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

Recurrent Implantation Failure Clinical Trial

Official title:

Effect of IVIg on Pregnancy Rate of Patient With Recurrent Implantation Failure With Immunological Causes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03174964
• Other study ID #: TabrizUMS-infertility-002
• Status: Completed
• Phase: Phase 2
• Start date: July 20, 2016
• Est. completion date: September 20, 2017

Study information

• Verified date: May 2017
• Source: Tabriz University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 20, 2017
• Est. primary completion date: February 10, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 41 Years

Eligibility

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

Related Conditions & MeSH terms

• Recurrent Implantation Failure

Intervention

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

Locations

Country	Name	City	State
Iran, Islamic Republic of	Alzahra hospital	Tabriz

Sponsors (1)

Lead Sponsor	Collaborator
Tabriz University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (7)

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 — View 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. Epub 2006 Dec 12. Review. — View 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. — View 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. Review. — View 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. Review. — View 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):12 — View 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. 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in NK cells, Treg AndTh17cells frequency.	Flowcytometry	15 day after ET
Primary	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
Primary	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
Primary	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	Fertility rate in patients with recurrent implantation failure (RIF)	By sonography	15 day after ET
Secondary	Fertility rate in patients with recurrent implantation failure (RIF)	By ELISA technique	15 day after ET
Secondary	Live berth rate in patients with recurrent implantation failure (RIF).	Monitoring by gynecologists	up to 1 year