Clin Pharmacol Ther. 2025 Dec 21. doi: 10.1002/cpt.70174. Online ahead of print.
ABSTRACT
Pregnancy loss after frozen embryo transfer (FET) remains an under-recognized complication in assisted reproductive technology (ART), particularly in non-Western settings. Existing prediction models rarely capture evolving hazards over gestation or externally validated. To address this, we developed and externally validated a parametric time-to-event model to predict the dynamic risks of pregnancy loss following FET using a large real-world Chinese cohort. The model incorporated routinely available clinical variables, including maternal demographics, progesterone concentration, endometrium thickness, and endometrium preparation protocols. A Gompertz distribution model captured the time-dependent hazard trajectory. Model performance was externally validated in two temporal cohorts, as well as in older women (≥40 years) and ethnic minority subgroups. Clinical utility was assessed by decision-curve analysis (DCA). Among 21,242 conceptions, 17.6% resulted in miscarriage or stillbirth, with risks peaking in the first trimester. Maternal age showed a nonlinear effect: compared with reference age 32, hazard increased by 67% at age 40 and more than doubled by age 45. Higher weight accelerated risk over time. Protective factors included greater endometrial thickness, higher progesterone levels, and use of mild- (hazard ratio, HR 0.80, 95% CI: 0.753-0862), late- (HR 0.90, 95% CI: 0.798-0.951), or modified-late stimulation (HR 0.80, 95% CI: 0.732-0.863) protocols. DCA indicated that model-guided risk-stratification strategies offered clear net benefit in older women across a broader range of risk threshold. This validated, time-resolved model supports individualized risk-stratification strategies and informed treatment decisions in FET-based ART across diverse clinical settings in China.
PMID:41422483 | DOI:10.1002/cpt.70174