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ENDOMETRİYOZİSTE OOSİT KALİTESİ

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(1)

ENDOMETR İ YOZ İ STE OOS İ T KAL İ TESİ

Pınar ÖZCAN, MD, PhD

Bezmialem University Hospital

Department of Obstetric&Gynecology

(2)

Endometriyoma cerrahisi over rezervini azaltabilir

Cerrahi öncesi

endometriyomanın varlığının fertilite üzerindeki olumsuz etkisi

ENDOMETRİYOZİS İLİŞKİLİ İNFERTİLİTENİN PATOJENİK MEKANİZMASI

Neden ve etki ili ş kisi

(3)

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

(4)

ENDOMETRİYOZİS İLİŞKİLİ

İNFERTİLİTENİN PATOJENİK MEKANİZMASI

¢ 

Follikülogeneziste değişiklikler

¢ 

Ovulatuar disfonksiyon

¢ 

Kötü oosit kalitesi

¢ 

Luteal faz defekti

¢ 

Azalmış fertilizasyon

¢ 

Anormal embriyogenezis

(5)

Folliküler mikroçevre kalitesi

Kumulus hücreleri-oosit arasındaki çift yönlü iletişimin yeterli olması

Oosit kalitesi

Granuloza hücre fonksiyonu, hormon reseptivitesi, hormon biosentezi

(6)

¢ 

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

ENDOMETRİYOZİS İLİŞKİLİ

İNFERTİLİTENİN PATOJENİK

MEKANİZMASI

(7)

INFLAMATUAR

RESPONSE-OXİDATİVE STRESS

Sanchez, Hum Repro 2014

(8)

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

(9)

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

(10)

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

2

FSH

LH

A

(11)
(12)

Gupta S, Fertil Steril 2008

(13)

Barcelos, RBM online 2015

(14)

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.

(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)

• Eritrositler

• Apopitotik endometrioma hücreleri

•  aktive olmuş makrofajlar

Granuloza hücre disfonksiyonu, mitokondrial defektler ve oosit telomer kısalması

OXIDAT İ VE STRESS

(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)

Singh A, Reproductive Toxicology 2013

Increased ROS and NO in endometriosis and infertility

associated with poor oocytes and embryo quality

(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

(25)

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.

(26)
(27)

T Elomeraz - 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)

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

(30)

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

(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

(32)

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