NMR-based profiling of ovarian follicular fluid and plasma

Success rates of in vitro fertilisation (lVF) are unsatisfactory and consequently, multiple embryo transfers are performed despite the risk of multiple pregnancies. A major goal in assisted conception is to perform elective single embryo transfer (eSET) without compromising a patient's chances of pregnancy. In order to achieve this goal, methods are required for identifying oocytes with the greatest potential Follicular fluid (FF), the fluid which surrounds an oocyte during its development in the ovary, may be a suitable medium in which to test for biomarkers of oocyte quality. Nuclear magnetic resonance (NMR)-based metabolomics is ideal for the global analysis of biological samples to identify trends and biomarkers in groups of individuals, but yet is still in its infancy in the field of female fertility. With this in mind, the aim of this work was to use these techniques to achieve a greater understanding of several aspects of infertility, with the ultimate goal of aiding eSET and success rates in IVF. FF and blood plasma from NF patients were analysed for biomarkers of oocyte quality; patients who had clinical pregnancies could be identified by high rates of anaerobic glycolysis and oocyte energy sources. Supervised analysis revealed that plasma may be predictive of FF composition, offering an alternative test medium which can be collected far less invasively than FF. The change in composition of FF and plasma during three phases of the menstrual cycle was investigated, aiding understanding of the changing environment of the oocyte during its development. This study also revealed the metabolic effects of the IVF-drug, human chorionic gonadotrophin (hCG). FF composition was also investigated for changes with the degree of vascularisation to the oocyte; lH-NMR- based metabolomics did not identify any difference in FF composition with vascularity, but 31P-NMR identified • that lower levels of phospholipids were associated with poorer vascularisation. Finally, serum samples from NF patients with three reproductive diseases implicated in fertility were compared to each other and to those of IVF patients without any diseases. No differences were found, suggesting that the NF drug regime may counteract any metabolic effects of these diseases. The studies performed here were on small-scales; however, some very interesting preliminary results have been produced and the potential of NMR-based metabolomics in the field of human female infertility has been demonstrated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo