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

Study Overview
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Brief Summary
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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.

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

Conditions
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Infertility, Hyperstimulation Syndrome, Ovaian, Thrombosis

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Studied group<br>Women exposed to ovarian hyperstimulation for In Vitro fertilisation | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantification of Microparticles subsets from endothelial origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of Microparticles subsets from erythrocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of Microparticles subsets from leukocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal | 
| Quantification of Microparticles subsets from platelet origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood | Venipuncture for blood sampling and exam with home made device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal | 
| Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood | Venipuncture for blood sampling and exam with home made device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal | 
| Quantification of Fibrin monomer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of D-dimer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of E-selectin in the circulating blood | Venipuncture for blood sampling and exam with commercial device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of soluble CD 146 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of Von Willbrand factor in the circulating blood | Venipuncture for blood sampling and exam with commercial device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of thrombin-antithrombin complex in the circulating blood | Venipuncture for blood sampling and exam with commercial device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of prothrombin fragment 1+2 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up | 
| Quantification of Microparticles subsets from endothelial origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Microparticles subsets from erythrocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Microparticles subsets from leukocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Microparticles subsets from platelet origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood | Venipuncture for blood sampling and exam with home made device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood | Venipuncture for blood sampling and exam with home made device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Fibrin monomer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of D-dimer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of E-selectin in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of soluble CD 146 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Von Willbrand factor in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of thrombin-antithrombin complex in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of prothrombin fragment 1+2 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation | 
| Quantification of Microparticles subsets from endothelial origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Microparticles subsets from erythrocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Microparticles subsets from leukocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Microparticles subsets from platelet origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood | Venipuncture for blood sampling and exam with home made device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood | Venipuncture for blood sampling and exam with home made device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Fibrin monomer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of D-dimer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of E-selectin in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of soluble CD 146 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Von Willbrand factor in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of thrombin-antithrombin complex in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of prothrombin fragment 1+2 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm | 
| Quantification of Microparticles subsets from endothelial origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Microparticles subsets from erythrocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Microparticles subsets from leukocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Microparticles subsets from platelet origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood | Venipuncture for blood sampling and exam with home made device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood | Venipuncture for blood sampling and exam with home made device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Fibrin monomer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of D-dimer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of E-selectin in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of soluble CD 146 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Von Willbrand factor in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of thrombin-antithrombin complex in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of prothrombin fragment 1+2 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos | 
| Quantification of Microparticles subsets from endothelial origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Microparticles subsets from erythrocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Microparticles subsets from leukocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Microparticles subsets from platelet origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood | Venipuncture for blood sampling and exam with home made device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood | Venipuncture for blood sampling and exam with home made device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Fibrin monomer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of D-dimer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of E-selectin in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of soluble CD 146 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Von Willbrand factor in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of thrombin-antithrombin complex in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase | 
| Quantification of Microparticles subsets from platelet origin in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Microparticles subsets from endothelial origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Microparticles subsets from erythrocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Microparticles subsets from leukocyte origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Microparticles subsets from platelet origin in the circulating blood | Venipuncture for blood sampling and exam with flow cytometry | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood | Venipuncture for blood sampling and exam with home made device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood | Venipuncture for blood sampling and exam with home made device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Fibrin monomer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of D-dimer in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of E-selectin in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of soluble CD 146 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of Von Willbrand factor in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of thrombin-antithrombin complex in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 
| Quantification of prothrombin fragment 1+2 in the circulating blood | Venipuncture for blood sampling and exam with commercial device | 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Superovulation, Blood Coagulation Disorders, Cell-Derived Microparticles, Fertilization in Vitro, Biomarkers