Abstract
Tänapäeval on viljatus reproduktiiveas inimeste hulgas tavaline probleem. Aina enam naisi lükkab laste saamist edasi, kuna esmalt soovitakse saavutada majanduslik kindlustatus, paraku väheneb vanusega munarakkude arv ja tõuseb viljatuse risk. Ka günekoloogilised haigused, nagu endometrioos suurendavad viljatuse tekke tõenäosust. Ei ole teada, kuidas täpselt endometrioos viljatust põhjustab ja endometrioosiga seotud viljatuse ravi on keeruline, koosnedes peamiselt kirurgilisest ravist, hormonaalsest ravist või nende kombinatsioonist ning sageli on vajalik kasutada ka in vitro viljastamise (IVF) protseduuri. Uute endometrioosi diagnoosimise- ja ravivõimaluste leidmist takistavad ka ebapiisavad teadmised selle haiguse patogeneesi molekulaarsetest mehhanismidest. Viljatuse ravi edukus IVF abil oleneb nii viljatuse põhjusest, partnerite vanusest, sugurakkude ja embrüote kvaliteedist, endomeetriumi retseptiivsusest kui ka valitud raviskeemi sobivusest. Viljatusravi tulemust võivad mõjutada ka elustiilifaktorid, näiteks füüsiline aktiivsus.
Antud doktoritöös uuriti endometrioosi erinevate raviskeemide ja füüsilise aktiivsuse mõju IVF ravi edukusele viljatusravi läbivatel patsientidel, ning hinnati endomeetriumi retseptiivsust ja molekulaarsete muutuste ulatust endometrioosi korral. Uuringus leiti, et naised vähendavad oluliselt oma füüsilist aktiivsust kunstliku viljastamise ajal. Füüsilise aktiivsuse määr ei olnud küll seotud rasestumisega edukusega, aga füüsiliselt aktiivsematel naistel õnnestus munasarjade stimulatsiooni järgselt saada rohkem munarakke ja embrüoid võrreldes nendega, kes vähendasid viljatusravi ajal oma füüsilist aktiivsust. Uuring näitas ka, et endometrioosi korral võib viljatuse ravis kasutada laparoskoopia, hormoonravi ja IVF kombineeritud raviskeemi. Endomeetriumi retseptiivsusega seotud geenide ekspressioon ei olnud endometrioosist mõjutanud. Molekulaarsed uuringud näitasid, et endomeetriumi ja endometrioosikollete rakud reageerivad tsütotoksilistele ühenditele erinevalt, mis võib tuleneda endometrioosi patogeneesis osalevate geenide erinevast ekspressioonitasemest.
Infertility is nowadays a common disorder among individuals of reproductive age. Women are postponing childbearing, mainly due to sociological factors, which leads to age-related decline in oocyte numbers and increases the risk of infertility. In addition, gynaecological diseases, such as endometriosis, increase the risk of infertility. Causes of endometriosis-associated infertility are unclear and the treatment mainly consists of medical or surgical approaches or combination of both, and in vitro fertilization (IVF) is often needed. Insufficient knowledge on the molecular mechanisms of endometriosis pathogenesis also hinders the search for new ways to diagnose and treat endometriosis. Success of infertility treatment depends on the cause of infertility, female and male age, gamete and embryo quality, endometrial receptivity, and suitability of the chosen treatment regimen. Lifestyle factors, such as physical activity during the IVF treatment may also affect the outcome of the procedure. The current study focused on the role of endometriosis treatment and physical activity in infertility treatment outcome and tried to unveil the molecular mechanisms behind endometriosis development. This study showed that women significantly decreased physical activity after starting the IVF treatment. The level of physical activity was not associated with pregnancy success, but physically more active women obtained higher numbers of oocytes and embryos in their treatment cycle. Endometriosis-related research showed that the combined treatment approach (laparoscopy, hormonal therapy and IVF) is suitable for endometriosis-associated infertility. Expression of genes associated with endometrial receptivity is not affected in women with endometriosis. Molecular studies revealed that endometrial cells in eutopic and ectopic locations react differently to treatment with cytotoxic compounds, a phenomenon that may be related to the altered expression of several genes involved in endometriosis pathogenesis.
Infertility is nowadays a common disorder among individuals of reproductive age. Women are postponing childbearing, mainly due to sociological factors, which leads to age-related decline in oocyte numbers and increases the risk of infertility. In addition, gynaecological diseases, such as endometriosis, increase the risk of infertility. Causes of endometriosis-associated infertility are unclear and the treatment mainly consists of medical or surgical approaches or combination of both, and in vitro fertilization (IVF) is often needed. Insufficient knowledge on the molecular mechanisms of endometriosis pathogenesis also hinders the search for new ways to diagnose and treat endometriosis. Success of infertility treatment depends on the cause of infertility, female and male age, gamete and embryo quality, endometrial receptivity, and suitability of the chosen treatment regimen. Lifestyle factors, such as physical activity during the IVF treatment may also affect the outcome of the procedure. The current study focused on the role of endometriosis treatment and physical activity in infertility treatment outcome and tried to unveil the molecular mechanisms behind endometriosis development. This study showed that women significantly decreased physical activity after starting the IVF treatment. The level of physical activity was not associated with pregnancy success, but physically more active women obtained higher numbers of oocytes and embryos in their treatment cycle. Endometriosis-related research showed that the combined treatment approach (laparoscopy, hormonal therapy and IVF) is suitable for endometriosis-associated infertility. Expression of genes associated with endometrial receptivity is not affected in women with endometriosis. Molecular studies revealed that endometrial cells in eutopic and ectopic locations react differently to treatment with cytotoxic compounds, a phenomenon that may be related to the altered expression of several genes involved in endometriosis pathogenesis.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Keywords
endometriosis, assisted reproduction, physical activity