Vascular Cell Activation, Cell-Derived Microparticles and In Vitro Fertilisation, and In Vitro Fertilisation

Vascular Cell Activation Throughout Ovarian Hyperstimulation for In Vitro Fertilisation: Role of Cell-Derived Microparticles in the Adverse Outcomes

Introduction: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic phenomenon, poorly understood and difficult to predict, complicating intense ovarian stimulation cycle. The most severe symptoms, which associate vascular permeability disorders and hypercoagulability, occur in 0.2 to 1% of the cases and often require intensive care.

Activation of endothelial, platelet, erythrocyte or leukocyte cells trigger the release of small specific vesicles, called microparticles, used as markers.

Classically leading to endothelial dysfunction and hypercoagulability, the endothelial activation phenomenon could constitute the main cause of OHSS or help predict its severity, as established for various other diseases (cerebral stroke, infarct and lupus…). However, so far, this endothelial activation role has never been studied.

Objectives:

Evaluate the serum level of microparticles as a predictor of adverse outcomes; correlate it to hypercoagulability and changes of endothelial permeability associated with this syndrome.

Methodology: Prospective Pilote Cohort study, evaluating before and throughout the ovarian stimulation cycle (6 samples/patient), the serum modulation of:

• Endothelial activation markers (endothelial-derived microparticles, E-selectin)
• Procoagulant markers (microparticles from platelet, erythrocyte or leukocyte origin, Von Willbrand factor, thrombin-antithrombin complex, prothrombin fragment 1+2)
• Endothelial disjunction marker (soluble CD 146) A group of 50 patients will be assessed Techniques: Flow cytometry for measurement of microparticles expressing non specific (Annexin V) and cell specific surface determinants (CD 31, CD 41, CD 45 or glycophorin A). Use of commercial kits for other serum markers.

Inclusion Criteria:

• Between 18 and 35 years old
• With Health Insurance
• Scheduled for their first ovarian stimulation in an IVF or ICSI program in our centre
• Whose blood samples will be collected in our hospital

Exclusion Criteria:

• Suffering or having suffered from a disease likely to alter their vascular system and thus modulate their rates of microparticles:

  • auto-immune disease (systemic lupus erythematosus26, antiphospholipid syndrome)
  • cardiovascular risk factors: cardiovascular disease history, diabetes, arterial hypertension, dyslipidemia
  • Tobacco addiction.

• Presenting a blood œstradiol rate > 5000 pg/ml at ovulation triggering (criterion of stimulation cancellation) and more generally, every patient which ovulation has not been triggered.