Endometriosis increases risk of some birth defects in infants

By Dr. Liji Thomas, MDReviewed by Lauren HardakerMay 13 2026

A Canadian study suggests inflammation linked to endometriosis may subtly shape fetal development, increasing the likelihood of some congenital anomalies even when fertility treatment is taken into account. 

Study: Risk of congenital anomalies among infants of patients with endometriosis: a population-based cohort study. Image credit: Anna Zhukkova/Shutterstock.com

Women with endometriosis may face a slightly higher risk of having infants with congenital anomalies, according to a large population-based study published in CMAJ.

Endometriosis and reproductive health

Several chronic maternal conditions increase the risk of congenital anomalies, but little is known about the effect of endometriosis on this risk.

Endometriosis is a chronic inflammatory condition in which endometrial-like tissue occurs outside the uterine lining. Existing research suggests that adverse pregnancy outcomes like pregnancy loss, pre-eclampsia, abruption, stillbirth, and preterm birth are more likely in women with endometriosis.

Putative mechanisms of anomaly in endometriosis

The underlying mechanisms of endometriosis could be linked to inflammation and oxidative stress, since these are associated with disrupted embryonic development. This could potentially contribute to congenital anomalies arising in the first trimester of pregnancy, but only genital anomalies have previously been reported to be more common in such cases.

The authors suggest that the potentially increased risk of anomalies may be due to epigenetic changes in DNA associated with chronic inflammation. Such changes could adversely influence the developmental program of cells and inhibit tissue-dependent gene activation. Another set of pathways might involve inflammation-associated placental abnormalities. However, the authors emphasize that these mechanisms remain theoretical and require further study.

Endometriosis is also linked to infertility in 30 %-60 % of cases, which pushes up the rate of conception following fertility treatment in this group. The role played by such treatments in the development of congenital anomalies in the offspring was another focus of the current study.

Endometriosis linked to a small increase in anomaly risk

The researchers performed a retrospective analysis of live births after 20 weeks' gestation in Ontario between October 2006 and March 2021, examining associations between endometriosis in the preconceptional period and live birth. The study included 1,460,564 births, of which 2.3 % (33,619 infants) were born to mothers with endometriosis.

Women with endometriosis had a higher age at delivery (33.4 years on average) compared to others, were less likely to be in the lowest income quintile, but were more likely to be subfertile and to conceive via fertility treatment.

Overall, 6.3 % (2,120 infants) born to patients with endometriosis had congenital anomalies, compared to 5.4 % (77,094 infants) born to mothers without endometriosis. Maternal endometriosis was associated with a 16 % higher risk of a congenital anomaly after adjusting for other risk factors. As an observational study, however, the findings demonstrate an association rather than proof of causation.

Apart from endometriosis, congenital anomalies were increased in the presence of chronic diabetes, chronic hypertension, higher comorbidity scores (more concomitant illnesses), substance and alcohol use, obesity, smoking, and parity.

Adjusting for race resulted in similar results, as did stratifying by method of diagnosis (medical versus surgical).

Endometriosis and specific anomalies

The risk of specific anomalies was between 13 % and 53 % higher in the offspring of women with endometriosis compared to others. The largest increases in relative risk among statistically significant anomalies were for unspecified cleft palate (by 52 %), hypospadias (by 47 %), and stenosis of the pulmonary arteries (by 41 %).

Cardiovascular and genital anomalies, and neoplasms and tumors, were increased by 23 % to 27 %, while undescended testes were found to be 36 % more common in the exposed infants.

Anomaly risk and fertility treatment in endometriosis

The authors estimated that about 11 % of the observed association was mediated by two assisted reproduction techniques: in vitro fertilization and intracytoplasmic injection. However, when broken down by anomaly type, IVF or intracytoplasmic injection mediated 75.6 % of the association with hemangiomas, 47 % of the risk of neoplasms and tumors, and 23.6 % of the risk of stenosis of the pulmonary arteries.

Further analysis in singleton pregnancies weakened some of these associations, particularly for neoplasms and tumors and stenosis of the pulmonary arteries, which were no longer statistically significant.

This suggests that most of the increased risk is attributable to endometriosis rather than fertility treatment. In addition, cleft palate anomalies and neoplasms and tumors were possibly explained in part by the higher rate of multifetal births, which are more common after fertility treatment.

Subfertility, and less invasive fertility treatments like ovulation induction and intrauterine insemination did not mediate the association of endometriosis with any anomaly. The authors suggest that women who conceived without invasive fertility treatments might have had less severe endometriosis.

Earlier research also suggests that fertility treatment success rates per cycle and overall vary with the stage of endometriosis. Thus, the stage of endometriosis could potentially be important in influencing the extent to which invasive fertility treatments mediate the risk of anomalies.

Future studies should include genetic and environmental data to identify the mechanisms linking endometriosis and congenital anomaly risk.

Study limitations

The study sample had an atypically low prevalence of endometriosis, perhaps because such patients are often subfertile and unlikely to form part of a delivery cohort. In addition, false positive endometriosis diagnoses introduce misclassification bias, making the association of endometriosis with anomalies appear weaker than it really is.

Misclassification of congenital defects is also likely, which would weaken the observed associations. Unmeasured confounding may have occurred because data not available in the administrative database used in this study, such as the stage of endometriosis and the number of treatment cycles for subfertility, were not included.

Finally, the study did not include pain management options like opioids or non-steroidal anti-inflammatory drugs (NSAIDs), often used for endometriosis, and their contribution to anomaly risk remains unknown.

Conclusions

The findings of this study suggest a small increase in congenital anomalies among offspring of women with endometriosis. Most of the observed association was accounted for by the condition itself, with a small portion estimated to be mediated by more invasive fertility treatments.

The authors emphasize that the absolute risk of anomaly remains low due to the low prevalence in the general infant population.

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