Supervisors: prof Raivo Uibo (TÜ biomeditsiini instituut), prof Andres Salumets (TÜ biomeditsiini instituut) ja prof Ülle Jaakma (EMÜ).
Opponent: professor Herbert Hooijkaas (Erasmuse Meditsiinikeskus, Rotterdami Erasmuse Ülikool, Holland)
Infertility has become a global medical and social problem affecting approximately 9% of reproductive-aged couples worldwide. Today, in vitro fertilization (IVF) has become the most successful treatment option for infertile couples with various causes. Despite improvements in fertilization and pregnancy rates, the overall success rate for IVF has remained low. The outcome of IVF procedure is highly dependent on the successfulness of controlled ovarian stimulation, wherefore more effective and optimal biomarkers are sought for better prognosis. Additionally, an underlying mechanism for IVF failure can be immune activation, including an increased production of autoantibodies and alterations in cytokine levels. In this doctoral thesis the presence and significance of humoral immune system activation in serum and follicular fluid of female IVF patients was evaluated in relation to infertility etiology and IVF treatment results. In the first part of the thesis the prevalence of common and infertility related autoantibodies in the blood serum was assessed. Results of the study showed that infertile women with various diagnoses presented with elevated levels of autoantibody reactivity towards several organ-specific and organ-non-specific autoantigens. Furthermore, some of the antibodies associated with cause of infertility or unsuccessful IVF treatment outcome. In the second part of the thesis various follicular fluid biomarkers were measured. We demonstrated that either reduced or elevated levels of certain proinflammatory cytokines, chemokines and apoptosis regulators in the follicular fluid were associated with cause of infertility and correlated with IVF treatment parameters. In conclusion, these results provide further proof that impairment of the immune system is characteristic to infertile women undergoing IVF treatment and that immune system alterations may be involved in the infertility pathogenesis of these patients.