A 28-year-old woman with PCOS has oligomenorrhea, biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound. She fails to ovulate on clomiphene citrate 150 mg for 3 cycles. The NEXT best ovulation induction strategy is:
- A Laparoscopic ovarian drilling (LOD) — first choice before any pharmacological escalation
- B Combined letrozole and clomiphene — synergistic effect with anti-estrogenic mechanisms
- C Gonadotropin (FSH) injections — replace clomiphene with exogenous FSH without further drug trials
- D Letrozole 2.5–5 mg on days 3–7 — superior to clomiphene in PCOS by reducing peripheral estrogen feedback ✓
Explanation
The LEGRO trial (2014, NEJM) established letrozole (aromatase inhibitor) as superior to clomiphene for ovulation induction and live birth rates in PCOS. Letrozole reduces peripheral estrogen by blocking aromatase, which lowers the negative feedback on the pituitary, allowing a more physiological FSH rise without the anti-estrogenic effect on endometrium and cervical mucus that clomiphene causes. After clomiphene failure, letrozole is the evidence-based next pharmacological step before moving to gonadotropins. LOD is an option but typically after pharmacological failure of both clomiphene and letrozole.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.