Details of a pioneering ‘three-parent baby’ IVF technique using mitochondrial replacement therapy (MRT) have been revealed, giving hope to those with inheritable disorders that they may be able to have healthy children in the future.
The initial purpose of three-person IVF was to create a child free of mitochondrial disease in cases where parents presented a risk of transmission. Mitochondria contain DNA, and it is through this DNA that the genetic transmission of disease occurs. The human embryo was therefore created from the DNA of three people: that of its biological father (using the spermatozoon), that of its biological mother (using the nucleus of the ovule) and the mitochondria of another woman, an egg donor. The donor’s ovum was ‘enucleated’ (its nucleus was removed) and the nucleus of the biological mother was inserted in its place.
Now, a new research paper and editorial, published today in the journal Reproductive BioMedicine Online (RBMO), has described and commented on the controversial procedure for the first time. The technique resulted in the birth of a healthy baby boy to a carrier of Leigh Syndrome, a progressive and fatal neurological disorder caused by a mutation in the mum’s mitochondrial DNA. At the time the paper was written, the baby was seven months old.
Professor Bart Fauser, Editor-in-Chief of RBMO, said the procedure represents a major change for women,
“For some years, reproductive specialists have been able to deselect genetically affected embryos with mitochondrial disease, using sophisticated diagnostic procedures in the IVF laboratory.
Now, for the first time, an egg with abnormal mitochondria can be changed to contain mostly normal mitochondria from a healthy egg donor. This is a major change of technology and an obvious advantage for women who are at risk of passing such diseases on to the next generation.”
Mitochondrial replacement therapy has enabled the parents in question to have a healthy child after the tragic loss of two other children to Leigh syndrome. The severity of the disease is associated with the percentage of affected mitochondria (the mutation load). The mum in this case is asymptomatic as her mutation load is only 24.5%, less than half the expected 60% threshold load for the disease. Her son, born on the 6th of April 2016 after IVF with MRT, had a mutation load ranging from 2.36 ¬to 9.23%, well below the expected threshold for the condition. It is not known if the mutation load will remain the same throughout his life.
The pioneering procedure used an electrofusion technique to transfer the nuclear genome from the mother’s egg (leaving behind most of the mother’s mitochondria) to the cytoplasm of a donor egg containing only healthy mitochondria. This egg was then fertilised by the father’s sperm and transferred to the mother’s womb and a baby boy was born at 37 weeks after an uneventful pregnancy.
The ovarian stimulation and egg collection procedures, mitochondrial replacement and fertilisation were carried out at a private fertility clinic in New York. The frozen embryo was then transferred to an affiliated fertility clinic in Mexico, where it was implanted in the patient’s womb.
Dr Jacques Cohen, the director of the ART Institute of Washington, commented on the unique case,
“Thirty years ago it was discovered that certain rare diseases are associated with abnormal, mutated mitochondria in human cells. Ten years after that initial discovery, egg microsurgery enabled IVF specialists to change the cytoplasm including mitochondria from patients who had failed IVF multiple times.
It is only now that the combination of this knowledge-base and clinical strategy has allowed the birth of a baby free of mitochondrial disease, after decades of ethical and political debate.”
The announcement of the birth of the first baby born using MRT was met with mixed reactions in the media – acknowledging the enormous scientific achievement but raising ethical concerns surrounding travel in order to bypass certain laws and federal regulations in the USA. The child’s Jordanian parents traveled to Mexico where they were treated by an American team from the New Hope Fertility Center in New York. It is believed that the procedure was carried out in Mexico due to its close proximity to the United States, and because it is a country where no regulatory framework has yet been put in place to prohibit the controversial new technique.
A baby girl – born in Ukraine on the 5th of January this year – is thought to only be the world’s second baby to have three genetic parents. The birth of these ‘three parent’ children, and other children to be born using MRT, will undoubtedly generate further debate surrounding the technique, and pave the way for changes in the law and regulation.
However, this reception is similar to that for other advances in reproductive medicine such as intra-cytoplasmic sperm injection (ICSI), pre-implantation genetic screening (PGS), egg freezing, and indeed IVF itself early on, where the public perception and/or legal regulatory framework had to adjust to catch up with the scientific advances.
Although the experimental technique is still in its infancy, the UK’s Human Fertilisation and Embryology Authority (HFEA) have licensed mitochondrial transfer for cautious adoption, on a case-by-case basis and this case played a role in influencing their decision. The first license to perform the technique in the UK was granted to Newcastle University and announced just last month on the 16th of March.
Dr. John Zhang, lead author, says it’s a major breakthrough, “This is it. We did it, finally. This brilliant technology is exciting for mankind.”
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