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On Friday, a young mother from Bristol will turn 30. She has no plans for a big party, preferring to mark the occasion with a few quiet drinks and a meal with friends and family.
Louise Brown's celebrations could hardly be more unassuming. Neither could they be more of a contrast to the international attention that followed her birth on July 25, 1978, as the world's first test-tube baby.
Ms Brown's low-key birthday is a perfect illustration of what has happened in reproductive medicine since Robert Edwards and the late Patrick Steptoe performed IVF on her mother, Lesley, in 1977.
An experimental procedure that was once so controversial that it was likened to infanticide by its critics has now become so routine that it accounts for 1.5 per cent of all births. Yet although pregnancy rates have improved, 70 per cent of IVF cycles performed in Britain still fail. This is partly because today's clinicians have little more idea than did Steptoe and Edwards about which IVF embryos will become healthy children. There also remains a sub-group of men and women who cannot be helped by existing fertility treatment.
These are the great challenges of modern reproductive medicine. Here, The Times outlines some of the ways in which IVF can be expected to improve by the time Ms Brown turns 40.
Genetic screening
A major reason why IVF embryos fail is that up to two thirds have the wrong number of chromosomes. As these defects cannot be detected by eye, embryos with no chance of developing are often used. A reliable method of screening would have a major impact on success rates.
A pre-implantation genetic screening (PGS) test is already available. However, a cell must be removed from an embryo of eight cells and if this is done badly the embryo can be killed. A trial recently found that the test could reduce the chance of pregnancy. A more advanced PGS is being developed. Embryos are tested at a later stage, when they have grown to blastocysts of 100 to 150 cells. As the embryos are larger, more cells can be removed without risking damage.
A trial led by Dagan Wells, of the University of Oxford, and Bill Schoolcraft, of the Colorado Centre for Reproductive Medicine, is already producing remarkable results. Of 14 women treated so far, all of whom had a poor prognosis because of advanced age or previous IVF failures, 11 are pregnant and one has given birth.
Dr Wells believes that blastocyst PGS could double success rates, and perhaps even raise them as high as 90 per cent. “Our experience with PGS suggests the success rate can probably be doubled from where we are now, perhaps more,” he said.
Metabolic profiling
Genetic screening is not the only new approach to assessing embryos that is poised to break through into routine clinical practice. Scientists are also developing non-invasive tests, which aim to judge quality from the culture media in which embryos grow. There are three broad ways of doing this, which are known together as metabolic profiling, or metabolomics.
The first is to examine proteins excreted by embryos, such as immune factors that reduce the chance of rejection by the mother's womb. Another is to look at which amino acids - the building blocks of proteins - are taken up by the embryo from the womb. Research by Henry Leese, of the University of York, and Daniel Brison, of the University of Manchester, has established that three or four amino acids are good indicators of quality.
The final method is infra-red spectroscopy, which examines the light scattered by the culture media. Studies led by Emre Seli, of Yale University, have shown that this can predict which embryos are likely to implant. A commercial scanner is expected to be on the market next year.
Dr Brison said he was confident that these would improve pregnancy rates, to as high as 40 per cent for standard embryo transfers and even to 60 to 70 per cent when blastocysts were used. “I think it's very likely that one of these methods will soon be on the market and very widely used,” he said. “Within five years, at least one - I'm not sure which one but at least one - will be in routine clinical use.”
Metabolomics, Dr Brison said, would be critical to cutting the 24 per cent multiple pregnancy rate to 10 per cent, which the Human Fertilisation and Embryology Authority wants clinics to achieve by 2012. “I think we can reach this target just using improved embryo grading and blastocyst culture, but if we want to get down to the target without compromising success rates, we will need this technology.”
Artificial sperm and eggs
For all the success of modern IVF, it still cannot help men and women who make no sperm or eggs (gametes) of their own. Stem-cell research, however, promises a solution, in the shape of artificial or in-vitro derived (IVD) gametes grown from scratch.
Karim Nayernia, of the University of Newcastle upon Tyne, has created mouse sperm from bone marrow stem cells, which have been used to fertilise eggs and produce pups. Eggs have been generated from mouse embryonic stem cells, though they have yet to give rise to any young.
Scientists believe that such techniques could plausibly be making human sperm and eggs within ten years. If made from cloned embryonic stem cells, or from adult cells reprogrammed into an embryonic state, IVD eggs and sperm could carry a patient's DNA. Men and women who have been sterilised by cancer treatment, early menopause or infection would then have the opportunity to have their own genetic children.
The most significant hurdle remains safety: all the mouse pups born from IVD sperm died prematurely, and there are fears about genetic abnormalities. Extensive animal trials are needed before human work can be contemplated. If these succeed, metabolomic and PGS technology could then assess whether human embryos made from IVD sperm and eggs appear genetically normal.
Dr Brison said: “We'll need to profile embryos made from in-vitro derived gametes as an important part of safety testing, and metabolic profiles will play a role in that.”
Professor Robin Lovell-Badge, a stem-cell scientist at the National Institute for Medical Research, said: “I'm very optimistic that these methods will be developed over the next couple of years, certainly in mice. Translating it to humans will take longer, but hopefully not too much longer.”
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