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From Medicineworld.org: Genetic Testing Still Smart Choice

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Genetic Testing Still Smart Choice


Genetic Testing Still Smart Choice
Screening embryos for genetic diseases during in vitro fertilization offers couples the best chance for a healthy child, but a genetic glitch could potentially cause doctors to misdiagnose a small fraction of them, University of Florida scientists say.

Citing concerns about the accuracy of preimplantation genetic diagnosis, the method a number of practitioners use to pick the healthiest embryos during IVF, UF scientists set out to study the procedure. Their work, described during a recent meeting of the American Society of Reproductive Medicine, reveals the technique is actually highly reliable. But because there is a slim chance a genetic abnormality can cause doctors to misdiagnose embryos, some concerns still need to be addressed, the scientists said.

Preimplantation genetic diagnosis has been used for more than a decade to screen embryos for hereditary diseases such as Down syndrome and other abnormalities. To do this, one cell from an eight-cell embryo is extracted and examined for chromosomal defects.

However, as a number of as half these embryos spawn cells with different genetic information as they divide, giving doctors an inaccurate idea of how the embryo will continue to develop, said Larissa Kovalinskaia, a UF research associate with the College of Medicine's IVF program. While a number of embryos with this abnormality - called chromosomal mosaicism - stop developing early, some go on to be born. Because these embryos' cells contain different sets of chromosomes, doctors cannot always accurately screen them for genetic diseases, Kovalinskaia said.

"As more data were coming out, saying that as a number of as 50 percent of (IVF) embryos were mosaic, we started worrying about the accuracy of preimplantation genetic diagnosis," she said. "When you take one cell, does it represent the entire embryo? What we've shown is that we can rely on PGD".

UF scientists estimate less than 3 percent of healthy embryos are discarded as abnormal and only 1.5 percent are implanted with undetected genetic defects because of mosaicism.

To find out how big of a problem mosaicism is, the scientists developed a mathematical model using data from UF's IVF program and other programs to illustrate the different paths an embryo takes as it develops. While half of embryos turn out normal, with no mosaicism, the other half produce irregular cells as they divide.

Embryos that become mosaic after their cells divide twice typically stop progressing by the time they have accumulated eight cells. Too a number of of their cells have chromosomes that don't match and these mixed messages lead the embryo to stop developing, Kovalinskaia said.

Embryos with only one or two irregular cells still have a chance to develop normally though, she said. These embryos tend to not develop this abnormality until after their cells have divided a third time, typically the time when doctors perform preimplantation genetic diagnosis. This is where the problem with diagnosis occurs, scientists say.

"Our pathway concept may help to explain the observed outcomes during preimplantation diagnosis," said Kenneth Drury, director of the UF IVF and Andrology Laboratory and a clinical professor in the College of Medicine who was one of the researchers. "When we biopsy an eight-cell embryo, if we choose (the one) normal cell in an abnormal embryo, we may believe that embryo is normal and transfer it.

"This occurs about 1 percent of the time, which means 99 percent of the time we will be accurate. Again the error is not due to a technical mistake but to natural errors occurring during early cell division in the embryo".

Extracting test cells before the embryo divides a third time could reduce the number of misdiagnoses because of mosaicism, the UF scientists suggest. Improving culture conditions could help too, Kovalinskaia said.

But the small margin of error shouldn't stop couples from having preimplantation genetic diagnosis, said Dr. Jamie Grifo, a professor of obstetrics and gynecology at New York University. The testing can work miracles for women prone to miscarriages or who carry genetic diseases, he said.

"If you are at risk for genetic diseases, it changes your outlook on starting a family," he said. "PGD allows them to get pregnant. It's a dramatic improvement when it works".

More than 45,000 babies are born each year with the aid of assisted reproductive technologies like IVF, according to the Centers for Disease Control and Prevention. The use of IVF has declined in recent years, but Grifo said that is largely because baby boomers are leaving their childbearing years. Technologies like preimplantation genetic diagnosis have helped too, making IVF more accurate, he said.

"There has been a lot of progress," Grifo said. "It's helped a number of patients".


Source: University of Florida


Did you know?
Screening embryos for genetic diseases during in vitro fertilization offers couples the best chance for a healthy child, but a genetic glitch could potentially cause doctors to misdiagnose a small fraction of them, University of Florida scientists say. Citing concerns about the accuracy of preimplantation genetic diagnosis, the method a number of practitioners use to pick the healthiest embryos during IVF, UF scientists set out to study the procedure. Their work, described during a recent meeting of the American Society of Reproductive Medicine, reveals the technique is actually highly reliable. But because there is a slim chance a genetic abnormality can cause doctors to misdiagnose embryos, some concerns still need to be addressed, the scientists said.

Medicineworld.org: Genetic Testing Still Smart Choice

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