The UK’s pioneering licensed IVF technique to reduce the risk of mitochondrial diseases carried out in Newcastle has seen eight babies born, research shows.
All eight babies show no signs of having mitochondrial DNA disease. The babies, four girls and four boys, including one set of identical twins, were born to seven women at high risk of transmitting serious disease caused by mutations in mitochondrial DNA.
The findings, reported by the Newcastle team who pioneered mitochondrial donation using fertilized human eggs, indicate that the new treatment, known as pronuclear transfer, is effective in reducing the risk of otherwise incurable mitochondrial DNA diseases.
Published in two papers in The New England Journal of Medicine (NEJM), the findings describe the reproductive and clinical outcomes of pronuclear transfer treatments performed to date. All babies were healthy at birth, meeting their developmental milestones, and the mother’s disease-causing mitochondrial DNA mutations were either undetectable or present at levels that are very unlikely to cause disease.
The technique was pioneered in human eggs by a team based at Newcastle University, UK and the Newcastle upon Tyne Hospitals NHS Foundation Trust.
The mother of a baby girl born following mitochondrial donation said, “As parents, all we ever wanted was to give our child a healthy start in life. Mitochondrial donation IVF made that possible. After years of uncertainty, this treatment gave us hope—and then it gave us our baby. We look at them now, full of life and possibility, and we’re overwhelmed with gratitude. Science gave us a chance.”
The mother of a baby boy added, “We are now proud parents to a healthy baby—a true mitochondrial replacement success. This breakthrough has lifted the heavy cloud of fear that once loomed over us.
“Thanks to this incredible advancement and the support we received, our little family is complete. The emotional burden of mitochondrial disease has been lifted, and in its place is hope, joy, and deep gratitude.”
Professor Sir Doug Turnbull, of Newcastle University, part of the Newcastle team, said, “Mitochondrial disease can have a devastating impact on families. [This] news offers fresh hope to many more women at risk of passing on this condition who now have the chance to have children growing up without this terrible disease. Within the framework of the NHS in a well-regulated environment, we are able to offer mitochondrial donation as part of a research study to affected women in the UK.”
Mitochondrial DNA disease
Every year, around one in 5,000 children is born with mitochondrial DNA mutations that can cause devastating disease. Mitochondria produce the energy required for life and contain a small piece of DNA that only encodes some of the instructions required for energy production.
Harmful mutations in mitochondrial DNA can result in reduced availability of energy, particularly affecting tissues that have high energy demands—for example, heart, muscle and brain.
Mitochondrial DNA is maternally inherited, and these diseases are therefore passed from mother to child. Although males can be affected, they do not pass on the disease. Despite years of research, there is still no cure for people with mitochondrial DNA disease.
In the absence of a cure for mitochondrial DNA diseases, attention has focused on IVF-based technologies to reduce the risk of disease by limiting transmission of disease-causing mitochondrial DNA mutations from mother to child.
The new IVF-based mitochondrial donation technology, pronuclear transfer, which was legalized in the UK in 2015, is designed to reduce the risk of mitochondrial DNA disease in children born to women who carry high levels of disease-causing mitochondrial DNA mutations.
The Newcastle team now include pronuclear transfer as part of a research study along with a range of reproductive options offered to women at risk of transmitting mitochondrial disease to their children.
Pronuclear transfer
The technique, known as pronuclear transfer, is performed after the egg is fertilized. It involves transplanting the nuclear genome (which contains all the genes essential for our individual characteristics, for example, hair color and height) from an egg carrying a mitochondrial DNA mutation to an egg donated by an unaffected woman that has had its nuclear genome removed. The resulting embryo inherits its parents’ nuclear DNA, but the mitochondrial DNA is inherited predominantly from the donated egg.
The reproductive outcomes paper
The UK-based Newcastle team who developed and optimized pronuclear transfer for use in fertilized human eggs now report on the outcomes of pronuclear-transfer treatment to reduce the risk of mitochondrial DNA disease.
Levels of disease-causing mitochondrial DNA detected in babies born after pronuclear transfer treatment ranged from undetectable to 16% in neonatal blood. The presence of mitochondrial DNA mutations in babies born after pronuclear transfer treatment results from carryover of maternal mitochondria surrounding the nuclear DNA at the time of transplantation. Carryover of maternal mitochondrial DNA is a known limitation of mitochondrial donation technologies.
The team is seeking to better understand and address this issue as part of an underpinning research program.
Professor Mary Herbert, lead author of the reproductive outcomes paper who carried out the research at Newcastle University said, “The findings give grounds for optimism. However, research to better understand the limitations of mitochondrial donation technologies will be essential to further improve treatment outcomes.
“Mitochondrial donation technologies are currently regarded as risk-reduction treatments owing to carryover of maternal mitochondrial DNA during the mitochondrial donation procedure. Our ongoing research seeks to bridge the gap between risk reduction and prevention of mitochondrial DNA disease by addressing this problem.”
Pronuclear-transfer treatment is offered as part of an integrated program that includes preimplantation genetic testing (PGT) for reducing the risk of mitochondrial DNA disease. In accordance with HFEA regulations, pronuclear transfer is offered only to those women who are unlikely to benefit from PGT treatment.
At the time of reporting the integrated program of PGT and pronuclear transfer, clinical pregnancies were confirmed in eight of 22 (36%) patients who underwent pronuclear transfer and 16 of 39 (41%) of patients who underwent PGT.
Pronuclear transfer has resulted in eight births and one further pregnancy. PGT has resulted in 18 births. In the children from pronuclear transfer, levels of disease-causing mitochondrial DNA mutations were either undetectable or well below the levels at which disease symptoms are observed.
The clinical outcomes paper
The Newcastle team describe the pathway developed to provide the best possible care for women with pathogenic mitochondrial DNA mutations. It describes in detail how the mothers of the first children born with the technique were monitored and supported in pregnancy, and their babies closely followed from birth.
Some of the mothers already had symptoms of mitochondrial disease, including vision loss and heart problems. Others had family members with the disease and remain at risk of developing symptoms and passing it on.
All eight babies, including a set of identical twins, were healthy at birth and are described as developing normally—five have had no medical problems since. In the paper, the team note that three babies overcame some early health issues that they believe they are not able to attribute directly to mitochondrial donation.
The Newcastle team offers advice and treatment to women with harmful mitochondrial DNA mutations in the UK. They are carefully monitored during pregnancy and after mitochondrial donation, six of seven progressed without incident. One woman developed a rare complication of pregnancy with a high level of fats detected in her blood (hyperlipidemia) which responded well to a reduced fat diet.
All eight babies, including the set of twins, were born by normal vaginal delivery or elective cesarean section. All babies had normal weight for gestational age. The level of disease-causing mitochondrial DNA mutation was measured in blood and urine cells and was undetectable in five babies.
Three babies had low levels of disease-causing mitochondrial DNA mutations—5 and 9%, 12 and 13%, 16 and 20% in blood and urine respectively. These levels are well below the 80% level required for clinical disease for these mutations. The researchers note that at follow-up at 18 months, the level of the disease-causing mutation in the child of 5 and 9% was undetectable in blood and urine.
All children are enrolled in an 18-month developmental study and, at the date of reporting, all the babies were meeting their relevant developmental milestones.
One child developed some brief startles (involving neck flexion and eye blinking) at age 7 months, which resolved without treatment after three months. Another, a breast-fed baby, developed high blood fats (hyperlipidemia) which had also affected the mother during pregnancy, and was successfully treated through a low-fat diet.
This child was also diagnosed with an abnormal heart rhythm (cardiac arrhythmia) which is being successfully treated with a reducing amount of anti-arrhythmic medication. (Although the children born following PGT are not routinely followed-up, the team note that a cardiac anomaly was detected in one child.) A third child had a urinary tract infection that responded quickly to antibiotic treatment.
The authors say that the children’s health conditions are not thought to be related to the maternal mitochondrial DNA mutations as the low levels detected in these babies would not be expected to cause disease symptoms. Symptoms of these mutations are only seen with levels above 80%.
Any effect of the pronuclear transfer procedure itself would be expected to have a more uniform clinical manifestation, that is, to affect children in the same way. However, follow-up studies will be of paramount importance in detecting any patterns in childhood conditions.
The team emphasize that follow-up studies are essential for detecting any patterns in childhood conditions and say they will continue to offer assessments up to the age of 5 years.
Professor Bobby McFarland, Director of the NHS Highly Specialized Service for Rare Mitochondrial Disorders (Newcastle Hospitals NHS Foundation Trust) and Professor of Pediatric Mitochondrial Medicine at Newcastle University, is first author of one of the papers.
He said, “While longer-term follow-up of children born following mitochondrial donation is of paramount importance, these early results are very encouraging. Seeing the joy and relief these children have brought to their parents is such a privilege.
“We believe the follow-up process we have put in place is thorough, since it allows us to detect and review even minor health conditions in children born after pronuclear transfer, such as a urinary tract infection.”
More information:
Mitochondrial Donation and PGT to Reduce Risk of Mitochondrial DNA Disease. New England Journal of Medicine www.nejm.org/doi/full/10.1056/NEJMoa2415539
Mitochondrial Donation in a Reproductive Care Pathway for mtDNA Disease, New England Journal of Medicine (2025). DOI: 10.1056/NEJMoa2503658
Citation:
Eight babies born after mitochondrial donation treatment to reduce transmission of mitochondrial DNA disease (2025, July 16)
retrieved 16 July 2025
from https://medicalxpress.com/news/2025-07-babies-born-mitochondrial-donation-treatment.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
The UK’s pioneering licensed IVF technique to reduce the risk of mitochondrial diseases carried out in Newcastle has seen eight babies born, research shows.
All eight babies show no signs of having mitochondrial DNA disease. The babies, four girls and four boys, including one set of identical twins, were born to seven women at high risk of transmitting serious disease caused by mutations in mitochondrial DNA.
The findings, reported by the Newcastle team who pioneered mitochondrial donation using fertilized human eggs, indicate that the new treatment, known as pronuclear transfer, is effective in reducing the risk of otherwise incurable mitochondrial DNA diseases.
Published in two papers in The New England Journal of Medicine (NEJM), the findings describe the reproductive and clinical outcomes of pronuclear transfer treatments performed to date. All babies were healthy at birth, meeting their developmental milestones, and the mother’s disease-causing mitochondrial DNA mutations were either undetectable or present at levels that are very unlikely to cause disease.
The technique was pioneered in human eggs by a team based at Newcastle University, UK and the Newcastle upon Tyne Hospitals NHS Foundation Trust.
The mother of a baby girl born following mitochondrial donation said, “As parents, all we ever wanted was to give our child a healthy start in life. Mitochondrial donation IVF made that possible. After years of uncertainty, this treatment gave us hope—and then it gave us our baby. We look at them now, full of life and possibility, and we’re overwhelmed with gratitude. Science gave us a chance.”
The mother of a baby boy added, “We are now proud parents to a healthy baby—a true mitochondrial replacement success. This breakthrough has lifted the heavy cloud of fear that once loomed over us.
“Thanks to this incredible advancement and the support we received, our little family is complete. The emotional burden of mitochondrial disease has been lifted, and in its place is hope, joy, and deep gratitude.”
Professor Sir Doug Turnbull, of Newcastle University, part of the Newcastle team, said, “Mitochondrial disease can have a devastating impact on families. [This] news offers fresh hope to many more women at risk of passing on this condition who now have the chance to have children growing up without this terrible disease. Within the framework of the NHS in a well-regulated environment, we are able to offer mitochondrial donation as part of a research study to affected women in the UK.”
Mitochondrial DNA disease
Every year, around one in 5,000 children is born with mitochondrial DNA mutations that can cause devastating disease. Mitochondria produce the energy required for life and contain a small piece of DNA that only encodes some of the instructions required for energy production.
Harmful mutations in mitochondrial DNA can result in reduced availability of energy, particularly affecting tissues that have high energy demands—for example, heart, muscle and brain.
Mitochondrial DNA is maternally inherited, and these diseases are therefore passed from mother to child. Although males can be affected, they do not pass on the disease. Despite years of research, there is still no cure for people with mitochondrial DNA disease.
In the absence of a cure for mitochondrial DNA diseases, attention has focused on IVF-based technologies to reduce the risk of disease by limiting transmission of disease-causing mitochondrial DNA mutations from mother to child.
The new IVF-based mitochondrial donation technology, pronuclear transfer, which was legalized in the UK in 2015, is designed to reduce the risk of mitochondrial DNA disease in children born to women who carry high levels of disease-causing mitochondrial DNA mutations.
The Newcastle team now include pronuclear transfer as part of a research study along with a range of reproductive options offered to women at risk of transmitting mitochondrial disease to their children.
Pronuclear transfer
The technique, known as pronuclear transfer, is performed after the egg is fertilized. It involves transplanting the nuclear genome (which contains all the genes essential for our individual characteristics, for example, hair color and height) from an egg carrying a mitochondrial DNA mutation to an egg donated by an unaffected woman that has had its nuclear genome removed. The resulting embryo inherits its parents’ nuclear DNA, but the mitochondrial DNA is inherited predominantly from the donated egg.
The reproductive outcomes paper
The UK-based Newcastle team who developed and optimized pronuclear transfer for use in fertilized human eggs now report on the outcomes of pronuclear-transfer treatment to reduce the risk of mitochondrial DNA disease.
Levels of disease-causing mitochondrial DNA detected in babies born after pronuclear transfer treatment ranged from undetectable to 16% in neonatal blood. The presence of mitochondrial DNA mutations in babies born after pronuclear transfer treatment results from carryover of maternal mitochondria surrounding the nuclear DNA at the time of transplantation. Carryover of maternal mitochondrial DNA is a known limitation of mitochondrial donation technologies.
The team is seeking to better understand and address this issue as part of an underpinning research program.
Professor Mary Herbert, lead author of the reproductive outcomes paper who carried out the research at Newcastle University said, “The findings give grounds for optimism. However, research to better understand the limitations of mitochondrial donation technologies will be essential to further improve treatment outcomes.
“Mitochondrial donation technologies are currently regarded as risk-reduction treatments owing to carryover of maternal mitochondrial DNA during the mitochondrial donation procedure. Our ongoing research seeks to bridge the gap between risk reduction and prevention of mitochondrial DNA disease by addressing this problem.”
Pronuclear-transfer treatment is offered as part of an integrated program that includes preimplantation genetic testing (PGT) for reducing the risk of mitochondrial DNA disease. In accordance with HFEA regulations, pronuclear transfer is offered only to those women who are unlikely to benefit from PGT treatment.
At the time of reporting the integrated program of PGT and pronuclear transfer, clinical pregnancies were confirmed in eight of 22 (36%) patients who underwent pronuclear transfer and 16 of 39 (41%) of patients who underwent PGT.
Pronuclear transfer has resulted in eight births and one further pregnancy. PGT has resulted in 18 births. In the children from pronuclear transfer, levels of disease-causing mitochondrial DNA mutations were either undetectable or well below the levels at which disease symptoms are observed.
The clinical outcomes paper
The Newcastle team describe the pathway developed to provide the best possible care for women with pathogenic mitochondrial DNA mutations. It describes in detail how the mothers of the first children born with the technique were monitored and supported in pregnancy, and their babies closely followed from birth.
Some of the mothers already had symptoms of mitochondrial disease, including vision loss and heart problems. Others had family members with the disease and remain at risk of developing symptoms and passing it on.
All eight babies, including a set of identical twins, were healthy at birth and are described as developing normally—five have had no medical problems since. In the paper, the team note that three babies overcame some early health issues that they believe they are not able to attribute directly to mitochondrial donation.
The Newcastle team offers advice and treatment to women with harmful mitochondrial DNA mutations in the UK. They are carefully monitored during pregnancy and after mitochondrial donation, six of seven progressed without incident. One woman developed a rare complication of pregnancy with a high level of fats detected in her blood (hyperlipidemia) which responded well to a reduced fat diet.
All eight babies, including the set of twins, were born by normal vaginal delivery or elective cesarean section. All babies had normal weight for gestational age. The level of disease-causing mitochondrial DNA mutation was measured in blood and urine cells and was undetectable in five babies.
Three babies had low levels of disease-causing mitochondrial DNA mutations—5 and 9%, 12 and 13%, 16 and 20% in blood and urine respectively. These levels are well below the 80% level required for clinical disease for these mutations. The researchers note that at follow-up at 18 months, the level of the disease-causing mutation in the child of 5 and 9% was undetectable in blood and urine.
All children are enrolled in an 18-month developmental study and, at the date of reporting, all the babies were meeting their relevant developmental milestones.
One child developed some brief startles (involving neck flexion and eye blinking) at age 7 months, which resolved without treatment after three months. Another, a breast-fed baby, developed high blood fats (hyperlipidemia) which had also affected the mother during pregnancy, and was successfully treated through a low-fat diet.
This child was also diagnosed with an abnormal heart rhythm (cardiac arrhythmia) which is being successfully treated with a reducing amount of anti-arrhythmic medication. (Although the children born following PGT are not routinely followed-up, the team note that a cardiac anomaly was detected in one child.) A third child had a urinary tract infection that responded quickly to antibiotic treatment.
The authors say that the children’s health conditions are not thought to be related to the maternal mitochondrial DNA mutations as the low levels detected in these babies would not be expected to cause disease symptoms. Symptoms of these mutations are only seen with levels above 80%.
Any effect of the pronuclear transfer procedure itself would be expected to have a more uniform clinical manifestation, that is, to affect children in the same way. However, follow-up studies will be of paramount importance in detecting any patterns in childhood conditions.
The team emphasize that follow-up studies are essential for detecting any patterns in childhood conditions and say they will continue to offer assessments up to the age of 5 years.
Professor Bobby McFarland, Director of the NHS Highly Specialized Service for Rare Mitochondrial Disorders (Newcastle Hospitals NHS Foundation Trust) and Professor of Pediatric Mitochondrial Medicine at Newcastle University, is first author of one of the papers.
He said, “While longer-term follow-up of children born following mitochondrial donation is of paramount importance, these early results are very encouraging. Seeing the joy and relief these children have brought to their parents is such a privilege.
“We believe the follow-up process we have put in place is thorough, since it allows us to detect and review even minor health conditions in children born after pronuclear transfer, such as a urinary tract infection.”
More information:
Mitochondrial Donation and PGT to Reduce Risk of Mitochondrial DNA Disease. New England Journal of Medicine www.nejm.org/doi/full/10.1056/NEJMoa2415539
Mitochondrial Donation in a Reproductive Care Pathway for mtDNA Disease, New England Journal of Medicine (2025). DOI: 10.1056/NEJMoa2503658
Citation:
Eight babies born after mitochondrial donation treatment to reduce transmission of mitochondrial DNA disease (2025, July 16)
retrieved 16 July 2025
from https://medicalxpress.com/news/2025-07-babies-born-mitochondrial-donation-treatment.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.
