Singleton term pregnancies resulting from frozen-thawed embryo transfer in hormone replacement cycles increase the risk of aberrant placentation, including velamentous umbilical cord insertion.

Purpose: The number of frozen-thawed embryo transfers (FETs) has recently increased, and FET must be completed in the ovulatory (NC-FET) or programmed hormone replacement cycle (HRC-FET). However, the relationship between FET and abnormal placentation is unclear. This study aimed to determine whether the two distinct endometrial preparation protocols affect the incidence of several pathologic conditions caused by abnormal placentation, such as placenta with velamentous umbilical cord insertion (VCI), hypertensive disorders of pregnancy (HDP), and placenta accreta spectrum (PAS).

Methods: For this retrospective cohort study, the medical records of 1,161 singleton term FET-conceived and -delivered cases were reviewed from January 2016 to July 2024. The study population was categorized into HRC-FET (Group A: n = 846) and NC-FET (Group B: n = 315) cases. After adjusting for confounding factors, the odds ratios (ORs) of the investigated targeted variables in Group A compared to Group B were calculated using multivariate logistic regression.

Results: The incidence of VCI and PAS in Groups A and B was 7.0% and 2.5% for VCI and 5.1% and 1.0% for PAS, respectively, with a significant difference (P < 0.01). The adjusted ORs for VCI, PAS, and HDP in Group A compared to those in Group B were 3.07 (P < 0.01), 5.73 (P < 0.01), and 1.24 (P = 0.42), respectively.

Conclusion: Pregnancies achieved through HRC-FET have higher risks of developing abnormal placentation (i.e., VCI and PAS) than those achieved through NC-FET. These pregnancies are high risk and should be managed carefully for a healthy perinatal course.