Women with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate therapy generally receive injected gonadotropins to induce ovulation. Consistent ovulation and pregnancy rates as high as 70 percent are reported, but this treatment is expensive and may lead to a multiple pregnancy or ovarian hyperstimulation. This preliminary trial evaluated an oral insulin-sensitizing agent, troglitazone, in 18 infertile women with clomiphene-resistant PCOS. Fifteen had primary infertility and three had secondary infertility present for 3 to 8 years. At least four cycles of clomiphene therapy had failed to produce ovulation. In the first treatment cycle, troglitazone was given in a daily dose of 400 mg during days 1 to 28 of the menstrual cycle, whether spontaneous or induced. The same regimen was used in the next four cycles, but, if the previous cycle had been anovulatory, clomiphene was added in a dose of 50 mg daily on days 3 through 7 after withdrawal bleeding was induced with medroxyprogesterone acetate. The clomiphene dose was increased in 50-mg increments up to 200 mg daily in subsequent cycles until ovulation occurred. Treatment then was repeated until the patient conceived or up to a maximum of seven cycles.Troglitazone was well tolerated by these patients. In the 18 who continued treatment for a total of 68 cycles, ovulation was documented in 65 percent of cycles and pregnancy in 10 percent of cycles. All but 3 of the 18 patients ovulated, and 39 percent of them became pregnant. Two women miscarried in the first trimester, but the other 5 delivered healthy infants at term. Troglitazone is an effective means of inducing ovulation in patients with PCOS who are resistant to therapy with clomiphene alone. The pregnancy rate of nearly 40 percent is promising, but in this respect combined troglitazone-clomiphene therapy does not seem to be definitively better than gonadotropin therapy.Hum Reprod 1999;14colon;2700ndash;2703
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