Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Vascular Cell Activation, Cell-Derived Microparticles and In Vitro Fertilisation, and In Vitro Fertilisation (PREDHSO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03051230
Recruitment Status : Completed
First Posted : February 13, 2017
Last Update Posted : February 13, 2017
Sponsor:
Collaborator:
Agence de La Biomédecine
Information provided by (Responsible Party):
Antoine Torre, Poissy-Saint Germain Hospital

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.

Condition or disease
Infertility Hyperstimulation Syndrome, Ovaian Thrombosis

Layout table for study information
Study Type : Observational
Actual Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Vascular Cell Activation Throughout Ovarian Hyperstimulation for In Vitro Fertilisation: Role of Cell-Derived Microparticles in the Adverse Outcomes
Actual Study Start Date : April 1, 2012
Actual Primary Completion Date : January 2, 2015
Actual Study Completion Date : February 1, 2017

Group/Cohort
Studied group
Women exposed to ovarian hyperstimulation for In Vitro fertilisation



Primary Outcome Measures :
  1. Quantification of Microparticles subsets from endothelial origin in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with flow cytometry

  2. Quantification of Microparticles subsets from erythrocyte origin in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with flow cytometry

  3. Quantification of Microparticles subsets from leukocyte origin in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal ]
    Venipuncture for blood sampling and exam with flow cytometry

  4. Quantification of Microparticles subsets from platelet origin in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with flow cytometry

  5. Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal ]
    Venipuncture for blood sampling and exam with home made device

  6. Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal ]
    Venipuncture for blood sampling and exam with home made device

  7. Quantification of Fibrin monomer in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with commercial device

  8. Quantification of D-dimer in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with commercial device

  9. Quantification of E-selectin in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with commercial device

  10. Quantification of soluble CD 146 in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with commercial device

  11. Quantification of Von Willbrand factor in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with commercial device

  12. Quantification of thrombin-antithrombin complex in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with commercial device

  13. Quantification of prothrombin fragment 1+2 in the circulating blood [ Time Frame: At day 3 of an unstimulated (i.e. natural) menstrual cycle, before IVF cycle, when basal hormonal assessments is performed for fertility work-up ]
    Venipuncture for blood sampling and exam with commercial device

  14. Quantification of Microparticles subsets from endothelial origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with flow cytometry

  15. Quantification of Microparticles subsets from erythrocyte origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with flow cytometry

  16. Quantification of Microparticles subsets from leukocyte origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with flow cytometry

  17. Quantification of Microparticles subsets from platelet origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with flow cytometry

  18. Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with home made device

  19. Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with home made device

  20. Quantification of Fibrin monomer in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with commercial device

  21. Quantification of D-dimer in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with commercial device

  22. Quantification of E-selectin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with commercial device

  23. Quantification of soluble CD 146 in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with commercial device

  24. Quantification of Von Willbrand factor in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with commercial device

  25. Quantification of thrombin-antithrombin complex in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with commercial device

  26. Quantification of prothrombin fragment 1+2 in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at first day of FSH stimulation ]
    Venipuncture for blood sampling and exam with commercial device

  27. Quantification of Microparticles subsets from endothelial origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with flow cytometry

  28. Quantification of Microparticles subsets from erythrocyte origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with flow cytometry

  29. Quantification of Microparticles subsets from leukocyte origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with flow cytometry

  30. Quantification of Microparticles subsets from platelet origin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with flow cytometry

  31. Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with home made device

  32. Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with home made device

  33. Quantification of Fibrin monomer in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with commercial device

  34. Quantification of D-dimer in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with commercial device

  35. Quantification of E-selectin in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with commercial device

  36. Quantification of soluble CD 146 in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with commercial device

  37. Quantification of Von Willbrand factor in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with commercial device

  38. Quantification of thrombin-antithrombin complex in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with commercial device

  39. Quantification of prothrombin fragment 1+2 in the circulating blood [ Time Frame: During ovarian stimulation for IVF (first cycle), at ovarian triggering day, i.e.when ≥ 3 ovarian follicles rich 17mm ]
    Venipuncture for blood sampling and exam with commercial device

  40. Quantification of Microparticles subsets from endothelial origin in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with flow cytometry

  41. Quantification of Microparticles subsets from erythrocyte origin in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with flow cytometry

  42. Quantification of Microparticles subsets from leukocyte origin in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with flow cytometry

  43. Quantification of Microparticles subsets from platelet origin in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with flow cytometry

  44. Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with home made device

  45. Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with home made device

  46. Quantification of Fibrin monomer in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with commercial device

  47. Quantification of D-dimer in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with commercial device

  48. Quantification of E-selectin in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with commercial device

  49. Quantification of soluble CD 146 in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with commercial device

  50. Quantification of Von Willbrand factor in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with commercial device

  51. Quantification of thrombin-antithrombin complex in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with commercial device

  52. Quantification of prothrombin fragment 1+2 in the circulating blood [ Time Frame: 4 days after ovarian triggering for IVF (first cycle), at the day of embryo transfer of the Day 2 embryos ]
    Venipuncture for blood sampling and exam with commercial device

  53. Quantification of Microparticles subsets from endothelial origin in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with flow cytometry

  54. Quantification of Microparticles subsets from erythrocyte origin in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with flow cytometry

  55. Quantification of Microparticles subsets from leukocyte origin in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with flow cytometry

  56. Quantification of Microparticles subsets from platelet origin in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with flow cytometry

  57. Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with home made device

  58. Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with home made device

  59. Quantification of Fibrin monomer in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with commercial device

  60. Quantification of D-dimer in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with commercial device

  61. Quantification of E-selectin in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with commercial device

  62. Quantification of soluble CD 146 in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with commercial device

  63. Quantification of Von Willbrand factor in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with commercial device

  64. Quantification of thrombin-antithrombin complex in the circulating blood [ Time Frame: 9 days after ovarian triggering for IVF (first cycle), at mid-luteal phase ]
    Venipuncture for blood sampling and exam with commercial device

  65. Quantification of Microparticles subsets from platelet origin in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device

  66. Quantification of Microparticles subsets from endothelial origin in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with flow cytometry

  67. Quantification of Microparticles subsets from erythrocyte origin in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with flow cytometry

  68. Quantification of Microparticles subsets from leukocyte origin in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with flow cytometry

  69. Quantification of Microparticles subsets from platelet origin in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with flow cytometry

  70. Quantification of Tissue Factor-Dependent Procoagulant Activity (MP-TF) in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with home made device

  71. Quantification of Plasmin Generation Capacity (MP-PGC) in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with home made device

  72. Quantification of Fibrin monomer in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device

  73. Quantification of D-dimer in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device

  74. Quantification of E-selectin in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device

  75. Quantification of soluble CD 146 in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device

  76. Quantification of Von Willbrand factor in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device

  77. Quantification of thrombin-antithrombin complex in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device

  78. Quantification of prothrombin fragment 1+2 in the circulating blood [ Time Frame: 16 days after ovarian triggering for IVF (first cycle), at the day of pregnancy test ]
    Venipuncture for blood sampling and exam with commercial device


Biospecimen Retention:   Samples Without DNA
After platelet removal, serum samples will be frozen stored before being processed


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 43 Years   (Adult)
Sexes Eligible for Study:   Female
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.
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.
Layout table for additonal information
Responsible Party: Antoine Torre, Medical Doctor, Poissy-Saint Germain Hospital
ClinicalTrials.gov Identifier: NCT03051230    
Other Study ID Numbers: PREDHSO
First Posted: February 13, 2017    Key Record Dates
Last Update Posted: February 13, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Antoine Torre, Poissy-Saint Germain Hospital:
Blood Coagulation Disorders
Cell-Derived Microparticles
Superovulation
Fertilization in Vitro
Biomarkers
Additional relevant MeSH terms:
Layout table for MeSH terms
Infertility
Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases