{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:25:11Z","timestamp":1740108311065,"version":"3.37.3"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"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":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Infertility is a topic of growing interest, and female infertility is often treated with gonadotropins. Evidence regarding comparative safety and efficacy of different gonadotropin formulations is available from clinical studies, while real-world data are missing. The present study aims to investigate effectiveness and safety of treatment with different gonadotropin formulations in women undergoing medically assisted procreation treatments in Latium, a region in central Italy, through a real-world data approach.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A retrospective population-based cohort study in women between the ages of 18 and 45\u00a0years who were prescribed with at least one gonadotropin between 2007 and 2019 was conducted. Women were enrolled from the regional drug dispense registry, and data on their clinical history, exposure to therapeutic cycles (based on recombinant \u201cREC\u201d or extractives \u201cEXT\u201d gonadotropin, or combined protocol \u201cCMD\u201d (REC\u2009+\u2009EXT)), and maternal\/infantile outcomes were linked from the regional healthcare administrative databases. Multivariate logistic regression models were applied to estimate the association between exposure and outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Overall, 90,292 therapeutic cycles prescribed to 35,899 women were linked to pregnancies. Overall, 15.8% of cycles successfully led to pregnancy. Compared to extractives, recombinant and combined treatments showed a stronger association with conception rate (RR<jats:sub>REC<\/jats:sub> adj\u2009=\u20091.06, 95% CI: 1.01\u20131.12; RR<jats:sub>CBD<\/jats:sub> adj\u2009=\u20091.17, 95% CI: 1.11\u20131.24). Maternal outcomes occurred in less than 5% of deliveries, and no significant differences between treatments were observed (REC vs EXT, pre-eclampsia: RR adj\u2009=\u20091.24, 95% CI: 0.86\u20131.79, ovarian hyperstimulation syndrome: RR adj\u2009=\u20091.25, 95% CI: 0.59\u20132.65, gestational diabetes: RR adj\u2009=\u20091.06, 95% CI: 0.84\u20131.35). Regarding infantile outcomes, similar results were obtained for different gonadotropin formulations (REC vs EXT: low birth weight: RR adj\u2009=\u20090.98, 95% CI: 0.83\u20131.26, multiple births: RR adj\u2009=\u20091.06, 95% CI: 0.92\u20131.23, preterm birth: RR adj\u2009=\u20091.03, 95% CI: 0.92\u20131.26).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Efficacy and safety profiles of REC proved to be similar to those of EXT. Regarding the efficacy in terms of conception rate and birth rate, protocols using the combined approach performed slightly better. Outcomes related to maternal and infantile safety were generally very rare, and safety features were overlapping between gonadotropin formulations.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00228-022-03330-1","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T10:06:21Z","timestamp":1651658781000},"page":"1185-1196","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effectiveness and safety of gonadotropins used in female infertility: a population-based study in the Lazio region, Italy"],"prefix":"10.1007","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6653-9605","authenticated-orcid":false,"given":"Alessandro Cesare","family":"Rosa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Pacchiarotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Addis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Ciardulli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Belleudi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Davoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ursula","family":"Kirchmayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"doi-asserted-by":"publisher","unstructured":"Bull World Health Organ 2010; 88:881\u2013882 | https:\/\/doi.org\/10.2471\/BLT.10.011210","key":"3330_CR1","DOI":"10.2471\/BLT.10.011210"},{"unstructured":"Scaravelli G, De Luca R, Vigiliano V, Bolli  S, Spoletini R, Mazzola M, Bertini A, Speziale L (2019) Attivit\u00e0 del registro nazionale italiano della procreazione medicalmente assistita. https:\/\/www.iss.it\/documents\/20126\/0\/Report+PMA+dati+2019.pdf\/30259d03-ba6c-5a41-2b0f-8ead6514624d?t=1646662121400. Accessed 03 May 2022","key":"3330_CR2"},{"doi-asserted-by":"publisher","unstructured":"Carson SA, Kallen AN (2021) Diagnosis and management of infertility: a review. JAMA 326(1):65\u201376. https:\/\/doi.org\/10.1001\/jama.2021.4788 (PMID: 34228062)","key":"3330_CR3","DOI":"10.1001\/jama.2021.4788"},{"doi-asserted-by":"publisher","unstructured":"Out HJ, Driessen SG, Mannaerts BM, Coelingh Bennink HJ (1997) Recombinant follicle-stimulating hormone (follitropin beta, Puregon) yields higher pregnancy rates in in vitro fertilization than urinary gonadotropins. Fertil Steril 68(1):138\u2013142. https:\/\/doi.org\/10.1016\/s0015-0282(97)81490-2 (PMID: 9207599)","key":"3330_CR4","DOI":"10.1016\/s0015-0282(97)81490-2"},{"doi-asserted-by":"publisher","unstructured":"Pacchiarotti A, Aragona C, Gaglione R, Selman H (2007) Efficacy of a combined protocol of urinary and recombinant follicle-stimulating hormone used for ovarian stimulation of patients undergoing ICSI cycle. J Assist Reprod Genet 24(9):400\u20135. https:\/\/doi.org\/10.1007\/s10815-007-9159-0. Epub 2007 Jul 26. PMID: 17653846; PMCID: PMC3454948.","key":"3330_CR5","DOI":"10.1007\/s10815-007-9159-0"},{"doi-asserted-by":"publisher","unstructured":"Pacchiarotti A, Selman H, Valeri C, Napoletano S, Sbracia M, Antonini G, Biagiotti G, Pacchiarotti A (2016) Ovarian stimulation protocol in IVF: an up-to-date review of the literature. Curr Pharm Biotechnol 17(4):303\u2013315. https:\/\/doi.org\/10.2174\/1389201017666160118103147 (PMID: 26775651)","key":"3330_CR6","DOI":"10.2174\/1389201017666160118103147"},{"doi-asserted-by":"publisher","unstructured":"Pacchiarotti A, Sbracia M, Frega A, Selman H, Rinaldi L, Pacchiarotti A (2010) Urinary hMG (Meropur) versus recombinant FSH plus recombinant LH (Pergoveris) in IVF: a multicenter, prospective, randomized controlled trial. Fertil Steril 94(6):2467\u20132469. https:\/\/doi.org\/10.1016\/j.fertnstert.2010.04.035 (Epub 2010 May 26 PMID: 20537626)","key":"3330_CR7","DOI":"10.1016\/j.fertnstert.2010.04.035"},{"doi-asserted-by":"publisher","unstructured":"Patki A, Bavishi H, Kumari C, Kamraj J, Venugopal M, Kunjimoideen KU, Nadkarni P, Sankari S, Chaudhary S, Sangeeta MJ, Manjunath CS, Kumar P (2018) Urinary versus recombinant gonadotropins for ovarian stimulation in women undergoing treatment with assisted reproductive technology. J Hum Reprod Sci\u00a011(2):119\u2013124. https:\/\/doi.org\/10.4103\/jhrs.JHRS_79_17. PMID: 30158806; PMCID: PMC6094533.","key":"3330_CR8","DOI":"10.4103\/jhrs.JHRS_79_17"},{"doi-asserted-by":"publisher","unstructured":"Weiss NS, Kostova E, Nahuis M, Mol BWJ, van der Veen F, van Wely M (2019) Gonadotrophins for ovulation induction in women with polycystic ovary syndrome. Cochrane Database Syst Rev 16;1(1):CD010290. https:\/\/doi.org\/10.1002\/14651858.CD010290.pub3. PMID: 30648738; PMCID: PMC6353048.","key":"3330_CR9","DOI":"10.1002\/14651858.CD010290.pub3"},{"doi-asserted-by":"publisher","unstructured":"Al-Inany H, Aboulghar M, Mansour R, Serour G (2003) Meta-analysis of recombinant versus urinary-derived FSH: an update 18(2):305\u2013313. https:\/\/doi.org\/10.1093\/humrep\/deg088 (PMID: 12571166)","key":"3330_CR10","DOI":"10.1093\/humrep\/deg088"},{"doi-asserted-by":"publisher","unstructured":"van Wely M, Kwan I, Burt AL, Thomas J, Vail A, Van der Veen F, Al-Inany HG (2011) Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles. Cochrane Database Syst Rev 16(2):CD005354. https:\/\/doi.org\/10.1002\/14651858.CD005354.pub2. PMID: 21328276; PMCID: PMC7388278","key":"3330_CR11","DOI":"10.1002\/14651858.CD005354.pub2"},{"unstructured":"Certificato di assistenza al parto (CeDAP) (2018) Analisi dell\u2019evento nascita - Anno.\u00a0https:\/\/www.salute.gov.it\/imgs\/C_17_pubblicazioni_3034_allegato.pdf","key":"3330_CR12"},{"issue":"5","key":"3330_CR13","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1097\/AOG.0b013e3182a603bb.PMID:24104771;PMCID:PMC3829199","volume":"122","author":"BT Bateman","year":"2013","unstructured":"Bateman BT, Mhyre JM, Hernandez-Diaz S, Huybrechts KF, Fischer MA, Creanga AA, Callaghan WM, Gagne JJ (2013) Development of a comorbidity index for use in obstetric patients. Obstet Gynecol 122(5):957\u2013965. https:\/\/doi.org\/10.1097\/AOG.0b013e3182a603bb.PMID:24104771;PMCID:PMC3829199","journal-title":"Obstet Gynecol"},{"key":"3330_CR14","first-page":"353","volume":"51","author":"E Bertino","year":"2010","unstructured":"Bertino E, Spada E, Occhi L, Coscia A, Giuliani F, Gagliardi L, Gilli G, Bona G, Fabris C, De Curtis M, Milani S (2010) Neonatal anthropometric charts: the Italian neonatal study compared with other European studies. JPGN 51:353\u2013361","journal-title":"JPGN"}],"container-title":["European Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-022-03330-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00228-022-03330-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00228-022-03330-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T09:15:24Z","timestamp":1654766124000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00228-022-03330-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,4]]},"references-count":14,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["3330"],"URL":"https:\/\/doi.org\/10.1007\/s00228-022-03330-1","relation":{},"ISSN":["0031-6970","1432-1041"],"issn-type":[{"type":"print","value":"0031-6970"},{"type":"electronic","value":"1432-1041"}],"subject":[],"published":{"date-parts":[[2022,5,4]]},"assertion":[{"value":"22 October 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2022","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 research was notified to \u2018Lazio Region Ethics Committee\u2019. This is an observational, retrospective, population-based study. Data were collected from Health Information Systems of the Lazio Region, Italy. The Department of Epidemiology is legitimised by the \u201cLazio\nRegion Committee\u201d in managing and analysing data from the regional Health Information Systems for epidemiological purposes. Patient data were completely anonymized, and results were reported in aggregate form only.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Consent to participate is not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}