LE + CC vs. LE for Ovulation Induction

This randomized controlled trial (RCT) aims to evaluate whether, in infertile women with WHO II/IV ovulatory disorders, (I) a combination of letrozole (LE) and clomiphene citrate (CC) compared to LE alone, and (II) adding intrauterine insemination (IUI) compared to timed intercourse, result in higher live birth rates. The study is designed as an open-label, multicenter, two-by-two factorial RCT across six fertility clinics in Vietnam. Participants will be randomized into four groups: (1) LE + CC + IUI, (2) LE alone + IUI, (3) LE + CC + intercourse, and (4) LE alone + intercourse. The primary outcome measure is the live birth rate after one treatment cycle. Based on prior data, the live birth rate for IUI in letrozole cycles is estimated at 12%. To detect a 10% increase in live birth rates with CC, 436 couples are needed (α = 0.05, power = 80%). Additionally, the live birth rate after IUI with LE-induced ovulation is approximately 18.7% (Diamond et al., 2015). To detect a 10% increase with CC, 560 couples are required (α = 0.05, power = 80%). Considering a 5% loss to follow-up and protocol deviations, the study plans to recruit 600 participants (150 per arm).