Dynamics of nitric oxide, altered follicular microenvironment, and oocyte quality in women with endometriosis

Fertil Steril. 2014 Jul;102(1):151-159.e5. doi: 10.1016/j.fertnstert.2014.03.053. Epub 2014 May 10.


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.

Design: Prospective cohort study.

Setting: University ART center.

Patient(s): Women with and without endometriosis undergoing ART (n=28).

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

Main outcome measure(s): 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.

Result(s): 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).

Conclusion(s): 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.

Keywords: Endometriosis; nitric oxide; oocyte aging; oocyte quality; peroxynitrite; superoxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Biomarkers / blood
  • Case-Control Studies
  • Cellular Microenvironment*
  • Cellular Senescence
  • Endometriosis / complications
  • Endometriosis / metabolism*
  • Endometriosis / pathology
  • Estradiol / blood
  • Female
  • Follicular Fluid / metabolism
  • Granulosa Cells / metabolism
  • Humans
  • Infertility, Female / etiology
  • Infertility, Female / metabolism*
  • Infertility, Female / pathology
  • Infertility, Female / therapy
  • Live Birth
  • Nitric Oxide / metabolism*
  • Oocytes / metabolism*
  • Oocytes / pathology
  • Ovarian Follicle / metabolism*
  • Ovarian Follicle / pathology
  • Oxidative Stress
  • Pregnancy
  • Pregnancy Rate
  • Prospective Studies
  • Reproductive Techniques, Assisted
  • Treatment Outcome


  • Biomarkers
  • Nitric Oxide
  • Estradiol