abnormal
areas, acetowhite areas, or unstained areas after applica-
tion of iodine).
• Interpretation:
Normal findings Abnormal findings
Full visualization of the • Acetowhite area
squamocolumnar junction is • Abnormal vascular patterns:
necessary: ❶ Mosaicism:
• Squamous epithelium It presents intraepithelial
appears pink vessels and vessel loops
• Columnar epithelium is running parallel to the
grape-like surface within acetowhite
• No acetowhite areas epithelium
• No unstained areas ❷ Punctation:
within squamous Punctations present
epithelium small vessels (fine) or large
• Normal vascular pattern vessels (coarse) that run
perpendicular to the surface
❸ Atypical vessels:
This includes vessels with
increased caliber, irregular
caliber, abnormal shape,
abnormal course, or abrupt
ends
Findings suggestive
Findings suggestive of high-grade
of low-grade lesions lesion
Acetowhite lesions Thin with irregular Dense with sharp
borders borders
Mosaicism Coarse Fine
Punctations Coarse Fine
II. Endocervical curettage (ECC)
• Indications:
ECC is indicated in the following situations:
–– Unsatisfactory colposcopy (incomplete visualization of
borders of SCJ or borders of abnormal area)
–– Colposcopy for HSIL
–– All cases with atypical glandular cell cytology
• Procedure: endocervical curettage is performed by intro-
ducing an endocervical curette 1–2 cm into the cervical
canal. This is not performed during pregnancy.
III. Cervical biopsy
• Multiple punch biopsies: it is taken from all abnormal

areas at the time of colposcopy.
• Excisional biopsy:
–– Indications:
Unsatisfactory colposcopy in the presence of CIN 2
or 3
Recurrent CIN 2 or 3
CIN 2 or 3 in ECC
–– Types of excisional biopsy:
Loop electrosurgical excision procedure
Cold knife conization

–– Technique:
The limits of the base of excisional biopsy can be
determined by application of Lugol’s iodine test, so
the samples include all abnormal areas.
The apex of the sample should typically be just
below the internal os to include the whole endocervi-
cal epithelium.
Bleeding from biopsy site
Infection
Cervical stenosis
Cervical incompetence (and preterm labor)
Management
• As per ASCCP recommendations in 2019, further recom-
mendations (colposcopy vs. surveillance) will be deter-
mined based on risk for CIN 3+. Risk is calculated using
prior history (including unknown history) and screening
results:
• If immediate CIN 3+ risk ≥4%, further intervention is
determined by immediate CIN 3+ risk:
–– If immediate risk is 4–24%: colposcopy is
recommended.
–– If immediate risk is 25–59%: expedited treatment or
colposcopy.
–– If immediate risk is ≥60%: expedited treatment is
preferred.
• If immediate CIN 3+ risk <4%, surveillance is deter-
mined by calculating 5-year CIN3+ risk:
–– If 5-year CIN3+ risk is <0.15%: return in 5 years.
–– If 5-year CIN3+ risk is 0.15–0.54%: return in 3 years.
–– If 5-year CIN3+ risk is ≥0.55%: return in 1 year.
• Per CIN grade, ASCCP recommends the following

management:
• CIN I: observation is preferred. However, treatment is
acceptable in patients with CIN I that persists for more
than 2 years.
• CIN II and III: Excision procedures are preferred to
ablation.
• AIS: Excision procedure.
I. Management of abnormal Pap test results
Unsatisfactory Management depends on HPV status:

Pap test • No HPV/unknown HPV status OR if
HPV is negative in a patient ≥25 years:
repeat screening after 2–4 months:
− If still unsatisfactory: colposcopy
− If satisfactory (abnormal or negative):
manage per ASCCP guidelines 2019
• If HPV is positive in a patient ≥25 years:
− Repeat screening after 2–4 months OR
− Colposcopy
• If HPV is positive (HPV 16 or 18):
colposcopy
Negative • If the patient is <30 years or if she is ≥30
Pap smear years with negative HPV status: continue
with absent with routine screening
transformation • If she is ≥30 years with unknown/no HPV:
zone or HPV testing is preferred (if negative,
endocervical routine screening is recommended).
cells Repeat cytology in 3 years is acceptable
• If she is ≥30 years with positive HPV:
either an HPV-based test in 1 year or
HPV genotyping and manage according
to ASCCP guidelines 2019
ASC-US Management according to ASCCP
guidelines 2019 (risk assessment)
ASC-H
LSIL • If preceded by ASC-H: repeat cytology

(<25 years) or HPV-based testing
(if ≥25 years). If both are negative,
repeat HPV-based testing after 3 years.
Otherwise, manage per ASCCP 2019
recommendations
• If preceded by HSIL: repeat colposcopy
and cytology (<25 years) or colposcopy
and HPV-based testing (if ≥25 years) at
1 year (or perform a diagnostic excision
procedure)
HSIL Colposcopy
• If squamocolumnar junction can be
visualized: diagnostic excisional procedure
(ablation procedure is acceptable)
• If squamocolumnar junction cannot
be visualized, upper limit of the lesion
cannot be reached, recurrent CIN2+, or
endocervical CIN2+: diagnostic excisional
procedure
AGC - NOS • All patients should undergo colposcopy,
endocervical curettage. Endometrial
sampling is indicated if:
❶ A patient is at increased risk of
endometrial cancer, e.g., chronic
anovulation
❷ Patients at or above the age of 35
• If it is normal or shows only CIN 1:
perform co-testing at 12 and 24 months; if
it shows any abnormalities, colposcopy is
advised
• If it shows CIN 2 or 3: manage per
protocol (ASCCP guidelines, 2019)
Atypical All patients should undergo colposcopy,
glandular cells, endocervical curettage. Endometrial
favor neoplastic sampling is done if any of the above
indications present. If no invasive disease is
detected, diagnostic excisional procedure is
performed
Adenocarcinoma Diagnostic excision biopsy should be

in situ performed to rule out invasive cancer:
• If margins are negative: hysterectomy.
Screening should continue for 25 years
(annually for 3 years and then every 3
years).
If fertility is desired, surveillance every
6 months for 3 years and then annually
for 2 years can be opted. Hysterectomy
should be performed after childbearing
• If margins are positive or ECC is positive:
re-excision to negative margins (even if
hysterectomy is planned)
Atypical Endometrial and endocervical sampling
endometrial cells is indicated. If there is no endometrial
pathology, colposcopy is performed
Management in abnormal Pap test in patients <25 years

ASC-US • Repeat cytology at 1-year (preferred) Or
• Reflex HPV testing: if negative, routine screening
can be resumed
ASC-H Colposcopy
LSIL Repeat cytology at 1-year:
• If ASC-H, HSIL or AGC: colposcopy is indicated
• If ASC-US or LSIL: repeat in 1-year
HSIL Colposcopy
I. Ablation procedures II. Excision procedures

Cold knife
Cryotherapy Laser ablation LEEP conization
Technique The The target area A thin wire Removal of
application of is vaporized by through which an the entire
a super-cooled laser to a depth electrical current cervical TZ
probe directly of at least 7mm is passed to cut including the
to cervical to reach the and coagulate cervical lesion
lesion base of the target area by scalpel
glands
I. Ablation procedures II. Excision procedures

Cold knife
Cryotherapy Laser ablation LEEP conization
Candidates −S
atisfactory colposcopy and − Unsatisfactory Similar to
negative ECC colposcopy in LEEP. It is
−S
mall and completely visible the presence of recommended
lesion (less than 50% of CIN 2 or 3 if margin
cervical surface area) −R ecurrent CIN status can be
2 or 3 concerning,
−C IN 2 or 3 in e.g., AIS
ECC
− I t can be
offered in
patients with
persistent CIN
I for at least 2
years
Advantages − Simple − I t can be − I t can be done −N

o thermal
procedure used if as an office damage to
−L ow cost a lesion procedure specimen
− Outpatient extends into − Tissue margins
procedure the fornix specimen
− No increased − N o increased available for
risk of risk of histopathology
preterm preterm
labor labor
Disadvantages − Copious − Post- − Thermal − Higher
vaginal treatment damage risk of
discharge vaginal interferes with hemorrhage
lasting for discharge (up assessment compared
weeks to 2 weeks) of specimen to LEEP
−N o available − More margins −H igher cost
biopsy expensive − Risk of cervical compared
than stenosis to LEEP
cryotherapy −R isk of − I t is not
−N o available bleeding an office
biopsy during and procedure
after the (anesthesia
procedure required)
−R isk of −R isk of
preterm preterm
labor (but labor
not extreme including
preterm labor extreme
<28 weeks) preterm
labor
(unlike
LEEP)
Cervical Carcinoma 435
Posttreatment follow-up
• Patients with excision margins negative for CIN: they should
be followed up by co-testing at 12 and 24 months. If both are
negative, co-testing is repeated after 3 years before returning
to routine screening
• Patients with excision margins or endocervical curettage
positive for CIN 2 or CIN 3: repeat cytology, and endocervical
sampling is recommended after 4–6 months. Repeat excision
or hysterectomy may be considered
• Patients with AIS or microinvasive carcinoma at the excision
margins are required to repeat diagnostic excision
Prognosis of CIN:
It may regress, persist without change, or progress to invasive
carcinoma:
• CIN I: 60% regress without treatment. Progression to can-
cer is <1%.
• CIN II: 5% progresses into invasive cancer if not treated.
• CIN III: 12% progresses into invasive cancer if not treated.
Cervical Carcinoma
Incidence: approximately, 8.1 cases per 100,000 women per
year are diagnosed with cervical cancer in the United States.
Etiology:
• Precancerous lesions: cervical intraepithelial neoplasia
(see before)
• Risk factors:
–– Demographic risk factors:
Age: the most common age is between 35 and 44
years.
Ethnicity: it is more common among Latin American
countries and US minorities.
Socioeconomic status: cervical cancer is more com-

mon among low socioeconomic population.
–– Behavioral risk factors:
Inadequate cervical cancer screening: using Pap test.
Early coitarche: this may be attributed to the increased
risk of acquiring oncogenic HPV infection.
Multiple sexual partners (either the patient or the
partner): this may also increase the risk of acquiring
oncogenic HPV infection.
Tobacco smoking: it increases the risk of cervical
cancer among HPV-positive women.
–– Medical risk factors:
Cervical high-risk human papillomavirus infection:
• HPV 16 is most commonly associated with
squamous cell cervical cancer (95% of squa-
mous cell carcinomas are associated with high-
risk HPV types).
• HPV 18 is most commonly associated with
adenocarcinoma.
High parity:
This may be attributed to action of hormonal sta-
tus, impaired immune response during pregnancy in
the cervical epithelium. During pregnancy, transfor-
mation zone shifts toward the ectocervix, and it
becomes more exposed to HPV infection.
Combined oral contraceptives (COCs):
• The risk may be attributed to:
❶ The action of COCs on HPV genome which
results in increase viral expression of oncop-
roteins E6 and E7
❷ Hormonal action of COCs on cervical
epithelium
Association of cervical cancer with COCs
is time related:
–– Risk is higher among COC users after 5 or

more years compared to non-users. The risk
proportionally increases with longer use.
–– The risk increases by 10% within the first
5 years of use, 60% after 5–9 years, and is
doubled at or beyond 10 years of use.
–– After cessation of COCs, this risk
decreases over time.
Immunosuppression:
HIV-positive women are at higher risk of CIN.
Pathology:
• Types of cervical carcinoma:
Squamous cell
Item carcinoma Adenocarcinoma
Incidence 80–90% 10–20%
Microscopic It always starts It arises from the
origin at or near the columnar epithelium
squamocolumnar lining the cervical canal
junction at the or cervical glands
external os
(transformation zone)
Macroscopic Variable Endocervical (cervical
origin (transformation zone canal)
is a dynamic area)
Squamous cell carcinoma
Cauliflower mass The lesion appears as a fungating
(commonest) necrotic mass, with indurated base,
and friable surface. The mass easily
bleeds with touch
Ulcerative lesion It appears an ulcer with a raised
everted edge and indurated base
Nodular lesion It appears as a firm nodule on the
cervix, which eventually ulcerates
Infiltrative lesion Malignant infiltration and fibrosis

result in cervical enlargement. The
cervix appears externally puckered
with a hard base
Adenocarcinoma
• In early cases, the cervix may appear normal
• As the tumor grows, the cervix becomes distended and barrel-
shaped
•E ventually, the tumor may grow outside the cervical canal
through the external os
Histologic subtypes of cervical cancer
Squamous cell • Keratinizing squamous cell carcinoma
carcinoma • Non-keratinizing squamous cell carcinoma
• Basaloid squamous cell carcinoma
• Verrucous squamous cell carcinoma
• Warty squamous cell carcinoma
• Papillary squamous cell carcinoma
•L ymphoepithelioma-like squamous cell
carcinoma
Adenocarcinoma • Endocervical type adenocarcinomas
• Endometrioid adenocarcinomas
• Papillary villoglandular adenocarcinoma
• Serous adenocarcinoma
• Clear cell adenocarcinoma
Other cervical • Adenosquamous carcinoma
carcinomas • Glassy cell carcinoma
• Adenoid cystic carcinoma
Neuroendocrine • Large cell neuroendocrine
tumors • Small cell carcinoma
• Mode of spread:
–– Direct (local) spread:
Downward: into the vagina
Upward: into the body of uterus
Anteriorly: into the bladder
Posteriorly: along the uterosacral ligaments to the

rectum
Laterally: into the parametrium where it may cause
ureteric obstruction, hydroureter and hydronephro-
sis, and eventually renal failure
Lymph node group Site Pathway
The paracervical At the crossing of Drain lymphatic
lymph nodes the ureter and the channels from the
uterine artery cervix
The obturator 1–3 in number, Drain the paracervical
lymph nodes located near the nodes
obturator foramen
The external iliac Related to Drain the obturator
lymph nodes external iliac nodes
vessels
The common iliac Related to Drain the external
lymph nodes common iliac iliac nodes and drain
vessels to lower aortic nodes
The sacral lymph In the sacral Drain lymphatic
nodes concavity and on vessels from the
the promontory posterior cervix
along the uterosacral
ligaments
–– Bloodstream: spread by bloodstream to distant organs

as the liver, lungs, brain, and bones and typically occurs
late when the disease is advanced
Diagnosis:
• Patient characteristics: patients are usually 35–44 years old
with positive risk factors, e.g., noncompliance to cervical
screening, smokers
• Symptoms:
–– Asymptomatic: early stages of invasive carcinoma may
be asymptomatic.
–– Early symptoms of cervical carcinoma:
❶ Vaginal bleeding: it is usually the first symptom.

• Initially, it may present as postcoital bleeding.
• Later, bleeding may become spontaneous, irregu-
lar, and variable in amount.
❷V
aginal discharge: it is the second commonest
symptom.
• Initially, it may be slight and watery.
• Later, it may become blood stained and odorous
secondary to ulceration and infection.
❸ Vaginal mass and dyspareunia
–– Late symptoms of cervical carcinoma:
❶P
ain: (indicates involvement of the tissues outside
the cervix)
• Visceral pain:
–– Deep pelvic pain: due to parametrial
involvement
–– Flank pain: due to ureteric obstruction
–– Dysuria: due to urinary bladder involvement
–– Pain with defecation: due to spread to uterosac-
ral ligaments or rectum
–– Suprapubic colicky pain: which may be present
in women with pyometra secondary to cervical
obstruction
• Somatic pain:
–– Sciatic pain or pain related to obturator nerve
course: due to nerve compression
–– Low back pain: due to uterosacral ligament
infiltration or metastasis to spinal column
❷ Urinary/fecal incontinence:
• Urinary and/or fecal incontinence may develop as
a manifestation of intestinal or urinary tract
fistulas.
• Fistulas can be caused by tumor growth, or as a
complication of surgery or radiotherapy.
❸ Leg swelling: due to pelvic lymphatic or venous

obstruction
–– General examination:
Assessment of lymphatic system (enlarged lymph
nodes)
Assessment of lower extremity edema
Inspection: for the presence of suspicious lesions in
the vulva and vagina
Speculum examination:
• The lesion may appear as a nodule, cauliflower
mass, or an ulcer. The lesion is indurated, is friable,
bleeds on touch, and may be fixed to surrounding
structures.
• In patients with endocervical carcinoma, the cer-
vix may appear normal, or enlarged
(barrel-shaped).
• The cervix is enlarged and indurated, with limited
cervical mobility.
• The parametrium may be indurated or nodular
due to malignant infiltration or infection.
Rectal examination:
Rectal examination is performed to assess disease
spread to the parametrium, uterosacral ligaments,
and rectum.
• Differential diagnosis:
Ulcerative Cervical • A flat, bright-red, and well-
lesions ectopy circumscribed area around the
external os
• There is no induration, friability, or
necrosis
Trophic • These ulcers may be present in
(decubitus) women with advanced uterine
ulcers prolapse
• These ulcers are moderate in size,
single or multiple, superficial, with
soft red base and clean-cut edges
Chancre of the • The ulcer is rounded and sharp
cervix edged
Herpetic • Young women at risk of sexually
ulcers transmitted diseases
• The ulcer is with no induration,
friability, or necrosis
Cauliflower Cervical • One or more soft well-defined
or nodular polyps growths; they may bleed on touch
lesions • They are not indurated or friable
Fibroid polyp • A firm well-defined polyp that
does not bleed on touch
• It has a pedicle attached to the
uterine body or cervix
• The rest of the cervix appears
normal
Condylomata • Warty growth over cervical surface
acuminata
Endometriosis • It may appear as blue-red or blue-
black lesions, usually small in size
• Work-up:
I. For early detection (screening)
Screening for cervical cancer includes Pap testing and col-

poscopic examination (see under screening for CIN)
II. To confirm the diagnosis (cervical biopsy)
• Value: cervical biopsy is essential to confirm diagnosis and

to identify type and histologic subtype of the tumor.
• Types of biopsy:
–– Punch biopsy: punch biopsies may be taken from visi-
ble lesions, with or without colposcopic examination.
–– Endocervical curettage: it may be performed in women
with abnormal pap testing who have unsatisfactory col-
poscopy, colposcopy for HSIL, or pap testing that shows
atypical glandular cell cytology.
–– Conization:
Conization can be performed in women with unsat-
isfactory colposcopy in the presence of CIN 2 or 3,
recurrent CIN 2 or 3, or if ECC shows CIN 2 or 3.
III. For staging (assessment of metastasis)
Radiological • CT scan (pelvis and abdomen):

investigations • To assess tumor size
• To assess local spread, e.g., parametrium,
bladder, rectum
• To assess intra-abdominal metastasis
• To assess lymph node metastasis
• To assess hydroureter and hydronephrosis
• Chest CT scan: to assess distant metastasis
to the lungs
• PET/CT scan:
It is used to assess distant metastasis in non-
early stages of the disease
Procedural • Cystoscopy: it can be performed to rule out
investigations spread to the bladder mucosa if bladder
invasion is suspected
• Sigmoidoscopy: it can be performed to rule
out spread to the rectal mucosa if rectal
invasion is suspected
IV. For preoperative assessment
Preoperative assessment is essential prior to any major

surgery. This includes physical examination and laboratory
tests (complete blood count, serum creatinine, serum electro-
lytes, serum albumin). Further tests may be recommended
according to patient medical history, e.g., blood glucose,
HgbA1C, electrocardiogram, and echocardiogram.
Treatment:
I. Prevention
• Vaccination against HPV infection: see HPV (under:

Genital infection)
• Adequate screening, management and follow-up for CIN
(see under: CIN)
II. Treatment
I. Clinical staging
Staging of cervical cancer is made through clinical examina-

tion, imaging and examination under anesthesia:
Stage FIGO staging description

0 Carcinoma in situ
I Carcinoma is strictly confined to the cervix (extension to
corpus should be disregarded)
IA: microinvasive cancer
Stage FIGO staging description

• IA1: measured invasion of stroma no greater than
3 mm in depth and no wider than 7 mm
• IA2: measured invasion of stroma greater than
3 mm and no greater than 5 mm in depth and no
wider than 7mm
IB: macroscopic cancer/microscopic greater than stage
IA
• IB1: clinical lesions no greater than 4 cm in size
• IB2: clinical lesions greater than 4 cm in size
II Carcinoma extends beyond the cervix but has not
extended to the pelvic wall
IIA: involvement of the vagina (but not the lower third
with no parametrial involvement):
• IIA1: clinically visible lesion ≤4 cm
• IIA2: clinically visible lesion >4 cm
IIB: parametrial involvement not reaching the pelvic
side wall
III Carcinoma has extended to the pelvic wall; on rectal
examination there is no cancer-free space between tumor
and the pelvic wall; tumor involves the lower third of
vagina; all cases with hydronephrosis or nonfunctioning
kidney should be included
IIIA: no extension to the pelvic wall, but involvement of
the lower third of vagina
IIIB: extension to the pelvic wall, or hydronephrosis or
nonfunctioning kidney due to the tumor
IV Carcinoma has extended beyond the pelvis or has
clinically involved mucosa of bladder or rectum
IVA: spread of growth to adjacent pelvic organs
IVB: spread to distant organs
II. Treatment according to stage

Stage Treatment
Stage I Stage If the patient wants to preserve fertility
IA1 Conization (cone biopsy)
• If margins are negative: no further treatment is indicated
• If the margins are positive: repeat conization versus radical
trachelectomy
If fertility is not a concern
• No lymphovascular invasion: simple hysterectomy (type I
hysterectomy)
• Lymphovascular invasion: radical hysterectomy with pelvic
lymphadenectomy may be recommended
Stage If the patient wants to preserve fertility

IA2 • Conization with pelvic lymph node dissection
• Radical trachelectomy with pelvic lymph node dissection
• External beam radiation therapy (EBRT) to the pelvis +
brachytherapy OR
• Radical hysterectomy with pelvic lymph node dissection
and sampling of para-aortic lymph nodes
• If lymph nodes are positive, parametrium is involved, or
excised tumor shows positive margins: radiation (EBRT)
and chemotherapy are usually recommended
• If lymph nodes are negative: radiation is only indicated in
the presence of:
❶ Large tumor
❷ Positive lymphovascular invasion
Stage If the patient wants to preserve fertility

IB1 Radical trachelectomy with pelvic lymph node dissection
• Same as stage IA2
• Chemotherapy may be given with radiation (concurrent
chemoradiation)
If the patient is not amenable to surgery
• Brachytherapy and external beam radiation therapy
Stage • Chemoradiation (primary treatment):

IB2 Chemotherapy: cisplatin or cisplatin plus fluorouracil
Radiation: both external beam radiation and
brachytherapy
• Radical hysterectomy with pelvic lymph node dissection
and para-aortic lymph node sampling (alternative
treatment): in addition to concurrent chemoradiation if
lymph nodes are positive, or in the presence of positive
margins
Stage Treatment
Stage Stage Same as stage IB1
II IIA1
Stage Same as stage IB2

IIA2
Stage • Chemoradiation:
IIB Chemotherapy: cisplatin or cisplatin plus fluorouracil
brachytherapy
Stage • Chemoradiation:
III Chemotherapy: cisplatin or cisplatin plus fluorouracil
brachytherapy
Stage Stage • Chemoradiation:

IV IVA Chemotherapy: cisplatin or cisplatin plus fluorouracil
brachytherapy
Stage Palliative treatment
IVB • Palliative radiotherapy:
❶ Brachytherapy: it may reduce the bleeding and size of
the tumor
❷ External radiation: for distant metastases and recurrent
pelvic masses
• Palliative surgery:
❶ Pelvic exenteration with diversion
❷ Diversion for management of malignant fistulas: e.g.,
implantation of the ureters into an ileal loop (ileal
conduit), colostomy
• Palliative medications:
❶ Chemotherapy: platinum drug (cisplatin or carboplatin)
along with another drug such as paclitaxel (Taxol).
❷ Targeted therapy: bevacizumab (Avastin) may be added
III. Cervical cancer during pregnancy
Treatment according to the stage
Previable pregnancy Viable pregnancy

Stage IA1 Conization Treatment after
delivery
Stage IA2 Pelvic lymphadenectomy, Treatment after
consider neoadjuvant delivery
chemotherapy if positive;
conization if negative
Stage IB1 Pelvic lymphadenectomy, Treatment after
(tumor <2 cm) consider neoadjuvant delivery
chemotherapy if positive;
conization if negative
Stage IB1 Pelvic lymphadenectomy Neoadjuvant
(tumor >2 cm) and neoadjuvant chemotherapy
chemotherapy
Stage IB2-IV Pelvic and para-aortic Neoadjuvant
lymphadenectomy chemotherapy
and neoadjuvant
chemotherapy
IV. Posttreatment follow-up
• Following radiotherapy:
Pelvic examination and/or imaging is performed following
chemotherapy. Anticipated response is progressive shrink-
age of the cervical mass. Tumors are expected to regress
for up to 3 months after therapy.
• Following surgery:
–– After a radical hysterectomy, 80% of recurrences are
detected within 2 years. Postoperative surveillance is
clinical, and it aims to early detect recurrences.
–– Surveillance visit should include history and physical
examination including pelvic examination and pap testing.
–– If history or examination is suspicious of recurrence,
imaging is indicated.
Prognosis:
The 5-year survival rate is as follows:
IA1 97.5
IA1 98%
IA2 95%
IB1 90%
IB2 75%
IIA 73%
IIB 66%
III 40%
IVA 22%
IVB 9%
Prognostic factors include:

❶ Cancer stage
❷ Lymph node involvement and the number of involved
lymph nodes
❸ Tumor size
❹ Depth of stromal invasion
❺ Lymphovascular space invasion
Further Reading
Bansal N, Herzog TJ, Shaw RE, et al. Primary therapy for early-stage
cervical cancer: radical hysterectomy vs radiation. Am J Obstet
Gynecol. 2009;201:485.e1.
Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the
cervix uteri. Int J Gynaecol Obstet. 2018;143(Suppl 2):22.
Bigby SM, Eva LJ, Fong KL, Jones RW. The natural history of vul-
var intraepithelial neoplasia, differentiated type: evidence for
progression and diagnostic challenges. Int J Gynecol Pathol.
2016;35:574.
Committee on Practice Bulletins—Gynecology. Practice Bulletin No.
168: cervical cancer screening and prevention. Obstet Gynecol
2016; 128:e111. Reaffirmed 2018.
Creasman WT. Cancer and pregnancy. Ann N Y Acad Sci.
2001;943:281.
De Giorgi V, Salvini C, Massi D, et al. Vulvar basal cell carcinoma:
retrospective study and review of literature. Gynecol Oncol.
2005;97:192.
Gallup DG, Talledo OE, Shah KJ, Hayes C. Invasive squamous
cell carcinoma of the vagina: a 14-year study. Obstet Gynecol.
1987;69:782.
Hiniker SM, Roux A, Murphy JD, et al. Primary squamous cell car-
cinoma of the vagina: prognostic factors, treatment patterns, and
outcomes. Gynecol Oncol. 2013;131:380.
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA
Cancer J Clin. 2011;61:69.
Koh WJ, Greer BE, Abu-Rustum NR, et al. Vulvar cancer, Version
1.2017, NCCN clinical practice guidelines in oncology. J Natl
Compr Canc Netw. 2017;15:92.
Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR,
Chon HS, Chu C, Clark R, Cohn D, Crispens MA. Cervical can-
cer, version 3.2019, NCCN clinical practice guidelines in oncol-
ogy. J Natl Compr Canc Netw. 2019;17(1):64–84.
Monk BJ, Wang J, Im S, et al. Rethinking the use of radiation and
chemotherapy after radical hysterectomy: a clinical-pathologic
analysis of a Gynecologic Oncology Group/Southwest Oncology
Group/Radiation Therapy Oncology Group trial. Gynecol Oncol.
2005;96:721.
Further Reading 451
ACOG Committee Opinion No. 463: Cervical cancer in adoles-

cents: screening, evaluation, and management. Obstet Gynecol.
2010;116:469.
Saraiya M, Watson M, Wu X, et al. Incidence of in situ and invasive
vulvar cancer in the US, 1998-2003. Cancer. 2008;113:2865.
Van der Linden M, Oonk MHM, van Doorn HC, et al. Vulvar
Paget disease: a national retrospective cohort study. J Am Acad
Dermatol. 2019;81:956.
Chapter 17
Uterine Corpus Cancers
Endometrial Hyperplasia
Classification:
I. World Health Organization old classification (WHO - 1994)
Risk of
malignant
Pathology transformation
Simple The glands are increased in 1%
hyperplasia number and become cystic and
without variable in size. No nuclear
atypia atypia
Simple It is similar to simple 10%
hyperplasia hyperplasia but with nuclear
with atypia atypia (irregular in shape
and size of the nuclei, dense
chromatin clumping, large
nucleoli, increased nuclear-to-
cytoplasmic ratio)

https://doi.org/10.1007/978-3-030-41128-2_17
454 Chapter 17. Uterine Corpus Cancers
Risk of
malignant
Pathology transformation
Complex The glands are crowded and 3%
hyperplasia complex and little or no
without intervening stroma, no nuclear
atypia atypia
Complex It is complex hyperplasia with 30%
hyperplasia nuclear atypia
with atypia
II. World Health Organization new classification

(WHO - 2014)
Risk of Risk of
coexisting malignant
Pathology cancer transformation
Hyperplasia This includes <1% <1%
without atypia previously
known simple
and complex
hyperplasia
without atypia
Atypical It includes 40% 14–45%
hyperplasia/ previously
endometrial known
intraepithelial hyperplasias
neoplasia with atypia
III. Endometrial intraepithelial neoplasia (EIN) classification
Benign endometrial •H yperplasia is attributed to prolonged

hyperplasia estrogen exposure
• This category ranges from persistent
proliferative endometrium to simple
hyperplasia
Endometrial Hyperplasia 455
Endometrial • This is considered endometrial

intraepithelial precancers
neoplasia • The stroma is replaced by
morphologically clonal epithelial
crowding (distinct from the
surrounding endometrium)
Diagnosis:
I. Screening
Endometrial sampling is indicated in symptomatic patients

depending on age and risk factors (see under: Endometrial
carcinoma).
II. Clinical features
• Symptoms: the patient may present with heavy menstrual

bleeding, irregular uterine bleeding, or postmenopausal
bleeding.
• Physical examination: the uterus may be normal sized or
slightly enlarged; adnexal examination is normal. However,
an estrogen-secreting ovarian tumor may be palpated.
III. Work-up
In patients with abnormal uterine bleeding, transvagi-
nal ultrasound allows for:
• Evaluation of endometrial thickness (for diagnosis of
endometrial carcinoma):
In premenopausal
In postmenopausal women women
−4 mm or less: endometrial cancer/ − Unlike postmenopausal
hyperplasia can be reasonably women, there is no
excluded cutoff for endometrial
−≥ 5 mm: further evaluation is biopsy
indicated to rule out endometrial
pathology (e.g., hysteroscopy,
endometrial biopsy)
• Evaluation of the adnexa: ultrasound may show the

following underlying or associated pathologies:
–– Polycystic ovaries.
–– A solid ovarian mass: ovarian granulosa cell tumor is
associated with 30% risk of endometrial hyperplasia
or, less commonly, carcinoma.
• Endometrial biopsy
–– Indications for endometrial biopsy:
❶ Women with postmenopausal bleeding (endometrial
thickness >4 mm)
❷ Premenopausal women aged ≥45 years with abnor-
mal uterine bleeding
❸ Women younger than 45 who present with abnormal
uterine bleeding and history of HNPCC, chronic
anovulation (e.g., PCOS, obesity), on tamoxifen
therapy, or if bleeding not responsive to medical
treatment
–– Techniques of endometrial biopsy:
❶ Office sampling ❷ Dilation and

(e.g., pipelle biopsy) curettage
Indication It is the standard It can be performed
sampling technique if office sampling
in most patients (less is inadequate,
cost, shorter time, less technically difficult,
surgical risks) or intolerable
Anesthesia No anesthesia/local Regional or general
anesthesia is required anesthesia
Procedure No dilation is required Cervical dilation is
required
Complications Risk of uterine Risk of uterine
perforation is 0.1–0.2% perforation is 1–2%
❸ Uterine brush (Tao brush): the brush may be supe-

rior to pipelle biopsy among postmenopausal (but
not premenopausal) women.
Treatment:
I. Prophylaxis
• Prophylaxis against unopposed endogenous estrogen:

–– Treatment of the cause of anovulation: e.g. thyroid
disorders, hyperprolactinemia
–– Endometrial protection of women with chronic anovu-
lation (e.g., PCOS): recommended options include oral
contraceptive pills, MPA (medroxyprogesterone
acetate), depot MPA injectables, or levonorgestrel-

releasing IUD.
• Prophylaxis against unopposed exogenous estrogen:
concurrent progestin is always used if hormonal therapy
with estrogen is warranted among women with preserved
uteri.
II. Definitive treatment
I. Simple endometrial hyperplasia without atypia
1. Premenopausal women
–– Oral progestins (medroxyprogesterone acetate
10–20 mg/day).
–– Progestin-releasing IUD.
–– Expectant management can be offered to low-risk
patients with ovulatory (regular) cycles.
• Follow-up:
–– If cycles become regular on treatment, no endometrial
sampling is needed, and treatment can be discontinued.
–– If cycles are persistently irregular, repeat endometrial
sampling every 3–6 months, and continue treatment.
2. Postmenopausal women
–– Oral progestins.
–– If oral progestins are contraindicated and the woman is
at high risk of endometrial cancer, hysterectomy may be
offered.
• Follow-up:
–– Repeat endometrial biopsy every 3–6 months. Treatment
can be stopped if bleeding stops.
II. Complex hyperplasia without atypia
–– Progestins (progestin-releasing IUD or oral proges-
tins) for 3–6 months.
offered.
• Follow-up:
–– Patients can get pregnant if their biopsies continue for
up to 1–2 years until it becomes normal. She can get
pregnant thereafter. Another endometrial biopsy may
be performed after delivery. Treatment may continue if
she is at high risk of endometrial cancer.
–– If pathology persists, higher-dose progestin therapy
(megestrol acetate at 80–160 mg or IUD) versus hyster-
ectomy should be discussed.
• Initiation:
–– Progestins (progestin-releasing IUD or oral proges-
tins) for 3–6 months.
offered.
• Follow-up:
Biopsy should be repeated every 3–6 months for 1 year
until it becomes normal. If it does not normalize, hysterec-
tomy (or high-dose progestins) should be considered.
III. Hyperplasia with atypia/EIN
If the diagnosis is made via office-based biopsy, D&C is indi-

cated to rule out coexisting endometrial carcinoma (40%).
However, it is not indicated if hysterectomy is decided.
Treatment of Hyperplasia with atypia in premenopausal Women
According to her fertility desire
No desire for future fertility Desire for fertility preservation
Hysterectomy High-dose progestin therapy, follow-up

with serial D&C biopsies every 3 months
for disease reversal (75–85%)
If the disease persists, hysterectomy

is recommended
Hysterectomy is the best option

Endometrial Carcinoma 461
Endometrial Carcinoma
Incidence:
the incidence of new cases of endometrial carcinoma is 27.5
per 100,000 women per year (the most common gynecologic
cancer in developed countries).
Etiology:
• Risk factors:
–– Age: the risk of endometrial cancer increases with age
(80% of cases occur in postmenopausal women above
the age of 55 years).
–– Excess exposure to unopposed estrogen:
Early age of menarche and late age of natural
menopause.
Chronic anovulation, e.g., PCOS (history of
infertility).
Nulliparity and low parity.
Obesity (peripheral conversion of androstenedione
to estrone in adipose tissue). The risk of endometrial
cancer is doubled among o verweight women (BMI
25–29.9) and is tripled among obese women (BMI of
30 or above).
Estrogen-secreting ovarian tumors (granulosa cell
tumor).
Prolonged estrogen therapy for menopausal symp-
toms without adjuvant progestin therapy.
Liver disease (estrogen is metabolized by the liver).
–– Diabetes mellitus type 2: diabetic patients are at twice
risk of endometrial cancer; 10–30% of endometrial can-
cer patients are diabetics. However, it is not clear
whether the risk is direct or is attributed to the associa-
tion between diabetes and obesity.
–– Infection: senile endometritis and pyometra (chronic
irritation).
–– Family history and genetic factor: premenopausal

women.
Lynch II syndrome (hereditary nonpolyposis colorectal
cancer (HNPCC)):
Definition: a familial cancer syndrome consisting of
breast, endometrial, ovarian, and colorectal cancers.
Other cancers include gastrointestinal, brain, renal,
and skin cancers.
Incidence: in <5% of patients with endometrial can-
cer, Lynch syndrome is associated with 70% risk of
endometrial cancer.
Etiology: mode of inheritance is autosomal domi-
nant. The disease is caused by mutations in mismatch
repair genes (MLH1, MSH2, MLH3, MSH6, TGBR2,
PMS1, and PMS2).
–– Tamoxifen therapy: it causes a two- to threefold higher
risk by having a modest “unopposed” estrogenic effect
on the endometrium. However, the risk is low (<1% per
year), and treatment should be given if indicated.
–– Prior pelvic radiation therapy: radiation to the pelvis
increases the risk of a second type of cancer including
endometrial cancer.
–– Precancerous lesions: endometrial hyperplasia (see
before).
–– Oral contraceptive use: use for 1 year confers 30–50%
reduced risk of endometrial cancer, and risk reduction
extends for approximately 10 years.
–– Intrauterine device (IUD): even non-hormone-
releasing IUDs are associated with lower risk of endo-
metrial cancer.
Pathology:
• Macroscopic appearance:
–– Localized type: the tumor grows as a localized mass
which may become polypoidal.
–– Diffuse type: malignant changes involve large area of

the endometrium, which becomes indurated without
exophytic growth.
• Microscopic appearance:
–– Endometrioid adenocarcinoma (90% of cases):
Variant with squamous differentiation:
• Adenoacanthoma: it is an adenocarcinoma mixed
with benign squamous metaplasia presenting
more than 10% of tumor size.
• Adenosquamous carcinoma: a mixed columnar
and squamous cell carcinoma.
Villoglandular variant
Secretory variant
Ciliated cell variant
–– Squamous cell carcinoma
–– Other histologic types: e.g., mucinous carcinoma, serous
carcinoma, clear cell carcinoma, and undifferentiated
carcinoma
–– Types of endometrial carcinoma:
Type I endometrial Type II endometrial

Feature carcinoma carcinoma
Unopposed Present Absent
estrogen
Menopausal Younger age Older age
status
Hyperplasia Present Absent
Race More common in More common in
white race black race
Grade Low High
Myometrial Minimal Deep
invasion
Specific subtypes Endometrioid Serous, clear cell
Behavior Stable Aggressive
• Histologic grading (FIGO system):
Grade Definition
1 5% of a nonsquamous or nonmorular solid growth
pattern
2 6–50% of a nonsquamous or nonmorular solid growth
pattern
3 >50% of a nonsquamous or nonmorular solid growth
pattern
• Mode of spread:
–– Direct spread:
Endometrial carcinoma is typically slow growing. The
tumor directly grows into the myometrium, cervix, and
fallopian tube. It may take several years to invade the
surrounding structures, e.g., bladder, rectum, and sig-
moid colon.
The upper third of •D

rains via hypogastric lymphatics to
the corpus including interiliac and then common iliac lymph
the fundus nodes and posteriorly to para-aortic
lymph nodes
•D
rains via the ovarian lymphatics into
para-aortic nodes
The middle and •D
rains mainly to obturator lymph
lower third of the nodes (lateral) and then into the
corpus internal iliac lymph nodes
The cornua of the • I t may drain along the round ligaments
uterus into inguinal lymph nodes
–– Bloodstream: to distant organs such as the liver, lungs,

brain, and bones
Diagnosis:
• Symptoms:
❶ Asymptomatic: asymptomatic presentation is not
common.
❷ Early symptoms of endometrial carcinoma:
➀ Vaginal bleeding: it is the most common symptom.
• Postmenopausal bleeding
• Pre- or perimenopausal: in the form of intermen-
strual bleeding, irregular or heavy menstrual
bleeding
➁ Vaginal discharge
➂ Simpson’s pain:
• Definition: it is colicky suprapubic pain associated
with endometrial cancer. It may last for 1–2 hours
a day.
• Incidence: approximately 15% of patients.
• Etiology: it is due to expulsive uterine
contractions.
❸ Late symptoms of endometrial carcinoma:
1. Pain: indicates peritoneal involvement or extrauter-
ine spread
• Visceral pain: e.g., deep-seated pelvic pain, dys-
uria, painful defecation
• Somatic pain: e.g., sciatic pain
2. Symptoms of tumor spread:
• Urinary/fecal incontinence: secondary to fistulae
• Symptoms of distant metastasis: e.g., shortness of
breath, hemoptysis
Obesity is a risk factor.
Examination of lymphatic system to rule out enlarged
supraclavicular and inguinal lymph nodes.
Breast examination: to rule out associated breast
cancer (Lynch II syndrome).
Abdominal examination: the uterus is usually not
abdominally palpable.
Lower limb examination: to rule out lower limb
edema secondary to obstruction of pelvic lymphatics.
Speculum examination: to assess cervical/vaginal
involvement
• Assessment of the vagina and cervix for signs of
disease spread.
• Assessment of the uterus: the uterus is usually nor-
mal sized or slightly enlarged. Uterine mobility is
evaluated to assess fixity to surrounding structures.
Rectal examination: rectal examination is performed
to rule out infiltration of uterosacral ligaments and
spread to the rectum.
• Work-up
I. For screening
• Among low-risk women:

There is currently no role for routine screening.
Evaluation of endometrial pathology is based on symp-
toms, age, and risk factors.
• Among women with Lynch syndrome:
Asymptomatic women may be offered annual endome-
trial sampling starting at age 30–35 years or 10 years
younger than the age at diagnosis of Lynch syndrome-
associated cancers in the family.
II. For diagnosis
Suspicious findings that warrant further evaluation include:
–– Increased endometrial thickness: endometrial thickness
greater than 4 mm is considered abnormal in postmenopausal
women. Endometrial thickness is not used to guide clinical
decision in premenopausal or perimenopausal women.
–– Loss of the subendometrial sonolucent layer, which
may indicate myometrial invasion.
–– The presence of an echogenic endometrial mass.
–– Intrauterine fluid and fluid in Douglas pouch.
• Hysteroscopy:
It may be performed at the time of endometrial sam-
pling to ensure that visually abnormal areas are adequately
biopsied.
III. For assessment of metastasis
Imaging • CT/MRI scan (pelvis and abdomen):

work-up • Indication: imaging is indicated only if
extrauterine spread is suspected, e.g., grade
3 tumor, non-endometrioid histology (type 2
endometrial cancer)
• Findings:
This may provide additional information on:
• The size of the tumor
• S pread to surrounding pelvic tissue/organs
• M etastases to pelvic and para-aortic lymph
nodes
• Liver metastasis
• Chest CT scan: to rule out lung metastasis in
these patients
• PET/CT scan: indicated in advanced cases
Procedural • Cystoscopy: to rule out bladder mucosal invasion
work-up if clinically or radiologically suspected
• Sigmoidoscopy: to rule out colorectal mucosal
invasion if clinically or radiologically suspected
IV. For assessment of familial predisposition
• Indications for genetic testing:

Women with endometrial cancer should be offered testing
for Lynch syndrome in the following indications:
❶ Age at diagnosis is less than 50 years.
❷ Synchronous Lynch-associated tumor, e.g., colorectal
cancer.
❸ At least one first-degree relative with a Lynch-associated
tumor diagnosed under the age of 50.
❹ At least two first- or second-degree relatives diagnosed
with Lynch-associated tumors at any age.
• Methods of genetic testing:
–– Tumor testing:
Test type: genetic testing of the tumor for tumor mic-
rosatellite instability and/or immunohistochemistry.
Results: if tumor microsatellite instability is absent
and expression of mismatch repair proteins is intact,
the diagnosis of Lynch syndrome is unlikely.
Otherwise, further testing is indicated.
–– Germline testing:
Test type: a blood sample is drawn for germline
sequencing and analysis of deletion/duplication.
Results: the diagnosis of Lynch syndrome is made if
mutation of a mismatch repair gene (MLH1, MSH2,
MSH6, PMS2) or the EPCAM gene (causing MSH2
loss of expression) is detected.
V. For preoperative evaluation
Preoperative assessment is essential prior to any major sur-

gery. This includes physical examination and laboratory tests
(complete blood count, serum creatinine, serum electrolytes,
serum albumin). Further tests may be warranted according to

patient medical history, e.g., blood glucose, HgbA1C, electro-
cardiogram, and echocardiogram.
Treatment:
I. Prophylactic treatment
• Appropriate management of endometrial hyperplasia see

under: Endometrial hyperplasia.
• Prophylactic surgery: women with Lynch syndrome should
be offered prophylactic hysterectomy after they complete
their families. In the meanwhile, annual endometrial can-
cer screening may be offered starting at the age of 30–35.
II. Treatment of diagnosed patients
1. Surgical staging
• Preoperative assessment of disease stage:

Endometrial biopsy is performed to confirm diagnosis.
If histopathology is consistent with non-endometrioid
endometrial carcinoma or if the tumor is grade 3, pelviab-
dominal and chest imaging is indicated.
• Surgical staging:
Final staging is achieved via surgical exploration and
histopathology. Staging can be performed via minimally
invasive or open approach.
Staging laparoscopy/ Staging laparotomy

robotic-assisted staging
Candidates Early stages (disease Extrauterine pelvic
confined to the genital spread. Resectable
tract) tumor
Approach • Laparoscopic/robotic- •S
tep 1: an adequate
assisted hysterectomy vertical abdominal
with bilateral salpingo- incision is required
oophorectomy (BSO) •S
tep 2: peritoneal
•S entinel lymph node washings for
biopsy: it is sent for cytologic assessment
frozen pathology; if •S
tep 3: for
negative, no further intraabdominal and
action is required pelvic exploration
•P eritoneal washings for for palpable lesions,
cytologic assessment biopsies can be
and omental biopsy are obtained
obtained if the tumor •S
tep 4: simple/
is grade 3 or type 2 radical
endometrial cancer hysterectomy and
BSO
•S
tep 5: pelvic
± para-aortic
lymphadenectomy
Based on this information, staging can be made, and treat-

ment plan can be determined.
FIGO 2009 staging

FIGO
stage Surgical-pathologic findings
I Tumor confined to the uterus
IA Tumor invades less than 50% of myometrium
IB Tumor invades at least 50% of the myometrium
II Tumor extends to cervical stroma but still confined to
the uterus
IIIA Tumor involves serosa and/or adnexa
IIIB Vaginal and/or parametrial involvement
FIGO 2009 staging

FIGO
stage Surgical-pathologic findings
IIIC Pelvic and/or para-aortic lymph node metastasis:
IIIC1: positive pelvic lymph nodes
IIIC2: positive para-aortic lymph node with or
without pelvic lymph nodes
IVA Tumor invades bladder mucosa and/or bowel mucosa
IVB Distant metastasis (i.e., inguinal nodes, omentum)
2. Treatment according to stage
Type 2 endometrial
Stage Type 1 endometrial cancer cancer
Stage If the patient is candidate for TH-BSO, pelvic
I surgery and para-
Stage IAG1 Stage 1 (rather aortic lymph
than IAG1) node sampling/
If there is no
TH-BSO dissection,
desire for future
PLUS omentectomy
fertility
Postoperative PLUS
Total
radiotherapy Postoperative
hysterectomy –
(vaginal brachy- chemotherapy
bilateral salpingo-
therapy, external (carboplatin and
oophorectomy
(TH-BSO) pelvic radiation, paclitaxel) and
radiation therapy
If future fertility or both)
is strongly
desired
Fertility
preservation
management
(see later)
If the patient is not candidate for
surgery
Radiotherapy (brachytherapy
followed by external pelvic radiation)
Type 2 endometrial
Stage Type 1 endometrial cancer cancer
Stage If the patient is candidate for TH-BSO,
II surgery omentectomy and
peritoneal biopsies,
Radical hysterectomy, BSO + pelvic
pelvic and para-
and para-aortic lymph node
aortic lymph node
dissection/sampling
dissections, and
PLUS
pelvic washings
Radiation therapy (vaginal
PLUS
brachytherapy and external pelvic
Postoperative
radiation)
chemotherapy
If the patient is not candidate for (carboplatin
surgery and paclitaxel),
radiation therapy,
Radiotherapy (vaginal or external or both
pelvic radiation)
Stage If the tumor is resectable TH-BSO,
III omentectomy and
Hysterectomy (simple or radical), peritoneal biopsies,
pelvic and para-aortic lymph pelvic and para-
node dissection, pelvic washings, aortic lymph node
omentectomy dissections, and
PLUS pelvic washings
Postoperative chemoradiation PLUS
(external pelvic radiation with or Postoperative
without brachytherapy) chemotherapy,
If the tumor is unresectable radiation therapy,
or both
Chemo and/or radiation. It may be
followed by surgery if the tumor
shrinks and becomes resected
Stage • Hormonal therapy: high doses of progestins may be
IV used in patients diagnosed with distant metastasis (if
the tumor is estrogen, progesterone receptor positive)
• Palliative chemotherapy: paclitaxel, doxorubicin, and
carboplatin or cisplatin
• Palliative surgery: TH-BSO may be performed to
prevent excessive bleeding
• Palliative radiotherapy: it can be used as an
alternative to surgery for the same indication
Fertility preservation management

• Patient counseling: the risk of disease progression should
be discussed with the patient.
• Hormonal therapy without hysterectomy: progestins are
administered to promote disease regression.
• Follow-up: endometrial biopsy is repeated every 3 months.
Treatment dose can be increased if needed. However, evi-
dence of disease progress or persistence despite treatment
indicates surgical treatment.
• Surgical staging: it is warranted after the patient completes
her family.
3. Postoperative follow-up
Clinical Thorough history and physical examination

follow-up including pelvic examination every 3–6 months
for 2 years and then every 6–12 months
thereafter.
Laboratory The role of serum CA 125 is controversial. It
follow-up may be used in selected patients, e.g., serous
carcinoma patients
Imaging Imaging is not routinely warranted unless
follow-up clinically indicated
Prognosis:
The prognosis of endometrial carcinoma is overall good
due to the following factors:
❶ The tumor is usually well differentiated (low grade).
❷ The tumor is slowly growing.
❸ Early diagnosis due to early presentation with postmeno-
pausal bleeding.
Poor prognostic variables in endometrial cancer:
❶ Advanced surgical stage
❷ High tumor grade (grade 3)
❸ Histologic type: papillary serous or clear cell adenocarci-

noma (type 2)
❹ Presence of deep myometrial invasion or lymphovascular
space invasion
❺ Peritoneal cytology positive for cancer cells
❻ Large tumor size
The 5-year survival rates per stage are as follows:
Stage I 80–90% Stage III 50–70%

Stage II 70–80% Stage IV 20%
Uterine Sarcoma
Incidence:
Uterine sarcoma accounts for 3–9% of all uterine malignant
neoplasms.
Risk factors:
• Age: mean age at diagnosis is 60 years old.
• Race: there is twofold increase in the risk of leiomyosar-
coma among black women.
• Tamoxifen: use of tamoxifen for 5 years or more increases
the risk.
• Pelvic radiation: it is more associated with risk of carcino-
sarcoma, which is no longer classified as a sarcoma, than
subtypes of uterine sarcoma
• Hereditary conditions:
–– Hereditary leiomyomatosis and renal cell carcinoma
(HLRCC) syndrome:it is an autosomal dominant syn-
drome that consists of cutaneous and uterine leiomyo-
mas and papillary renal cell cancer.
–– Hereditary retinoblastoma: survivors are at higher risk
for sarcomas including uterine sarcoma.
Uterine Sarcoma 475
Classification:
I. Homologous
• Endometrial:
Low-grade endometrial High-grade
sarcoma endometrial sarcoma
Macroscopic Diffuse infiltrative non- Soft fleshy fungating
features capsulated tumor with mass that may
fingerlike projections project into the
that may invade the uterine cavity and
parametrium extend into the
vagina
Microscopic Masses of round and oval Cords or sheets of
features stromal cells with mild endometrial stromal-
atypia like cells
Clinical Vaginal bleeding, Profuse vaginal
features asymmetrically enlarged bleeding, colicky
uterus pain, protruding mass
through the cervix
• Myometrial:
–– Leiomyosarcoma represents 30% of sarcomas:
Epithelioid leiomyosarcoma: it is characterized by
round to polygonal cells and abundant eosinophilic
or clear cytoplasm.
Myxoid leiomyosarcomas: it is characterized by
myxoid appearance.
• Nonspecific supporting tissue (e.g., connective tissue,
blood vessels, lymphatic vessels):
–– Rhabdomyosarcoma
–– Hemangiopericytoma
II. Heterologous
These tumors contain adenosarcoma and non-native tissue,

e.g., rhabdomyoblastic differentiation, cartilaginous differen-
tiation, and osseous differentiation.
Surgical staging (FIGO staging):

FIGO Surgical-pathologic findings
stage
I Tumor confined to the uterus
IA Tumor is 5 cm or less
IB Tumor >5 cm
II Tumor extends beyond the uterus into the pelvis, but
not outside of the pelvis. No lymph nodes or distant
metastasis
IIIA Tumor spreads to one abdominal site
IIIB Tumor spreads to more than one site
IIIC Pelvic and/or para-aortic lymph node metastasis
IVA Tumor invades bladder mucosa and/or rectal mucosa
IVB Distant metastasis
Diagnosis
• Symptoms:
–– Postmenopausal bleeding (most common)
–– Abnormal uterine bleeding
–– Abdominal pain and distension
–– Urinary symptoms
–– Asymptomatic (1–2%)
Groin or supraclavicular lymph nodes are assessed for
lymph node metastasis (uncommon with uterine
sarcomas).
–– Pelvic examination: the uterus is often enlarged.
Uterine Sarcoma 477
• Work-up:
–– Imaging:
Magnetic resonance imaging (MRI), computed
tomography (CT), or PET-CT:
–– Imaging is used to identify uterine masses and
assess pelvic or abdominal metastasis including
lymph node metastasis.
–– It is difficult to differentiate leiomyomas from
uterine sarcomas based on MRI findings.
Chest CT: to rule out lung metastasis
–– Endometrial biopsy: final diagnosis is made based on
histopathology.
• Differential diagnosis:
–– Uterine leiomyoma
–– Leiomyoma variant
–– Uterine adenomyoma
–– Hematometra
–– Uterine carcinosarcoma
–– Endometrial carcinoma
Treatment
FIGO Leiomyosarcoma/ Endometrial stromal

stage undifferentiated sarcoma sarcomas
Stages I •H
ysterectomy, BSOa, Hysterectomy, BSO
and II pelvic and para-aortic with or without
lymph node dissection or pelvic lymph node
sampling (of suspicious dissection (depends
nodes on imaging), on preoperative
abdominal exploration imaging)
for any pelvic, peritoneal No adjuvant
spread treatment
•S
tage I cancers may not
need adjuvant treatment.
Adjuvant chemotherapy is
recommended for stage II
cancers
FIGO Leiomyosarcoma/ Endometrial stromal

stage undifferentiated sarcoma sarcomas
Stage III Surgery as above Surgery as above
PLUS PLUS
Partial or complete Partial or complete
vaginectomy if the vagina is vaginectomy if the
involved vagina is involved
PLUS PLUS
Radiotherapy (with or Adjuvant therapy
without chemo) (radiation, hormone
therapy, or both)
This tumor is
not sensitive to
chemotherapy
Stage IV IVA: surgery (if resectable) IVA: surgery (if
PLUS chemoradiation resectable) PLUS
IVB: chemoradiation chemoradiation,
hormonal treatment
IVB:
chemoradiation,
hormonal treatment
Recurrent Same as stage IV
sarcoma
a
Oophorectomy is controversial. It is indicated in postmenopausal
women or if the disease is not confined to the uterus. However, in
young women with normal-looking ovaries, the risk of microscopic
metastasis is 3%. However, oophorectomy is justified if the tumor is
hormone-dependent
Prognosis
The 5-year survival rates of subtypes of uterine sarcoma are
as follows:
Localized Regional Distant
Leiomyosarcoma 64% 35% 13%
Undifferentiated sarcoma 68% 48% 20%
Endometrial stromal sarcoma 98% 91% 67%
Gestational Trophoblastic Neoplasia 479
Gestational Trophoblastic Neoplasia

Definition:
• Gestational trophoblastic disease (GTD): a spectrum of
placental tumors that share a common tumor marker
(β-hCG) including hydatidiform mole, invasive mole, cho-
riocarcinoma, placental site trophoblastic tumor, and epi-
thelioid trophoblastic tumor.
• Gestational trophoblastic neoplasia (GTN): the malignant
subgroup of gestational trophoblastic diseases:
–– Invasive mole
–– Choriocarcinoma
–– Placental site trophoblastic tumor
–– Epithelioid trophoblastic tumor
Incidence:
• Gestational trophoblastic tumors account for less than 1%
of female reproductive system cancers.
• The incidence of GTD is 1:1000 pregnancies in the United
States. However, most of these cases are benign (hydatidi-
form moles).
• The incidence of choriocarcinoma is 2–7:100,000 pregnan-
cies in the United States.
Classification of GTN:
Histologic Behavior
Origin characters
Invasive It almost Chorionic The disease
mole exclusively villi with is locally
originates trophoblastic invasive. It
from molar proliferation and does not
pregnancy invasion into metastasize
myometrium, distantly
peritoneum,
parametrium, or
vagina
Histologic Behavior
Origin characters
Gestational It may arise • I t is formed Blood-
choriocarcinoma following of sheets of borne
molar malignant distant
pregnancy trophoblastic metastasis
(50%), cells occurs
abortion •C horionic villi early in the
(25%), normal are absent course of
pregnancy the disease
(23%), or
ectopic
pregnancy
(2%)
Placental site It most This tumor The tumor
trophoblastic commonly consists of grows
tumor develops intermediate within the
following trophoblasts at uterus.
normal placental site Distant
pregnancy metastasis
occurs
late in the
course of
the disease.
The
disease is
associated
with low
levels of
β-hCG
Epithelioid The disease • The tumor is Distant
trophoblastic may not macroscopically metastasis
tumor be linked nodular. is common;
to a recent Microscopically, 25% of
pregnancy it consists of patients are
small cells, diagnosed
similar to with distant
placental site metastasis
tumor at the time
of diagnosis
Mode of spread (choriocarcinoma):

• Direct spread: to other pelvic organs such as the tubes,
ovaries, and parametrium
• Bloodstream:
–– The tumor metastasizes early to distant organs such as
the liver, lungs, brain, and bones (blood-borne).
–– Secondaries in the vulva and vagina may develop due to
retrograde venous spread.
–– The common sites of metastases are the lungs (80%),
vagina (30%), brain (10%), and liver (10%).
Diagnosis:
Patients have a recent history of abortion, delivery, or
molar pregnancy.
• Symptoms:
–– Persistent or irregular vaginal bleeding (the common-
est symptom):
Bleeding may start immediately or several weeks or
months following abortion, labor, or molar pregnancy.
–– Vaginal discharge: bloodstained odorous discharge.
–– Amenorrhea: due to continuous production of high lev-
els of β-hCG.
–– Acute abdominal pain – women with GTN may experi-
ence acute pain secondary to:
Uterine perforation and intraperitoneal hemorrhage
(tumor invasion)
Rupture or torsion of associated theca lutein cysts
–– Symptoms associated with metastasis – these symp-
toms may present the first manifestation of the
disease:
Vulvar or vaginal lesions (vaginal metastasis)

Dyspnea and hemoptysis (lung metastases)
Jaundice (liver metastases)
Neurological symptoms, e.g., headache (brain
metastases)
–– Inspection and speculum examination: hemorrhagic
nodules may be noted in the vagina and vulva.
–– Bimanual examination:
The uterus may be of normal sized or enlarged and
soft.
The ovaries may be enlarged and cystic (theca lutein
cysts are present in 30% of patients, due to ovarian
stimulation by high level of β-hCG).
• Work-up:
I. For early diagnosis (screening)
• Following management of molar pregnancy, serial serum

β-hCG is indicated every week till it is negative then every
month for 1 year
• During β-hCG follow-up, the following criteria are used
for diagnosis of GTN:
–– Plateau of β-hCG for 3 weeks or longer
–– Rise of β-hCG for 3 consecutive weeks or longer
–– Elevation of β-hCG for 6 months or more
The diagnosis can also be made through histopathology
II. For staging
• Pelviabdominal CT/MRI: to detect pelvic or abdominal

spread including liver metastasis
• Chest CT: to rule out lung metastasis
• Head CT: to rule out brain metastasis
III. To follow-up treatment
Serial β-hCG is so essential for diagnosis, determination of

prognosis, and follow-up after treatment.
Treatment:
I. Assessment of the patient for treatment planning
1. Staging (FIGO anatomic staging)
Clinical staging (FIGO staging)

Stage I Disease confined to the uterus
Stage II GTN extends outside of the uterus but is limited to
Stage the genital structures (adnexa, vagina, broad ligament)
III GTN extends to the lungs, with or without known
Stage genital tract involvement
IV All other metastatic sites (brain, liver)
2. Patient risk group (low vs. high)
Modified WHO Prognostic Scoring System as Adapted by

FIGO
Scores 0 1 2 4
Age <40 ≥40 – –
Antecedent Mole Abortion Term –
pregnancy
Interval from <4 4–6 7–12 ≥13
antecedent
pregnancy (in
months)
Pretreatment <1000 1000– 10,000– ≥100,000
serum β-hCG 10,000 100,000
(mIU/mL)
Largest tumor – 3–5 cm ≥5 cm –
size
Site of Lung Spleen, Gastroin- Liver,
metastases kidney testinal brain
Number of – 1–4 5–8 >8
metastases
Previous failed – – 1 ≥2
chemotherapy
Blood type O or A AB or B
Low risk = WHO score of 0 to 7; high risk = WHO score of >7
II. Treatment according to patient risk and histologic type
1. Choriocarcinoma
Treatment of choriocarcinoma according to patient risk and histologic type

Stage I
Fertility desired Fertility not desired
Initial treatment Resistant cases Initial treatment Resistant cases
Single-agent Combination chemotherapy Single-agent chemotherapy Combination

chemotherapy ± local excision + hysterectomy chemotherapy
Stages II & III
Low risk High risk
Initial treatment Resistant cases Initial treatment Resistant cases
Single-agent Combination Combination 2nd-line combination

chemotherapy chemotherapy chemotherapy chemotherapy
Stage IV
Initial treatment Resistant cases

Distant
metastasis
Combination 2nd line combination
chemotherapy chemotherapy
Brain metastasis Liver metastasis
Whole brain radiation/ Resection/hepatic artery infusion

IV and intrathecal methotrexate of chemotherapy/Radiation
2. Rare types of GTN
• Placental site trophoblastic tumor:

–– If nonmetastatic: it can be managed as stage I
choriocarcinoma.
–– If metastatic: combination chemotherapy (EMA/EP
regimen).
• Epithelioid trophoblastic tumor: hysterectomy is the pri-
mary treatment.
III. Posttreatment follow-up
• Stage I through stage III disease:

–– Weekly measurement of β-hCG levels until they are
normal for 3 consecutive weeks
–– Monthly measurement of β-hCG values until levels are
normal for 12 months
–– Effective contraception during the entire interval of
hormonal follow-up
• Stage IV disease:
–– Weekly determination of β-hCG levels until they are
normal for 3 consecutive weeks
–– Monthly determination of β-hCG levels until they are
normal for 24 months
1. Types of chemotherapy for GTN
Low-risk group therapy High-risk group therapy

Drugs A single agent is used: Multiple agents are used:
used ❶ M ethotrexate (MTX): ❶ T he MAC triple therapy:
it is the standard methotrexate, actinomycin
treatment D, and cyclophosphamide
❷ A
ctinomycin D: it ❷ E MA/CO protocol:
may be used as an etoposide, methotrexate,
alternative if MTX and actinomycin D,
is contraindicated cyclophosphamide, and
(e.g., renal or hepatic oncovin “vincristine”
dysfunction) ❸ EMA/EP protocol:
etoposide, methotrexate,
and actinomycin D,
etoposide and cisplatin.
This protocol can be used as
second line if the disease is
refractory to EMA/CO
Further Reading 487
Prognosis:
• Nonmetastatic GTN: cure rate is approximately 100%
with chemotherapy.
• Metastatic GTN:
–– Low-risk GTN: cure rate is approximately 100% with
chemotherapy.
–– High-risk GTN: cure rate is approximately 75% with
chemotherapy.
• The risk of recurrence is less than 1% if hCG is normalized
for at least 1 year after treatment.
Further Reading
tice bulletin, clinical management guidelines for obstetrician-
gynecologists, number 65, august 2005: management of
endometrial cancer. Obstet Gynecol. 2005;106:413.
Berkowitz RS, Goldstein DP. Clinical practice. Molar pregnancy. N
Engl J Med. 2009;360:1639.
Cagayan MS. High-risk metastatic gestational trophoblastic
neoplasia. Primary management with EMA-CO (etoposide,
methotrexate, actinomycin D, cyclophosphamide and vincristine)
chemotherapy. J Reprod Med. 2012;57:231.
Committee on Practice Bulletins-Gynecology, Society of
Gynecologic Oncology. ACOG practice Bulletin No. 147: lynch
syndrome. Obstet Gynecol. 2014;124:1042. Reaffirmed 2019.
Emons G, Beckmann MW, Schmidt D, et al. New WHO classifica-
tion of endometrial Hyperplasias. Geburtshilfe Frauenheilkd.
2015;75:135.
Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho
KR, Chon HS, Chu C, Cohn D, Crispens MA, Damast S. Uterine
neoplasms, version 1.2018, NCCN clinical practice guidelines in
oncology. J Natl Compr Cancer Netw. 2018;16(2):170–99.
Lancaster JM, Powell CB, Chen LM, et al. Society of Gynecologic
Oncology statement on risk assessment for inherited gynecologic
cancer predispositions. Gynecol Oncol. 2015;136:3.
Ngan S, Seckl MJ. Gestational trophoblastic neoplasia management:
an update. Curr Opin Oncol. 2007;19:486.
Ngan HYS, Seckl MJ, Berkowitz RS, et al. Update on the diagno-
sis and management of gestational trophoblastic disease. Int J
Gynaecol Obstet. 2018;143(Suppl 2):79.
Orbo A, Vereide A, Arnes M, et al. Levonorgestrel-impregnated
intrauterine device as treatment for endometrial hyperplasia: a
national multicentre randomised trial. BJOG. 2014;121:477.
Ricci S, Stone RL, Fader AN. Uterine leiomyosarcoma: epidemiol-
ogy, contemporary treatment strategies and the impact of uterine
morcellation. Gynecol Oncol. 2017;145:208.
Rosen MW, Tasset J, Kobernik EK, et al. Risk factors for endometrial
Cancer or hyperplasia in adolescents and women 25 years old or
younger. J Pediatr Adolesc Gynecol. 2019;32:546.
Sagae S, Yamashita K, Ishioka S, et al. Preoperative diagnosis
and treatment results in 106 patients with uterine sarcoma in
Hokkaido, Japan. Oncology. 2004;67:33.
Sanderson PA, Critchley HO, Williams AR, et al. New concepts for
an old problem: the diagnosis of endometrial hyperplasia. Hum
Reprod Update. 2017;23:232.
Tidy J, Hancock BW, Osborne R, Lawrie TA. First‐line chemother-
apy in low‐risk gestational trophoblastic neoplasia. Cochrane
Database Syst Rev. 2012;7
Torres ML, Weaver AL, Kumar S, et al. Risk factors for developing
endometrial cancer after benign endometrial sampling. Obstet
Gynecol. 2012;120:998.
Chapter 18
Ovarian Tumors
Classification of ovarian tumors
I. Primary ovarian tumors
Classification Types
Epithelial tumors • Serous tumor
• Mucinous tumor
• Brenner tumor
• Endometrioid tumor
• Clear cell (mesonephroid) tumor
Germ cell tumors Tumors of Dysgerminoma

germ cell
origin
Tumors of I. Tumors of embryonic cells

embryonic • Teratomas:
origin • Immature teratoma
• M
ature teratoma: either solid or
cystic (dermoid cyst)
• M
onodermal tumors, e.g., struma
ovarii
• Embryonal carcinoma
II. Tumors of extraembryonic cells
• Yolk sac tumor (endodermal
sinus tumor)
• N on-gestational choriocarcinoma
• Mixed tumors

https://doi.org/10.1007/978-3-030-41128-2_18
490 Chapter 18. Ovarian Tumors
Classification Types
Sex cord-stromal • Granulosa cell tumor
tumors • Theca cell tumor
• Granulosa-theca cell tumor
• Sertoli cell tumor
• Leydig cell tumor
• Sertoli–Leydig cell tumor (androblastoma)
• Gynandroblastoma
• Fibroma/fibrosarcoma
II. Secondary ovarian tumors
Tumors may metastasize to the ovary from different organs,

most commonly the endometrium, breast, stomach, and
colon.
I. Primary Ovarian Tumors
I. Epithelial tumors
❶ Serous tumors:
• Incidence: The most common type of ovarian tumors
• Types:
Chapter 18. Ovarian Tumors 491
Macroscopic features Microscopic features

Simple serous ▪ Size: variable (usually The cyst is lined
cystadenoma small to moderate by cuboidal or low
size) columnar epithelium
▪ Surface: smooth which may be ciliated
▪ Laterality: usually (fallopian tube-like
unilateral (90%) structure)
▪ Cut section:
unilocular, thin
walled, filled with
clear serous fluid
Papillary serous ▪ Size: variable The cyst is lined
cystadenoma ▪ Surface: smooth by cuboidal or low
▪ Laterality: usually columnar epithelium
unilateral which may be ciliated.
▪ Cut section: Papillae consist of
multilocular, thin connective tissue
walled, filled with core covered with
clear serous fluid, columnar epithelium.
with intracystic or Psammoma bodies
extracystic papillae appear within the
stroma as small
spherical laminated
structures.(formed by
deposition of calcium
in degenerating
epithelial cells)
Borderline Macroscopic features Malignant changes
serous tumor are similar to papillary without stromal
tumors invasion
Serous cyst- Gross features of Malignant featuring
adenocarcinoma malignancy, e.g., solid cells (dense chromatin,
areas, short thick increased nucleus/
papillae, infiltration cytoplasmic ratio, large
of the capsule, nucleoli) invading the
hemorrhage, and stoma
necrosis
❷ Mucinous tumors:
• Incidence: The second most common epithelial tumor
• Types:
Microscopic
Macroscopic features features
Mucinous ▪ Size: usually large The cyst is lined
cystadenoma ▪ Surface: usually by columnar
smooth and lobulated occasionally
▪ Laterality: usually ciliated epithelium
unilateral (90%) with goblet
▪ Cut section: the tumor cells (resembles
is cystic multilocular, endocervix or
filled with mucin. intestinal lining)
Mucin is colorless,
but it may be stained
yellow or brownish
due to bleeding
Borderline Features are similar to Cellular malignant
mucinous tumor mucinous cystadenoma changes without
invading
underlying stoma
Mucinous cyst- Gross features of Malignant cells
adenocarcinoma malignancy, e.g., solid with stromal
areas, short thick invasion
papillae, infiltration
of the capsule,
hemorrhage, and
necrosis
❸ Brenner tumor:
• Incidence: it is a rare tumor. It usually affects women
above the age of 40.
–– Size: small to moderate (usually <2 cm in diameter).
–– Surface: smooth.
–– Cut section: solid, yellowish.
–– Behavior: it is a benign tumor (5% are associated
with malignancy).
–– It consists of transitional or squamous epithelial cells
embedded in a connective tissue stroma
–– The nuclei of these cells are characterized by longitu-
dinal grooving (coffee bean appearance)
• Endometrioid carcinoma:
It is a rare form of malignant ovarian tumors that may
arise from the surface epithelium or ovarian
endometriosis.
• Clear cell (mesonephroid) carcinoma:
–– Incidence: rare ovarian tumor
–– Macroscopic features:
Laterality: unilateral.
Cut section: a solid tumor with small cystic spaces.
Behavior: it is highly aggressive malignant tumor.
–– Microscopic features:
Clear cell adenocarcinoma consists of clear or “hob-
nail” cells, which have scanty cytoplasm and large pro-
truding nuclei
II. Germ cell tumors

Incidence Macroscopic features Microscopic features
494
Mature cystic • 1 0–15% of all ovarian tumors •S ize: small or moderate in size, The cyst is lined by stratified
teratoma • I t is the most common ovarian slowly growing squamous epithelium or granulation
(dermoid cyst) tumor at young ages (20–30 • Surface: smooth surface tissue, and it contains a mixture
years) •L aterality: unilateral, bilateral in of endodermal, ectodermal, and
• I t is the commonly diagnosed 10–15% of cases mesodermal structures which are
during pregnancy, either as •C ut section: cystic, thick walled, found
an incidental finding during unilocular, filled with sebaceous
obstetric ultrasound or because material. It contains:
of risk of complications during • A small mass bulging from
pregnancy and puerperium the wall (embryonic node or
Rokitansky tubercle)
• A mixture of differentiated
structures from different origins
Chapter 18. Ovarian Tumors
may be present: ectodermal

origin (e.g., hair and teeth),
mesodermal origin (e.g.,
cartilage), and endodermal origin
(e.g., thyroid tissue)
•B ehavior: risk of malignant
transformation is low (1%). The
most common cancer type is
squamous cell carcinoma
Solid teratoma It is uncommon. The most The tumor is solid, pinkish grey in It consists of mixture of germ layers
common age at diagnosis is color; it may be benign (mature) or
10–20 years malignant (immature)
Dysgerminoma 2% of all ovarian tumors. •S ize: usually moderate sized The tumor consists of bundles or
The tumor is most commonly tumors alveoli of large round cells embedded
diagnosed among children and • Surface: smooth or nodular surface in a connective tissue stroma,
young women (below the age • Laterality: usually unilateral (90%) infiltrated with lymphocytes
of 20) •C ut section: solid, capsulated, with
areas of necrosis and hemorrhage
•B ehavior: low-grade malignant
tumor
Endodermal sinus The most common age at • Laterality: unilateral The tumor consists of microcysts lined
tumor (yolk sac diagnosis is below 20 • Cut section: partly cystic by flattened cells. Schiller–Duval
tumor) •B ehavior: highly aggressive bodies (glomerulus-like structures)
malignant tumor (poor prognosis) are noted
Embryonal It consists of endodermal sinus tumor and choriocarcinoma. It secretes α-fetoprotein and β-hCG
carcinoma
Non-gestational •P
rimary non-gestational choriocarcinoma usually arises as a component of a mixed germ cell tumor. Pure non-
choriocarcinoma gestational choriocarcinoma is extremely rare
•N
on-gestational choriocarcinoma is more aggressive and is associated with poor prognosis compared to
gestational choriocarcinoma
Struma ovarii It is a benign teratoma which consists, primarily, of thyroid tissue. It is formed of loculi containing colloid. The
tumor may cause thyrotoxicosis (5%), and it is associated with low risk of malignant transformation (5%)
495
III. Sex cord-stromal tumors
Macroscopic Microscopic
Incidence features features
Fibroma of the 5% of all •S
ize: small to Bundles
ovary ovarian tumors moderate of spindle-
•S
urface: smooth, shaped cells
lobulated; it may among dense
have a pedicle connective
(thus, liable to tissue stroma
torsion); large
dilated veins may
be noted on tumor
surface
•L
aterality:
unilateral
•C
ut surface:
solid tumor, firm,
whitish in color
with whorled
appearance
•B
ehavior:
fibrosarcoma is
diagnosed in 0.5%
of cases
Granulosa cell 2% of all •S ize: the tumor It consists of

tumor ovarian tumors varies in size, from clusters of cells
a small nodule to (similar to
a large mass granulosa cells
• Surface: smooth of the Graafian
•L aterality: usually follicle)
unilateral
•C ut section: solid,
white, yellow, or
orange colored
•B ehavior: low-
grade malignant
tumor, most cases
are diagnosed at
stage I, 5-year
survival rate is
90–100%
Macroscopic Microscopic
Incidence features features
Theca <1% of • The tumor is solid It consists of
cell tumor ovarian in consistency, theca interna-
(thecoma) tumors. The whitish or like cells
mean age of yellowish in color
these tumors is • I t is almost always
53 years benign
Sertoli–Leydig <0.5% of • The tumor has a The tumor
cell tumor ovarian smooth surface consists of
(androblastoma) tumors (most • The tumor is solid, Sertoli cells
commonly with cystic areas arranged in
diagnosed filled with clear cords, nests,
during second fluid and tubules,
and third interspersed
decades of by nests of
life) polygonal cells
(Leydig cells)
II. Secondary Ovarian Tumors
• Incidence: 15–20% of all ovarian cancers.

• Origin:
–– Gastrointestinal tract (e.g., stomach, colon, and gall-
bladder): 40%.
–– The breasts: 30%.
–– The uterus: 20%.
–– Any tumor can metastasize to the ovary.
• Size: small to moderate in size (usually <10 cm).
• Laterality: bilateral involvement is common (70%).
Krukenberg tumor
Definition
Krukenberg tumor is a subtype of secondary ovarian tumors
characterized by mucin-rich signet ring cells
Incidence
1–2% of all ovarian tumors. Mean age at diagnosis is 45 years
Origin
The primary tumor most likely originates in the gastrointestinal
tract. Gastric cancer contributes to 70% of these cases
Mode of spread
Mode of spread is not clear whether it is lymphatic,
hematogenous, or transcoelomic. However, current evidence is
supportive of lymphatic theory
Macroscopic features
• Size: moderate in size
• Surface: lobulated tumor with a smooth surface
• Laterality: bilateral (>80%)
• Cut section: solid
• Mobility: freely mobile due to absence of adhesions
Microscopic features
The tumor is characterized by mucin-producing signet ring cells,
stromal involvement with sarcomatoid proliferation
Risk of Ovarian cancer:

• Risk factors:
–– Age: it is the most significant risk factor of ovarian can-
cer. More than 50% of ovarian cancer patients are
above the age of 63.
–– Family history (family cancer syndrome):
They comprise 5–10% of ovarian cancers:
Hereditary breast and ovarian cancer syndrome
(BRCA 1 and 2):
Lifetime ovarian cancer risk with BRCA1 and
BRCA2 mutations is 35–70% and 10–30%,
respectively.
Hereditary nonpolyposis colon cancer (HNPCC,

Lynch syndrome):
• Lifetime ovarian cancer risk is 10%.
• Genes involved in this syndrome include MLH1,
MLH3, MSH2, MSH6, PMS1, PMS2, and
TGFBR2.
Peutz–Jeghers syndrome (STK11 gene mutation):
• This syndrome is characterized by development
of multiple GI polyps at early age that are associ-
ated with high risk of GI cancers (esophagus,
stomach, small intestine, colon).
• The syndrome is associated with increased risk of
ovarian cancer.
–– Parity:
Nulliparity and delayed first pregnancy (above the
age of 35) increases the risk of ovarian cancer.
–– Obesity:
Obesity (BMI > 30) may have a higher risk of ovar-
ian cancer.
–– Multiparity and breastfeeding
–– Long-term COCs: reduces the risk of ovarian cancer by
50% for up to 25 years after the cessation.
–– Tubal ligation and hysterectomy: hysterectomy may
reduce lifetime risk by one-third.
Mode of spread of ovarian cancer:

• Direct spread: spread of cancer to neighboring organs, e.g.,
tubes, uterus, bladder, intestine, and lateral pelvic wall.
• Lymphatic spread:
Ovarian cancer spreads through ovarian lymphatics to
para-aortic nodes.
• Spread by the bloodstream: to distant organs as the liver,
lungs, and bones.
• Transcoelomic spread: to intraperitoneal organs, e.g., peri-
toneum, omentum, liver, and diaphragm.
Diagnosis of ovarian tumors:

• Symptoms:
–– Asymptomatic:
Ovarian cancers are commonly asymptomatic or
may be associated with non-specific symptoms, e.g.,
abdominal discomfort and bloating. Therefore, ovarian
cancer may be diagnosed incidentally and is commonly
diagnosed at late stages.
–– Pressure symptoms:
Patients may report constipation, urinary symptoms,
and dyspnea.
–– Abdominal/pelvic pain:
Patients may report dull aching abdominal pain.
Acute pain may be attributed to complications, e.g., tor-
sion, rupture, or hemorrhage. Rupture of mature cystic
teratoma results in chemical peritonitis.
–– Loss of weight:
Ovarian cancer is associated with rapid unintentional
loss of weight.
–– Abdominal enlargement:
Abdominal enlargement may be attributed to ovar-
ian mass, ascites, or both. Ascites may be caused by:
Intraperitoneal metastatic spread.
Peritoneal irritation by either benign or malignant
tumors. Ascites and hydrothorax associated with ovar-
ian fibroma is called Meigs syndrome. Pseudo-Meigs
syndrome refers to ascites and hydrothorax associated
with ovarian tumors other than fibroma.
Pseudomyxoma peritonei may develop secondary to
mucinous cyst-adenocarcinoma. The term refers to
spread of mucin-secreting tumor cells inside the
abdomen and pelvis with subsequent intra-abdomi-
nal accumulation of mucin.
–– Abnormal uterine bleeding:
Irregular or postmenopausal bleeding in women
with ovarian cancer may be caused by hormonal
effect of estrogen-secreting tumor (granulosa cell
tumor) or coexistent uterine tumor (e.g., Lynch II

syndrome).
Amenorrhea during reproductive-aged women may
result from androgen-secreting tumors or due to can-
cer cachexia.
–– Symptoms of hormone-secreting ovarian tumors:
Androgen-secreting tumors: may cause amenorrhea,
breast atrophy, genital atrophy, hirsutism, and hoarse-
ness of voice.
Estrogen-secreting tumors: symptoms are related to
patient age; children may present with precocious
puberty, reproductive-aged women may present with
irregular uterine bleeding, and older women may
present with postmenopausal bleeding.
Assessment of supraclavicular lymph node
enlargement
Assessment of lower extremity edema and
varicosities
Large ovarian masses can be palpated abdominally,
and the lower pole of the mass may be felt above
symphysis pubis.
Benign tumors are likely smooth, cystic, mobile, and
non-tender. Malignant tumors are likely irregular,
partially or completely solid, and fixed to surrounding
structures with limited mobility and may be tender.
Ascites is commonly associated with ovarian tumors.
The mass is separate from the uterus.
The uterus is typically mobile, unless fixed by adhe-
sions or metastasis. Uterine mobility is not transmit-
ted to the mass.
Nodularity of Douglas pouch may indicate meta-
static disease.
• Work-up:
I. For early detection of ovarian cancer
Screening of ovarian cancer is not recommended among

average risk women. However, some screening protocols
have been studied particularly among high-risk population
including women with strong family history or BRCA1 and
BRCA2 gene mutations. However, no screening strategy is
proved to reduce mortality:
• Genetic surveillance:
–– Indication: two family members with premenopausal
breast cancer or ovarian cancer among their first- or
second-degree relatives
–– Results and interpretation:
Genetic testing includes screening for familial cancer
syndromes, e.g., Lynch syndrome and BRCA 1 and 2.
BRCA testing may result in one of three categories of
results:
A positive test (frameshift mutations): patients
should be offered prophylactic surgery (see under
prophylactic treatment).
Unclassified sequence variants (missense mutations):
interpretation is challenging. A patient should be
offered genetic counseling, and management may be
individualized according to family history.
A negative test (no mutations): a patient can be reas-
sured that her lifetime risk of ovarian cancer is com-
parable to general population.
• Combined imaging and laboratory surveillance: CA 125
and transvaginal ultrasound screening may be offered
to high-risk patients specially if they temporarily decline

prophylactic surgery to preserve fertility
II. Work-up to establish diagnosis
Final diagnosis is only made by histopathological assessment

of the excised mass after surgery. However, the following
modalities may suggest the nature of the mass and contribute
to surgical staging in case of malignancy.
• Ultrasonography:
Ultrasonography is the best initial imaging modality to
assess adnexal masses. It may provide the following
information:
–– It may identify origin of the mass (ovarian vs. uterine).
–– Suggestive features of malignancy in ultrasound may
include:
Large masses
Thick irregular septa
Presence of solid areas
Infiltration through ovarian capsule
Attachment to surrounding structures
Presence of ascites
Irregular distribution of blood vessels and reduced
resistance index on Doppler ultrasound
Liver metastases
• Abdomen/pelvis CT scan: it provides information on
metastasis to pelvic peritoneum, omentum, para-aortic
nodes, diaphragm, and intra-abdominal organs.
• Abdominal/pelvic MRI: it provides precise information on
tissue characteristics, thus, likelihood of benignity of the
mass.
Large tumor
Liver
metastasis Ascites
Thick irregular Fungation

septa
(multilocular) Solid areas
III. Work-up for distant metastasis/coexisting tumors
• Chest CT scan: to assess lung metastases.

• Mammography: breast cancer screening is recommended
if no recent mammogram is available. Metastatic ovarian
cancer may originate from breast cancer. Coexisting breast
cancer may be present in women with familial cancer syn-
dromes. In addition, estrogen-secreting tumors may
increase risk of breast cancer.
IV. For follow-up
• Pelvic-abdominal imaging: (e.g., CT scan) to assess recur-

rence of the disease
• Tumor markers:
–– Value: Tumor markers are not used to diagnose ovarian
cancers. However, follow-up of their level may help to
monitor response to treatment and to detect
recurrence.
–– List of tumor markers:
Epithelial Non-mucinous •C
A 125 (postmenopausal
tumors tumors level >35 IU/ml is abnormal)
•H
uman epididymis protein
4 (HE4) is a new marker of
epithelial ovarian tumors.
It may be used alone or in
conjugation with CA 125a
Mucinous tumors CA-19-9, carcinoembryonic

antigen (CEA)
Germ cell Dysgerminoma hCG may be elevated
tumors
Choriocarcinoma HCG
Yolk sac tumor Alpha-fetoprotein (AFP)
Embryonal HCG and AFP
carcinoma
Sex cord- Granulosa cell Inhibin A and B ± estradiol
stromal tumors
tumors
Sertoli–Leydig cell Inhibin A and B ± AFP
tumors
a
CA 125 is non-specific, and it may be elevated in other common
benign conditions such pelvic inflammatory disease, endometriosis,
leiomyomas, pregnancy, liver cirrhosis, and menses
V. Preoperative evaluation
Preoperative assessment is essential prior to any major sur-

gery. This includes physical examination and laboratory tests
(complete blood count, serum creatinine, serum electrolytes,
serum albumin). Further tests may be warranted according to
patient medical history, e.g., blood glucose, HgbA1C, electro-
cardiogram, and echocardiogram
Final risk assessment:

After initial assessment and work-up, a decision, whether this
ovarian mass is likely benign or is suspicious, should be made.
One or more of the following criteria warrants referral to

gynecologic oncologist:
• Postmenopausal women with:
–– Elevated CA 125 (>35 IU/mL)
–– Ultrasound findings suggestive of malignancy
• Premenopausal women with:
–– Elevated CA 125 level (>200 IU/mL)
–– Ultrasound findings suggestive of malignancy
• Premenopausal or postmenopausal women with:
An elevated score on a formal risk assessment test, e.g:
❶ Risk of malignancy index (RMI):
RMI = ultrasound score (U) x menopausal status
(M) × CA 125
➀ Ultrasound score:
1 point is given for each of: multilocular cysts, solid
areas, metastases, ascites, bilaterality:
–– U = 0 (if ultrasound score is 0)
–– U = 1 (for an ultrasound score of 1)
–– U = 3 (for ultrasound score is 2–5)
➁ Menopause:
–– M = 1 if the patient is premenopausal
–– M = 3 if the patient is postmenopausal
➂ CA 125: Serum CA 125 is measured in IU/ml.
❷ Risk of ovarian malignancy algorithm (ROMA):
ROMA incorporates results of CA 125, HE4 tests,
and menopausal status
Treatment:
I. Prophylactic treatment
Prevention of ovarian cancer

Women with suspected family history e.g. ovarian and
premenstrual breast cancer
Genetic testing, e.g, BRCA1 and BRCA2
Negative Positive Uncertain (variants of undetermined

significance)
No further action
is needed Management
Interested in fertility Not interested according to family
preservation in fertility history
Combined contraceptive Risk-reducing bilateral

pills and transvaginal salpingo-
ultrasound every 6 oophorectomy is
months are offered. offered at 35–40 year
Bilateral salpingo- of age. Hormonal
oophorectomy is therapy is given till the
recommended when she natural age of
completes her family menopause
Annual mammography starting after the age of 30 years
II. Treatment of women with ovarian masses
Treatment plan is directed by preoperative assessment.

Ovarian cysts that are likely benign based on sonographic
features, CA 125, and final risk assessment can be managed
as such. Suspicion of malignancy indicates exploratory
laparotomy.
I. Treatment of benign tumors
Treatment of benign ovarian tumors

According to patient age
Postmenopausal Premenopausal
Surgery (salpingo-
oophorectomy) and Complex cyst Simple cyst
histopathology.
Follow-up is appropriate if
risk assessment is
reassuring, e.g, simple cyst More than 10 cm Less than 10 cm
<5 cm with normal CA Ovarian cystectomy vs.
125 follow-up* (depends on
size, sonographic COCs may be offered for
features) * 2–3 months vs. follow-up
after 3 months**
If no residual ovarian If residual ovarian tissue

tissue can be preserved can be preserved
Oophorectomy Ovarian No Regression

cystectomy regression (functional
cyst)
Short term follow-up.
If the cyst is stable,
no further follow-up is
indicated
* Follow-up with ultrasound may be performed every 3–6 months and then yearly, if the cyst
remains stable
** COCs act by suppressing formation of new functional cysts rather than acting on an
existing cyst, which would regress shortly if it is functional. Therefore, follow-up ultrasound
can be used to differentiate whether a cyst is likely functional or not
I. Treatment during pregnancy
During • Simple ovarian cysts (less than 5 cm) typically

pregnancy resolve, and they can be managed conservatively.
Simple looking cysts can be followed up with
ultrasound every trimester. Complex cysts and
cysts larger than 5 cm are more likely to persist.
CA 125 is not a useful biomarker in pregnancy
• Suspicious and large ovarian masses:
• I f surgery is indicated, it should be ideally
performed between 12 and 22 weeks
• I f surgery should be performed before
10 weeks of gestation, progesterone
supplementation is recommended. If surgery
has to be performed after the age of viability,
a complete course of antenatal corticosteroids
is recommended prior to surgery
During labor • If the patient delivers vaginally: reassessment of
the mass is performed after 6–8 weeks
• If the patient delivers via Cesarean section:
ovarian mass is assessed during surgery and is
managed according to intraoperative findings
(similar approach to nonpregnant women)
II. Treatment of malignant tumors
I. Exploratory laparotomy
Laparotomy is the recommended approach for surgical staging

and management of ovarian cancer. If the diagnosis is uncertain
or resectability of the tumor is doubtful, diagnostic laparoscopy
may be performed to assess the mass and abdomen and to take
biopsies from suspicious metastases if frozen section is available
before the decision of full abdominal exploration is made:
• Step 1: an adequate vertical abdominal incision.

• Step 2: peritoneal washings (or collection of ascitic fluid)
for cytologic assessment.
• Step 3: intra-abdominal and pelvic exploration and biopsy
of suspected lesions.
Signs of malignancy at operation

• Ascites (especially bloodstained ascites)
• Presence of adhesions
• Bilaterality of the tumor
• Solid or partly solid
• Extracystic papillae
• Large dilated blood vessels over tumor surface
• Areas of hemorrhage and necrosis in the tumor
• Infiltration of the capsule
•P resence of peritoneal nodules, metastases in liver, omentum,
or Douglas pouch
• Enlargement of pelvic/para-aortic lymph nodes
• Step 4: multiple peritoneal biopsies and infra-colic

omentectomy.
• Step 5: assessment of lymph nodes. Any suspicious pelvic
or para-aortic lymph nodes should be removed.
If frozen section is available, preliminary pathology during
surgery may guide debulking; frozen section allows assess-
ment of margin status of excised masses and any suspicious
lesions specially if several fibrosed lesions are present follow-
ing prior radiotherapy.
II. Surgical staging
Abdominal exploration and histopathology are the essence

of surgical staging, which is used to determine treatment plan
of these patients.
FIGO surgical staging system for ovarian cancer

IA Cancer growth is confined to one ovary
IB Cancer growth is confined to both ovaries
IC Cancer affects one or both ovaries, and the disease
extends to the surface of one or both ovaries, ovarian
capsule(s) are ruptured, or there is ascites with positive
peritoneal cytology
IIA The tumor metastasizes to the uterus and/or tubes
IIB The tumor metastasizes to other pelvic tissues
IIIA IIIA1: The tumor is confined to pelvic organs with
metastasis to retroperitoneal (pelvic and/or para-aortic)
lymph nodes
IIIA2: The tumor grossly confined to the pelvis,
microscopic abdominal-peritoneal spread (without
visible lesions), with or without retroperitoneal lymph
node spread
IIIB Gross abdominal metastatic implants < 2 cm in size with
negative lymph nodes
IIIC Gross abdominal metastatic implants ≥ 2 cm in size and/
or metastasis to pelvic, para-aortic, or inguinal lymph
nodes
IV Distant metastases (including malignant pleural effusion
and liver metastases)
III. Treatment according to the stage and histopathology
I. Epithelial ovarian cancer

Stage I Surgery
512
Fertility sparing surgery Radical surgery

•C andidates: Women interested in conception, • Total abdominal hysterectomy and bilateral
stage IA grade 1, normal wedge biopsy of the salpingo-oophorectomy
other ovary Plus omentectomy: because it is a common site for
• Surgery: minute metastases
Unilateral salpingo-oophorectomy without Plus appendectomy
chemotherapy followed by hysterectomy with
removal of the other ovary after the patient
completes her family
Chemotherapy
• Indications: stage IA or IB, grade 3, and stage IC and II

• Regimen: 3–6 cycles of carboplatin and paclitaxel
Stage II, Surgery (debulking operation or cytoreduction)
III, and
IV • Primary cytoreductive surgery: • Interval cytoreductive surgery:
• Definition: surgery prior to adjuvant treatment • Definition: debulking surgery done following
which aims to achieve optimal debulking. 3–4 courses of neoadjuvant chemotherapy to
Optimal debulking refers to resection of the promote shrinkage of the tumor
disease leaving less than 1 cm of residual • Advantages of interval cytoreductive surgery:
disease at the end of surgery •S ome unrespectable tumors may become
• Advantages of primary cytoreductive surgery: resectable as they shrink in response to
• R emoval of necrotic tissue improves drug chemotherapy
delivery to living tissues including the tumor • P reoperative shrinkage of the tumor may
• R emoving the bulk of the disease promotes facilitate optimal debulking of tumors that
response of the remaining macroscopic/ would be otherwise suboptimally debulked
microscopic disease to chemotherapy using
fewer cycles and enhances immune response
to the disease
Chemotherapy
• Intravenous chemotherapy: • Intraperitoneal chemotherapy:
It consists of 6 cycles of carboplatin and paclitaxel Candidates include patients with optimally
debulked stage III disease
513
II. Germ cell ovarian tumors
Treatment of germ cell ovarian tumors

According to stage
Stage I Stage II, III, IV
Surgery Adjuvant treatment Surgery Adjuvant treatment
Indications Cytoreduction Bleomycin,

Fertility Radical All patients except stage IA (primary or etoposide and
sparing dysgerminoma and stage IA interval) cisplatin, (BEP)
G1 immature teratoma chemotherapy
Total Regimen
Unilateral hysterectomy, Chemotherapy (bleomycin,
salpingo- bilateral etoposide, and cisplatin, BEP)
oophorectomy salpingo- +
after exclusion of oophorectomy
Radiotherapy
contralateral
for dysgerminoma
disease (10–15%
(radio-sensitive)
of dysgerminomas
are bilateral)
III. Sex cord-stromal ovarian tumors
Treatment of sex cord-stromal ovarian tumors

According to staging
Low risk (stage IA) Intermediate risk (stage IB, IC, II) High risk (stage III, IV)
Surgery alone Radical surgery + BEP Cytoreduction + BEP chemotherapy

chemotherapy for 3 for 3 cycles (if completely resected) or
cycles (relatively chemo- 4 cycles (if residual disease is left
insensitive tumors) after surgery)
IV. Treatment of borderline tumors
Borderline epithelial tumors (tumors of low malignant poten-

tial tumors) are staged using the same staging criteria of
invasive ovarian cancer.
Tumor is Surgery alone without chemotherapy or

confined to radiotherapy
the ovaries • Women not interested in future fertility:
surgical staging, total hysterectomy-bilateral
salpingo-oophorectomy, omentectomy
• Women interested in future fertility: unilateral
salpingo-oophorectomy and surgical staging to
assess tumor spread. No further treatment is
required. Follow-up with serial ultrasound/CA
125 is recommended
Tumor spread • Surgical debulking
outside the •P ostoperative chemotherapy: is indicated if
ovaries invasive tumor implants are present
Recurrent • I f the tumor recurs after an index surgery, a
borderline second debulking surgery may be considered
ovarian •C hemotherapy in another option for recurrent
tumors borderline tumors
III. Post-treatment follow-up
• Follow-up visits are scheduled every 2–4 months for the

first 2 years following treatment, then twice yearly for
additional 3 years, and then annually.
• At each visit:
–– Review of symptoms.
–– Physical examination.
–– Serum CA 125 if it was initially elevated.
–– If indicated clinically, imaging tests, e.g., abdomen/pelvis
CT scan, may be helpful to exclude recurrent disease.
IV. Treatment of relapse
Treatment of relapse is according to the type of relapse iden-

tified in the next table:
Types of
relapse Definition Treatment of relapse
Platinum- Women who progress Palliative non-platinum
refractory during primary chemotherapy
disease chemotherapy
Platinum- Women who relapse
resistant within 6 months
ovarian cancer
Platinum- Women who relapse Secondary
sensitive more than 6 to cytoreductive surgery
relapse 12 months after OR
completion of primary salvage chemotherapy
therapy (carboplatin combined
with paclitaxel given
sequentially, followed
by doxorubicin)
Prognosis:
The 5-year survival rate is:
Stage I 80–90% Stage III 15–30%
Stage II 60–70% Stage IV 5–15%
• Unfortunately, most cases of ovarian cancer (70%) are

diagnosed at an advanced stage (stage III or IV) making
outcome of the treatment less favorable. Delayed diagno-
sis is attributed to:
–– The ovary is a hidden organ that is not self-seen or felt,
and ovarian tumors grow within a roomy abdominal
cavity before they may become symptomatic.
–– Symptoms are non-specific.
Ovarian Torsion 517
–– Ovaries are located inside the peritoneal cavity and are

not covered by visceral peritoneum. Therefore, intra-
abdominal dissemination occurs early once ovarian
capsule is infiltrated.
–– No efficient screening strategy is available to date.
Prognostic factors for ovarian cancer
• Patient age.
• Performance status.
• Cancer stage and grade.
• Disease histology, e.g., mucinous tumors is associated with
overall good prognosis. Endodermal sinus tumors are
associated with poor prognosis.
• Disease volume after surgical debulking.
• Volume of ascites.
Ovarian Torsion
• Incidence:
2%–15% of surgical interventions for ovarian masses
are attributed to ovarian torsion.
• Risk factors:
–– Ovarian masses (80% of ovarian torsion cases occur in
the presence of ovarian masses of 5 cm or larger)
–– Pregnancy and the puerperium (10%–22% of torsion
cases occur in pregnancy)
–– Absence of peri-adnexal adhesions
• Diagnosis:
–– Symptoms:
Patients typically present with lower abdominal pain
of acute onset followed by nausea and vomiting.
Symptoms may be intermittent, and each episode is
associated with sudden onset.
Low-grade fever may be present.
Personal history of ovarian cysts may be present.
–– Physical examination: Lower abdominal tenderness

associated with tender pelvic-abdominal mass.
–– Work-up:
Laboratory tests:
• Serum HCG: to rule out pregnancy including
ectopic pregnancy. HCG is elevated in some germ
cell tumors.
• White blood cell count: to rule out infection, e.g.,
tubo-ovarian abscesses.
Imaging studies:
• Ultrasonography: is the diagnostic modality of
choice. Affected ovary may show an adnexal mass,
and it may be enlarged due to edema and vascular
engorgement. Doppler flow may be absent or
decreased. Doppler finding may be associated
with high specificity and is a helpful tool. However,
decision should be driven by clinical assessment
rather than sonographic findings alone.
• Whirlpool sign may be present. It refers to the find-
ings of a twisted vascular pedicle associated with
circular vessels within the mass illustrated by
Doppler.
–– Final diagnosis is made at the time of surgery if indi-
cated for highly suspected ovarian torsion.
• Treatment:
–– Laparoscopy:
Laparoscopy is the preferred approach for surgical
assessment and intervention. Laparotomy may be
resorted to if cancer is suspicious.
• Detorsion and ovarian cystectomy:
Current evidence supports detorsion followed by
ovarian cystectomy for benign-appearing ovarian
masses. Even ovarian tissues that look visually necrotic
may retain ovarian function following detorsion, and
Further Reading 519
therefore, oophorectomy should not be performed

based on tissue appearance. Salpingo-oophorectomy
may be indicated if malignancy is suspected.
Further Reading
Aabo K, Adams M, Adnitt P, et al. Chemotherapy in advanced ovar-
ian cancer: four systematic meta-analyses of individual patient
data from 37 randomized trials. Advanced Ovarian Cancer
Trialists’ Group. Br J Cancer. 1998;78:1479.
Berek JS, Crum C, Friedlander M. Cancer of the ovary, fallopian
tube, and peritoneum. Int J Gynaecol Obstet. 2012;119(Suppl
2):S118.
Dasgupta R, Renaud E, Goldin AB, Baird R, Cameron DB,
Arnold MA, Diefenbach KA, Gosain A, Grabowski J, Guner
YS, Jancelewicz T. Ovarian torsion in pediatric and adolescent
patients: a systematic review. J Pediatr Surg. 2018;53(7):1387–91.
Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the
ovary. FIGO 26th Annual Report on the Results of Treatment
in Gynecological Cancer. Int J Gynaecol Obstet. 2006;95(Suppl
1):S161.
Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi
JK, Amso NN, Apostolidou S, Benjamin E, Cruickshank D,
Crump DN. Ovarian cancer screening and mortality in the UK
Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a
randomised controlled trial. The Lancet. 2016;387(10022):945–56.
Morgan RJ, Armstrong DK, Alvarez RD, Bakkum-Gamez JN,
Behbakht K, Chen LM, Copeland L, Crispens MA, DeRosa
M, Dorigo O, Gershenson DM. Ovarian cancer, version 1.2016,
NCCN clinical practice guidelines in oncology. J Natl Compr
Canc Netw. 2016;14(9):1134–63.
Prat J. FIGO Committee on Gynecologic Oncology. Staging classifi-
cation for cancer of the ovary, fallopian tube, and peritoneum. Int
J Gynaecol Obstet. 2014;124:1.
Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer:
a review. Cancer Biol Med. 2017;14(1):9.
US Preventive Services Task Force, Grossman DC, Curry SJ, et al.
Screening for ovarian cancer: US Preventive Services Task Force
Recommendation Statement. JAMA. 2018;319:588.
Chapter 19
Perioperative Care
Surgical Recovery
Enhanced Recovery After Surgery (ERAS) protocols aim at
optimizing postoperative outcomes by maintaining normal
physiology during recovery. ERAS protocols include pre-,
intra-, and postoperative measurements that improve patient
satisfaction through shorter postoperative hospital stay, bet-
ter pain control, and more rapid return of bowel function
Preoperative recommendations:
• Smoking cessation: is recommended at least 4 weeks
before surgery.
• Cessation of alcohol at least 4 weeks before surgery:
among high-risk drinkers (alcohol consumption that
increases the risk for adverse health events).
• Correction of anemia.
• Pre-procedure fasting: patients are allowed to eat light
meals up to 6 hours before surgery. They may continue to
drink clear fluids up to 2 hours before surgery. Only preop-
erative medications are allowed beyond this point of time.
If given, carbohydrate loading drink is administered in the
morning of surgery to be completed at least 2 hours before
surgery.

https://doi.org/10.1007/978-3-030-41128-2_19
522 Chapter 19. Perioperative Care
• Pain medications: oral celecoxib 400 mg, acetaminophen

1,000 mg, and gabapentin 600 mg may be given prior to
transfer to operative room.
• Mechanical bowel preparation not indicated usually.
Intraoperative recommendations:
• Intraoperative analgesia (consider adding here that anal-
gesia is a team goal so that there are treatments available
from both anesthesia and surgeons):
–– Regional anesthesia
–– IV opioids, combined with ketamine, ketorolac, or both
may be given during surgery.
–– At closure time, transversus abdominis plane block or
local infiltration of the incision may be considered.
• Anti-nausea measures (2–3 anti-nausea regimens should
be considered):
–– Before incision: transdermal scopolamine 1.5 mg patch
may be considered within 30 minutes prior to incision in
women at high risk of postoperative vomiting
–– At induction: consider dexamethasone 8 mg IV
–– Before emergence: consider ondansetron 4 mg IV
• Antimicrobial measures:
–– One dose of first-generation cephalosporin or
amoxicillin-
clavulanic acid within 60 minutes before
incision. A repeat dose is considered if blood loss
>1,500 ml or if surgical duration is more than 4 hours.
Higher doses should be considered in women weighing
>120 kg (e.g., cefazolin standard dose is 2 g, the dose is
3 g for weight >120 kg).
–– Skin cleansing: using an alcohol-based agent. Hair clip-
ping of hair bearing area (e.g., suprapubic area).
–– Vaginal cleansing: using 4% chlorhexidine gluconate or
povidone-iodine.
• Fluid replacement: if needed, consider less crystalloid and
more colloid administration.
Surgical Recovery 523
• Thermal regulation: patient should be maintained normo-

thermic throughout the procedure.
• Thromboprophylaxis: assessment of risk of venous throm-
boembolism; sequential compression devices are
recommended for all patients. Heparin should be consid-
ered in high-risk patients.
• Avoidance of drains.
• Avoidance of vaginal packs.
• If intraoperative NG tube is placed, it should be removed
at extubation.
Postoperative recommendations
• IV fluids:
–– On arrival to the floor, intraoperative fluids should be
discontinued. Maintain IV fluids at rate of 40 ml/hour
until the morning of postoperative day 1, or if the
patient is able to achieve 600 ml of oral intake prior to
that.
• Initiation of activity:
–– Evening of surgery: patient is recommended to spend
>2 hours out of bed. This activity should include at least
one walk and sitting in chair.
–– Postoperative day 1 till discharge: patient should spend
>8 hours out of bed. Patient should do at least four
walks, sit in chair, and is able to be up in chair in all
meals.
• Postoperative analgesia:
–– Scheduled ketorolac or NSAIDs, scheduled acetamino-
phen (if it is not contraindicated due to hepatic impair-
ment), and scheduled gabapentin.
–– If NSAIDs are intolerable or contraindicated, tramadol
can be used instead.
–– Oral opioids are used if non-opioid options fail to con-
trol pain.
–– IV or PCA hydromorphone may be used for break-
through pain.
• Gastrointestinal care:
–– Start regular diet 4 hours after surgery.
–– Fluid intake: in the same day of surgery, fluid intake
should range between 800 and 2,000 ml by midnight,
and it should be between 1,500 and 2,000 ml during
hospital stay.
–– Chewing gum may help to restore bowel function.
–– Osmotic laxatives: senna, docusate sodium, magnesium
oxide, or magnesium hydroxide may be given.
–– In diabetic patients, blood glucose should be main-
tained between 180 and 200 mg/dL.
• Catheters: urinary catheters should be removed within 24
hours unless otherwise indicated to stay longer.
• Discharge criteria: patient can go home if adequate mobi-
lization is achieved, pain is well controlled with oral medi-
cations, and the patient is able to tolerate general diet
without nausea/vomiting.
Venous Thromboembolism Surgical

Prophylaxis
Thromboprophylaxis is an essential part of perioperative
care. In absence of thromboprophylaxis, the risk of deep
venous thrombosis is 15–40% following gynecologic major
surgeries. Perioperative assessment of risk is crucial to deter-
mine appropriate thromboprophylaxis strategy.
Classification of risk:
• Low risk:
All these criteria should be present:
–– Short surgery: less than 30 minutes
–– Young patients: younger than 40 years
–– Additional risk factors: none
Venous Thromboembolism Surgical Prophylaxis 525
Additional risk factors include immobility, paresis, cancer

and cancer therapy, history of venous thromboembolism,
pregnancy and puerperium, estrogen therapy or SERMs
(selective estrogen receptor modulators), heart or respiratory
failure, thrombophilias, inflammatory bowel disease, obesity,
nephrotic syndrome, smoking, varicose veins, and central
venous catheterization.
• Moderate risk:
–– Short surgery (less than 30 minutes) with additional risk
factors OR patients aged between 40 and 60 years with-
out additional risks
–– Major surgery PLUS young patients (<40 years) PLUS
no additional risk factors
• High risk:
–– Short surgery (less than 30 minutes) in patients older
than 60 years OR with additional risk factors
–– Major surgery PLUS patients older than 40 years OR
additional risk factors
• Highest risk:
–– Major surgery in older patients (>60 years) PLUS can-
cer, hypercoagulable condition, or history of venous
thromboembolism
Management according to risk category:

• Low-risk patients:
These patients do not need medical or mechanical pro-
phylaxis. Patients are encouraged to ambulate early and
hydrate adequately.
• Moderate-risk patients:
–– Graduated compression stockings or pneumatic com-
pression devices: it is applied before surgical procedure
and until the patient is ambulatory.
–– Unfractionated heparin: subcutaneous heparin (5,000

units) is administered 2 hours before surgery and every
12 hours thereafter during hospital stay.
–– Low molecular weight heparin: it is administered 12
hours prior to surgery and then daily thereafter during
hospital stay (e.g., enoxaparin 40 mg).
• High-risk patients:
–– Pneumatic compression devices: it is applied before
surgical procedure and during hospital stay.
–– Unfractionated heparin: subcutaneous heparin (5,000
units) is administered 2 hours before surgery and every
8 hours thereafter during hospital stay.
–– Low molecular weight heparin: it is administered 12
hours prior to surgery (or 6–12 hours postoperatively)
and then daily thereafter during hospital stay (e.g.,
enoxaparin 40 mg).
• Highest-risk patients:
–– Combination prophylaxis: application of pneumatic
compression devices PLUS administration of one hepa-
rin regimen.
–– Low molecular weight heparin: It is administered 12
hours prior to surgery and then daily thereafter during
hospital stay and after discharge for a total of 28 days
postoperatively (e.g., enoxaparin 40 mg).
Caprini risk assessment:

• Caprini risk assessment tool scores risk factors of venous
thromboembolism based on their impact. Risk factors
receive a score of 1 (e.g., age 41–60 years), 2 (e.g., malig-
nancy), 3 (e.g., history of venous thromboembolism), or 5
(e.g., hip, pelvis, or leg fracture).
• Risk is classified into very low risk (score of 0), low risk
(score of 1–2), moderate risk (score of 3–4), or high risk
(score ≥5).
• Very low-risk women do not need any specific prophylaxis.
Low-risk patients are managed by mechanical prophylaxis.
Antibiotic Prophylaxis 527
Mechanical prophylaxis or heparin may be used in women

at moderate risk. High-risk women should be managed by
mechanical and pharmacological prophylaxis.
Antibiotic Prophylaxis
Prophylaxis against infection after gynecologic procedures
depends on the type of procedure and intraoperative events.
Risk factors of surgical site infection:

• General risk factors:
–– Smoking
–– Obesity (BMI ≥30)
–– Poor nutritional status
–– ASA (American Society of Anesthesiologists) physical
status
–– Poor perioperative hyperglycemic control (180–200 mg/
dL or more)
–– Immunodeficiency
–– Subcutaneous tissue ≥3 cm in depth
• Infection-related risk factors:
–– Remote site infection, e.g., UTI
–– Vaginal colonization (e.g., group B streptococcal infec-
tion and bacterial vaginosis)
–– Positive MRSA status
Classification of surgical wounds:
Class I (clean The following criteria should be fulfilled for

wound) class I wounds:
• Uninfected operative wound
• No intraoperative entry to the respiratory,
alimentary, genital, or urinary tracts
• Primary closure of the wound
If a closed drain is placed, the wound is still
classified as class I
Class II (clean- Criteria of class II wounds include

contaminated controlled entry to the respiratory,
wound) alimentary, genital, or urinary tracts, e.g.,
biliary surgery, appendectomy, and vaginal
surgery
Class III Criteria of class III wounds include:
(contaminated • Trauma surgery involving open fresh
wound) wounds
• Accidental breaks in sterile technique
during surgery, e.g., spillage of
gastrointestinal contents
• Incisions where acute, non-purulent
inflammation is present
Class IV Criteria of class IV wounds include:
(infected wound) • Trauma surgery involving old wounds
• Surgeries on top of clinical infection or
perforated viscera in the surgical field
Antibiotic regimens per procedure:
Prophylactic antibiotics Prophylactic antibiotics not indicated

indicated
• Hysterectomy (any • Hysteroscopy
route) • Laparoscopy (with no vaginal or
• Colporrhaphy bowel entry)
• Vaginal sling placement • D&C (non-obstetric indications)
• Laparotomy without • Oocyte retrieval
organ entry to the • Office procedures including
bowel or the vagina urodynamic studies, colposcopy,
• Uterine evacuation and related procedures, e.g., LEEP,
(pregnancy-related) punch biopsies, endocervical
curettage, intrauterine device
insertion, hysterosalpingography,
or saline infusion sonography
• Cefazolin is the medication of choice in all gynecologic

procedures. The dose is 2 grams IV within 60 minutes of
the procedure (3 grams for women weighing >120 kg). A
repeat dose is recommended if the procedure extends
beyond 4 hours or if blood loss is significant (>1500 ml).
Further Reading 529
• For uterine evacuation, doxycycline 200 mg is preferred

prior to the procedure.
• In patients with major allergic reaction to penicillins, e.g.,
anaphylaxis, urticaria, clindamycin, OR metronidazole
may be given in addition to gentamicin.
• Patients with history of or current MRSA colonization or
infection are recommended to receive IV vancomycin
15 mg/kg prior to surgery.
Further Reading
tice bulletin no. 84: prevention of deep vein thrombosis and pul-
monary embolism. Obstet Gynecol. 2007;110:429. Reaffirmed
2018.
tice bulletin no. 195: prevention of infection after gynecologic
procedures. Obstet Gynecol. 2018;131:e172.
Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. Centers for
Disease Control and Prevention guideline for the prevention of
surgical site infection, 2017. JAMA Surg. 2017;152:784.
Caprini JA. Risk assessment as a guide to thrombosis prophylaxis.
Curr Opin Pulm Med. 2010;16(5):448–52.
Nelson G, Altman AD, Nick A, Meyer LA, Ramirez PT, Achtari C,
Antrobus J, Huang J, Scott M, Wijk L, Acheson N. Guidelines for
postoperative care in gynecologic/oncology surgery: Enhanced
Recovery After Surgery (ERAS®) Society recommendations—
Part II. Gynecol Oncol. 2016;140(2):323.
Index
A examination, 68, 70
Abnormal uterine bleeding hormonal withdrawal tests, 71
(AUB) imaging tests, 71
acute uterine bleeding, 54, 55 laboratory testing, 70
chronic uterine bleeding, 55, patient history, 66, 68
56, 58 polycystic ovary syndrome
contraceptive history, 50 complications, 76–78
family history, 50 definition, 73
gynecologic history, 49 diagnosis, 74, 76
history of present illness, 48, differential diagnosis, 79
49 etiology and pathogenesis,
hysteroscopy, 54 73
laboratory workup, 51 incidence, 73
medical history, 50 treatment, 79, 80, 82, 84
microbiological tests, 53 primary amenorrhea, 63–65
obstetric history, 49 secondary amenorrhea, 63, 65,
pathological tests, 52 66
personal history, 48 serum hormone levels, 70
physical examination, 50 Amsel diagnostic criteria, 107
sonography, 53, 54 Anterior abdominal wall
surgical history, 50 muscle layer, 27–29
types of, 45, 47 peritoneum, 28
Acanthosis nigricans, 75 skin and subcutaneous layer,
Adenocarcinoma, 438 27
Adenomyosis, 233 transversalis fascia, 28
definition, 257 vascular supply, 29
diagnosis, 258, 259 Antibiotic prophylaxis, 527–529
etiology, 257 Antral follicle count (AFC), 362
pathology, 258 Aromatase inhibitors, 253
treatment, 259 Asherman syndrome
Amenorrhea classification, 375
chromosomal analysis, 71 definition, 375

https://doi.org/10.1007/978-3-030-41128-2
532 Index
Asherman syndrome (cont.) post-treatment follow up, 448,

diagnosis, 376, 377 449
etiology, 375 preoperative assessment, 444
treatment, 378 prevention, 444
Asymptomatic endometriosis, prognosis, 449
250 screening for, 62, 442
Atrophic vaginitis, 118, 119 types of, 437
Cervical intra-epithelial
neoplasia (CIN)
B Bethesda system, 423, 424
Bacterial vaginosis cervical biopsy, 429, 430
complications and CIN-proven biopsy, 433, 434
associations, 108 colposcopy, 427, 428
definition, 105 definition, 422
diagnosis, 106–108 ECC, 429
etiology, 105 HPV test, 426
treatment, 108, 109 incidence, 422
Bartholinitis and Bartholin cyst normal pap test, 430
diagnosis, 120, 122 pap test, 425, 426
etiology, 120 physical signs, 424
treatment, 122, 124 post-treatment follow-up, 435
Bethesda system, 423, 424 prognosis of, 435
Bladder cancer, 235 risk factors, 423
Borderline mucinous tumor, 492 screening guidelines, 425
Borderline serous tumor, 491 site of carcinogenesis, 422
Breast cancer, 164 symptoms, 424
Brenner tumor, 492 traditional classification, 423
Cervical stenosis, 404
Chancroid, 131, 132
C Chromopertubation, 354
Caprini risk assessment, 526 Chronic abdominal wall pain, 236
Celiac disease, 235 Chronic constipation, 236
Cervical agenesis, 404 Chronic pelvic pain
Cervical carcinoma, 164 causes, 233, 235–237
bloodstream, 439 definition, 233
cervical biopsy, 443 diagnosis, 237, 238
clinical staging, 444–447 endometriosis, 241–243
diagnosis, 439–441 treatment, 240, 241
differential diagnosis, 442 work-up, 239
direct (local) spread, 438 Clomiphene citrate (CC)
during pregnancy, 448 clinical outcome, 367
etiology, 435, 436 contraindications, 366
incidence, 435 induction regimen, 366
lymphatic spread, 439 mechanism of action, 366
macroscopic features, 437 side effects and complications,
microscopic types, 438 366
Index 533
Coitus interrupts, 204 transdermal patches, 157

Colorectal carcinoma, 235 types of, 151
Colposcopy, 427, 428 vaginal ring, 157
Combined hormonal WHO Medical Eligibility
contraceptives (CHC), Criteria Classification
251 categories, 152
Combined oral contraceptives Cystometry
(COCs), 156, 157, 436 detrusor pressure, 335
Congenital anomalies of vagina, filling phase, 335, 336
397, 398 interpretation, 337
Congenital anomalies of vulva, voiding phase, 336
396, 397
Contraception
administration, 167, 168, D
170–185 Desquamative inflammatory
advantages, 162, 163 vaginitis
adverse effects, 164 clinical presentation, 119
barrier methods, 153–170 treatment, 120
coitus interrupts, 204 work-up, 119
combined oral contraceptive Diagnostic laparoscopy, 249
pills, 156 Disorders of sex development
disadvantages, 164 (DSD)
effectiveness, 151, 158 46 XX karyotype
emergency contraception, 197, clinic features, 394
198, 200, 201 etiology, 393, 394
female sterilization, 205–208 treatment, 394
fertility awareness methods, 46 XY karyotype
202, 204 characters, 395
indications, 158 etiology, 395
intrauterine devices (see gonadal dysgenesis, 396
Intrauterine devices treatment, 395
(IUDs)) Diverticular disease, 235
intra-uterine system (IUS) Dual energy x-ray
(see Intra-uterine absorptiometry
system (IUS)) (DEXA), 267
lactational amenorrhea Dysmenorrhea, 98, 245
method, 202 Dyspareunia, 246
male sterilization, 209
mode of action, 158
POPs (see Progestin only pills E
(POPs)) Electromyogram, 339, 340
postpartum contraception, Emergency contraception, 197,
196, 197 198, 200, 201
progestin-only implants, Endocervical curettage (ECC),
178–180 429
side effects, 165, 167 Endometrial ablation, 227
534 Index
Endometrial cancer, 53 work up, 248

Endometrial carcinoma Endometriosis-related infertility,
diagnosis, 465, 466 246
endometrial sampling, 467 Enhanced Recovery After Surgery
etiology, 461, 462 (ERAS) protocols
fertility preservation intraoperative
management, 473 recommendations, 522,
FIGO 2009 staging, 470–472 523
genetic testing, 468 postoperative
hysteroscopy, 467 recommendations, 523,
incidence of, 461 524
pathology, 462–464 preoperative
postoperative follow up, 473, recommendations, 521
474 Epithelial ovarian cancer, 511
prophylactic treatment, 469 Estrogen therapy, 264
screening, 466 External genital organs
surgical staging, 469, 470 deep structures, 5
trans-vaginal sonography, 467 superficial structures, 3, 5
Endometrial cycle, 32, 33 vascular and nerve supply, 6
Endometrial hyperplasia External genital warts
with atypia/EIN, 460 diagnosis, 135
clinical features, 455 etiology, 134
complex hyperplasia, 459, 460 treatment, 135, 137
EIN classification, 454 External genitalia, 42
endometrial biopsy, 456, 457
prophylaxis, 457
screening system, 455 F
simple endometrial Fallopian tube anomalies, 404
hyperplasia, 458 Fecundability, 343
trans-vaginal sonography, Female genital mutilation
455, 456 (FGM)
WHO classification, 453, 454 classification, 330
Endometrial intraepithelial clinical assessment, 331
neoplasia (EIN) complications, 331
classification, 454 definition, 330
Endometrial polyps, 53 management, 331, 332
Endometriosis, 233 Female sterilization, 205–208
classification system, 244, 245 Fertility awareness methods, 202,
diagnosis, 245–247, 249 204
differential diagnosis, 248 Fertility preservation
etiology, 241 cryopreservation, 390
incidence, 241 definition, 389
pathology, 242, 244 future options, 391, 392
risk factors, 242 indications, 389, 390
treatment, 250, 251, ovarian function, 391
253–255, 257 uterus protection, 391
Index 535
Fibroid-related infertility, 230 Germ cell tumors,

Fibromyalgia, 237 493–495, 514
Functional incontinence, 276 Gestational trophoblastic disease
(GTD), 479
Gestational trophoblastic
G neoplasia (GTN)
Genital herpes classification of, 479, 480
clinical picture, 125 definition, 479
etiology, 124 diagnosis, 481–483
treatment, 126, 127 FIGO anatomic staging, 483
types, 124 incidence of, 479
work-up, 125, 126 mode of spread, 481
Genital infections patient risk, 484
atrophic vaginitis, 118, 119 post-treatment follow-up, 486
bacterial vaginosis (see prognosis, 487
Bacterial vaginosis) rare types of, 485
bartholinitis and bartholin GnRH analogue, 252
cyst GnRH antagonist, 253
diagnosis, 120, 122 Gonadal dysgenesis
etiology, 120 abnormal karyotype
treatment, 122, 124 diagnosis, 84
chancroid, 131–132 incidence, 84
desquamative inflammatory types, 84
vaginitis (see work up, 87, 88
Desquamative normal karyotype, 89
inflammatory vaginitis) Granuloma inguinale
external genital warts, 134, (donovanosis), 132
136, 137
genital herpes, 124–127
granuloma inguinale H
(donovanosis), 132 Hirsutism, 75, 81, 82
lymphogranuloma venereum, History of present illness (HPI),
133–134 48, 49
molluscum contagiosum, 137 Human papilloma virus (HPV)
pelvic inflammatory disease, testing, 426
138–140, 142–144, Hymeneal anomalies, 397
146–148 Hyperandrogenism, 75
syphilis, 127, 129, 130 Hyperprolactinemia
toxic shock syndrome, 148, 149 causes, 93, 94
trichomoniasis definition, 92
complications, 112 diagnosis, 94, 95
diagnosis, 110, 111 Hysterosalpingo-contrast
etiology, 109 sonography, 354
treatment, 112, 113 Hysterosalpingography (HSG),
vulvovaginal candidiasis, 353
113–115, 117 Hysteroscopy, 54, 354
536 Index
I advantages, 187
Infertility, 76, 82 complications, 189–191
aromatase inhibitors, 367 contraindications, 186
Asherman syndrome disadvantages, 187
classification, 375 effectiveness, 186
definition, 375 indications, 186
diagnosis, 376, 377 missed IUD strings,
etiology, 375 194, 195
treatment, 378 mode of action, 186
clomiphene citrate (see types of, 185
Clomiphene citrate Intra-uterine system (IUS)
(CC)) administration, 185
definition, 343 advantages, 182
diagnosis, 347 contraindications, 184
evaluation, 344 disadvantages and side
general treatment, 364 effects, 183
genetic testing, 351 indications, 183
GnRH agonist, 369 mode of action, 182
GnRH antagonists, 369 types of, 182
gonadotrophins, 367, 368 Invasive vaginal carcinoma,
history, 344, 345 419–422
hormonal testing, 350 Invasive vulval carcinoma
imaging, 351 clinical staging, 414
incidence, 343 diagnosis, 415
initial workup, 347 incidence, 412
multifetal gestation, 372–375 pathology, 413
ovarian factor infertility, 359 prognosis, 416
patient presentation, 364, 365 risk factors, 412
physical examination, 346 treatment, 415, 416
prevention, 355–358 Irritable bowel syndrome (IBS),
pulsatile GnRH, 370–372 235
semen analysis, 348–350
testicular biopsy, 351–354
WHO classification, 358 K
work-up Krukenberg tumor, 498
assessment of ovarian
reserve, 361–363
diagnosis of anovulation, L
360, 361 Lactational amenorrhea method,
premature ovarian failure, 202
363 Laparotomy, 509
Inflammatory bowel disease Liver cancer, 165
(IBD), 235 Lymphogranuloma venereum
Internal reproductive organs, 40 (LGV)
Interstitial cystitis, 234 diagnosis, 133, 134
Intrauterine devices (IUDs) etiology, 133
administration, 192, 193 treatment, 134
Index 537
M Myocardial infarction, 164

Magnetic resonance guided Myofascial pain syndrome, 236
focused ultrasound
(MRgFUS), 229
Male sterilization, 209 N
Menopause Non-hormonal treatment
definition, 261 (NSAIDs), 250
hormonal therapy, 263, 264
manifestations and
complications of, 261, O
262 Office endometrial biopsy, 61
non-hormonal therapy, 266 Open hysterectomy, 227
work-up, 263 Oral contraceptive pills (OCPs),
Menouria syndrome, 323 80
Menstrual disorder Osteitis pubis, 237
AUB (see Abnormal uterine Osteopenia and osteoporosis
bleeding (AUB)) definition, 266
dysmenorrhea, 98 prevention, 267
hyperprolactinemia, 92, 94, 95 risk factors, 266
postmenopausal bleeding screening and early detection,
definition, 59 267
diagnosis, 60, 61 treatment, 268, 269
etiology, 59, 60 Outflow tract obstruction
invasive diagnostic causes, 89
procedures, 62, 63 diagnosis, 90, 91
non-invasive diagnostic pathology, 90
procedures, 61 treatment, 91
premenstrual syndrome, 99, Ovarian anomalies, 404
101, 102 Ovarian cycle, 30
Menstrual irregularities, 74 Ovarian cysts, 234
Migraine, 164 Ovarian remnant syndrome, 234
Minimally invasive hysterectomy, Ovarian torsion, 517–519
226 Ovarian tumors
Mixed incontinence breast cancer screening, 504
behavioral therapy, 285, 286 epithelial ovarian cancer, 511
physical therapy, 286, 287 diagnosis, 503
Molluscum contagiosum, 137 FIGO Surgical Staging
Mucinous cyst-adenocarcinoma, System, 511
492 follow-up, 504, 505
Mucinous tumors, 492 germ cell ovarian tumors, 514
Müllerian anomalies post-treatment follow up, 515
classification, 398 preoperative assessment, 505,
clinical features, 399, 400 506
work-up, 400, 401 primary ovarian tumors
Müllerian inhibiting substance brenner tumor, 492
(MIS), 396 epithelial tumors, 490
538 Index
Ovarian tumors (cont.) Pelvic avascular spaces, 21–24

germ cell tumors, 493–495 Pelvic congestion syndrome, 237,
mucinous tumors, 492 241
serous tumors, 490, 491 Pelvic floor
sex cord-stromal tumors, coccygeus muscle, 20
496 levator ani muscle, 18
types, 489 perineal membrane, 18
prognosis, 516, 517 tension myalgia, 236
prophylactic treatment, 507 Pelvic inflammatory disease
screening of, 502 (PID), 234
secondary ovarian tumors complications, 143, 144
diagnosis of, 500, 501 definition, 138
Krukenberg tumor, 498 diagnosis, 139
mode of spread, 499 differential diagnosis, 142, 143
physical examination, 501 etiology, 138
protective factors, 499 treatments, 144, 146, 148
risk factors, 498 work-up, 140, 142
sex cord-stromal ovarian Pelvic organ prolapse
tumors, 514 definition, 293
treatment etiology, 293, 294
of borderline tumors, 515 traditional classification, 294
during pregnancy, 509 Pelvic organ prolapse
of malignant tumors, 509, quantification
510 (POP-Q)
planning, 507 abdominal sacrocolpopexy,
of relapse, 516 310, 311
Overflow incontinence, 275 anatomical changes and
complications, 298, 299
conservative management,
P 305
Pain associated endometriosis, differential diagnosis, 303, 304
255 history, 299–301
Papillary serous cystadenoma, hysteropexy, 311–313
491 physical examination, 301,
Pap testing, 425, 426 302
Pelvic-abdominal vasculature role of, 298
abdominal aorta, 24 staging, 296–298
celiac trunk, 24 surgical management, 306,
inferior mesenteric artery, 25 307
internal iliac (hypogastric) vaginal approach, 307–310
artery, 25 vaginal pessary, 305, 306
ovarian artery, 26 work-up, 303
pudendal bundle, 26 Pelvic organs
superior mesenteric artery, 24 fallopian tubes, 14
uterine artery, 26 ovaries, 14
Pelvic adhesive disease, 234 pelvic ureter, 15, 16
Index 539
rectum, 17, 18 Premenstrual syndrome (PMS)

sigmoid colon, 17 definition, 99
urethra, 17 diagnosis, 100, 101
urinary bladder, 16 Progesterone therapy, 264
uterus, 11–13 Progestin-only implants, 178–180
vagina, 9, 10 Progestin-only injectables (POI)
vascular and lymphatic administration, 178
connections, 14 advantages, 175
Pelvic outlet, 7, 8 contraindications, 177
Peritoneum, 28 disadvantages, 176
Polycystic ovary syndrome efficacy, 175
complications, 76–78 indications, 177
definition, 73 mode of action, 175
diagnosis, 74, 76 side effects and complications,
differential diagnosis, 79 176
etiology and pathogenesis, 73 types of, 174
incidence, 73 Progestin only pills (POPs)
treatment, 79, 80, 82, 84 administration, 173, 174
Post-ablation tubal syndrome, advantages, 172
234 contraindications, 171
Postmenopausal bleeding (BMP) disadvantages, 172
definition, 59 efficacy, 171
diagnosis, 60, 61 indications, 171
etiology, 59, 60 mode of action, 170
invasive diagnostic side effects, 173
procedures, 62, 63 types of, 170
non-invasive diagnostic Progestins, 251
procedures, 61 Puberty
Postpartum contraception, 196, definition, 34
197 diagnosis of, 34, 35
Precocious puberty precocious puberty
definition, 35 definition, 35
diagnosis, 38 diagnosis, 38
etiology, 36, 38 etiology, 36, 38
incidence, 35 incidence, 35
treatment, 39 treatment, 39
types of, 35, 36 types of, 35, 36
Pregnancy loss pubertal changes, 34
definition, 381
etiology, 381, 382
history, 383 R
imaging tests, 385 Rectovaginal fistula
karyotyping, 385 definition, 326
laboratory tests, 384, 385 diagnosis, 327
management, 386 etiology, 326
physical examination, 384 physical examination, 327
540 Index
Rectovaginal fistula (cont.) T

surgery, 329 Thromboprophylaxis
symptoms, 327 caprini risk assessment, 526
treatment, 328 risk classification, 524, 525
work-up, 327, 328 risk management, 525, 526
Recurrent cystitis, 235 Total incontinence, 276
Toxic shock syndrome
diagnosis, 149
S etiology, 148
Saline infusion sonography, 54 treatment, 149
Selective estrogen receptor Trans-vaginal sonography, 53, 61
modulator (SERM), Transversalis fascia, 28
366 Trichomoniasis
Selective serotonin reuptake complications, 112
inhibitors, 266 diagnosis, 110, 111
Serous cyst-adenocarcinoma, 491 etiology, 109
Serous tumors, 490 treatment, 112, 113
Sex cord-stromal tumors, 496, 514
Sexually transmitted disease, 423
Sheehan syndrome U
definition, 91 Ureterovaginal fistula
diagnosis, 92 definition, 324
treatment, 92 diagnosis, 324, 325
Simple serous cystadenoma, 491 etiology, 324
Squamous cell carcinoma, 438 treatment, 325, 326
Stress incontinence, 275 Urethral pressure, 339
behavioral therapy, 285, 286 Urge incontinence, 275
bulking agents, 289, 290 behavioral therapy, 285, 286
classification, 277 bladder diary, 279, 280
definition, 276 cystourethroscopy, 285
pathogenesis, 277 definition, 278
pessaries, 287 electromyography, 285
physical therapy, 286, 287 etiology, 278
risk factors, 276 history, 278, 279
surgical treatment, 290–292 palpation/bimanual
Stroke, 164 examination, 281
Subfertility, 343 pharmacological therapy, 287,
Submucous leiomyomas, 53 288
Syphilis physical therapy, 286, 287
clinical presentation, 128, 129 post void residual, 282
diagnostic work-up, 129, 130 rectal examination, 281
etiology, 127 sacral neuromodulation, 289
incidence, 127 screening neurologic
treatment, 130 examination, 281
Index 541
speculum examination, 281 V

urethra inspection, 280, 281 Vaginal agenesis, 401–403
urethral pressure profiles, 284, Vaginal intraepithelial neoplasia
285 (VAIN), 417, 418
urinalysis, 282, 283 Venous thrombo-embolism
urodynamic studies, 283, 284 (VTE), 164
uroflowmetry, 284 Vesicouterine fistula, 323
Uroflowmetry, 284, 338, 339 Vesicovaginal fistula (VVF)
Uterine artery/fibroid causes, 315, 316
embolization (UAE/ definition, 315
UFE), 228 diagnosis, 317, 318
Uterine leiomyoma, 234 inflammatory fistula,
asymptomatic and fibroids, 216 321–323
classification, 212, 213 malignant fistula, 321
complications, 222 non-surgical treatment, 319
definition, 211 post-radiation fistula, 321
etiology, 211 preventive management, 318,
gynecologic symptoms, 217, 218 319
incidence, 211 surgical treatment, 319, 320
infertility, 219, 220, 222 Vulval intraepithelial neoplasia
interventional radiology, (VIN)
228–230 classification, 409
obstetric symptoms/ colposcopic examination, 411
complications, 218 follow-up, 412
pathology, 213, 214, 216 ISSVD classification
treatment, 223, 225, 226, 228 2015, 409
Uterine sarcoma management, 411
classification, 475, 476 physical signs, 410
differential diagnosis, 477 symptoms, 410
endometrial biopsy, 477 treatment, 412
FIGO staging, 476 vulvar Paget's disease, 410
imaging, 477 Vulvar Paget's disease, 410
incidence, 474 Vulvar pruritus
physical examination, 476 clinical evaluation, 270, 271
risk factors, 474 treatment, 271
subtypes of, 478 Vulvovaginal candidiasis
symptoms, 476 diagnosis, 114, 116
treatment, 477, 478 etiology, 113, 114
Uterine vascularity, 53 treatment, 116, 117

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Gynecology

A CREOG and Board Exam Review

ISBN 978-3-030-41127-5 ISBN 978-3-030-41128-2 (eBook)

© Springer Nature Switzerland AG 2020

This Springer imprint is published by the registered company Springer

Part I General Gynecology

3 Genital Infection������������������������������������������������������������� 105

7 Menopause ��������������������������������������������������������������������� 261

15 Anomalies of Female Genital Tract����������������������������� 393

The External Genital Organs (The Vulva)

© Springer Nature Switzerland AG 2020 3

The labia majora: two folds of the skin (hair bearing)

–– Eccrine sweat glands: they may give rise to syr-

Superficial The ischial The perineal body

–– Vestibular bulbs (erectile tissue):

• Vascular and nerve supply:

Lymphatic • Areas external to the hymenal ring: drain to

Anatomy of the vulva

• The bony pelvic outlet:

• Posterior triangle (anal triangle):

–– The subcutaneous portion: this part is

The • Anteriorly: this part is adjacent to the vesical neck

Anatomical relations of the vagina and the uterus

lower fibrous cervix. The fundus is the upper portion of the

Posteriorly It is adjacent to the cul-de-sac and loops of the

Cervical •T he transverse cervical (Mackenrodt or cardinal)

–– Vascular and lymphatic connections:

Lymphatic • The uterine corpus:

• The Fallopian tubes:

Lymphatic drainage Along the ovarian lymphatics to para-

Lymphatic drainage Para-aortic lymph nodes

• The pelvic ureter:

Anorectal junction is angled at 90 degrees by the

The Pelvic Floor

The pubococcygeus The iliococcygeus The puborectalis

• Supportive action: of pelvic organs including the bladder and uterus

• Sphincter action: for the urethra, vagina, and rectum

• The coccygeus muscle:

Pelvic floor muscles

Space Boundaries Contents Surgical importance

Rectovaginal space • Anteriorly: the vagina - This space is developed

• Superiorly: the cul-de-sac cul-de-sac peritoneum

• The inferior mesenteric artery:

➋ Lateral sacral arteries

• Pudendal bundle (nerve and vessels):

–– Branches (nerve and vessels):

Anatomy of Anterior Abdominal Wall

• Skin and subcutaneous layer:

Internal Lumbosacral Costal cartilages of the

Transversus Internal surfaces of Linea alba

Rectus Pubic symphysis Anterior surface of the

–– The medial umbilical folds: they are lateral to the

The ovarian cycle:

Phase Events Follicular phases

Phase Events Follicular phases

The endometrial cycle:

Phase Duration Characters

Proliferative 9–10 days • The principal hormone: estrogen

Physiologic Changes with Puberty

• Definition of puberty: puberty is a series of normal physi-

Tanner 2 Elevation of the breast Sparse long, slightly

Tanner 3 More enlargement of the Dark, coarse, and curled

Tanner 4 Elevation of the areola Hair adult in type,

Part I General Gynecology

3 Genital Infection�� 105

7 Menopause �� 261

15 Anomalies of Female Genital Tract�� 393

The External Genital Organs (The Vulva)

Lymphatic • Areas external to the hymenal ring: drain to

The • Anteriorly: this part is adjacent to the vesical neck

Cervical •T he transverse cervical (Mackenrodt or cardinal)

The Pelvic Floor

Anatomy of Anterior Abdominal Wall

Physiologic Changes with Puberty

➊ Idiopathic or constitutional (90%): it refers to hypo-

The uterus • Absence of anti-Müllerian hormone in female

The vagina • The most inferior portion of the uterovaginal

Abnormal Uterine Bleeding