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Response to Department of Health Consultation on Draft Regulations to Permit the Use of New Treatment Techniques to Prevent the Transmission of a Serious Mitochondrial Disease from Mother to Child

21 May 2014
This policy document is a response by the Progress Educational Trust (PET) to the Consultation on Draft Regulations to Permit the Use of New Treatment Techniques to Prevent the Transmission of a Serious Mitochondrial Disease from Mother to Child (.pdf 451KB) issued by the UK Government's Department of Health (DH).
Responses to this consultation were summarised and responded to by DH (.pdf 252KB) in July 2014.
PET has also responded to public consultations on mitochondrial donation conducted by the Nuffield Council on Bioethics (NCoB) in February 2012 and by the Human Fertilisation and Embryology Authority (HFEA) in December 2012, has responded to a survey on mitochondrial donation conducted by the HFEA in July 2015, and has drafted briefings for MPs and Peers on the science and ethics of mitochondrial donation.

1. Regulation 2 defines the removal or insertion of nuclear DNA involved in mitochondrial donation. Do you agree with this definition?
Yes. The definition of the removal or insertion of nuclear DNA is satisfactory.

2. Regulations 4 (eggs) and 7 (embryos) only allow mitochondrial donation where all the nuclear DNA is transferred from an egg or embryo to another egg or embryo from which all the nuclear DNA has been removed. Do you agree with this description and restriction?
Yes, we agree with this description and restriction.
After the removal of nuclear DNA from the donor egg or embryo during maternal spindle transfer and pronucelar transfer procedures, it is highly unlikely that any of the donor's nuclear DNA would remain and be transferred. Furthermore, genetic screening tests are available to confirm that all nuclear DNA has been removed from the donor egg or embryo. Whether and in what circumstances such tests are warranted should be a decision for the HFEA.

3. Regulations 5 (eggs) and 7 (embryos) require that, in order to agree that mitochondrial donation can go ahead, the HFEA must decide if there is both a particular risk that the egg or embryo of the patient has a mitochondrial abnormality and a significant risk that a person with the particular mitochondrial abnormality will have or develop a serious physical or mental disability, a serious illness or other serious medical condition. Do you agree that the HFEA should have this role?
The HFEA is the most appropriate body to have this role. It has substantial experience of regulating innovative techniques in assisted conception and embryo research, and of managing the transition of such techniques from novel to routine – for example, with preimplantation genetic diagnosis (PGD). The HFEA is also very familiar with mitochondrial donation, having conducted an extensive public consultation and three scientific reviews on the subject to date.
That said, it is important not to invest too much significance in the HFEA's experience of regulating other comparable procedures on a case-to-case basis. While a case-by-case approach is appropriate while mitochondrial donation techniques are novel, a clear indication should be given to the HFEA that it must review regularly its approval arrangements. Certainly, no requirement for applications to be assessed on a case-by-case basis should be enshrined in these regulations.
The HFEA should develop a process to clarify how mitochondrial donation will be regulated in the longer term. This may involve identifying if and when the relevant techniques can be considered routine, and implementing different arrangements accordingly.
The regulatory burden upon clinician and patient should be kept to a minimum, and case-to-case consideration adds lengthy delays which may reduce a woman's chance of having a baby. The determination of 'serious' in the context of these regulations should be assessed by the clinician, the patient and their family. Again, the regulation of PGD may serve as a model, as this too involves procedures for determining what is 'serious'.
The wording in draft regulations 5(a) and 8(a) relating to the 'particular risk' of an egg or an embryo having 'a mitochondrion abnormality caused by mitochondrial DNA' should be changed. Risk in this context should not be ascribed to the egg or embryo, but instead to the woman who is the patient and carrier of mitochondrial disease.
The eggs and embryos produced by women in this group will have variable levels of mutated mitochondria, because of the phenomenon of the mitochondrial genetic bottleneck. A patient's overall risk is therefore a far more meaningful criterion than risk ascribed to a particular egg or embryo from that patient.
Similarly, paragraph 2.11 of the consultation document uses the formulation 'a donated egg or embryo that is free of a mitochondrial disorder'. This formulation has not been included in the draft regulations, and indeed we do not think that it should be. It is the donor who should show no evidence of having or carrying mitochondrial disease, rather than a particular egg or embryo.

4. Do you agree with the principle that centres should not be permitted to undertake mitochondrial donation without first obtaining authorisation to do so from the HFEA?
Yes, we agree with this principle. Furthermore, we believe that the HFEA should outline the process of obtaining this authorisation, rather than the regulations prescribing this process.
Scalability needs to be built into this process, so that as patient uptake increases, treatment is not delayed due to an overly bureaucratic approach. Again, lessons can be learned from the regulation of PGD.

5. Do you agree that people donating eggs and embryos for the purposes of mitochondrial donation should not have the same status as those donating eggs and embryos for use in fertility treatment but rather regarded more like organ or tissue donors?
Yes, we agree that that people donating eggs and embryos for the purposes of mitochondrial donation should not have the same status as those donating eggs and embryos for use in fertility treatment.
The NCoB considered this question in its exhaustive report Novel Techniques for the Prevention of Mitochondrial DNA Disorders: An Ethical Review (.pdf 1.13MB), and arrived at the same conclusion.

6. Regulation 10 provides that the HFEA should tell a person aged 16, on request, if they were born following mitochondrial donation. Do you agree with this?
Yes, we agree with this.
In relation to non-identifying information disclosed under the 1990 and 2008 Human Fertilisation and Embryology Acts, people over the age of 16 can apply jointly to the HFEA to find out if they might be genetically related via gamete or embryo donation, if they say they are considering entering into a civil partnership, marriage, or intimate physical relationship.
Paragraph 2.29 of the consultation document explains draft regulation 11 as stipulating that if such applications are made in respect of mitochondrial donation, applicants 'will not be treated as related to anyone who shares the same mitochondrial donor as them, or to the donor themselves. This is because there is a very small (0.01%) genetic relationship between the mitochondrial donor and any child born through mitochondrial donation.'
While we agree with the outcome of this policy decision, we feel that the wording of this explication is potentially misleading. A person conceived following mitochondrial donation clearly is genetically 'related' to the mitochondrial donor, whatever the nature and proportion of the donor's contribution.
A better way of approaching this question would be to explain that while children of consanguineous parents have a known elevated risk of autosomal, recessive nuclear genetic disorders there is no analogous risk from mitochondrial donation. The fact that mitochondria are not passed down the paternal line is still another reason why concerns regarding consanguinity do not apply to this type of donation.

7. Regulation 10 also provides that the information that the HFEA should provide in response to such a request should not identify the mitochondrial donor and be limited to screening tests carried out on the donor and about her family medical history, and any other non-identifying information that the donor has provided with the intention that it is made available in these circumstances. Do you agree with this approach?
Yes, we agree with this approach.
The mitochondrial donor does not donate nuclear genes. Mitochondrial donation creates neither observable nor other shared characteristics between the donor and the person conceived following donation (except for the fact that hopefully, neither donor nor the resulting person will have mitochondrial disease). Nor does mitochondrial donation, for most people at the present time, create any psychosocial expectations around a connection of kinship, or any connection analogous to kinship.
We believe that in order to facilitate the gathering of information relevant to this type of donation, the HFEA should create new forms, and should not use its current forms for gamete donors. We also believe that the provision of personal information such as pen portraits and goodwill messages (as currently occurs with gamete donors) should not be expected of mitochondrial donors.

8. Regulation 13 provides that the HFEA should tell a mitochondrial donor, on request, when a child has been born from their donation, how many and their sex. Do you agree with this approach?
Yes, we agree with this approach, which recognises the value of the mitochondrial donor's contribution. However, it is important that this regulation not be seen to be conferring any parental rights or obligations on the donor.
The regulations allow some flexibility, but ultimately, a mitochondrial donor should not be made to feel that they are under any obligation to have contact with any children born as a result of their donation. Nor should a mitochondrial donor be 'nudged' in this direction by DH or the HFEA, via a suggestion that it is in any way beneficial or preferable for them to have contact with children born as a result of their donation.

9. Do you have comments on any other aspect of the draft regulations?
PET welcomes the draft regulations to allow the licensing of new IVF techniques for avoiding the transmission of mitochondrial DNA disease. It is important that these regulations are not overly prescriptive, so that future developments and refinements of the techniques may be introduced without the need to return to Parliament.
The lay public and experts alike have been consulted exhaustively on the ethics, efficacy and safety of these new techniques in recent years, by the Nuffield Council on Bioethics and by the HFEA. The response to these comprehensive pieces of work was prevailingly supportive of the Government passing regulations to permit use of the techniques.
PET has been interested in the avoidance of inherited mitochondrial disease for many years, during which time a number of different terms have been used to capture the process. These changes in terminology are confusing, and PET urges the Government to use 'mitochondrial donation' henceforth in all its work in this area.
The funding of treatment using mitochondrial donation needs to be addressed urgently by Government. The treatments should be funded throughout the UK by the NHS as a specialised service, via the rare diseases budget.
DH will be well aware that procedures such as PGD have in the past been prohibitively difficult for some eligible patients to access, for reasons of restricted NHS resourcing. Now that PGD is funded as a specialised service, the situation has improved enormously. PET urges the Government to begin this process now, to avoid further unnecessary delays for patients who will wish to access this treatment once regulations have been passed.
The draft consultation document in Annex C, 'Regulatory Triage Assessment', gives an expected implementation date of 1 October 2014 and we trust that this will be adhered to. There have already been several delays in arriving at these draft regulations, and it is critical for those who wish to use these treatment options that the regulations are not subject to any further delay.