Endometrial preparation protocols for frozen embryo transfer: risk assessment and individualized management

Abstract Frozen embryo transfer (FET) cycles have increased exponentially in the last decade. For many years, the most widely accepted protocol for endometrial preparation for FET cycles has been the artificial cycle (AC-FET), mainly due to the ease of coordinating the timing of embryo transfer with the operational needs of the IVF lab, the medical team and the patient. Accumulating data support that, due to the presence of corpus luteum, natural cycle frozen embryo transfer (NC-FET) is associated with better maternal and perinatal outcomes, especially lower preeclampsia risk, as compared with AC-FET. In this context, novel protocols for endometrial preparation in NC-FET are being tested, to allow better planning of NC-FET either through a flexible ovulation trigger or via initiation of progesterone administration independent of ovulation. Although several clinicians recommend a complete shift to NC-FET for all normo-ovulatory women to prevent pregnancy complications, reverting to a “back to nature” approach is not a comprehensive solution to the problem. Abandoning AC-FET, without any other action, will not solve the problem, simply because not all patients have the same risk. Preeclampsia is a multifactorial disease, and several factors, aside from AC-FET, may present a much higher risk of developing the condition. Therefore, a thorough assessment of preeclampsia risk before selecting a FET protocol, optimizing first-trimester screening algorithms and implementing primary prevention measures for truly at-risk patients—rather than stigmatizing and abandoning AC-FET—should be prioritized.