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

Infertility Clinical Trial

— PREDHSO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03051230
• Other study ID #: PREDHSO
• Status: Completed
• Phase: N/A
• First received: February 1, 2017
• Last updated: February 8, 2017
• Start date: April 1, 2012
• Est. completion date: February 1, 2017

Study information

• Verified date: February 2017
• Source: Poissy-Saint Germain Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 1, 2017
• Est. primary completion date: January 2, 2015
• Gender: Female
• Age group: 18 Years to 43 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperstimulation Syndrome, Ovaian
• Infertility
• Thrombosis

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Poissy-Saint Germain Hospital	Agence de La Biomédecine

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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