Fertility Treatment and Risk of Melanoma: A Certainty-Rated Systematic Review and Meta-Analysis of 3,733,499 Women.
Dimitrios Stylianakis, Cinzia Solinas, Fausto Petrelli et al.
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In 30 seconds
This certainty-rated systematic review and random-effects meta-analysis examined observational evidence on fertility treatment and incident melanoma in women. Twelve studies included 3,733,499 women, of whom 219,357 were exposed. Fertility treatment was associated with a modestly higher melanoma risk (HR 1.24, 95% CI 1.02-1.50), although certainty was very low and causality cannot be established. The association was stronger for drug-only ovulation induction (HR 1.39, 95% CI 1.01-1.92), while ART/IVF estimates were near-null. The authors conclude that current evidence does not justify changes in fertility-treatment practice.
Key findings
- Across fertility treatments, melanoma risk was modestly elevated (HR 1.24, 95% CI 1.02-1.50; I 2 = 0%).
- Drug-only ovulation induction was associated with HR 1.39 (95% CI 1.01-1.92); certainty was very low.
- For ART/IVF, the estimate was near-null (HR 1.09, 95% CI 0.81-1.48); certainty was low.
- SIR-based analyses were non-significant and highly heterogeneous (SIR 1.25, 95% CI 0.66-2.38; I 2 = 80%).
Why it matters
The pooled estimates suggest any excess melanoma risk is small, but uncertainty and incomplete adjustment for ultraviolet exposure and other risk factors limit interpretation. Distinguishing treatment pathways is relevant because estimates differed between drug-only ovulation induction and ART/IVF. The findings support careful interpretation of observational associations rather than assuming fertility treatment causes melanoma.
What to keep in mind
All included studies were observational, none had an overall low risk of bias, and ultraviolet-exposure adjustment was incomplete. Certainty was very low to low, and causality cannot be established.