Micronized progesterone plus dydrogesterone versus micronized progesterone alone for luteal phase support in frozen-thawed cycles (MIDRONE): a prospective cohort study

Study Question: Does the addition of oral dydrogesterone to vaginal progesterone as luteal phase support improve pregnancy outcomes during frozen embryo transfer (FET) cycles compared with vaginal progesterone alone? Summary Answer: Luteal phase support with oral dydrogesterone added to vaginal progesterone had a higher live birth rate and lower miscarriage rate compared with vaginal progesterone alone. What is Known Already: Progesterone is an important hormone that triggers secretory transformation of the endometrium to allow implantation of the embryo. During IVF, exogenous progesterone is administered for luteal phase support. However, there is wide inter-individual variation in absorption of progesterone via the vaginal wall. Oral dydrogesterone is effective and well tolerated when used to provide luteal phase support after fresh embryo transfer. However, there are currently no data on the effectiveness of luteal phase support with the combination of dydrogesterone with vaginal micronized progesterone compared with vaginal micronized progesterone after FET. Study Design Size, Duration: Prospective cohort study conducted at an academic infertility center in Vietnam from 26 June 2019 to 30 March 2020. Participants/Materials, Settings, Methods: We studied 1364 women undergoing IVF with FET. Luteal support was started when endometrial thickness reached 8 mm. The luteal support regimen was either vaginal micronized progesterone 400 mg twice daily plus oral dydrogesterone 10 mg twice daily (second part of the study) or vaginal micronized progesterone 400 mg twice daily (first 4 months of the study). In women with a positive pregnancy test, the appropriate luteal phase support regimen was continued until 7 weeks’ gestation. The primary endpoint was live birth after the first FET of the started cycle, with miscarriage <12 weeks as one of the secondary endpoints. Main Results and the Role of Chance: The vaginal progesterone + dydrogesterone group and vaginal progesterone groups included 732 and 632 participants, respectively. Live birth rates were 46.3% versus 41.3%, respectively (rate ratio [RR] 1.12, 95% CI 0.99–1.27, P¼0.06; multivariate analysis RR 1.30 (95% CI 1.01–1.68), P¼0.042), with a statistically significant lower rate of miscarriage at