Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence?

Abstract

The potential reproductive benefits of metformin, a drug endowed with the capacity to ameliorate insulin resistance in polycystic ovary syndrome (PCOS), has garnered much interest over the past 2 decades. In this review, randomized-controlled trials (RCT) and meta-analyses of RCT comparing metformin are critically appraised and summarized. PubMed and CENTRAL databases were consulted. Evidence is insufficient to favour the use of metformin or metformin plus clomiphene citrate instead of clomiphene citrate for ovulation induction in women with newly diagnosed PCOS. Evidence is also insufficient to recommend metformin as a primary treatment for non-obese women with PCOS. Metformin plus clomiphene citrate should be considered as an effective option in clomiphene citrate-resistant PCOS. In women with PCOS undergoing gonadotrophin ovulation induction, metformin significantly increased pregnancy and live birth rates (P< 0.0001 and P = 0.020, respectively) with reduced risk of cancelled cycles. A beneficial effect of metformin co-treatment in increasing clinical pregnancy rates and reducing the risk of OHSS in PCOS patients undergoing assisted reproduction techniques has been shown. No evidence was found of reduced risk of spontaneous abortion or increased risk of major anomalies in women with PCOS taking metformin during the first trimester.

Insulin resistance in patients with recurrent pregnancy loss is associated with lymphocyte population aberration

“…Metformin therapy in pregnant women with PCOS has been associated with a significant reduction in the rate of early pregnancy loss [Al-Biate 2015] and improves the pregnancy rate in in vitro fertilization repeaters without PCOS [Jinno et al 2010]. The beneficial effects of metformin therapy could increase the clinical pregnancy rates and reduce the IR in women with PCOS [Abu Hashim 2016]. Collectively, our study indicated that prescription of metformin prior to the pregnancy could not only increase insulin sensitivity and decrease the HOMA-IR score but also improve lymphocyte population aberration, which indicated that IR, cellular Figure 1.…”

Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis

“…However, the evidence was of low quality and findings should be interpreted with cautions especially in CCR-PCOS patients. In addition, there was either no difference or insufficient evidence for the comparisons of metformin with CC, placebo and other therapies in PCOS patients 43–45 .…”

Effects of Metformin on Symptoms of Polycystic Ovarian Syndrome Among Women of Reproductive Age

“…As per the literature, the effectiveness of metformin has emerged as a subject of great interest in the 21st century. Hashim et al [ 19 ] reviewed the CENTRAL and PubMed database for evaluating the reproductive benefits of this drug. The assessment of presenting randomized controlled trials (RCTs) and reports of meta-analysis indicated that the empirical evidence is not sufficient enough to indicate any association between the ability to conceive and the administration of metformin among patients of PCOS [ 19 - 20 ].…”