The report, which is the panel’s fourth, documents its comprehensive review of developments in pre-clinical research into mitochondrial donation across the world, including the safety and efficacy experiments that the panel recommended be undertaken in its previous report  before clinical use of the Maternal Spindle Transfer (MST) and Pronuclear Transfer (PNT) techniques  be permitted.
Following a close examination of the scientific evidence, which includes submissions received from researchers through a global call for evidence, and research identified by the panel itself , the panel has concluded that:
- Significant progress has been made in addressing remaining issues that were identified in previous reports: embryos generated by MST and PNT develop to the blastocyst stage with efficiencies and a quality comparable to those obtained in IVF/ICSI procedures and carryover of mtDNA is reassuringly low - below 2%. However, the panel could not rule out the risk of levels of carried-over mtDNA increasing during subsequent development - a phenomenon known as 'reversion' - that might follow clinical application of these techniques in a proportion of cases .
- There is no available evidence to suggest that one technique should be preferred over the other, although PNT is currently more refined in the UK.
- With such innovative techniques, patients should be made aware that there can be no guarantee of safety and efficacy, and must accept and understand the potential limitations and risks of any proposed treatment before undergoing it.
- As a result, it would be appropriate to offer either mitochondrial donation technique as a clinical risk reduction treatment for carefully selected patients for whom preimplantation genetic diagnosis (PGD) would be inappropriate, or unlikely to succeed – i.e. only in those patients who for medical reasons are, due to high levels of abnormal (pathogenic) mitochondrial DNA, unlikely to have any suitable embryos for transfer.
- Therefore, the panel states that “MST and PNT are now at an acceptable stage for cautious clinical use” and “could be initially implemented as a risk reduction treatment for carefully selected patients” .
The report, which incorporates discussions with, and work by, some of the world’s leading researchers on mitochondrial donation, including Professor Doug Turnbull of Newcastle’s Centre for Mitochondrial Research, Dr Shoukrat Mitalipov of the Center for Embryonic Cell and Gene Therapy in Oregon, Professor Dieter Egli of Columbia University in New York, and Dr John Zhang of the New Hope Fertility Centre in New York, further recommends that:
- Patients who become pregnant following the use of MST or PNT should be offered pre-natal testing (PND)
- All patients be encouraged to participate in long-term follow-up of children born from the use of MST and PNT
- Despite any risks associated with a mtDNA/nuclear DNA mismatch being theoretical, consideration should nevertheless be given to mtDNA haplogroup matching as precautionary step in donor selection.
- Certain promising areas for further research be noted, especially an exploration of the methods to further reduce or eliminate mtDNA carryover and/or the phenomenon of reversion.
Andy Greenfield, panel chair and HFEA board member, said:
“This is probably the most comprehensive review of the scientific research into mitochondrial donation undertaken by anyone, anywhere, and I’m extremely grateful to my fellow panellists for their time, commitment and clarity of thought in what is a highly complex and fast-moving area of science.
“We think that the cautious approach to the use of mitochondrial donation in treatment that we recommend strikes the right balance between offering access to this exciting new treatment to couples at real risk of having a genetically-related child with mitochondrial disease, while doing all we can to ensure that the treatment is safe and effective.”
Sally Cheshire, Chair of the HFEA, commended the panel’s dedication and expertise:
“We welcome this report, not only because it is key to the HFEA board’s determination of whether now is the right time to permit the clinical use of mitochondrial donation treatments, but also because, as a standalone work, it will be highly valued by everyone interested in this area of science. There can be no doubt that the panel’s efforts over the last five years represent a kitemark in terms of the investigation that can and should be undertaken whenever scientific research moves towards clinical practice.
“While the detail is fiercely complex, the reason behind all the hard work done by the panel over four reviews is very simple: helping future generations of children to live happy and healthy lives. It is now down to us as an Authority to consider these recommendations and decide if the treatments can be offered.”
Parliament passed regulations permitting the use of MST and PNT in February 2015, and the regulatory framework has been in place since October 2015, but clinics have been advised to wait until after the HFEA had considered the recommendations in this review before applying for permission to offer mitochondrial disease to patients. Thus the panel’s report represents the first of four remaining stages towards the potential use of the techniques in treatment.
In the next stage, the HFEA board will consider the panel’s recommendations at a meeting to be held in London on 15 December 2016, and will decide whether clinics may begin applying to offer the treatment. If the board accepts the recommendations, the first applications can be received.
The third stage involves the consideration, by two HFEA committees, of different aspects of a clinic’s application. The Licensing Committee will assess a clinic’s suitability, looking at existing staff expertise, skill and experience at the clinic, as well as its equipment and general environment. Should that suitability test be met, the Statutory Approvals Committee will then determine whether individual patients and families have a particular risk of an abnormality in their mitochondrial DNA; and whether there is a significant risk that a child born with that abnormality will have, or will develop, a serious physical or mental disability, a serious illness or another serious medical condition .
Should the applicant clinic meet both of these regulatory requirements, the final stage would be the approval of the application, and the use of the technique(s) in treatment.
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NOTES TO EDITORS:
 The third review, published in 2014
 See section 2 for an explanation of these techniques.
 See Annex 3.
 See sections 3 and 4.
 See page 7.
 The full regulatory framework.