ESHRE: To screen or not to screen?
I went to a fascinating session on pre-implantation genetic screening (PGS) this morning. That's where a cell is taken from the early embryo during IVF, and screened for chromosomal abnormalities before it is implanted into the mother.
It's used mainly for couples seen as at high risk of chromosomal problems, for example if the mother is old (say 38 or older), or if she has had recurrent miscarriages.
Leeanda Wilton of Melbourne IVF gave a great presentation on the technologies available so far. In the past the screening has been done using a technique called FISH -- where fluorescent probes of different colours check for the presence of certain chromosomes in the cell. Only 5-9 chromosomes can be screened this way though, and she's done work to show that this does let through embryos that have problems in other chromosomes. She and her colleagues are pioneering a method called comparative genomic hybridisation (CGH), where the whole genome is screened. DNA from the embryo cell and from a normal test cell (one dyed green, one dyed red) are washed over the chromosomes from a normal cell and by looking at the relative amounts of red and green you can make sure that the correct amounts of each part of the genome are present in the embryo.
That takes a few days though, so you have to freeze the embryo while you wait for the results. Now she's working on doing the hybridisation on microarrays, which is much quicker, and much more accurate (I mentioned this idea in a news story on Monday, see http://www.nature.com/news/2006/060612/full/060612-16.html). "We're moving towards having an almost off the shelf DNA chip on which you could analyse anything that turns up," she said. "These are very exciting times."
One member of the audience pushed her on the problem that many embryos are mosaic at the 8-cell stage - in perhaps 60-70% of them different cells can have different complements of chromosomes. So if you're just taking one of those cells for screening, how can you be sure it will be representative?
Wilton admitted this is a problem that can't be sidestepped. But she says that when her group has looked at all the cells in an embryo, she reckons they would only have made the wrong decision about whether to keep or trash an embryo only about 5% of the time.
Excitement was tempered further by a talk by Catherine Staussen, from the Dutch-speaking Free University of Brussels. She's been looking at clinical trials that have tried to test whether PGS actually improves the success rate of IVF. Unfortunately the data are few and far between. But based on what is available, she concludes that there is no evidence to support that idea that screening improves a woman's chance of having a healthy baby. She gave several possible reasons for that - perhaps the current methods aren't screening enough chromosomes (the trials only looked at the FISH technique). Perhaps PGS is having an adverse effect on the tested embryos, that cancels out any benefit from the screening. Perhaps as the previous questioner noted, mosaicism in the embryos means they can't be diagnosed properly from a single cell. Or perhaps there are other reasons why IVF fails, not related to the embryo's chromosomes.
She said more trials definitely need to be done, but at the moment there's no argument that screening embryos makes any difference. This didn't go down well in the audience, especially with Yury Verlinsky, who is director of the Reproductive Genetics Institute in Chicago, and pioneered pre-implantation genetic diagnosis. "This is a beautiful approach but you're giving the wrong answers!" he said. "Abnormality of human embryos is an obvious fact. If you remove those 70%, how can there be no benefit?"
"You must carry out your own randomised clinical trials on your own procedures to convince us that it works," countered Staessen. "So far that [evidence] doesn't exist."
Comments
In my experience going through IVF, PGS has been very helpful, and has progressed since this blog was posted.
One must take into account the experience of those undergoing IVF: without PGS, a couple would undergo a transfer of a batch of embryos and wait an agonizing two weeks to find out of any of them have implanted. This process involves a lot of guesswork, a period of agonzing waiting, a risk of miscarriage if an abnormal embryo implants, and also a risk of multiple births for normal embryos.
While PGS might not increase the rate of pregnancy overall, the couple using it will know which embryos to use and which ones not to use, saving them much time and much agonizing uncertainty, and preventing potential miscarraiges and multiple births.
The lab that my clinic works with now analyzes 12 chromosomes, and embryos do not need to be frozen while we wait for the results.
So there have obviously been scientific advances since 2003, but one must also take into account the ways in which PGS can help infertile couples avoid the risks of undue stress, miscarriage, and high order multiple births.
Posted by: KH | December 15, 2006 02:56 PM