Anovulation and ovulation induction — structured SAQ (15 marks)

(a) WHO classification and group assignment (3 marks)

One mark per point. ^[1]

• WHO classification verbatim: Group I — hypothalamic-pituitary failure (hypogonadotropic hypogonadism): low FSH and LH, low oestradiol. Group II — eugonadotropic anovulation: normal FSH and LH, normal oestradiol; PCOS accounts for 80 to 90%. Group III — ovarian failure (hypergonadotropic hypogonadism): high FSH, low oestradiol; POI.
• Group assignment: this patient is WHO Group II. Her FSH (6 IU/L) and oestradiol (normal) are normal, defining eugonadotropic anovulation. She meets Rotterdam criteria for PCOS (oligo/anovulation + hyperandrogenism + polycystic ovarian morphology), with 17-OHP normal (excludes non-classic CAH) and prolactin/TSH normal.
• FIGO HyPO-P update (2023): the FIGO system reorganises the WHO groups into Hypothalamic, Pituitary, Ovarian, and PCOS axes, but the gonadotropin-oestrogen logic driving the first-line drug is unchanged. Her high AMH (8.4 ng/mL) flags her as a high OHSS responder in any future stimulation.^[1]

(b) Letrozole-first ladder with PPCOS II (5 marks)

One mark per step, with the PPCOS II numbers for full credit. ^[2][3]

• Step 0 — pre-conception care: folic acid 400 micrograms daily (5 mg given BMI over 30), smoking cessation, weight optimisation (5 to 10% loss restores spontaneous ovulation in 30 to 60%), check rubella and varicella, screen chlamydia.
• Step 1 — letrozole first-line: letrozole 2.5 mg daily on cycle days 2 to 6 (or 3 to 7), titrating to 5 mg then 7.5 mg in subsequent cycles if no ovulation. Confirm ovulation each cycle with mid-luteal progesterone.
• PPCOS II verbatim (Legro et al, NEJM 2014): cumulative live birth 27.5% with letrozole vs 19.1% with clomiphene (rate ratio 1.44, 95% CI 1.10 to 1.87); cumulative ovulation 61.7% vs 48.3%. Cochrane 2022 (Franik et al) confirms superiority with fewer multiples.
• Cumulative live birth: across up to 6 letrozole cycles reaches 60 to 70% in anovulatory PCOS.
• Clomiphene is second-line (50 to 150 mg days 2 to 6) and is limited to 6 cycles because of the cumulative ovarian-cancer risk; it has anti-oestrogenic effects on cervical mucus and endometrium and a higher twin rate than letrozole.^[2][3]

(c) Low-dose step-up gonadotropin protocol (4 marks)

One mark per point; the cancellation thresholds are mandatory. ^[4]

• Indication: letrozole and clomiphene resistance (failure to ovulate or conceive after 6 ovulatory cycles).
• Protocol: recombinant FSH 37.5 to 50 IU subcutaneously daily from cycle day 2 to 3; hold the dose 7 to 14 days; increase by 50% only if no follicular response.
• Monitoring: transvaginal ultrasound every 2 to 3 days from day 7; serum oestradiol alongside.
• Trigger: hCG 5000 to 10,000 IU when the dominant follicle reaches 17 to 18 mm; time intercourse or IUI 36 hours later.
• Cancellation thresholds (mandatory): cancel if more than 2 dominant follicles over 16 mm develop, OR if oestradiol exceeds 1000 pg/mL (around 3600 pmol/L), to prevent high-order multiple pregnancy and OHSS. Convert to IVF with follicle aspiration if the couple wishes to proceed.^[4]

(d) OHSS-aware IVF protocol (3 marks)

One mark per measure named, with rationale. ^[4]

• Antagonist protocol (not the long agonist): shorter gonadotropin exposure, lower follicular synchrony.
• GnRH-agonist trigger (triptorelin 0.2 mg) instead of hCG for final oocyte maturation: the shorter luteinising half-life halves OHSS risk.
• Freeze-all strategy with elective single frozen embryo transfer in a subsequent cycle: separates stimulation from implantation (pregnancy exacerbates OHSS).
• Metformin 1500 to 2000 mg daily continued through stimulation: independently reduces OHSS risk.
• PCOS patients carry a 2 to 3x baseline OHSS risk because of the exaggerated follicular cohort — this is why the bundle matters.^[4]