Predictive Value of the Miscarriage Prediction Index for Early Miscarriage After Frozen Embryo Transfer

Purpose: To evaluate whether the Miscarriage Prediction Index (MPI), a novel ratio derived from early pregnancy hormonal changes, can identify women at increased risk of early miscarriage after frozen embryo transfer. Methods: This retrospective cohort study included 1337 women with confirmed intrauterine pregnancies following frozen embryo transfer at two reproductive centers. Serum hormone levels were measured during early pregnancy, and the Miscarriage Prediction Index (MPI), reflecting the balance between trophoblastic activity and estrogenic support, was calculated from dynamic hormonal changes. Participants were followed through 12 weeks of gestation. Statistical analyses assessed the association between MPI and early miscarriage risk and explored age-related differences. Results: Higher MPI values were significantly associated with an increased risk of early miscarriage and reduced likelihood of ongoing pregnancy. The relationship between MPI and miscarriage risk was nonlinear, with risk rising markedly beyond specific threshold values. MPI showed modest discriminatory performance, with an AUC of 0.670 (95% CI, 0.627– 0.719) in the development cohort and 0.688 (95% CI, 0.630– 0.747) in the external cohort. The association was stronger in women younger than 35 years, while MPI demonstrated modest and consistent predictive performance in both development and external cohorts and provided additional predictive information beyond maternal age alone. Conclusions: Elevated MPI is associated with early miscarriage risk after frozen embryo transfer and may reflect early endocrine imbalance and pregnancy instability. Age-specific MPI may better interpret MPI values and support more individualized risk stratification, early identification miscarriage, and monitoring among women, which may provide a potential window for timely clinical assessment and intervention. Keywords: miscarriage, estradiol levels, clinical pregnancy, frozen-thawed embryo transfer