A new technique is set to improve the success rate of PGD (preimplantation genetic diagnosis) the testing of embryos for gene mutations that cause disease. Five UK women are already pregnant after undergoing the procedure - dubbed 'preimplantation genetic haplotyping (PGH)' - at Guy's and St Thomas' Hospital in London. The research was presented today at the annual meeting of the European Society of Human Reproduction (ESHRE), and will appear in the July issue of the journal Reproductive BioMedicine Online.
PGD involves taking a single cell from a 2-4 day old IVF embryo, performing a genetic or chromosome test on that cell, and then returning one or two unaffected embryos to the womb. PGD is expensive, and its success rate is usually lower than that of 'standard' IVF because doctors have fewer healthy embryos to choose from. However, for some families at risk of passing on a genetic disorder to their children, it offers a more acceptable alternative to starting a pregnancy and terminating affected fetuses.
At present, PGD can only be used for disease mutations that are well characterised, and for which genetic tests are already available. It can also be used to treat families at risk of passing on 'X-linked' disorders that usually affect only boys, by selecting female embryos. However, the new technique could potentially overcome both these limitations. In PGH, instead of detecting the mutation itself, scientists look at a set of nearby DNA 'markers' that can distinguish the chromosome with the faulty version of the gene from one carrying the healthy version. In order to do this, the scientists first increase the amount of DNA available to test, using a new method called multiple displacement analysis.
One of the advantages of PGH is that it can be offered to families carrying rare mutations, as well as those with more common, previously identified mutations. It also means that for families affected by an X-linked disease, such as Duchenne muscular dystrophy (DMD), doctors will be able to distinguish affected male embryos from unaffected ones - potentially increasing the number of healthy embryos that can be returned to the womb. The team has already used the technique seven times, which has resulted in five pregnancies - the most advanced of which is 16 weeks. Two of the couples were at risk of passing on a rare cystic fibrosis gene mutation, while two others used PGH to avoid DMD. A fifth woman had previously had a hydatidiform mole, a rare condition in which a placental tumour grows in the womb instead of a baby.
According to team leader Peter Braude, the technique represents 'a paradigm shift, a big, big change'. He added that 'because we don't now have to know the precise details of every mutation we want to screen for, it opens the doors for all sorts of disorders. It will make diagnosis more accurate and improve success rates'. Marita Pohlschmidt, director of research at the Muscular Dystrophy Campaign, told the Times newspaper that the new test 'will hopefully increase the chance of success and reduce the strain on couples during this often intensely emotional time'.
Meanwhile, according to a report in the Sunday Times, a team at University College Hospital (UCH) is planning to apply to the Human Fertilisation and Embryology Authority for a licence to carry out PGD for autism. Although in most cases, autism is thought to be caused by a poorly-understood combination of several different genetic and non-genetic factors, in some families the condition is clearly inherited. Joy Delhanty, professor of human genetics at UCH, told the newspaper that 'normally we would not consider this unless there were at least two affected boys in the immediate family'.