ENDOMETRİYOZİSTE OOSİT KALİTESİ. Pınar ÖZCAN, MD, PhD Bezmialem University Hospital Department of Obstetric&Gynecology

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1 ENDOMETRİYOZİSTE OOSİT KALİTESİ Pınar ÖZCAN, MD, PhD Bezmialem University Hospital Department of Obstetric&Gynecology

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

ENDOMETRİYOZİS FEKUNDİTEYİ AZALTIR MİLD MODERATE SEVERE 7.

3 ENDOMETRİYOZİS FEKUNDİTEYİ AZALTIR MİLD MODERATE SEVERE 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 Kumulus hücreleri-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 RESPONSE-OXİDATİVE STRESS Sanchez, Hum Repro 2014

8 The burnout hypothesis may explain the mechanism partly responsible for the reduced ovarian reserve in women with endometriomas. Formation of 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 be associated with a vicious circle of dysregulated folliculogenesis that eventually results in burnout of the stockpile of dormant follicles Reduced vascularization Increased oxidative stress Dysregulated folliculogenesis Oocyte apoptosis Follicular atresia Kitajima M, Fertil Steril 2014

9 Ovaries with endometriomas, which may be more prone to local pelvic inflammation, showed activated follicular recruitment and atresia of early follicles. The potential contribution of inflammation to follicle burnout in case of endometriomas is discussed Kitajima M, Fertil Steril 2014

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

12 Gupta S, Fertil Steril 2008

13 Barcelos, RBM online 2015

The mechanism underlying the anti-apoptotic

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

15 Saito H, Gynecol Obstet Invest 2002

16 Saito H, Gynecol Obstet Invest 2002

17 Changes reflected ovarian interstitial microvascular injury of OEC, pathologically supported the findings of blood flow changes within ovarian interstitial arteries, and prospectively predicted OEC-induced ovarian interstitial vessel injury. Qui JJ, Arch Gynecol Obstet 2012

18 Opeion H, Hum Repr 2013

19 OXIDATİVE STRESS Eritrositler Apopitotik endometrioma hücreleri aktive olmuş makrofajlar Granuloza hücre disfonksiyonu, mitokondrial defektler ve oosit telomer kısalması

20 Jomova K, Current Pharmaceutical Design, 2011

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

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

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

24 The normal ovarian cortex surrounding endometriotic tissues was affected more severely by oxidative stress, granulosa cells from patients with infertility and endometriosis exhibit more signs of severe oxidative DNA damage Matsuzaki S, Fertil Steril 2010

Altered follicular microenvironment with

explain poor oocyte quality in women with

25 Altered follicular microenvironment with increased oxidative stress and NO insufficiency, and their secondary impact on GCs and oocytes, is the likely mechanism to explain poor oocyte quality in women with endometriosis that fail to conceive after ART. Goud PT, Fertil Steril 2014

27 TElomeraz- Dna Hasari

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 with mild endometriosis can impair nuclear maturation and promote meiotic anomalies in bovine oocytes matured in vitro. These findings provide evidence about the mechanisms associated with infertility in women with early stage endometriosis Da Broi MG, Hum Reprod 2014

30 Induced peritoneal endometriosis in a mouse model is associated with a decrease in oocyte quality and embryo number Cohen J, J Assist Reprod Genet 2015

31 SONUÇ 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

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