Genetically Causal Associations Between Adenomyosis/Endometriosis and Adverse Pregnancy Outcomes - A Two-Sample Mendelian Randomization Study

J. Wang, L. Wang, Wang X, Ai A, Qiao P
In: International Journal of Women's Health, Vol Volume 18, Iss Issue 1, Pp 1-10 (2026) · 2026 · W7124234605
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A two-sample Mendelian randomization study found a genetically causal association between endometriosis and multiple consecutive miscarriage, but no significant links were observed between adenomyosis or endometriosis and other adverse pregnancy outcomes.

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This two-sample Mendelian randomization study utilized summary statistics from genome-wide association studies to evaluate whether genetically predicted adenomyosis or endometriosis causally influences adverse pregnancy outcomes. The primary inverse-variance weighted analysis indicated that endometriosis may act as a risk factor for multiple consecutive miscarriages, while no significant associations were found between adenomyosis and preterm birth, birth weight, or other evaluated pregnancy complications. Sensitivity analyses, including MR-Egger regression and leave-one-out tests, confirmed the robustness of these findings by ruling out horizontal pleiotropy and identifying outliers without altering the overall conclusions. This paper is centrally about endometriosis and adenomyosis, specifically investigating their genetically causal links to adverse pregnancy outcomes such as miscarriage.

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Abstract

Jingyun Wang,1,* Lu Wang,1,* Xiaohui Wang,1 Ai Ai,1 Ping Qiao2 1Department of Reproductive Medicine, Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2Department of Obstetrics, Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Qiao, Email [email protected] Ai Ai, Email [email protected]: Observational studies have indicated a potential link between adenomyosis/endometriosis and adverse pregnancy outcomes (APOs), yet the potential relationship remains uncertain.Patients and Methods: This study investigates whether genetically predicted adenomyosis/endometriosis influences APOs through a two-sample Mendelian randomization (MR) analysis, utilizing summary statistics from genome-wide association studies (GWAS). The primary analytical method employed was the inverse-variance weighted (IVW) approach, alongside supplementary techniques including weighted median, MR Egger regression, and weighted mode. Sensitivity analyses, such as Cochran’s Q test, the MR-Egger intercept test, the MR-PRESSO (Pleiotropy RESidual Sum and Outlier) test, and a leave-one-out analysis, were conducted to ensure result robustness.Results: Results from the IVW method indicate that endometriosis may pose a risk factor for multiple consecutive miscarriage (OR = 1.07, 95% CI: 1.00– 1.14, P = 0.05). No significant associations were noted between adenomyosis and preterm birth (OR = 0.92, 95% CI: 0.75– 1.11, P = 0.38), birth weight (OR = 1.02, 95% CI: 0.96– 1.10, P = 0.50), or other APOs. The MR-Egger regression suggested no horizontal pleiotropy, while the MR-PRESSO test identified outliers concerning birth weight but did not reveal significant associations. Leave-one-out analysis corroborated the robustness of the findings.Conclusion: This study provides evidence of a potential relationship between endometriosis and multiple consecutive miscarriage, emphasizing the importance of addressing comorbidities and making informed pregnancy decisions in the presence of endometriosis.Keywords: endometriosis, adenomyosis, adverse pregnancy outcomes, pregnancy loss, genetic variant, mendelian randomization, causal association
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International Journal of Women's Health (Jan 2026) Genetically Causal Associations Between Adenomyosis/Endometriosis and Adverse Pregnancy Outcomes - A Two-Sample Mendelian Randomization Study Abstract Jingyun Wang,1,* Lu Wang,1,* Xiaohui Wang,1 Ai Ai,1 Ping Qiao2 1Department of Reproductive Medicine, Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2Department of Obstetrics, Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Qiao, Email [email protected] Ai Ai, Email [email protected]: Observational studies have indicated a potential link between adenomyosis/endometriosis and adverse pregnancy outcomes (APOs), yet the potential relationship remains uncertain.Patients and Methods: This study investigates whether genetically predicted adenomyosis/endometriosis influences APOs through a two-sample Mendelian randomization (MR) analysis, utilizing summary statistics from genome-wide association studies (GWAS). The primary analytical method employed was the inverse-variance weighted (IVW) approach, alongside supplementary techniques including weighted median, MR Egger regression, and weighted mode. Sensitivity analyses, such as Cochran’s Q test, the MR-Egger intercept test, the MR-PRESSO (Pleiotropy RESidual Sum and Outlier) test, and a leave-one-out analysis, were conducted to ensure result robustness.Results: Results from the IVW method indicate that endometriosis may pose a risk factor for multiple consecutive miscarriage (OR = 1.07, 95% CI: 1.00– 1.14, P = 0.05). No significant associations were noted between adenomyosis and preterm birth (OR = 0.92, 95% CI: 0.75– 1.11, P = 0.38), birth weight (OR = 1.02, 95% CI: 0.96– 1.10, P = 0.50), or other APOs. The MR-Egger regression suggested no horizontal pleiotropy, while the MR-PRESSO test identified outliers concerning birth weight but did not reveal significant associations. Leave-one-out analysis corroborated the robustness of the findings.Conclusion: This study provides evidence of a potential relationship between endometriosis and multiple consecutive miscarriage, emphasizing the importance of addressing comorbidities and making informed pregnancy decisions in the presence of endometriosis.Keywords: endometriosis, adenomyosis, adverse pregnancy outcomes, pregnancy loss, genetic variant, mendelian randomization, causal association

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