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

Observational data suggest that pregnancy conceived via frozen embryo transfer using a natural cycle protocol may have a lower rate of preeclampsia compared with using a programmed cycle protocol.

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Volume 113, Issue 2, Pages 252–257


Bhuchitra Singh, M.D., M.P.H., M.S., Lauren Reschke, M.D., James Segars, M.D., Valerie L. Baker, M.D.


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.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.