Clomiphene Resistant PCOS: Treatment Options

Clomiphene Citrate (Clomid, Serophene) was introduced into clinical medicine for the treatment of anovulation in the 1960’s. Its introduction represented a major breakthrough in the medical management for ovulation induction. Prior to Clomiphene, patients with PCOS who were anovulatory had few options besides weight loss and surgical wedge resection of the ovaries. While wedge resection was successful, it required a major surgical procedure and was associated with a high incidence of tubal scarring, both of which limited its widespread application. Sufficient weight loss has proven difficult for even the most motivated patients. Early studies with Clomiphene suggested that up to 80% of patients could respond favorably (by successfully ovulating) and approximately half of those who ovulated achieved pregnancy. Of those who ovulated, 50% did so by taking 50 mg (one tablet) a day for 5 days early in the cycle. Another 20% ovulated at 100 mg/day and about 10% ovulated by taking 150 mg/day. The remaining 20% ovulated at either 200 or 250 mg/day. The Physician’s Desk Reference (PDR) does not recommend increasing the dose above 100mg/day, however; many physicians consider either 150 or 200 mg/day to be the maximal dose. The question then becomes: What can be done for the patient who fails to ovulate at maximal doses of clomiphene? A corollary to this question is: Does anything predict which patients will respond to clomiphene?