Is artificial endometrial preparation more associated with early-onset or late-onset preeclampsia after frozen embryo transfer?

Purpose: To explore whether the risks of early- or late-onset preeclampsia vary among frozen embryo transfer (FET) with different regimens for endometrial preparation and fresh embryo transfer (FreET).

Methods: We retrospectively included a total of 24129 women who achieved singleton delivery during their first cycles of in vitro fertilization (IVF) between January 2012 and March 2020. The risks of early- and late-onset preeclampsia after FET with endometrial preparation by natural ovulation cycles (FET-NC) or by artificial cycles (FET-AC) were compared to that after FreET.

Results: After adjustment via multivariable logistic regression, the total risk of preeclampsia was higher in the FET-AC group compared to the FreET group [2.2% vs. 0.9%; adjusted odds ratio (aOR): 2.00; 95% confidence interval (CI): 1.45-2.76] and FET-NC group (2.2% vs. 0.9%; aOR: 2.17; 95% CI: 1.59-2.96).When stratified by the gestational age at delivery based on < 34 weeks or ≥ 34 weeks, the risk of late-onset preeclampsia remained higher in the FET-AC group than that in the and FreET group (1.8% vs. 0.6%; aOR: 2.56; 95% CI: 1.83-3.58) and the FET-NC group (1.8% vs. 0.6%; aOR: 2.63; 95% CI: 1.86-3.73). We did not find a statistically significant difference in the risk of early-onset preeclampsia among the three groups.

Conclusions: An artificial regimen for endometrial preparation was more associated with an increased risk of late-onset preeclampsia after FET. Given that FET-AC is widely used in clinical practice, the potential maternal risk factors for late-onset preeclampsia when using the FET-AC regimen should be further explored, considering the maternal origin of late-onset preeclampsia.