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Objective: To characterize chromosomal error types and parental origin of aneuploidy in cleavage-stage embryos using an informatics-based technique that enables the elucidation of aneuploidy-causing mechanisms., Design: Analysis of blastomeres biopsied from cleavage-stage embryos for preimplantation genetic screening during IVF., Setting: Laboratory., Patient(s): Couples undergoing IVF treatment., Intervention(s): Two hundred seventy-four blastomeres were subjected to array-based genotyping and informatics-based techniques to characterize chromosomal error types and parental origin of aneuploidy across all 24 chromosomes., Main Outcome Measure(s): Chromosomal error types (monosomy vs. trisomy; mitotic vs. meiotic) and parental origin (maternal vs. paternal)., Result(s): The rate of maternal meiotic trisomy rose significantly with age, whereas other types of trisomy showed no correlation with age. Trisomies were mostly maternal in origin, whereas paternal and maternal monosomies were roughly equal in frequency. No examples of paternal meiotic trisomy were observed. Segmental error rates were found to be independent of maternal age., Conclusion(s): All types of aneuploidy that rose with increasing maternal age can be attributed to disjunction errors during meiosis of the oocyte. Chromosome gains were predominantly maternal in origin and occurred during meiosis, whereas chromosome losses were not biased in terms of parental origin of the chromosome. The ability to determine the parental origin for each chromosome, as well as being able to detect whether multiple homologs from a single parent were present, allowed greater insights into the origin of aneuploidy., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Preimplantation genetic screening (PGS) has been used in an attempt to determine embryonic aneuploidy. Techniques that use new molecular methods to determine the karyotype of an embryo are expanding the scope of PGS.Methods: We introduce a new method for PGS, termed 'parental support', which leverages microarray measurements from parental DNA to 'clean' single-cell microarray measurements on embryonic cells and explicitly computes confidence in each copy number call. The method distinguishes mitotic and meiotic copy errors and determines parental source of aneuploidy.Results: Validation with 459 single cells of known karyotype indicated that per-cell false-positive and false-negative rates are roughly equivalent to the 'gold standard' metaphase karyotype. The majority of the cells were run in parallel with a clinical commercial PGS service. Computed confidences were conservative and roughly concordant with accuracy. To examine ploidy in human embryos, the method was then applied to 26 disaggregated, cryopreserved, cleavage-stage embryos for a total of 134 single blastomeres. Only 23.1% of the embryos were euploid, though 46.2% of embryos were mosaic euploid. Mosaicism affected 57.7% of the embryos. Counts of mitotic and meiotic errors were roughly equivalent. Maternal meiotic trisomy predominated over paternal trisomy, and maternal meiotic trisomies were negatively predictive of mosaic euploid embryos.Conclusions: We have performed a major preclinical validation of a new method for PGS and found that the technology performs approximately as well as a metaphase karyotype. We also directly measured the mechanism of aneuploidy in cleavage-stage human embryos and found high rates and distinct patterns of mitotic and meiotic aneuploidy. [ABSTRACT FROM AUTHOR]