Clomiphene citrate alone, in combination with metformin or in combination with pioglitazone as first line therapy in induction of ovulation in infertile women with polycystic ovary syndrome, a randomized controlled trial

Study objective: To compare the efficacy of clomiphene citrate (CC) alone, combined CC and metformin and combined CC and pioglitazone as first line therapy for induction of ovulation and achievement of pregnancy in overweight and obese infertile women due to polycystic ovary syndrome (PCOS).Design: A randomized controlled trial.Setting: The infertility clinic of Ain Shams University maternity hospital.Materials and methods: 106 overweight and obese women complaining of infertility due to PCOS were randomly assigned to receive ovulation induction using CC, 100 mg daily for 5 days beginning on the third day of spontaneous or induced menses, either alone (Group 1) in combination with metformin, 850 mg twice daily, (Group 2) or in combination with pioglitazone, 30 mg daily, (Group 3). Folliculometry was started from cycle day 9 and repeated every 2 days. hCG (10000 IU) was given intramuscular when at least one follicle ⩾18 mm was formed. Serum β-hCG was measured 16 days after hCG injection to diagnose pregnancy.Main outcome measure: Biochemical pregnancy rate.Results: There were no statistically significant differences between the three study groups regarding the biochemical pregnancy rates (7.4% (2/27), 11.1% (3/27) and 18.5% (5/27) for groups 1, 2 and 3, respectively) and the number of women who succeeded to have mature follicles (74.1% (20/27), 74.1% (20/27) and 81.5% (22/27) for groups 1, 2 and 3, respectively).Conclusion: There is no potential benefit from adding pioglitazone or metformin to CC while inducing ovulation in overweight and obese women complaining of infertility due to PCOS. Further larger extended trials are needed to assess using insulin sensitizers for longer duration which could give a better chance to evaluate the cumulative effect of these drugs