How are COMT and fertility related?

The relationship between COMT (catechol-O-methyltransferase) and fertility is an area with limited and conflicting evidence. COMT is a key enzyme in the breakdown of estrogens and catecholamines. Certain variants (e.g., rs4680, Val158Met) can alter enzyme activity: the Met variant leads to slower estrogen inactivation, which could theoretically influence hormone levels and modulate fertility. Some studies suggest links to endometriosis risk or recurrent miscarriage, but effect sizes are small, population-dependent, and not robustly replicated. Consumer DNA tests reporting COMT variants do not provide clinically actionable information for fertility. The evidence level is 'unclear', as most associations stem from mechanistic or small observational studies. Individual fertility counseling should rely on comprehensive hormonal and clinical assessments, not single gene variants.