Don’t panic. Most of our genetic information is carried in chromosomes. However, mitochondrial DNA contains 37 genes, all of which are related to producing energy in the cells. Three-person IVF is about taking all the genetic information of the mother and father, and only removing the mitochondrial DNA contributed from the mother.
“For some years, reproductive specialists have been able to deselect genetically affected embryos with mitochondrial disease, using sophisticated diagnostic procedures in the IVF laboratory,” Professor Bart Fauser, Editor-in-Chief of RBMO, said. “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.”
- MRT has enabled the parents to have a healthy child after the loss of two children to Leigh syndrome. The severity of the disease is associated with the percentage of affected mitochondria (the mutation load). The mother 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 6 April 2016 after IVF with MRT, had a mutation load ranging from 2.36 ¬to 9.23%, depending on the tissues tested, well below the expected threshold for the condition. It is currently unknown whether the mutation load will remain the same throughout his life.
- The researchers 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 fertilized 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. Two methods of cell fusion have been used in the past by various groups researching MRT. Most groups have utilized a virus to accomplish cell fusion, however, the extent of viral DNA carryover is unknown.
- The other method involves a metered electrical pulse to initiate cell fusion. Comparably, electrofusion is a more demanding technically but has no risk of viral DNA carryover.
- The ovarian stimulation and egg collection procedures, mitochondrial replacement and fertilization 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.
- “30 years ago it was discovered that certain rare diseases are associated with abnormal, mutated mitochondria in human cells. 10 years after that initial discovery, egg microsurgery enabled IVF specialists to change the cytoplasm including mitochondria from patients who had failed IVF multiple times,” commented Dr Jacques Cohen, Director of the ART Institute of Washington and product developer for Althea Science and Life.
- “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 to Mexico to bypass federal regulations in the USA. The birth of this child, and other children to be born using MRT, will generate debate surrounding the technique throughout the world, and pave the way for changes in the law and regulation.
- 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.
- Indeed, whilst this is still an experimental technique in its infancy, in the UK the 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 on March 16, 2017.
Is this legal?
It was legally approved in the UK in 2015 after years of debate and research. A Nature study published in June 2016 found the technique would lead to normal pregnancies.
The procedure has not been approved in the US, though a committee of the Institute of Medicine is investigating its ethical and social implications. As a result, the child born using the technique this year was in fact conceived through IVF that reportedly took place in Mexico, where there are no legal rulings on it.
Why isn’t it legal everywhere?
The technique raises a host of ethical questions, from the discarding of embryos resulting from the pronuclear technique to the concept of “designer babies”. But concerns have also been raised about medical risks that may come with it. These range from the potential for tiny amounts of mutated mitochondrial DNA being transferred to the embryo, to signs of malformations recorded in some animals models. However, the June Nature study did thoroughly investigate the procedure, looking at more than 500 eggs from 64 donor woman, and found the embryo developed normally.
A more recent study published on November 30, 2016, in Nature has shown that embryos created from four women who were at high risk of passing on the disease, could still pass on the mutation even using the technique. It was concluded that defective mitochondria can still develop in one out of eight babies.