Immune activation in female infertility: Significance of autoantibodies and inflammatory mediators
Failid
Kuupäev
2013-06-19
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Infertiilsus ehk viljatus on ülemaailmne meditsiiniline ja sotsiaalne probleem, millega puutub kokku kuni 9% reproduktiivses eas paaridest. Kehavälise viljastamise protseduur (IVF) on osutunud kõige efektiivsemaks ravimeetodiks erinevate viljatuse põhjuste korral. IVF ravi tulemuslikkus on otseselt sõltuv follikulogeneesi stimulatsiooni tulemuslikkusest, mille hindamiseks otsitakse jätkuvalt efektiivsemaid ja optimaalsemaid biomarkereid, et nende põhjal paremini ennustada IVF ravi edukust. IVF ravi ebaõnnestumist on seostatud immuunsüsteemi häiretega, sealhulgas suurenenud autoantikehade produktsiooni ja muutunud tsütokiinide profiiliga. Käesolevas doktoriväitekirjas määrati humoraalse immuunsüsteemi aktivatsiooni markereid erineva viljatuse põhjusega naispatsientidel ning hinnati nende tähenduslikkust viljatuse etiopatogeneesis ja viljatusravi tulemuse ennustamisel. Selleks määrati töö esimeses osas patsientide vereseerumis esinevaid nii üldisi organspetsiifikata kui ka spetsiifiliselt reproduktiivorganite vastu suunatud autoantikehi. Tulemused näitasid, et erineva põhjusega viljatutel naistel, kes läbisid IVF protseduuri, esines sagedasti mitmesuguseid organ-spetsiifikata või -spetsiifilisi autoantikehi. Teatud antikehareaktsioonide esinemine oli seotud viljatuse diagnoosi või IVF ravitulemusega. Töö teises osas mõõdeti patsientide follikulaarvedelikust erinevate biomarkerite kontsentratsioone. Follikulaarvedelikust määratud proinflammatoorsete tsütokiinide, kemokiinide ja apoptoosi regulaatorite profiilid erinesid patsientide hulgas haiguspõhiselt. Peale selle leiti biomarkereid, mille esinemine oli seotud viljatusravi erinevate parameetritega. Töö tulemustest võib järeldada, et erineva põhjusega viljatutele IVF naispatsientidele on iseloomulik üldine immuunsüsteemi aktivatsioon. Immuunsüsteemi häired võivad olla seotud neil patsientidel esineva viljatuse patogeneesiga.
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.
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.
Kirjeldus
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