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Title: The effect of maternal overweight and obesity on the viability and metabolism of human oocytes and early embryos
Author: Leary, Christine
ISNI:       0000 0004 5370 6816
Awarding Body: University of Hull and University of York
Current Institution: University of Hull
Date of Award: 2015
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Overweight and obese (OWOB) women are reported to have a lower chance of becoming pregnant. The nutritional enrichment of the periconceptional environment apparent in obese women may be detrimental for embryo viability. This is the first study to examine the development and metabolism of embryos derived from OWOB women compared with those from normal weight women. Measurements of oocyte quality, embryo development and utilisation of exogenous and endogenous metabolites were performed. Results were compared for normal weight and OWOB and examined in relation to blastocyst development and pregnancy outcome. Patients attending the Hull IVF Unit for fertility treatment (n=176) donated supernumerary embryos (n=808) from day 5 to 7/9 of development. Full ethical approval was obtained. Oocytes from overweight or obese women were smaller than those from women of healthy weight, yet post-fertilization they reached the morula stage faster and, as blastocysts, showed reduced glucose consumption and elevated endogenous triglyceride levels. There were no differences in the metabolism of pyruvate or lactate. Amino acid metabolism was more active in embryos generated from OWOB women and significant differences were seen in the turnover of individual amino acids that were also predictive of blastocyst formation and pregnancy outcome. The significant findings were independent of male BMI. In vitro culture supplementation with insulin did not influence glucose consumption, but did appear to modulate developmental progression to the blastocyst stage as well as the utilisation of specific amino acids. Whereas, when the medium was supplemented with l-carnitine (LC), embryos consumed LC from the medium, and at 0.05mM LC addition; embryos showed reduced intracellular triglyceride levels and increased exogenous glucose consumption. However, at 0.5mM LC addition; embryo viability was compromised in cohorts of embryos from women with a BMI <25kg/m². The data support the hypothesis that embryo viability is compromised in OWOB women. This may reduce not only the chances of conception, but have long-term implications for the health of the offspring in later life.
Supervisor: Sturmey, Roger ; Leese, Henry J. ; Killick, Stephen ; Lesny, Piotr Sponsor: Hull IVF Charitable Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine