{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:19:59Z","timestamp":1768979999882,"version":"3.49.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100020430","name":"LG Chem","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020430","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod. Sci."],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To evaluate the safety and effectiveness of recombinant human follicle-stimulating hormone (rhFSH [Follitrope\u2122]) in infertile women undergoing in vitro fertilization (IVF). To identify predictors of ovarian response that induce optimal clinical outcomes. This multicenter prospective study enrolled infertile women who were scheduled to undergo IVF after ovarian stimulation with rhFSH (Follitrope\u2122) following the gonadotropin-releasing hormone (GnRH) agonist or GnRH antagonist protocol. Predictive factors for ovarian response were identified in the GnRH antagonist group based on the number of oocytes retrieved. A total of 516 infertile women were enrolled, among whom 136 (except one who withdrew before administration) received rhFSH using the GnRH agonist protocol and 379 using the antagonist protocol. The mean number of oocytes retrieved was 13.4 in the GnRH agonist group and 13.6 in the GnRH antagonist group. The clinical pregnancy rates were 32.3% (30\/93) and 39.9% (115\/288) in the GnRH agonist and antagonist groups, respectively. The incidence of ovarian hyperstimulation syndrome was 1.8% and 3.4% in the GnRH agonist and antagonist groups, respectively. No other significant safety risks associated with rhFSH administration were identified. Body mass index, basal serum FSH and anti-M\u00fcllerian hormone levels, and antral follicle count were identified as predictors of ovarian response by multiple regression with backward elimination, and the final regression model accounted for 26.5% of the response variability. In real-world practice, rhFSH (Follitrope\u2122) is safe and effective in inducing ovarian stimulation in infertile women. Patient characteristics identified as predictors can be considered to be highly related to optimal clinical outcomes.<\/jats:p>","DOI":"10.1007\/s43032-023-01228-6","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T15:02:26Z","timestamp":1681743746000},"page":"2842-2852","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effectiveness and Safety of Recombinant Human Follicle-Stimulating Hormone (Follitrope\u2122) in Inducing Controlled Ovarian Stimulation in Infertile Women in Real-World Practice: a Prospective Cohort Study"],"prefix":"10.1007","volume":"30","author":[{"given":"Chang-Woo","family":"Choo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Sun","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyu Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoung Yong","family":"Moon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bum-Chae","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Je","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chae Hee","family":"Sim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Eun","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung-Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Jeong","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoojin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jei Won","family":"Moon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Soo","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung Jae","family":"Won","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An Na","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju-Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang Rye","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hyun","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joong-Yeup","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heemin","family":"Gwak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9864-9777","authenticated-orcid":false,"given":"Ji Hyang","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"issue":"6","key":"1228_CR1","doi-asserted-by":"publisher","first-page":"4918","DOI":"10.18632\/aging.102919","volume":"12","author":"L Hu","year":"2020","unstructured":"Hu L, Zhang S, Quan S, Lv J, Qian W, Huang Y, et al. Efficacy and safety of recombinant human follicle-stimulating hormone in patients undergoing in vitro fertilization-embryo transfer. Aging. 2020;12(6):4918\u201330.","journal-title":"Aging"},{"key":"1228_CR2","first-page":"CD012693","volume":"2","author":"SF Lensen","year":"2018","unstructured":"Lensen SF, Wilkinson J, Leijdekkers JA, La Marca A, Mol BWJ, Marjoribanks J, et al. Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF\/ICSI). Cochrane Database Syst Rev. 2018;2:CD012693.","journal-title":"Cochrane Database Syst Rev"},{"issue":"2","key":"1228_CR3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/S1472-6483(10)60256-8","volume":"18","author":"F Olivennes","year":"2009","unstructured":"Olivennes F, Howles CM, Borini A, Germond M, Trew G, Wikland M, et al. Individualizing FSH dose for assisted reproduction using a novel algorithm: the CONSORT study. Reprod Biomed Online. 2009;18(2):195\u2013204.","journal-title":"Reprod Biomed Online"},{"issue":"1","key":"1228_CR4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12958-020-00610-2","volume":"18","author":"P Sydow","year":"2020","unstructured":"Sydow P, Gmeinwieser N, Pribbernow K, Keck C, Wiegratz I. Effectiveness and safety of follitropin alfa (Ovaleap\u00ae) for ovarian stimulation using a GnRH antagonist protocol in real-world clinical practice: a multicenter, prospective, open, non-interventional assisted reproductive technology study. Reprod Biol Endocrinol. 2020;18(1):54.","journal-title":"Reprod Biol Endocrinol"},{"issue":"1","key":"1228_CR5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S1472-6483(10)60973-X","volume":"12","author":"CM Howles","year":"2006","unstructured":"Howles CM. Recombinant gonadotrophins in reproductive medicine: the gold standard of today. Reprod Biomed Online. 2006;12(1):11\u20133.","journal-title":"Reprod Biomed Online"},{"issue":"2","key":"1228_CR6","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1093\/humupd\/2.2.172","volume":"2","author":"CM Howles","year":"1996","unstructured":"Howles CM. Genetic engineering of human FSH (Gonal-F). Hum Reprod Update. 1996;2(2):172\u201391.","journal-title":"Hum Reprod Update"},{"issue":"7","key":"1228_CR7","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1093\/humrep\/der106","volume":"26","author":"SK Sunkara","year":"2011","unstructured":"Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011;26(7):1768\u201374.","journal-title":"Hum Reprod"},{"issue":"2","key":"1228_CR8","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s00404-019-05156-2","volume":"300","author":"M Zhu","year":"2019","unstructured":"Zhu M, Wang S, Yi S, Huang X, Meng J, Chen L, et al. A predictive formula for selecting individual FSH starting dose based on ovarian reserve markers in IVF\/ICSI cycles. Arch Gynecol Obstet. 2019;300(2):441\u20136.","journal-title":"Arch Gynecol Obstet"},{"issue":"4","key":"1228_CR9","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.rbmo.2017.01.012","volume":"34","author":"A Allegra","year":"2017","unstructured":"Allegra A, Marino A, Volpes A, Coffaro F, Scaglione P, Gullo S, et al. A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF\/ICSI cycles. Reprod Biomed Online. 2017;34(4):429\u201338.","journal-title":"Reprod Biomed Online"},{"issue":"2","key":"1228_CR10","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1055\/s-0035-1546424","volume":"33","author":"ES Jungheim","year":"2015","unstructured":"Jungheim ES, Meyer MF, Broughton DE. Best practices for controlled ovarian stimulation in in vitro fertilization. Semin Reprod Med. 2015;33(2):77\u201382.","journal-title":"Semin Reprod Med"},{"issue":"9","key":"1228_CR11","first-page":"1903","volume":"6","author":"Q Lai","year":"2013","unstructured":"Lai Q, Zhang H, Zhu G, Li Y, Jin L, He L, et al. Comparison of the GnRH agonist and antagonist protocol on the same patients in assisted reproduction during controlled ovarian stimulation cycles. Int J Clin Exp Pathol. 2013;6(9):1903\u201310.","journal-title":"Int J Clin Exp Pathol"},{"issue":"7","key":"1228_CR12","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1093\/humrep\/der092","volume":"26","author":"AP Ferraretti","year":"2011","unstructured":"Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of \u2018poor response\u2019 to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616\u201324.","journal-title":"Hum Reprod"},{"issue":"4","key":"1228_CR13","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.fertnstert.2013.12.026","volume":"101","author":"RG Steward","year":"2014","unstructured":"Steward RG, Lan L, Shah AA, Yeh JS, Price TM, Goldfarb JM, et al. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril. 2014;101(4):967\u201373.","journal-title":"Fertil Steril"},{"issue":"4","key":"1228_CR14","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/S1472-6483(10)60633-5","volume":"13","author":"MH van der Gaast","year":"2006","unstructured":"van der Gaast MH, Eijkemans MJ, van der Net JB, de Boer EJ, Burger CW, van Leeuwen FE, et al. Optimum number of oocytes for a successful first IVF treatment cycle. Reprod Biomed Online. 2006;13(4):476\u201380.","journal-title":"Reprod Biomed Online"},{"issue":"3","key":"1228_CR15","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1111\/j.1447-0756.2007.00529.x","volume":"33","author":"SY Moon","year":"2007","unstructured":"Moon SY, Choi YS, Ku SY, Kim SH, Choi YM, Kang IS, et al. Comparison of the efficacy and safety of a new recombinant human follicle-stimulating hormone (DA-3801) with follitropin-alpha (Gonal-F) in women undergoing controlled ovarian hyperstimulation for assisted reproductive technology. J Obstet Gynaecol. 2007;33(3):305\u201315.","journal-title":"J Obstet Gynaecol"},{"issue":"12","key":"1228_CR16","doi-asserted-by":"publisher","first-page":"3217","DOI":"10.1093\/humrep\/del284","volume":"21","author":"AN Andersen","year":"2006","unstructured":"Andersen AN, Devroey P, Arce JC. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial. Hum Reprod. 2006;21(12):3217\u201327.","journal-title":"Hum Reprod"},{"issue":"6","key":"1228_CR17","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1080\/01443615.2022.2036955","volume":"42","author":"EJ Han","year":"2022","unstructured":"Han EJ, Lyu SW, Kwak IP, Kwon H, Choi DH, Kim JY, et al. Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study. J Obstet Gynaecol. 2022;42(6):2197\u2013202.","journal-title":"J Obstet Gynaecol."},{"issue":"2","key":"1228_CR18","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3109\/09513590.2012.712002","volume":"29","author":"R Marci","year":"2013","unstructured":"Marci R, Caserta D, Lisi F, Graziano A, Soave I, Lo Monte G, et al. In vitro fertilization stimulation protocol for normal responder patients. Gynecol Endocrinol. 2013;29(2):109\u201312.","journal-title":"Gynecol Endocrinol"},{"issue":"1","key":"1228_CR19","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/S0015-0282(99)00450-1","volume":"73","author":"P Brinsden","year":"2000","unstructured":"Brinsden P, Akagbosu F, Gibbons LM, Lancaster S, Gourdon D, Engrand P, et al. A comparison of the efficacy and tolerability of two recombinant human follicle-stimulating hormone preparations in patients undergoing in vitro fertilization-embryo transfer. Fertility and Sterility. 2000;73(1):114\u20136.","journal-title":"Fertility and Sterility."},{"issue":"5","key":"1228_CR20","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.rbmo.2015.01.005","volume":"30","author":"M Rettenbacher","year":"2015","unstructured":"Rettenbacher M, Andersen AN, Garcia-Velasco JA, Sator M, Barri P, Lindenberg S, et al. A multi-centre phase 3 study comparing efficacy and safety of Bemfola(\u00ae) versus Gonal-f(\u00ae) in women undergoing ovarian stimulation for IVF. Reprod Biomed Online. 2015;30(5):504\u201313.","journal-title":"Reprod Biomed Online"},{"issue":"4","key":"1228_CR21","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.rbmo.2015.06.015","volume":"31","author":"R Fleming","year":"2015","unstructured":"Fleming R, Seifer DB, Frattarelli JL, Ruman J. Assessing ovarian response: antral follicle count versus anti-M\u00fcllerian hormone. Reprod Biomed Online. 2015;31(4):486\u201396.","journal-title":"Reprod Biomed Online"},{"issue":"6","key":"1228_CR22","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/humupd\/dmu062","volume":"21","author":"S Iliodromiti","year":"2015","unstructured":"Iliodromiti S, Anderson RA, Nelson SM. Technical and performance characteristics of anti-M\u00fcllerian hormone and antral follicle count as biomarkers of ovarian response. Hum Reprod Update. 2015;21(6):698\u2013710.","journal-title":"Hum Reprod Update"},{"issue":"10","key":"1228_CR23","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1111\/j.1471-0528.2012.03412.x","volume":"119","author":"A La Marca","year":"2012","unstructured":"La Marca A, Papaleo E, Grisendi V, Argento C, Giulini S, Volpe A. Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle-stimulating hormone starting dose in in vitro fertilisation cycles. Int J Gynaecol Obstet. 2012;119(10):1171\u20139.","journal-title":"Int J Gynaecol Obstet"},{"issue":"5","key":"1228_CR24","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.rbmo.2012.02.027","volume":"26","author":"R Fleming","year":"2013","unstructured":"Fleming R, Broekmans F, Calhaz-Jorge C, Dracea L, Alexander H, Nyboe Andersen A, et al. Can anti-M\u00fcllerian hormone concentrations be used to determine gonadotrophin dose and treatment protocol for ovarian stimulation? Reprod Biomed Online. 2013;26(5):431\u20139.","journal-title":"Reprod Biomed Online"},{"issue":"4","key":"1228_CR25","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.fertnstert.2015.01.004","volume":"103","author":"RA Anderson","year":"2015","unstructured":"Anderson RA, Anckaert E, Bosch E, Dewailly D, Dunlop CE, Fehr D, et al. Prospective study into the value of the automated Elecsys antim\u00fcllerian hormone assay for the assessment of the ovarian growing follicle pool. Fertil Steril. 2015;103(4):1074\u201380.e4.","journal-title":"Fertil Steril"},{"issue":"1","key":"1228_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/humupd\/dmm034","volume":"14","author":"BC Fauser","year":"2008","unstructured":"Fauser BC, Diedrich K, Devroey P. 2007 EARWG. Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update. 2008;14(1):1\u201314.","journal-title":"Hum Reprod Update"}],"container-title":["Reproductive Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-023-01228-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43032-023-01228-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-023-01228-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T15:15:22Z","timestamp":1694618122000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43032-023-01228-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":26,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["1228"],"URL":"https:\/\/doi.org\/10.1007\/s43032-023-01228-6","relation":{},"ISSN":["1933-7191","1933-7205"],"issn-type":[{"value":"1933-7191","type":"print"},{"value":"1933-7205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,17]]},"assertion":[{"value":"28 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 March 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the applicable institutional review boards and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Participation and Publication"}},{"value":"Heemin Gwak is an employee of LG Chem, Ltd. The other authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}