{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:38:45Z","timestamp":1783017525630,"version":"3.54.6"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Reprod. Sci."],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1007\/s43032-026-02127-2","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:38:35Z","timestamp":1780324715000},"page":"1054-1060","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Injectable Collagenase Clostridium Histolyticum as a Non-surgical Treatment for Uterine Fibroids: A Scoping Review"],"prefix":"10.1007","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0191-5610","authenticated-orcid":false,"given":"Christine","family":"Aoun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charbel","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Boueri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naim","family":"Slaiby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Jallad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"2127_CR1","doi-asserted-by":"publisher","unstructured":"Wallach EE, Vlahos NF. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol. 2004;104(2):393\u2013406. https:\/\/doi.org\/10.1097\/01.AOG.0000136079.62513.39.","DOI":"10.1097\/01.AOG.0000136079.62513.39"},{"issue":"2","key":"2127_CR2","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1097\/01.grf.0000159538.27221.8c","volume":"48","author":"GL Ryan","year":"2005","unstructured":"Ryan GL, Syrop CH, Van Voorhis BJ. Role, Epidemiology, and Natural History of Benign Uterine Mass Lesions. Clin Obstet Gynecol. 2005;48(2):312\u201324. https:\/\/doi.org\/10.1097\/01.grf.0000159538.27221.8c.","journal-title":"Clin Obstet Gynecol"},{"issue":"1","key":"2127_CR3","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1067\/mob.2003.99","volume":"188","author":"DD Baird","year":"2003","unstructured":"Baird DD, Dunson DB, Hill MC, et al. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol Jan. 2003;188(1):100\u20137. https:\/\/doi.org\/10.1067\/mob.2003.99.","journal-title":"Am J Obstet Gynecol Jan"},{"issue":"4","key":"2127_CR4","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.fertnstert.2007.01.093","volume":"87","author":"WH Parker","year":"2007","unstructured":"Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril. 2007;87(4):725\u201336. https:\/\/doi.org\/10.1016\/j.fertnstert.2007.01.093.","journal-title":"Fertil Steril"},{"issue":"3","key":"2127_CR5","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1210\/jcem.79.3.8077380","volume":"79","author":"EA Stewart","year":"1994","unstructured":"Stewart EA, Friedman AJ, Peck K, et al. Relative overexpression of collagen type I and collagen type III messenger ribonucleic acids by uterine leiomyomas during the proliferative phase of the menstrual cycle. J Clin Endocrinol Metabolism. 1994;79(3):900\u20136. https:\/\/doi.org\/10.1210\/jcem.79.3.8077380.","journal-title":"J Clin Endocrinol Metabolism"},{"issue":"1","key":"2127_CR6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1093\/humupd\/dmx032","volume":"24","author":"MS Islam","year":"2018","unstructured":"Islam MS, Ciavattini A, Petraglia F, et al. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics. Hum Reprod Update. 2018;24(1):59\u201385. https:\/\/doi.org\/10.1093\/humupd\/dmx032.","journal-title":"Hum Reprod Update"},{"issue":"3","key":"2127_CR7","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/j.fertnstert.2004.04.030","volume":"82","author":"PC Leppert","year":"2004","unstructured":"Leppert PC, Baginski T, Prupas C, et al. Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium. Fertil Steril. 2004;82(3):1182\u20137. https:\/\/doi.org\/10.1016\/j.fertnstert.2004.04.030.","journal-title":"Fertil Steril"},{"key":"2127_CR8","doi-asserted-by":"publisher","unstructured":"Bartels CB, Cayton KC, Chuong FS, Holthouser K, Arian SE, Abraham T, Segars JH. An evidence-based approach to the medical management of fibroids: a systematic review. Clin Obstet Gynecol. 2016;59(1):30\u201352. https:\/\/doi.org\/10.1097\/GRF.0000000000000171.","DOI":"10.1097\/GRF.0000000000000171"},{"key":"2127_CR9","doi-asserted-by":"publisher","first-page":"818243","DOI":"10.3389\/frph.2022.818243","volume":"4","author":"O Uimari","year":"2022","unstructured":"Uimari O, Subramaniam KS, Vollenhoven B, et al. Uterine Fibroids (Leiomyomata) and Heavy Menstrual Bleeding. Front Reprod Health. 2022;4:818243. https:\/\/doi.org\/10.3389\/frph.2022.818243.","journal-title":"Front Reprod Health"},{"key":"2127_CR10","doi-asserted-by":"publisher","first-page":"403","DOI":"10.2147\/ijwh.S133212","volume":"9","author":"MJ Fuldeore","year":"2017","unstructured":"Fuldeore MJ, Soliman AM. Patient-reported prevalence and symptomatic burden of uterine fibroids among women in the United States: findings from a cross-sectional survey analysis. Int J Womens Health. 2017;9:403\u201311. https:\/\/doi.org\/10.2147\/ijwh.S133212.","journal-title":"Int J Womens Health"},{"key":"2127_CR11","doi-asserted-by":"publisher","unstructured":"Ahmed WM, Maatoug J, Al-Dahshan A et al. Uterine fibroids in women of childbearing age: a cross-sectional study at the primary health care corporation in Qatar. BMC Womens Health. 2025\/09\/29 2025;25(1):453. https:\/\/doi.org\/10.1186\/s12905-025-04004-7","DOI":"10.1186\/s12905-025-04004-7"},{"issue":"1","key":"2127_CR12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ijgo.2010.11.011","volume":"113","author":"MG Munro","year":"2011","unstructured":"Munro MG, Critchley HOD, Broder MS, et al. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynecol Obstet. 2011;113(1):3\u201313. https:\/\/doi.org\/10.1016\/j.ijgo.2010.11.011.","journal-title":"Int J Gynecol Obstet"},{"issue":"2","key":"2127_CR13","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1590\/0100-3984.2022.0048","volume":"56","author":"MS Palheta","year":"2023","unstructured":"Palheta MS, Medeiros FDC, Severiano ARG. Reporting of uterine fibroids on ultrasound examinations: an illustrated report template focused on surgical planning. Radiologia Brasileira. 2023;56(2):86\u201394. https:\/\/doi.org\/10.1590\/0100-3984.2022.0048.","journal-title":"Radiologia Brasileira"},{"key":"2127_CR14","doi-asserted-by":"publisher","unstructured":"Zapata LB, Whiteman MK, Tepper NK et al. Intrauterine device use among women with uterine fibroids: a systematic review. Contraception. 2010\/07\/01\/ 2010;82(1):41\u201355. https:\/\/doi.org\/10.1016\/j.contraception.2010.02.011","DOI":"10.1016\/j.contraception.2010.02.011"},{"key":"2127_CR15","unstructured":"Friedman AJ, Hoffman DI, Comite F et al. Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. Obstet Gynecol. 1991;77(5):720\u20135."},{"key":"2127_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/2414609","volume":"2018","author":"TD Lewis","year":"2018","unstructured":"Lewis TD, Malik M, Britten J, et al. A comprehensive review of the pharmacologic management of uterine leiomyoma. Biomed Res Int. 2018;2018:1\u201311. https:\/\/doi.org\/10.1155\/2018\/2414609.","journal-title":"Biomed Res Int"},{"key":"2127_CR17","doi-asserted-by":"publisher","unstructured":"Whiteman MK, Hillis SD, Jamieson DJ et al. Inpatient hysterectomy surveillance in the United States, 2000\u20132004. Am J Obstet Gynecol. 2008\/01\/01\/ 2008;198(1):34.e1\u201334.e7. https:\/\/doi.org\/10.1016\/j.ajog.2007.05.039","DOI":"10.1016\/j.ajog.2007.05.039"},{"key":"2127_CR18","doi-asserted-by":"publisher","unstructured":"Radosa MP, Owsianowski Z, Mothes A et al. Long-term risk of fibroid recurrence after laparoscopic myomectomy. Eur J Obstet Gynecol Reprod Biol. 2014\/09\/01\/ 2014;180:35\u201339. https:\/\/doi.org\/10.1016\/j.ejogrb.2014.05.029","DOI":"10.1016\/j.ejogrb.2014.05.029"},{"issue":"06","key":"2127_CR19","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1055\/s-0037-1607264","volume":"35","author":"A Al-Hendy","year":"2017","unstructured":"Al-Hendy A, Myers E, Stewart E. Uterine fibroids: burden and unmet medical need. Semin Reprod Med. 2017;35(06):473\u201380. https:\/\/doi.org\/10.1055\/s-0037-1607264.","journal-title":"Semin Reprod Med"},{"issue":"3","key":"2127_CR20","doi-asserted-by":"publisher","first-page":"e2111","DOI":"10.1016\/j.ajog.2011.12.002","volume":"206","author":"ER Cardozo","year":"2012","unstructured":"Cardozo ER, Clark AD, Banks NK, et al. The estimated annual cost of uterine leiomyomata in the United States. Am J Obstet Gynecol. 2012;206(3):e2111\u20139. https:\/\/doi.org\/10.1016\/j.ajog.2011.12.002.","journal-title":"Am J Obstet Gynecol"},{"issue":"12","key":"2127_CR21","doi-asserted-by":"publisher","first-page":"3743","DOI":"10.1007\/s43032-024-01727-0","volume":"31","author":"D Hazimeh","year":"2024","unstructured":"Hazimeh D, Coco A, Casubhoy I, et al. The annual economic burden of uterine fibroids in the United States (2010 versus 2022): a comparative cost-analysis. Reprod Sci Dec. 2024;31(12):3743\u201356. https:\/\/doi.org\/10.1007\/s43032-024-01727-0.","journal-title":"Reprod Sci Dec"},{"issue":"6","key":"2127_CR22","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.jhsa.2007.04.002","volume":"32","author":"MA Badalamente","year":"2007","unstructured":"Badalamente MA, Hurst LC. Efficacy and safety of injectable mixed collagenase subtypes in the treatment of Dupuytren\u2019s contracture. J Hand Surg Am Jul\u2013Aug. 2007;32(6):767\u201374. https:\/\/doi.org\/10.1016\/j.jhsa.2007.04.002.","journal-title":"J Hand Surg Am Jul\u2013Aug"},{"issue":"1","key":"2127_CR23","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.juro.2013.01.087","volume":"190","author":"M Gelbard","year":"2013","unstructured":"Gelbard M, Goldstein I, Hellstrom WJ, et al. Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol Jul. 2013;190(1):199\u2013207. https:\/\/doi.org\/10.1016\/j.juro.2013.01.087.","journal-title":"J Urol Jul"},{"issue":"2014","key":"2127_CR24","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1155\/2014\/783289","volume":"2014","author":"PC Leppert","year":"2014","unstructured":"Leppert PC, Segars JH, Jayes FL, et al. The extracellular matrix contributes to mechanotransduction in uterine fibroids. Obstet Gynecol Int. 2014;2014(2014):215\u201326. https:\/\/doi.org\/10.1155\/2014\/783289.","journal-title":"Obstet Gynecol Int"},{"key":"2127_CR25","unstructured":"U.S. Food and Drug Administration. Drugs@FDA: FDA-approved drugs. https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=BasicSearch.process. Accessed April 1, 2026."},{"issue":"7","key":"2127_CR26","doi-asserted-by":"publisher","first-page":"467","DOI":"10.7326\/m18-0850","volume":"2","author":"AC Tricco","year":"2018","unstructured":"Tricco AC, Lillie E, Zarin W, et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med Oct. 2018;2(7):467\u201373. https:\/\/doi.org\/10.7326\/m18-0850.","journal-title":"Ann Intern Med Oct"},{"issue":"12","key":"2127_CR27","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1177\/1933719114553449","volume":"21","author":"LN Brunengraber","year":"2014","unstructured":"Brunengraber LN, Jayes FL, Leppert PC. Injectable clostridium histolyticum collagenase as a potential treatment for uterine fibroids. Reproductive Sci. 2014;21(12):1452\u20139. https:\/\/doi.org\/10.1177\/1933719114553449.","journal-title":"Reproductive Sci"},{"key":"2127_CR28","doi-asserted-by":"publisher","unstructured":"Corder RD, Gadi SV, Vachieri RB et al. Using rheology to quantify the effects of localized collagenase treatments on uterine fibroid digestion. Acta Biomaterialia. 2021\/10\/15\/ 2021;134:443\u2013452. https:\/\/doi.org\/10.1016\/j.actbio.2021.08.003","DOI":"10.1016\/j.actbio.2021.08.003"},{"issue":"7","key":"2127_CR29","doi-asserted-by":"publisher","first-page":"e475","DOI":"10.1002\/ctm2.475","volume":"11","author":"MS Islam","year":"2021","unstructured":"Islam MS, Afrin S, Singh B, et al. Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids. Clin Transl Med. 2021;11(7):e475. https:\/\/doi.org\/10.1002\/ctm2.475.","journal-title":"Clin translational Med"},{"issue":"5","key":"2127_CR30","doi-asserted-by":"publisher","first-page":"e5961","DOI":"10.1016\/j.ajog.2016.05.006","volume":"215","author":"FL Jayes","year":"2016","unstructured":"Jayes FL, Liu B, Moutos FT, et al. Loss of stiffness in collagen-rich uterine fibroids after digestion with purified collagenase Clostridium histolyticum. Am J Obstet Gynecol. 2016;215(5):e5961\u20138. https:\/\/doi.org\/10.1016\/j.ajog.2016.05.006. 2016\/11\/01.","journal-title":"Am J Obstet Gynecol"},{"issue":"9","key":"2127_CR31","doi-asserted-by":"publisher","first-page":"2699","DOI":"10.1007\/s43032-021-00573-8","volume":"28","author":"B Singh","year":"2021","unstructured":"Singh B, Sims H, Trueheart I, et al. A phase I clinical trial to assess safety and tolerability of injectable collagenase in women with symptomatic uterine fibroids. Reproductive Sci. 2021;28(9):2699\u2013709. https:\/\/doi.org\/10.1007\/s43032-021-00573-8.","journal-title":"Reproductive Sci"},{"issue":"7350","key":"2127_CR32","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature10137","volume":"474","author":"S Dupont","year":"2011","unstructured":"Dupont S, Morsut L, Aragona M, et al. Role of YAP\/TAZ in mechanotransduction. Nat (London). 2011;474(7350):179\u201383. https:\/\/doi.org\/10.1038\/nature10137.","journal-title":"Nat (London)"},{"key":"2127_CR33","doi-asserted-by":"publisher","unstructured":"Wenzl R, Huber J, Illievich U, Jirecek S, Holzer A. Laparoscopic versus open myomectomy: a double-blind study to evaluate postoperative pain. Anesthesia & Analgesia. 2006;102(5):1480\u20131484. https:\/\/doi.org\/10.1213\/01.ane.0000204321.85599.","DOI":"10.1213\/01.ane.0000204321.85599"},{"key":"2127_CR34","doi-asserted-by":"publisher","unstructured":"Osaheni O, Idehen HO, Imarengiaye CO. Analgesia for postoperative myomectomy pain: A comparison of ultrasound-guided transversus abdominis plane block and wound infiltration. Niger J Clin Pract. 2020;23(11):1523\u20131529. https:\/\/doi.org\/10.4103\/njcp.njcp_162_19.","DOI":"10.4103\/njcp.njcp_162_19"}],"container-title":["Reproductive Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-026-02127-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43032-026-02127-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43032-026-02127-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:37:41Z","timestamp":1783013861000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43032-026-02127-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["2127"],"URL":"https:\/\/doi.org\/10.1007\/s43032-026-02127-2","relation":{},"ISSN":["1933-7191","1933-7205"],"issn-type":[{"value":"1933-7191","type":"print"},{"value":"1933-7205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"1 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2026","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 is a systematic review of the literature on Clostridium, and therefore did not require Institutional Review Board approval.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The authors declare no financial, personal, political, intellectual, or religious interests related to this work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}