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SECTION 1: ANATOMY, PHYSIOLOGY AND DEVELOPMENT OF FEMALE REPRODUCTIVE ORGANS

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CHAPTER 2 - ANATOMY OF THE FEMALE GENITAL TRACT

External Genitalia (Vulva)

• Mons pubis - fatty tissue over pubic bone; divided by pudendal cleft into labia majora
• Labia majora and labia minora - separated by the interlabial sulci
• Labia minora fuses anteriorly to form the clitoral hood (prepuce) and posteriorly forming the vestibule
• Clitoral glans and hood
• Urethral meatus
• Vaginal introitus and hymen

• Anterior boundary: frenulum of clitoris
• Posterior boundary: posterior fourchette
• Contains: vaginal introitus, urethral meatus, Bartholin gland openings, fossa navicularis

• Bartholin glands - posterolateral to vaginal introitus; homologue of male bulbourethral (Cowper's) glands; produce lubrication; can form cysts/abscesses
• Skene glands - lateral to urethral meatus; homologue of male prostate; produce lubrication

• Divided into anterior (urogenital) triangle and posterior (anal) triangle by line between ischial tuberosities
• Anterior triangle contains urethra, vagina, external genitalia
• Posterior triangle contains anal canal, ischiorectal fossa; bounded by levator ani (superior), perineal membrane (anterior), coccyx (posterior), sacrotuberous ligaments (posterolateral)

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Internal Genitalia

• Flexible fibromuscular tube; flattened at rest; mostly horizontal in upright posture
• Layers (centre to periphery): mucosa (stratified squamous epithelium) → lamina propria (collagen, elastic tissue, vascular/lymph supply) → muscular layer → areolar connective tissue
• Blood supply: vaginal artery (branch of internal iliac artery) + anastomoses with uterine, internal pudendal, inferior vesical, middle haemorrhoidal arteries
• Nerve supply: autonomic nervous system, lumbosacral plexus S2-S4, pudendal nerve
• Most sensory innervation is in the distal vagina

• Narrow distal uterus; average length ~3 cm; mostly fibrous tissue
• Central canal = os (external os at vaginal end, internal os at uterine end)
• Ectocervix: squamous epithelium; endocervix: columnar epithelium
• Transformation zone (T-zone) = squamocolumnar junction - site where CIN (cervical intraepithelial neoplasia) occurs
• Columnar epithelium produces mucus (varies with hormones, facilitates sperm transport)

• Parts: fundus, body (corpus), isthmus, cervix
• Layers: endometrium (inner mucosa), myometrium (smooth muscle), perimetrium (outer serosa)
• Blood supply: uterine artery (branch of internal iliac)
• Ligaments supporting the uterus: round ligament, broad ligament, cardinal (Mackenrodt's) ligament, uterosacral ligament

• Parts: interstitial (intramural) → isthmus → ampulla → infundibulum (with fimbriae)
• Site of fertilisation: ampulla
• Lined by ciliated columnar epithelium

• Almond-shaped; 3 x 2 x 1 cm in reproductive age
• Attached to broad ligament by mesovarium; to uterus by ovarian ligament; to pelvic wall by suspensory (infundibulopelvic) ligament
• Blood supply: ovarian artery (from aorta) and uterine artery
• Cortex contains follicles; medulla contains blood vessels

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• Lower vagina develops from urogenital sinus (endoderm)
• Upper vagina, cervix, uterus, fallopian tubes develop from Mullerian (paramesonephric) ducts
• Failure of Mullerian duct fusion → uterine anomalies (bicornuate, septate, didelphys uterus)
• Abnormalities in lower urogenital sinus → transverse/horizontal vaginal septa

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CHAPTER 3 - NORMAL HISTOLOGY OF OVARY AND ENDOMETRIUM

Endometrial Phases

• Driven by rising oestrogen
• Endometrium grows from 1-2 mm to several mm
• Glands: initially straight and narrow → become longer and tortuous
• Histology: multiple mitotic cells; low columnar → pseudostratified pattern before ovulation
• Stroma: dense, compact; few visible vascular structures

• Driven by progesterone (+ oestrogen)
• Progesterone is antagonistic to oestrogen; decreases endometrial oestrogen receptor concentration → inhibits mitosis
• Characteristic: PAS-positive glycogen-containing vacuoles in glands
  • Initially: subnuclear vacuoles (Day 16-17)
  • Progress: vacuoles move toward glandular lumen
  • By Days 19-20: apocrine secretion into lumen
  • By Day 21-22 (postovulatory Day 6-7): secretory activity maximal - endometrium optimally prepared for blastocyst implantation
• Stroma: oedema from Day 22; spiral arteries become visible and coil progressively

• Without pregnancy: corpus luteum regresses → oestrogen and progesterone fall → endometrium shed (functionalis layer)
• Basalis layer remains and regenerates the endometrium in the next cycle

• Located in the basalis layer; may originate from bone marrow (shown in bone marrow transplant studies)
• Clinically relevant in Asherman syndrome (intrauterine synechiae)

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Ovarian Histology

• Primordial follicles: oocyte surrounded by single layer of flat granulosa cells
• Primary follicles: oocyte + single layer of cuboidal granulosa cells
• Secondary follicles: multiple layers of granulosa cells + zona pellucida
• Graafian (dominant) follicle: fluid-filled antrum, theca interna and externa, cumulus oophorus
• Corpus luteum: post-ovulation structure; secretes progesterone and oestrogen
• Corpus albicans: regressed corpus luteum (fibrous scar)

• Maximum ~7 million oogonia at 20 weeks of fetal life
• At birth: ~1-2 million primordial follicles
• At puberty: ~300,000-400,000
• Over reproductive life: ~400-500 follicles actually ovulate; the rest undergo atresia

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CHAPTER 4 - PHYSIOLOGY OF OVULATION AND MENSTRUATION

The Hypothalamic-Pituitary-Ovarian (HPO) Axis

1. CNS / Hypothalamus
2. Pituitary gland
3. Ovary
4. Uterus (endometrium)

• Located at base of brain, above optic chiasm, below third ventricle
• 3 zones: periventricular, medial (cell bodies), lateral (axons)
• Secretes GnRH (Gonadotropin-Releasing Hormone) in pulses from the arcuate nucleus
• GnRH is released into the portal circulation → acts on anterior pituitary

• Pulsatile secretion is essential - the pulse frequency determines LH:FSH ratio
• Slow frequency → preferential FSH secretion
• Fast frequency → preferential LH secretion

• Extension of hypothalamus; derived from neuroectoderm
• Axons from supraoptic and paraventricular nuclei (magnocellular system)
• Secretes: Oxytocin and Arginine Vasopressin (AVP/ADH)

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The Menstrual Cycle (Normal = 28 days)

• Day 1 = first day of vaginal bleeding (menses)
• Average cycle length: 28 days (range 21-35 days)
• Average duration of menses: 3-7 days

1. As the corpus luteum of previous cycle regresses → progesterone and inhibin A fall → FSH rises
2. Rising FSH stimulates follicular growth → follicles secrete oestrogen and inhibin B
3. Oestrogen causes endometrial proliferation
4. The two-cell, two-gonadotropin theory: LH acts on theca cells → produce androgens; FSH acts on granulosa cells → aromatize androgens into oestrogens
5. Rising oestrogen and inhibin B → negative feedback → FSH falls
6. Dominant follicle selection: has most FSH receptors and produces most oestrogen; survives despite falling FSH
7. Dominant follicle diameter at ovulation: ~18-25 mm

• Sustained high oestrogen levels → LH surge (positive feedback) → ovulation within 36-40 hours
• LH surge also triggers: progesterone production begins, follicle rupture, oocyte maturation resumption

1. Ruptured follicle → corpus luteum (under LH maintenance)
2. Corpus luteum secretes: oestrogen + progesterone + inhibin A
3. These suppress FSH and LH (negative feedback)
4. Endometrium: transforms to secretory type (ideal for implantation)
5. Corpus luteum survives 12-16 days without pregnancy then regresses → oestrogen and progesterone fall → menstruation

• Embryo secretes hCG (mimics LH action) → sustains corpus luteum → continued progesterone secretion → maintains secretory endometrium → pregnancy continues

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CHAPTER 5 - DEVELOPMENT OF FEMALE REPRODUCTIVE ORGANS AND RELATED DISORDERS

• Gonads are indifferent until ~7 weeks; sex determination by SRY gene (on Y chromosome)
• In the absence of SRY → ovarian development (default pathway)
• Wolffian (mesonephric) ducts: regress in females (in males → epididymis, vas deferens, seminal vesicle)
• Mullerian (paramesonephric) ducts: persist in females → fallopian tubes, uterus, upper vagina

• Arcuate uterus (minor septum at fundus - most common variant)
• Septate uterus (complete septum - most common anomaly; associated with recurrent miscarriage)
• Bicornuate uterus (partial fusion failure)
• Unicornuate uterus (one Mullerian duct fails to develop)
• Didelphys uterus (complete failure of fusion → double uterus, double cervix)

• Transverse vaginal septum (from urogenital sinus/Mullerian junction)
• Imperforate hymen - presents at puberty with haematocolpos (blood in vagina) / haematometra

• Turner syndrome (45,XO): streak gonads, no functional ovaries, primary amenorrhoea
• Pure gonadal dysgenesis (46,XX or 46,XY): streak gonads

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CHAPTER 6 - PUBERTY, ADOLESCENCE AND RELATED GYNAECOLOGICAL PROBLEMS

Puberty

1. Thelarche (breast budding) - first sign, average age 8-13 years
2. Pubarche (pubic hair)
3. Axillary hair
4. Growth spurt (peaks ~12 years; ~8-10 cm/year)
5. Menarche (first period) - average age 12.5 years (range 10-16); occurs ~2 years after thelarche

• Rising FSH and LH (pulsatile GnRH)
• Rising oestrogen from ovaries
• Adrenal androgens (adrenarche) - cause pubic/axillary hair

• Central (true): premature activation of HPO axis
• Peripheral (pseudo): GnRH-independent (ovarian tumour, adrenal tumour, McCune-Albright syndrome)

• Primary dysmenorrhoea (painful periods; prostaglandin-mediated; treated with NSAIDs/OCP)
• Primary amenorrhoea (no period by age 16)
• Polycystic ovary syndrome (PCOS)
• Imperforate hymen/vaginal septum (presenting with haematocolpos at menarche)

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CHAPTER 7 - MENOPAUSE AND RELATED PROBLEMS

• Decreased oestrogen (oestradiol) and inhibin
• Markedly elevated FSH (>40 IU/L) - best biochemical marker
• Elevated LH
• Shift from oestradiol to oestrone (weaker, produced in adipose tissue) as dominant oestrogen

• Vasomotor symptoms: hot flashes, night sweats (most common, ~75% of women)
• Mood changes, irritability, depression
• Sleep disturbance
• Irregular periods

• Vaginal dryness (atrophic vaginitis)
• Dyspareunia (painful intercourse)
• Urinary frequency, urgency, recurrent UTIs

• Osteoporosis - oestrogen protects bone; postmenopause: accelerated bone loss (2-3%/year in first 5-7 years)
• Cardiovascular disease - oestrogen is cardioprotective; risk increases after menopause
• Cognitive changes

• Types: oestrogen-only (for women post-hysterectomy) vs combined oestrogen + progestogen (for women with intact uterus - to prevent endometrial hyperplasia/cancer)
• Benefits: relieves vasomotor symptoms, prevents osteoporosis, improves urogenital atrophy
• Risks: increased breast cancer risk (combined HRT), increased VTE risk, possible increased CVD risk (if started late)
• Window of opportunity: HRT most beneficial when started within 10 years of menopause / before age 60

• SSRIs/SNRIs (for hot flashes and mood)
• Clonidine (for hot flashes)
• Black cohosh (limited evidence; may act as SERM)
• Phytoestrogens (soy, red clover - mild effect)
• Bisphosphonates (for osteoporosis)

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CHAPTER 8 - BREAST AND GYNAECOLOGIST

• Glandular tissue (15-20 lobes) + adipose tissue + Cooper's ligaments (fibrous septa suspending breast)
• Nipple-areolar complex; Montgomery glands on areola
• Blood supply: internal mammary artery (medial), lateral thoracic artery (lateral), intercostal perforators
• Lymphatic drainage: primarily to axillary nodes (75%), also internal mammary nodes

• Puberty: oestrogen → ductal growth; progesterone → alveolar development
• Pregnancy: marked proliferation (lobular-alveolar development)
• Lactation: prolactin → milk production; oxytocin → milk ejection
• Menopause: involution of glandular tissue → replaced by fat

• Fibroadenoma: most common benign breast tumour in young women; oestrogen sensitive; "breast mouse" (mobile, firm, painless lump)
• Fibrocystic change: most common breast disorder; cyclical pain and nodularity
• Breast cysts: common in perimenopausal women
• Mastitis/breast abscess: common in lactating women; Staphylococcus aureus most common organism

• Gynaecologists screen for breast cancer (mammography: 2-yearly from age 50; or from age 40 with risk factors)
• Risk factors: BRCA1/BRCA2 mutations, family history, early menarche, late menopause, nulliparity, obesity, HRT use
• BRCA1 and BRCA2: autosomal dominant; BRCA1 mutation also carries increased ovarian cancer risk

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CHAPTER 9 - SEXUAL DEVELOPMENT AND VARIATIONS OF SEXUAL DEVELOPMENT (DSD)

• Chromosomal sex (XX or XY) → Gonadal sex → Hormonal sex → Phenotypic sex
• SRY gene (Sex-determining Region of Y): directs gonadal ridge to form testes → produces testosterone and MIF (Mullerian Inhibiting Factor)
• In absence of SRY → ovarian development (default)

• Androgen Insensitivity Syndrome (AIS):
  • Complete AIS (CAIS): 46,XY; end-organ unresponsive to androgens; phenotypically female; no pubic/axillary hair; primary amenorrhoea; testes in inguinal canal or labia; short/absent vagina
  • Partial AIS (PAIS): ambiguous genitalia
• 5-alpha reductase deficiency: 46,XY; cannot convert testosterone → DHT; born with ambiguous/female-appearing genitalia; virilise at puberty
• Gonadal dysgenesis (Swyer syndrome): 46,XY with streak gonads; phenotypically female; primary amenorrhoea

• Congenital Adrenal Hyperplasia (CAH): most common cause of ambiguous genitalia in 46,XX
  • Most common: 21-hydroxylase deficiency → excess androgens → virilisation of female fetus
  • Clitoromegaly, labioscrotal fusion
  • Salt-wasting form (75%): also mineralocorticoid deficiency → hypotension, hyponatraemia, hyperkalaemia (life-threatening in newborns)
• Aromatase deficiency: cannot convert androgens → oestrogens

• Streak gonads (no oocytes)
• Short stature, webbed neck, shield chest, cubitus valgus, coarctation of aorta
• Primary amenorrhoea, sexual infantilism
• Treatment: oestrogen replacement at puberty

• Phenotypically male; hypogonadism; gynaecomastia; infertility
• Elevated FSH/LH; low testosterone

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HIGH-YIELD EXAM POINTS - QUICK REVISION

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Levels of Support of the Uterus

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Overview - What Provides Uterine Support?

1. Endopelvic fascia and its condensations (ligaments)
2. Levator ani muscle complex (primary muscular support)
3. Perineal membrane
4. Bony pelvis attachments

The levator ani muscles provide the primary/active support - they keep the pelvic floor closed. The ligaments (passive support) stabilize the organs in correct position so the muscles can work optimally.

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DeLancey's Three Levels of Support

LEVEL I - Apical / Vertical Suspension

• Suspends the uterus and upper one-third of vagina vertically to the sacrum and lateral pelvic sidewall
• The paracolpium (endopelvic fascia) extends from the uterine arteries at the top to where the vagina fuses with the levator ani below
• Uterosacral ligament: runs from cervix/upper vagina posteriorly to sacrum; maintains vaginal length and axis
• Cardinal ligament (Mackenrodt's ligament): runs from cervix/upper vagina laterally to the pelvic sidewall; the most important ligament for uterine support

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LEVEL II - Lateral / Horizontal Attachment

• Arcus tendineus fasciae pelvis (ATFP) - "white line" running from lower pubic bone to ischial spine
• Superior fascia of levator ani muscle
• Supports the middle one-third of vagina - maintains midline vaginal position
• The paracolpium at this level changes from vertical (Level I) to a direct lateral attachment of the midvagina to the pelvic wall
• ATFP is a fibrous band from the lower pubic bone (1 cm lateral to midline) to just above the ischial spine

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LEVEL III - Distal / Perineal Fusion

• Perineal membrane (urogenital diaphragm)
• Perineal body
• External anal sphincter
• Bulbospongiosus and transverse perineal muscles
• Levator ani muscles directly
• The lower one-third of vagina fuses directly with these structures - no separate ligamentous support
• This level prevents the distal vagina from descending

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Summary Table

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Individual Ligaments of the Uterus (Classic Classification)

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The Levator Ani Muscle Complex

• All innervated by S3-S4 (levator ani nerve + pudendal nerve)
• The gap between the levator ani muscles = levator hiatus (allows urethra, vagina, rectum to pass through)
• Birth injury to the pubococcygeal portion of levator ani is seen in 55% of women with prolapse

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Important Surgical Relationships (Exam Favourites)

• Ureter and uterine artery: the ureter passes under the uterine artery within the cardinal ligament at the level of the internal os - "bridge over water" / "water under the bridge" - the artery is the bridge, the ureter is the water
• The ureter is at risk during clamping of the cardinal ligament during hysterectomy
• Uterosacral ligament runs just lateral to the ureter in the broad ligament

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Degrees of Uterine Prolapse

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Causes of Prolapse (Loss of Support)

• Childbirth injury (most common) - tears in levator ani, cardinal/uterosacral ligaments
• Menopause - reduced oestrogen → atrophy of supporting tissues
• Chronic raised intra-abdominal pressure - chronic cough, constipation, obesity, heavy lifting
• Congenital weakness of connective tissue
• Neuropathy (pudendal nerve damage in labour)

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