Evaluation of Early Frozen Blastocyst Transfer in A True Natural Cycle Protocol in Comparison to A Hormone Replacement Protocol: A Single-Center Cohort Study

Timing of frozen embryo transfer (FET) within a purported window of implantation is of increasing interest,and there is a paucity of evidence surrounding the transfer of frozen embryos early within these frozen embryo transferprotocols. This study aimed to evaluate whether live birth rates were equivalent after FET of blastocysts 4 days afterluteinizing hormone (LH) surge in a true natural cycle protocol, compared to a hormone replacement (HR) protocol. Single-centre, retrospective cohort study involving patients undergoing autologous frozenblastocyst transfer from January 1st, 2013, to December 31st, 2016. Cycles were grouped according to their protocol:true natural cycle (hormonal detection of LH surge with FET scheduled four days later) versus HR cycle (lutealphase gonadotropin-releasing hormone agonist suppression, oral or vaginal estradiol and intramuscular progesteronestarting five days before FET). A total of 850 cycles were included, 501 true natural cycles and 349 HR cycles. Theprimary outcome was the live birth rate, secondary outcomes included clinical pregnancy rate and miscarriage. Logbinomialregression models were performed adjusting for a priori selected variables. Adjusted resulted in live birth rates of 38.7 and 40.4%, [adjusted risk ratio (aRR): 0.96, 95% confidence interval(CI): 0.76-1.22, P=0.729] in the natural cycle and HR groups, respectively. The secondary outcome analyses didnot demonstrate any statistically significant difference in the rate of positive human chorionic gonadotropin (hCG),clinical intrauterine pregnancy rate, or miscarriage rate. The timing of the FET four days after LH surge in a true natural cycle protocol results in equivalent livebirth rates compared to a HR protocol. Results of this study suggest that the window of implantation within the naturalcycle may be less finite than currently believed and further prospective studies evaluating the timing of frozen embryotransfer are warranted.