A new way of screening out bad eggs could boost IVF pregnancy rates and level the playing field for older women seeking their own child.
Around 75% of all miscarriages are thought to be caused by aneuploidies - an embryo having the wrong number of chromosomes - and the risk of these occurring increases as a woman gets older.
Until now, one of the only ways of screening eggs or embryos for aneuploidies was to use a technique called fluorescence in-situ hybridization (FISH), where a cell is removed and stained with small pieces of fluorescent DNA, revealing the structure of specific chromosomes. But the technique cannot spot abnormalities in at least 13 of the 23 pairs of chromosomes in human cells.
Now, a team led by Geoffrey Sher and Levent Keskintepe at the Sher Institute for Reproductive Medicine in Las Vegas, US, have mapped the number of chromosomes in an unfertilised egg using a method normally used in cancer research. This mapping can then be used to predict which eggs will produce embryos with the correct number of chromosomes.
Too few, too many
The new technique is known as "comparative genomic hybridization" (CGH). It involves taking a sample of DNA from the polar body - a chromosome-containing structure that is expelled from the egg before it fuses with a sperm.
The DNA is amplified and mixed with fluorescent probes that bind to it. The resultant level of fluorescence indicates whether there are any missing or duplicated chromosomes.
Sher's team used CGH to analyse 132 eggs from 14 egg donors aged 21 to 29. The eggs were fertilised, and CGH was then used to examine the resulting embryos at 3 days old.
They found that 87% of eggs that had a normal number of chromosomes before fertilisation developed into chromosomally normal embryos, suggesting that the number of chromosomes in an embryo is mostly determined by the egg rather than the sperm.
The team also found that 65% of the donor eggs were chromosomally abnormal. "This is surprising, as it suggests that the incidence of chromosomal abnormalities in younger women is higher than we thought," says Alan Handyside at the UK's London Bridge Fertility Centre, who was not involved with Sher's research. Only 20% of the abnormal eggs developed into 5-day-old embryos - all of which were chromosomally abnormal.
Sher's team then tested whether screening a woman's eggs for aneuploidies could improve her chances of pregnancy. They recruited 41 women with unexplained infertility (and an average age of 37.5 years). Their eggs - or donor eggs, in 13 cases - were screened for aneuploidies using CGH.
In the group, 35 women had at least one embryo that could be implanted - that had come from a chromosomally normal egg being fertilised. Of these women, 28 became pregnant, 18 have now given birth, and a further eight are expected to do so shortly. Two of the women miscarried.
"This is a projected live birth rate of 74% - more than twice the average for IVF," Sher points out.
He has now begun a clinical trial in collaboration with Simon Fishel at the CARE fertility clinic in Nottingham, UK. In it, CGH is used to analyse a single cell taken from a 3-day-old embryo, which is then frozen and implanted at a later date - a process Sher terms "staggered-IVF" (St-IVF).
"We believe that using the embryo rather than the egg will produce even greater success rates," he says. Freezing the embryo is necessary because CGH takes 5 days to complete. Any embryos that have been damaged by the freeze-thaw process can be identified visually.
Note of caution
Meanwhile, Handyside says he is in the process of applying for a license that would enable him to perform a different type of screening called "array CGH" on biopsies taken from early stage embryos. This test could be done within 24 hours, making freezing the embryos unnecessary, he says.
While Sher's team is to be congratulated on using CGH to better understand sources of infertility, the numbers of women included in his study "are too small to be useful indicators of clinical treatment options," cautions Alison Murdoch, head of the IVF research facility at the University of Newcastle, UK.
However, Sher believes that older women with no other underlying cause of infertility could ultimately undergo repeated ovarian stimulations, with the resulting eggs or embryos then being screened until one is found that will result in a successful pregnancy.
Such staggered-IVF "could change the face of IVF treatment, particularly in countries that highly regulate the number of embryos that can be transferred," says Fishel. "When you are only able to choose two, it would be far better to choose the ones that are most likely to be viable."
Journal reference: Fertility and Sterility (DOI: 10.1016/j.fertnstert.2006.08.108)
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