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

Sponsor

Centre Hospitalier Universitaire, Amiens (Other)

Overall Status

Recruiting

CT.gov ID

NCT05648136

Collaborator

(none)

150

Enrollment

Location

Arms

Anticipated Duration (Months)

6.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Repeated Embryo Implantation Failure Recurrent Miscarriage Immune System	Biological: blood sample	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Dec 2, 2022

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: patients 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	Biological: blood sample 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
Active Comparator: control 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.	Biological: blood sample 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

Arm

Intervention/Treatment

Experimental: patients

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

Biological: blood sample

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

Active Comparator: control

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.

Biological: blood sample

Outcome Measures

Primary Outcome Measures

Variation of the proportion of CD4+ subpopulations between both patient groups [18 months]
Variation of the proportion of CD8+ subpopulations between both patient groups [18 months]
Variation of the proportion of TH1 subpopulations between both patient groups [18 months]
Variation of the proportion of TH2 subpopulations between both patient groups [18 months]
Variation of the proportion of TH17 subpopulations between both patient groups [18 months]
Variation of the proportion of Treg subpopulations between both patient groups [18 months]
Variation of the proportion of ILC 1 subpopulations between both patient groups [18 months]
Variation of the proportion of ILC 2 subpopulations between both patient groups [18 months]
Variation of the proportion of ILC 3 subpopulations between both patient groups [18 months]
Variation of the proportion of TNFα concentrations between both patient groups [18 months]
Variation of the proportion of IFN gamma concentrations between both patient groups [18 months]
Variation of the proportion of TGF-β concentrations between both patient groups [18 months]
Variation of the proportion of IL-10 concentrations between both patient groups [18 months]
Variation of the proportion of IL-17 concentrations between both patient groups [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 39 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.