The association between serum antinuclear antibodies and premature ovarian insufficiency: a meta-analysis

Autoimmune dysfunction is a recognized contributor to primary ovarian insufficiency (POI), and antinuclear antibodies (ANA) are widely used to assess autoimmune activity. Although many studies have examined the association between ANA and POI, their findings remain inconsistent. This meta-analysis aims to clarify the correlation between ANA positivity and POI and to evaluate the potential of ANA as a serological marker of autoimmune involvement in POI.

We systematically searched PubMed, EMBASE, Cochrane Library, CNKI, VIP, and WanFang Data for case-control studies published up to August 2024. Manual reference screening was also performed. Studies comparing antinuclear antibody (ANA) positivity between women with primary ovarian insufficiency (POI) and controls were included. A random-effects model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity and publication bias were assessed using the I² statistic and Begg's test.

According to the analysis of all 13 studies, ANA positivity was significantly associated with POI (OR 2.57, 95% CI: 1.62-4.08, Z = 4.001, P < 0.001). No significant heterogeneity was observed in the primary outcome (I² = 11.9%). Subgroup analyses revealed statistically significant associations in the following: (1) FSH > 40 U/L subgroup (OR = 2.74, 95% CI: 1.78-4.21, I² = 0%); (2) age < 35 subgroup (OR = 2.83, 95% CI: 1.73-4.63, I² = 3.8%); (3) indirect immunofluorescence (IIF) subgroup (OR = 3.22, 95% CI: 1.28-8.09, I² = 34.6%) and dot immunogold filtration assay (DIGFA) subgroup (OR = 3.84, 95% CI: 1.31-11.27, I² = 0%); (4) non-ovarian infertility controls (OR = 4.42, 95% CI: 1.25-15.60, I² = 0%), healthy controls (OR = 2.13, 95% CI:1.23-3.68, I² = 0%), and hypogonadotropic amenorrhea controls (OR = 6.62, 95% CI: 2.25-19.52, I² = 0%) groups.

ANA positivity is significantly associated with an increased risk of POI, supporting its potential role as a serological marker for early screening. Routine ANA testing may be particularly valuable in women under 35 years of age or with FSH > 40 IU/L. Future large-scale studies should focus on optimizing ANA detection methods (e.g., enzyme-linked immunosorbent assay [ELISA] vs. IIF), quantifying titers, and evaluating nuclear patterns to improve diagnostic accuracy and clinical applicability.