{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:47:30Z","timestamp":1775749650799,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T00:00:00Z","timestamp":1433203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our objective was to compare the effectiveness of metformin plus clomiphene citrate vs. gonadotrophins, laparoscopic ovarian diathermy, aromatase inhibitors, <jats:italic>N<\/jats:italic>\u2010acetyl\u2010cysteine and other insulin sensitizers+clomiphene for improving fertility outcomes in women with clomiphene\u2010resistant polycystic ovary syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>PubMed, SCOPUS and CENTRAL databases were searched until April 2014 with the key words: PCOS, polycystic ovary syndrome, metformin, clomiphene citrate, ovulation induction and pregnancy. The search was limited to articles conducted with humans and published in English.<\/jats:p><\/jats:sec><jats:sec><jats:title>Sample<\/jats:title><jats:p>The PRISMA statement was followed. Twelve randomized controlled trials (<jats:italic>n<\/jats:italic>\u00a0=\u00a01411 women) were included.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>Ovulation and clinical pregnancy rates per woman randomized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with gonadotrophins, the metformin+clomiphene combination resulted in significantly fewer ovulations (odds ratio 0.25; 95% confidence interval 0.15\u20130.41; <jats:italic>p\u00a0&lt;\u00a0<\/jats:italic>0.00001, 3 trials, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a085%, <jats:italic>n<\/jats:italic>\u00a0=\u00a0323) and pregnancies (odds ratio 0.45; 95% confidence interval 0.27\u20130.75; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.002, 3 trials, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00%, <jats:italic>n<\/jats:italic>\u00a0=\u00a0323). No significant differences were found when metformin+clomiphene was compared with laparoscopic ovarian diathermy (odds ratio 0.88; 95% confidence interval 0.53\u20131.47; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.62, 1 trial, <jats:italic>n<\/jats:italic>\u00a0=\u00a0282; odds ratio 0.96; 95% confidence interval 0.60\u20131.54; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.88, 2 trials, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00%, <jats:italic>n<\/jats:italic>\u00a0=\u00a0332, for ovulation and pregnancy rates, respectively). Likewise, no differences were observed in comparison with aromatase inhibitors (odds ratio 0.88; 95% confidence interval 0.58\u20131.34; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.55, 3 trials, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0= 3%, <jats:italic>n<\/jats:italic>\u00a0=\u00a0409; odds ratio 0.85; 95% confidence interval 0.53\u20131.36; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.50, 2 trials, <jats:italic>n<\/jats:italic>\u00a0=\u00a0309, for ovulation and pregnancy rates, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>There is evidence for the superiority of gonadotrophins, but the metformin+clomiphene combination is mainly relevant for clomiphene\u2010resistant polycystic ovary syndrome patients and, if not effective, a next step could be gonadotrophins. More attempts with metformin+clomiphene are only relevant if there is limited access to gonadotrophins.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.12673","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T14:46:00Z","timestamp":1431441960000},"page":"921-930","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Combined metformin\u2010clomiphene in clomiphene\u2010resistant polycystic ovary syndrome: a systematic review and meta\u2010analysis of randomized controlled trials"],"prefix":"10.1111","volume":"94","author":[{"given":"Hatem","family":"Abu Hashim","sequence":"first","affiliation":[{"name":"Department of Obstetrics &amp; Gynecology Faculty of Medicine Mansoura University Mansoura Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama","family":"Foda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Endocrinology Unit 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