PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene

• Published in: Human reproduction (Oxford) Vol. 25; no. 7; pp. 1675 - 1683
• Main Authors: Johnson, N.P., Stewart, A.W., Falkiner, J., Farquhar, C.M., Milsom, S., Singh, V.-P., Okonkwo, Q.L., Buckingham, K.L.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2010
• Subjects: anovulation; Anovulation - drug therapy; Anovulation - etiology; Biological and medical sciences; Clomiphene - therapeutic use; clomiphene citrate; Female; Gynecology. Andrology. Obstetrics; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Infertility, Female - drug therapy; Infertility, Female - etiology; Medical sciences; metformin; Metformin - adverse effects; Metformin - pharmacology; Metformin - therapeutic use; Ovulation Induction; polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Pregnancy; randomized controlled trial; Treatment Outcome; clomiphene citrate; metformin; anovulation; polycystic ovary syndrome; randomized controlled trial; Non steroidal estrogen; Citrate; Polycystic ovary; Hypoglycemic agent; Randomization; Biguanides; Selective estrogen receptor modulator; Cyst; Clinical trial; Female; Benign neoplasm; Human; Menstruation disorders; Anovulation; Ovulation inducer; Female sterility; Clomifene; Female genital diseases; Ovarian diseases; Vertebrata; Mammalia; Metformin
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/deq100

BACKGROUND Ovulation induction treatment with metformin, either alone or in combination with clomiphene citrate (CC), remains controversial even though previous randomized trials have examined this. METHODS A double blinded multi-centre randomized trial was undertaken including 171 women with anovulatory or oligo-ovulatory polycystic ovary syndrome. Women with high body mass index (BMI) > 32 kg/m2 received placebo (‘standard care’) or metformin; women with BMI ≤ 32 kg/m2 received CC (‘standard care’), metformin or both. Treatment continued for 6 months or until pregnancy was confirmed. Primary outcomes were clinical pregnancy and live birth. RESULTS For women with BMI > 32 kg/m2, clinical pregnancy and live birth rates were 22% (7/32) and 16% (5/32) with metformin, 15% (5/33) and 6% (2/33) with placebo. For women with BMI ≤ 32 kg/m2, clinical pregnancy and live birth rates were 40% (14/35) and 29% (10/35) with metformin, 39% (14/36) and 36% (13/36) with CC, 54% (19/35) and 43% (15/35) with combination metformin plus CC. CONCLUSIONS There is no evidence that adding metformin to ‘standard care’ is beneficial. Pregnancy and live birth rates are low in women with BMI > 32 kg/m2 whatever treatment is used, with no evidence of benefit of metformin over placebo. For women with BMI ≤ 32 kg/m2 there is no evidence of significant differences in outcomes whether treated with metformin, CC or both. ClinicalTrials.gov number NCT00795808; trial protocol accepted for publication November 2005: Johnson, Aust N Z Journal Obstet Gynaecol 2006;46:141–145.