Causal Relationship Between Abortion and Endometriosis: A Bidirectional Two-Sample Mendelian Randomization Study

Yan Huang, Huang Y, Zhang D, Deyu Zhang, Zhou Y, Yingfang Zhou, Chufang Peng
American journal of reproductive immunology (New York, N.Y. : 1989) · 2025 · vol. 93(3) , pp. e70064 · doi:10.1111/aji.70064 · PMID:40028715 · W4408161632
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-07 ⓘ

This Mendelian randomization study found no causal relationship between medical, spontaneous, or other types of abortion and endometriosis, nor a causal effect of endometriosis on abortion likelihood.

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This study employed a bidirectional two-sample Mendelian randomization analysis to investigate the potential causal link between various types of abortion and endometriosis. Using summary statistics from the FinnGen database and UK Biobank, the researchers applied inverse variance weighted methods alongside sensitivity analyses to assess associations in both directions. The results demonstrated no statistically significant causal relationship between medical, spontaneous, or other abortions and the risk of developing endometriosis, nor did endometriosis causally influence the likelihood of experiencing an abortion. This paper is centrally about endometriosis — specifically examining whether abortion serves as a causal risk factor for its development.

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Abstract

PROBLEM: The relationship between abortion and endometriosis (EMS) has been inconsistent in previous observational studies and remains controversial. We intended to examine the causal relationship between abortion and EMS. METHODS OF STUDY: We conducted a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics, drawing data from the FinnGen database and the UK Biobank. The primary analysis utilized the random-effects inverse variance weighted (IVW) approach, complemented by weighted median, weighted mode, and MR-Egger methods. Comprehensive sensitivity analyses were conducted, encompassing the Cochran's Q statistic for assessing heterogeneity and MR-PRESSO to detect pleiotropy. Additionally, Leave-One-Out (LOO) analysis was conducted to confirm the stability of our results. RESULTS: The IVW method revealed no statistically significant causal association between various types of abortion and EMS. Specifically, the odds ratios (ORs) were as follows: medical abortion (OR 0.96, 95% CI: 0.78-1.18, p = 0.72), spontaneous abortion (OR 0.99, 95% CI: 0.81-1.21, p = 0.92), and other types of abortions (OR 1.01, 95% CI: 0.99-1.03, p = 0.36), indicating no significant effects on the risk of EMS. Similarly, analysis in the reverse direction showed no significant causal effects of EMS on the likelihood of experiencing any type of abortion, with ORs for medical abortion (0.97, 95% CI: 0.91-1.03, p = 0.33), spontaneous abortion (0.98, 95% CI: 0.92-1.04, p = 0.50), and other abortions (1.30, 95% CI: 0.76-2.23, p = 0.34). Sensitivity analyses supported these findings, demonstrating no evidence of horizontal pleiotropy or significant heterogeneity. CONCLUSION: Our MR results do not support a causal relationship between abortion and EMS.
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Abstract

Problem The relationship between abortion and endometriosis (EMS) has been inconsistent in previous observational studies and remains controversial. We intended to examine the causal relationship between abortion and EMS.

Methods

of Study We conducted a Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary statistics, drawing data from the FinnGen database and the UK Biobank. The primary analysis utilized the random-effects inverse variance weighted (IVW) approach, complemented by weighted median, weighted mode, and MR–Egger methods. Comprehensive sensitivity analyses were conducted, encompassing the Cochran's Q statistic for assessing heterogeneity and MR-PRESSO to detect pleiotropy. Additionally, Leave-One-Out (LOO) analysis was conducted to confirm the stability of our results.

Results

The IVW method revealed no statistically significant causal association between various types of abortion and EMS. Specifically, the odds ratios (ORs) were as follows: medical abortion (OR 0.96, 95% CI: 0.78–1.18, p = 0.72), spontaneous abortion (OR 0.99, 95% CI: 0.81–1.21, p = 0.92), and other types of abortions (OR 1.01, 95% CI: 0.99–1.03, p = 0.36), indicating no significant effects on the risk of EMS. Similarly, analysis in the reverse direction showed no significant causal effects of EMS on the likelihood of experiencing any type of abortion, with ORs for medical abortion (0.97, 95% CI: 0.91–1.03, p = 0.33), spontaneous abortion (0.98, 95% CI: 0.92–1.04, p = 0.50), and other abortions (1.30, 95% CI: 0.76–2.23, p = 0.34). Sensitivity analyses supported these findings, demonstrating no evidence of horizontal pleiotropy or significant heterogeneity.

Conclusion

Our MR results do not support a causal relationship between abortion and EMS. Conflicts of Interest The authors declare that they have no competing interests. Data Availability Statement All data generated or analyzed during this study are included in this article and supplementary information files.

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Condition tags

endometriosis

MeSH descriptors

Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous Abortion, Spontaneous

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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