Antinuclear antibodies and female reproductive health: Evidence, clinical implications and management

Antinuclear antibodies (ANA) are biomarkers of immune dysregulation whose reproductive significance depends on the clinical setting and antibody profile. This narrative review synthesizes clinical and experimental evidence on ANA in infertility, assisted reproductive technology (ART), recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), endometriosis and pregnancy complications. Follicular-fluid studies and experimental models implicate oocyte maturation, embryo development, trophoblast function and placental immune regulation, providing biological plausibility without establishing ANA-mediated causation in human reproductive failure. Clinical studies show enrichment of ANA in infertility and RPL populations, whereas subsequent pregnancy prognosis, ART outcomes and perinatal associations vary with population, assay, titer and endpoint. We distinguish isolated ANA positivity from specific ANA-associated autoantibodies and established autoimmune disease because these findings carry different clinical implications. Disease-directed treatment for systemic lupus erythematosus or antiphospholipid syndrome is considered separately from empirical treatment in ANA-positive infertility patients. Some intervention studies report improved early reproductive outcomes, but current evidence does not support routine corticosteroids, hydroxychloroquine, aspirin or heparin solely on the basis of ANA positivity. ANA positivity is therefore best interpreted as a context-dependent marker that may guide targeted assessment rather than an independent therapeutic target. Prospective studies linking defined antibody profiles to tissue mechanisms, reproductive outcomes and treatment response are needed to establish clinically useful applications.