A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome.
OBJECTIVE
To review the effectiveness of metformin in restoring regular menstrual cycles and ovulation and achieving pregnancy in women with polycystic ovary syndrome (PCOS).


METHODS
Systematic review of pertinent studies identified using the bibliographic databases MEDLINE and EMBASE. References of selected articles identified were hand-searched for additional relevant citations.


METHODS
Women with PCOS undergoing treatment with metformin alone, metformin combined with other methods of ovulation induction such as clomiphene citrate (CC) or gonadotropin injections, or metformin combined with in vitro fertilization (IVF).


RESULTS
Thirty published studies were included in the overall review. Studies consisted of 12 randomized controlled trials, two cohort studies, and 16 uncontrolled descriptive studies. Due to a strong variability in the use of metformin according to study population, exposure, and outcome of interest, it was not possible to combine the data of the 12 randomized controlled trials to perform a meta-analysis. Limited data on predominately obese PCOS patients demonstrate that metformin alone improves both restoration of regular menses and spontaneous ovulation, but there are no data supporting an improvement in pregnancy rate. The addition of metformin to CC results in an improved ovulation and pregnancy rate in both unselected and CC-resistant PCOS women. There are insufficient data to make any conclusions on the effect of metformin on FSH ovulation induction or IVF.


CONCLUSIONS
The effectiveness and role of metformin in the treatment of PCOS anovulatory infertility in clinical practice is difficult to assess from currently available research. Further well-designed prospective, perhaps multicenter, randomized controlled trials with the primary end point of pregnancy or live-birth rate are required.
Costello
Michael F
MF
School of Women's and Children's Health, Division of Obstetrics and Gynaecology, University of New South Wales, Royal Hospital for Women, Sydney, New South Wales, Australia. mfcostello@unsw.edu.au
Eden
John A
JA
D002996:Clomiphene / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005307:Fertilization in Vitro; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy / Q000209:etiology; D016239:MEDLINE; D008687:Metformin / Q000627:therapeutic use*; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic
D002996:Clomiphene; D005640:Follicle Stimulating Hormone; D008687:Metformin