Eight years after Britain became the first country to regulate a reproductive technique known as mitochondrial replacement, news broke that a child had been born using the technique.
The UK’s fertility regulator, the Human Fertility and Development Authority (HFEA), has confirmed that as of April 2023, fewer than five UK children have been born using this method. The confirmation was made in response to a Freedom of Information request by the agency. Guardian newspaper. HFEA did not provide further information about this operation or the children.
“This is interesting news, but it also says nothing about whether the method actually worked,” says Duggan Wells, a reproductive geneticist at the University of Oxford, UK. “There are open questions and we need answers as soon as possible.”
Mitochondrial replacement therapy (MRT), legalized in the UK in 2015, aims to prevent the inheritance of serious health conditions caused by mutations in mitochondria, the organelles that produce the cells’ energy. . Such mutations often affect the heart, brain and muscles.
This procedure — also called third person in vitro Fertilization (IVF) – involves the transfer of nuclear genetic material from an egg or single-cell embryo containing disease-causing mitochondria to a donor egg or embryo from which the nuclear genetic material has been removed.
gray regulation
This procedure is also practiced in other countries, but its use is not regulated. In 2016, US doctors announced that MRT surgery in Mexico had successfully prevented mitochondrial disease in infants. Mitochondrial transplants have also been performed in Greece and Ukraine to treat infertility, and children have been born. Last year, Australia became the second country to approve the MRT. However, in many other countries, including the United States, this procedure is still restricted.
Mitochondrial transfer revealed Guardian It took place at Newcastle Fetility Centre, the only clinic in the UK licensed to carry out MRT. Current regulations require the HFEA to approve each use on a case-by-case basis.
The researchers are eager to learn more from the UK procedure as they launch their own trials. “If there’s a negative thing to consider, sooner or later you need to know about it,” says Wells.
Robin Lovell Budge, a developmental biologist at the Francis Crick Institute in London, has issued a statement to the UK Science Media Center to learn how well the procedure worked and whether the infant is free of mitochondrial disease. said it was extremely important. She also wants to know “whether there’s a risk of developing problems later in life, or if women are at risk of their offspring getting the disease.”
This risk can occur during procedures in which a small number of mitochondria are necessarily transferred into the donor’s egg or embryo. Professor Wells would like to know the extent of this ‘carry-over’ in the UK cases and whether mitochondria with very low levels of mutations cause health problems.
mutant mitochondria
Scientists also want to know whether levels of transferred mutant mitochondria are stable over time. Animal and cell studies have found that, in some cases, imported mitochondria can increase significantly over time and replace donor mitochondria within the cell. This is a phenomenon known as inversion.1.
And this can happen in humans too. Earlier this year, Wells and her colleagues used MRT to treat fertility in a trial of 25 couples in Greece and observed improvement. Five of the six children born had almost entirely donor-derived mitochondrial DNA in cells from blood, umbilical cords, and other tissues taken. However, one child’s cells contained high levels of mitochondria inherited from her mother, 30-60% of her total.Fewer than 1% of the mitochondria were inherited from the mother’s egg when the embryo implanted2.
This reversal does not appear to have affected children’s health. “If we were doing the same steps to avoid mitochondrial DNA disruption, this might be cause for concern,” says Wells. “That’s the big question for us. Have we seen any reversal in these children?”
It is not clear why the proportion of potentially disease-causing mitochondria increases so dramatically after mitochondrial transplantation and during development. One possibility is that genetic factors may allow the mother’s mitochondrial lineage to replicate more efficiently than mitochondria in the donor egg or embryo, Wells said. If so, he added, it might be worth matching donors and recipients based on mitochondrial DNA similarity. This may reduce the replication capacity of one strain over another.
There may be other ways to prevent reversal, said Shukhrat Mitalipov, a reproductive biologist at the Oregon Health and Science University in Portland, who participated in an infertility trial. In five children whose mitochondria came almost entirely from donors, the researchers had frozen the mother’s eggs before transferring the nuclear genetic material into fresh donor eggs. Both eggs were fresh during transfer creating offspring in which reversal occurred. “We are still puzzled as to whether freezing the mother’s eggs is actually beneficial,” he says.
Britain’s first MRT birth also provides an opportunity to consider the country’s cautious approach to permitting the operation.
“There is some comfort to the public that this kind of cutting-edge procedure, which pushes scientific as well as ethical boundaries, is being conducted under proper supervision. ,” says Wells. But the fact that he has only one clinic in the UK where he can do MRT is probably a bottleneck to treatment, he added. “There are pluses and minuses.”
This article is reprinted with permission and was first published May 10, 2023.
