{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:01:22Z","timestamp":1791662482511,"version":"4.3.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Maternal spindle transfer (MST) and pronuclear transfer (PNT) raise a number of important ethical and regulatory issues. These IVF procedures that transfer nuclear DNA to enucleated oocytes or zygotes aim to prevent transmitting mitochondrial disease by female carriers of mitochondrial DNA (mtDNA) mutations and enable them to have healthy genetically related children. MST\/PNT might also prove effective in treating oocyte-related infertility, but are not permitted in the UK and Australia, unlike MST\/PNT for mtDNA disorders. The paper discusses the regulation of MST\/PNT for both applications in relation to their risks and efficacy, highlighting the scarcity of clinical data. Based on risk reduction, it has even been proposed to treat oocyte-related infertility first before moving to mtDNA disorders. We argue that a prohibition of MST\/PNT for infertility is not justified, neither should it initially be applied only for infertility because of the little evidence yet available regarding its efficacy and potential risks. We propose a staged approach to identify MST\/PNT-treatable causes of oocyte-related infertility first, followed by a preclinical study and clinical trial and, if positive, wider application. Importantly, we call for transparency in publishing regular trial results, deeper ethical reflection, and more consistent policies that consider comparable uncertainties in mtDNA disorders and oocyte-related infertility.<\/jats:p>","DOI":"10.1093\/humrep\/deag027","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:47:02Z","timestamp":1770814022000},"page":"483-487","source":"Crossref","is-referenced-by-count":1,"title":["From disease prevention to fertility treatment: rethinking the use of mitochondrial donation for oocyte-related infertility in the light of safety and efficacy"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7376-4145","authenticated-orcid":false,"given":"Flor","family":"Pasturino","sequence":"first","affiliation":[{"name":"Philosophy and Ethics Group, Department of Industrial Engineering & Innovation Sciences, Eindhoven University of Technology , Eindhoven,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0410-4902","authenticated-orcid":false,"given":"Guido M W R","family":"De Wert","sequence":"additional","affiliation":[{"name":"Department of Health, Ethics and Society, Research Institutes GROW and CAPHRI, Maastricht University , Maastricht,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-577X","authenticated-orcid":false,"given":"Cathy","family":"Herbrand","sequence":"additional","affiliation":[{"name":"Centre for Reproduction Research, De Montfort University , Leicester,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1620-908X","authenticated-orcid":false,"given":"Hubert J M","family":"Smeets","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Research Institutes MHeNS and GROW, Maastricht University , Maastricht,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"2026040814594546100_deag027-B1","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/humupd\/7.4.428","article-title":"Cytoplasmic transfer in assisted reproduction","volume":"7","author":"Barritt","year":"2001","journal-title":"Hum Reprod Update"},{"key":"2026040814594546100_deag027-B2","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/molehr\/gan035","article-title":"Permanent embryo arrest: molecular and cellular concepts","volume":"14","author":"Betts","year":"2008","journal-title":"Mol Hum Reprod"},{"key":"2026040814594546100_deag027-B3","first-page":"1","article-title":"Mitochondrial replacement techniques for treating infertility","volume":"0","author":"Braun","year":"2024","journal-title":"J Med Ethics"},{"key":"2026040814594546100_deag027-B4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/humupd\/dmaf004","article-title":"Genetic and reproductive strategies to prevent mitochondrial diseases","volume":"31","author":"Castelluccio","year":"2025","journal-title":"Hum Reprod Update"},{"key":"2026040814594546100_deag027-B5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/B978-0-12-821751-1.00001-4","article-title":"Mitochondrial disease in neurology\u2014past, present, and future","volume":"194","author":"Chinnery","year":"2023","journal-title":"Handb Clin Neurol"},{"key":"2026040814594546100_deag027-B6","doi-asserted-by":"crossref","first-page":"635370","DOI":"10.3389\/fendo.2021.635370","article-title":"Prospects of germline nuclear transfer in women with diminished ovarian reserve","volume":"12","author":"Christodoulaki","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026040814594546100_deag027-B7","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1146\/annurev-genom-111119-101815","article-title":"The regulation of mitochondrial replacement techniques around the world","volume":"21","author":"Cohen","year":"2020","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2026040814594546100_deag027-B8","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.fertnstert.2023.02.008","article-title":"First Pilot Study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility","volume":"119","author":"Costa-Borges","year":"2023","journal-title":"Fertil Steril"},{"key":"2026040814594546100_deag027-B10","volume-title":"Hope or Hype: The Obsession with Medical Advances and the High Cost of False Promises","author":"Deyo","year":"2005"},{"key":"2026040814594546100_deag027-B11","author":"European Society of Human Reproduction and Embriology","year":"2019"},{"key":"2026040814594546100_deag027-B12","first-page":"950","article-title":"Proactive regulation of new technology: mitochondrial donation legislation in Australia","volume":"43","author":"Floreani","year":"2022","journal-title":"Adelaide Law Rev"},{"key":"2026040814594546100_deag027-B13","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1056\/NEJMc1500960","article-title":"Mitochondrial donation\u2013how many women could benefit?","volume":"372","author":"Gorman","year":"2015","journal-title":"N Engl J Med"},{"key":"2026040814594546100_deag027-B14","author":"Greenfield","year":"2016"},{"key":"2026040814594546100_deag027-B15","author":"Hamzelou","year":"2024"},{"key":"2026040814594546100_deag027-B16","volume-title":"Nuclear Transplantation in Cases of Mutations in Mitochondrial DNA","author":"Health Council of the Netherlands","year":"2001"},{"key":"2026040814594546100_deag027-B17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/humupd\/dms008","article-title":"PGD and heteroplasmic mitochondrial DNA point mutations: a systematic review estimating the chance of healthy offspring","volume":"18","author":"Hellebrekers","year":"2012","journal-title":"Hum Reprod Update"},{"key":"2026040814594546100_deag027-B18","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/1467-9566.12631","article-title":"Mitochondrial donation, patient engagement and narratives of hope","volume":"40","author":"Herbrand","year":"2018","journal-title":"Sociol Health Illn"},{"key":"2026040814594546100_deag027-B19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.rbms.2021.07.005","article-title":"Silences, omissions and oversimplification? the UK debate on mitochondrial donation","volume":"14","author":"Herbrand","year":"2022","journal-title":"Reprod Biomed Soc Online"},{"key":"2026040814594546100_deag027-B20","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1056\/NEJMoa2415539","article-title":"Mitochondrial donation and preimplantation genetic testing for mtDNA disease","volume":"393","author":"Hyslop","year":"2025","journal-title":"N Engl J Med"},{"key":"2026040814594546100_deag027-B22","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1161\/CIRCULATIONAHA.121.056286","article-title":"Heteroplasmy of wild-type mitochondrial DNA variants in mice causes metabolic heart disease with pulmonary hypertension and frailty","volume":"145","author":"Lechuga-Vieco","year":"2022","journal-title":"Circulation"},{"key":"2026040814594546100_deag027-B23","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/humupd\/dmh016","article-title":"Cytoplasmic transfer in oocytes: biochemical aspects","volume":"10","author":"Levy","year":"2004","journal-title":"Hum Reprod Update"},{"key":"2026040814594546100_deag027-B24","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.stemcr.2021.05.012","article-title":"ISSCR guidelines for stem cell research and clinical translation: the 2021 update","volume":"16","author":"Lovell-Badge","year":"2021","journal-title":"Stem Cell Reports"},{"key":"2026040814594546100_deag027-B25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3390\/laws13020020","article-title":"Implications of law\u2019s response to mitochondrial donation","volume":"13","author":"Ludlow","year":"2024","journal-title":"Laws"},{"key":"2026040814594546100_deag027-B26","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/humrep\/deaa308","article-title":"Germline transmission of donor, maternal and paternal mtDNA in primates","volume":"36","author":"Ma","year":"2021","journal-title":"Hum Reprod"},{"key":"2026040814594546100_deag027-B28","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1016\/j.fertnstert.2019.07.623","article-title":"Mitochondrial replacement theraphy give no benefits to patients of advanced maternal age","volume":"112","author":"Mazur","year":"2019","journal-title":"Fertil Steril"},{"key":"2026040814594546100_deag027-B29","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1056\/NEJMoa2503658","article-title":"Mitochondrial donation in a reproductive care pathway for mtDNA disease","volume":"393","author":"McFarland","year":"2025","journal-title":"N Engl J Med"},{"key":"2026040814594546100_deag027-B30","author":"Mullin","year":"2017"},{"key":"2026040814594546100_deag027-B31","author":"National Health and Medical Research Council","year":"2017"},{"key":"2026040814594546100_deag027-B34","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1017\/jme.2022.98","article-title":"Mitochondrial replacement therapy: in whose interests?","volume":"50","author":"Noohi","year":"2022","journal-title":"J Law Med Ethics"},{"key":"2026040814594546100_deag027-B35","author":"Nuffield Council on Bioethics","year":"2012"},{"key":"2026040814594546100_deag027-B38","doi-asserted-by":"crossref","first-page":"104101","DOI":"10.1016\/j.rbmo.2024.104101","article-title":"Attitude of Belgian women towards enucleated egg donation for treatment of mitochondrial diseases and infertility","volume":"49","author":"Pennings","year":"2024","journal-title":"Reprod Biomed Online"},{"key":"2026040814594546100_deag027-B39","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s10815-022-02428-w","article-title":"Enucleated oocyte donation: first for infertility treatment, then for mitochondrial diseases","volume":"39","author":"Pennings","year":"2022","journal-title":"J Assist Reprod Genet"},{"key":"2026040814594546100_deag027-B40","volume-title":"Biomedical Innovation in Fertility Care: Evidence Challenges, Commercialization, and the Market for Hope","author":"Perrotta","year":"2024"},{"key":"2026040814594546100_deag027-B41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/1363459314555378","article-title":"Editorial introduction: the sociology of hope in contexts of health, medicine, and healthcare","volume":"19","author":"Petersen","year":"2015","journal-title":"Health (London)"},{"key":"2026040814594546100_deag027-B42","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1093\/humrep\/det463","article-title":"Beyond the dichotomy: a tool for distinguishing between experimental, innovative and established treatment","volume":"29","author":"Provoost","year":"2014","journal-title":"Hum Reprod"},{"key":"2026040814594546100_deag027-B43","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/bioe.12332","article-title":"The mitochondrial replacement \u2018therapy\u2019 myth","volume":"31","author":"Rulli","year":"2017","journal-title":"Bioethics"},{"key":"2026040814594546100_deag027-B44","doi-asserted-by":"crossref","first-page":"8353","DOI":"10.3390\/ijms22158353","article-title":"Molecular drivers of developmental arrest in the human preimplantation embryo: a systematic review and critical analysis leading to mapping future research","volume":"22","author":"Sfakianoudis","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026040814594546100_deag027-B45","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/B978-0-12-821751-1.00004-X","article-title":"Reproductive options in mitochondrial disease","volume":"194","author":"Smeets","year":"2023","journal-title":"Handb Clin Neurol"},{"key":"2026040814594546100_deag027-B46","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1093\/humrep\/deaa112","article-title":"Germline nuclear transfer in mice may rescue poor embryo development associated with advanced maternal age and early embryo arrest","volume":"35","author":"Tang","year":"2020","journal-title":"Hum Reprod"},{"key":"2026040814594546100_deag027-B47","author":"Walas","year":"2024"},{"key":"2026040814594546100_deag027-B48","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.rbmo.2018.03.009","article-title":"Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest","volume":"36","author":"Wang","year":"2018","journal-title":"Reprod Biomed Online"},{"key":"2026040814594546100_deag027-B49","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s10815-018-1188-3","article-title":"A novel mutation in the TUBB8 gene is associated with complete cleavage failure in fertilized eggs","volume":"35","author":"Yuan","year":"2018","journal-title":"J Assist Reprod Genet"},{"key":"2026040814594546100_deag027-B50","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41591-025-04001-1","article-title":"Genetic architecture and phenotypic diversity of oocyte and early embryo competence defects in female infertility","volume":"32","author":"Zhang","year":"2025","journal-title":"Nat Med"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/4\/483\/67330815\/deag027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/41\/4\/483\/67330815\/deag027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:59:57Z","timestamp":1775674797000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/41\/4\/483\/8510675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,3,13]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deag027","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,13]]}}}