CGH technique for embryo screening in IVF

14 November 2008

The low success rate of in vitro fertilisation (IVF) – just over 28% for women under 35 and lower for older women in the UK (see HFEA figures) – is partly attributable to the failure of aneuploid embryos (those with an abnormal number of chromosomes) to implant properly. Most such embryos would be non-viable in any case, and even the least severe forms of aneuploidy have significant clinical effects; for example, Down Syndrome, Edwards Syndrome and Patau Syndrome. In order to increase the chances of establishing a successful pregnancy, pre-implantation genetic screening (PGS) can be used to identify and select chromosomally normal embryos for implantation. This is currently done using fluorescent in situ hybridisation (FISH); however, this technique is only applied to find aneuploidies in up to eight specific chromosomes that are known to malfunction most frequently. In addition, the benefits of using this method for PGS have not been clearly established. The British Fertility Society in its recent guidelines recommended that PGS (using FISH) only be offered within the context of randomised trials, until further evidence of its effectiveness is gathered (see previous news).

An alternative technique for PGS is the use of comparative genomic hybridisation (CGH) (see previous news). CGH allows regions on every chromosome to be analysed for aneuploidies compared with current techniques, which are restricted to specific chromosomal defects. A number of studies have indicated that this technique may increase the success rate of IVF and the results of the first clinical study of this technique were presented at the annual meeting of the American Society of Reproductive Medicine. The study carried out by scientists at the University of Oxford and the Colorado Centre for Reproductive Medicine in the US has shown that CGH may be a better approach for pre-implantation genetic screening (reported by BBC news). The clinical trials were undertaken on 23 women with an average age of 37, in order to assess the effectiveness of CGH; chromosome screens were obtained for 91% of embryos tested and 70% percent of the cycles that went to embryo transfer resulted in clinical pregnancy (see press release). The results of this study suggest that the rate of implantation following CGH is dramatically greater than that achieved using other screening methods (BBC news). Dr. Dagan Wells from the University of Oxford is currently applying for a licence for its use in the UK. Although work on CGH has been on-going for a number of years, it has not been widely adopted as it is requires expertise, is labour intensive and takes several days. However, technological advances are making it a more amenable method of screening and if conjugated with microarray platforms (referred to as array CGH) it can allow high-throughput processing of multiple samples simultaneously.

Techniques for pre-implantation genetic diagnosis (PGD) or pre-implantation haplotyping (see previous news) are used for the diagnosis of mutations that cause specific serious genetic disorders. In contrast, techniques such as array CGH and karyomapping (see previous news) are applied to the whole genome and can be used to identify multiple genetic abnormalities as well as specific mutations. The advantage of these techniques is that they allow more thorough screening in order to identify chromosomally normal embryos thereby increases the chances of a healthy pregnancy - one of the purposes of IVF. However, the clinical significance of some mutations or chromosomal changes (i.e. deletions/duplications) identified by these techniques is not yet known nor is their influence on the successful establishment of a healthy pregnancy. Consequently, these techniques raise a number of ethical issues; a European ethics task force is already assessing the use of microarrays in PGS in order to develop a code of practice and regulate their use (see previous news).

 

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