Costello, M. F., & Eden, J. A. (2003). A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome. Fertility and Sterility, 79(1), 1-13. https://doi.org/10.1016/s0015-0282(02)04554-5
Costello MF, Eden JA. A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome. Fertil Steril. 2003;79(1):1-13. doi:10.1016/s0015-0282(02)04554-5
Costello, Michael F., and John A. Eden. "A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome." Fertility and Sterility, vol. 79, no. 1, 2003, pp. 1-13.
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Metformin improved ovulation in mostly obese women with PCOS
A 2003 review of 30 studies found that metformin improved ovulation in mostly obese women with PCOS, also named PMOS (Polyendocrine Metabolic Ovarian Syndrome). In four placebo-controlled trials, 56 out of 100 women ovulated on metformin and 35 out of 100 on placebo. Adding metformin to clomiphene improved ovulation and pregnancy rates in women with PCOS.
Key Findings
Nine uncontrolled studies of metformin in women with oligomenorrhea (infrequent periods) or amenorrhea (absent periods) reported regular menses in approximately 62% of women after treatment.
In four placebo-controlled trials, 62 of 111 women (56%) ovulated on metformin alone, compared with 34 of 98 (35%) on placebo (P = .002; RR 1.5, 95% CI 1.2 to 2.0).
The one trial of metformin alone that reported pregnancy found that 4 of 23 women conceived on metformin and 1 of 19 on placebo, a difference that was not significant.
In a trial of 90 obese women with PCOS, ovulation was 80% with metformin plus clomiphene citrate (CC) against 65% with CC alone, and pregnancy per patient was 29% against 8%.
In one randomized trial in women resistant to CC, metformin plus CC gave ovulation and pregnancy rates of 75% and 55%, compared with 27% and 7% for placebo plus CC.
Interpretation
This review looked at 30 published studies, including 12 randomized trials, on metformin and PCOS. The authors note the trials used different doses and measured different outcomes, so they could not combine them into one analysis. The findings support larger trials of metformin that track pregnancy and birth rates directly.
RRM Context
Restorative reproductive medicine looks for the cause when ovulation stops in PCOS. The review names insulin resistance as a prominent feature of the syndrome. Evaluation before treatment includes both partners. Only two of five studies of metformin with clomiphene in unselected women ruled out pelvic problems or male infertility.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To review the effectiveness of metformin in restoring regular menstrual cycles and ovulation and achieving pregnancy in women with polycystic ovary syndrome (PCOS).
Design
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.
Patients
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.
