ENDOMETR İ YOZ İ STE OOS İ T KAL İ TESİ
Pınar ÖZCAN, MD, PhD
Bezmialem University Hospital
Department of Obstetric&Gynecology
Endometriyoma cerrahisi over rezervini azaltabilir
Cerrahi öncesi
endometriyomanın varlığının fertilite üzerindeki olumsuz etkisi
ENDOMETRİYOZİS İLİŞKİLİ İNFERTİLİTENİN PATOJENİK MEKANİZMASI
Neden ve etki ili ş kisi
MİLD
MODERATE
SEVERE
7.4 2.8 0
Olive, Fertil Steril 1985 Dmowski, Fertil Steril 2002
ENDOMETR İ YOZ İ S FEKUND İ TEY İ
AZALTIR
ENDOMETRİYOZİS İLİŞKİLİ
İNFERTİLİTENİN PATOJENİK MEKANİZMASI
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Follikülogeneziste değişiklikler
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Ovulatuar disfonksiyon
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Kötü oosit kalitesi
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Luteal faz defekti
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Azalmış fertilizasyon
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Anormal embriyogenezis
Folliküler mikroçevre kalitesi
Kumulus hücreleri-oosit arasındaki çift yönlü iletişimin yeterli olması
Oosit kalitesi
Granuloza hücre fonksiyonu, hormon reseptivitesi, hormon biosentezi
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Uzamış foliküler faz
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Azalmış foliküler büyüme hızı
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Azalmış dominant folikül büyüklüğü
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Azalmış foliküler östradiol konsantrasyonu
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Bozulmuş LH surge
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Folliküler LH reseptörlerinde yetersizlik
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Mural ve oositi çevreleyen kumulus granuloza hücrelerinde apopitozis
ENDOMETRİYOZİS İLİŞKİLİ
İNFERTİLİTENİN PATOJENİK
MEKANİZMASI
INFLAMATUAR
RESPONSE-OXİDATİVE STRESS
Sanchez, Hum Repro 2014
Kitajima M, Fertil Steril 2014
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
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
Theca externa cells
Theca interna cells
Capillary network Basement membrane Cumulus Oophorus cells Oocyte
Zona pellucida Granulosa
cells
Follicular antrum
LH receptors on theca cells
FSH receptors on granulosa cells
E
2FSH
LH
A
Gupta S, Fertil Steril 2008
Barcelos, RBM online 2015
Ono YJ, PLOS one, 2014
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.
Saito H, Gynecol Obstet Invest 2002
Saito H, Gynecol Obstet Invest 2002
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
Opeion H, Hum Repr 2013
• Eritrositler
• Apopitotik endometrioma hücreleri
• aktive olmuş makrofajlar
Granuloza hücre disfonksiyonu, mitokondrial defektler ve oosit telomer kısalması
OXIDAT İ VE STRESS
Jomova K, Current Pharmaceutical Design, 2011
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
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
Singh A, Reproductive Toxicology 2013
Increased ROS and NO in endometriosis and infertility
associated with poor oocytes and embryo quality
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
Goud PT, Fertil Steril 2014
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.
T Elomeraz - Dna Hasari
Alteration of oocyte cytoskeleton might be one of the causes of poor oocyte quality in patients with endometriosis.
Mansour G, Fertil Steril 2009
Da Broi MG, Hum Reprod 2014
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
Cohen J, J Assist Reprod Genet 2015
Induced peritoneal endometriosis in a mouse model is associated with a decrease in oocyte quality and embryo number
SONUÇ
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