Mamas, T; (2013) Investigation of aneuploidy in preimplantation embryos. Doctoral thesis , UCL (University College London).

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Abstract

Aneuploidy is common in human preimplantation embryos. This thesis examines aneuploidy detection using an array platform, aneuploidy in embryos from fertile couples and recombination in gametes through the detection of cross-over events in embryos. The first aim of this project was the optimisation of array comparative genomic hybridisation (aCGH) to examine all chromosomes in single blastomeres and trophectoderm samples from embryos, prior to clinical implementation. Accurate detection of errors was possible on single cells from epithelial cell lines of known chromosomal status. The same cell lines were used to mimic mosaic trophectoderm samples to examine the effect of mosaicism on aCGH. Aneuploidy could be confidently detected when more than 50% of the cells in the sample were abnormal. Aneuploidy studies have been mainly performed on embryos, from couples undergoing preimplantation genetic screening (PGS), which are expected to be highly abnormal. The second aim was to determine the aneuploidy level in embryos from couples undergoing preimplantation genetic diagnosis (PGD) for monogenic disorders. Fluorescence in situ hybridisation (FISH) was used to examine five chromosomes in 86 embryos from 19 couples and all chromosomes were examined in 53 embryos from six couples by aCGH. Diploid mosaic embryos were the most predominant group when FISH analysis was carried out, whereas the majority of embryos were euploid after aCGH. Post-zygotic rather than meiotic errors were more common in embryos from PGD cycles when compared to embryos from PGS cycles. Aneuploidy is known to associate with aberrant recombination. The third aim was to examine meiotic recombination. Polymorphic markers on five chromosomes were used to detect cross-over events in 77 embryos from 10 couples. Female recombination was higher than male. Increasing age had a negative effect on recombination. No significant effect of recombination on morphology and aneuploidy was observed, however euploid embryos had more recombination than aneuploid.

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