New techniques designed to identify healthy embryos
Nov 12, 2008 - 4:43:59 AM
At the 64th Annual Meeting of the American Society for Reproductive Medicine in San Francisco, researchers today shared new techniques designed to identify healthy embryos while sparing them excessive stress.
As women age, their eggs are more vulnerable to mistakes that can occur in the copying, dividing, and organization of their chromosomes. Although some clinics advise women of advanced maternal age having assisted reproductive technology treatment to have pre-implantation genetic screening (PGS) of their embryos to ensure that only embryos without chromosomal errors are transferred, the ASRM Practice Committee has concluded that the evidence does not support the use of PGS to increase pregnancy rates in women of advanced age. Aneuploidy exists in eggs and embryos of young women as well as older women, and it has been established that embryos containing both normal and aneuploid cells can correct themselves and result in normal live births.
Elpida Fragouli, PhD and her colleagues found that a comprehensive genetic analysis of eggs, done by analyzing the chromosomes they discard in polar bodies, can detect almost twice as many maternally-derived abnormalities as routine PGS done on blastomeres. This approach reduces the risk of injury to embryos. Fifty women, averaging 40-plus years of age, had 293 fertilized eggs chromosomally analyzed via the first and second polar bodies. These zygotes were then frozen for future transfer pending the outcome of their testing. Chromosome errors were found in 43% of first polar bodies and in 40% of second. The technique revealed that these errors could affect any chromosome in the human egg.
Another technique, developed by Dagan Wells, PhD and his team, uses analysis of trophectoderm cells – cells from the outer part of a blastocyct destined to develop into the placenta – to maximize the amount of chromosomal information obtained on an embryo, while minimizing the risk it is exposed to. By using trophectoderm cells, the researchers were able to take several cells from each embryo reducing the risk of misdiagnosis. Cells from 106 blastocysts belonging to 17 patients, averaging 37 years old with histories of failed IVF attempts and miscarriages were examined and full chromosome screens were obtained for 91% of the blastocysts. Although 44% of the embryos were chromosomally abnormal, all of the embryos survived biopsy. Seventy percent of the cycles that went to embryo transfer resulted in clinical pregnancy.
Mandy Katz-Jaffe, PhD and her group are working on a way to use measurements of the gene expression of cumulous cells- protective cells that surround the egg – to gauge the egg’s chromosomal competence. In their experiment, cumulous cells were collected from the eggs of patients undergoing IVF. Chromosomes from the eggs’ first and second polar bodies were analyzed to obtain a comprehensive aneuploidy screen of each egg. Six eggs in the study were found to be normal and six were identified as aneuploid. Then RNA from cumulous cells belonging to each of the 12 eggs was isolated and analyzed to see which genes were active in the cumulous cells. Two new gene sets associated with aneuploid eggs were identified.
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