[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-435681-105":59,"doc-detail-435681-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","mitochondrial-donation-beyond-the-first-healthy-births-letter-to-the-editor","Mitochondrial donation: beyond the first healthy births - Letter to the Editor","","Mitochondrial donation is presented as a potential way to reduce maternal transmission of mitochondrial disorders, with early reports of the first healthy births in the UK. The letter outlines mitochondrial replacement techniques, including maternal spindle and pronuclear transfer, while emphasizing persistent heteroplasmy, unknown causes of DNA reversion, and emerging mito-nuclear incompatibility risks. Ethical challenges are discussed, alongside the need for long-term follow-up, international registries, and robust regulation and transparent public communication.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mitochondrial-donation-beyond-the-first-healthy-births-letter-to-the-editor/435681/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mitochondrial-donation-beyond-the-first-healthy-births-letter-to-the-editor/435681.png","ImageObject",300,407,{"name":92,"@type":93},"ahduag","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What goal do mitochondrial replacement techniques (MRT) serve?","Question",{"text":113,"@type":114},"MRT aims to reduce the risk of passing mitochondrial diseases from mother to offspring by transferring nuclear DNA into a donor egg with healthy mitochondria.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why is heteroplasmy still a major concern after mitochondrial donation?",{"text":118,"@type":114},"Heteroplasmy can vary widely in newborns, and UK regulations limit heteroplasmy testing after embryo transfer, constraining early detection and risk prediction.",{"name":120,"@type":111,"acceptedAnswer":121},"What long-term safeguards does the letter recommend?",{"text":122,"@type":114},"The letter calls for long-term follow-up of children, systematic tracking in international registries, and robust ethical and regulatory frameworks supported by transparent public communication.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},435681,1790789510,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":24,"preview_page_count":4},3985747870414,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Letter to the Editor  \nMitochondrial donation: beyond the first healthy births  \nSabahat Hafeez, MBBSa , Akshay Lohana, MBBSb , Siddhant Kumar Yadav, MBBSc ,*  \nHistorically, mitochondrial disorders have been regarded as unavoidably inherited from affected mothers to their children. However, recent reports from the UK have shown that mitochondrial donation can offer the possibility of reducing this transmission, with the first healthy births now reported [1] . While these findings mark progress, outcomes remain far from uniform. Our article aligned with Titan’s 2025 guidelines[2] .  \nMitochondrial replacement techniques (MRT) are reproductive methods that aim to reduce the risk of passing mitochondrial diseases from mother to offspring[3] . They do so by transferring the nuclear DNA from an affected mother’s egg into a donor egg with healthy mitochondria. This process can be performed either before or after fertilization, techniques referred to as maternal spindle transfer or pronuclear transfer, respectively[1] .  \nOne major concern regarding mitochondrial donation is the persistence of heteroplasmy. Heteroplasmy levels in newbornshave ranged from undetectable (\u003C0.06%) to as high as 16%, despite consistently low levels in discarded embryos. Yet, in the UK, regulations prohibit heteroplasmy testing after embryo transfer, limiting early detection and risk prediction [1] . Additional risks related to heteroplasmy have also been highlighted. Despite low initial heteroplasmy, studies have reported reversion to maternal mitochondrial DNA, rising from 4% to as high as 60%, indicating genomic instability after MRT[3,4] . The cause is unknown, but this reversion questions long-term reliability and reinforces the need for long-term follow-up, ideally across generations[5] .  \nA further issue arises from the complex interaction between the mitochondrial and nuclear genomes. Since mitochondrial function depends on close interaction between mitochondrial DNA and nuclear DNA, MRT alters this natural inheritance by introducing donor mitochondrial  \naDepartment of Paediatrics, Aga Khan University Hospital, Karachi, Sindh, Pakistan, bDepartment of Medicine, Liaquat University of Medical & Health Sciences, Jamshoro, Sindh, Pakistan and cDepartment of Medicine, Patan Academy of Health Sciences, Lagankhel, Lalitpur, Nepal  \nSponsorships or competing interests that may be relevant to content are disclosed at the end of this article.  \n*Corresponding author. Address: Department of Medicine, Patan Academy of Health Sciences, Lagankhel , Lalitpur 44700, Nepal. Tel.: +9779819676222.  \nE-mail: [1254mbbs-siddhant@pahs.edu.np](1254mbbs-siddhant@pahs.edu.np) (S.K. Yadav).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Annals of Medicine & Surgery (2026) 88:1050–1051  \nReceived 5 October 2025; Accepted 12 November 2025  \nPublished online 21 November 2025  \n[http://dx.doi.org/10.1097/MS9.0000000000004387](http://dx.doi.org/10.1097/MS9.0000000000004387)  \nDNA. This may create mito-nuclear incompatibility. Animal studies have shown that this incompatibility can lead to impaired growth and mitochondrial activity. However, human evidence is mixed: some studies have linked mismatched ancestry to preterm labor and reduced intracellular mitochondrial DNA, which itself has been associated with conditions like Parkinson’s disease. Meta-analyses are inconclusive and contradictory, with estimates ranging from negligible risk to one in 130 post-MRT births [4] .  \nThe ethical concerns are just as significant. One ethical challenge is that pronuclear transfer involves the creation and subsequent disposal of an embryo","cbCaivRKrVDW0tor","https://ap.wps.com/l/cbCaivRKrVDW0tor","pdf",164479,"English","# Mitochondrial donation and early outcomes\n## Mitochondrial replacement techniques (MRT)\n## Heteroplasmy, DNA reversion, and reliability\n## Mito-nuclear interaction and evidence\n## Ethical challenges and “three-parent baby” considerations\n## International practice disparities and legal follow-up\n## Recommendations for responsible adoption","[{\"question\":\"What goal do mitochondrial replacement techniques (MRT) serve?\",\"answer\":\"MRT aims to reduce the risk of passing mitochondrial diseases from mother to offspring by transferring nuclear DNA into a donor egg with healthy mitochondria.\"},{\"question\":\"Why is heteroplasmy still a major concern after mitochondrial donation?\",\"answer\":\"Heteroplasmy can vary widely in newborns, and UK regulations limit heteroplasmy testing after embryo transfer, constraining early detection and risk prediction.\"},{\"question\":\"What long-term safeguards does the letter recommend?\",\"answer\":\"The letter calls for long-term follow-up of children, systematic tracking in international registries, and robust ethical and regulatory frameworks supported by transparent public communication.\"}]","Mitochondrial donation: beyond the first healthy births - Letter to the Editor | PDF",1790674736]