New, less invasive genetic test greatly improves pregnancy rates in older women with poor prognosis

June 29, 2009

Amsterdam, The Netherlands: A new test examining chromosomes in human eggs a few hours after fertilisation can identify those that are capable of forming a healthy baby, a researcher told the 25th annual conference of the European Society of Human Reproduction and Embryology today (Monday 29 June). Dr. Elpida Fragouli, from the Department of Obstetrics and Gynaecology, University of Oxford, UK, and Reprogenetics UK, said that her team's work had already enabled seven ongoing pregnancies in a group of older women with a history of multiple failed IVF attempts.

"Out of 35 patients who had embryo transfers after the test, we achieved a pregnancy rate of 20%, which is exceptional considering the extremely poor prognosis of the women involved." she said. "This represents a doubling of the usual pregnancy rate for women who fall into this category, which is otherwise, at best, under 10% and, at worst, zero. To date, we have two live births from this group, and all the other women who became pregnant have maintained their pregnancies. The study is continuing, and we believe that we will achieve more pregnancies with the help of this technology in the future."

The scientists used the Comparative Genomic Hybridisation (CGH) technique to count the chromosomes in each egg. Unlike conventional screening strategies, using the fluorescent in situ hybridisation (FISH) method, which allows less than half of the chromosomes of an embryonic cell to be examined, CGH enables the evaluation of the entire chromosome complement. CGH was used to examine the fertilised eggs by looking at polar bodies, tiny cells that are a by-product of egg development. The chromosomes of polar bodies provide an indication of whether the corresponding egg is normal or abnormal; if the polar bodies have the wrong number of chromosomes, so does the egg.

Looking at polar bodies is a less invasive way of obtaining information about the chromosome content of an egg and its resulting embryo than other alternatives, such as day-three biopsy, which take place during conventional screening strategies involving the use of the FISH technique. The removal of the polar bodies does not adversely affect the subsequent development of the embryo. Additionally, the results obtained after CGH analysis of polar bodies are not affected by the presence of chromosomal mosaicism (the presence of two populations of cells with different genotypes) and therefore may be more accurate than conventional methods based upon screening of cells removed from embryos.

The scientists examined 400 fertilised eggs generated by women with a very poor reproductive history and with an average age of 42 who were undergoing IVF because of being unable to conceive or to maintain a pregnancy. They found that more than half of all the eggs produced by these women had chromosomal abnormalities, and therefore the resulting embryos were also chromosomally abnormal. Some of the women had a tendency to produce eggs that were extremely abnormal and carried multiple chromosome errors. This could explain the poor reproductive history of these women, the scientists say.

"But where we could find fertilised eggs free of chromosomal abnormalities, the resulting embryos were also normal and their transfer to the mother led to pregnancies," said Dr. Fragouli. "Results suggest that the use of this technique will improve IVF success rates for poor prognosis patients. It is also likely to achieve a reduction in congenital abnormalities such as Down's syndrome, as well as a reduction in the frequency of spontaneous miscarriage."

The incidence of chromosomal abnormalities in human eggs is closely related to maternal age, and can affect more than 60% of all eggs in women over 40 years of age. Being able to select the right egg can not only lead to more successful IVF, but also enhance the use of single embryo transfer, especially in countries where embryo testing is forbidden and only eggs can be tested. "Being able to examine the first polar body means that this test can be used in countries where embryo testing is forbidden by law," said Dr. Fragouli.

"We are close to applying technical innovations which will make this test even better, faster, and cheaper. We are also going to be using the test in cases where fertility preservation is required, due to cancer, for example," she said.
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European Society of Human Reproduction and Embryology

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