Skip to main content

Preimplantation genetic screening during in vitro fertilization, clinical applications and insight into embryological development

Taylor, Tyl (2017) Preimplantation genetic screening during in vitro fertilization, clinical applications and insight into embryological development. Doctor of Philosophy (PhD) thesis, University of Kent, none. (KAR id:65094)

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 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.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Griffin, Darren K.
Thesis advisor: Gitlin, Susan
Uncontrolled keywords: aneuploidy, IVF, blastocyst, mosaicism, blastocyst biopsy, embryos
Divisions: Faculties > Sciences > School of Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 07 Dec 2017 15:10 UTC
Last Modified: 23 Jan 2020 04:14 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/65094 (The current URI for this page, for reference purposes)
  • Depositors only (login required):

Downloads

Downloads per month over past year