A multi-center, randomized, open-label, parallel group study of a natural micronized progesterone vaginal tablet as a luteal support agent in Japanese women undergoing assisted reproductive technology

Purpose To verify sufficient progesterone supplementation during the luteal phase and to determine the efficacy and safety of a natural micronized progesterone vaginal tablet (FE 999913) in Japanese women undergoing in vitro fertilization‐embryo transfer or intracytoplasmic sperm injection. Methods In a multi‐center, randomized, open‐label, parallel group trial, 108 subjects were randomized to receive FE 999913 vaginally twice daily (n = 54) or three times daily (n = 54) for up to 10 weeks. Primary endpoints were the proportion of subjects with serum progesterone concentration ≥10 ng/ml on day 5 and ongoing pregnancy rate at week 5. Results Ninety‐four subjects completed the trial and 90 subjects underwent embryo transfer. The proportion of subjects with serum progesterone concentration ≥10 ng/ml on day 5 was 98.9 % and the lower limit of 95 % CI of the difference between the current trial and MEGASET trial was −3.6 %, which was within the non‐inferiority criterion. The ongoing pregnancy rate was 22.2 %, which is similar to that in actual clinical settings in Japan. No safety concerns were observed. Conclusions FE 999913 was useful in this trial from the aspects of sufficient supplementation of progesterone, comparable pregnancy rate with that in clinical practice in Japan, and safety. Clinical trial registration ClinicalTrials.gov identifier: NCT01710514.