Anovulation and ovulation induction — structured oral station (12 minutes)

Opening prompt — "What is your working diagnosis and which WHO group is she?"

Model response — apply the classification: ^[1]

• "She is WHO Group II — eugonadotropic anovulation, of which PCOS accounts for 80 to 90%. Her FSH (6 IU/L) and oestradiol are normal — the defining biochemistry of Group II. She meets the Rotterdam criteria for PCOS (oligo/anovulation + hyperandrogenism + polycystic ovarian morphology), her 17-hydroxyprogesterone is normal, excluding non-classic CAH, and her prolactin and TSH are normal. Group I requires low FSH and low oestradiol; Group III requires high FSH and low oestradiol. Her high AMH (8.4 ng/mL) flags her as a high OHSS responder in any future stimulation."
• "The 2023 FIGO HyPO-P update reorganises the WHO system into hypothalamic, pituitary, ovarian, and PCOS axes, but the gonadotropin-oestrogen logic that drives the first-line drug is unchanged."^[1]

Probe 1 — "What is your first-line ovulation induction, and what is the evidence?"

• "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. This is first-line for WHO Group II / PCOS on the strength of PPCOS II (Legro et al, NEJM 2014), which showed cumulative live birth 27.5% with letrozole vs 19.1% with clomiphene — a rate ratio of 1.44 — with higher ovulation (61.7% vs 48.3%) and fewer multiples. The Cochrane 2022 review by Franik and colleagues confirms the superiority. Clomiphene is now second-line."
• "Letrozole works by inhibiting aromatase, lowering oestrogen centrally, releasing the HPO axis from negative feedback, and raising endogenous FSH — driving mono-follicular recruitment without the multi-follicular excess of gonadotropins."^[2][3]

Probe 2 — "Letrozole fails after 6 ovulatory cycles. What is your next step?"

• "Low-dose step-up gonadotropin ovulation induction. Recombinant FSH 37.5 to 50 IU subcutaneously daily from cycle day 2 to 3, holding the dose 7 to 14 days and increasing by 50% only if no follicular response. I monitor with transvaginal ultrasound every 2 to 3 days from day 7, alongside serum oestradiol. I trigger with hCG 5000 to 10,000 IU when the dominant follicle reaches 17 to 18 mm."
• "The cancellation thresholds are mandatory: I cancel if more than 2 dominant follicles over 16 mm develop, or if oestradiol exceeds 1000 pg/mL, because continuing risks high-order multiple pregnancy and OHSS. If the couple wishes to proceed, I convert to IVF with follicle aspiration to empty the follicles and remove the OHSS stimulus."^[4]

Probe 3 — "She proceeds to IVF. Describe the OHSS-aware protocol."

• "She is a high responder — her AMH of 8.4 and her PCOS put her at 2 to 3x baseline OHSS risk. My bundle combines four measures: a GnRH antagonist protocol rather than the long agonist, to keep gonadotropin exposure short and follicular synchrony low; a GnRH-agonist trigger — triptorelin 0.2 mg — instead of hCG for final oocyte maturation, which halves OHSS risk via its shorter luteinising half-life; a freeze-all strategy with elective single frozen embryo transfer in a subsequent cycle, separating stimulation from implantation because pregnancy exacerbates OHSS; and metformin 1500 to 2000 mg continued through stimulation, which independently reduces OHSS risk."^[4]

Probe 4 — "How would your first-line drug differ if her FSH and oestradiol were low (Group I)?"

• "Group I is hypogonadotropic hypogonadism — hypothalamic-pituitary failure, often functional hypothalamic amenorrhoea. I would restore weight and energy balance first; many resume ovulation with weight gain alone. For persistent Group I, first-line is pulsatile GnRH by subcutaneous pump every 90 minutes, because it preserves near-physiological mono-follicular recruitment and a low multiple-pregnancy rate. Gonadotropins (FSH/LH) are the alternative when GnRH is unavailable. I would always exclude hyperprolactinaemia and pituitary tumour before any induction."^[1]

Probe 5 — "And if her FSH were high on two samples (Group III)?"

• "Group III is premature ovarian insufficiency — the follicular reserve is depleted below the threshold needed to sustain ovulation. Ovulation induction is futile because no drug can recruit follicles that are not there. The realistic fertility option is donor-oocyte IVF. I would offer HRT or a combined hormonal contraceptive to age 51 for bone and cardiovascular protection. I would counsel honestly — spontaneous pregnancy is uncommon (around 5 to 10% in some series), and post-diagnosis egg-freezing is futile."^[1]

Probe 6 — "She is frightened the fertility drugs will give her cancer. What do you say?"

This is a scored communication domain — demonstrate it out loud: ^[2]

• Move to her eye level, use her name, acknowledge the fear: "Letrozole is not associated with an increased cancer risk — it is a short course each cycle and it leaves your system quickly. The only drug in this area with a caution is clomiphene, which is why we limit it to 6 cycles. The bigger risk of these drugs is over-response — OHSS and multiple pregnancy — which is exactly why we monitor you with scans and blood tests, and why we cancel a cycle if too many follicles develop. You are safe in our care."^[2]