Ovarian stimulating drug use and risk of ovarian tumor in infertile women: a meta-analysis

To explore whether ovarian-stimulating drugs increase the risk of ovarian cancer in infertile women. This meta-analysis involved searching PubMed, Cochrane Library, Web of Science, and Embase. The methodological quality of observational studies was assessed using the modified Newcastle-Ottawa Scale. Data were summarized as OR with 95% CIs. The primary objective was to assess the effect of ovarian-stimulating drugs on ovarian tumors and the secondary objective was to assess this effect in different sub-groups. Forty studies were eligible for this meta-analysis. Overall, compared with unexposed infertile women and unexposed general population, ovarian-stimulating drugs increased the risk of invasive ovarian cancer (OR 1.23, 95% CI 1.14 to 1.32, p =.001) and borderline cancer (OR = 1.32, 95% CI 1.19 to 1.47, p < .001) in women receiving any fertility drugs. Our sub-group analysis showed a higher risk of both invasive and borderline ovarian cancer in infertile women using ovarian-stimulating drugs compared to infertile women with no exposure and the general unexposed population. An increased risk of ovarian cancer was observed in nulliparous women, but not in parous women. In addition, a cumulative clomiphene dose of <900 mg and a number of gonadotropin cycles ≥6 were factors that increased the risk of invasive ovarian cancer. Combined treatment with clomiphene and gonadotropin was associated with an increased risk of borderline cancer. Risk analyses further revealed that prolonged use of oral contraceptives (>60 months) and a family history of ovarian cancer significantly increased the odds of developing ovarian cancer among women treated with ovarian-stimulating drugs. Our study showed that ovarian-stimulating drugs increased the risk of ovarian tumors.