Incremental clomiphene therapy: a new method for treating persistent anovulation

Thirty anovulatory patients, previously unresponsive to clomiphene citrate in standard dosage, were treated with a new incremental method of clomiphene therapy. Clomiphene was given continuously with dosage increments every 5 days, up to a maximum dose of 3750 mg, and ovarian response was monitored with urinary estrogen estimation and with ultrasound. Twenty-one patients (70%) ovulated on this regimen and 8 (27%) conceived; 6 patients who ovulated but did not conceive had other infertility factors. Clomiphene response was associated with a progressive rise in follicle-stimulating hormone, luteinizing hormone, and estrogen excretion; these parameters were unchanged in nonresponders. Side effects of treatment were minimal and only 1 case of hyperstimulation occurred. Preliminary testing with estrogen-amplified gonadotropin-releasing hormone did not differentiate responders from nonresponders. Incremental clomiphene treatment appears to be a less complicated alternative for patients who would otherwise require exogenous gonadotropin therapy.