The LOTUS I and LOTUS II trials compared letrozole versus clomiphene citrate in anovulatory PCOS for ovulation induction. Which of the following best summarises the key finding?
- A Letrozole achieved higher live birth rates and ovulation rates with similar multiple pregnancy rates ✓
- B Clomiphene achieved higher ovulation rates and live birth rates than letrozole
- C Both drugs were equivalent in live birth rates; letrozole had fewer anti-estrogenic endometrial side effects only
- D Letrozole was effective only in lean PCOS, not obese PCOS subgroups
Correct answer: A. Letrozole achieved higher live birth rates and ovulation rates with similar multiple pregnancy rates
Explanation
The landmark Legro et al. (NEJM 2014) trial (often cited in context with LOTUS data) demonstrated that letrozole achieved significantly higher live birth rates (27.5% vs 19.1%) and ovulation rates compared to clomiphene in PCOS, with no increase in multiple gestation. Letrozole works by temporary aromatase inhibition → FSH rise → mono-follicular ovulation, without the anti-oestrogenic effects on endometrium and cervical mucus that characterise clomiphene. It is now the first-line agent for anovulatory infertility in PCOS per ESHRE/ASRM 2023 guidelines.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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