Endometriyozis-oosit kalitesi

1. Endometriyozis-oosit kalitesi Pınar ÖZCAN, MD, PhD Bezmialem Universitesi Tıp Fakültesi Kadın Hastalıkları ve Doğum ABD

2. ENDOMETRİYOZİS İLİŞKİLİ İNFERTİLİTENİN PATOJENİK MEKANİZMASI Endometriyoma cerrahisi over rezervini azaltabilir Neden ve etki ilişkisi Cerrahi öncesi endometriyomanın varlığının fertilite üzerindeki olumsuz etkisi

3. Endometriyozisfekunditeyi azaltır Olive, Fertil Steril 1985 Dmowski, Fertil Steril 2002

4. ENDOMETRİYOZİS İLİŞKİLİ İNFERTİLİTENİN PATOJENİK MEKANİZMASI • Follikülogeneziste değişiklikler • Ovulatuar disfonksiyon • Kötü oosit kalitesi • Luteal faz defekti • Azalmış fertilizasyon • Anormal embriyogenezis

5. Granuloza hücre fonksiyonu, hormon reseptivitesi, hormon biosentezi Folliküler mikroçevre kalitesi Kumulushücreleri-oosit arasındaki çift yönlü iletişimin yeterli olması Oosit kalitesi

6. ENDOMETRİYOZİS İLİŞKİLİ İNFERTİLİTENİN PATOJENİK MEKANİZMASI • Uzamış foliküler faz • Azalmış foliküler büyüme hızı • Azalmış dominant folikül büyüklüğü • Azalmış foliküler östradiol konsantrasyonu • Bozulmuş LH surge • Folliküler LH reseptörlerinde yetersizlik • Mural ve oositi çevreleyen kumulus granuloza hücrelerinde apopitozis

7. Inflamatuarresponse-oxidativestress

8. E2 A Theca externa cells FSH receptors on granulosa cells Theca interna cells LH receptorson theca cells Granulosa cells FSH Follicular antrum Zona pellucida Oocyte Cumulus Oophorus cells LH Capillary network Basement membrane

10. Gupta S, Fertil Steril 2008

11. Barcelos, RBM online 2015

12. Themechanism underlying the anti-apoptotic effects of testosterone on granulosa cells,and found that a low-testosterone status is a potentially important step in thedevelopment of premature ovarian insufficiency in patients with endometriosis. Ono YJ, PLOS one, 2014

13. Saito H, Gynecol Obstet Invest 2002

14. Saito H, Gynecol Obstet Invest 2002

15. Changes reflectedovarian interstitial microvascular injury of OEC, pathologicallysupported the findings of blood flow changeswithin ovarian interstitial arteries, and prospectivelypredicted OEC-induced ovarian interstitial vessel injury. Qui JJ, Arch Gynecol Obstet 2012

16. Opeion H, Hum Repr 2013

17. The‘‘burnout’’ hypothesis may explain the mechanism partly responsible for the reduced ovarian reserve in women with endometriomas. Formationof endometriomas may cause focal inflammation in ovarian cortex. This inflammation could result in structural alteration to the ovarian cortex,which manifest as massive fibrosis and loss of cortex-specific stroma that maintains follicular nests. Focal loss of follicular density may beassociated with a vicious circle of dysregulatedfolliculogenesis that eventually results in burnout of the stockpile of dormant follicles Reduced vascularization Increasedoxidativestress Dysregulatedfolliculogenesis Oocyteapoptosis Follicularatresia Kitajima M, Fertil Steril 2014

18. Ovaries with endometriomas, which may be more prone to local pelvicinflammation, showed activated follicularrecruitment and atresia of early follicles. The potential contribution of inflammation to follicle‘‘burnout’’ in case of endometriomas is discussed Kitajima M, Fertil Steril 2014

19. Oxıdativestress • Eritrositler • Apopitotikendometrioma hücreleri • aktive olmuş makrofajlar Granuloza hücre disfonksiyonu, mitokondrialdefektler ve oosit telomer kısalması

20. Jomova K, Current Pharmaceutical Design, 2011

21. Iron and its major storage proteins representmolecular signs of the gonadotoxic insult to individual follicles developingadjacent to the cyst during IVF cycles. This is reflected by the low rate ofoocyte retrieval from endometrioma-proximal follicles Sanchez AM Hum Rep 2014

22. Fertilization rate and percentage of Grades I and II embryoformation were observed to be significantly lower and DNA fragmentedembryo significantly higher in women with endometriosis Janaa SK, Reproductive Toxicology 2010

23. Increased ROS and NO in endometriosis andinfertility associated with poor oocytes and embryo quality Singh A, Reproductive Toxicology 2013

24. The normal ovariancortexsurrounding endometriotic tissues was affected more severely byoxidativestress, granulosacellsfrom patients with infertility and endometriosis exhibit more signs of severe oxidative DNA damage Matsuzaki S, Fertil Steril 2010

25. Alteredfollicularmicroenvironmentwith increased oxidative stress and NO insufficiency, and their secondaryimpact on GCs and oocytes, is the likely mechanism toexplain poor oocyte quality in women with endometriosisthat fail to conceive after ART. Goud PT, Fertil Steril 2014

27. Telomeraz- dna hasarı

28. Alteration of oocyte cytoskeleton might be one of the causes of poor oocyte quality in patients with endometriosis. Mansour G, Fertil Steril 2009

29. FF of infertile women withmild endometriosis can impair nuclearmaturation and promote meioticanomalies in bovine oocytes matured in vitro. These findings provide evidenceabout the mechanisms associated with infertility in women withearlystageendometriosis Da Broi MG, Hum Reprod 2014

30. Inducedperitonealendometriosisin a mouse model is associated with a decrease inoocyte quality and embryo number Cohen J, J Assist Reprod Genet 2015

31. Eve götürülecek mesaj • Endometriyozis oosit kalitesi üzerinde detrimental etkiye sahip Kortex-spesifik stroma kaybı Ovarian angiogenezisin inhibisyonu Artmış granuloza hücre apoptozisi Ovarian steroid enzime pathwaylerinde değişiklikler Hücre siklusu kinetiklerinde değişimler DNA hasarı, kromozomal instabilite Gene ekspresyonlarında değişiklikler

32. Teşekkürler