Frozen embryo transfer: a review on the optimal endometrial preparation and timing

Study question: What is the optimal endometrial preparation protocol for a frozen embryo transfer (FET)?

Summary answer: Although the optimal endometrial preparation protocol for FET needs further research and is yet to be determined, we propose a standardized timing strategy based on the current available evidence which could assist in the harmonization and comparability of clinic practice and future trials.

What is known already: Amid a continuous increase in the number of FET cycles, determining the optimal endometrial preparation protocol has become paramount to maximize ART success. In current daily practice, different FET preparation methods and timing strategies are used.

Study design, size, duration: This is a review of the current literature on FET preparation methods, with special attention to the timing of the embryo transfer.

Participants/materials, setting, methods: Literature on the topic was retrieved in PubMed and references from relevant articles were investigated until June 2017.

Main results and the role of chance: The number of high quality randomized controlled trials (RCTs) is scarce and, hence, the evidence for the best protocol for FET is poor. Future research should compare both the pregnancy and neonatal outcomes between HRT and true natural cycle (NC) FET. In terms of embryo transfer timing, we propose to start progesterone intake on the theoretical day of oocyte retrieval in HRT and to perform blastocyst transfer at hCG + 7 or LH + 6 in modified or true NC, respectively.

Limitations reasons for caution: As only a few high quality RCTs on the optimal preparation for FET are available in the existing literature, no definitive conclusion for benefit of one protocol over the other can be drawn so far.

Wider implications of the findings: Caution when using HRT for FET is warranted since the rate of early pregnancy loss is alarmingly high in some reports.

Study funding/competing interest(s): S.M. is funded by the Research Fund of Flanders (FWO). H.T. and C.B. report grants from Merck, Goodlife, Besins and Abbott during the conduct of the study.

Trial registration number: Not applicable.