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ENDOMETRİYOZİS ve OOSİT
KALİTESİ
Pınar ÖZCAN, MD, PhD
Department of Obstetric&Gynecology, Bezmialem University
Hospital
Division of Reproductive Endocrinology and Infertility,
Department of Obstetrics, Gynecology and Reproductive
Biology, Brigham and Women's Hospital, Harvard Medical
School
ENDOMETRİYOZİS İLİŞKİLİ İNFERTİLİTENİN
PATOJENİK MEKANİZMASI
Endometriyoma cerrahisi
over rezervini azaltabilir
Neden ve etki ilişkisi
Cerrahi öncesi
endometriyomanın
varlığının fertilite
üzerindeki olumsuz
etkisi
ENDOMETRIYOZIS FEKUNDITEYI AZALTıR
MİLD
7.4
MODERATE
2.8
SEVERE
0
Olive, Fertil Steril 1985
Dmowski, Fertil Steril 2002
ENDOMETRİYOZİS İLİŞKİLİ İNFERTİLİTENİN
PATOJENİK MEKANİZMASI
Follikülogeneziste
değişiklikler
 Ovulatuar disfonksiyon
 Kötü oosit kalitesi
 Luteal faz defekti
 Azalmış fertilizasyon
 Anormal embriyogenezis

Granuloza hücre fonksiyonu, hormon
reseptivitesi, hormon biosentezi
Folliküler mikroçevre
kalitesi
Kumulus hücreleri-oosit
arasındaki çift yönlü iletişimin
yeterli olması
Oosit kalitesi
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

INFLAMATUAR RESPONSEOXIDATIVE STRESS
Sanchez, Hum Repro 2014
Sanchez, J Steroid Biochemistry & Molecular Biology 2016
Giacomini E, E J Obs&Gynecol 2016
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
Dysregulated folliculogenesis
Oocyte apoptosis
Follicular atresia
Increased oxidative stress
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
Kitajima M, Fertil Steril 2014
Theca externa cells
Theca interna cells
LH receptors
on theca cells
Granulosa
cells
FSH receptors
on granulosa
cells
Follicular
antrum
FSH
Zona pellucida
Oocyte
Cumulus
Oophorus
cells
LH
E2
A
Capillary network
Basement membrane
Sanchez, J Steroid Biochemistry & Molecular Biology 2016
‘‘The rise of oxygen changed the course
of evolution.’’
THE DARK SIDE OF OXYGEN
Donnez J, Fertil Steril 2016
Gynecol Endocrinol 2015
Barcelos, RBM online 2015
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
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
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
Saito H, Gynecol Obstet Invest 2002
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
Increased ROS and NO in endometriosis and infertility associated
with poor oocytes and embryo quality
Singh A, Reproductive Toxicology 2013
TELOMERAZ- DNA HASARı
Alteration of oocyte cytoskeleton might be
one of the causes of poor oocyte quality in
patients with
endometriosis.
Mansour G, Fertil Steril 2009
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
SONUC

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