Evaluating the Role of Metformin in Reproductive Outcomes for Non-Obese Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is known to impact 10-12% of women of reproductive age, with a high infertility rate of 70 to 80% among those affected. Initial treatment typically involves following preconception guidelines, including lifestyle modifications, folic acid supplementation, and cessation of tobacco and alcohol use. Pharmacological treatments and surgical options have also been integrated into management strategies to enhance fertility, among which metformin, an insulin sensitizer and oral hypoglycemic agent is gathering attention.

The present study aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness of metformin in improving reproductive outcomes in non-obese, infertile women with PCOS. The researchers conducted a comprehensive search of PubMed (from inception to present), Ovid Medline, Ovid EMBASE, Scopus, and the Cochrane Library. They included RCTs that compared the efficiency of metformin with other treatments for infertility in non-obese women with PCOS. Our systematic review identified 21 eligible RCTs involving 2,638 patients with PCOS. 

The results included:

• Metformin use in non-obese women with PCOS was associated with a modest increase in clinical pregnancy rates compared to placebo (47.7% vs. 42.9%).
• Additionally, metformin was found to be comparable to clomiphene citrate (CC) regarding clinical pregnancy rates, with a tendency for a lower risk of multiple pregnancies.
• However, metformin was associated with a higher miscarriage rate. 
• Notably, combining metformin with CC significantly reduced miscarriage risk compared to metformin alone, showing no difference when compared to CC alone. 
• In contrast, the combination of metformin and CC resulted in a lower clinical pregnancy rate compared to letrozole and a lower risk of multiple pregnancies.

While this study suggests that metformin may be more effective than a placebo for certain pregnancy outcomes, further robust evidence from definitive trials is necessary before metformin can be recommended as a treatment option for non-obese infertile women with PCOS in line with 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.