Uric Acid and Metabolic Phenotype in Placental Complications After Programmed Frozen Embryo Transfer

Abstract

Programmed frozen embryo transfer (FET) is associated with increased obstetric risk, but the contribution of maternal metabolic characteristics remains uncertain. We examined first-trimester serum uric acid, metabolic phenotype and subsequent placental complications in a retrospective cohort of 158 singleton pregnancies after programmed FET with autologous oocytes, delivered in Tashkent, Uzbekistan, during 2022–2024. Metabolic phenotype was defined as pre-pregnancy body mass index ≥30 kg/m² and/or homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5. The primary composite comprised pre-eclampsia, recorded placental dysfunction with abnormal uteroplacental Doppler, or placental abruption. Uric acid was measured at 8+0–12+6 weeks. The metabolic phenotype was present in 82 pregnancies, and 54 pregnancies (34.2%) developed the composite outcome. Median uric acid was higher with versus without the phenotype (211.5 versus 176.5 µmol/L) and with versus without the composite outcome (222.5 versus 180.0 µmol/L; both p < 0.001). The adjusted odds ratio per 10 µmol/L was 1.45 (95% confidence interval 1.24–1.69). The phenotype estimate attenuated from 3.69 unadjusted to 1.29 (0.52–3.22) after adjustment. Apparent discrimination was 0.809 for uric acid alone and 0.824 for the multivariable model, with an optimism-corrected model area of 0.802. Among 156 women without pregestational diabetes, metabolic phenotype remained associated with recorded gestational diabetes. Early uric acid was associated with subsequent placental complications within this cohort; these findings do not establish mediation, clinical screening utility or benefit from urate lowering.