Abstract

Abstract Study question Endometrial receptivity as determined by Endometrial Receptivity Analysis (ERA) can change after a successful live birth from a frozen a frozen embryo transfer (FET) Summary answer 27 of 33 patients with a previous live birth from FET had an altered endometrial receptivity profile by ERA after a subsequent unsuccessful FET. What is known already The endometrial window of implantation is approximately 24 hours wide with a complex interaction of autocrine, paracrine, and endocrine factors. Successful embryo implantation involves a 3-step process of apposition, adhesion, and invasion of an embryo into a receptive endometrium. The ERA was developed using the expression profile of 248 genes using Next Generation Sequencing to determine if the endometrium is receptive, early receptive, late receptive, pre-receptive or post-receptive to objectively determine the optimal timing of progesterone exposure prior to embryo transfer. Some studies have shown statistically significant improvements in live birth rates while other studies have shown no difference. Study design, size, duration Case series of 33 patients with successful live birth following euploid FET using 5 days of progesterone (P + 5) with subsequent unsuccessful FET using the same protocol from January 2018 – December 2020. 27 of 33 patients who repeated their ERA were found to be non-receptive using P + 5. The new ERA profile results were used for their next FET. Implantation and live birth rates were calculated. Participants/materials, setting, methods A single private practice fertility clinic performed 340 ERA cycles from January 2018 – December 2020 with 276 subsequent FET cycles. An observational study of 33 patients with a previous live birth using P + 5 elected to repeat their ERA cycle after an unsuccessful FET. Implantation and live birth rates were calculated for their subsequent FET after completing the repeat ERA. Main results and the role of chance Repeat ERA result for patients with a previous live birth using P + 5 revealed that 6 patients still needed P + 5 (18.2%) for a receptive endometrial profile, 8 patients (24.2%) needed an extra 12 hours (P + 5.5), 18 patients (54.5%) needed an extra 24 hours (P + 6) and only one patient (3.0%) needed an extra 48 hours (P + 7). No patient that repeated their ERA after a previous live birth had a post-receptive profile (P + 4 or P + 4.5) and one patient had successful live births after using 3 different ERA profiles (P + 5, P + 6 and P + 7). All patients except one had repeat ERA results that were pre-receptive with only one patient changing from P + 6 to P + 5. FET cycles using P + 5 and P + 7 had a 100% implantation and pregnancy rate, while patients using P + 5.5 had the lowest implantation rate (62.5%) and live birth rate (37.5%). Patients with an ERA profile of P + 6 had an implantation rate of 94.1% and live birth rate of 88.2%. The small number of patients in this case series make a type I error possible because of the low number of patients in each ERA profile category with insufficient power to reach statistical significance. Limitations, reasons for caution Implantation rate for the clinic during the study period was 75% and live birth rate of 68% using euploid embryos. Our high baseline implantation and live birth rates, coupled with low numbers of patients in this observational study, make these results less generalizable to the IVF population at large. Wider implications of the findings It is widely accepted that ERA results are reproducible and do not change during a woman’s reproductive life. These results suggest that some women may have an altered window of receptivity after both successful and unsuccessful FET cycles. It may be reasonable to repeat ERA cycles for carefully selected patients. Trial registration number N/A

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