Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.733276
Title: Preimplantation genetic screening during in vitro fertilization, clinical applications and insight into embryological development
Author: Taylor, Tyl
ISNI:       0000 0004 6497 2247
Awarding Body: University of Kent
Current Institution: University of Kent
Date of Award: 2017
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Abstract:
Aneuploidy (extra or missing individual chromosomes) is the leading cause of miscarriage, embryo wastage and in-vitro fertilization (IVF) failure. Aneuploidy increases with maternal age and is widespread in human preimplantation embryos. Thus, aneuploidy screening before implantation during an IVF cycle (preimplantation genetic screening or PGS), to increase pregnancy rates and decreasing miscarriage rates, is also widespread. Despite this, PGS faces challenges in terms of both biological and technical limitations that may impede its full potential. Biologically, the phenomenon of chromosomal mosaicism (the presence of two or more cell lines - typically, one aneuploid and one euploid) may lead to false positives or false negatives, and the discard or transfer of euploid or aneuploid embryos, respectively. Technically, it is uncertain whether diagnosis on the biopsied piece is representative of the remaining embryo. Because these dilemmas it is unknown if PGS will only benefit a few selected groups of patients or potentially the entire IVF patient population. In a series of published works, this thesis demonstrates a significant contribution to field of preimplantation genetics, provides insight into technical and biological limitations of PGS, and into the etiology of aneuploidy and mosaicism. Specifically, I introduce a novel technique to "map" chromosomal mosaicism, by reconstructing a virtual image of the blastocyst with the approximate location of individual cells and their corresponding chromosomal makeup. I also demonstrate the ability of PGS to be performed on blastocysts that were previously frozen; thus, blastocysts have to be thawed/warmed, biopsied, vitrified and rewarmed prior to use. From a clinical standpoint, I present evidence of the differences in PGS outcomes between day 5 and day 6 blastocysts: The data suggests that day 6 blastocysts are less likely to be euploid than day 5 blastocysts. Furthermore, day 6 euploid blastocysts exhibit similar pregnancy and implantation rates when compared to their day 5 counterparts. I also published on a study examining differences in PGS outcomes in those patients that are defined as "presumed fertile" as opposed to those that are "infertile". Another study examined pregnancy and implantation rates between two competing platforms, quantitative polymerase chain reaction (qPCR) and array comparative genomic hybridization (aCGH). I also examined the pregnancy rates of poor quality embryos on day 6 that would have been discarded. From a biological standpoint, I examined the mechanisms through which embryos diagnosed as aneuploid on day 3 could develop to a euploid blastocyst, demonstrating that euploid blastocysts can develop from aneuploid cleavage stage embryos. I also demonstrated differences in aneuploidy rates between polar, mural, and a piece defined as "mid" trophectoderm, and blastocysts diagnosed as aneuploid may not reflect the chromosomal constitution of the whole embryo proper. This work herein presented provides a deeper understanding of the technical limitations of PGS and into the etiology of the chromosomal basis of early human development.
Supervisor: Griffin, Darren ; Gitlin, Susan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.733276  DOI: Not available
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