P-578 Oral, Vaginal or Intramuscular Progesterone in Programmed Frozen Embryo Transfer Cyles: A Pilot RCT

Abstract

Abstract Study question What should be the optimal luteal phase support in programmed frozen embryo transfer (FET) cycles using vitrified-thawed blastocysts? Summary answer 40mg/day oral dydrogesterone, 180mg/day progesterone (P) vaginal gel and 100mg/day im P in oil revealed similar reproductive outcomes in programmed FET cycles. What is known already Luteal phase should be supported either in fresh (Yanushpolsky et al, 2015) or in FET cycles (Pabuccu et al, 2020). Endometrium preparation in FET cycles is outmost important for successful implantation. For this purpose, natural or programmed protocols have been suggested. In programmed FET cycles, exogenous P replacement is of critical importance, as estrogen use will inhibit ovulation and corpus luteum formation.Higher serum P level was associated with increased rates of ongoing pregnancy or live birth in programmed FET cycles (Melo et al 2021). Therefore, lack of a corpus luteum justifies precise and adequate luteal support. Study design, size, duration This was a randomized, parallel, phase IV-pilot RCT (NCT03948022), comparing 3 different luteal support options in programmed FET cycles. A total of 168 women aged between 20-40 years and having available blastocyst(s) were eligible for the study between April-December 2020. After excluding cases, 163 patients were randomly assigned to one of the P arms based on a computer- generated list to administer: 1-oral dydrogesterone 40mg/day (DYD) 2-vaginal %8 P gel 180mg/day (VAG) 3-im 100mg/day P (IM) Participants/materials, setting, methods Estradiol 2 mg TID was started on day 2 or 3 of menstruation for at least 7 days. On day 8, endometrial thickness was assessed. When it was >8 mm, each patient was randomly assigned to one of the intervention arms. After 5 days of P administration, ET was performed on the 6th day preceding serum P measurement. Primary outcome was ongoing pregnancy rate defined as viable healthy pregnancy beyond 20th week of gestation. Main results and the role of chance A total of 151 women out of 163 completed the primary follow-up after randomization. 12 patients were excluded from the final analysis mainly due to protocol violation and discontinuation of intervention. Each patient contributed to a single cycle in the analysis and given data does not include cumulative pregnancies including surplus frozen embryo transfers. Demographic data including; mean woman age, body mass index, serum AMH, TSH and infertility etiologies were comparable among all groups without statistically significance (p > 0.5) Limitations, reasons for caution Lack of a power analysis is the main limitation of this study, potentially coming with type-1 error. Properly designed and powered RCTs are needed. Wider implications of the findings There have been very limited data available for oral progestogen use particularly in FET cycles, unlike many reports for vaginal and im P. Comperable reproductive outcomes with significantly lower side effect profile of oral progestagen merits further attention in programmed FET cycles. Trial registration number NCT03948022