{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:46:11Z","timestamp":1791999971801,"version":"4.4.0"},"reference-count":62,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck","award":["CrossRef Funder ID: 10.13039\/100009945"],"award-info":[{"award-number":["CrossRef Funder ID: 10.13039\/100009945"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although the full primary structures of the alfa and beta subunits of reference r-hFSH-alfa and its biosimilars are identical, cell context-dependent differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation profiles. In the present study, we compared the structural features of reference r-hFSH-alfa with those of five biosimilar preparations approved in different global regions outside Europe (Primapur\u00ae, Jin Sai Heng\u00ae, Follitrope\u00ae, Folisurge\u00ae, and Corneumon\u00ae) with respect to glycosylation, macro- and microheterogeneity, and other post-translational modifications and higher order structure. The mean proportion of N-glycosylation-site occupancy was highest in reference r-hFSH-alfa, decreasing sequentially in Primapur, Jin Sai Heng, Corneumon, Follisurge and Follitrope, respectively. The level of antennarity showed slightly higher complexity in Corneumon, Primapur and Follitrope versus reference r-hFSH-alfa, whereas Jin Sai Heng and Folisurge were aligned with reference r-hFSH-alfa across all N-glycosylation sites. Sialylation level was higher in Corneumon and Follitrope, but small differences were detected in other biosimilar preparations compared with reference r-hFSH-alfa. Jin Sai Heng showed higher levels of N-glyconeuramic acid than the other preparations. Minor differences in oxidation levels were seen among the different products. Therefore, in summary, we identified var ious differences in N-glycosylation occupancy, antennarity, sialylation and oxidation between reference r-hFSH-alfa and the biosimilar preparations analyzed.<\/jats:p>","DOI":"10.3390\/ijms23126762","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T11:45:44Z","timestamp":1655466344000},"page":"6762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Comparative Assessment of the Structural Features of Originator Recombinant Human Follitropin Alfa Versus Recombinant Human Follitropin Alfa Biosimilar Preparations Approved in Non-European Regions"],"prefix":"10.3390","volume":"23","author":[{"given":"Lucio","family":"Manzi","sequence":"first","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nunzio","family":"Sepe","sequence":"additional","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Migliaccio","sequence":"additional","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Lanzoni","sequence":"additional","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Iozzino","sequence":"additional","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Colarusso","sequence":"additional","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Montenegro","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Palmese","sequence":"additional","affiliation":[{"name":"Characterization & Innovative Analytics Unit\u2014Analytical Development Biotech\u2014Global Analytical Development\u2014Global Development & Launch\u2014Global Healthcare Operation, Merck Serono S.p.A., 00176 Rome, Italy, an affiliate of Merck KGaA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"D\u2019Hooghe","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"},{"name":"Department of Development and Regeneration, Laboratory of Endometrium, Endometriosis & Reproductive Medicine, KU Leuven, Herestraat 49-Box 805, B-3000 Leuven, Belgium"},{"name":"Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University Medical School, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-3886","authenticated-orcid":false,"given":"Alfredo","family":"Ulloa-Aguirre","sequence":"additional","affiliation":[{"name":"Research Support Network (RAI), Universidad Nacional Aut\u00f3noma de M\u00e9xico-Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n SZ, Tlalpan, Mexico City 14000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Koloda","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Russian Medical Academy of Continuous Professional Education, Centre of Reproduction \u201cLife Line\u201d, 121471 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9920-3208","authenticated-orcid":false,"given":"Monica","family":"Lispi","sequence":"additional","affiliation":[{"name":"Merck Healthcare KGaA, 64293 Darmstadt, Germany"},{"name":"PhD School of Clinical and Experimental Medicine, Unit of Endocrinology, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"ref_1","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., de Herder, W.W., Dhatariya, K., Dungan, K., Hershman, J.M., Hofland, J., and Kalra, S. (2022). Physiology of GnRH and Gonadotropin Secretion. Endotext, MDText.com."},{"key":"ref_2","first-page":"200","article-title":"Initial and cyclic recruitment of ovarian follicles","volume":"21","author":"McGee","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bergandi, L., Canosa, S., Carosso, A.R., Paschero, C., Gennarelli, G., Silvagno, F., Benedetto, C., and Revelli, A. (2020). Human Recombinant FSH and Its Biosimilars: Clinical Efficacy, Safety, and Cost-Effectiveness in Controlled Ovarian Stimulation for In Vitro Fertilization. Pharmaceuticals, 13.","DOI":"10.3390\/ph13070136"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3389\/fendo.2019.00429","article-title":"The Development of Gonadotropins for Clinical Use in the Treatment of Infertility","volume":"10","author":"Lunenfeld","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_5","unstructured":"European Medicines Agency (2022, June 14). GONAL-f\u00ae Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/gonal-f-epar-product-information_en.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/bs.pmbts.2016.08.003","article-title":"Clinical Applications of Gonadotropins in the Male","volume":"143","year":"2016","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1007\/s12325-020-01512-w","article-title":"The Frequency of Ovarian Hyperstimulation Syndrome and Thromboembolism with Originator Recombinant Human Follitropin Alfa (GONAL-f) for Medically Assisted Reproduction: A Systematic Review","volume":"37","author":"Velthuis","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.rbmo.2018.10.012","article-title":"Follitropin delta in repeated ovarian stimulation for IVF: A controlled, assessor-blind Phase 3 safety trial","volume":"38","author":"Bosch","year":"2019","journal-title":"Reprod. BioMed. Online"},{"key":"ref_9","unstructured":"European Medicines Agency (2022, June 14). Biosimilars in the EU: Information Guide for Healthcare Professionals. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/leaflet\/biosimilars-eu-information-guide-healthcare-professionals_en.pdf."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1111\/nyas.14522","article-title":"Regulatory challenges with biosimilars: An update from 20 countries","volume":"1491","author":"Kang","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_11","unstructured":"European Medicines Agency (2022, June 14). European Public Assessment Report (EPAR): Ovaleap\u00ae (Follitropin Alfa). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/ovaleap."},{"key":"ref_12","unstructured":"European Medicines Agency (2022, June 14). European Public Assessment Report (EPAR): Bemfola\u00ae (Follitropin Alfa). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/bemfola."},{"key":"ref_13","unstructured":"European Medicines Agency (2022, June 14). Guideline on Similar Biological Medicinal Products Containing Biotechnology-Derived Proteins as Active Substance: Non-Clinical and Clinical Issues. 18 December 2014. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-similar-biological-medicinal-products-containing-biotechnology-derived-proteins-active_en-2.pdf."},{"key":"ref_14","unstructured":"(2022, June 14). International Conference on Harmonisation. ICH Q5E Biotechnological\/Biological Products Subject to Changes in Their Manufacturing Process: Comparability of Biotechnological\/Biological Products. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-q-5-e-comparability-biotechnological\/biological-products-step-5_en.pdf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biologicals.2020.02.005","article-title":"The regulatory landscape of biosimilars: WHO efforts and progress made from 2009 to 2019","volume":"65","author":"Thorpe","year":"2020","journal-title":"Biologicals"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s40259-015-0147-0","article-title":"The Diversity of Biosimilar Design and Development: Implications for Policies and Stakeholders","volume":"29","author":"Grampp","year":"2015","journal-title":"BioDrugs"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mastrangeli, R., Satwekar, A., Cutillo, F., Ciampolillo, C., Palinsky, W., and Longobardi, S. (2017). In-vivo biological activity and glycosylation analysis of a biosimilar recombinant human follicle-stimulating hormone product (Bemfola) compared with its reference medicinal product (GONAL-f). PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184139"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.rbmo.2017.03.020","article-title":"Biosimilars to recombinant human FSH medicines: Comparable efficacy and safety to the original biologic","volume":"35","author":"Fauser","year":"2017","journal-title":"Reprod. BioMed. Online"},{"key":"ref_19","unstructured":"European Medicines Agency (2022, June 14). Guideline on Non-Clinical and Clinical Development of Similar Biological Medicinal Products Containing Recombinant Human Follicle Stimulating Hormone (r-hFSH). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-non-clinical-clinical-development-similar-biological-medicinal-products-containing_en.pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.rbmo.2015.01.005","article-title":"A multi-centre phase 3 study comparing efficacy and safety of Bemfola\u00ae versus Gonal-f\u00ae in women undergoing ovarian stimulation for IVF","volume":"30","author":"Rettenbacher","year":"2015","journal-title":"Reprod. BioMed. Online"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12958-015-0135-8","article-title":"Randomized, active-controlled, comparative phase 3 efficacy and safety equivalence trial of Ovaleap\u00ae (recombinant human follicle-stimulating hormone) in infertile women using assisted reproduction technology (ART)","volume":"6","author":"Strowitzki","year":"2016","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ejogrb.2018.04.006","article-title":"Treatment strategies and cumulative live birth rates in WHO-II ovulation disorders","volume":"225","author":"Braam","year":"2018","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1093\/humrep\/deh501","article-title":"What is the most relevant standard of success in assisted reproduction?: The cumulated singleton\/twin delivery rates per oocyte pick-up: The CUSIDERA and CUTWIDERA","volume":"19","author":"Germond","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1056\/NEJMoa0803072","article-title":"Cumulative live-birth rates after in vitro fertilization","volume":"360","author":"Malizia","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S1472-6483(10)61827-5","article-title":"Intact follicle culture: What it can tell us about the roles of FSH glycoforms during follicle development","volume":"5","author":"Nayudu","year":"2002","journal-title":"Reprod. BioMed. Online"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.fertnstert.2009.10.005","article-title":"Ovarian stimulation protocols based on follicle-stimulating hormone glycosylation pattern: Impact on oocyte quality and clinical outcome","volume":"94","author":"Selman","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12958-016-0167-8","article-title":"Biosimilar FSH preparations- are they identical twins or just siblings?","volume":"14","author":"Orvieto","year":"2016","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12958-021-00727-y","article-title":"Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F(R)) in couples undergoing assisted reproductive technology treatment: A systematic review and meta-analysis","volume":"19","author":"Chua","year":"2021","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1477-7827-12-128","article-title":"Human steroidogenesis: Implications for controlled ovarian stimulation with exogenous gonadotropins","volume":"12","author":"Andersen","year":"2014","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"636038","DOI":"10.3389\/fendo.2021.636038","article-title":"New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect","volume":"12","author":"Dias","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4172\/2153-0637.1000129","article-title":"Comparison of Follicle-Stimulating Hormone Glycosylation Microheterogenity by Quantitative Negative Mode Nano-Electrospray Mass Spectrometry of Peptide-N Glycanase-Released Oligosaccharides","volume":"5","author":"Bousfield","year":"2015","journal-title":"J. Glycom. Lipidom."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1080\/03009734.2018.1467983","article-title":"Low-glycosylated forms of both FSH and LH play major roles in the natural ovarian stimulation","volume":"123","author":"Wide","year":"2018","journal-title":"Ups. J. Med. Sci."},{"key":"ref_33","first-page":"1647","article-title":"Dynamics of basal and gonadotropin-releasing hormone-releasable serum follicle-stimulating hormone charge isoform distribution throughout the human menstrual cycle","volume":"80","author":"Zambrano","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3389\/fendo.2019.00503","article-title":"Glycosylation Pattern and in vitro Bioactivity of Reference Follitropin alfa and Biosimilars","volume":"10","author":"Riccetti","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/humrep\/16.4.599","article-title":"Is there any physiological role for gonadotrophin oligosaccharide heterogeneity in humans? I. Gondatrophins are synthesized and released in multiple molecular forms. A matter of fact","volume":"16","author":"Timossi","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1210\/en.2019-00001","article-title":"Follicle-Stimulating Hormone Glycobiology","volume":"160","author":"Bousfield","year":"2019","journal-title":"Endocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"279","DOI":"10.6061\/clinics\/2014(04)10","article-title":"Gonadotropin therapy in assisted reproduction: An evolutionary perspective from biologics to biotech","volume":"69","author":"Esteves","year":"2014","journal-title":"Clinics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/nbt1252","article-title":"Post-translational modifications in the context of therapeutic proteins","volume":"24","author":"Walsh","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1034\/j.1399-3089.2002.02138.x","article-title":"Anti-N-glycolylneuraminic acid antibodies identified in healthy human serum","volume":"9","author":"Zhu","year":"2002","journal-title":"Xenotransplantation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100906","DOI":"10.1016\/j.jbc.2021.100906","article-title":"Sialic acid O-acetylation: From biosynthesis to roles in health and disease","volume":"97","author":"Visser","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1023\/B:PHAM.0000029275.41323.a6","article-title":"Structure-immunogenicity relationships of therapeutic proteins","volume":"21","author":"Hermeling","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/S1472-6483(10)60163-0","article-title":"Analytical identification of additional impurities in urinary-derived gonadotrophins","volume":"19","author":"Bassett","year":"2009","journal-title":"Reprod. BioMed. Online"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S1472-6483(10)60613-X","article-title":"Comparative assessment of the consistency and quality of a highly purified FSH extracted from human urine (urofollitropin) and a recombinant human FSH (follitropin \u03b1)","volume":"13","author":"Lispi","year":"2006","journal-title":"Reprod. BioMed. Online"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Meher, B.R., Dixit, A., Bousfield, G.R., and Lushington, G.H. (2015). Glycosylation Effects on FSH-FSHR Interaction Dynamics: A Case Study of Different FSH Glycoforms by Molecular Dynamics Simulations. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137897"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.mce.2013.08.021","article-title":"Structural biology of glycoprotein hormones and their receptors: Insights to signalling","volume":"382","author":"Jiang","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0303-7207(01)00657-8","article-title":"Assessment of the in vitro and in vivo biological activities of the human follicle-stimulating isohormones","volume":"186","author":"Timossi","year":"2002","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_47","unstructured":"Asian-Pacific Biotech News (2022, June 14). An Exclusive on LG Life Sciences. Available online: https:\/\/www.asiabiotech.com\/12\/1203\/0022_0028.pdf."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ejogrb.2019.07.032","article-title":"A multicenter, randomized, phase III study comparing the efficacy and safety of follitropin alpha biosimilar and the original follitropin alpha","volume":"241","author":"Barakhoeva","year":"2019","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_49","unstructured":"Drugs.com (2022, June 14). Follitrope. Available online: https:\/\/www.drugs.com\/international\/follitrope.html."},{"key":"ref_50","unstructured":"(2022, June 14). Generics and Biosimilar Initiative. Folisurge Summary of Product Characteristics. Available online: https:\/\/www.gabionline.net\/biosimilars\/general\/Similar-biologics-approved-and-marketed-in-India."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4918","DOI":"10.18632\/aging.102919","article-title":"Efficacy and safety of recombinant human follicle-stimulating hormone in patients undergoing in vitro fertilization-embryo transfer","volume":"12","author":"Hu","year":"2020","journal-title":"Aging"},{"key":"ref_52","unstructured":"Medsintez Plant (2022, June 14). The First Russian Medicine for Infertility, Primapur\u00ae by Medsintez Plant, Will Reach Clinics in the New Year. Available online: http:\/\/www.medsintez.com\/en\/novosti\/199-the-first-russian-medicine-for-infertility-primapur-by-medsintez-plant-will-reach-clinics-in-the-new-year."},{"key":"ref_53","unstructured":"PR Newswire (2022, June 14). China Recombinant Human Follitropin Market Report 2018\u20132022. Featuring Merck Serono (GONAL-f) & GeneScience Pharmaceuticals Co., Ltd. (Jinsaiheng). Available online: https:\/\/www.prnewswire.com\/news-releases\/china-recombinant-human-follitropin-market-report-2018-2022-featuring-merck-serono-gonal-f-genescience-pharmaceuticals-co-ltd-jinsaiheng-300776822.html."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1080\/09513590.2020.1792437","article-title":"Efficacy and safety of follitropin alpha biosimilars compared to their reference product: A meta-analysis","volume":"37","author":"Budani","year":"2020","journal-title":"Gynecol. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1095\/biolreprod65.5.1542","article-title":"Embryonic development after follicle culture is influenced by follicle-stimulating hormone isoelectric point range","volume":"65","author":"Vitt","year":"2001","journal-title":"Biol. Reprod."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S1472-6483(10)62135-9","article-title":"FSH isoform composition of commercial gonadotrophin preparations: A neglected aspect?","volume":"9","author":"Andersen","year":"2004","journal-title":"Reprod BioMed. Online"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1080\/13625187.2017.1361528","article-title":"Real-world research and the role of observational data in the field of gynaecology\u2014A practical review","volume":"22","author":"Heikinheimo","year":"2017","journal-title":"Eur. J. Contracept. Reprod. Health Care"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"deab126.022","DOI":"10.1093\/humrep\/deab126.022","article-title":"Effectiveness and treatment cost of assisted reproduction technology for women stimulated by gonadotropin in France: A cohort study using the National Health Database","volume":"36","author":"Benchaib","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_59","unstructured":"Iegemiddelverk, S. (2022, June 14). Decision on Admission to the Exchange List for Follitropin Alfa. Available online: https:\/\/legemiddelverket.no\/."},{"key":"ref_60","unstructured":"Australian Government Department of Health (2022, June 14). Therapeutic Goods Administration. Australian Public Assessment Report for Follitropin Alfa, Available online: https:\/\/www.tga.gov.au\/sites\/default\/files\/auspar-follitropin-alfa-rch-160408.docx."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sinegubova, M., Vorobiev, I., Klishin, A., Eremin, D., Orlova, N., Orlova, N., and Polzikov, M. (2022). Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur\u00ae) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010096"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pignataro, M.F., Herrera, M.G., and DoderClick or tap here to enter text.o, V.I. (2020). Evaluation of Peptide\/Protein Self-Assembly and Aggregation by Spectroscopic Methods. Molecules, 25.","DOI":"10.3390\/molecules25204854"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/12\/6762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:33:57Z","timestamp":1760139237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/12\/6762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,17]]},"references-count":62,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ijms23126762"],"URL":"https:\/\/doi.org\/10.3390\/ijms23126762","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,17]]}}}