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

Purpose: 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.