Ever since the late 1970s, when in vitro fertilization first made the dream of childbirth come true for some previously infertile couples, doctors have tried to improve the technique’s efficiency. Still, only 20 to 30 percent of would-be parents undergoing in vitro fertilization (IVF) start a successful pregnancy during a single attempt. The procedure costs an average of $10,000 in the United States and puts couples on an emotional roller-coaster.
Using a new technique to examine chromosomes of IVF embryos at the time they’re implanted in the womb, researchers now report abnormalities never seen later in development.
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Some of the newly observed flaws might explain why IVF has been so hit-or-miss. The technique may also boost IVF’s success rate, some researchers say.
Most embryos start out with a bad deck of chromosomes, scientists report in the November Molecular Human Reproduction. Dagan Wells and Joy D.A. Delhanty of the University College London Medical School applied their technique to four-to-eight-cell embryos donated by couples undergoing IVF treatment. The researchers found that only 3 of the 12 embryos they inspected had the normal 23 pairs of chromosomes in every cell examined. The other embryos had extra or missing chromosomes.
What’s more, six of the embryos had a mixture of normal and abnormal cells, a phenomenon called mosaicism. “The question is whether any embryos with a mixture of normal and abnormal cells can survive,” Wells says.
“It has been a mystery why about two-thirds of early embryos fail to implant and develop,” says geneticist Lucille Voullaire of Royal Children’s Hospital in Melbourne, Australia. “These data help solve this riddle by confirming that many embryos already have major chromosome abnormalities as early as the eight-cell stage.”
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In the February Human Genetics, a team led by Voullaire published similar conclusions after examining 19 chromosome pairs per cell.
Using a modified version of the polymerase chain reaction technique, Wells and Delhanty made about 100,000 copies of the embryonic DNA. Then, they applied a tool called comparative genomic hybridization to visualize all 23 chromosome pairs at once. By contrast, the analytical tool used in IVF clinics spotlights 5 to 9 pairs.
Today’s IVF specialists primarily use visual inspection to choose which embryos to implant. Yet Wells and Delhanty report that some embryos that look healthy when viewed through a microscope have severe chromosome abnormalities and would have little chance of producing a viable pregnancy.
The British team believes its technique could help IVF specialists, who can analyze only one cell per embryo, better judge which embryos to implant.
Voullaire agrees. “If a single . . . cell from an eight-cell embryo tests normal, the chance the embryo will develop successfully should be increased,” she says.
Not everyone is so optimistic. The amount of mosaicism Wells and Delhanty observe indicates that one cell may give little insight into the health of the others. “If [mosaicism] turns out to be very common, then screening embryos by [the new] technique would not increase implantation rates or reduce miscarriage rates,” says James A. Grifo, director of reproductive endocrinology at New York University Medical Center.
Wells concedes that only the most sophisticated clinics would have the know-how to use the technique.
“It’s an incredible technical feat,” seconds Grifo. He cautions that the method “requires highly trained individuals and hours of work through the night.”