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Scientific and Clinical Advances Group (SCAG) meeting
Thursday 21st February 2008
Lay summary
1. Review of preimplantation genetic screening (PGS)
Background
1.1. Some patient groups are thought to have a high risk of IVF failure because their
embryos contain abnormal chromosomes (the structures that contain DNA in the
nucleus of each cell). These patients can undergo PGS to genetically screen
their embryos for abnormalities.
1.2. PGS involves removing one or two cells from an embryo created by IVF or ICSI
and looking at the chromosomes in that cell. Only embryos that do not have any
abnormalities will be transferred.
1.3. PGS can be licensed for: advanced maternal age, recurrent miscarriage,
recurrent implantation failure, family history of aneuploidy (abnormal
chromosomes) and male factor infertility.
1.4. A number of recent studies have suggested that PGS does not increase success
rates. SCAG therefore decided to review the available literature published about
PGS.
1.5. The literature review revealed a lack of high quality data from large randomised
trials. Some small scale non-randomised studies showed that PGS can increase
success rates. However the few larger controlled trials found that it did not
improve success rates.
1.6. The British Fertility Society (BFS) 2007 guidelines recommend that:
“Patients should be informed that there is no robust evidence that PGS for
advanced maternal age improves live birth rate per cycle started. Indeed from
the evidence currently available the live birth rate may be significantly reduced
following PGS…There is an urgent need for adequately powered prospective
randomised controlled studies to assess the place of PGS in patients with
different indications, including recurrent miscarriage and repeated implantation
failure.”
Recommendations to SCAG
1.7. The recommendations to SCAG from the literature review were:
- Guidance and patient information should refer to BFS guidelines and inform
patients that more trials are needed to assess the effectiveness of PGS
- Centres should monitor the latest literature and professional guidance
Outcomes
1.8. SCAG approved the recommendations but wanted more data and information.
Members knew of a number of larger studies being published over the next few
months and a conference on PGS being held in mid-March.
1.9. Members agreed that these studies should be analysed along with data held by
the HFEA. The Executive could then make recommendations to the Authority
regarding how this information could be used to potentially amend the Authority’s
policy and licensing of PGS.
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2. Treatment for mitochondrial disease
Background
2.1. Mitochondria are small complex structures that produce energy in cells. Most
cells contain up to several hundred mitochondria. Though the majority of a cell’s
DNA is contained in the nucleus, each mitochondrion contains a small amount of
DNA. This DNA encodes a few genes needed for the cell to make energy.
2.2. Mitochondrial disease occurs when there are mutations in these genes. This
can result in a number of relatively rare but very serious diseases. There are
few treatments for mitochondrial disease and for many patients the disease
progresses and can be fatal.
2.3. Some mitochondrial diseases are inherited. Mitochondrial disease is only
passed on from the mother because mitochondria are only present in the egg
after fertilisation. Mitochondria in the sperm are not transferred during
fertilisation.
2.4. Under the Human Fertilisation and Embryology Bill, an egg or embryo ‘permitted’
for treatment cannot have its mitochondrial or nuclear DNA altered. However
there is a regulation-making power to allow this for the treatment of serious
mitochondrial disease.
2.5. SCAG members were updated on three techniques that could develop into
treatments for mitochondrial disease: germinal vesicle transfer, pronuclei
transfer and microcytoplast cryopreservation.
2.6. The first two techniques, germinal vesicle and pronuclei transfer, both involve
removing the nucleus from a patient’s egg that contains unhealthy mitochondria.
The nucleus is then transferred into a donor egg with healthy mitochondria that
has had its own nucleus removed. This egg will therefore contain the patient’s
nuclear DNA and mitochondrial DNA from the donor egg.
Remove donor
nucleus
Healthy
mitochondria
Transfer patient nucleus
Unhealthy
mitochondria
Patient egg
Donor egg
Diagram of nuclear transfer
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2.7. In germinal vesicle transfer the nucleus is transferred from an egg just before it
becomes fully mature, known as the germinal vesicle stage. The nucleus in this
stage of development is called the germinal vesicle.
2.8. Pronuclei transfer is carried out just after an egg has been fertilised by a sperm.
The two nuclei of the egg and sperm at this stage are called pronuclei. Both the
egg and sperm pronuclei are transferred during pronuclei transfer.
2.9. Newcastle Fertility Centre at Life was granted a licence to carry out a research
project on pronuclei transfer. The group recently announced that they
successfully developed human embryos to blastocyst stage (day 5 or 6 of
embryo development) after carrying out pronuclei transfer.
2.10. These techniques mean that the resulting embryo will contain DNA from three
sources: the patient whose nucleus was transferred, the male sperm donor and
the mitochondrial DNA from the egg donor. Some of the mitochondria from the
patient may also be transferred when the nucleus is transferred. Having DNA
from three different sources raises potential safety issues.
2.11. The third technique, microcytoplast cryopreservation, involves removing a
segment from an egg and freezing it separately to the remaining egg. The
segment and remaining egg are then reconstructed later into a complete egg.
This may potentially allow egg segments with healthy mitochondria to be
reconstructed to an egg with unhealthy mitochondria to treat mitochondrial
disease.
Recommendations to SCAG
2.12. SCAG was asked to consider whether germinal vesicle or pronuclei transfer
would be safe to use in treatment. They were also asked to consider whether
centres would be likely to want to use microcytoplast cryopreservation for
research or treatment.
Outcomes
2.13. Members concluded that the safety issues of germinal vesicle and pronuclei
transfer have not yet been assessed. They thought that there needs to be more
published literature on the safety issues surrounding these techniques.
2.14. Members did not think that microcytoplast cryopreservation was a viable
technique for either research or treatment and thought there was a risk of
destroying the egg.
3. Gene transfer into embryos and male germ lines
Background
3.1. The Human Fertilisation and Embryology Bill as it stands will allow researchers
to alter the genetic structure of embryos i.e. by inserting specific genes into an
embryo’s DNA, for research.
3.2. There have also been recent animal studies which inserted genes into the male
germ line (cells which will form sperm). The technique may be able to ‘kick-start’
sperm production in infertile males.
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3.3. It is not known for sure if this technique genetically alters the actual sperm.
Human sperm that has been genetically altered is not permitted for treatment
under the Bill.
Recommendations to SCAG
3.4. SCAG members were asked to consider the possible uses of gene transfer into
embryos, which the Authority are likely to receive research licence applications
for once the Bill receives Royal Assent. They were also asked to consider the
likely timescale and safety issues around gene transfer into the male germ line.
Outcomes
3.5. Members thought that the HFEA will receive applications to do gene transfer
research on embryos as soon as the Bill received Royal Assent. There are likely
to be many different reasons researchers will want to do gene transfer into
embryos. These include research into early human embryo development and
research into the fate of different cells in the embryo.
3.6. The Bill has taken away all inhibitions on genetically altering human embryos for
research. SCAG thought that there were large ethical and public interest issues
and that these should be referred to ELAG for debate.
3.7. Members thought that there were huge safety issues for gene transfer into male
germ line cells. The DH observer clarified that all early sperm cells are under
the remit of the Bill. Therefore genetically altering any of these cells would not
be permitted for treatment. However gene transfer techniques that only target
the cells that nurture early sperm cells as they develop (Sertoli cells) would not
be in the Bill’s remit.
4. Alternatives to embryonic stem cells
Background
4.1. There are a range of techniques being developed to derive embryonic stem (ES)
cells or ES-like cells that do not destroy viable embryos.
4.2. There are two techniques that appear to be advancing most rapidly. The first
technique is directly reprogramming adult cells, such as skin cells, into cells
which behave like ES cells. These are called induced pluripotent stem (iPS)
cells and can develop into different cell types in the same way ES cells can.
However researchers currently have to use viruses to reprogramme the cells.
This may cause mutations and potentially tumours, making the technique
unsuitable for therapy.
4.3. The second technique is removing a single cell (called a blastomere) from an
embryo and deriving embryonic stem cells from this cell. The remaining embryo
can then potentially continue to develop as normal. A team in the US has just
managed to derive five human ES cell lines from individual cells without
destroying the embryo.
4.4. The HFEA is legally required to ensure human embryo research is “necessary or
desirable” for defined purposes. Therefore if alternative methods of deriving ES
cells are developed, it may not be “necessary” for research groups to destroy
viable embryos.
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Recommendations to SCAG
4.5. Members were asked to decide if any of the different research areas should be
passed on the Research Licence Committees to be considered as part of their
research application process.
Outcomes
4.6. Members concluded that currently the alternatives to deriving ES cells are not
viable. However they thought it is important that all alternatives are pursued and
that information on these techniques should be passed on to Research Licence
Committees.
4.7. Members also thought that this information and details on the outcome of
research projects involving human embryos should be made available to the
wider public.
4.8. The Executive will consider the most appropriate way to communicate this
information to the Licence Committee and the wider public.
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