Association between ovarian tumors and exposure to assisted reproductive technologies and ovarian stimulation: a systematic review and meta-analysis.

Introduction:  The question of whether assisted reproductive technologies (ART) and ovulation induction are related to a higher incidence of ovarian tumors (OTs) is still controversial in the literature.

Methods: We performed a comprehensive search of PubMed, Embase, and Web of Science databases for case-control and cohort studies that investigated ART and ovulation induction exposure as risk factors for OT in infertile women. Odds ratios (OR) with 95% confidence intervals (CI) were employed for all endpoints.

Results: A total of nine case-control and twelve cohort studies were included, encompassing 439,477 women. ART was not associated with a higher risk of OTs (OR 1.05; 95% CI 0.86-1.29; p = 0.64; I² = 36%), nor when considering only borderline OTs (OR 1.13; 95% CI 0.84-1.51; p = 0.42; I² = 31%). In a subgroup analysis by study type, the risk difference of OTs remained non-significant for case-control (OR 1.12; 95% CI 0.70-1.78; p = 0.65; I² = 60%) and cohort studies (OR 1.05; 95% CI 0.87-1.27; p = 0.60; I² = 1%). For borderline OTs, the difference between groups was also non-significant for case-control studies (OR 1.44; 95% CI 0.73-2.87; p = 0.30; I² = 40%) and cohort studies (OR 1.00; 95% CI 0.75-1.34; p = 0.99; I² = 24%).

Conclusion: In this systematic review and meta-analysis, ART exposure in infertile women was not associated with a higher risk of OTs in general or borderline tumors, even when accounting for study type differences.