CLINICAL QUESTION

Are fertility treatments associated with an increased incidence in female-specific malignancies compared with no treatment?

BOTTOM LINE

This umbrella meta-analysis of observational studies compared the incidence of female-specific cancers in patients who underwent fertility treatments with the incidence among control patients in the general population and identified positive associations for ovarian and borderline ovarian tumors. In vitro fertilization (IVF) as an infertility strategy had a significant association; however, evidence was relatively weak, and it is not clear whether the original studies or meta-analyses accounted for differences in cancer risks due to infertility alone. The most we can conclude is that the fertility treatments, especially IVF, clomiphene, and human menopausal gonadotropin, may be associated with an increased risk of ovarian cancer and borderline ovarian tumors. The authors found no associations with breast cancer. (Level of Evidence = 2a−)

SYNOPSIS

The authors conducted an umbrella meta-analysis of observational meta-analyses (n = 11 with 188 original studies and millions of participants) to study the associations between the incidence of female-specific cancers in patients who underwent fertility treatments compared with the general population control patients with no fertility treatment. The cancers studied were breast, ovarian, endometrial, cervical, and borderline ovarian tumors. The authors conducted analyses to account for heterogeneity and excess influence of small studies. They were also careful about grading the strength of evidence for associations. They did not account for differences in baseline cancer risks between infertile and general populations. The authors found that the estimated summary effect provided weak evidence of associations at the P = .05 level for ovarian cancer (odds ratio [OR] = 1.21; 95% CI, 1.00–1.45) and borderline ovarian tumors (OR = 1.87; 95% CI, 1.18–2.97). The incidence of ovarian cancer with IVF was statistically significant (OR = 1.65; 95% CI, 1.07–2.54). The drugs clomiphene and human menopausal gonadotropin (together and separately) had statistically significant associations.