Evaluating the equivalence of clomiphene citrate with and without metformin in ovulation induction in PCOS patients
Objective: To evaluate the benefit of Metfomin added to Clomiphene Citrate in a primary ovulation induction protocol in PCOS patients Design: Prospective randomised controlled study Setting: Tygerberg Academic Hospital, Stellenbosch University and the Institute of Reproductive Medicine at Vincent Pallotti Hospital, Cape Town Patients: 107 patients presenting with PCOS Study: Group A was pre-treated with metformin 850 mg twice a day for at least 6 weeks before clomiphene was added and the metformin was used throughout the study period. Group B received clomiphene without pre-treatment with metformin. In both groups clomiphene was given at a starting dose of 50 mg day 4-8 and increase with increments of 50 mg to a maximum of 150 mg if no response was achieved. Results: The ovulation rate achieved in women in the M+C/C arm was 34/52 (65.4%) compared to 36/55 (65.5%) in the C/C arm. The treatment effect ((M+C/C) - C/C) is 0% with 95% confidence interval of -18.1% to 18%. The per protocol ovulation results were 34/42 (81%) in the M+C/C arm compared to 36/48 (75%) in the C/C arm. The ovulation rate difference was 6% with 95% confidence interval -11% to 22%. In a comparison of successful ovulating versus non-ovulating women from the trial the following were significant baseline determinants: lower median weight in the ovulating group (77 kg versus 86 kg, p∈=∈.021), lower median bmi (29.0 versus 32.9, p∈=∈.009), lower median DHEAS at baseline (4.6 compared to 7.0, p∈=∈.049), lower median 17OH-progesterone (2.2 versus 4.6, p∈=∈.027) and higher baseline median SHBG ( 37.8 compared to 28.5, p∈=∈.036). Conclusion: Although identical ovulation rates were observed in both arms equivalence could not be concluded with respect to the specified criteria. © 2009 Springer Science+Business Media, LLC.