The Use of Arrays in Preimplantation Genetic Diagnosis and Screening

Background: In preimplantation genetic diagnosis (PGD), polymerase chain reaction has been used to detect monogenic disorders, and in PGD/preimplantation genetic screening (PGS), fluorescence in situ hybridization (FISH) has been used to analyze chromosomes. Ten randomized controlled trials (RCTs) using FISH-based PGS on cleavage-stage embryos and one on blastocyst-stage embryos have shown that PGS does not increase delivery rates. Is the failure of PGS due to a fundamental flaw in the idea, or are the techniques that are being used unable to overcome their own, inherent flaws? Array-based technology allows for analysis of all of the chromosomes. Two types of arrays are being developed for use in PGD; array comparative genomic hybridization (aCGH) and single nucleotide polymorphism-based (SNP) arrays. Each array can determine the number of chromosomes, however, SNP-based arrays can also be used to haplotype the sample.

Objective(s): To describe aCGH and SNP array technology and make suggestions for the future use of arrays in PGD and PGS.

Conclusion(s): If array-based testing is going to prove useful, three steps need to be taken: [1] Validation of the array platform on appropriate cell and tissue samples to allow for reliable testing, even at the single-cell level; [2] deciding which embryo stage is the best for biopsy: polar body, cleavage, or blastocyst stage; [3] performing RCTs to show improvement in delivery rates. If RCTs are able to show that array-based testing at the optimal stage for embryo biopsy increases delivery rates, this will be a major step forward for assisted reproductive technology patients around the world.