The environmental risk factors associated with ectopic pregnancy: An umbrella review

Ectopic pregnancy(EP) is the implantation of a fertilized ovum outside of the uterine cavity. The incidence of EP has steadily increased around the world. The present umbrella review evaluated risk factors prior to conception associated with EP based on meta-analyses and systematic reviews.

We searched PubMed, Scopus, and Web of Science until June 25, 2021. All meta-analyses that had focused on assessing the risk factors associated with EP were included. We calculated summary effect estimates, 95% CI, heterogeneity I², 95% prediction interval, small-study effects, excess significance biases, and sensitive analysis. The quality of the meta-analyses was evaluated with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2).

Two risk factors including chlamydia trachomatis (OR: 3.03) and smoking (OR: 1·77) were graded as suggestive evidence (class III). IUD with pregnant control (OR: 10.63) and endometriosis for case-control studies (OR: 2·66) and tubal ligation with pregnant control (OR: 9.3) were graded as risk factors with weak evidence (class IV). Tubal ligation with non-pregnant control was a protective factor (class IV). IUD with non-pregnant control and endometriosis for cohort studies were not as risk factors for EP.

Two risk factors including chlamydia trachomatis and smoking were graded as suggestive evidence. IUD with pregnant control and endometriosis for case-control studies and tubal ligation with pregnant control were graded as risk factors with weak evidence. Strong evidence for risk factors of EP was not achieved, indicating the degree of uncertainty and bias, which bring an emergency to conduct further no-bias studies.

PROSPERO (CRD42021281632).