NCT03051230

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.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Apr 2012

Longer than P75 for all trials

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2012

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 2, 2015

Completed
2.1 years until next milestone

First Submitted

Initial submission to the registry

February 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2017

Completed
12 days until next milestone

First Posted

Study publicly available on registry

February 13, 2017

Completed
Last Updated

February 13, 2017

Status Verified

February 1, 2017

Enrollment Period

2.8 years

First QC Date

February 1, 2017

Last Update Submit

February 8, 2017

Conditions

Keywords

Blood Coagulation DisordersCell-Derived MicroparticlesSuperovulationFertilization in VitroBiomarkers

Outcome Measures

Primary Outcomes (78)

  • 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

Study Arms (1)

Studied group

Women exposed to ovarian hyperstimulation for In Vitro fertilisation

Eligibility Criteria

Age18 Years - 43 Years
Sexfemale
Age GroupsAdult (18-64)
Sampling MethodProbability 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.

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Biospecimen

Retention: SAMPLES WITHOUT DNA

After platelet removal, serum samples will be frozen stored before being processed

MeSH Terms

Conditions

InfertilityThrombosisBlood Coagulation Disorders

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital DiseasesEmbolism and ThrombosisVascular DiseasesCardiovascular DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Doctor

Study Record Dates

First Submitted

February 1, 2017

First Posted

February 13, 2017

Study Start

April 1, 2012

Primary Completion

January 2, 2015

Study Completion

February 1, 2017

Last Updated

February 13, 2017

Record last verified: 2017-02