Evaluating the equivalence of clomiphene citrate with and without metformin in ovulation induction in PCOS patients.
OBJECTIVE
To evaluate the benefit of Metformin added to Clomiphene Citrate in a primary ovulation induction protocol in PCOS patients.


METHODS
Prospective randomised controlled study.


METHODS
Tygerberg Academic Hospital, Stellenbosch University and the Institute of Reproductive Medicine at Vincent Pallotti Hospital, Cape Town.


METHODS
107 patients presenting with PCOS.


METHODS
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).


CONCLUSIONS
Although identical ovulation rates were observed in both arms equivalence could not be concluded with respect to the specified criteria.
Siebert
T I
TI
Reproductive Biology Unit, Department of Obstetrics and Gynaecology, Stellenbosch University and Tygerberg Academic Hospital, Tygerberg, South Africa. mms1@sun.ac.za
Kruger
T F
TF
Lombard
Carl
C
D002996:Clomiphene / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D010060:Ovulation / Q000187:drug effects; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*; D011446:Prospective Studies
D005300:Fertility Agents, Female; D002996:Clomiphene; D008687:Metformin