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The aim of the current paper was to define, if possible, the best evidence\u2010based recommendations regarding the use of CC and\/or metformin as the initial treatment of PCOS women with anovulatory infertility.<\/jats:p><jats:p>\n\t\t\t\t\t\t<jats:bold>Design\u2002<\/jats:bold> Systematic review and meta\u2010analysis of the head\u2010to\u2010head randomized controlled trials (RCTs) available in the literature.<\/jats:p><jats:p>\n\t\t\t\t\t\t<jats:bold>Methods\u2002<\/jats:bold> A bibliographic search was performed using the following bibliographic databases: Medline, EMBASE, Biological Abstracts, Cochrane Controlled Trials Register and Cochrane Database of Systematic Reviews. Reference lists of included studies, other relevant review articles and textbooks were checked for additional citations of interest.<\/jats:p><jats:p>\n\t\t\t\t\t\t<jats:bold>Results\u2002<\/jats:bold> Four head\u2010to\u2010head RCTs were identified and qualified for inclusion in the analysis. No difference in fertility improvement was observed comparing CC with metformin (O<jats:italic>R<\/jats:italic>\u00a0=\u00a01\u00b722, 95% CI 0\u00b723\u20136\u00b755, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7815), whereas a significant (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00\u00b70001) heterogeneity was observed. Homogeneous data showed no difference in fertility improvement between the combination treatment and CC monotherapy (O<jats:italic>R<\/jats:italic>\u00a0=\u00a00\u00b799, 95% CI 0\u00b770\u20131\u00b740, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7982), but a significant difference in comparison with metformin monotherapy (O<jats:italic>R<\/jats:italic>\u00a0=\u00a00\u00b723, 95% CI 0\u00b714\u20130\u00b737, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b70001).<\/jats:p><jats:p>\n\t\t\t\t\t\t<jats:bold>Conclusions\u2002<\/jats:bold> In PCOS patients with anovulatory infertility and not previously treated, the administration of metformin plus CC is not better than monotherapy (metformin alone or CC alone), whereas to date no specific recommendation can be given regarding the use of CC or metformin as first\u2010step drug.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2008.03369.x","type":"journal-article","created":{"date-parts":[[2008,8,7]],"date-time":"2008-08-07T13:20:13Z","timestamp":1218115213000},"page":"311-321","source":"Crossref","is-referenced-by-count":65,"title":["Clomiphene citrate, metformin or both as first\u2010step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): a systematic review of head\u2010to\u2010head randomized controlled studies and meta\u2010analysis"],"prefix":"10.1111","volume":"70","author":[{"given":"Stefano","family":"Palomba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Pasquali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Francesco","family":"Orio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Nestler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,19]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh098"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/09513598709023610"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199509283331307"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-032046"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.03.018"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(94)90209-7"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(02)04554-5"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7421.951"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh440"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.06.014"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmm026"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31816a4ed4"},{"key":"e_1_2_5_14_2","first-page":"43","article-title":"The use of metformin to augment the induction of ovulation in obese infertile patients with polycystic ovary syndrome","volume":"6","author":"El\u2010Biely M.M.","year":"2001","journal-title":"Middle East Fertility Society Journal"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(01)02280-4"},{"key":"e_1_2_5_16_2","first-page":"50","article-title":"Presentation of polycystic ovary syndrome and its management with clomiphene alone and in combination with metformin","volume":"17","author":"Raja A.","year":"2005","journal-title":"Journal of Ayub Medical College Abbottabad"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2003.09.036"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2005.10.042"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.12.002"},{"key":"e_1_2_5_20_2","first-page":"337","volume-title":"Polycystic Ovary Syndrome","author":"Zawadzki J.K.","year":"1992"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh322"},{"key":"e_1_2_5_22_2","unstructured":"The Cochrane Collaboration(2006)Cochrane handbook for systematic reviews of interventions (formerly the reviewers\u2019 handbook).Handbook4.2.6."},{"key":"e_1_2_5_23_2","unstructured":"Menstrual DisordersandSubfertility Group's(MDSG)trials register. 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