{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:58:11Z","timestamp":1789016291256,"version":"build-2803163510"},"reference-count":20,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"unspecified","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014688","name":"Region Uppsala","doi-asserted-by":"publisher","award":["LUL-1027432"],"award-info":[{"award-number":["LUL-1027432"]}],"id":[{"id":"10.13039\/501100014688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007212","name":"V\u00e4stra G\u00f6talandsregionen","doi-asserted-by":"publisher","award":["ALFGBG-1005815"],"award-info":[{"award-number":["ALFGBG-1005815"]}],"id":[{"id":"10.13039\/100007212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007212","name":"V\u00e4stra G\u00f6talandsregionen","doi-asserted-by":"publisher","award":["NHV-1004826"],"award-info":[{"award-number":["NHV-1004826"]}],"id":[{"id":"10.13039\/100007212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006636","name":"Forskningsr\u00e5det om H\u00e4lsa, Arbetsliv och V\u00e4lf\u00e4rd","doi-asserted-by":"publisher","award":["Dnr 2024-01521"],"award-info":[{"award-number":["Dnr 2024-01521"]}],"id":[{"id":"10.13039\/501100006636","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Region Stockholm","award":["FoUI-1002199"],"award-info":[{"award-number":["FoUI-1002199"]}]},{"DOI":"10.13039\/501100007687","name":"Swedish Society of Medicine","doi-asserted-by":"crossref","award":["SLS-1016429"],"award-info":[{"award-number":["SLS-1016429"]}],"id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,3,6]]},"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Endometriosis is a chronic, inflammatory and oestrogen-dependent disease frequently causing infertility. Assisted reproductive technologies (ART) are often required to achieve pregnancy, especially in women with advanced endometriosis. To date, there is no randomised controlled trial (RCT) exploring reproductive outcomes after first-line surgery followed by ART versus first-line ART in women with stage III-IV endometriosis. The aim in this study is to investigate if endometriosis surgery prior to ART in women with endometriosis stage III-IV and infertility results in improved reproductive outcomes compared with first-line ART.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A national multicentre prospective open label RCT including 350 subjects with stage III-IV endometriosis and infertility. Women aged 18\u201338\u2009will be randomised 1:1 to endometriosis surgery prior to ART or first-line ART. Follow-up until 3 years from the first treatment.<\/jats:p>\n                    <jats:p>The primary outcome is the cumulative live birth rate 3 years after inclusion. Secondary outcomes are cumulative pregnancy rate, reproductive outcomes per in vitro fertilisation cycle, miscarriage rate, time to pregnancy and live birth, plasma progesterone levels on the day of frozen embryo transfer in hormone replacement cycles, obstetrical outcomes and complications, infections after oocyte retrieval, intraoperative and postoperative complications, pain, quality of life and cost-effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study protocol, patient information and informed consent are approved by Swedish Ethical Review Authority (dnr: 2024\u201304293-01, approved 7 October 2024, amendment, dnr: 2025\u201303699-02, approved 17 June 2025).<\/jats:p>\n                    <jats:p>An interim analysis is scheduled to ensure the safety of the interventions.<\/jats:p>\n                    <jats:p>The results of Endo-SOFT (Endometriosis: Surgery Or Fertility Treatment) will be published in scientific journals and are expected to influence clinical guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT07240363\">NCT07240363<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-111928","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T17:42:36Z","timestamp":1774806156000},"page":"e111928","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Endo-SOFT: study protocol for a national multicentre randomised controlled trial \u2013 first-line surgery versus first-line assisted reproductive technologies in patients with advanced endometriosis"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct07240363","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9131-7040","authenticated-orcid":false,"given":"Anna","family":"Marklund","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden"},{"name":"Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-7604","authenticated-orcid":false,"given":"Julia","family":"W\u00e4ngberg Nordborg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Gynecology and Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Asciutto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Uppsala University Hospital, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2253-4682","authenticated-orcid":false,"given":"Evangelia","family":"Elenis","sequence":"additional","affiliation":[{"name":"Women's and Children\u2019s Health, Uppsala Universitet, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2164-6145","authenticated-orcid":false,"given":"Jynfiaf","family":"Francis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Gynecology and Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligita","family":"Jokubkiene","sequence":"additional","affiliation":[{"name":"Obstetric, Gynaecological and Prenatal Ultrasound Research, Department of Clinical Sciences, Lund University, Malmo, Sweden"},{"name":"Department of Obstetrics and Gynecology, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Wennmo Zuk","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, S\u00f6dersjukhuset, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-567X","authenticated-orcid":false,"given":"Hanna","family":"\u00c5mark","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, S\u00f6dersjukhuset, Stockholm, Sweden"},{"name":"Departement of Clinical Science and Education S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-6181","authenticated-orcid":false,"given":"Kenny A","family":"Rodriguez-Wallberg","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Reproductive Medicine, Division of Gynecology and Reproduction, Karolinska Universitetssjukhuset, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7135-3132","authenticated-orcid":false,"given":"Karin","family":"Sundfeldt","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Goteborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6674-3849","authenticated-orcid":false,"given":"Maria","family":"Forslund","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Gynecology and Reproductive Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-8583","authenticated-orcid":false,"given":"Malin","family":"Brunes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, S\u00f6dersjukhuset, Stockholm, Sweden"},{"name":"Departement of Clinical Science and Education S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"2026032910423298000_16.3.e111928.1","doi-asserted-by":"crossref","unstructured":"Becker CM , Bokor A , Heikinheimo O , et al . ESHRE guideline: endometriosis. Hum Reprod Open 2022;2022. doi:10.1093\/hropen\/hoac009","DOI":"10.1093\/hropen\/hoac009"},{"key":"2026032910423298000_16.3.e111928.2","doi-asserted-by":"crossref","unstructured":"Giudice LC KL . Endometriosis. London, England: Lancet, 2004.","DOI":"10.1016\/S0140-6736(04)17403-5"},{"key":"2026032910423298000_16.3.e111928.3","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev335"},{"key":"2026032910423298000_16.3.e111928.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.05.031"},{"key":"2026032910423298000_16.3.e111928.5","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew085"},{"key":"2026032910423298000_16.3.e111928.6","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13082"},{"key":"2026032910423298000_16.3.e111928.7","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.fertnstert.2022.07.024","article-title":"Prevalence of endometrioma and deep infiltrating endometriosis at transvaginal ultrasound examination of subfertile women undergoing assisted reproductive treatment","volume":"118","author":"Alson","year":"2022","journal-title":"Fertil Steril"},{"key":"2026032910423298000_16.3.e111928.8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0015-0282(16)48674-7","article-title":"Expectant management and hydrotubations in the treatment of endometriosis-associated infertility","volume":"44","author":"Olive","year":"1985","journal-title":"Fertil Steril"},{"key":"2026032910423298000_16.3.e111928.9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/uog.13366","article-title":"Impact of endometriosis and its staging on assisted reproduction outcome: systematic review and meta-analysis","volume":"44","author":"Barbosa","year":"2014","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2026032910423298000_16.3.e111928.10","doi-asserted-by":"crossref","unstructured":"Liang Y , Liu M , Zhang J , et al . First-line surgery versus first-line assisted reproductive technology for women with deep infiltrating endometriosis: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024;15. doi:10.3389\/fendo.2024.1352770","DOI":"10.3389\/fendo.2024.1352770"},{"key":"2026032910423298000_16.3.e111928.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(97)81391-X"},{"key":"2026032910423298000_16.3.e111928.12","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ejogrb.2022.11.013","article-title":"First-line surgery vs first-line ART to manage infertility in women with deep endometriosis without bowel involvement: A multi-centric propensity-score matching comparison","volume":"280","author":"Ferrier","year":"2023","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2026032910423298000_16.3.e111928.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.07.002"},{"key":"2026032910423298000_16.3.e111928.14","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv035"},{"key":"2026032910423298000_16.3.e111928.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-017-4640-1"},{"key":"2026032910423298000_16.3.e111928.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.09.035"},{"key":"2026032910423298000_16.3.e111928.17","doi-asserted-by":"crossref","unstructured":"Saridogan E , Becker CM , Feki A , et al . Recommendations for the surgical treatment of endometriosis. Part 1: ovarian endometrioma. Human Reproduction Open 2017;2017. doi:10.1093\/hropen\/hox016","DOI":"10.1093\/hropen\/hox016"},{"key":"2026032910423298000_16.3.e111928.18","first-page":"269","article-title":"Recommendations for the surgical treatment of endometriosis Part 2: deep endometriosis\u2020\u2021\u00b6","volume":"11","year":"2020","journal-title":"Facts Views Vis Obgyn"},{"key":"2026032910423298000_16.3.e111928.19","unstructured":"Group NeSS . National guideline \u2013 endometriosis surgery (highly specialized care). n.d. Available: https:\/\/www.sfog.se\/wp-content\/uploads\/2025\/03\/vaardprogram-nhv-endometrioskirurgi-2024.pdf2024"},{"key":"2026032910423298000_16.3.e111928.20","unstructured":"Rekommendation assisterad befruktning- dubbeldonation och embryodonation. SKR; 2022. Available: https:\/\/skr.se\/download\/18.1e10e3a11847c6a2a5a20b51\/1668778314464\/WEBB-KOMB-14-2022-Meddelande-Rekommendation%20assisterad%20befruktning.pdf"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2025-111928","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T17:42:38Z","timestamp":1774806158000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2025-111928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":20,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,25]]},"published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1136\/bmjopen-2025-111928"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2025-111928","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]}}}