Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Implantation Failure

NCT03174964 | Completed Phase 2 DMC

• 1 other identifier: TabrizUMS-infertility-002
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Implantation Failure

Keywords

Recurrent Implantation Failure; IVIg; Pregnancy Rate

Outcome Measures

Primary Outcomes (4)

• Changes in NK cells, Treg AndTh17cells frequency.

  Flowcytometry

  15 day after ET

• Changes in secretion levels of cytokines related to Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10)

  Elisa

  15 day after ET

• Changes in secretion The amount of Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines.

  Elisa

  15 day after ET

• Changes in Th17 and Treg cells(IL-17,IL-21, TGF-B and IL-10) cytokines and related transcription factor

  RT pcr

  15 day after ET

Secondary Outcomes (3)

• Fertility rate in patients with recurrent implantation failure (RIF)

  15 day after ET

• Fertility rate in patients with recurrent implantation failure (RIF)

  15 day after ET

• Live berth rate in patients with recurrent implantation failure (RIF).

  up to 1 year

Study Arms (2)

Treatment group

EXPERIMENTAL

IVIg group

Drug: IVIg

Control group

NO INTERVENTION

Patients who do not receive any treatment despite a history of Recurrent Implantation Failure problem as controls

Interventions

IVIg DRUG

Patients will take a dose of 400mg/kg of IVIg 2 days before ET.

Treatment group

Eligibility Criteria

• Age: 20 Years - 41 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tabriz University of Medical Sciences: lead

Study Sites (1)

Alzahra hospital

Tabriz, Iran

Location

Related Publications (7)

• 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.

  PMID: 22889462 RESULT

• 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.

  PMID: 19710204 RESULT

• 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.

  PMID: 19819893 RESULT

• 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.

  PMID: 24628478 RESULT

• 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.

  PMID: 12765346 RESULT

• 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.

  PMID: 17166218 RESULT

• 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.

  PMID: 21095154 RESULT

MeSH Terms

Interventions

Immunoglobulins, Intravenous

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mehdi Yousefi, Immunologist

  SCARM institute

  STUDY DIRECTOR

• Mohammad Nouri, Ph.D

  Head of SCARM institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2017
• First Posted: June 5, 2017
• Study Start: July 20, 2016
• Primary Completion: February 10, 2017
• Study Completion: September 20, 2017
• Last Updated: September 17, 2018

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)