Clinical trial NCT03174964: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Implantation Failure
Keywords: Recurrent Implantation Failure
IVIg
Pregnancy Rate
Lead sponsor: Tabriz University of Medical Sciences
Sponsor class: OTHER
First posted: 2017-06-05
Enrollment: 50
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Changes in NK cells, Treg AndTh17cells frequency.
timeFrame: 15 day after ET
measure: Changes in secretion levels of cytokines related to Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10)
timeFrame: 15 day after ET
measure: Changes in secretion The amount of Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines.
timeFrame: 15 day after ET
measure: Changes in Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines and related transcription factor
timeFrame: 15 day after ET
Secondary outcomes:
measure: Fertility rate in patients with recurrent implantation failure (RIF)
timeFrame: 15 day after ET
measure: Fertility rate in patients with recurrent implantation failure (RIF)
timeFrame: 15 day after ET
measure: Live berth rate in patients with recurrent implantation failure (RIF).
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Tabriz
country: Iran, Islamic Republic of
facility: Alzahra hospital
Study officials:
affiliation: SCARM institute
name: Mehdi Yousefi, Immunologist
role: STUDY_DIRECTOR
affiliation: Head of SCARM institute
name: Mohammad Nouri, Ph.D
role: STUDY_CHAIR
References:
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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.
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