Human Gametes and Preimplantation Embryos by David K. Gardner Denny Sakkas Emre Seli & Dagan Wells

Author:David K. Gardner, Denny Sakkas, Emre Seli & Dagan Wells
Language: eng
Format: epub
Publisher: Springer New York, New York, NY

Clinical Application of ArrayCGH to Detect Aneuploidy in Embryos

The first report of the successful clinical application of arrayCGH in the context of PGS was by Hellani et al. [39], who used a 60mer oligo-array produced by Agilent Technologies to detect the aneuploidy in blastomeres from >8-cell embryos from 8 patients who had been unsuccessful in previous IVF cycles. A cautious approach was taken and two cells were tested from each embryo. Approximately 60 % of embryos had a chromosomal error but despite this, 6 of the patients had at least one euploid embryo for transfer and 5 of these had a positive pregnancy test [39].

In the past 5 years there have been numerous abstracts and conference presentations describing the clinical application of microarray technology to PGS of embryos suggesting positive outcomes. These have predominantly focussed on patients with an apparent indication, including couples where the woman is of advanced age, or those who have experienced multiple implantation failures or recurrent miscarriage. To date, very few of these studies have appeared in the peer-reviewed scientific literature.

Only rarely has PGS been offered to patients who have no apparent increased risk of aneuploidy in their embryos. However, recent research carried out by Yang et al. [40], investigated whether PGS using arrayCGH could improve outcomes for young patients on their first cycle of IVF with the transfer of just a single embryo. The rationale for this was to promote single embryo transfer, reducing the incidence of multiple pregnancy and its associated risks, while maximising pregnancy rate. In this study, the first randomised controlled trial involving arrayCGH, blastocysts were biopsied on day-5 and the trophectoderm sample obtained was subjected to arrayCGH using the BlueGnome 24sure system. Single, euploid blastocysts were transferred on day-6 and the outcomes compared to a control group of patients whose best embryo was selected on day-6 on the basis of morphology alone. This demonstrated a significantly higher clinical pregnancy rate and ongoing pregnancy rate [40]. The improvement in outcomes is consistent with recent studies using mCGH and arrayCGH that have indicated that even good quality blastocysts from young IVF patients are often aneuploid [41, 42].

Further studies need to be done, but based on the results of Yang and colleagues it is tempting to suggest that the application of PGS with 24-chromosome screening should be broadened to include all patients who have sufficient, good quality embryos. Indeed, it may be that ‘good prognosis’ patients will benefit from this technology more than the groups of patient traditionally offered PGS, at least in terms of enhanced pregnancy rate. In theory, the use of an embryo selection technique that reveals non-viable embryos would improve the success rates achieved in single embryo transfer cycles, providing more singleton pregnancies and leading to a significant reduction in the number of cryopreserved embryos. This would provide an economic benefit to clinics as well as patients. Additionally, it should reduce the time to pregnancy for many patients as they would not be undergoing repeated transfers of thawed embryos which were affected with an aneuploidy that made them non-viable.

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