Fertility techniques for genetic disease examined

Behind the Headlines

Friday March 11 2011

Genetic material was transferred between two fertilised eggs

BBC News reports that the UK human fertility watchdog is assessing the viability of “controversial” fertility treatments that could give “couples at risk of passing on serious inherited disorders a way to have a healthy child”.

It said the techniques are still at the research stage, and new legislation would be needed to allow them to be used. To investigate whether this is justified, the Human Fertilisation and Embryology Authority (HFEA) has been asked by the health secretary Andrew Lansley to deliver a full review of these techniques.

The treatment is called three-parent in vitro fertilisation (IVF). It involves the transfer of genetic material between two fertilised eggs, with the aim of replacing a part of the egg cell called the “mitochondria”. Mutations in mitochondrial DNA cause at least 150 hereditary conditions.

Embryos made using this technique would have nuclear DNA from both parents, and mitochondria from a donor egg. Mitochondrial DNA makes up a very small part of the total DNA in cells, so the offspring would still mostly be derived from the nuclear DNA of the mother and father and mainly inherit their characteristics.

The HFEA states that it has put together a panel of experts to “collate and summarise the current state of expert understanding on the safety and efficacy of methods to avoid mitochondrial disease through assisted conception”. A full review of these assisted reproduction methods is to be submitted to the Department of Health next month.


What is mitochondrial disease?

Mitochondrial DNA mutations can result in neurological, muscular and heart problems and deafness. Some of these conditions are serious and can be fatal at birth.

Around 1 child in 6,500 is born with a mitochondrial disease, and at least 1 adult in every 10,000 is affected by disease caused by mutations in their mitochondrial DNA. As each cell has multiple mitochondria, whether or not a person is affected by a mitochondrial disease depends on the proportion of their mitochondria that carry the mutation. Disease occurs in people carrying the mutation in at least 60% of their mitochondria.


What do the experimental techniques involve?

The nucleus is extracted from the egg and transplanted into a second, donor egg. In this way the genetic material contained within the cell nucleus would come from the couple, but the mitochondria within the cell would come from the donor. Compared with the nucleus, which contains a large quantity of DNA from both the mother and father, mitochondria contain a small amount of genetic material, but this comes from the mother only.

The hope is to avoid inherited diseases coded for in the mother’s mitochondrial DNA by transplanting the nucleus into a donor cell with ‘healthy’ mitochondria. 


What is the existing legislation?

As specified by the Human Fertilisation and Embryology (HFE) Act, 1990, at present, only eggs and embryos “that have not had their nuclear or mitochondrial DNA altered” can be used for assisted reproduction.

However, in 2008 a provision was added to allow for regulations to be made to allow the alteration of DNA if it will prevent the transmission of serious mitochondrial disease, provided that such procedures were clearly demonstrated to be safe and effective. The review now taking place will enable policy makers to assess whether new legislation is now needed to allow for the developing procedures, which do not fall within the current legislation.


How are mitochondrial diseases currently screened for?

In the UK, it is possible to screen for mutated mitochondrial DNA during assisted reproduction, but alteration of the DNA is not allowed. Preimplantation genetic diagnosis (PGD) assesses the mitochondrial DNA contained within polar bodies in the egg cell (the by-products from division that created the egg cell) for abnormalities. It is also possible to remove blastomeres (cells produced following division of the fertilised egg) from the embryo and examine these instead.

Using this method, it is possible to estimate the levels of ‘mutated’ mitochondrial DNA in the egg cell before it is implanted, and the risks of disease in the offspring. This technique is permitted to test for more than 100 genetic conditions. Although it reduces risk of the offspring being affected, it does not completely eliminate the possibility of passing a mitochondrial disease from mother to child.


What are the new techniques?

The new techniques currently at the developmental stage, and which the HFEA is investigating, are:

Pronuclear transfer

This technique involves transferring the pronuclei from a fertilised egg (which has mutated mitochondria) and placing them into an egg that has healthy mitochondria. Pronuclei are the nuclei of sperm and egg cells found in the fertilised egg, before the two nuclei fuse.

Spindle transfer

This involves transferring the genetic material from the nucleus of the mother’s developing egg cell (which has not been impregnated by sperm) with mutated mitochondria and placing it into an egg cell that has healthy mitochondria.

New legislation would be needed to permit either of these techniques in the UK, as they both alter the mitochondrial DNA of the egg or embryo.


Are there any safety concerns with these techniques?

The Scientific and Clinical Advances Committee (SCAAC) of the HFEA last reviewed these techniques in May 2010. They considered that both were “promising” but posed different safety concerns. They concluded at that time that more safety testing was needed around both techniques of pronuclear transfer and spindle transfer, particularly related to the risk of chromosomal abnormalities in the newborn. For spindle transfer specifically, they considered that further study in primates was needed. For pronuclear transfer they considered that much further research was needed including:

  • animal studies
  • studies using normal human egg cells
  • research on the interaction between mitochondria and the nucleus
  • research on the incidence of chromosomal abnormality in embryos produced in this way
  • research looking at whether embryos generated in this way show a similar pattern of gene expression to normal embryos
  • research that would allow examination of mitochondrial activity in cells that develop from embryos formed in this way


What happens next?

Since the review by the SCAAC last year, research into these techniques has continued and more is being learnt about their safety and how effective they are. The current review is broader. It will involve scientific evidence submitted by experts in the field, including published studies, unpublished research or any statements covering the safety or effectiveness of assisted reproductive techniques to avoid the transmission of mitochondrial disease. There will be a workshop review and then submission of the report to the Department of Health, expected by mid April.

A Department of Health spokesperson was quoted by the BBC as saying, “This treatment is not currently possible under current legislation. When the group reports back and based on the evidence available, we can decide whether it is the right time to consider making these regulations”.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

New fertility technique to be assessed by regulator. BBC News, March 11 2011


Links to the science

Review of scientific methods to avoid mitochondria disease. Human Fertilisation and Embryology Authority.


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