Prolonging the time of progesterone supplementation to improve the pregnancy outcomes of single day 6 blastocyst transfer in frozen-thawed cycles: study protocol for a randomized controlled trial

Abstract

Background Infertility is one of the most important and underappreciated reproductive health problems in developing countries. Currently, in vitro fertilization and embryo transfer is the most effective treatment strategy for infertility. In a frozen-thawed cycle, single-blastocyst transfer can not only ensure relatively higher pregnancy and live birth rates but also effectively reduce the risk of maternal and neonatal complications. In frozen-thawed cycles, progesterone is initiated to promote the final phase of endometrial preparation prior to embryo transfer. However, the optimal duration of exposure to progesterone has remained inconclusive. Therefore, we designed a randomized controlled trial (RCT) to compare the effects of different prolonged progesterone transformation times (P+6 and P+7) on the pregnancy outcomes of D6 single blastocyst transfer in a frozen-thawed cycle. Methods This is a single-center, prospective, randomized controlled clinical trial involving 900 patients with single blastocyst transfer in the frozen-thawed cycle, aged from 20 to 38 years, with less than three transfers, and with HRT-cycle single D6 blastocyst transfer in the current cycle. Participants will be randomly assigned (1:1) into two parallel groups: the transfer of day 6 blastocysts on the 7th day of progesterone supplementation and the transfer of day 6 blastocysts on the 6th day of progesterone supplementation. The primary outcome measure is the clinical pregnancy rate. Secondary outcome measures include the miscarriage rate and live birth rate. Discussion This is the first randomized controlled trial to compare the transfer of day 6 blastocysts on the 6th and 7th day of progesterone supplementation. The results of this study will provide evidence for whether to prolong the duration of exposure to progesterone prior to embryo transfer. Trial registration ClinicalTrials.gov, ID: NCT04938011. Registered on 19 June 2021.

Association between duration of progesterone supplementation and clinical outcomes in artificial frozen-thawed embryo transfer cycles

“…Thus, delaying the day of embryo transfer is feasible (36, 37). Perhaps, the extended day is also theoretically covered by the implantation window (29). This viewpoint seems to have been recognized in the present study.…”

“…However, there are always some unavoidable factors that lead to the incomplete synchronous development of the embryos and endometrium (27,28). Although some previous studies have indicated that appropriately delaying the transfer time may improve the outcomes of FET (29), another data did not show any difference in clinical pregnancy rates between protocols with or without prolonged progesterone supplementation before FET (30).…”

“…Most reproductive medicine centers believe that a stable clinical pregnancy rate can be obtained by administering the protocol of transferring the Day 3 embryos with progesterone administration for 3 days and transferring blastocysts with progesterone administration for 5 days in HRT cycles (25,26,35). Some reproductive medicine centers still consider that a similar or even higher clinical pregnancy rates can be achieved by prolonging the program by one day (29,30). These scholars maintained that prolonging the time of endometrial transformation using progesterone can diminish uterine contractions, improve endometrial receptivity, and foreshorten the period between development and implantation after embryo transplantation in the FET cycle (29).…”

“…Some reproductive medicine centers still consider that a similar or even higher clinical pregnancy rates can be achieved by prolonging the program by one day (29,30). These scholars maintained that prolonging the time of endometrial transformation using progesterone can diminish uterine contractions, improve endometrial receptivity, and foreshorten the period between development and implantation after embryo transplantation in the FET cycle (29).…”

“…However, the hypothesis that prolonging the duration of progesterone administration could increase the pregnancy rates has not yet been confirmed (29,30,36,37). Better implantation outcomes can be obtained by prolonging the exposure of progesterone to the endometrium during HRT cycles, which prolongs the endometrial receptivity period by increasing the interaction between the embryo and endometrium (38).…”