<i><b>Helen Pearson</i></b>
<b>July 25 2003</b> – Scientists are meeting in London today – the twenty-fifth birthday of Louise Brown, the world's first 'test-tube' baby – to discuss how far in vitro fertilization (IVF) has come and how far it has to go. Many technical and ethical hurdles remain, they say. During IVF, doctors mix sperm and eggs in a dish and transplant the resulting embryos into the mother. The method, pioneered by British doctors Patrick Steptoe and Robert Edwards, and its spin-off assisted reproduction techniques have now produced around a million babies.
Before, infertility clinics were "all doom and gloom", says meeting organizer Allan Templeton of the University of Aberdeen, UK. "IVF just transformed things."
A quarter-century later, the technique is still far from perfect. One of the most pressing issues is the risk of multiple pregnancies, which arises because more than one embryo is placed in the womb. Twins or triplets can be "extremely bad news" for the health of mother and children, says Templeton.
Some European countries allow no more than two IVF embryos to be transferred to the womb. But in the US private healthcare system, where clinics compete to achieve a high pregnancy success rate, this practice is taking longer to catch on.
Several recent studies have highlighted another concern: the possibility that babies born by IVF and other assisted reproduction techniques might be at greater risk of genetic diseases. This will only become clear as the first generation of IVF babies grows up and more extensive studies are done.
Spin off
Since Louise was born, IFV has been honed and expanded. The variable success rate has rocketed to about one in four pregnancies per cycle in young women, by culturing embryos for longer or in different nutritional juices. And since 1991, infertile men have been helped too, by intracytoplasmic sperm injection (ICSI), which shoots a lone healthy sperm directly into an egg.
The biggest medical obstacle to IVF's universal success, say researchers, is the poor quality and number of eggs in older women. They become scarcer with age, as around 20 eggs go to waste each time one is ovulated. "It's possibly the single most important issue," says Roger Gosden of the Jones Institute for Reproductive Medicine in Norfolk, Virginia.
Scientists might eventually work out how to stall the loss of eggs and effectively delay menopause, Gosden predicts. This would involve identifying and blocking the molecules that age the ovary – some of these molecules have already been discovered in mice.
Another solution might be to grow fresh eggs for older or post-menopausal women from ovarian or other tissues in the lab. A study published in May this year coaxed mouse stem cells, grown from tiny embryos, into forming eggs1.
Match point
Considered revolutionary and ethically controversial from the first, IVF continues to spawn debate. One raging at the moment is the use of pre-implantation genetic diagnosis on IVF embryos. The British Whittaker family recently selected and bore a tissue-matched IVF baby to provide a bone-marrow transplant for their child with a rare blood disease.
People are unsure where to draw the line. Should a parent, for example, be allowed to have a baby to save his or her own life? Some think that allowing any type of selection will lead couples to want designer babies, screened for appearance or other traits. Even the medical community is "very split", says assisted-reproduction expert Peter Braude of Guy's, King's and St Thomas' School of Medicine in London.
The ability to manipulate embryos in the laboratory has also given rise to other highly controversial scientific fields, such as human therapeutic cloning. In this technique, which is banned in many countries, embryos are created to grow stem cells, which can generate new tissues that might replace diseased ones.
Over the next 25 years, experts anticipate that IVF will become more standardized, more affordable and hence available to all of the roughly one in six couples who experience some form of infertility. Implanting only one embryo may become routine – as might the use of genetic chips to select those embryos that are most likely to implant and survive.
But experts doubt that another technique will revolutionize reproductive biology in the same way as IVF. "It's like the internal combustion engine," says Templeton. "That was the breakthrough."
