Serum uric acid is associated with ovarian reserve and neonatal outcomes in women undergoing IVF/ICSI: observational and genetic evidence

Elevated serum uric acid (SUA) has been linked to adverse outcomes in polycystic ovary syndrome, yet its broader role in female fertility is unclear. This retrospective cohort study of 16,223 women undergoing a first in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycle investigated associations between pre-treatment SUA and reproductive parameters. Higher SUA levels were independently associated with elevated luteinizing hormone (LH), testosterone, and anti-Müllerian hormone (AMH), and with lower estradiol and follicle-stimulating hormone. Each 50 µmol/L SUA increase correlated with a 16-gram reduction in neonatal birth weight and a 0.06-week decrease in gestational age, with a threshold effect near 350 µmol/L. Bidirectional Mendelian randomisation analyses supported a causal effect of elevated SUA on increased LH and testosterone, while reverse analysis suggested lower AMH may elevate SUA. These findings identify SUA as a biomarker influencing ovarian reserve and neonatal outcomes through bidirectional mechanisms, including a potential SUA-AMH feedback loop. Routine SUA monitoring in fertility treatment is supported, and interventions for individuals with SUA ≥350 µmol/L warrant clinical investigation.