The PPCCOS trial (2014) compared clomiphene citrate, letrozole, and their combination for ovulation induction in PCOS. Subsequent to that, the PPCCOS-II (Legro et al., 2014) Engl J Med trial definitively compared letrozole and clomiphene as first-line in PCOS. What was the primary outcome difference?
- A Letrozole had significantly higher live birth and ovulation rates compared to clomiphene, particularly in obese PCOS ✓
- B Letrozole and clomiphene had equivalent live birth rates across all BMI groups
- C Clomiphene had higher ovulation rates but letrozole had fewer multiple pregnancies
- D Letrozole was superior in ovulation induction but clomiphene had superior implantation rates
Correct answer: A. Letrozole had significantly higher live birth and ovulation rates compared to clomiphene, particularly in obese PCOS
Explanation
The Legro et al. 2014 NEJM RCT (750 infertile PCOS women) found letrozole had significantly higher live birth rates (27.5% vs 19.1%, p=0.007) and ovulation rates compared to clomiphene, with the advantage most pronounced in obese women. This landmark trial established letrozole as first-line ovulation induction in PCOS (now endorsed by WHO, ESHRE/ASRM, and NICE 2023 guidelines), replacing clomiphene as first-line for most PCOS patients. Letrozole also had fewer multiple pregnancies and less endometrial thinning.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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