Embryo Culture Duration Is an Independent Risk Factor for Gestational Diabetes in Frozen Embryo Transfer Pregnancies

Abstract Objective To investigate whether prolonged embryo culture increases the risk of gestational diabetes mellitus (GDM) in pregnancies conceived via frozen embryo transfer (FET). Research Design and Methods In this retrospective cohort study, 26,100 FET pregnancies from 2018 to 2022 were analyzed. GDM was diagnosed by a 75-g oral glucose tolerance test. Embryo culture duration (Day 3 vs. Day 5 vs. Day 6) and morphology were evaluated. Multivariable logistic regression adjusted for maternal age, BMI, and fasting glucose. Interaction analyses assessed the combined effect of blastocyst transfer and maternal metabolic risk factors. Results GDM occurred in 14.0% of pregnancies. Blastocyst-stage transfers were associated with a significantly higher GDM risk than cleavage-stage transfers (Day 3: 15.1%, Day 5: 17.4%, Day 6: 18.2%; p=0.01). Prolonged embryo culture remained an independent risk factor in adjusted models (OR 1.045, 95% CI 1.019–1.071, p<0.01). Embryo morphology showed no significant association with GDM. The combination of blastocyst transfer and maternal metabolic risk factors further increased GDM incidence. Conclusions Prolonged embryo culture is an independent risk factor for GDM after FET. These findings suggest embryo development stage influences maternal glucose metabolism and should be considered in ART protocols, particularly for women with existing metabolic vulnerabilities.