In 1998, physician John E. Nestler and colleagues published “Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome,” hereafter “Metformin,” in the New England Journal of Medicine. Polycystic ovary syndrome, or PCOS, is an endocrine, or hormone-related, disorder that affects one in ten women of reproductive age, is characterized by symptoms such as an irregular menstrual cycle and high androgen levels, and can lead to infertility, or the inability to become pregnant. In the article, the authors report on the results of a randomized control trial they conducted in which they administered the insulin-lowering medication metformin to a group of thirty-five obese infertile female patients with PCOS, and compared them to twenty-six women receiving a placebo to see if metformin could improve spontaneous or drug-induced ovulation rates. They found that it could. As of 2026, “Metformin” is one of the most cited articles supporting metformin’s usage as a second-line treatment for infertility in women with PCOS.