Clomiphene for anovulatory infertility.

Evidence • Systematic review of RCTs of antiestrogens in PCOS1: -In 3 RCTs (N = 133) that examined clomiphene (50 to 250 mg/d, 1 to 5 cycles) versus placebo, the pregnancy rate was higher with clomiphene (20% vs 3%); the number needed to treat (NNT) was 6. Live births and miscarriages were not reported. -Limitations: small sample, variable dosing and number of cycles, high dropout rate, poor adverse event reporting. • Systematic review of insulin-sensitizing drugs in PCOS2: -In a subgroup analysis of clomiphene versus metformin, for those with BMI ≥ 30 kg/m2 (2 RCTs, N = 500), clomiphene was superior to metformin for pregnancy (NNT = 7) and live birth (NNT = 5) rates; for those with BMI < 30 kg/m2 (3 RCTs, N = 349), metformin was superior to clomiphene for pregnancy (NNT = 8); the effect on live births was unclear. -There was substantial heterogeneity in trials’ reporting of pregnancy and live births. -Adding metformin to clomiphene improved pregnancy rates (NNT = 13; 11 RCTs) with no effect on birth rates.