Sirvi Kuupäev , alustades "2010-01-08T05:57:20Z" järgi

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Genomics and transcriptomics of human induced ovarian folliculogenesis
(2010-01-08T05:57:20Z) Altmäe, Signe
Infertility is an increasing medical and social problem affecting more than 10% of couples of their fertile age. In Estonia, accordingly, more than 15 000 infertile couples could be suspected. In vitro fertilization (IVF) procedure is the most successful treatment for various causes of infertility. Regardless of constant improvement of pregnancy rate in IVF, the success rates are still around 30% per cycle. IVF procedure consists of three steps – the stimulation of the ovaries (called controlled ovarian hyperstimulation (COH)), fertilisation of the retrieved oocytes and culturing of embryos, and finally the embryo transfer. The expected outcome of the IVF treatment depends greatly on the effectiveness of COH, where follicle-stimulating horomone (FSH) is used to induce the (poly)folliculogenesis, as well as on the quality of oocytes. Sufficient number of mature oocytes is crucial for high pregnancy rates, compensating possible losses during follicular puncture, fertilization, embryo development and implantation, meanwhile hormone overdoses can lead to the life-threatening conditions known as ovarian hyper-stimulation syndrome (OHSS). The response to the FSH stimulation varies substantially among individuals and is difficult to predict. Several markers have been proposed, but the search for optimal markers that could predict COH outcome and also a good-quality oocyte, enabling thereby better IVF treatment outcome, is ongoing. In the current thesis we studied polymorphisms in genes involved in folliculogenesis – aromatase gene, estrogen receptor genes and genes involved in folate metabolism, and their influence on COH and IVF outcome in women undergoing IVF procedure. Also the importance of different polymorphisms in the etiology of female infertility was assessed. In addition, in order to add more understanding to the field of follicular biology in IVF treatment, gene expression profiles of mural granulosa cells and cumulus granulosa cells were analysed. The results of the current thesis demonstrate that the genetic variation in genes involved in folliculogenesis influences the stimulatory effect of FSH used in ovarian stimulation in IVF patients and are associated with etiology of female infertility. The knowledge of the individual’s genetic background would enable to predict the FSH doses needed for optimal ovarian stimulation in IVF treatment in order to avoid the poor response or hyper-response to the hormonal ovarian stimulation. Further, the data of the granulosa cell gene expression add information to the process of hormonal stimulation in IVF, which could be applied in improving IVF treatment protocols and embryo selection. These findings, together with previous studies have great importance for future development in infertility treatment, allowing to individualise the patient’s COH protocols and to make thereby IVF procedure safer and more effective.