Frozen-thawed embryo transfer: the potential importance of the corpus luteum in preventing obstetrical complications

Abstract

The use of frozen-thawed embryo transfer (FET) has increased over the past decade with improvements in technology and increasing live birth rates. FET facilitates elective single-embryo transfer, reduces ovarian hyperstimulation syndrome, optimizes endometrial receptivity, allows time for preimplantation genetics testing, and facilitates fertility preservation. FET cycles have been associated, however, with an increased risk of hypertensive disorders of pregnancy for reasons that are not clear. Recent evidence suggests that absence of the corpus luteum (CL) could be at least partly responsible for this increased risk. In a recent prospective cohort study, programmed FET cycles (no CL) were associated with higher rates of preeclampsia and preeclampsia with severe features compared with modified natural FET cycles. FET cycles are commonly performed in the context of a programmed cycle in which the endometrium is prepared with the use of exogenous E₂ and P. In these cycles, ovulation is suppressed and therefore the CL is absent. The CL produces not only E₂ and P, but also vasoactive products, such as relaxin and vascular endothelial growth factor, which are not replaced in a programmed FET cycle and which are hypothesized to be important for initial placentation. Emerging evidence has also revealed other adverse obstetrical and perinatal outcomes, including postpartum hemorrhage, macrosomia, and post-term birth specifically in programmed FET cycles compared with natural FET cycles. Despite the widespread use of FET, the optimal protocol with respect to live birth rate, maternal health, and perinatal outcomes has yet to be determined. Future practice regarding FET should be based on high-quality evidence, including rigorous controlled trials.

Keywords: Frozen embryo transfer; natural cycle; preeclampsia; pregnancy outcomes; programmed cycle.