Preimplantation genetic diagnosis (PGD) for inherited disorders using single nucleotide polymorphism (SNP) arrays: clinical outcomes from 300 cycles

Abstract

from a second biopsy for each embryo. Phase 2 involved clinical utilization of combined SGD and CCS testing with follow-up.RESULTS: Workup time approximated 1 month for each case. Phase 1 testing examined 152 embryos and demonstrated 99% concordance with reference lab data with all discrepancies confirmed as an error with the reference labs results. Phase 2 involved clinical application of these methods in 43 patients (304 embryos). A definitive result was reported for 99.7% (303/304) embryos, with 0.3% (1/304) having an inconclusive result likely due to recombination. All cases for which a sample was available in a newborn child confirmed the PGD result. In patients receiving a transfer with follow-up, clinical outcomes were excellent with an implantation rate of 75% (12/16), with 92% of patients achieving pregnancy.CONCLUSIONS: This methodology has demonstrated excellent concordance with current methods of SGD and provides a unique opportunity to avoid pitfalls of WGA when targeting additional loci in the genome in parallel with CCS. Additional advantages of the method include the ability to manage microdeletion and duplication cases and the potential for a 4 hour turnaround time. In addition, it is well established that SNP markers are denser than STRs thus generally reducing the distance of markers from mutations and the potential impact of recombination.