Reacción a "First results on babies born with pioneering technology that reduces risk of mitochondrial disease"

In 2016, John Zhang, a medical specialist from an assisted reproduction clinic in New York called the “New Hope Fertility Center,” crossed the border into Mexico to carry out a procedure that was prohibited in the U.S. and not yet regulated in Mexico. A couple from Jordan had come to this clinic in hopes of having viable offspring. The couple had previously had two children who had died due to Leigh syndrome, one of several mitochondrial diseases that are usually devastating and have no cure. Mitochondria (our energy factories) are generally inherited from the mother, through the egg. The mother had approximately 25% of her mitochondria affected, which were the ones she had passed on to her two deceased children.

Dr. Zhang did not use the procedure that had been pioneeringly approved in the United Kingdom, due to the Muslim religion of the couple, which opposed the destruction of human embryos. Instead, he opted to extract the nucleus from the mother’s egg (technically the metaphase plate, an incomplete nuclear division stage in which all eggs ready to be fertilized are found) and transferred it into the egg of another woman (with healthy mitochondria), from which the nucleus had also been removed. Once the mother’s nucleus was transferred to the second woman’s egg, he used the resulting egg for in vitro fertilization with the father’s sperm to create embryos. Dr. Zhang created five embryos this way, of which only one developed normally. It was implanted into the mother’s uterus and resulted in the birth of a healthy baby. This was the first baby born using the “three-parent technique”: two mothers and one father.

In the United Kingdom, the British Human Fertilisation and Embryology Authority (HFEA) had approved in 2015 another technically different procedure—also called the “three-parent technique”—to address issues related to mitochondrial diseases. In this case, the father’s sperm is used to fertilize (via intracytoplasmic sperm injection, or ICSI) two eggs: one from the mother carrying the affected mitochondria, and one from another woman with healthy mitochondria. After fertilization begins, two pronuclei (one from the father and one from the mother) appear transiently and are destined to fuse and form the first nucleus of the zygote. Before this happens, researchers can extract the two pronuclei from the fertilized egg created with the mother’s egg and the father’s sperm, and transfer them to the egg of the second woman, also fertilized with the father’s sperm, from which the pronuclei have been removed. The final result is that the egg with the healthy mitochondria from the donor woman now contains the two pronuclei from the couple, and their baby is born free of mitochondrial disease and is genetically their child. The healthy mitochondria come from the donor woman. This method, which is somewhat more aggressive but less risky than the previous one, involves destroying one embryo to create another—something the Muslim couple treated by Dr. Zhang found unacceptable. The first baby born in the United Kingdom through the officially approved British three-parent procedure was born in 2023.

Ten years after the technique was approved in the UK, a team of British and Australian doctors and researchers published this week in the prestigious New England Journal of Medicine (NEJM) the results of applying the British three-parent technique to 22 women who carried pathogenic mutations in their mitochondria (and were therefore at high risk of having children with these incurable diseases). Of the 22 women treated, only 8 gave birth (36%), and one more pregnancy is still ongoing. The eight babies born are healthy, with no signs or only very low levels of affected mitochondria—levels not sufficient to cause disease. So far, the eight children are doing well. Only a couple of them developed minor clinical issues, apparently unrelated to the procedure, which resolved either through treatment or spontaneously.

Additionally, the researchers applied a second technique (preimplantation genetic testing, or PGT) to women who had heteroplasmy (a mix of healthy and affected mitochondria) to assess the percentage of affected mitochondria in embryos obtained through in vitro fertilization and to select those with lower levels of affected mitochondria. In this case, they achieved 16 pregnancies among 39 women (41%), resulting in 18 babies born with less than 7% of affected mitochondria.

In Spain, Law 14/2006 of May 26, on assisted human reproduction techniques, does not explicitly refer to this technique (which didn’t exist when the legislation was passed), so strictly speaking, the procedure is neither expressly prohibited nor explicitly authorized in our country. Essentially, it is not regulated. The legal and ethical uncertainties that remain have so far prevented the three-parent technique from being used in Spain.

However, this new study shows that the technique has a notable success rate (36%) and could well be offered to couples in which the mother carries affected mitochondria, to allow them to have children free from terrible mitochondrial diseases. Personally, I believe we should allow this technique in our country in those assisted reproduction clinics that are properly trained in this sophisticated embryonic intervention methodology.