Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Implantation Failure
Primary Purpose
Recurrent Implantation Failure
Status
Completed
Phase
Phase 2
Locations
Iran, Islamic Republic of
Study Type
Interventional
Intervention
IVIg
Sponsored by

About this trial
This is an interventional treatment trial for Recurrent Implantation Failure focused on measuring Recurrent Implantation Failure, IVIg, Pregnancy Rate
Eligibility Criteria
Inclusion Criteria:
- Enrolled patients will experience at least 3 times recurrent pregnancy loss.
- Patients dont have history of any type of immunotherapy.
- Patients must have abnormal NK cell or NK cell cytotoxicity or Th1/Th2 ratio
Exclusion Criteria:
- Patients or their spouse has abnormal karyotype or chromosomal and genetically disorders.
- Patients who have bleeding problems.
- Patients who have chronic disorders those are forced to use the specific drug.
- Patients who have positive test for HIV, HCV or HBV infection.
- Patients who have a history of asthma and allergies.
- Patients who have uterus abnormalities
Sites / Locations
- Alzahra hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Treatment group
Control group
Arm Description
IVIg group
Patients who do not receive any treatment despite a history of Recurrent Implantation Failure problem as controls
Outcomes
Primary Outcome Measures
Changes in NK cells, Treg AndTh17cells frequency.
Flowcytometry
Changes in secretion levels of cytokines related to Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10)
Elisa
Changes in secretion The amount of Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines.
Elisa
Changes in Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines and related transcription factor
RT pcr
Secondary Outcome Measures
Fertility rate in patients with recurrent implantation failure (RIF)
By sonography
Fertility rate in patients with recurrent implantation failure (RIF)
By ELISA technique
Live berth rate in patients with recurrent implantation failure (RIF).
Monitoring by gynecologists
Full Information
NCT ID
NCT03174964
First Posted
May 28, 2017
Last Updated
September 13, 2018
Sponsor
Tabriz University of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03174964
Brief Title
Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Implantation Failure
Official Title
Effect of IVIg on Pregnancy Rate of Patient With Recurrent Implantation Failure With Immunological Causes
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
July 20, 2016 (Actual)
Primary Completion Date
February 10, 2017 (Actual)
Study Completion Date
September 20, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tabriz University of Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Infertility and miscarriage ordinary events in reproductive failure in humans, as are affected one couple in every six couples of reproductive age and abortion is including in approximately 15-20% of all pregnancies. Over the decades since the beginning of Assisted Reproductive Technology (ART) and in vitro fertilization (IVF) pregnancy rate still remains below 30% and Recurrent Implantation Failure in one of the most important limiting factor is the assisted reproductive techniques. According to studies conducted in recent years one of the most important mechanisms of implantation failure is maternal immune system because the fetus as an allograft toxic (Semi allograft) to the mother. Studies have demonstrated that ratio of Th1 to Th2 cells increase in maternal peripheral blood cells can be directly associated with implantation failure. It also increases the number of natural killer (NK) cells and Th17 cells and their cytokines in peripheral blood of mother and is also associated with an increased risk of infertility. Several studies have also shown that the fertile persons in compare to infertile have increased amount of Treg cells and inhibitory cytokines associated with it. The studies have shown that if patients are properly selected RIF and placed under appropriate immunotherapy approaches it will be seen a significant increase in fertility. In previous years, followed by the production of intravenous immunoglobulin (IVIg) and determine its effect on immune suppression, IVIg uses for the treatment of various diseases such as thrombocytopenic purpura, Guillain-Barre syndrome, Kawasaki disease and Myasthenia gravis. It is also valuable drug for the treatment of patients with infertility problems have also been used but still remains how well the drug and its mechanism of action are unknown. Probably one of the mechanisms of IVIg is its effect in suppressing the activity of NK cells. Likely IVIg cause to increase Cluster of Differentiation 94 (CD94) molecule as an inhibitor molecule on the NK cells and reduced the cytotoxic activity of NK cells. So because of reduce the cytotoxic activity of NK cells by IVIg in patients with RIF injection increases the likelihood of successful implantation. Previous studies have shown that the incidence of genetic abnormalities in children who have received immunosuppressive drugs such as IVIg like normal people and normal society. In this study we used IVIg before IVF to suppress the immune system in patients with immunological causes of RIF and the results will be compared with a control group that did not receive any type of drug.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Implantation Failure
Keywords
Recurrent Implantation Failure, IVIg, Pregnancy Rate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment group
Arm Type
Experimental
Arm Description
IVIg group
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Patients who do not receive any treatment despite a history of Recurrent Implantation Failure problem as controls
Intervention Type
Drug
Intervention Name(s)
IVIg
Intervention Description
Patients will take a dose of 400mg/kg of IVIg 2 days before ET.
Primary Outcome Measure Information:
Title
Changes in NK cells, Treg AndTh17cells frequency.
Description
Flowcytometry
Time Frame
15 day after ET
Title
Changes in secretion levels of cytokines related to Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10)
Description
Elisa
Time Frame
15 day after ET
Title
Changes in secretion The amount of Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines.
Description
Elisa
Time Frame
15 day after ET
Title
Changes in Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines and related transcription factor
Description
RT pcr
Time Frame
15 day after ET
Secondary Outcome Measure Information:
Title
Fertility rate in patients with recurrent implantation failure (RIF)
Description
By sonography
Time Frame
15 day after ET
Title
Fertility rate in patients with recurrent implantation failure (RIF)
Description
By ELISA technique
Time Frame
15 day after ET
Title
Live berth rate in patients with recurrent implantation failure (RIF).
Description
Monitoring by gynecologists
Time Frame
up to 1 year
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
41 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Enrolled patients will experience at least 3 times recurrent pregnancy loss.
Patients dont have history of any type of immunotherapy.
Patients must have abnormal NK cell or NK cell cytotoxicity or Th1/Th2 ratio
Exclusion Criteria:
Patients or their spouse has abnormal karyotype or chromosomal and genetically disorders.
Patients who have bleeding problems.
Patients who have chronic disorders those are forced to use the specific drug.
Patients who have positive test for HIV, HCV or HBV infection.
Patients who have a history of asthma and allergies.
Patients who have uterus abnormalities
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mehdi Yousefi, Immunologist
Organizational Affiliation
SCARM institute
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Mohammad Nouri, Ph.D
Organizational Affiliation
Head of SCARM institute
Official's Role
Study Chair
Facility Information:
Facility Name
Alzahra hospital
City
Tabriz
Country
Iran, Islamic Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
22889462
Citation
Sugiura-Ogasawara M, Suzuki S, Ozaki Y, Katano K, Suzumori N, Kitaori T. Frequency of recurrent spontaneous abortion and its influence on further marital relationship and illness: the Okazaki Cohort Study in Japan. J Obstet Gynaecol Res. 2013 Jan;39(1):126-31. doi: 10.1111/j.1447-0756.2012.01973.x. Epub 2012 Aug 13.
Results Reference
result
PubMed Identifier
19710204
Citation
Santos MA, Kuijk EW, Macklon NS. The impact of ovarian stimulation for IVF on the developing embryo. Reproduction. 2010 Jan;139(1):23-34. doi: 10.1530/REP-09-0187.
Results Reference
result
PubMed Identifier
19819893
Citation
King K, Smith S, Chapman M, Sacks G. Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage. Hum Reprod. 2010 Jan;25(1):52-8. doi: 10.1093/humrep/dep349. Epub 2009 Oct 9.
Results Reference
result
PubMed Identifier
24628478
Citation
Goring SM, Levy AR, Ghement I, Kalsekar A, Eyawo O, L'Italien GJ, Kasiske B. A network meta-analysis of the efficacy of belatacept, cyclosporine and tacrolimus for immunosuppression therapy in adult renal transplant recipients. Curr Med Res Opin. 2014 Aug;30(8):1473-87. doi: 10.1185/03007995.2014.898140. Epub 2014 Apr 3.
Results Reference
result
PubMed Identifier
12765346
Citation
Yamada H, Morikawa M, Furuta I, Kato EH, Shimada S, Iwabuchi K, Minakami H. Intravenous immunoglobulin treatment in women with recurrent abortions: increased cytokine levels and reduced Th1/Th2 lymphocyte ratio in peripheral blood. Am J Reprod Immunol. 2003 Feb;49(2):84-9. doi: 10.1034/j.1600-0897.2003.01184.x.
Results Reference
result
PubMed Identifier
17166218
Citation
Hutton B, Sharma R, Fergusson D, Tinmouth A, Hebert P, Jamieson J, Walker M. Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review. BJOG. 2007 Feb;114(2):134-42. doi: 10.1111/j.1471-0528.2006.01201.x. Epub 2006 Dec 12.
Results Reference
result
PubMed Identifier
21095154
Citation
Kolls JK, Khader SA. The role of Th17 cytokines in primary mucosal immunity. Cytokine Growth Factor Rev. 2010 Dec;21(6):443-8. doi: 10.1016/j.cytogfr.2010.11.002. Epub 2010 Nov 20.
Results Reference
result
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Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Implantation Failure
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