Health of cells may be revealed by tell-tale molecules.
It may soon be possible to assess the health of an embryo created by in vitro fertilization (IVF) without interfering with a single cell on its future body. New assays that look for tell-tale molecules secreted by healthy embryos could help reproductive biologists select the embryos that are most likely to produce a baby.
In IVF, several embryos are usually created. Embryologists try to select the healthiest by visual inspection of the number of cells or the rate at which they divide, and transfer these back to the womb.
But these assessments are subjective and fallible. In the United States, on average less than 40% of IVF cycles end in pregnancy. To improve the odds, doctors routinely transfer multiple embryos, increasing the risk of twins or triplets.
Now researchers are working on selection methods that are quicker, more objective and leave the embryo intact. Several research groups and companies presented preliminary studies at the meeting of the American Society for Reproductive Medicine in New Orleans last week.
Such tests could boost pregnancy rates as well as reduce the need to transfer several embryos and risk multiple births. “Everyone's arriving at the same realization,” says Dagan Wells, who studies gene expression in eggs at Yale University in New Haven, Connecticut.
Everyone's arriving at the same realization.
Many groups are trying to find a fingerprint of proteins or metabolites that only healthy embryos secrete. Emre Seli at Yale and David Burns at McGill University in Montreal, Canada, have used spectroscopy to identify such a signature in the media in which embryos are grown. Two trials reported at the meeting showed that the test could predict which embryos would implant with more than 70% accuracy. Seli says he will start recruiting women into a larger clinical trial within months.
Others are trying to assess eggs after they are collected but before fertilization. Selecting the most promising could allow fewer embryos to be created. This would be particularly useful in countries with legal restrictions such as Italy, where the law permits only three eggs at a time to be fertilized.
A group led by Samir Hamamah, who heads the assisted-reproduction unit at the Hôpital Arnaud de Villeneuve in Montpellier, France, is extracting and analysing the proteins in the cumulus cells that nestle intimately around an egg when it is ovulated. Hamamah reported in New Orleans that he has identified a handful of proteins that are manufactured at higher or lower levels in the cumulus cells of human eggs that go on to be fertilized compared with those that do not (S. Hamamah et al. RBM Online, http://www.rbmonline.com/Article/2559).
Like any development in reproductive biology, such tests are unlikely to come without controversy. Some researchers claim that tests for an antigen called HLA-G in the growth medium of an embryo can predict the outcome of IVF. But not everyone is convinced that its levels really correlate with pregnancy. Any new test should be shown to boost pregnancy rates in clinical trials before it is offered to patients, says Mandy Katz-Jaffe at the Colorado Center for Reproductive Medicine in Englewood.
Katz-Jaffe believes she can take such screening methods one step further. She is working on an ambitious test that will not only distinguish healthy embryos, but reveal whether or not an embryo carries a specific chromosomal abnormality.
At present, technicians can extract a cell from an embryo and test it for genetic defects, a procedure called preimplantation genetic diagnosis (PGD). But it's unclear whether this subtly damages the embryo. Katz-Jaffe is searching for proteins that are secreted at different levels by embryos with specific chromosomal defects, for example an extra copy of chromosome 21.
But Santigao Munne, an expert in PGD at diagnostic genetics company Reprogenetics in Livingston, New Jersey, questions whether this approach can replace PGD: “It's a lot of noise,” he says. He believes that rather than detecting signs of particular abnormalities, such assays may simply be picking up molecules released by embryos that have stopped growing.
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Pearson, H. Safer embryo tests could boost IVF pregnancy rates. Nature 444, 12–13 (2006). https://doi.org/10.1038/444012b
The integrity of cfDNA in follicular fluid and spent medium from embryo culture is associated with embryo grade in patients undergoing in vitro fertilization
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