The PPCOS II trial (2012) compared letrozole versus clomiphene citrate for ovulation induction in infertile women with PCOS. Its principal finding was:

• A Clomiphene produced higher ovulation rates but comparable live birth rates to letrozole
• B Letrozole and clomiphene had equivalent live birth rates, but letrozole had fewer multiple gestations
• C Metformin plus clomiphene outperformed letrozole monotherapy for live birth rate
• D Letrozole was associated with significantly higher live birth rates (27.5% vs 19.1%) than clomiphene ✓

Explanation

The PPCOS II randomised trial (Legro et al., NEJM 2014) enrolled 750 infertile women with PCOS and demonstrated that letrozole (5 days/cycle) produced significantly higher cumulative live birth rates over 5 cycles compared to clomiphene (27.5% vs 19.1%, OR 1.6, p=0.007) and also higher ovulation rates (61.7% vs 48.3%). This trial established letrozole as the preferred first-line ovulation induction agent in PCOS over clomiphene, and ESHRE/ASRM 2018 PCOS guidelines now recommend letrozole as first-line oral ovulation induction agent.

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

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