Assisted reproduction via MRT involves preimplantation genetic screening of the mother, preimplantation genetic diagnosis after the egg is fertilized, and in vitro fertilization. It has all the risks of those procedures.
In addition, both procedures used in MRT entail their own risks. On one level, the procedures physically disrupt two oocytes, removing nuclear genetic material from the recipient egg or fertilized egg and inserting the nuclear genetic material into the donor unfertilized or fertilized egg; the manipulations for both procedures may cause various forms of damage that were not well understood as of 2016.
Maternal mitochondria will be carried over to the donor egg; as of 2016 it was estimated that using techniques current in the UK, maternal mitochondria will comprise only around 2% or less of mitochondria in the resulting egg, a level that was considered safe by the HFEA and within the limits of mitochondrial variation that most people have.
Because MRT procedures involve actions at precise times during egg development and fertilization, and involves manipulating eggs, there is a risk that eggs may mature abnormally or that fertilization may happen abnormally; as of 2016 the HFEA judged that laboratory techniques in the UK had been well enough developed to manage these risks to proceed cautiously with making MRT available.
Because mitochondria in the final egg will come from a third party, different from the two parties whose DNA is in the nucleus, and because nuclear DNA encodes genes that make some of the proteins and mRNA used by mitochondria, there is a theoretical risk of adverse "mito–nuclear" interactions. While this theoretical risk could possibly be managed by attempting to match the haplotype of the donor and the recipient, as of 2016 there was no evidence that this is an actual risk.
Because MRT is a relatively new technology, there are concerns that it is not yet safe for public use as there have been limited studies that used MRT in large animal models.
Finally, there is a risk of epigenetic modification to DNA in the nucleus and mitochondria, caused by the procedure itself or by mito–nuclear interactions. As of 2016 these risks appeared to be minimal but were being monitored by long-term study of children born from the procedure.