Effects of Infertility Drug Exposure on the Risk of Borderline Ovarian Tumors: A Systematic Review and Meta-Analysis

Whether infertility drug exposure increases the risk of borderline ovarian tumors (BOTs) remains controversial. The present study was conducted with a comprehensive search for studies published from January 1990 to December 2021 in the online databases Cochrane Library, PubMed, Web of Science and EMBASE. We considered the first diagnosis of a BOT as the primary outcome. The odds ratio (OR) was calculated with corresponding 95% confidence intervals (CIs) for the risk of BOTs in patients who were treated with infertility drugs. Ten studies, a total of 2,779,511 women, qualified for inclusion in this meta-analysis. The pooled OR of 1.56 (95% CI: 1.09–2.22) revealed a significant positive association between infertility drugs and an increased risk for BOTs, but for specific drugs, only CC plus Gn had statistical significance. No publication bias was detected using the Egger and Begg tests (p > 0.05). A significant difference in BOT incidence was observed among infertile women and nulliparous women who were treated with or without infertility drugs. In conclusion, the use of infertility drugs may increase the risk of BOTs, but a dose-dependent relationship was not observed between the number of assisted reproduction technology cycles and the risk of BOTs, and infertile women who successfully became pregnant might have a reduced risk. Registration: PROSPERO, CRD42022330775.