Melanoma risk following fertility treatment in infertile women: a systematic review and meta-analysis

Infertility treatments, particularly ovulation-inducing medications, have raised concerns regarding their potential association with melanoma development. Although theoretical mechanisms suggest that hormonal stimulation during these therapies could influence melanoma risk, current evidence remains inconclusive. This meta-analysis aims to determine whether women undergoing fertility treatments have a higher incidence of melanoma compared with untreated infertile women. We conducted a systematic review and meta-analysis in PubMed, Web of Science, Cochrane Library, and Scopus. A random-effects model with 95% confidence intervals (CIs) was used to estimate the pooled hazard ratios and risk ratios. Statistical analyses were performed using R software (version 4.4.3). A total of eight cohort studies were included, reporting 11 061 cases of melanoma, with follow-up periods ranging from 8.8 to 21 years. The pooled hazard ratio analysis demonstrated a statistically significant modest increase in melanoma risk among women exposed to any fertility treatment compared with untreated controls (hazard ratio: 1.16; 95% CI: 1.04-1.29). Clomiphene use showed a nonsignificant trend toward increased risk (hazard ratio: 1.75; 95% CI: 0.93-3.33). Similarly, no significant associations were found for assisted reproductive technology (hazard ratio: 1.10; 95% CI: 0.81-1.36) or gonadotropins (hazard ratio: 1.03; 95% CI: 0.49-2.16). The risk ratio analysis across all fertility treatments also did not demonstrate statistical significance (risk ratio: 1.45; 95% CI: 0.76-2.78). This meta-analysis suggests a modest, statistically significant increase in melanoma risk among infertile women treated with fertility-inducing medications overall. Future large‑scale, prospective cohort studies are needed to clarify the association between fertility treatments and melanoma development.