Metformin Administration and Laparoscopic Ovarian Drilling Improve Ovarian Response to Clomiphene Citrate (CC) in Oligo-anovulatory CC-resistant Women With Polycystic Ovary Syndrome

Clomiphene citrate (CC) is, at present, viewed as the agent of first choice for treating subfertile women with polycystic ovary syndrome (PCOS), but some are resistant to this medication. Laparoscopic ovarian drilling (LOD) has been proposed as a means of inducing ovulation in CC-resistant women with PCOS, and good reproductive outcomes have been reported. Metformin also appears to promote ovulation in CC-resistant women. This prospective study compared the efficacy of CC treatment in eight overweight women 22 to 34 years of age with PCOS, oligoamenorrhea, and primary infertility who remained anovulatory after receiving metformin (group A) and 20 others (group B) who had undergone LOD. The dose of metformin was 850 mg twice daily. Group B patients received placebo tablets after LOD. CC was given in a dose of 150 mg daily for 5 days, from days 3 to 7 of progesterone-induced uterine bleeding. The study continued for 6 months. Participants were advised to have intercourse four times every 2 days once a follicle 18 mm or more in diameter was evident sonographically. Women in groups A and B were clinically comparable and were studied over 36 and 74 cycles, respectively. There were no group differences in rates of ovulation, pregnancy, or live births at the end of the study. Nearly one third of women in each group ovulated, and approximately 17% became pregnant. Abortions were slightly more frequent in group B women, but live birth rates were similar: 67% in group A and 58% in group B. Treatment was, in general, well tolerated, and women in the two treatment groups had similar rates of adverse events. No adverse effects from CC were noted in either group. CC treatment is able to induce ovulation in overweight, infertile, CC-resistant women with PCOS who remain anovulatory after metformin therapy or LOD. Both these treatments apparently are able to make the ovaries more responsive to CC.