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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EMetformin is a commonly used treatment in polycystic ovary syndrome (PCOS), and it is widely believed that metformin improves reproductive outcomes in patients with PCOS. This article discusses the pathophysiology of PCOS as well as management of PCOS-associated infertility.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPolycystic Ovary Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInfertility\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPolycystic Ovary Disorder\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EObstetrics \u0026amp; Gynecology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EInfertility\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EMetformin is a commonly used treatment in polycystic ovary syndrome (PCOS), and it is widely believed that metformin improves reproductive outcomes in patients with PCOS. Richard S. Legro, MD, Milton S. Hershey Medical Center, Hershey Pennsylvania, USA, discussed the pathophysiology of PCOS as well as management of PCOS-associated infertility.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EApproximately 80% of women with anovulatory infertility also have PCOS. The original characterization of PCOS noted amenorrhea, hirsutism, hyperandrogenemia, sterility, and large pale polycystic ovaries. Decades later, the previous characteristics are still applicable when making a diagnosis of PCOS, regardless of which criteria is used.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EPCOS can be associated with several risk factors for cardiovascular disease, including elevated body mass index, insulin resistance, and elevated lipids, as well as an increase in carotid intimal medial thickness [Talbot EO et al. \u003Cem\u003EArterio Thromb Vase Biol\u003C\/em\u003E 2000].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThere is evidence that treatment of insulin resistance in patients with PCOS can improve symptoms, including infertility. Although treatment with D-\u003Cem\u003Echiro\u003C\/em\u003E-inositol and troglitazone increased the rate of ovulation, they have substantial side effects that prohibit their use [Nestler JE et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1999; Azziz R et al. \u003Cem\u003EClin Endocrinol Metab\u003C\/em\u003E 2001]. However, open-label treatment of 26 women with PCOS with metformin was demonstrated to reduce hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, as well as improved menstruation and rate of pregnancy [Velazquez EM et al. \u003Cem\u003EMetabolism\u003C\/em\u003E 1994].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EIncreasingly, women with PCOS who wish to conceive are referred for \u003Cem\u003Ein vitro\u003C\/em\u003E fertilization (IVF) therapy, which in turn has resulted in a high rate of multiple pregnancies. Dr. Legro discussed other methods of increasing fertility in women with PCOS. In a highly cited study, metformin plus clomiphene improved the ovulation rate to 90% compared with 8% in patients who received placebo [Nestler JE et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1998]. In addition, a randomized study demonstrated that continued therapy with metformin reduced PCOS-related pregnancy complications [Vanky E et al. \u003Cem\u003EHum Reprod\u003C\/em\u003E 2004]. In a more recent study, women with PCOS treated with clomiphene alone had significantly increased rates of live birth compared with patients who received metformin alone (p\u0026lt;0.001) and was not significantly different from a combination therapy with both [Legro RS et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2007]. In addition, fecundity per ovulation was greater in patients who received clomiphene compared with metformin. Despite these finding, a meta-analysis found that metformin and clomiphene, as monotherapy or in combination, did not improve the number of live births [Tang T et al. \u003Cem\u003ECochrane Database Syst Rev\u003C\/em\u003E 2012], suggesting that metformin has a limited effect on reproductive outcomes in women with PCOS (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/15951\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/15951\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15951\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EEffect of Metformin on Live Births by Women With PCOS\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-11\u0022\u003EDr. Legro concluded by highlighting several reasons why metformin continues to be used in women with PCOS to improve reproductive outcomes, despite a lack of evidence supporting its use for that indication. He noted that most of the positive studies using metformin used surrogate variables such as ovulation rate, and the initial randomized trials were small and irreproducible. In addition, a safety bias occurs because metformin has a good risk-benefit ratio.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/7\/20.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp9eq\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzp9eq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}