Hormone Replacement Cycle Frozen-Thawed Embryo Transfer Is Associated With Elevated Perinatal Risk Compared With Natural Ovulatory Cycle Frozen-Thawed and Fresh Embryo Transfers: Retrospective Analysis of 7,593 Live Birth Cycles.

PURPOSE: This study investigated whether perinatal complications in assisted reproductive technology are attributable to embryo cryopreservation or the specific endometrial preparation method, comparing Fresh Embryo Transfer (Fresh ET), Natural Cycle Frozen-thawed Embryo Transfer (NC-FET), and Hormone Replacement Cycle FET (HRC-FET).

METHODS

A retrospective cohort analysis of 7,593 live-birth cycles (908 Fresh ET, 4,707 HRC-FET, 1,978 NC-FET) performed from 2015 to 2023 was conducted. Multivariable analyses using generalized estimating equations, adjusted for endometrial preparation method, maternal age, BMI, history of delivery, and endometrial thickness, were conducted for the five major complications.

RESULTS

Compared with Fresh ET, HRC-FET was associated with significantly increased risks for hypertensive disorders of pregnancy, placenta accreta spectrum, and postpartum hemorrhage due to uterine atony. No significantly increased risks for these adverse outcomes were observed in association with NC-FET. No significant differences were observed for gestational diabetes or placenta previa across groups.

CONCLUSIONS

The increased risks of adverse maternal and placental outcomes were associated with the HRC protocol rather than the cryopreservation process. These associations suggest that ovulatory-based endometrial preparation strategies, typically characterized by the presence of a corpus luteum, should be considered when medically and logistically feasible to enhance perinatal safety.