IVF, the next generation: Gene testing breakthrough offers fresh hope to thousands

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The Independent Online

Thousands of women at risk of giving birth to sick children could benefit from a revolutionary technique to ensure that their babies are free of genetic disorders.

Five women in Britain are pregnant after having their embryos screened by the technique, which can screen out the genes for common disorders such as cystic fibrosis and Duchenne muscular dystrophy.

The gene for cystic fibrosis is carried by one in 25 Britons and affects 7,500 children. Duchenne muscular dystrophy affects one in every 3,500 male births. These are just two of more than 4,000 single-gene disorders that could be identified by the technique.

It is the first time that "test-tube" embryos have been identified and selected by a new medical procedure hailed by its inventors as a "paradigm shift" in the screening of defective genes.

The pregnant women are all carriers of severe genetic disorders and have opted for the experimental test in the hope of having healthy, unaffected babies following in-vitro fertilisation (IVF).

For about 10 years it has been possible to test IVF embryos for certain genetic diseases in order to implant only healthy embryos, but this complicated method of pre-implantation genetic diagnosis (PGD) has limitations, according to experts.

The latest procedure is more accurate, more powerful and marks a radical development in the technology of testing embryos, said Peter Braude, professor of obstetrics and gynaecology at King's College London.

"We really think this is a big, big change in terms of what we usually do. This changes everything, it really does," said Professor Braude, a scientific adviser to the Human Fertilisation and Embryology Authority.

PGD involves taking a single cell from an IVF embryo and delicately testing the minute quantities of DNA it contains for the presence of a known mutation for genetic disorders such as cystic fibrosis.

The new procedure, called pre-implantation genetic haplotyping (PGH), takes a single cell and multiplies its entire genetic complement a millionfold before testing whether the embryo has inherited the defective part of a chromosome from its father or mother.

"We don't have to know the precise details of the genetic mutation and it just opens doors to all sorts of disorders," Professor Braude said. "It improves dramatically the diagnostic success rate because you can make the diagnosis more reliably and you have more embryos at the end of it. It's more accurate, it has a higher reliability, it's going to be available for a whole range of disorders," said Professor Braude, who announced the breakthrough at the European Society of Human Reproduction and Embryology in Prague.

Two of the five pregnant women tested by PGH are carriers of the defective gene for Duchenne muscular dystrophy, two carry mutations for cystic fibrosis and the fifth suffers from a rare condition that can result in cancerous tumours during pregnancy.

Duchenne's disease affects boys, who inherit it from mothers who carry a genetic mutation. The women themselves are healthy and unaffected. At present, couples who want an unaffected child are offered prenatal sex testing and a termination if the foetus is male. Another alternative is sex selection of IVF embryos to implant only females - this leads to the deliberate destruction of male embryos, even though only half are at risk of Duchenne's.

PGH can identify the 50 per cent of male embryos that will be unaffected, said Alison Lashwood, a consultant nurse at Guy's and St Thomas' hospitals in London. "We can tell the difference between the affected and the unaffected males and that, for some couples, will make a difference between whether they get an embryo transfer or not," Ms Lashwood said. "At least using this technology we are hopefully increasing the number of embryos, and we'll help some people to achieve pregnancy," she said.

Pam Renwick, the geneticist at Guy's Hospital who has pioneered the test's development, said that the technique can be applied to any genetic disease where the mutation has been located on a region of a particular chromosome. "It's a universal test for all families and it has the added advantage that we can now select for unaffected males, which increases the number of embryos for transfer into the womb," Dr Renwick said.

The PGH test can also distinguish between female embryos that are healthy carriers of a defective gene from those that are completely free, non-carriers. This raises the ethical issue of whether to offer couples the opportunity to discard female embryos that are healthy carriers in favour of healthy non-carriers. Some couples have already asked whether it is possible to use genetic tests to choose non-carrier embryos, even though carrier female embryos would lead normal, healthy lives - like their mothers.

"We have had requests for PGD for carriers. We've not actually taken anyone through who has asked for that at this stage," said Ms Lashwood. "At the end of the day, we are aiming for couples to take home a baby. So our recommendations are about which embryo looks the best for becoming pregnancy," she said.

Professor Braude said: "If you are looking at the eugenic implications of saying that we're trying to eliminate a disease from a family, that's a completely different story from what we are trying to do," he said. "This is nothing to do with screening. This is to do with families at significant risk who can choose this technique over prenatal diagnosis and termination of pregnancy. The easy way is you get pregnant, test the pregnancy and abort it if it is no good. Some people have done that repeatedly and don't want to do it again, or they have religious objections to termination."

Linda Ball, 37: 'I just couldn't bring myself to consider an abortion'

Duchenne muscular dystrophy is a severe muscle-wasting disease that mainly affects boys who inherit a defective X chromosome from their mothers who are healthy carriers.

At present, couples with a family history of the disorder are offered pre-natal tests that can determine the sex of their foetus.

Pregnant mothers carrying male offspring are offered terminations even though there is only a 50:50 chance of the diseased gene being passed to their sons.

The brother of Linda Ball died of Duchenne's when he was 18 - she was 13. She now has a son Daniel, five, with it, and a daughter, Helena, one.

Mrs Ball, 37, from Daventry, said because of the experience of her dead brother, she knew that she was at risk of carrying the mutation before she became pregnant.

"When I started trying for children, I thought I would have a pre-natal test and an abortion if I knew I was carrying a son. As soon as I got pregnant with Daniel, I couldn't bring myself to consider an abortion," she said.

"When I was pregnant with Helena, we thought about the test, though I knew I couldn't have an abortion. We decided to have it, as if we knew it was a girl it would be a weight off our minds."

The new test would in theory get round the problem of aborting a viable pregnancy, and Mrs Ball says she would have considered it had it been available. "It's more clinical than having a test and an abortion. Of course there is debate about when a life becomes a life," she said.

"We don't know if Helena is a carrier. If she wants to, she can have the test at 16.

"She has a real choice: if she wants to become pregnant but doesn't want a boy with the same illness as her brother, she might be able to make that decision."