Modification effect of multiple gestation on the relationship between maternal body mass index and miscarriage in frozen-thawed embryo transfer: a retrospective cohort study.

Abstract

Background: Elevated maternal body mass index (BMI) increases miscarriage risk in assisted reproductive technology, but it is unclear whether this risk differs between singleton and twin pregnancies. Twin gestations impose greater metabolic and hemodynamic demands, which may amplify the adverse effects of elevated BMI. This study aimed to determine whether pregnancy plurality modifies the association between maternal BMI and miscarriage risk following frozen-thawed embryo transfer (FET).

Methods: In this retrospective cohort study, 13,911 FET cycles performed at a tertiary reproductive medicine center between January 2019 and June 2024 were included. Maternal BMI was categorized as underweight (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary outcome was total miscarriage (pregnancy loss before 28 weeks), with secondary outcomes including early miscarriage (< 12 weeks), late miscarriage (12-28 weeks), clinical pregnancy and live birth. Generalized estimating equation (GEE) models were used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs), accounting for repeated cycles from the same patient. Subgroup analyses stratified by pregnancy plurality (singleton vs. twin) and interaction tests were performed to evaluate whether plurality modifies the association between BMI and miscarriage.

Results: Overall, early and late miscarriage rates were 11.71% and 4.59%. After adjustment, obesity (BMI ≥ 30 kg/m²) was significantly associated with increased risks of early miscarriage (adjusted odds ratio [aOR] 1.74, 95% CI 1.31-2.31), late miscarriage (aOR 2.35, 95% CI 1.55-3.57) and total miscarriage (aOR 2.04, 95% CI 1.58-2.62) compared with normal-weight women. Overweight women also exhibited elevated risks of late miscarriage (aOR 1.66, 95% CI 1.30-2.12) and total miscarriage (aOR 1.30, 95% CI 1.13-1.50). Subgroup analyses demonstrated that the association between elevated BMI and total miscarriage was significantly stronger in twin pregnancies than in singleton pregnancies (P for interaction = 0.018). Increasing BMI was not associated with clinical pregnancy or live birth.

Conclusions: Elevated maternal BMI was associated with an increased risk of miscarriage after FET, and this association may be more pronounced in twin pregnancies. These findings highlight preconception weight optimization and support elective single embryo transfer in overweight and obese patients.