Reproductive gynaecology

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Reproductive Gynaecology
By
Ahmed Elbohoty MD, MRCOG
Assistant professor of obstetrics and gynecology
Ain Shams University
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Steroid nucleus for
all steroidogenic
hormones
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18C Estrone
Estradiol
Estriol
Estetrol
19 C DHEA
Androstendion
Testosterone
DHT
21 C Progesterone
Aldosterone
Cortisone
27 C Cholesterol
Steroidogenesis
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Steroidogenesis
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Hypothalamus
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— Composed of multiple nuclei with diverse
functions
• Connect the nervous and endocrine systems Via the
pituitary gland
• Secretes neurohormones which regulate
homeostasis
• Medial preoptic nucleus secretes gonadotropin-
releasing hormone (GnRH)
Connections
Hypothalamus
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Negative and positive feedbacks
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Releasing hormones
• Gonadotropin-releasing hormone (GnRH)
– pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-
NH2 (MW of GnRH @ 1,182 )
regulate the release of FSH and LH
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GnRH Pulses
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The pulse mean frequency for GnRH & LH
secretion:
• Early follicular phase 90 minutes
• Late follicular phase 60–70 minutes
• Early luteal phase 100 minutes
• Late luteal phase 200 minutes

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Number of oocytes in all life stages
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Gonadotrophins (FSH/LH)
Glycoprotein
LH ½ life 20 minutes
FSH ½ life 3 hours.
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FSH
— Produced by anterior pituitary gland
— Initiation (primordial) stage of follicular development
does not require FSH
— Promotes folliculogenesis and maturation by affecting
granulosa cells in the ovaries
— Induce LH receptors in Granulosa cells
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LH
— Produced by anterior pituitary gland
— Supports folliculogenesis by initially stimulating theca
cells in the ovaries to produce androgens, which are
the hormonal precursors for estradiol production, and
later affecting granulosa cells to promote
folliculogenesis
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FSH & LH threshold
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FSH
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For optimal follicular development, levels of LH should be above a certain ‘threshold’ but below
the LH ‘ceiling’
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28-21
Maturation of Follicle and Oocyte
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Regressing Corpus Luteum
Preovulatory Follicle
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Aromatase
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Two-cell, two-gonadotropin concept

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Role of LH
— Early Follicular Phase (Day 1-7)
— Stimulation of androgen synthesis by theca cells as substrate for
estrogen production in granulosa cells
— “Two-cell, Two-Gonadotropin Concept” Late Follicular Phase (Day 7-
14)
— Along with FSH, LH stimulates growth of follicles to reach preovulatory
stages
—
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Role of LH
— Periovulatory Phase
— Triggers ovulation & follicular rupture
— Disrupts cumulus - oocyte complex
— Induces oocyte meiotic maturation
— Induces granulosa cell luteinisation
— Post-ovulatory Phase
— Start production of progesterone by Granulosa cells
— Maintenance of corpus luteum (luteal function maintained by hCG if
pregnancy occurs)
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The Ovarian Cycle
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EndocrineControlofthe
OvarianCycle
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Endometrium
Functional zone – layer closest to the cavity – contains
majority of glands. Thicker portion – undergoes
changes with monthly cycle
Basal zone – layer just under myometrium, attaches
functional layer to myometrial tissue, has terminal
ends of glands. Remains constant
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FollicularPhase
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LutealPhase
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Menstruation
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Mechanisms of contraception
Primary mechanismContraception method
- OvulationCHC
DMPA injection
Implant
-fertilizationCupper IUD
Endometrial atrophyLevonorgestrel IUS
Cervical mucousPOP
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HCG
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•It is a transition period between sexually
immature child to sexually mature, fertile
adult involves growth and maturation of
many tissues.
•Its timing has much individual variability.
•Normal puberty begins between 8 and 13
years of age in girls and between 9.5 and 14
years of age in boys.
•The average age for menarche is 12.7 years.
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Puberty:

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Mechanism
• In young children, LH and FSH levels are insufficient to initiate gonadal
function due to hypersensitivity of the gonadostate to estrogen –ve
feedback and intrinsic CNS inhibitor.
• With puberty age:
• pulsatile GnRH release from hypothalamus
• Increases LH & FSH secretion by gonadotrophs of anterior pituitary
• Gonadotrophins act peripherally to stimulate gonadal
development & secondary sexual characteristics via sex steroids
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Fat and puberty
• A BMI of more than 19
kg/m2 is essential prior
to menarche for puberty
to progress normally.
There has been some
evidence that a critical
fat mass of 22% is
required for this
sequence of events to
occur.
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Event Time Responsible hormone
Thelarche 10-11 years E2
Pubarche 10.5-11.5 years Androgens
Maximal growth velocity 11-12 years GH
Menarche 11.5-13 years E2
Adult pubic hair 13.5-16 years Androgens
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Tanner 'S Sexual Maturity Rating
BreastStages
Prepubertal1
Breast buds seen2
Larger breast buds3
Mound formed4
Fully formed5
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Tanner Stages

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Pubic hairStages
Prepubertal1
Few hairs at labia majora2
Mainly central growth of hair3
Triangular shaped area of pubic hair4
Adult shape, spread to thighs5
Tanner Stages
Precocious Puberty
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l Before the age of 8
l 5 times greater in girls than boys
l 75% is idiopathic
l However in younger Girls (less than 5) it is
usually CNS lesion present
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Effects
l Most serious
effect: short
stature
l Intellectual,
psychosocial
development
follows
chronologic age,
not stage of
puberty
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Early Puberty is more associated with
• Breast cancer
• Endometrial cancer
• Type 2 diabetes
• Hypertension
• Obesity
• Adolescent risk behavior
• Adult height
• Psychosexual development
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• Both prematurity and small for gestational age, as
well as overweight and obesity, have been
associated with precocious pubarche. In addition,
excess weight gain in childhood may predispose to
precocious pubarche in susceptible individuals.
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Premature sexual development is
classified as:
•Central, true or gonadotrophin-
dependent
•Peripheral, pseudo or gonadotrophin-
independent
•Isolated variants: precocious
thelarche, pubarche or menarche.
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Central precocious puberty
• Idiopathic
• Central nervous system pathology/lesion
• Hypothalamic hamartoma
• Tumour: astrocytoma, glioma, craniopharyngioma,
pituitary adenoma
• Congenital disorder: hydrocephalus, myelomeningocele,
arachnoid cyst
• Acquired: central nervous system irradiation, post head
trauma, post infection: encephalitis/meningitis,
chemotherapy
• Secondary to peripheral precocious puberty
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Peripheral precocious puberty
• Ovarian cause
◦ Estrogen-secreting: granulosa cell tumour, functional
ovarian cyst
◦ Androgen-secreting: Sertoli–Leydig cell tumour,
arrhenoblastoma (contrasexual)
• Adrenal cause
• Congenital adrenal hyperplasia (contrasexual) ◦
Cushing syndrome (contrasexual)
◦ Neoplasm: estrogen or androgen-secreting
adenoma/carcinoma (isosexual or contrasexual)
• Exogenous sex hormones: e.g. oral contraceptives, skin
cream, anabolic steroid
• McCune–Albright syndrome
• Severe longstanding hypothyroidism4/16/20 Elbohoty 53
Variants of normal pubertal development
• Premature thelarche/thelarche variant
• Isolated premature menarche
• Premature pubarche/adrenarche (contrasexual)
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Isosexual or Heterosexual.
•Central precocious puberty is always
isosexual, whereas peripheral
precocious puberty can be isosexual
or heterosexual.
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Ovarian causes
• Ovarian tumours can be either feminising or masculinising.
Autonomously functioning ovarian follicular cysts account
for most cases of isosexual precocity.
• Other causes include granulosa cell tumours, which may
present with premature breast development, abdominal
pain or vaginal bleeding.
• Androgen-producing ovarian tumours (for example, Sertoli–
Leydig cell tumour, arrhenoblastoma) present with
progressive virilisation and cause contrasexual precocious
puberty rarely
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Adrenal causes
• While adrenal disorders such as congenital adrenal hyperplasia
and adrenal tumours may cause premature sexual development,
this does not, however, involve gonadarche and so there is no
breast development.
• Girls with classic congenital adrenal hyperplasia, of which the
most common form is 21-hydroxylase deficiency, usually present
in the neonatal period with ambiguous genitalia and a salt-losing
crisis.
• Milder forms may, however, present with virilisation in late
childhood.
• Adrenal tumours can produce androgens as well as cortisol and
there may, therefore, be iso- or heterosexual precocious
pseudopuberty in addition to the clinical signs of cushing
syndrome.
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McCune - Albright Syndrome
• G protein linked receptors mutation leads to Constitutive activity
• A receptor which is capable of producing its biological response in the
absence of a bound ligand such as autonomous
endocrine hyperfunction leading to ovarian production of estrogen
without gonadotrophins
• Fibrous dysplasia of skull and long bone
• "Cafe-au lait" patches with serrated edges
• Autonomous endocrine overactivity :
• Precocious puberty
• Hyperthyroidism
• Hypercortisolism
• Pituitary adenomas secreting GH/ PRL
• Hyperparathyroidism
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Polyostotic fibrous dysplasia
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– To distinguish benign constitutional from pathological
causes.
– History(age, course, Medical , Drug, family history,
CNS …
– Exam (neurologic and endocrine ,…
– Xray: Bone Age
– FSH, LH,TFTs
– Steroids (DHEAS, Testosterone, estradiol,
progesterone, 17-hydroxyprogesterone)
Evaluation of Abnormal Puberty
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History
• Age of onset, sequence and progression of pubertal
changes
• Family history: timing of onset of puberty in mother
and siblings
• Neurological symptoms
• Exogenous sex steroid exposure in food, drugs or
cosmetics (e.g. steroid creams, estrogen, anabolic
steroids)
• Social history: history of adoption or child sexual
abuse
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Clinical examination
• Height and weight measurements ploRed using age-specific
growth charts
• Body mass index
• Pubertal Tanner staging
• Neurological examinaTon
• ExaminaTon of eyes including visual fields and fundoscopy
• Skin lesions (e.g. caf ́e au lait spots)
• Abdominal examinaTon
• ExaminaTon of external genitalia
• Signs of virilisaTon: clitoromegaly, deepening of voice,
hirsuTsm
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Biochemical investigations
• Serum LH and FSH levels (baseline)
• GnRH (LHRH) stimulation test
• Estradiol/testosterone levels
• Adrenal steroids, e.g. 17 OH progesterone,
dehydroepiandrosterone sulphate and androstenedione (raised
in congenital adrenal hyperplasia and adrenal tumours)
• Adrenocorticotrophic hormone stimulation test (to identify
steroid synthesis defects, e.g. congenital adrenal hyperplasia)
• Free thyroxine and thyroid-stimulating hormone
• Serum prolactin levels (may be raised in chronic hypothyroidism,
McCune–Albright syndrome or prolactinomas or point towards
pituitary stalk compression)
• Urinary steroid profile (to identify and quantify excess adrenal
androgens)
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GnRH (LHRH) stimulation test
• It is performed by measuring FSH and LH levels
sequentially after administering a GnRH analogue
bolus.
• In healthy pubertal children: the LH response
exceeds the FSH response.
• In prepubertal children and in thelarche variant:
the FSH response exceeds the LH response.
• In cases of CPP: pubertal response with
luteinising hormone predominance (LH:FSH ratio
>1)
• Peak LH levels vary, depending on the specific
assay used, but values of >8 iu/l are usually
considered diagnostic of CPP.4/16/20 Elbohoty 65
Imaging
• Left wrist X-ray for bone age
• The bone age is advanced, often by more than 2 years.
• Magnetic resonance imaging (MRI) of the brain (or
computed tomography [CT] if MRI is unavailable) is advised
in all girls with progressive CPP to exclude a central nervous
system lesion.
• CT adrenals (adrenal masses)
• Pelvic ultrasound (size, shape of uterus, endometrial
thickness and ovarian morphology)
• A uterine volume >2 ml or length >34 mm, a pear-shaped uterus
and endometrial thickening (endometrial echo) on pelvic
ultrasound
• Skeletal survey/bone scan (McCune–Albright syndrome)
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The goal of treatment is to:
• Halt or cause regression of secondary sexual characterisTcs
• Prevent early menarche
• Retard skeletal maturaTon
• Improve final height
• Avoid psychosocial/behavioural sequelae.
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Treatment
l MDT
l Diagnose and treat 2ry causes
l In the majority of girls with CPP no apparent
cause is found, although it is important to look
for evidence of any underlying disorder.
l Arrest maturation until normal pubertal age:
GnRH Agonists—monitor with estrogen levels.
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GnRH a
• GnRH agonist treatment does not improve final height in girls beyond
8 years of age, and there is only modest improvement in final height
in girls aged 6–8 years. The combined use of growth hormone and
GnRH agonists is controversial, but may allow more growth in children
who are particularly short
• Consider other effects of precacious puberty as the psychological and
social effects on the child and her family for the decision to start
GnRHa
• Treatment with GnRHa is usually stopped when it is time for normal
puberty to begin.
• The long- acting preparations available include leuprorelin, triptorelin
and goserelin, given subcutaneously or intramuscularly every 3–4
weeks or as a long-acting depot at 10 to 12-weekly intervals.
• In addition, an implantable GnRH agonist, histrelin (effective for 1
year) has been used successfully.4/16/20 Elbohoty 69
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The adverse effects of GnRHa
•Headaches, hot flushes, mood swings and
injection site reactions such as rashes,
bruising and sterile abscess formation.
•Adult bone mineral density appears not to
be adversely affected by childhood GnRHa
therapy.
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Peripheral precocious puberty
• It is relatively uncommon in girls.
• Clinical features are dependent on the aetiology
but often include rapid growth, advanced bone age,
pubic/axillary hair and clitoromegaly.
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Delayed Sexual Development

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Consequences of Late Puberty
• Self esteem
• Adult height
• Osteoporosis
• Psychosexual development
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Amenorrhea
•Primary amenorrhoea:
• A failure of menstruation by the age of 16 years in the
presence of normal secondary sexual characteristics,
or
• 14 years in the absence of other evidence of puberty.
• The most common causes for primary amenorrhoea are gonadal dysgenesis
(43%), Mullerian agenesis (15%), constitutional (14%) and PCOS (7%)
•Secondary amenorrhoea
• Absent periods for at least six months in a woman
who has previously had regular periods, or
• 12 months if she has previously had oligomenorrhoea
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Causes
• Physiological
• Hypothalamic-pituitary (hypofunction/dysfunction)
• Ovarian (hypofunction/dysfunction)
• Uterine and Outflow obstruction
• General
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Physiological
• Pregnancy
• Lactation
• Menopause
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Hypothalamic-pituitary
(hypofunction/dysfunction)
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• Weight loss
• Exercise
• Chronic illness
• Psychological stress
• Genetic, e.g. Kallmans syndrome
• Idiopathic
• Hydrocephalus, craniopharyngioma, empty
sella syndrome
• Prolactinoma
Genetic syndromes for 1ry ammenorhea
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Ovarian (hypofunction/dysfunction)
• PCOs
• POI
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Uterine and Outflow obstruction
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Assessment of amenorrhea
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History
• Age, last menstrual period, exposure to pregnancy, fertility
• Emotional stress, weight change, exercise
• Drugs, acute or chronic illnesses
• Hot flushes, breast discharge, headaches
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Primary amenorrhoea• You should consider how you might phrase your questions to a shy teenager in order to maximise your
rapport.
• Evidence of psychological dysfunction or emotional stress (progress in school, position in family dynamics)
• Mother and sister's gynaecological history of relevance
• Mother's obstetric history with index child
• Family history of genetic disorders or diabetes
• Family history of delayed puberty
• Pubertal development – lack of pubertal development suggests deficient estradiol secretion, which could
be due to a hypothalamic or pituitary disorder, ovarian failure, and/or a chromosomal abnormality
• The presence of galactorrhoea – may be due to hyperprolactinemia
• Symptoms of hypothyroidism
• Weight loss or gain
• Hirsutism or virilisation – virilisation may be due to due to an androgen-secreting ovarian or adrenal
tumor, or 5-alpha-reductase deficiency
• Menopausal symptoms
• Sexual activity
• Headache or visual disturbance, poluria, polydipsia – suggestive of CNS tumor such as
craniopharyngioma
• Anosmia – one of the causes is Kallmans syndrome
• Chronic systemic illness, chemotherapy, radiotherapy.4/16/20 Elbohoty 87
Secondary amenorrhoea
• All women of reproducXve age group should have a pregnancy
test.
• Irregular menstrual cycles, hirsuiXsm, acne – associated with
polycysXc ovary syndrome
• Malaise, faXgue, anorexia, weight loss – may be due to chronic
illness
• Heterotopic ossificaXon (h/o) following head injury
• Headaches – may be suggesXve of CNS tumor
• Galactorrhoea – may be due to prolacXnoma
• h/o postpartum haemorrhage – may be associated with
Sheehans syndrome
• h/o dilaXon and cure]age – may be associated with Ashermans
syndrome
• MedicaXons – contracepXon, anXdepressants and
anXpsychoXcs, chronic opioid use.
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Red flag symptoms needing urgent
attention include:
• Rapid virilisation – may be due to androgen-
secreting tumors
• Headach, visual field affection – may be associated
with intracranial tumors.
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Examination
• Obese or cachectic
• 2ry sexual character
• Hyperandrogenism
• Stigma of chromosomal problems: short stature,
webbed neck, wide carrying angel
• Vulva, vagina, uterus, ovaries
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1ry amenorrhea
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• Weight, height, body mass index (BMI)
• Shortened height may suggest a chromosomal abnormality, Low hairline, webbed
neck, widely spaced nipples etc are suggestive of Turners syndrome
• Women with gonadal dysgenesis and hypoestrogenaemia are at risk of a shortened
final adult height. Their growth pattern should be documented and compared with that
of first-degree relatives
• Blood pressure
• Clinical thyroid status
• Dysmorphic signs
• Any hirsuitism, acne etc.
• Tanner breast and axillary hair stages
• Abdomen/pelvis
• Perineum
• Mass arising from pelvis, Groin node/herniae
• Note the presence and distribution of pubic hair, clitoral size, configuration of hymen,
relationship of anus, vagina and urethra to hymen, the degree of estrogenisation and
perineal hygiene.
• The hymen and vestibule may be visualised with gentle lateral spread of the labia
majora with two fingers and a deep inspiration/valsalva manoeuvre by the patient
Secondary amenorrhoea
• The woman's height and weight should be recorded.
• Raised BMI is associated with polycysTc ovarian syndrome
and reduced BMI with stress or anorexia nervosa.
• Male paRern baldness and features of virilisaTon may be
due to androgen secreTng tumors of the ovary.
• Assess for galactorrhoea by doing a breast examinaTon.
• Look out for features of hypothroidism.
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INVESTIGATION
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Test Primary amenorrhoea Secondary amenorrhoea
Pregnancy Pregnancy must be ruled out Pregnancy must be ruled out
FSH/LH levels FSH will indicate the establishment of puberty and pituitary–
ovarian feedback.
If secondary sexual characteristics have developed and there is a
raised LH, the cause may be polycystic ovary syndrome.
In the absence of secondary sexual characteristics:
•High FSH and LH with short stature may indicate Turners
syndrome
•High FSH and LH with normal height may indicate ovarian failure
or male karyotype
•Low FSH and LH with short stature may indicate intracranial
lesions such as craniopharyngioma tumors
•Low FSH and LH with normal height may indicate weight loss,
anorexia nervosa or exercise
High FSH levels (>20 u/l on two occasions) is
suggestive of premature ovarian failure if the woman
is less than 40 years.
Low or normal FSH levels are found with weight loss,
stress and excessive exercise.
Increased LH/FSH ratio if found with polcystic ovary
syndrome.
Prolactin levels Prolactin elevation points to pituitary malfunction. If >1000 mIU/ml
(normal prolactin levels are <500 mIU/ml), the woman should be
referred to an endocrinologist and MRI of the brain should be
performed to diagnose pituitary adenomas
Prolactin >1000 mIU/ml needs further investigations
and referral to the endocrinologist
Thyroid function tests Perform test Perform test
Testosterone levels Testosterone >5nmol/l is found with androgen insensitivity,
androgen secreting tumors, Cushings syndrome and late onset
congenital adrenal hyperplasia
Testosterone >5 nmol/l is found with androgen
secreting tumors and Cushings syndrome
Estrogen and progesterone challenge
tests.
N/A Perform test
Sex hormone binding globulin N/A Perform test
Free androgen index N/A Perform test
Dehydroepiandrosterone and
androstenedione
N/A Perform test
Transabdominal ultrasound Invaluable when bimanual examination is inappropriate and/or
there is reason to question internal organ development and
potential functional integrity
N/A
Transvaginal ultrasound Provides more detailed information, particularly for ovarian
morphology and possible upper tract malformation
Test for polycystic ovaries, normal uterine anatomy
and Ashermans syndrome
MRI If uterus is absent – may indicate complete Mullerian agenesis or
Mayer-Rokinstanksy-Kustner-Hauser syndrome, or androgen
insensitivity.
If uterus is present – may show streak ovaries as in Turners
syndrome or outflow tract obstruction .
Perform test
Sonohysterography or
hysterosalpingography
N/A Test for Ashermans syndrome
Karyotyping Perform test Test if diagnosed with premature ovarian failure
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Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a
suspected disorder of sex development (Revised 2015)
Clinical Endocrinology
Volume 84, Issue 5, pages 771-788, 13 AUG 2015 DOI: 10.1111/cen.12857
http://onlinelibrary.wiley.com/doi/10.1111/cen.12857/full#cen12857-fig-0002
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Amenorrhea
Absent Uterus
Karyotype
46-XX
Mullerian
Agenesis
(MRKH syndrome)
Complete Andogen
Insenitivity (TSF
syndrome)
46-XY
Normal breasts
& sexual hair
Absent breasts
& sexual hair
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Partial Andogen
Insenitivity (TSF
syndrome)
Management of causes
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Constitutional delay
• Constitutionally, delayed puberty is characterized by a
positive family history, short stature, delayed secondary
sexual characteristics and delayed epiphyseal maturation
(identified by hand X-ray bone ageing).
• Final height prognosis remains in the appropriate range for
the parental centiles.
• Other causes should be ruled out and puberty induced.
4/16/20 Elbohoty 99
Amenorrhoea of hypothalamic/CNS
origin
Primary
amenorrhoea
Secondary
amenorrhoea
Weight loss Weight loss
Exercise Exercise
Genetic, e.g.
Kallmans
syndrome
Chronic illness
Idiopathic Idiopathic
Psychological
stress
4/16/20 Elbohoty 100

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Treatment
• The cause to be addressed, which can uncover major
conflicts of psychological disturbance and distorted body
image in the case of eating disorders.
• The role of dietician and psychiatrist is very important in
these patients
• Menstruation can be achieved by using combined pills.
• In cases of kallaman or hemosiderosis seeking fertility:
• Ovulation may be induced by using gonadotrophins
4/16/20 Elbohoty 101
Sports women
• Whereas it is the role of the coach to focus on optimising
performance, it is the responsibility of the physician to
prioritise the woman’s health
• There is a lack of knowledge among healthcare professionals
with regard to the impact of intense exercise on
gynaecological health, and less than 10% of physicians feel
comfortable managing amenorrhoeic athletes
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• Energy availability (EA) is determined by subtracting energy
expenditure from energy intake relative to fat-free mass.
• Optimal EA arises when there is sufficient energy remaining
to maintain bodily functions.
• It has been proposed that 45 kcal/kg fat-free mass/day
equates to energy balance.
• Low EA: lnegative energy balance. When expenditure
outweighs intake
• Relative Energy Deficiency in Sport (RED-S) Chronic low EA:
can impact on a number of key physiological systems,
including metabolism, bone health, immunity,
cardiovascular health and psychological wellbeing, as well as
menstrual and reproductive function. This syndrome of
inter-related health consequences4/16/20 Elbohoty
103
Female athlete triad
• It explored the relationship between
• EA
• Menstrual function
• Bone health in women.
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4/16/20 Elbohoty 105
RED
• It is prevalent in approximately 5% of the general population, it
has been shown to affect up to 65% of long-distance runners and
up to 79% of ballet dancers
• LH pulsatility is disrupted when energy availability decreases
below critical value of 20-25 Kcal/Kg fat free mass / day
• Amenorhic sports women have been shown to have 53% of the
energy availability of below a critical value of their menstruating
counterparts
• Intense exercise, defined as more than an hour a day with an
estimated energy expenditure of 6 kcal/minute, has been shown
to increase 6 times of infertility
• IVF outcomes in the context of exercise longevity found that
women who exercised for more than 4 hours/week for 1–9 years
were 40% less likely to achieve a live birth, had a three-fold
increased risk of cycle cancellation and had double the risk to
suggest physical activity with high impact or physical strain may
confer a higher miscarriage4/16/20 Elbohoty 106

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4/16/20 Elbohoty 107
Bone effects
• Sportswomen with hypothalamic amenorrhoea
have also been demonstrated to experience BMD
deterioration, with studies previously
demonstrating 10–20% lower BMD in
amenorrhoeic sportswomen compared with their
eumenorrhoeic counterparts.
• Following the onset of hypoestrogenism, osteoclast
resorption accelerates in the initial 6 months and
peaks within 3 years
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UI
• Sportswomen are at risk of urinary incontinence as a result
of raised intra-abdominal pressure, which is synonymous
with intense physical exertion.
• If intra-abdominal pressure exceeds the capacity of the
urethral sphincters, it manifests as urinary leakage.
• Urinary incontinence is even more prevalent in elite
sportswomen with eating disorders, highlighting the inter-
relationship between eating disorders and health
implications in sportswomen.
• UI is almost twice as common during training as during
competition, owing to higher catecholamine levels during
competition, which help maintain urethral closure by acting
on urethral alpha receptors
4/16/20 Elbohoty 109
Hormone profile
• Low FSH and low LH with coexistent low estradiol.
• Anti-mullerian hormone concentrations may be low in this
population and therefore may not be a reliable method of
detecting ovarian reserve.
4/16/20 Elbohoty 110

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4/16/20 Elbohoty 111
Management
Conservative Management
• If hypothalamic amenorrhoea due to low EA is diagnosed,
the overall treatment strategy is to increase energy intake
or reduce energy expenditure.
• Expert dietician input is essential to help to tailor an
appropriate diet to increase energy input in a sufficient
manner to restore physiological function, following an
individualised assessment of energy expenditure.
Additional protein and carbohydrate intake should be
advised to restore liver glycogen, which may facilitate LH
pulsatility resumption
• Increase energy intake by between 300 and 600 kcal/day.
• Barrier contraceptive methods should be used in women
who need continuing treatment and follow-up, at least until
they are deemed low risk.
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Hormonal management
• In adult sportswomen who have been undergoing
conservative management for more than 12 months, the
American College of Sports Medicine recommends the
addition of hormonal therapy, although it is essential
continued attempts to improve energy availability are
maintained.
• Transdermal estrogen, with associated progestogen, should
be used, as it does not interfere with IGF-I, and it has been
shown to improve BMD in sportswomen with menstrual
dysfunction.
• Transdermal estrogen does not act as a contraceptive and
therefore if contraception is required, it should be combined
with a levonorgestrel-containing intrauterine system or
barrier method.
4/16/20 Elbohoty 113
Avoid
• The combined oral contracepTve pill (COCP) or hormone
replacement therapy should not be used as primary
treatment to restore menses or improve BMD in women
with RED-S. ]
• The high estrogen dose in tradiTonal COCPs downregulates
insulin-like growth factor 1 (IGF- I) secreTon,an important
bone-trophic hormone, which may conversely hinder the
aRainment of opTmal BMD. Moreover, exogenous hormone
therapy may mask the condiTon for which it is given,
making it difficult to assess clinical response.
• Bisphosphanate should be avoided in women of
reproducTve age, owing to the unpredictable length of Tme
they are stored in bone and are potenTally terratogenic4/16/20 Elbohoty 114

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Kallmann's syndrome
• This is a rare (1:50 000) congenital absence of GnRH
neurons whose cell bodies should migrate from the
olfactory area to the arcuate nucleus of the hypothalamus,
with the axons extending down the tuberoinfundibular tract
to connect with the portal vasculature of the anterior
pituitary gland.
• It may be sporadic or inherited (autosomal dominant or X-
linked recessive) and is associated with anosmia and colour-
blindness.
4/16/20 Elbohoty 115
Pituitary: Hyperprolactinemia
4/16/20 Elbohoty 116

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Prolactin is under tonic dopamine inhibition:
factors known to increase prolactin secretion (e.g.
TRH) are probably of less relevance.
4/16/20 Elbohoty 117
It decreases GnRH pulsatility
at the hypothalamic level and,
4/16/20 Elbohoty 118

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Hyperprolactinaemia
Physiological
hyperprolactinaemia occurs
in
pregnancy,
lactation and
severe stress,
as well as during sleep .
4/16/20 Elbohoty 119
Hyperprolac9naemia
Mildly increased prolacSn levels (400–600 mU/L)
may be physiological and asymptomaSc but higher
levels require a diagnosis.
Levels above 5000 mU/L always imply a prolacSn-
secreSng pituitary tumour.
4/16/20 Elbohoty 120

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Hyperprolactinaemia has many causes
Common pathological causes include :
- prolactinoma,
- co-secretion of prolactin in tumours causing acromegaly, -
polycystic ovary syndrome,
- primary hypothyroidism
and ‘idiopathic’ hyperprolactinaemia.
Dopamine antagonist drugs :
(metoclopramide, domperidone, most antipsychotics) are a
common iatrogenic cause, as well as most other antiemetics (except
cyclizine) and opiates.
4/16/20 Elbohoty 121
4/16/20 Elbohoty 122

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Clinical features
Hyperprolactinaemia stimulates milk production in the breast and
inhibits GnRH and gonadotrophin secretion per se.
It usually presents with:
- Galactorrhoea, (60% of cases)
- Oligomenorrhoea or amenorrhoea
- Decreased libido in both sexes
- Decreased potency in men
- Subfertility
- Symptoms or signs of oestrogen or androgen deficiency
- Delayed or arrested puberty in the peripubertal patient
Additionally, headaches and/or visual field defects occur if there is a
pituitary tumour.
4/16/20 Elbohoty 123
Investigations
Hyperprolactinaemia should be confirmed by repeat
measurement.
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Serum level
Serum prolactin
concentration
Interpretation Action
<500 mu/l Normal range None
<1000 mu/l Consistent with stress or
recent breast examination
Repeat
700-2500 mu/l Hypothyroidism/ PCOS Check TSH, T4,
FSH/LH, testosterone, SHBG
<3000 mu/l Non-functioning
macroadenoma
MRI or CT head scan will
demonstrate hypothalamic
tumours, non-functioning pituitary
tumours causing hypothalamic
compression and
micro/macroadenomas of the
pituitary. Threshold for imaging:
>1500 mu/l on two occasions.
1500-4000 mu/l Functioning
microadenoma
4/16/20 Elbohoty 125
• Further tests are appropriate after physiological and drug causes
have been excluded:
• Visual fields should be checked Only 5% will display visual field
defects with adenomas
• Primary hypothyroidism
• must be excluded since this is a cause of hyperprolactinaemia.
• Anterior pituitary function
• should be assessed if there is any clinical evidence of
hypopituitarism or radiological evidence of a pituitary tumour.
4/16/20 Elbohoty 126

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64
Investigations
MRI of the pituitary
is necessary if there are any clinical features suggestive of
a pituitary tumour, and desirable in all cases when
prolactin is significantly elevated (above 1500 mU/L).
4/16/20 Elbohoty 127
Asymptomatic, incidentally detected microadenomas of the pituitary are common (up to
10% of the population). They rarely grow, and if they do, progression is slow. They
should be imaged at one, two and five years and if there has been no change, no further
follow-up is required.
In the presence of a pituitary mass on MRI :
the level of prolactin helps determine whether the
mass is a prolactinoma or a non-functioning
pituitary tumour causing stalk-disconnection
hyperprolactinaemia:
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4/16/20 Elbohoty 129
levels of above 5000 mU/L in the presence of a
macroadenoma,
or above 2000 mU/L in the presence of a
microadenoma (or with no radiological abnormality),
strongly suggest a prolactinoma
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Treatment
Treatment Dosage strategy Complications
Bromocriptine Start at 1.25 mg nocturnally for five
nights, and gradually titrate up to 7.5 mg
daily in two or three divided doses over
about three weeks
Common adverse effects: nausea, vomiting,
headache and postural hypotension (minimised
by initiating therapy at night and then taking
tablets with food). Longer-term adverse effects:
Raynaud's syndrome, constipation and
psychiatric changes (e.g. aggression, which can
occur at the start of therapy)
Carbergoline 0.25–1 mg twice-weekly up to 1 mg
daily
Longer acting and better tolerated by many of
the 10% of patients with unacceptable adverse
effects of bromocriptine. However both can also
have psychiatric adverse effects and are not
licensed for use in pregnancy. They should
remain second-line
Quinagolide 25–150 microgram daily in divided
doses
Surgery: trans-sphenoidal
resection of the adenoma
Reserved for those with intolerable
adverse effects to medication, non-
functioning macroadenomas (10%) or in
the presence of suprasellar extension
that has not resolved with medical
therapy
Pan-hypopituitarism which presents early and
must be anticipated and treated
Pituitary irradiation Seldom required with the availability of
modern neurosurgical skills
Associated with a significant risk of subsequent
medium/long-term panhypopituitarism that
warrants lengthy surveillance.
4/16/20 Elbohoty 131
Medical treatment :
Hyperprolactinaemia is controlled with a
dopamine agonist.
Cabergoline
(500 µg once or twice a week judged on clinical
response and prolactin levels) is the best tolerated
and longest-acting drug and is the first drug of
choice.
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Medical treatment :
Bromocriptine
is the longest-established therapy and therefore
preferred if pregnancy is planned: initial doses
should be small (e.g. 1 mg), taken with food and
gradually increased to 2.5 mg two or three times
daily.
Side-effects, which prevent effective therapy in a
minority of cases, include nausea and vomiting,
dizziness and syncope, constipation and cold
peripheries.
Quinagolide
(75–150 µg once daily) is an alternative.
4/16/20 Elbohoty 133
Complications seen when
cabergoline is used in higher
doses in Parkinson’s disease,
include :
pulmonary, retroperitoneal and
pericardial fibrotic reactions and
cardiac valve lesions.
Patients need monitoring,
although such adverse effects
appear to be very rare in patients
on lower, ‘endocrine’ doses.
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In most cases a dopamine
agonist will be the first and
only therapy
4/16/20 Elbohoty 135
Medical treatment :
Prolactinomas usually shrink in size on a dopamine
agonist, and in macroadenomas any pituitary mass
effects commonly resolve
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For macroadenomas
• Reduction in tumour size
• > 50% :40%
• 25-50%: 29%
• < 25%: 12.5%
• No reduction: 18.5%
4/16/20 Elbohoty 137
Trans-sphenoidal surgery :
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Follow up
• Dopamine agonists may be titrated down to the
lowest maintenance dose once macroadenoma
shrinkage has been achieved and for several (2–5)
years.
• Serum prolactin levels may be measured three-
monthly until stable.
• If medication is withdrawn, serial prolactin
measurement should resume with imaging after one
year.
• Microadenomas grow slowly, if they grow at all. It is
sufficient to perform serum prolactin and imaging
annually for two years and then limit to hormonal
assay annually thereafter.4/16/20 Elbohoty 139
Hyperprolactinaemia and pregnancy
• Approximately 80% of patients with hyperprolactinaemia
achieve pregnancy on dopamine agonist treatment.
• There is no increase in the rates of spontaneous miscarriage,
ectopic pregnancy or other complications of pregnancy, and
breastfeeding may be undertaken normally without fear of
stimulating tumour growth.
• The risk of clinically significant enlargement of
microprolactinomas in pregnancy is low (approximately
2.6%). However, this risk is much higher with
macroprolactinomas (15–35%) and 8.5% of these may
require surgery.
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Management:
• For microadenoma:
• Bromocriptine is usually discontinued early in pregnancy in women with
microprolactinaemia and most will have a very low risk of tumour
expansion during the pregnancy.
• An MRI should be performed if the woman develops visual symptoms of
mass expansion.
• For Macroadenoma:
• The risk of tumour expansion is so high that many centres recommend
continuation of medical treatment throughout the pregnancy with
monitoring of visual fields at least each trimester.
• Medical treatment is preferred to surgery where possible and
will generally provide optimal control in most cases with
microprolactinomas or macroprolactinomas with no supracellar
extension.
• Because of its better established safety profile, bromocriptine is
generally the first line of treatment.
4/16/20 Elbohoty 141
Amenorrhoea of ovarian origin
• Insufficiency (Premature ovarian insuficiency)
• Dysfunction (PCOs)
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POI
• The mean age for this natural phenomenon is 50
years (standard deviation 4 years).
• When the menopause occurs before the age of 40
years, it is considered premature ovarian
insufficiency
• A widely used definition of POI is 4 months of
amenorrhoea and two follicle stimulating hormone
levels 30 iu/ml at an interval of at least 1 month.
• The ovarian follicular function fluctuates in about
50% of women with POF and 5–10% of women with
the diagnosis may eventually conceive.
4/16/20 Elbohoty 143
Causes
• Idiopathic 88%
• X chromosome abnormalities 7%
• Turner/Turner syndrome-like karyotype
• FMR-1 premutation (Xq27.3)
• Bone morphogenetic protein
• OtherX chromosome abnormalities (deletion, translocation,
others)
• 46XY gonadal dysgenesis 0.5%
• Autosomal causes 1.6%
• FSH receptor mutation
• Blepharophimosis ptosis epicanthus inversus syndrome Iatrogenic
causes
• Iatrogenic causes 2.1 %
• Chemotherapy/radiotherapy
• Autoimmune causes 0.8%
4/16/20 Elbohoty 144

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History
• Amenorrhoea or oligomenorrhoea is the main presenting
feature.
• In the majority of cases, amenorrhoea is secondary and
follows normal pubertal development.
• In 20% of cases, amenorrhoea may be primary and pubertal
development may be delayed.
• Occasionally the pattern of menstrual irregularity presents
with failure of menses to return after cessation of hormonal
contraception.
• Some women also have symptoms of estrogen deficiency in
the form of hot flushes, night sweats and loss of libido.
4/16/20 Elbohoty 145
Excluding other common causes
of amenorrhoea
• Pregnancy
• Hypothalamic amenorrhoea (caused by anorexia nervosa,
exercise, stress and weight loss)
• Hyperprolactinaemia (symptoms include headaches and
galactorrhoea)
• Polycystic ovary syndrome (symptoms include hirsutism
and acne).
4/16/20 Elbohoty 146

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History of the cause
• A history of chemotherapy, radiotherapy or pelvic surgery in
the past is clearly relevant.
• A history of obstetric catastrophe, severe bleeding,
dilatation and curettage or infection indicates a uterine
cause (Asherman syndrome).
• A history of autoimmune disorders, including
hypothyroidism or adrenal insufficiency, should also be
elicited.
• A family history of POI can be recorded in 14–31% of cases
and a definite familial disorder can be identified in some of
these.
• Perrault syndrome (XX gonadal dysgenesis with
sensorineural deafness), FSH receptor mutations and fragile
X premutations are relatively more common among women
with a familial history of POF.4/16/20 Elbohoty 147
Examination
• Height, weight and body mass index
• The recognition of any dysmorphic features suggesting a
chromosomal or genetic cause of POF is important.
• The skin should be examined for hirsutism, acne, striae,
acanthosis nigrans and vitiligo.
4/16/20 Elbohoty 148

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75
Baseline tests: to diagnose
• Human chorionic gonadotrophin level
• Serum prolactin and thyroxine levels to rule out
hyperprolactinaemia and thyroid dysfunction, respectively.
• If there are signs of hyperandrogenism, serum
dehydroepiandrosterone and testosterone should be
measured.
• Serum FSH, LH and estradiol
• Follow-up tests are arranged according to the clinical history
and initial test results e.g. where there are initial increased
gonadotrophin levels, testing should be repeated after 4-6
weeks.
• A persistent increase confirms a diagnosis of POF
4/16/20 Elbohoty 149
Second-line investigations for the
cause :
• Karyotyping and FMR-1 premutation analysis are useful.
• Screening for autoimmune diseases (anti-adrenal, anti-21-
hydroxylase, anti-thyroid peroxidase and anti-thyroglobulin
antibodies) is indicated.
• Ovarian antibody screening is also recommended, as many
ovarian antigens have the potential for antibody formation.
Besides providing a clear explanation for the woman as to
the cause of her POF, this may help identify those at high
risk for other autoimmune conditions.
4/16/20 Elbohoty 150

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Investigations for the effect
•A dual-emission X-ray absorptiometry (DEXA)
scan should be considered for baseline
assessment, as women with POF have a risk of
almost 50% for osteopenia.
4/16/20 Elbohoty 151
Reproductive health and contraception
• Among women with POF, 5–10% experience spontaneous
resolution leading to pregnancy, although factors which
could predict this improved outcome have not been
elucidated.
• Thus contraception needs to be practised if the woman
wants to avoid pregnancy.
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Prophylaxis
• Women diagnosed with cancers and requiring
chemotherapy or radiotherapy that can give rise to ovarian
failure have the opportunity to prevent ovarian follicular
damage.
• This can be achieved by
• cryopreservation of oocyte, embryo or ovarian tissue.
• gonadal shielding
• ovarian transposition
• ovarian suppression by gonadotrophin-releasing hormone
analogues
4/16/20 Elbohoty 153
Management
• education, counselling and psychological support
• prevention and treatment of estrogen deficiency symptoms
• specific fertility management
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HRT
• For women with a uterus, progestogen must be added as a
supplement to avoid the unopposed effects of estrogen on the
endometrium.
• Initially women usually require a moderate dosage (oral
estradiol, commonly 2 mg/day, or a transdermal patch of 100
µg), to overcome the systemic adverse effects of estrogen
deficiency and to estrogenise the vaginal epithelium fully.
• Androgen replacement should be considered even with normal
adrenal function, as loss of ovarian activity can reduce androgen
production by 50%, which can have profound effects on general
and sexual wellbeing.
• Transdermal testosterone patch, Intrinsa® has recently been
licensed in the UK for women with hypoactive sexual desire
disorder who have undergone bilateral oophorectomy and
hysterectomy and are receiving concomitant estrogen therapy.
4/16/20 Elbohoty 155
Induction of ovulation
• Another treatment option that provides some hope for
women with POF is estrogen suppression followed by
exogenous gonadotrophins.
• Women with POF have chronically high gonadotrophin
levels which downregulate FSH receptors on granulosa cells,
so that the remaining follicles become refractory to
exogenous stimulation.
• Pretreatment with estrogens suppresses FSH serum levels
and allows the restoration of FSH receptors in the remaining
follicles.
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Genetic gonadal dysgenesis
4/16/20 Elbohoty 157
Most girls with Turner
syndrome are diagnosed in the
neonatal period or in infancy
due to phenotypic
abnormalities.
Up to 25% will enter puberty
spontaneously but only 10%
will progress through puberty
and only 1% will develop
ovulatory cycles.
Presntation
• The incidence of TS is approximately 1:2500 to 1:3000 live
births, because a high proportion (close to 99%) of
pregnancies with TS miscarry.
• TS is noted in approximately one in ten first trimester
miscarriages
• The karyotype of TS is classically a monosomy X with a full
complement of autosomes, represented as 45 XO.
• There can also be a mosaic karyotype (46 XX, 45 XO)
• Rarer karyotype variants include isochromosome of the
short or long arm of the X chromosome (46 X,iXq and 46
X,iXp) and other mosaic karyotypes (47 XXX, 45 XO and 46
XY, 45 XO).
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Karotyping and reproduction
• Women with TS with spontaneous menarche have low levels of
mosaicism not detected by routine karyotyping.
• 8% of women with TS conceive naturally and have live births.
• There appears to be an increased risk of miscarriage (31–45%)
after natural conceptions for women with TS.
• Women who have TS and a monosomy X karyotype (45 XO and
mosaic 46 XX, 45 XO) can be reassured that they are not at risk
of passing TS on to their children. However, women with TS who
have deletions of the X chromosome or a ring X chromosome as
their karyotype are at risk of passing on the abnormal X
chromosome to their daughters and needs genetic counselling
4/16/20 Elbohoty 159
Screening
protocol for
women
with Turner
syndrome
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Pregnancy with donner eggs
• Good pregnancy rate (27.5%) with the use of donor oocytes
in women with TS.
• Miscarriage rates appear to be similar to that of the general
population (25%), but with an increased risk of
hypertensionrelated complications (15–17%), aortic
dissection (1–2%) and caesarean section rates (80–100%).
The incidence of preterm birth (birth at fewer than 37
weeks of gestation) has been reported to be higher (12–
38%) and there is a higher risk of babies being small for
gestational age (weighing less than 2500 g; 18–57%).
• There is evidence to suggest donor oocyte pregnancy acts as
an independent risk factor for pregnancy complications and
the use of donor oocytes in women with TS further
increases this risk4/16/20 Elbohoty 161
Management of puberty and growth
• During adolescence, the gynaecologist has a role in the
multidisciplinary care of girls with Turner syndrome to optimise
pubertal development in respect to appropriate body image.
• Adolescent women with primary amenorrhoea undergo artificial
induction of puberty in conjunction with specialised optimisation
of growth through the care of the paediatric endocrinologist.
• Those with a mosaic karyotype are more likely to begin puberty
but then fail to menstruate at all, or may suffer early secondary
amenorrhoea.
• Uterine growth must also be promoted in anticipation of
potential pregnancy achieved in due course through oocyte
donation and IVF techniques.
• Until that time, cyclical menses may be achieved with the COCP
or hormone replacement therapy.4/16/20 Elbohoty 162

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Y chromosomal material
• Any evidence of Y chromosomal material warrants surgical
excision of the gonads to remove any risk of malignant
change (gonadoblastoma) within them.
4/16/20 Elbohoty 163
Mullerian abnormalities
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Development
4/16/20 Elbohoty 165
4/16/20 Elbohoty
The lower end beyond the cavity proceeds as a solid cord and projects into the
dorsal wall of the urogenital sinus producing an elevation: “The Mϋllerian
Tubercle”.
This contact induces the formation of endodermall upgrowth from the
urogenital sinus: The Sino-Vaginal Bulbs. These extend into the caudal tip of
the Mullerianduct and constitute the vaginal plate. Recanalization occurs by the
20th week. 166

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Incidence
• Incidence ranges from 2–4% of women.
4/16/20 Elbohoty 167
Septate uterus 35%
Bicornuate uterus 26%
Arcuate uterus 18%
Unicornuate uterus 10%
Uterus didelphys 8 %
Associated reproductive outcome
Fertile & infertile women 3-4%
Recurrent pregnancy loss 5-10%
Late miscarriage and preterm labour >25%
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III UTERUS CONGENITAL ABNORMALITIES
4/16/20 Elbohoty 169
CHAPTER 37 ANATOMIC DISORDERS OF
THE FEMALE REPRODUCTIVE SYSTEM
Classification
4/16/20 Elbohoty 170

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4/16/20 Elbohoty 171
4/16/20 Elbohoty 172

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MRKH syndrome (uterovaginal agenesis)
U5C4V4
• The incidence of this condition is thought to be
approximately 1:5000 female births
• Patients with MRKH syndrome present in their teenage
years with primary amenorrhoea in the presence of normal
secondary sexual characteristics.
• These patients have normal ovaries and therefore puberty
occurs at the normal time and in the normal sequence but
without menstruation.
4/16/20 Elbohoty 173
Congenital absence of vagina
Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
4/16/20 Elbohoty 174

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Associated abnormalities
• 40% is associated with renal tract abnormalities
• 12% an absent kidney
• other renal abnormalities include ectopic kidney, horseshoe
kidney and ectopic ureter.
• 12–20% has Skeletal abnormalities (Klippel–Fiel anomaly, fused
vertebrae, radial aplasia, absent thumb, scoliosis and radial
hypoplasia).
• 10–25% Auditory malformations
• Conductive deafness due to stapedial ankylosis and
sensorineural deafness are reported.
• Malformations of the ear and auditory canal are also reported.
• Rarely, major cardiac malformations such as tetralogy of Fallot,
patent ductus arteriosus and truncus arteriosus are reported.4/16/20 Elbohoty 175
Types
• In type I MRKH syndrome
• the caudal portions of the mullerian ducts are involved.
This is characterised by the presence of two rudimentary
uterine buds connected by a peritoneal fold, normal
fallopian tubes and absence of the upper part of the
vagina
• In type II MRKH syndrome
• there is asymmetrical hypoplasia of the uterine buds
with or without hypoplasia of one or both fallopian
tubes; 7–10% of these women have a rudimentary
uterus with functional endometrium and as many as
25% have cavitated mullerian remnants.
• The ovaries are absent, hypoplastic or extrapelvic (pelvic
brim) in 10–15% of cases
4/16/20 Elbohoty 176

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4/16/20 Elbohoty 177
Diagnosis
• Clinical diagnosis: examination reveals the presence of
secondary sexual characteristics in association with a
normal hormone profile and genital examination reveals an
absent or a blind vagina.
• Imaging confirms the diagnosis
• Karyotyping: 46xx
• Sex hormones: normal values for female
4/16/20 Elbohoty 178

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Management
• Aim:
• to allow the patients to become sexually active
• management of the psychological impact of this condition.
• Create the vagina:
• use of vaginal dilators as the treatment of first choice and this has
been supported by a policy statement from the American College
of Obstetricians and Gynaecologists.
• The technique involves passive dilatation of the vaginal dimple
using graduated dilators.
• 25% of patients complained that they had either poor lubrication
or dyspareunia but this did not interfere with their enjoyment of
sexual intercourse.
• A surgical approach is rarely required but there have been a
wide range of surgical procedures suggested with success
rates ranging from 80–90%.4/16/20 Elbohoty 179
Surgical treatment
• Surgery is undertaken if non-surgical methods fail or if the
woman chooses a surgical option at the outset.
• Many procedures being only of historical interest due to the
serious risks and complications.
• The McIndoe procedure, sigmoid vaginoplasty and Williams’
vulvovaginoplasty are among these outdated procedures
4/16/20 Elbohoty 180

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What is done in UK
4/16/20 Elbohoty 181
Vecchietti procedure
• The principle is to create a neovagina
by gradual stretching of the vaginal
skin.
• placing an olive-shaped bead onto the
vaginal dimple, which is pulled up
gradually by threads that run through
the olive from the perineum into the
pelvis subperitoneally, across the
vesicorectal space and out through the
abdomen, where they are attached to a
traction device placed suprapubically.
Gradually increasing traction is applied
to produce 1.0–1.5 cm of invagination
per day.
• It takes 7– 9 days to create the
neovagina.
• The dilating olive and the traction
device are removed once the
neovagina is at least 7–8 cm long. Once
the neovagina is created it is
maintained by using vaginal dilators or
by regular sexual activity.
4/16/20 Elbohoty 182

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Davydov procedure
• A neovagina is created using the woman’s own peritoneum as lining.
• The procedure involves dissection of rectovesical space, abdominal mobilisation
of the peritoneum to create vaginal fornices and attachment of the peritoneum
to the introitus. Postoperatively a vaginal mould is inserted for 6 weeks and
regular vaginal dilators are used until commencement of regular sexual
activity.Good anatomical and functional success is reported with this procedure.
• No major complications are reported other than growth of granulation tissue at
the vaginal vault. The laparoscopic approach has the added benefit of clear
visualisation of the anatomy, a shorter hospital stay and less postoperative pain.
4/16/20 Elbohoty 183
Fertility options
• As the ovaries function normally, in vitro fertilisation and
surrogacy are possible ways of producing genetically related
offspring using the woman’s own eggs.
• Transvaginal egg retrieval is challenging in some cases where
there is an artificially created vagina and abnormally
positioned ovaries. Transabdominal or, rarely, laparoscopic
egg retrieval may be necessary.
• Surrgocy
• Adoption is another option.
• Uterine transplantation
4/16/20 Elbohoty 184

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4/16/20 Elbohoty 185
Obstructive outflow tract disorders of
the vagina
• Management of these cases is dependent upon the level of
obstruction
• Both the anatomical and functional success becomes
increasingly poor with higher obstructions.
4/16/20 Elbohoty 186

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Imperforate hymen
• The hymen is a thin membrane that occurs at the junction
of the sinovaginal bulb with the urogenital sinus and is
usually perforated during fetal life.
• Failure of this perforation leads to the membrane remaining
intact and as puberty begins, menstrual blood collects
behind the membrane and the vagina begins to distend.
4/16/20 Elbohoty 187
Presentation
• This is often painless until the vagina becomes sufficiently
distended does a haematocolpos result and cause
discomfort.
• Occasionally, if the mass is sufficiently large, it may affect
micturition and defaecation, and may be palpable
abdominally.
• Inspection of the vulva reveals a membrane that is blue in
appearance with the darkened blood transilluminating
through the thin membrane.
4/16/20 Elbohoty 188

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95
4/16/20 Elbohoty
Imperforate hymen
189
DD
• Transverse vaginal septum
4/16/20 Elbohoty 190
Imperforate hymen Vaginal septum
Consitency Thin Thick
Location At the vesibule Inside the vagina
Look Bulging Not

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Management
• Surgical treatment involves a cruciate incision to relieve
the obstruction and the remaining quadrants of the hymen
may be left in situ or may be excised (better excised and
sutures are taken)
• Following surgery, the haematocolpos will completely drain
within 3–5 days and usually with no sequelae to this
condition whatsoever especially in cases presenting early.
4/16/20 Elbohoty 191
Transverse vaginal septum
•About 1:30 000–50 000.
•Location:
•Anywhere along the length of the vagina
•Upper 46%,
•Mid 30–40%
•Lower 15–20%
4/16/20 Elbohoty 192

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Presentation
• Increasing cyclical abdominal pain and
the absence of menstruation.
• It is not uncommon for the diagnosis
to be missed for several months.
• Only when a clinically palpable mass is
discovered does the possibility of an
obstructed outflow tract disorder arise
and ultrasound imaging will confirm
the presence of a haematocolpos and
occasionally a small haematometra.
• If there has been sufficient time lapse
between the onset of menarche and
the diagnosis, a haematosalpinx can
also occur.4/16/20 Elbohoty 193
Transverse Vaginal Septum
4/16/20 Elbohoty 194

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Management
• The surgical management of this condition requires the excision
of the septal defect in its entirety and subsequently an end-to-
end anastomosis of the upper and lower vagina.
• It is imperative that dissection occurs laterally to excise all of the
septal tissue or the risk of stenosis will occur.
• A firm vaginal mould should be inserted through the site of the
anastomosis for a minimum of 10 days and thereafter the
patient should be instructed in the use of vaginal dilators for 2–3
months to ensure that stenosis does not occur and that a
functional result will ensue.
• Excellent results are normally obtained for lower and middle
septal defects but for higher septal defects, the results are less
encouraging.
• When the upper vaginal portion is short, there is a risk of
damage to the bladder or the rectum and great care has to be
taken during the procedure.
• When these higher septal defects are resected, a mould may
need to remain in situ for 3–6 months to obtain the best results.4/16/20 Elbohoty 195
Reproductive Prognosis
• Pregnancy rate with this type of disorder vary with the level
of obstruction
• 100% in patients with lower third obstruction
• 40% in middle third
• 20% in the upper third
• The likely explanation for this is the incidence of
endometriosis at the time of the obstructive problem which
may cause architectural damage to the pelvis.
• Mode of delivery:
• Patients with lower third problems: vaginal delivery with the use
of an episiotomy to prevent lateral damage during head descent.
• Patients with middle & upper third problems: caesarean section
4/16/20 Elbohoty 196

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Longitudinal vaginal septum
• Longitudinal vaginal septum that divides these may be
partial or complete and patients usually present with either
difficulty with inserting tampons or discomfort during
intercourse.
• They may not present at all until pregnancy when it is an
incidental finding.
4/16/20 Elbohoty 197
Presentation
• If one of the hemi-vaginas fails to
completely canalise, a blind vaginal cavity
results and at the time of puberty when
menstruation begins, menses from the
unobstructed vagina are found to flow
normally, whereas the obstructed hemi-
vagina accumulates menstrual fluid.
• This can create a confusing clinical
situation which often leads to late
diagnosis.
• A clinically palpable mass should lead the
clinician to suspect outflow tract disorder.
• Dysmenorrhoea can be quite severe and
patients are sometimes admitted as
emergencies.
4/16/20 Elbohoty 198

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Justification for excision
• Excision of the vaginal septum is usually advisable both to
improve the chance of achieving a pregnancy in those who
are trying to conceive but also to avoid difficulties that may
arise during childbirth.
4/16/20 Elbohoty 199
Management
• The surgical management of these conditions involves
careful excision of the vaginal septum in its entirety but care
has to be taken because this type of septum can be very
thick.
• It is ill-advised to drain a hemi-vagina as a temporary means
as this may result in ascending infection, septicaemia and a
life-threatening situation.
• It is imperative therefore that these procedures are carried
out by surgeons whose skills allow them to do this surgery
effectively and that the operation performed is curative.
• It can carried out by sharp dissection, diathermy or laser.
4/16/20 Elbohoty 200

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101
Prognosis
• The results of surgery in these circumstances are excellent
and dyspareunia is rarely a problem.
• It is important to inform the patients that their uterus
didelphus remains and therefore obstetric complications
need to be explained.
• U3C2V3
4/16/20 Elbohoty 201
4/16/20 Elbohoty
Rudimentary horn
202
• Non communicating
• Communicating

102. 4/16/20
102
• With functioning endometrium: haematometra, with
retrograde menstruation and severe dysmenorrhoea.
• Presentation:
• In girls with severe dysmenorrhoea that is unresolved through
normal medication
• An ultrasound scan should be performed to identify whether or
not there is a rudimentary horn present.
• Magagement:
• The horn needs to be removed surgically and the uterus
reconstructed.
• If this is carried out meticulously, reproductive performance is the
same as with a unicornuate uterus.
4/16/20 Elbohoty 203
Non-communicating rudimentary horn:
Occasionally, these horns may be
communicating
• In which case they are usually asymptomatic.
• Management: if diagnosed prior to pregnancy, they
should be removed because a pregnancy in a
communicating horn can lead to uterine rupture
and maternal fatality.
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Septate uterus configurations
• Include partial septum, and complete septum in association with
cervical septum or duplicated cervix.
• Most women with a septate uterus have efficient reproductive
function.
• Arcuate uterus, although developmentally considered part of the
spectrum of resorption failure, is considered a normal variant and
should be differentiated from septate uterus for purposes of prognosis
and surgical management.
4/16/20 Elbohoty 205
Reproductive effects
• Limited data based on observational studies.
• There is insufficient evidence to conclude that a uterine
septum is associated with infertility.
• Several observational studies indicate that hysteroscopic
septum incision is associated with improved clinical
pregnancy rates in women with infertility.
• There is fair evidence that a uterine septum contributes to
miscarriage and preterm birth.
• Some evidence suggests that a uterine septum may
increase the risk of other adverse pregnancy outcomes such
as malpresentation, intrauterine growth restriction,
placental abruption, and perinatal mortality.
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A complete septate uterus
• A complete septate uterus has a single uterine fundus, with
a septum extending from the top of the endometrial cavity
and continuing through the cervix or may extend into a
duplicated cervix. Both may be seen in combination with a
longitudinal vaginal septum.
• This configuration must be differentiated from the uterus
didelphys in which the uterine horns are separated.
• Both of these anomalies have duplicated cervices and can
be associated with a longitudinal vaginal septum.
4/16/20 Elbohoty 207
Bicornuate uterus
• In addition, a combined bicornuate/septate configuration
of the uterus has been described in which the external
fundus has an indentation consistent with a bicornuate
shape, but at hysteroscopy there is 2 cavities.
4/16/20 Elbohoty 208

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The arcuate uterus
• It is typically considered a normal variant
• The AFS classification system placed arcuate uterus in its
own category as, in contrast to other uterine malformations,
it does not cause adverse clinical outcomes.
• However, it is important to differentiate arcuate from
septate uterus to better direct surgical intervention when
appropriate for the septate uterus.
• Arcuate describes a uterus with an externally normal-
appearing fundus and a small smooth indentation at the top
of the endometrial cavity.
4/16/20 Elbohoty 209
Diagnosis
• 3-D ultrasound, sonohysterography, and MRI are good
diagnostic tests for distinguishing a septate and bicornuate
• It is recommended that imaging or imaging with
hysteroscopy should be used to diagnose uterine septa
rather than laparoscopy with hysteroscopy because this
approach is less invasive.
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Management
• Some limited studies indicate:
• hysteroscopic septum incision is associated with a reduction in subsequent miscarriage rates
and improvement in live-birth rates in patients with a history of recurrent pregnancy loss or
infertility.
• There is insufficient evidence to conclude that obstetric outcomes are
different when comparing the size as defined by length or width of
uterine septa.
• There is insufficient evidence to recommend a specific method for
hysteroscopic septum incision (cold scissors, unipolar or bipolar
cautery, or laser).
• Although the available evidence suggests that the uterine cavity is
healed by 2 months postoperatively, there is insufficient evidence to
advocate a specific length.
• There is insufficient evidence for preoperative measures to thin the
endometrium (GnRH agonists) or measures against adhesion
prevention for hysteroscopic septum incision.
4/16/20 Elbohoty
211
Ashermans Syndrome
• A condition where the uterine walls adhere to one
another
4/16/20 Elbohoty 212

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Cause
• Trauma or infection to endometrium:
• A pregnancy-related E&C
• Endometritis
• Complicated CS
• Uterine suturing for anterior and posterior wall
• Myomectomy (submucus)
4/16/20 Elbohoty 213
Presentation
•Mild cases
– no clinical symptoms normal
menstruation is maintained.
•More severe: there may be
oligomenorrhea, hypomenorrhea,
dysmenorrhea, amenorrhea, infertility
and miscarriage
4/16/20 Elbohoty 214

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Diagnosis
• HSG
• Sonohystrosalpingography
• 3D US
• Hysteroscopy
4/16/20 Elbohoty 215
4/16/20 Elbohoty 216

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109
Focal synaechia
4/16/20 Elbohoty 217
Extensive
4/16/20 Elbohoty 218

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110
Management
• Direct visualization of the uterine cavity at hysteroscopy in
conjunction with a tool for adhesiolysis
• In the presence of extensive or dense adhesions, treatment
should be performed by an expert hysteroscopist
4/16/20 Elbohoty 219
• Barriers such as hyaluronic acid and auto-
cross-linked hyaluronic acid gel seem to
reduce the risk of adhesion recurrence and
may be of benefit after treatment of IUAs. At
this time, their effect on posttreatment
pregnancy rates is unknown, and they should
not be used outside of rigorous research
protocols.
• Postoperative hormone treatment using
estrogen, with or without a progestin, may
reduce recurrence of IUAs.
Not usually recommended
• There is no evidence that hysteroscopic adhesiolysis guided by
external imaging techniques or laparoscopy prevents uterine
perforation or improves clinical outcome; however, such an
approach used in appropriately selected patients may minimize
the consequences if perforation occurs.
• Because of the suppressive or inflammatory effect on the
endometrium, neither progestin-releasing nor copper or T-
shaped IUDs should be used after surgical division of intrauterine
adhesions.
• There are limited data supporting a benefit for using a Foley
catheter or an IUD after surgical lysis of IUAs. There exists the
potential for increased infection rates, and neither technique can
be recommended for routine use outside of clinical trials.4/16/20 Elbohoty 220