{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:42:18Z","timestamp":1786549338759,"version":"build-2736575974"},"reference-count":25,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>This study aimed to assess whether co-treatment with gonadotropin-releasing hormone agonists during cyclophosphamide therapy protects ovarian function and preserves fertility in women with systemic lupus erythematosus. We performed a systematic review and meta-analysis of comparative cohort studies including premenopausal women with systemic lupus erythematosus treated with intravenous cyclophosphamide with or without gonadotropin-releasing hormone agonists. The primary outcome was primary ovarian insufficiency, with pregnancy and serious adverse events as secondary outcomes. Two reviewers independently selected studies, extracted data, and assessed risk of bias. Pooled risk ratios with 95% confidence intervals were calculated using fixed-effect models. Five cohort studies including 162 women (93 with gonadotropin-releasing hormone agonists and 69 controls) met the inclusion criteria; no randomized controlled trials were available. Premature ovarian insufficiency occurred in 5 of 93 women receiving gonadotropin-releasing hormone agonists and in 28 of 69 controls, corresponding to a risk ratio of 0.16 (95% confidence interval (CI): 0.07\u20130.37). Pregnancy was more frequent after gonadotropin-releasing hormone agonist co-treatment (19 of 87 versus 6 of 60 women; risk ratio: 1.82, 95% CI: 0.86\u20133.86), although this difference did not reach statistical significance. The incidence of serious adverse events was similar between groups (10 of 36 versus 10 of 34 women; risk ratio: 0.99; 95% CI: 0.50\u20131.93). In premenopausal women with systemic lupus erythematosus receiving cyclophosphamide, co-treatment with gonadotropin-releasing hormone agonists markedly reduces the risk of primary ovarian insufficiency without evidence of added serious toxicity and may increase subsequent pregnancy. However, the absence of randomized controlled trials represents a major limitation, and larger prospective randomized or well-controlled studies with a standardized long-term reproductive follow-up are needed to confirm these findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus is an autoimmune disease that often affects young women. When the disease is severe, the drug cyclophosphamide, which can damage the ovaries and cause early menopause and infertility, may be used. With our study, we wanted to assess whether adding injections of gonadotropin-releasing hormone agonists, drugs that temporarily switch off the ovaries, can protect fertility. We combined results from five studies including 162 women with systemic lupus erythematosus who received cyclophosphamide with or without these hormone injections. Early permanent loss of ovarian function occurred in 5 of 93 women who received the injections, compared with 28 of 69 women who did not. More women in the injection group later became pregnant (19 of 87 versus 6 of 60). Serious side effects were similar in both groups. These findings suggest that temporary ovarian suppression during cyclophosphamide treatment can reduce the risk of losing fertility in young women with systemic lupus erythematosus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/raf-25-0191","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:25:01Z","timestamp":1785147901000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-13","source":"Crossref","is-referenced-by-count":0,"title":["Gonadotropin-releasing hormone agonists during cyclophosphamide for ovarian protection in systemic lupus erythematosus"],"prefix":"10.1530","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-0965","authenticated-orcid":true,"given":"Mauro Francesco Pio","family":"Maiorano","sequence":"first","affiliation":[{"name":"Unit of Obstetrics and Gynecology, Department of Interdisciplinary Medicine (DIM), University of Bari \u201cAldo Moro\u201d, Policlinico of Bari 1 , ,","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Cormio","sequence":"additional","affiliation":[{"name":"Unit of Obstetrics and Gynecology, Department of Interdisciplinary Medicine (DIM), University of Bari \u201cAldo Moro\u201d, Policlinico of Bari 1 , ,","place":["Bari, Italy"]},{"name":"Gynecologic Oncology Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d 2 , ,","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Loizzi","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d 2 , ,","place":["Bari, Italy"]},{"name":"Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari \u201cAldo Moro\u201d, Policlinico of Bari 3 , ,","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigida Anna","family":"Maiorano","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IRCCS San Raffaele Hospital 4 , ,","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Corrado","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Unit, Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS 5 , ,","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Silvestris","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Unit, IRCCS Istituto Tumori \u201cGiovanni Paolo II\u201d 2 , ,","place":["Bari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026081210413908100_bib1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1191\/096120300678828596","article-title":"Preservation of fertility and ovarian function and minimizing gonadotoxicity in young women with systemic lupus erythematosus treated by chemotherapy","volume":"9","author":"Blumenfeld","year":"2000","journal-title":"Lupus"},{"key":"2026081210413908100_bib2","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.semarthrit.2011.05.008","article-title":"Gonadotropin-releasing hormone agonists may minimize cyclophosphamide-associated gonadotoxicity in systemic lupus erythematosus and autoimmune diseases","volume":"41","author":"Blumenfeld","year":"2011","journal-title":"Semin Arthritis Rheum"},{"key":"2026081210413908100_bib3","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1001\/jamasurg.2021.0522","article-title":"MOOSE reporting guidelines for meta-analyses of observational studies","volume":"156","author":"Brooke","year":"2021","journal-title":"JAMA Surg"},{"key":"2026081210413908100_bib4","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/biomet\/37.3-4.256","article-title":"The comparison of percentages in matched samples","volume":"37","author":"Cochran","year":"1950","journal-title":"Biometrika"},{"key":"2026081210413908100_bib5","article-title":"Use of gonadotropin-releasing hormone agonists for ovarian preservation in patients receiving cyclophosphamide for systemic lupus erythematosus: a meta-analysis","volume":"74","author":"Ejaz","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"2026081210413908100_bib6","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1136\/annrheumdis-2019-215089","article-title":"2019 update of the EULAR recommendations for the management of systemic lupus erythematosus","volume":"78","author":"Fanouriakis","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"2026081210413908100_bib7","doi-asserted-by":"crossref","first-page":"S128","DOI":"10.4103\/0973-3698.194546","article-title":"Fertility and pregnancy in systemic lupus erythematosus","volume":"11","author":"Jones","year":"2016","journal-title":"Indian J Rheumatol"},{"key":"2026081210413908100_bib8","article-title":"Systemic lupus erythematosus","volume-title":"StatPearls [Internet]","author":"Justiz Vaillant","year":"2025"},{"key":"2026081210413908100_bib9","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1111\/1756-185X.13318","article-title":"Effect of a gonadotropin-releasing hormone analog for ovarian function preservation after intravenous cyclophosphamide therapy in systemic lupus erythematosus patients: a retrospective inception cohort study","volume":"21","author":"Koga","year":"2018","journal-title":"Int J Rheum Dis"},{"key":"2026081210413908100_bib10","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1200\/JCO.2018.78.0858","article-title":"Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer: a systematic review and meta-analysis of individual patient-level data","volume":"36","author":"Lambertini","year":"2018","journal-title":"J Clin Oncol"},{"key":"2026081210413908100_bib11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.autrev.2005.10.001","article-title":"Prevention of gonadal toxicity and preservation of gonadal function and fertility in young women with systemic lupus erythematosus treated by cyclophosphamide: the PREGO study","volume":"5","author":"Manger","year":"2006","journal-title":"Autoimmun Rev"},{"key":"2026081210413908100_bib12","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/1529-0131(199805)41:5<831::AID-ART9>3.0.CO;2-1","article-title":"Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy","volume":"41","author":"Mok","year":"1998","journal-title":"Arthritis Rheum"},{"key":"2026081210413908100_bib13","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1093\/jnci\/djy185","article-title":"Final analysis of the prevention of early menopause study (POEMS)\/SWOG intergroup S0230","volume":"111","author":"Moore","year":"2019","journal-title":"J Natl Cancer Inst"},{"key":"2026081210413908100_bib14","first-page":"343","article-title":"Treatment with gonadotropin-releasing hormone agonists in systemic lupus erythematosus patients receiving cyclophosphamide: a long-term follow-up study","volume":"22","author":"Orefice","year":"2020","journal-title":"Isr Med Assoc J"},{"key":"2026081210413908100_bib15","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1136\/annrheumdis-2017-eular.6381","article-title":"Ovarian function preservation with gonadotropin-releasing hormone analogues in patients with systemic lupus erythematosus treated with cyclophosphamide","volume":"76","author":"Pacucci","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"2026081210413908100_bib16","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2026081210413908100_bib17","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/acr.24130","article-title":"2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases","volume":"72","author":"Sammaritano","year":"2020","journal-title":"Arthritis Care Res"},{"key":"2026081210413908100_bib18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jclinepi.2023.05.010","article-title":"The development methods of official GRADE articles and requirements for claiming the use of GRADE: a statement by the GRADE guidance group","volume":"159","author":"Sch\u00fcnemann","year":"2023","journal-title":"J Clin Epidemiol"},{"key":"2026081210413908100_bib19","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1002\/art.21263","article-title":"Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus","volume":"52","author":"Somers","year":"2005","journal-title":"Arthritis Rheum"},{"key":"2026081210413908100_bib20","first-page":"713","article-title":"Gender impact in systemic lupus erythematosus","volume":"22","author":"Soto","year":"2004","journal-title":"Clin Exp Rheumatol"},{"key":"2026081210413908100_bib21","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"2026081210413908100_bib22","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1200\/JCO-24-02782","article-title":"Fertility preservation in people with cancer: ASCO guideline update","volume":"43","author":"Su","year":"2025","journal-title":"J Clin Oncol"},{"key":"2026081210413908100_bib23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1517\/14740338.3.1.39","article-title":"Safety of gonadotropin-releasing hormone agonists and antagonists","volume":"3","author":"Tarlatzis","year":"2004","journal-title":"Expert Opin Drug Saf"},{"key":"2026081210413908100_bib24","doi-asserted-by":"crossref","first-page":"573","DOI":"10.7326\/0003-4819-147-8-200710160-00010","article-title":"The STROBE statement: guidelines for reporting observational studies","volume":"147","author":"von Elm","year":"2007","journal-title":"Ann Intern Med"},{"key":"2026081210413908100_bib25","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2174\/1874312900802010089","article-title":"Pregnancy outcome in systemic lupus erythematosus is improving: results from a case\u2013control study and literature review","volume":"2","author":"Yan Yuen","year":"2008","journal-title":"Open Rheumatol J"}],"container-title":["Reproduction and Fertility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article-pdf\/doi\/10.1530\/RAF-25-0191\/522849\/raf-25-0191.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article-pdf\/doi\/10.1530\/RAF-25-0191\/522849\/raf-25-0191.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:41:55Z","timestamp":1786545715000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article\/7\/3\/RAF250191\/77903\/Gonadotropin-releasing-hormone-agonists-during"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1530\/raf-25-0191","relation":{},"ISSN":["2633-8386"],"issn-type":[{"value":"2633-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"RAF250191"}}