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Rewriting Life

DNA Sequencing of IVF Embryos

Researchers are testing whether high-throughput DNA sequencing can help screen out abnormal embryos during in vitro fertilization.

The most common reason for IVF embryos to fail is that they have an abnormal number of chromosomes.

A reproductive clinic in New Jersey is testing whether DNA sequencing can help make in vitro fertilization less risky.

In the trial, researchers will use DNA sequencing to count the number of chromosomes in each of the embryos they create by fertilizing a woman’s eggs in a dish. An abnormal number of chromosomes is the most common reason for IVF to fail, experts say, and as many as 30 percent of fertilized human eggs have such abnormalities. By selecting only those embryos with the normal number of chromosomes to transfer into the uterus, doctors hope to improve the success rate of IVF.

Traditionally in an IVF procedure, doctors visually inspect embryos and then transfer those that appear healthy after a few days of growth—often more than one at a time, because many of the embryos won’t result in a successful pregnancy. If multiple embryos do implant successfully, however, it can be risky for both them and the mother, says Richard Scott, a reproductive endocrinologist and lead researcher in the trial, which is being conducted at Reproductive Medicine Associates of New Jersey.

To reduce such risks, some clinics, including Scott’s, are moving toward transferring only a single embryo, and new DNA analysis technologies are helping to ensure that they pick the most viable and healthy one. Researchers have already shown that other methods of chromosome screening can improve the success rate of IVF. DNA sequencing offers a more affordable way to do such tests because samples from multiple embryos can be analyzed simultaneously. That gain in efficiency lowers the cost of the procedure and could make chromosome screening feasible for more couples.

Lower-cost testing is especially important for IVF because it’s often necessary to screen many embryos for one couple, says Dagan Wells, an IVF researcher at the University of Oxford. “One patient does not equal one test,” he says. “Many patients who may want to use this kind of screening are denied because of the cost of the method.”

Last summer, Wells, who works with another New Jersey-based fertility clinic, called Reprogenetics, announced the birth of the first child whose chromosome content had been checked using next-generation sequencing during IVF embryo selection (see “Baby Born After Genome Analyzed in IVF Test”).

Several companies already sell prenatal blood tests that detect abnormalities such as Down syndrome by using sequencing to count chromosomes in a mother’s blood, which contains DNA from both mother and baby (see “A Brave New World of Prenatal DNA Sequencing”). Researchers have also shown that it is possible to determine the genome sequence of a fetus using DNA gathered from the mother’s blood and the father’s saliva (see “Using Parents’ Blood to Decode the Genome of a Fetus”). Scientists can even read the genome of a human egg before it is fertilized (see “Single-Cell Genomics Could Improve IVF Screening”).

Both New Jersey clinics are testing whether using DNA sequencing to count embryo chromosomes does indeed improve the success of IVF. The trial by Reproductive Medicine Associates will transfer two embryos into each participating mother, whereas the Reprogenetics trial will transfer just one.

In addition to asking whether screening for abnormal chromosome numbers can improve IVF conception rates, Reproductive Medicine Associates is also testing whether sequencing can successfully screen for genetic diseases known to affect a family, says Scott. For instance, if both parents carry a copy of the mutation responsible for cystic fibrosis, they have a one in four chance of passing the disease on to their child. Embryos could be analyzed for the mutation so that only those without it would be transferred.

DNA sequencing also enables researchers to explore other potential causes of IVF failure beyond changes in chromosome numbers. Reprogenetics is testing whether an embryo’s particular mitochondrial genome, the discrete genetic sequence found in the energy-producing structures of cells, has an effect on the procedure’s success.

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