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

As a pioneering center in mitochondrial replacement therapies (MRT), Embryotools welcomes the recent publication by Hyslop et al. in The New England Journal of Medicine, reporting outcomes from pronuclear transfer (PNT) to prevent the transmission of mitochondrial DNA (mtDNA) disease. The study reports the birth of eight babies—four girls and four boys, including one set of identical twins—born to seven women at high risk of transmitting severe mtDNA disorders. Importantly, all infants are healthy and show no signs of mitochondrial disease. However, the detection of low-level postnatal mtDNA heteroplasmy (“reversal”) in 3 of the 8 infants (5%–16%) deserves particular discussion.

Due to UK regulations that prohibit testing for heteroplasmy in embryos, the timing of this reversal could not be pinpointed. Their analysis relied on arrested embryos and blood samples from newborns, which limits interpretation. In contrast, our recent pilot trial using maternal spindle transfer (MST)—a form of MRT where mitochondrial replacement occurs in the oocyte before fertilization—in infertile patients led to seven live births, two of which also showed reversal, a comparable frequency. However, our approach included direct assessment of heteroplasmy in blastocysts and, longitudinally, in multiple tissues including amniotic fluid. This allowed us to accurately define that reversal occurred between the blastocyst stage and mid-gestation (~15 weeks), reinforcing the importance of prenatal testing to detect reversal early and guide clinical decision-making. In our study, all infants are also healthy and have been followed up showing no adverse events.

This phenomenon—mtDNA ‘reversal’—has previously been described in human cells in vitro but not in MRT-derived children. Minimal levels of maternal mtDNA carryover can expand substantially, potentially compromising the efficacy of MRTs to prevent mitochondrial disease. The biological mechanisms underlying this selective amplification remain unclear but appear to occur early in development, and instances may therefore be detectable using prenatal testing. It is worth noting that the impact of mtDNA reversal in infertility treatments is likely less concerning, as maternal mtDNA in these cases does not carry pathogenic mutations. Moreover, with appropriate matching of mtDNA haplotypes between the mother and donor, the biological consequences of low-level heteroplasmy could be further minimized or even rendered clinically irrelevant.

Currently, only the UK and Australia have regulated the use of MRT to prevent transmission of mtDNA mutations. We believe that other countries should adopt similar regulatory models. In particular, MRT should also be contemplated for infertility treatment. Infertility is a disease recognized by the WHO, and MRT can offer a genetic link to the mother for patients who would otherwise rely on egg donation. This justification aligns with the ethical principles underpinning MRT for disease prevention. As a pioneer group in this technology, Spain should lead in regulating these applications to ensure patient safety and prevent reproductive tourism to countries where such techniques may be offered without appropriate oversight.

In light of these findings, we reaffirm the urgent need to continue performing well-regulated, larger, long-term studies to fully evaluate the safety, efficacy, and clinical implications of MRTs. Ongoing research under appropriate oversight is essential to ensure the responsible development of these technologies, improve genetic counseling, and support informed decision-making by patients and clinicians alike.

We also advocate for thoughtful regulatory evolution that upholds patient autonomy, scientific excellence, and the principle of reproductive justice.