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Type: Journal article
Title: Metformin versus clomiphene citrate for infertility in non-obese women with polycystic ovary syndrome: a systematic review and meta-analysis
Author: Misso, M.
Costello, M.
Garrubba, M.
Wong, J.
Hart, R.
Rombauts, L.
Melder, A.
Norman, R.
Teede, H.
Citation: Human Reproduction Update, 2012; 19(1):2-11
Publisher: Oxford Univ Press
Issue Date: 2012
ISSN: 1355-4786
Organisation: Robinson Institute
Statement of
Marie L. Misso, Michael F. Costello, Marie Garrubba, Jennifer Wong, Roger Hart, Luk Rombauts, Angela M. Melder, Robert J. Norman and Helena J. Teede
Abstract: BACKGROUND: Recent studies suggest that metformin may be more effective in women with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to determine and compare the effectiveness of metformin and clomiphene citrate for improving fertility outcomes in women with PCOS and a BMI, 32 kg/m2 (BMI 32 kg/m2 was used to allow for international differences in BMI values which determine access to infertility therapy through the public health system). METHODS: Databases were searched for English language articles until July 2011. Inclusion criteria: women of any age, ethnicity and weight with PCOS diagnosed by all current criteria, who are infertile; at least 1000 mg of any type of metformin at any frequency, including slow release and standard release, compared with any type, dose and frequency of clomiphene citrate. Outcomes: rates of ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse events, quality of life and cost effectiveness. Data were extracted and risk of bias assessed. A random effects model was used for meta-analyses of data, using risk ratios (relative risk). RESULTS: The search returned 4981 articles, 580 articles addressed metformin or clomiphene citrate and four randomized controlled trials (RCTs) comparing metformin with clomiphene citrate were included. Upon meta-analysis of the four RCTs, we were unable to detect a statistically significant difference between the two interventions for any outcome in women with PCOS and a BMI , 32 kg/m2, owing to significant heterogeneity across the RCTs. CONCLUSIONS: Owing to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage and multiple pregnancy rates in women with PCOS and a BMI , 32 kg/m2. However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to determine whether there is a difference in effectiveness between metformin and placebo (or no treatment) or between metformin and clomiphene citrate for ovulation induction in women with PCOS who are non-obese. Until then, caution should be exercised when prescribing metformin as first line pharmacological therapy in this group of women.
Keywords: Humans
Polycystic Ovary Syndrome
Infertility, Female
Fertility Agents, Female
Hypoglycemic Agents
Body Mass Index
Ovulation Induction
Pregnancy Rate
Live Birth
Randomized Controlled Trials as Topic
Rights: © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
DOI: 10.1093/humupd/dms036
Appears in Collections:Aurora harvest
Obstetrics and Gynaecology publications

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