Robust randomized trials demonstrate that, compared with clomiphene citrate, letrozole yields higher ovulation, pregnancy, and live-birth rates—particularly in anovulatory polycystic ovary syndrome—while at the same time reducing the incidence of multiple gestation and avoiding the anti-estrogenic endometrial effects seen with selective estrogen-receptor modulators. This evidence concerns the gene ESR1 and polycystic ovary syndrome.