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Background <p>Infertility affects up to 12% of couples worldwide, and approximately 30% of cases remain unexplained despite comprehensive diagnostic evaluation. Increasing evidence suggests that immunological mechanisms may contribute to reproductive failure. This review evaluates evidence on the role of autoantibodies in women suffering from reproductive failures.</p> Material and methods <p>A systematic review of studies retrieved from Pubmed, Embase and Google Scholar on women with reproductive failures reporting on anti-ovarian antibodies (AOA), anti-zona pellucida antibodies, anti-gonadotropin antibodies, anti-sperm/seminal anti-bodies&#xa0;was performed. Study quality was assessed using the Newcastle–Ottawa Scale. Meta-analysis was feasible only for AOA.</p> Results <p>Of 175 identified publications, 24 met the inclusion criteria. In women with unexplained infertility and those undergoing assisted reproductive technology (ART), AOA positivity was significantly more frequent compared with healthy controls, with pooled odds ratios (OR) of 8.31 and 8.45, respectively, and low statistical heterogeneity. Corresponding pooled prevalence estimates were approximately 38% in both groups. In women with premature ovarian failure (POF), AOA positivity was also increased compared with controls (pooled OR 6.84), although this association was accompanied by substantial between-study heterogeneity. For other reproductive autoantibodies, reported prevalences varied widely across studies, ranging from absent to more than 70% in individual reports, depending on antibody class, assay methodology, and study population. Overall, substantial methodological heterogeneity was observed, including differences in participant selection, control definitions, antigen sources, and laboratory techniques.</p> Conclusions <p>Current evidence indicates that humoral autoimmunity is associated with reproductive failure, with AOAs showing the most consistent associations, especially in women with unexplained infertility and in ART populations (odds ratios &gt; 8). In contrast, findings in premature ovarian failure and other reproductive autoantibodies are heterogeneous and methodologically limited. Current evidence is not yet sufficient to recommend routine testing for AOAs or the other investigated antibodies as part of the standard diagnostic work-up. Antigen-specific, subgroup-focused approaches may therefore represent a more informative direction for future research.</p>

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The role of auto-antibodies in reproductive failure in women: a systematic review and meta-analysis of anti-ovarian antibodies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Chiara Kirchler,
  • Iris Müller,
  • Vanessa Blazovich,
  • Christian Anzur,
  • Ruth Fritsch-Stork

摘要

Background

Infertility affects up to 12% of couples worldwide, and approximately 30% of cases remain unexplained despite comprehensive diagnostic evaluation. Increasing evidence suggests that immunological mechanisms may contribute to reproductive failure. This review evaluates evidence on the role of autoantibodies in women suffering from reproductive failures.

Material and methods

A systematic review of studies retrieved from Pubmed, Embase and Google Scholar on women with reproductive failures reporting on anti-ovarian antibodies (AOA), anti-zona pellucida antibodies, anti-gonadotropin antibodies, anti-sperm/seminal anti-bodies was performed. Study quality was assessed using the Newcastle–Ottawa Scale. Meta-analysis was feasible only for AOA.

Results

Of 175 identified publications, 24 met the inclusion criteria. In women with unexplained infertility and those undergoing assisted reproductive technology (ART), AOA positivity was significantly more frequent compared with healthy controls, with pooled odds ratios (OR) of 8.31 and 8.45, respectively, and low statistical heterogeneity. Corresponding pooled prevalence estimates were approximately 38% in both groups. In women with premature ovarian failure (POF), AOA positivity was also increased compared with controls (pooled OR 6.84), although this association was accompanied by substantial between-study heterogeneity. For other reproductive autoantibodies, reported prevalences varied widely across studies, ranging from absent to more than 70% in individual reports, depending on antibody class, assay methodology, and study population. Overall, substantial methodological heterogeneity was observed, including differences in participant selection, control definitions, antigen sources, and laboratory techniques.

Conclusions

Current evidence indicates that humoral autoimmunity is associated with reproductive failure, with AOAs showing the most consistent associations, especially in women with unexplained infertility and in ART populations (odds ratios > 8). In contrast, findings in premature ovarian failure and other reproductive autoantibodies are heterogeneous and methodologically limited. Current evidence is not yet sufficient to recommend routine testing for AOAs or the other investigated antibodies as part of the standard diagnostic work-up. Antigen-specific, subgroup-focused approaches may therefore represent a more informative direction for future research.