Lotus I: A phase III randomized controlled trial of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization, with focus on the Russian subpopulation

Objective. Compare efficacy and safety of oral dydrogesterone (DYD) and micronized vaginal progesterone (MVP) for luteal support in IVF, with focus on Russian subjects. Subject and methods. Double-blind, randomized, multicenter non-inferiority study (Lotus I). Women undergoing IVF were randomized to DYD 10 mg or MVP 200 mg TID. Primary objective was the presence of fetal heartbeats at pregnancy week 10 (12 weeks’ gestation). Results. In the full analysis sample (FAS), 497 (DYD [106 Russian]) and 477 (MVP [103 Russian]) subjects were randomized. DYD was non-inferior to MVP (FAS): difference in pregnancy rate at 12 weeks’ gestation of 4.7% in favor of DYD (95% CI: −1.2–10.6%). In Russian subjects, this difference was 14.2% in favor of DYD (95% CI: 1.1–27.2%). DYD and MVP had similar safety profiles. No health issues reported for Russian infants (6-month follow-up). Conclusion. In Russian subjects and overall, DYD was as efficacious as MVP. DYD may replace MVP for luteal support in IVF.