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Identifying viable embryos

Molecular techniques may one day help fertility doctors reduce the number of multiple births

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6:02pm, May 13, 2008
Magazine issue: Vol. 173 #18, June 7, 2008
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Australian researchers have taken fingerprinting children to the next level. A group at MonashUniversity in Melbourne is using DNA fingerprinting and other molecular techniques to identify viable embryos created during fertility procedures.

Such research could improve the chance a woman will get pregnant when only one embryo is transferred to the womb. Currently, many fertility clinics in the United States implant two or more embryos created during in vitro fertilization. That can result in pregnancies with multiple “test tube babies,” and pregnancies with multiples carry health risks for the mothers and for the babies.

Risks of multiple-birth pregnancies include premature birth, low birth weight, cerebral palsy and other disabilities, infant death and pregnancy complications.

“The goal is to have healthy children one at a time,” says David Ball, an embryologist at Seattle Reproductive Medicine.

But many people who have fertility problems are willing to have multiple embryos implanted in order to increase the chance of getting pregnant. “Patients look at it as they’re paying a lot of money and they want to be sure it works,” Ball says “They’d rather have two [babies] than none.”

Part of the problem is that doctors can not definitively distinguish which embryos will result in pregnancy and which will not, says Richard Paulson, reproductive medicine specialist at the Keck School of Medicine of the University of Southern California.

Fertility clinics examine embryos under a microscope and discard those that have obvious abnormalities, but several labs are moving toward molecular methods to identify the best embryo from the bunch. Paulson, who was not involved in the study, is testing the nutrient solution in which embryos are grown to see if healthy embryos make substances that distinguish them from unhealthy embryos.

In the new study, Gayle Jones and her colleagues at Monash and in Athens, Greece, extracted cells from embryos made during in vitro fertilization. The researchers found they could safely remove up to 20 cells from the outer layer of cells in a 5-day-old embryo.

After the team removed the cells, the embryos were transferred to their mothers’ uteruses. Some of the embryos developed into healthy babies. Others failed to implant in the womb or were not carried to full term.

DNA fingerprints of cheek swabs or umbilical cord blood from the full-term babies were matched to DNA fingerprints from the embryos to determine which embryos were viable.

Fingerprinting is an advantage of the new study’s strategy because it provides direct feedback about which embryos produce healthy babies, Paulson says.

The researchers then examined molecular signatures of the viable and nonviable embryos. Viable embryos turned on genes that encode cell adhesion molecules and cell communication proteins, the researchers report online May 13 in an advance publication of Human Reproduction. Both types of molecules are likely to be important for the embryo to latch on to the uterine wall and grow.

Right now, the technique is still experimental and Jones and her colleagues aren’t saying which genes are important for viability.

“It’s not for any intellectual property reasons,” Jones says. “It’s just that we have no confidence that we’ve found a predictive set of genes yet.”

If the scientists can whittle the possible candidate genes down to a manageable number, fertility clinics could do viability tests to find optimal embryos to transfer.

“We will be able to give clinics and patients confidence to accept single embryo transfers without affecting the pregnancy rate,” Jones says.

Ball calls the approach “promising,” but says it may take time before clinics can justify the cost and risk of performing such technologically challenging tests.

“None of these procedures are easy to do. It takes a level of expertise in the clinic and requires expensive equipment,” Ball says. But, “the theory of it is very appealing.”

The technique is invasive, requiring removal of cells from the embryo, which could damage the chance of implantation, Paulson says. But current technologies provide no noninvasive way to asses an embryo’s genetic makeup.

“I don’t think this is ready for prime time, but I do think it’s a very powerful research tool,” Paulson says. He predicts that within five to 10 years fertility clinics will be able to use such sophisticated techniques and be able to find the very best embryo to transfer.

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