A innovative IVF procedure has successfully delivered its first UK baby. Mitochondrial donation treatment (MDT) aims to prevent children from inheriting incurable diseases by using tissue from the eggs of healthy female donors to create IVF embryos that are free from harmful mutations carried by their mothers.
Mitochondrial DNA (mtDNA) diseases are rare disorders whose prevalence is estimated around 1 in 5000. Mitochondria is inherited from the mother, so all the children an affected woman has can be at risk of severe, and often fatal, diseases.
The Human Fertilisation & Embryology Authority (HFEA) explained that the procedure involved eggs or embryos being "created using a woman's nuclear genetic material and healthy donated mitochondria". The authority said that two mitochondrial replacement techniques (MRT) for mitochondrial donation had been developed and approved by Parliament – maternal spindle transfer (MST) and pronuclear transfer ( PNT ).
The resulting embryos contain the woman's and her partner's, or sperm donor's, genetic material, so the embryos would be the woman's "biological children", explained the HFEA.
The procedure had led to the phrase 'three-parent babies', according to the Guardian, though "more than 99.8% of the DNA" in the babies came from the mother and father.
"Media-constructed phrases like 'three parent babies' do not really help the debate," criticised Professor Darren Griffin, professor of genetics, University of Kent. He added that the research was not new and that the initial findings had already been published. In 2016, a US doctor announced the world’s first birth using MDT, for a Jordanian woman who carried mitochondrial mutations that caused Leigh syndrome.
Pioneering Centre in Newcastle
MDT research was pioneered at the Newcastle Fertility Centre, which Professor Griffin described as "world-leading". The Newcastle clinic is the first and only national centre licensed to perform the procedure.
Sarah Norcross, director of the Progress Educational Trust (PET), pointed out that the UK was the first country to legislate for the clinical use of mitochondrial donation. She emphasised that the relevant law was passed only after many years of "careful research, assessment, and deliberation". The use of the technology was only permitted on a case-by-case basis, said the HFEA.
Peter Thompson, chief executive, HFEA, said that mitochondrial donation treatment is offered within a regulatory environment, to ensure that mitochondrial donation was provided in a safe and ethical manner. All applications for treatment were assessed on an individual basis against the tests set out in the law, and only after independent advice from experts, he reassured.
"This measured approach was and is appropriate, given the relative novelty of this technology," underlined Ms Norcross.
Process of Refinement
The Guardian reported that the HFEA had approved at least 30 cases, and that as of late April this year the number of births was less than five.
Ms Norcross remarked that the news of a small number of babies with donated mitochondria being born in the UK was the next step in what would probably remain a "slow and cautious" process of assessing and refining mitochondrial donation.
Professor Robin Lovell-Badge, group leader, Francis Crick Institute, commented that it would be interesting to know how well the technique worked at a practical level, whether the babies are free of mitochondrial disease, and whether there is any risk of them developing problems later in life or, if female, if their offspring are at risk of having the disease.
He cautioned that "such problems might arise if there is 'reversion', where the initially small amounts of the mother’s mitochondrial DNA, with the disease-causing variant gene, that are carried over with her nuclear DNA, are amplified".
Reversion, or reversal, is one of the risks of the procedure, where a small number of abnormal mitochondria that are inevitably carried over from the mother's egg to the donor egg can multiply when the baby is in the womb.
"The reason why reversal is seen in the cells of some children born following MRT procedures, but not in others, is not fully understood," Dagan Wells, professor of reproductive genetics, Oxford University, who took part in the research, told the Guardian.
He highlighted that the stage of development when reversal happens was unclear, but postulated that it probably occurred at a very early stage. "This means that prenatal testing, carried out [at] about 12 weeks of pregnancy, may well succeed in identifying if reversal has occurred," he suggested.
Professor Lovell-Badge emphasised that the Newcastle team were "aware of the fairly low chance of this happening before the clinical application of the techniques, but without MRT being used, the risks of the children having mitochondrial disease would be very high".
Privacy for Families, Transparency for Professionals
Ms Norcross stressed it was important for the technology to be used in a measured and carefully regulated way while it was assessed. It was also very important that "we respect the privacy of children with donated mitochondria, and their parents, not least because these parents are likely to have had prior experience of illness and bereavement in their family", she counselled.
"So far, the clinical experience with MRT has been encouraging, but the number of reported cases is far too small to draw any definitive conclusions about the safety or efficacy," said Professor Wells. "Long-term follow-up of the children born is essential".
Professor Lovell-Badge commented that scientists, clinicians, and patients, will want to see the details.
"These are still early days for mitochondrial donation treatment," cautioned Mr Thompson, and added that he understood the Newcastle team hoped to publish information of their mitochondrial treatment programme in peer reviewed journals shortly.
