Metformin in the Treatment of Infertility in PCOS: An Alternative Perspective Original paper

What was reviewed?

This editorial provides an alternative perspective on the use of metformin in treating female infertility associated with polycystic ovary syndrome (PCOS), challenging the conservative stance of the 2007 ESHRE/ASRM consensus. The review critically evaluates the evidence base behind current recommendations, which suggest restricting metformin use to women with glucose intolerance. Nestler discusses pharmacological distinctions between metformin and clomiphene, evaluates the outcomes of landmark randomized controlled trials and meta-analyses, and considers patient-specific factors such as the urgency of conception and risk of multiparity. The editorial also addresses the potential benefits of metformin alone, combination therapy with clomiphene, and pre-treatment strategies, highlighting the need for individualized approaches to ovulation induction in PCOS patients.

Who was reviewed?

This editorial reviews data from women with PCOS, specifically those experiencing anovulatory infertility. The populations considered in the referenced trials and meta-analyses include both obese and non-obese women, with varying degrees of insulin resistance and diverse reproductive goals. The review pays particular attention to subgroups, women seeking immediate pregnancy (often seen by reproductive endocrinologists) versus those with a longer fertility timeline (frequently managed by gynecologists or medical endocrinologists), and distinguishes between those with and without glucose intolerance. The editorial also references studies with large and well-defined cohorts, such as the 1,639 subjects in the cited meta-analysis, and incorporates clinical experience from academic centers.

Most important findings

The key findings revolve around the nuanced role of metformin in PCOS-related infertility. The editorial notes that while clomiphene is more effective for rapid ovulation induction, metformin is associated with improved ovulation rates over longer treatment periods, especially in women not seeking immediate conception. Meta-analyses demonstrate that metformin enhances ovulation in a significant proportion of women with PCOS (up to 69% improvement in menstrual cyclicity, with 88% of responders achieving normal cycles). The addition of metformin to clomiphene increases cumulative ovulation and pregnancy rates, though the impact on live birth rates remains statistically inconclusive, possibly due to insufficient study power. Notably, metformin appears to reduce the risk of multiparity compared to clomiphene, an important consideration in clinical decision-making. The editorial also explores the benefit of pre-treatment with metformin, particularly in obese women, as a means to improve weight loss, ovulation induction success, and potentially reduce pregnancy complications.

Key implications

This review underscores the importance of individualized therapy in managing PCOS-related infertility. Metformin should not be restricted solely to women with glucose intolerance; rather, its use should be tailored according to patient fertility timelines and risk profiles. For women desiring rapid conception, clomiphene remains first-line, but adding metformin can boost ovulation rates. For those with a longer horizon, metformin (with lifestyle modification) offers a lower-risk approach that may restore ovulatory cycles and reduce the likelihood of multiple gestations. The editorial highlights the need for further research on metformin’s long-term reproductive outcomes and its role in combination or sequential therapy. Clinicians are encouraged to consider patient preferences, metabolic status, and the evolving evidence base to optimize fertility treatments in PCOS.