Antinuclear antibody (ANA) is a common autoantibody. In recent years, the association between ANA positivity and adverse pregnancy outcomes has received increasing attention. However, findings from relevant studies remain controversial, and there is no consensus on clinical management strategies for individuals with ANA positivity.To systematically review the impact of ANA positivity on pregnancy outcomes in women, encompassing recurrent pregnancy loss (RPL), assisted reproductive technology (ART) outcomes, and mid-to-late pregnancy complications, and to explore its pathogenic mechanisms and the evidence base for current treatment strategies.

A systematic search was performed in databases including PubMed and Web of Science to identify original studies, meta-analyses, and systematic reviews investigating the association between ANA and pregnancy outcomes.

The association between ANA and RPL has been confirmed by multiple studies. Relevant data indicate that the positivity rate of ANA in patients with RPL is statistically significantly higher than that in the normal pregnancy population. ANA positivity may increase the risk of ART failure. The prevalence of ANA is significantly higher in women with RPL compared with controls, and the association between high-titer ANA and RPL is stronger. However, some prospective studies suggest that ANA positivity does not significantly affect the live birth rate in subsequent pregnancies among patients with RPL. Current evidence is insufficient to establish a clear association between ANA positivity and conditions such as preeclampsia, fetal growth restriction, or stillbirth, highlighting the need for high-quality prospective cohort studies. The exact pathological mechanisms underlying ANA-mediated miscarriage remain incompletely understood, but may involve immune complex deposition at the maternal–fetal interface, inflammatory responses, complement activation, impaired trophoblast function, and regulatory T cell dysfunction. Small-sample studies suggest that immunomodulatory therapies such as prednisone and hydroxychloroquine may improve ART outcomes in patients with ANA positivity. However, these findings lack validation from large-scale randomized controlled trials, and excessive immunosuppression carries potential risks. ANA positivity significantly reduces clinical pregnancy and embryo implantation rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and increases the risk of miscarriage.

ANA positivity is clearly associated with early reproductive impairments, including IVF failure and RPL, whereas its impact on mid-to-late pregnancy complications remains uncertain. High-titer ANA may be of greater clinical significance. It is recommended that ANA screening be incorporated into the etiological evaluation of patients with unexplained infertility and RPL. However, treatment decisions should be guided by individualized risk stratification. Future efforts should focus on standardizing ANA testing protocols, conducting prospective multicenter studies, and exploring precision therapeutic strategies based on immunological phenotypes.