On 4 September 2015 Triin Laisk-Podar will defend her doctoral thesis titled „Genetic variation as a modulator of susceptibility to female infertility and a source for potential biomarkers“ in the Faculty of Medicine in the University of Tartu.
Professor Andres Salumets, University of Tartu
Associate Professor Marina Aunapuu, University of Tartu
Senior Research Fellow Maire Peters, University of Tartu
Professor Cornelis B. Lambalk, MD, PhD (VU University Medical Centre (Netherlands)
A wise man once said that the reproduction of mankind is a great marvel and mystery, and he was absolutely right, considering how many couples actually tackle with infertility. In Estonia, the majority of female infertility cases are due to tubal infertility (TFI) that is mostly caused by sexually transmitted infections, and polycystic ovary syndrome (PCOS), which is an endocrine disorder characterised by androgen excess and insulin resistance. In vitro fertilisation can help achieve pregnancy in these cases, but unfortunately the pregnancy rate per treatment cycle is only 30% and depends greatly on how the ovaries respond to the treatment. Over the years, great effort has been directed towards elucidating the molecular mechanisms behind the conditions causing infertility and it has been concluded that individual genetic variation is definitely one of the factors to blame. The studies of individual genetic variation form a good basis for finding biomarkers to predict natural reproductive function and perhaps even infertility treatment success. The general objective of the current thesis was to assess the associations between PCOS, TFI and selected candidate genes. In addition, several genetic variants that could be related to ovarian function and infertility treatment parameters were evaluated. Thus, DNA samples were collected from healthy women and infertile women and 47 genetic variants were studied in association with diagnoses of interest and different clinical parameters. In addition, to determine how many TFI cases are caused by a chlamydia infection, the prevalence of chlamydia-specific antibodies was measured in the blood sera of women with TFI. As a result, we found that ~50% of all TFI cases in Estonia might be caused by a previous chlamydia infection and identified genetic variants in the mannose binding lectin gene that modulate immune response and may be associated with susceptibility to TFI. No associations were found between selected variants in genes for insulin and androgen receptor and PCOS. However, we showed that genetic variants related to menopause timing are associated with ovarian function and infertility treatment parameters and could be considered as biomarker candidates if combined with clinical data. In conclusion, this study gave new knowledge about the genetics of female reproduction, but also highlighted the need for further research.