The most appropriate treatment is a selective estrogen receptor modulator (SERM) such as clomiphene citrate. SERMs are the established first-line treatment for ovulation induction in anovulatory patients with infertility from polycystic ovary syndrome (PCOS). Typically, therapy is started after menses and is given orally for 5 days. Common side effects include vasomotor symptoms and mood changes. Escalating doses of clomiphene are typically prescribed if a patient does not ovulate on lower doses. More recently, evidence suggests the effectiveness and possible superiority of aromatase inhibitor therapy (such as with letrozole) in women with PCOS for ovulation induction. However, this therapy is not currently FDA approved for this indication.

A small subset of patients with PCOS may require in vitro fertilization, but this therapy is typically explored only after several failed cycles of ovulation induction with clomiphene citrate.

In patients with clomiphene resistance, gonadotropin therapy would be an appropriate next step; however, caution is warranted because higher-order multiple gestation may result.

A 2012 Cochrane review of the effect of insulin-sensitizing drugs in women with infertility and PCOS included 44 trials, the majority of which involved metformin. Rates of pregnancy were improved with metformin compared with placebo and metformin plus clomiphene compared with clomiphene alone, but metformin did not change rates of live births compared with placebo or with clomiphene compared to clomiphene alone.