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

These are papers, the scientific community has waited for, for a long time, as they describe the experience of the Newcastle team on pronuclear transfer to prevent the transmission of mtDNA disease, for which they got approval in 2017. The papers describe the current experience in PNT and PGT for preventing the transmission of mtDNA disease. It is good to present a reproductive care pathway, although it is not fully complete and some of the criteria might be reevaluated based on the presented data. The care pathway starts with carriers of mtDNA mutations. I would also include women who have affected children with de novo mtDNA mutations. This concerns about 25% of the mtDNA patients. The recurrence risk is low and generally prenatal diagnosis is offered for reassurance. Furthermore, women with a very low mtDNA mutation load, with skewing mtDNA mutations or large scale deletions could also opt for prenatal diagnosis.

For a reproductive care pathway for mtDNA disease, these groups should be included as well. It is clear that for the remainder according to the HFEA guidelines PNT should only be offered if PGT is unsuitable. It is great that the PNT as an addition to the reproductive choices for mtDNA disease seems to deliver as 8 children without the mtDNA condition were born. However, there are still concerns, as 2 PNT children had a higher mutation load than the carry-over, which means that reversal can occur and could be a risk for having affected children in future treatments. Also, two children had rare medical complications, which according to the authors were not related to the treatment, as this would then be expected for all of them. I do not think that is true as technical variation occurs and donors will be different. It is good to carefully monitor this, as one of the aims of HFEA guided clinical application is to find-out if PNT by itself is safe, not only to prevent mtDNA disease. The discussion on this is not very strong.

Finally, a key unanswered question is why it took so long to come out with these results. Eight births with no mtDNA disease in 7 years deviates largely from the expected150 yearly births, as described by the same group in NEJM in 2015, if all women would opt for this procedure. It seems that the children born are quite recent (only one >18 months), so one wonders if there is a learning curve, change in procedure or whatsoever, explaining the increasing success rate. It would be fair to discuss this in more detail as it would make it much clearer and more realistic which women of the target group will benefit from MD. And that is still a positive message.”