Preparing and Timing of the Endometrium in Modified Natural Cycle Frozen-thawed Embryo Transfers (mNC-FET) - a Randomized Controlled Multicenter Trial

Single embryo transfer and freezing of surplus embryos has lowered twin birth rates after in vitro fertilization (IVF) to a level of less than 5% in Denmark. However, several treatments with repeated frozen embryo transfers (FET) before a viable pregnancy is confirmed are burdensome to the patients. New freezing techniques has optimized the quality of the embryo transferred in FET cycles, but optimization of the endometrium in the luteal phase is still lacking behind. In a mNC-FET, which is the routine in many clinics, ovulation is induced with an hCG injection when the leading follicle is ≥17 mm. The hCG trigger is important for controlling the time of ovulation, but triggering an unhealthy follicle at an inappropriate time may cause luteal phase insufficiency and thus suboptimal function of the endometrium. Danish public fertility clinics are not routinely using progesterone supplementation in mNC-FET, but there may be a rationale to do so, and some implantations may be rescued. In this study we will compare live birth rates in mNC-FET with and without progesterone supplementation in the luteal phase, and further we will explore the optimal timing of blastocyst warming and transfer by comparing embryo transfer at hCG trigger +6 days versus +7 days. This is a superiority study with the aim to detect an increase in live birth rates of 10%. Hence, this adequately powered RCT may make a major contribution to knowledge on mNC-FET to the benefits of patients. We will include 604 patients divided 1:1 (302:302) in each arm +/- progesterone and these will further be divided 1:1 in blastocyst warming and transfer +6 and +7 days after hCG injection. The primary endpoint is live birth rate per transfer.