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Fertil Steril. 2025 Aug 6:S0015-0282(25)01796-0. doi: 10.1016/j.fertnstert.2025.07.1219. Online ahead of print.
ABSTRACT
OBJECTIVE: To study whether changing the frozen embryo transfer (FET) protocol for endometrial preparation impacts pregnancy outcomes for women who did not achieve a live birth after their initial FET.
DESIGN: Retrospective cohort study.
SETTING: Private practice clinic.
SUBJECTS: The study included 17,989 FET cycles after a prior failed FET that took place from 2012 to 2022. There were four groups of patients studied: those who underwent a programmed FET after a failed initial programmed FET, those who underwent a natural FET after a failed initial natural FET, those who underwent a natural FET after a failed initial programmed FET, and those who underwent a programmed FET after a failed initial natural FET.
EXPOSURE: The subsequent FET protocol, after a failed initial FET.
MAIN OUTCOME MEASURES: The primary outcome was live birth. Secondary outcomes included clinical pregnancy and pregnancy loss.
RESULTS: For patients who failed an initial programmed FET, there was no difference in live birth for those who switched to natural FET protocol versus repeated a programmed FET (42.1% versus 40.7%, adjusted RR 1.02, 95% CI [0.97, 1.08]). Secondary outcomes of clinical pregnancy and pregnancy loss were also not statistically different. For patients who failed an initial natural FET, there was also no difference in live birth for those who switched to a programmed FET protocol versus repeated a natural FET (39.9% versus 38.2%, adjusted RR 1.06 95% CI [1.00, 1.13]). These findings were consistent in a subgroup analysis restricting to euploid transfers. In a planned subgroup analysis examining various types of natural FET, for women who initially failed programmed FET, live birth was higher for those who changed protocols to a true natural FET, versus those who repeated a programmed FET (50.3% versus 40.7%, adjusted RR 1.2, 95% CI [1.03, 1.39]).
CONCLUSION: For women who do not achieve a live birth after an FET in the setting of adequate endometrial preparation, there is no significant association with live birth, clinical pregnancy or pregnancy loss after changing or repeating the transfer protocol. Further research is needed to clarify the effect of changing to a true natural FET protocol.
PMID:40780420 | DOI:10.1016/j.fertnstert.2025.07.1219