Dynamics of nitric oxide, altered follicular microenvironment, and oocyte quality in women with endometriosis.
OBJECTIVE
To study follicular microenvironment in terms of free radical dynamics, oocyte quality, and assisted reproductive technology (ART) outcomes among women with (group A) and without (group B) endometriosis.


METHODS
Prospective cohort study.


METHODS
University ART center.


METHODS
Women with and without endometriosis undergoing ART (n=28).


METHODS
Follicular fluid (FF), granulosa cells (GCs), immature oocytes (IOs), and ART data on sibling cohort oocytes in groups A and B were compared.


METHODS
ART live birth outcomes, maturation, and aging among in vitro matured (IVM) oocytes, nitrate levels in FF, and nitrotyrosine (NT) footprints and apoptosis in the GCs.


RESULTS
Clinical characteristics and ART live birth outcomes were no different between groups A and B. Women from group A had significantly lower peak serum E2 (2,068.8±244.6 pg/mL vs. 2,756.2±205.0 pg/mL) and higher apoptosis (80.0% vs. 22.2%) and NT staining (70.0% vs. 22.2%) in GCs compared with group B. Fewer IOs underwent IVM to MII (0.6±0.3) in group A compared with group B (1.4±0.2). IVM oocytes had significantly higher incidence of cortical granule loss (83.3% vs. 24.0%) and spindle disruption (66.7% vs. 16.0%) and higher zona pellucida dissolution timing (133.8±9.4 s vs. 90.5±5.8 s) in group A compared with group B. FF nitrate levels were significantly higher in women who failed to conceive in group A (478.2±43.1 nmol/L) compared with those that did conceive (173.3±19.0 nmol/L).


CONCLUSIONS
Increased protein nitration, GC apoptosis, resistance to IVM, and oocyte aging indicate the involvement of oxidative dysregulation of NO in the pathophysiology of altered follicular milieu and poor oocyte quality in women with endometriosis.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan; Division of Reproductive Endocrinology and Infertility, University of California Davis Medical Center, Sacramento, California; Californa IVF Fertility Center, Davis and Sacramento, California. Electronic address: pravin.goud@ucdmc.ucdavis.edu.
Pravin T
PT
Goud
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan; California National Primate Research Center, University of California, Davis, California.
Anuradha P
AP
Goud
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
Narendra
N
Joshi
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
Elizabeth
E
Puscheck
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
Michael P
MP
Diamond
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.
Husam M
HM
Abu-Soud
D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D060833:Cellular Microenvironment; D016922:Cellular Senescence; D004715:Endometriosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D050498:Live Birth; D009569:Nitric Oxide / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism* / Q000473:pathology; D006080:Ovarian Follicle / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D011247:Pregnancy; D018873:Pregnancy Rate; D011446:Prospective Studies; D027724:Reproductive Techniques, Assisted; D016896:Treatment Outcome
D015415:Biomarkers; D009569:Nitric Oxide; D004958:Estradiol
Endometriosis; nitric oxide; oocyte aging; oocyte quality; peroxynitrite; superoxide