Metformin enhances Reproductive Outcomes for Non-Obese, Infertile Women with PCOS

Statistics suggest that polycystic ovary syndrome (PCOS) affects 10–12% of women of reproductive age while between 70 and 80% of women with PCOS have infertility The first line of treatment consists of advice to adhere to preconception guidelines, which include folic acid therapy, lifestyle modifications, and quitting alcohol and tobacco use. In order to increase fertility, treatment plans have included both surgical and pharmaceutical management. Among these, metformin, an insulin sensitiser and oral hypoglycemic medication, is becoming more and more popular.

The present study aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to examine the role of metformin in enhancing the reproduction outcomes for non-obese, infertile women with polycystic ovary syndrome.

The study included 21 RCTs in all, including 2,638 patients that compared the effectiveness of metformin with other modalities in treating infertility in non-obese women with PCOS were included. The eligible outcomes for inclusion were pregnancy rate, miscarriage rate, live birth rate, ovarian hyperstimulation (OHSS) and multiple pregnancy.

The findings of the study revealed:

• According to the meta-analysis, metformin was linked to a somewhat higher rate of clinical pregnancies than a placebo (47.7% vs. 42.9%).
• With a possible decreased risk of multiple pregnancies, metformin demonstrated similar efficacy to clomiphene citrate (CC) for pregnancy rates.
• Nevertheless, a greater prevalence of miscarriages was associated with metformin.
• When compared to metformin alone, the risk of miscarriage was considerably decreased when metformin was added to CC medication; however, no difference was observed when CC was used as a monotherapy. 
• The combination of metformin and CC led to a lower clinical pregnancy rate and a lower incidence of multiple pregnancies when compared to letrozole.

While the findings suggest that metformin may offer some benefits over placebo for certain pregnancy outcomes, further well-designed, adequately powered trials are necessary to establish its role in treating non-obese infertile women with PCOS according to current guidelines.

Source: Magzoub R, Kheirelseid EAH, Perks C, Lewis S. Does metformin improve reproduction outcomes for non-obese, infertile women with polycystic ovary syndrome? Meta-analysis and systematic review. Eur J Obstet Gynecol Reprod Biol. 2022 Apr;271:38-62. doi: 10.1016/j.ejogrb.2022.01.025. Epub 2022 Feb 1. PMID: 35149444.