{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:42:19Z","timestamp":1790242939803,"version":"4.1.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T00:00:00Z","timestamp":1497830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T00:00:00Z","timestamp":1497830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The comparative efficacies of ovulation-induction treatments in patients with clomiphene citrate-resistant (CCR) polycystic ovary syndrome (PCOS) are not well known. Therefore, we conducted a network meta-analysis to rank the reproductive efficacies of these treatments. We ultimately included 26 randomized clinical trials with 2722 participants and 9 types of therapies: clomiphene citrate (CC), metformin, letrozole, follicle stimulating hormone (FSH), human menopausal gonadotropin (hMG), unilateral laparoscopic ovarian drilling (ULOD), bilateral laparoscopic ovarian drilling (BLOD), the combination of metformin with letrozole (metformin+letrozole), and the combination of metformin with CC (metformin+CC). The network meta-analysis demonstrates that hMG therapy result in higher pregnancy rates than BLOD, ULOD and CC therapies. Pregnancy, live birth and ovulation rates are significantly higher in metformin+letrozole and FSH groups than CC group. The abortion rate in the metformin+letrozole group is significantly lower than that in the metformin+CC group. Ranking probabilities show that, apart from gonadotropin (FSH and hMG), metformin+letrozole is also potentially more effective in improving reproductive outcomes than other therapies. In conclusion, owing to the low quality of evidence and the wide confidence intervals, no recommendation could be made for the treatment of ovulation-induction in patients with CCR PCOS.<\/jats:p>","DOI":"10.1038\/s41598-017-03803-9","type":"journal-article","created":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T11:25:51Z","timestamp":1497353151000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comparative effectiveness of 9 ovulation-induction therapies in patients with clomiphene citrate-resistant polycystic ovary syndrome: a network meta-analysis"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9068-5944","authenticated-orcid":false,"given":"Yiping","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhe","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingpu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,19]]},"reference":[{"key":"3803_CR1","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1007\/s00404-012-2261-2","volume":"285","author":"H Abu Hashim","year":"2012","unstructured":"Abu Hashim, H. Clomiphene citrate alternatives for the initial management of polycystic ovary syndrome: an evidence-based approach. Arch Gynecol Obstet \n                           285, 1737\u20131745, doi:10.1007\/s00404-012-2261-2 (2012).","journal-title":"Arch Gynecol Obstet"},{"key":"3803_CR2","doi-asserted-by":"publisher","unstructured":"Balen, A. H. et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Human reproduction update, doi:10.1093\/humupd\/dmw025 (2016).","DOI":"10.1093\/humupd\/dmw025"},{"key":"3803_CR3","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1097\/GCO.0000000000000163","volume":"27","author":"AH Klement","year":"2015","unstructured":"Klement, A. H. & Casper, R. F. The use of aromatase inhibitors for ovulation induction. 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The Cochrane database of systematic reviews, Cd010290, doi:10.1002\/14651858.CD010290.pub2 (2015).","DOI":"10.1002\/14651858.CD010290.pub2"},{"key":"3803_CR6","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1093\/humupd\/dms003","volume":"18","author":"ML Misso","year":"2012","unstructured":"Misso, M. L. et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Human reproduction update \n                           18, 301\u2013312, doi:10.1093\/humupd\/dms003 (2012).","journal-title":"Human reproduction update"},{"key":"3803_CR7","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1111\/aogs.12673","volume":"94","author":"H Abu Hashim","year":"2015","unstructured":"Abu Hashim, H., Foda, O. & Ghayaty, E. Combined metformin-clomiphene in clomiphene-resistant polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Acta obstetricia et gynecologica Scandinavica \n                           94, 921\u2013930, doi:10.1111\/aogs.12673 (2015).","journal-title":"Acta obstetricia et gynecologica Scandinavica"},{"key":"3803_CR8","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD001122.pub4","author":"C Farquhar","year":"2012","unstructured":"Farquhar, C., Brown, J. & Marjoribanks, J. Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. The Cochrane database of systematic reviews, Cd001122, doi:10.1002\/14651858.CD001122.pub4 (2012).","journal-title":"The Cochrane database of systematic reviews"},{"key":"3803_CR9","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1080\/09513590.2016.1197196","volume":"32","author":"N Ding","year":"2016","unstructured":"Ding, N. et al. Luteal phase clomiphene citrate for ovulation induction in women with polycystic ovary syndrome: a systematic review and meta-analysis. Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology \n                           32, 866\u2013871, doi:10.1080\/09513590.2016.1197196 (2016).","journal-title":"Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology"},{"key":"3803_CR10","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1177\/0962280207080643","volume":"17","author":"G Salanti","year":"2008","unstructured":"Salanti, G., Higgins, J. P., Ades, A. E. & Ioannidis, J. P. Evaluation of networks of randomized trials. Statistical methods in medical research \n                           17, 279\u2013301, doi:10.1177\/0962280207080643 (2008).","journal-title":"Statistical methods in medical research"},{"key":"3803_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2165\/00019053-200624010-00001","volume":"24","author":"AE Ades","year":"2006","unstructured":"Ades, A. E. et al. 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