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Immune Profile Analysis and Biomarker Identification in Women With Repeated Implantation Failure or Unexplained Recurrent Spontaneous Miscarriage (ERIM)

Primary Purpose

Repeated Embryo Implantation Failure, Recurrent Miscarriage, Immune System

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
blood sample
Sponsored by
Centre Hospitalier Universitaire, Amiens
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Repeated Embryo Implantation Failure focused on measuring repeated embryo implantation failure, recurrent spontaneous miscarriage, immunological analysis, immune system

Eligibility Criteria

18 Years - 39 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria: For patients : Women aged 18 to 39 years women with a history of RIF or unexplained RM women with a negative diagnostic work-up (including pelvic ultrasound and hysteroscopy, parental karyotype, thyroid function test, and anti-thyroid and anti-phospholipid antibodies) women with a basal FSH level <10IU/l and AMH level >1.5ng/ml women with a regular menstrual cycle of 30+/-5 days women receiving a new cycle of in vitro fertilization (IVF) +/- intracytoplasmic sperm injection (ICSI) for patients in the RIF group or a first cycle of IVF +/-ICSI for patients in the RM group women received written and oral information and signed an informed consent For control groups: Controls recruited in the Obstetrics and Gynecology Department with at least one live birth after a spontaneous pregnancy (with a time to conception of less than 12 months for each pregnancy) Voluntary oocyte donors recruited within the CECOS de Picardie (having presented at least one live birth with a delay necessary to conceive of less than 12 months) Controls recruited in the Reproductive Medicine and Biology Department having presented at least one live birth (spontaneous with a delay to conceive of less than 12 months for each pregnancy or after one or two MPA procedures) and benefiting from an IVF+/-ICSI procedure for secondary infertility Controls recruited in the department of Medicine and Reproductive Biology with a normal infertility assessment and benefiting from an IVF procedure with ICSI on male indication. Exclusion Criteria: Ongoing pelvic and/or systemic infection Chronic infectious endometritis Active neoplasia Autoimmune and autoinflammatory disease Celiac disease Thrombophilia (including positive anti-phospholipid antibodies) Endocrine pathology (including dysthyroidism and diabetes) Endometriosis Polycystic ovary syndrome and ovulatory disorders Premature ovarian failure IVF by oocyte donation Tubal obstructions or lesions, uterine and cervical anomalies Partners with extreme oligoastheno-spermia and/or sperm DNA fragmentation >30 Sperm donations Patients unable to give informed consent

Sites / Locations

  • Centre Hospitalier Universitaire d'AmiensRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

patients

control

Arm Description

Women aged 18 to 39 years with a history of RIF or unexplained RM with a negative diagnostic work-up (including pelvic ultrasound and hysteroscopy, parental karyotype, thyroid function test, and anti-thyroid and anti-phospholipid antibodies) with a basal FSH level <10IU/l and AMH level >1.5ng/ml with a regular menstrual cycle of 30+/-5 days receiving a new cycle of in vitro fertilization (IVF) +/- intracytoplasmic sperm injection (ICSI) for patients in the RIF group or a first cycle of IVF +/-ICSI for patients in the RM group received written and oral information and signed an informed consent

Controls recruited in the Obstetrics and Gynecology Department with at least one live birth after a spontaneous pregnancy (with a time to conception of less than 12 months for each pregnancy) Voluntary oocyte donors recruited within the CECOS de Picardie (having presented at least one live birth with a delay necessary to conceive of less than 12 months) Controls recruited in the Reproductive Medicine and Biology Department having presented at least one live birth (spontaneous with a delay to conceive of less than 12 months for each pregnancy or after one or two MPA procedures) and benefiting from an IVF+/-ICSI procedure for secondary infertility Controls recruited in the department of Medicine and Reproductive Biology with a normal infertility assessment and benefiting from an IVF procedure with ICSI on male indication.

Outcomes

Primary Outcome Measures

Variation of the proportion of CD4+ subpopulations between both patient groups
Variation of the proportion of CD8+ subpopulations between both patient groups
Variation of the proportion of TH1 subpopulations between both patient groups
Variation of the proportion of TH2 subpopulations between both patient groups
Variation of the proportion of TH17 subpopulations between both patient groups
Variation of the proportion of Treg subpopulations between both patient groups
Variation of the proportion of ILC 1 subpopulations between both patient groups
Variation of the proportion of ILC 2 subpopulations between both patient groups
Variation of the proportion of ILC 3 subpopulations between both patient groups
Variation of the proportion of TNFα concentrations between both patient groups
Variation of the proportion of IFN gamma concentrations between both patient groups
Variation of the proportion of TGF-β concentrations between both patient groups
Variation of the proportion of IL-10 concentrations between both patient groups
Variation of the proportion of IL-17 concentrations between both patient groups

Secondary Outcome Measures

Full Information

First Posted
December 5, 2022
Last Updated
December 5, 2022
Sponsor
Centre Hospitalier Universitaire, Amiens
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1. Study Identification

Unique Protocol Identification Number
NCT05648136
Brief Title
Immune Profile Analysis and Biomarker Identification in Women With Repeated Implantation Failure or Unexplained Recurrent Spontaneous Miscarriage
Acronym
ERIM
Official Title
Immune Profile Analysis and Biomarker Identification in Women With Repeated Implantation Failure or Unexplained Recurrent Spontaneous Miscarriage
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 2, 2022 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire, Amiens

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Implantation is a determining step in human reproduction which requires the transition from a pro-inflammatory state to an anti-inflammatory state allowing the implantation of a competent embryo within a receptive endometrium, and then the maternal immunotolerance towards the alloantigenic fetus. Repeat implantation failures (RIFs), that refers to the fail to achieve a clinical pregnancy after the transfer of at least 3-4 good quality embryos or two blastocysts, and unexplained recurrent spontaneous miscarriage (RM) (≥2-3) could be related in some patients to immune imbalances characterized by an excessive and prolonged inflammatory response and/or a defect of anti-inflammatory regulation. In this context, several therapies have been evaluated in patients with RIFs or RMs in order to restore the immune balance, with heterogeneous results. No serum biomarker assay has been routinely approved to identify patients with immune imbalances that may explain repeated pregnancy failures and to predict the success of the subsequent IVF/ICSI cycle. The immunological analysis on peripheral blood will be based on the determination of the proportions of immune subpopulations (e.g. CD4+ et CD8+, TH1, TH2, TH17, Treg, ILC 1, ILC2, and ILC3) on the one hand and the circulating level of plasma cytokines on the other hand.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Repeated Embryo Implantation Failure, Recurrent Miscarriage, Immune System
Keywords
repeated embryo implantation failure, recurrent spontaneous miscarriage, immunological analysis, immune system

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
patients
Arm Type
Experimental
Arm Description
Women aged 18 to 39 years with a history of RIF or unexplained RM with a negative diagnostic work-up (including pelvic ultrasound and hysteroscopy, parental karyotype, thyroid function test, and anti-thyroid and anti-phospholipid antibodies) with a basal FSH level <10IU/l and AMH level >1.5ng/ml with a regular menstrual cycle of 30+/-5 days receiving a new cycle of in vitro fertilization (IVF) +/- intracytoplasmic sperm injection (ICSI) for patients in the RIF group or a first cycle of IVF +/-ICSI for patients in the RM group received written and oral information and signed an informed consent
Arm Title
control
Arm Type
Active Comparator
Arm Description
Controls recruited in the Obstetrics and Gynecology Department with at least one live birth after a spontaneous pregnancy (with a time to conception of less than 12 months for each pregnancy) Voluntary oocyte donors recruited within the CECOS de Picardie (having presented at least one live birth with a delay necessary to conceive of less than 12 months) Controls recruited in the Reproductive Medicine and Biology Department having presented at least one live birth (spontaneous with a delay to conceive of less than 12 months for each pregnancy or after one or two MPA procedures) and benefiting from an IVF+/-ICSI procedure for secondary infertility Controls recruited in the department of Medicine and Reproductive Biology with a normal infertility assessment and benefiting from an IVF procedure with ICSI on male indication.
Intervention Type
Biological
Intervention Name(s)
blood sample
Intervention Description
Blood sampling by venipuncture will be performed : for patients and controls: between the 20th and 24th day of the menstrual cycle (implantation window) preceding the following IVF+/-ICSI cycle for patients receiving an endometrial biopsy: on the same day as the endometrial biopsy for patients and controls receiving follicular stimulation for ovarian puncture: the day of the oocyte puncture for patients and controls undergoing embryo transfer: on the day of embryo implantation
Primary Outcome Measure Information:
Title
Variation of the proportion of CD4+ subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of CD8+ subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of TH1 subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of TH2 subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of TH17 subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of Treg subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of ILC 1 subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of ILC 2 subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of ILC 3 subpopulations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of TNFα concentrations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of IFN gamma concentrations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of TGF-β concentrations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of IL-10 concentrations between both patient groups
Time Frame
18 months
Title
Variation of the proportion of IL-17 concentrations between both patient groups
Time Frame
18 months

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
pregnancy
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: For patients : Women aged 18 to 39 years women with a history of RIF or unexplained RM women with a negative diagnostic work-up (including pelvic ultrasound and hysteroscopy, parental karyotype, thyroid function test, and anti-thyroid and anti-phospholipid antibodies) women with a basal FSH level <10IU/l and AMH level >1.5ng/ml women with a regular menstrual cycle of 30+/-5 days women receiving a new cycle of in vitro fertilization (IVF) +/- intracytoplasmic sperm injection (ICSI) for patients in the RIF group or a first cycle of IVF +/-ICSI for patients in the RM group women received written and oral information and signed an informed consent For control groups: Controls recruited in the Obstetrics and Gynecology Department with at least one live birth after a spontaneous pregnancy (with a time to conception of less than 12 months for each pregnancy) Voluntary oocyte donors recruited within the CECOS de Picardie (having presented at least one live birth with a delay necessary to conceive of less than 12 months) Controls recruited in the Reproductive Medicine and Biology Department having presented at least one live birth (spontaneous with a delay to conceive of less than 12 months for each pregnancy or after one or two MPA procedures) and benefiting from an IVF+/-ICSI procedure for secondary infertility Controls recruited in the department of Medicine and Reproductive Biology with a normal infertility assessment and benefiting from an IVF procedure with ICSI on male indication. Exclusion Criteria: Ongoing pelvic and/or systemic infection Chronic infectious endometritis Active neoplasia Autoimmune and autoinflammatory disease Celiac disease Thrombophilia (including positive anti-phospholipid antibodies) Endocrine pathology (including dysthyroidism and diabetes) Endometriosis Polycystic ovary syndrome and ovulatory disorders Premature ovarian failure IVF by oocyte donation Tubal obstructions or lesions, uterine and cervical anomalies Partners with extreme oligoastheno-spermia and/or sperm DNA fragmentation >30 Sperm donations Patients unable to give informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amandine Dernoncourt, DR
Phone
03. 22. 66. 82. 30
Email
dernoncourt.amandine@chu-amiens.fr
Facility Information:
Facility Name
Centre Hospitalier Universitaire d'Amiens
City
Amiens
State/Province
Picardie
ZIP/Postal Code
80000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amandine Dernoncourt, DR
Phone
03. 22. 66. 82. 30
Email
dernoncourt.amandine@chu-amiens.fr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Immune Profile Analysis and Biomarker Identification in Women With Repeated Implantation Failure or Unexplained Recurrent Spontaneous Miscarriage

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