A 28-year-old woman with PCOS is treated with clomiphene citrate 100 mg for ovulation induction. She fails to ovulate. The NEXT most appropriate pharmacological step is:
- A Add metformin to clomiphene therapy
- B Proceed directly to gonadotropin injections
- C Switch to letrozole 2.5–5 mg for ovulation induction ✓
- D Offer laparoscopic ovarian drilling
Correct answer: C. Switch to letrozole 2.5–5 mg for ovulation induction
Explanation
Letrozole (an aromatase inhibitor) is now recommended as first-line ovulation induction in PCOS over clomiphene, with superior live birth rates demonstrated in the PPCOS II trial. In clomiphene-resistant PCOS (failure at 150 mg for 3 cycles), letrozole 2.5–5 mg days 3–7 is the appropriate next step before escalating to gonadotropins. Letrozole avoids the antiestrogenic effects on endometrium and cervical mucus seen with clomiphene. Gonadotropins and ovarian drilling are reserved for letrozole failure.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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