Clinical trial NCT03051230: Vascular Cell Activation, Cell-Derived Microparticles and In Vitro Fertilisation, and In Vitro Fertilisation
Official title: Vascular Cell Activation Throughout Ovarian Hyperstimulation for In Vitro Fertilisation: Role of Cell-Derived Microparticles in the Adverse Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infertility
Hyperstimulation Syndrome, Ovaian
Thrombosis
Keywords: Blood Coagulation Disorders
Cell-Derived Microparticles
Superovulation
Fertilization in Vitro
Biomarkers
Lead sponsor: Poissy-Saint Germain Hospital
Sponsor class: OTHER
Collaborators: name: Agence de La Biomédecine
First posted: 2017-02-13
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Infertile volunteers, aged 18 to 35 years, with neither cardiovascular disease nor Lupus erythematosus related disease, scheduled for In Vitro fertilisation, and assessed from their day 3 basal hormonal assessment, at least to the ovarian triggering of their IVF cycle were included.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Quantification of Microparticles subsets from endothelial origin in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of Microparticles subsets from erythrocyte origin in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of Microparticles subsets from leukocyte origin in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal
measure: Quantification of Microparticles subsets from platelet origin in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal
measure: Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal
measure: Quantification of Fibrin monomer in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of D-dimer in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of E-selectin in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of soluble CD 146 in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of Von Willbrand factor in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of thrombin-antithrombin complex in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of prothrombin fragment 1+2 in the circulating blood
timeFrame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up
measure: Quantification of Microparticles subsets from endothelial origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Microparticles subsets from erythrocyte origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Microparticles subsets from leukocyte origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Microparticles subsets from platelet origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Fibrin monomer in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of D-dimer in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of E-selectin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of soluble CD 146 in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Von Willbrand factor in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of thrombin-antithrombin complex in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of prothrombin fragment 1+2 in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation
measure: Quantification of Microparticles subsets from endothelial origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Microparticles subsets from erythrocyte origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Microparticles subsets from leukocyte origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Microparticles subsets from platelet origin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Fibrin monomer in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of D-dimer in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of E-selectin in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of soluble CD 146 in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Von Willbrand factor in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of thrombin-antithrombin complex in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of prothrombin fragment 1+2 in the circulating blood
timeFrame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm
measure: Quantification of Microparticles subsets from endothelial origin in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Microparticles subsets from erythrocyte origin in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Microparticles subsets from leukocyte origin in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Microparticles subsets from platelet origin in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Fibrin monomer in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of D-dimer in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of E-selectin in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of soluble CD 146 in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Von Willbrand factor in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of thrombin-antithrombin complex in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of prothrombin fragment 1+2 in the circulating blood
timeFrame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos
measure: Quantification of Microparticles subsets from endothelial origin in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Microparticles subsets from erythrocyte origin in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Microparticles subsets from leukocyte origin in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Microparticles subsets from platelet origin in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Fibrin monomer in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of D-dimer in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of E-selectin in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of soluble CD 146 in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Von Willbrand factor in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of thrombin-antithrombin complex in the circulating blood
timeFrame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase
measure: Quantification of Microparticles subsets from platelet origin in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Microparticles subsets from endothelial origin in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Microparticles subsets from erythrocyte origin in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Microparticles subsets from leukocyte origin in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Microparticles subsets from platelet origin in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Fibrin monomer in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of D-dimer in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of E-selectin in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of soluble CD 146 in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of Von Willbrand factor in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of thrombin-antithrombin complex in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
measure: Quantification of prothrombin fragment 1+2 in the circulating blood
timeFrame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: