Commentary
Embryo aneuploidy and the role of morphological and genetic screening

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Abstract

Chromosome abnormalities are common among human oocytes and are usually lethal to any embryos they produce. It therefore seems logical that a reliable technique for distinguishing between normal and aneuploid embryos would be a useful tool for physicians and embryologists, assisting the choice of which embryo(s) to prioritize for uterine transfer. This concept has led to the development of a variety of methods for the detection of chromosome abnormalities in oocytes and embryos, most often referred to as preimplantation genetic screening (PGS). However, several well-controlled studies have been unable to show an advantage of chromosome screening in terms of pregnancy and birth rates. Some investigators have suggested that damage to embryos, sustained during cleavage-stage biopsy, might explain why PGS has not always provided the anticipated benefits. This paper asks whether there is evidence that a non-invasive, morphological analysis could allow chromosomally normal embryos to be accurately identified and reviews data from the most recent publication concerning IVF outcome following PGS.

During an IVF cycle, it is typical for several embryos to be produced. However, not all of these embryos will have the same chance of producing a child. One of the main reasons for the variability in embryo potential is chromosome abnormality. This problem is common in embryos and causes them to fail to implant or miscarry. In order to maximize the success rates of IVF treatment, it is important to make sure that the embryos transferred to the uterus are chromosomally normal. This paper considers two possible methods for the identification of embryos with the correct number of chromosomes: morphological analysis (evaluation of the appearance of the embryo under the microscope) and preimplantation genetic screening (a method based upon testing of cells biopsied from the embryo). These alternative strategies are discussed with specific reference to the findings of another recent paper published in this journal.

Section snippets

Introduction: chromosome abnormalities, embryos and screening

Data from numerous studies using a wide variety of techniques have demonstrated beyond doubt that a high proportion of human oocytes are affected by chromosome abnormalities. The phenomenon is closely associated with female age. For a woman over 40 years old undergoing IVF treatment, it is typical for more than half of the oocytes retrieved to be chromosomally abnormal (Fragouli et al., 2006, Fragouli et al., 2010a, Kuliev et al., 2003, Pellestor et al., 2003, Sandalinas et al., 2002). Embryos

Biological perspectives

A number of previous studies have looked at the relationship between morphology and aneuploidy. Most investigations have confirmed that a link exists, but have found that correlations are weak and likely to be of little assistance in the selection of euploid embryos for transfer (Alfarawati et al., 2010, Eaton et al., 2009, Hardarson et al., 2003, Magli et al., 2007, Moayeri et al., 2008, Munné et al., 2007, Staessen and Van Steirteghem, 1998). To date, most studies have focused on embryos at

Clinical potential

Whatever the underlying biological cause, there does appear to be a link between aneuploidy and abnormal morphology at the cleavage and blastocyst stages. The clinical question is: can morphological analysis assist the identification of euploid embryos for uterine transfer? In the study by Finn et al., the probability of selecting a chromosomally normal embryo at random was 0.26. Whereas if transfer had been restricted to those embryos achieving the morphological appearance most closely

The efficacy of preimplantation genetic screening

As well as reporting morphological data, Finn and colleagues have also provided a summary of their experience using preimplantation genetic screening (PGS), assessing the copy number of nine chromosomes using FISH in order to assist the transfer of euploid embryos in poor-prognosis patients. Although many laboratories have now moved to comprehensive chromosome analysis methods (e.g. CGH, microarray-CGH and single-nucelotide polymorphism array), a better understanding of the potential benefits

Acknowledgements

Dagan Wells is funded by NIHR Biomedical Research Centre Programme.

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