Metformin Improves Pregnancy and Live-Birth Rates in Women with Polycystic Ovary Syndrome (PCOS): A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial

• Published in: The journal of clinical endocrinology and metabolism Vol. 97; no. 5; pp. 1492 - 1500
• Main Authors: Morin-Papunen, Laure, Rantala, Anni S., Unkila-Kallio, Leila, Tiitinen, Aila, Hippeläinen, Maritta, Perheentupa, Antti, Tinkanen, Helena, Bloigu, Risto, Puukka, Katri, Ruokonen, Aimo, Tapanainen, Juha S.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.05.2012; Copyright by The Endocrine Society
• Subjects: Abortion, Spontaneous - prevention & control; Adult; Biological and medical sciences; Birth Rate; Double-Blind Method; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Infertility, Female - drug therapy; Infertility, Female - etiology; Medical sciences; Metformin - therapeutic use; Polycystic Ovary Syndrome - complications; Pregnancy; Pregnancy Rate; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Human; Obesity; Nutrition; Rate; Nutrition disorder; Female sterility; Metabolic diseases; Polycystic ovary; Birth; Female genital diseases; Pregnancy; Ovarian diseases; Improvement; Hypoglycemic agent; Biguanides; Cyst; Double blind study; Female; Benign neoplasm; Metformin; Woman; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2011-3061

The role of metformin in the treatment of infertility in women with polycystic ovary syndrome (PCOS) is still controversial.Objective and Outcomes:We investigated whether metformin decreases the early miscarriage rate and improves the pregnancy rates (PR) and live-birth rates (LBR) in PCOS.Methods:This was a multicenter, randomized (1:1), double-blind, placebo-controlled study. Three hundred twenty women with PCOS and anovulatory infertility were randomized to metformin (n = 160, Diformin; obese women, 1000 mg two times daily; nonobese subjects, 500 mg + 1000 mg daily) or identical doses of placebo (n = 160). After 3 months' treatment, another appropriate infertility treatment was combined if necessary. If pregnancy occurred, metformin/placebo was continued up to the 12th week.Results:Miscarriage rates were low and similar in the two groups (metformin 15.2% vs. placebo 17.9%, P = 0.8). Intent-to-treat analysis showed that metformin significantly improved PR and LBR (vs. placebo) in the whole study population (PR: 53.6 vs. 40.4%, P = 0.006; LBR: 41.9 vs. 28.8%, P = 0.014) and PR in obese women (49.0 vs. 31.4%, P = 0.04), and there was a similar trend in nonobese (PR: 58.6 vs. 47.6%, P = 0.09; LBR: 46.7 vs. 34.5%, P = 0.09) and in obese women with regard to LBR (35.7 vs. 21.9%, P = 0.07). Cox regression analysis showed that metformin plus standard infertility treatment increased the chance of pregnancy 1.6 times (hazard rate 1.6, 95% confidence interval 1.13–2.27).Conclusion:Obese women especially seem to benefit from 3 months' pretreatment with metformin and its combination thereafter with routine ovulation induction in anovulatory infertility.