Combined Pioglitazone and Clomiphene Citrate Versus Metformin and Clomiphene Citrate in Clomiphene Citrate Resistant Women with PCOS

Background: Clomiphene citrate (CC) is the first line therapy for induction of ovulation in PCOS. Since hyperin-sulinaemia plays a pivotal pathophysiological role in PCOS, it is rational to implicate the use of insulin sensitizers in CC resistant PCOS women. Objective: To investigate and compare the efficacy of addition of two insulin sensitizers, pioglitazone and metformin, to CC in patients with PCOS who are resistant to clomiphene citrate. Setting: The study was conducted at the infertility outpa-tient clinic in Kasr Al-Aini Teaching Hospital, Cairo University. Patients and Methods: We conducted a randomized, clinical trial on sixty women with PCOS who were CC resis-tant. Patients underwent clinical and biochemical evaluation at baseline. Patients were then randomized to either oral treatment with metformin (1000mg twice daily) or pioglitazone 30mg/day. All patients received CC 100mg starting from day 3 of a spontaneous or induced cycle and for 5 days. The combined insulin sensitizer-clomiphene citrate regimen was used for 3 successive cycles. The initial evaluation was repeated at the end of the study period. Primary outcome measures included ovulation rate, mean no. of dominant follicles/ovulatory cycle, serum progesterone and pregnancy rate. Secondary outcome measures included the effect of therapy on other clinical and laboratory parameters. Results: The study involved sixty CC-resistant PCOS cases; thirty in each group. The patients were comparable at baseline. Subjects in the pioglitazone (+CC) arm had a significant decrease in WHR while the BMI significantly increased. Serum LH, free testosterone, fasting insulin and QUICKI significantly decreased on pioglitazone therapy. Subjects in the metformin (+CC) arm exhibited significant decreases in BMI, WHR, free testosterone, fasting insulin and QUICKI index. No significant difference was found in the ovulation rate between the two groups (p=0.56); 57/82 cycles (69.5%) in the pioglitazone (+CC) group versus 55/84 cycles (65.5%) in the metformin (+CC) group. Similarly there were no sig-nificant differences between the two groups regarding the mean number of dominant follicles (p=0.67) and serum progesterone (p=0.8). Conception rate/cycle was not significantly different between the two groups; 17.07% in the pioglitazone (+cc) group versus 15.48% in the metformin (+cc) group (0.78). Conclusion: Pioglitazone is as effective as and not superior to metformin in terms of successful ovulation induction and pregnancy achievement.