A 26-year-old woman with PCOS and infertility is started on clomiphene citrate. She does not ovulate after three cycles with the maximum dose. The MOST appropriate next pharmacological step before considering ART is:

• A Add metformin to clomiphene and continue for three more cycles
• B Proceed to ovarian drilling (laparoscopic electrocautery) immediately
• C Start low-dose FSH gonadotrophin injections without further oral agents
• D Switch to letrozole (aromatase inhibitor) as it has higher live birth rates in PCOS ✓

Explanation

The LETANOVA and LEGRO (2014, NEJM) trials established that letrozole is superior to clomiphene citrate for ovulation induction in PCOS, with higher live birth rates and lower multiple pregnancy rates. Letrozole is now considered first-line for PCOS-associated anovulatory infertility in many guidelines. Ovarian drilling is a surgical option for clomiphene-resistant PCOS but requires laparoscopy. Gonadotrophin injections are appropriate but carry higher risk of OHSS and multiple pregnancy.

Reference: Shaw's Textbook of Gynaecology, 17th ed.

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Written and medically reviewed by the StethoPrep medical team.