Progress towards the application of mitochondrial donation

Following the 15 December announcement by the Human Fertilisation and Embryology Authority (HFEA) that it had approved “the cautious use of mitochondrial donation in treatment”, we reviewed the progress since our October 2015 post, “Three-parent babies” in UK from today? and the further steps that are necessary before mitochondrial donation can is finally applied in practice in the UK.

Background

The Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015 SI 572 came into force on 29 October 2015, and through Part 2, “provides for specified eggs and embryos, which contain donated mitochondria, to be permitted for use in assisted conception treatment under section 3(2) of the Human Fertilisation and Embryology Act 1990 (“the 1990 Act”) in certain circumstances.”

The Human Fertilisation and Embryology Authority, (HFEA) Briefing Note of October 2014, stressed that Parliament’s approval of the draft Regulations did not, per se, directly lead to such treatments being offered in humans; the consequences were that mitochondrial donation became part of the regulatory scheme set out in the Human Fertilisation and Embryology Act and administered by the HFEA, under which it is required to assess two things:

• that any clinic that wishes to offer mitochondrial donation is competent to offer it; and
• that each case of treatment is appropriate, using criteria set out in the Regulations.

The Briefing Note stated:

“The decision will rest with an HFEA committee and will be based on the evidence submitted and the latest scientific advice. The committee will, in effect, carry out a further assessment at the time of the application of the safety and efficacy of the proposed technique. This will, therefore, provide an opportunity for an assessment of the results of the further experiments suggested by the expert panel.

There are likely to be few very applications to carry out mitochondrial donation. At present, only one research team in the UK is likely to be in a position to offer it to patients in the near future”.

Recent HFCA Decision

On 30 November 2016, an independent expert panel, convened by the HFCA to undertake a review of mitochondrial donation techniques, recommended that approval be given for their “cautious” use in “specific circumstances”. The panel’s report includes a comprehensive review of global developments in pre-clinical research into mitochondrial donation, including the safety and the efficacy experiments that the panel recommended be undertaken in its previous report (in 2014) before clinical use of the Maternal Spindle Transfer (MST) and Pronuclear Transfer (PNT) techniques be permitted.

The panel concluded that significant progress has been made in addressing remaining issues identified in previous reports, but the panel could not rule out the risk of levels of carried-over mtDNA increasing during subsequent development in a proportion of cases. There was no available evidence to suggest that one technique should be preferred over the other, although PNT is currently more refined in the UK. 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. In summary, the panel stated 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 panel’s report represented the first of four remaining stages towards the potential use of the techniques in treatment. The next stage was the meeting of the HFEA board on 15 December 2016 at which the panel’s recommendations were accepted. Following this decision, clinics wishing to offer the treatment must apply to the HFEA.

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. Once this stage has been passed, licensed clinics may then apply to the Statutory Approvals Committee for permission to treat individual patients, as required by the regulations. Only when these committees have both approved the application can the final stage of treatment begin.

Comment

On 15 December, the Newcastle Fertility Centre confirmed that “within 24 hours [it would] be applying for a licence to help patients who risk transmitting mitochondrial disease to their children”. The Newcastle team aims to offer treatment for up to 25 women a year affected by mitochondrial disease but the treatment could be held back if they don’t have enough healthy donated eggs; the Newcastle Fertility Centre is looking for healthy women who are up to 35 years old to consider donating their eggs to help this cause.

However, the Society for the Protection of Unborn Children (SPUC) has condemned the HFEA decision, saying that the technique undermines respect for human life and reproduction, and raises very serious safety concerns. On the two techniques, Bioethicist Dr Anthony McCarthy of SPUC said:

“Pronuclear Transfer destroys two human embryos by removing the nuclear material from an embryo with faulty mitochondria, whose life is ended, and creating a new embryo by placing this nuclear material into the shell of a second embryo who is also destroyed…The fact that there are now calls in Newcastle for egg donors – in practice, to produce healthy embryos solely for spare parts – tells us much about attitudes to women used to produce embryos this way, and harms and endangers us all.”

“Maternal Spindle Transfer uses a donor egg which is enucleated and then given the nucleus from the egg of the woman with the mitochondrial condition, such that when the egg is fertilised an embryo is formed, it is hoped free from disease (this embryo has ‘three parents’ as the donor egg is from a mother who makes a genetic contribution to the embryo). While no embryos need be destroyed in the technique itself, the new life has come to be through a production process which fragments maternity and will in practice be subject to quality-control.”