Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss

Recurrent Pregnancy Loss Clinical Trial

Official title:

Effect of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss With Immunological Causes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03174951
• Other study ID #: TabrizUMS-infertility-003
• Status: Completed
• Phase: Phase 2
• Start date: September 20, 2016
• Est. completion date: June 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

Miscarriage occurs in about 1-2% of human pregnancies and is one of the common pregnancy problems before 12 weeks of pregnancy. Anatomical and chromosomal abnormalities, microbial factors and auto and alloimmune reactions have been speculated to attribute in recurrent miscarriage. Unexplained recurrent miscarriage (URM) is defined as three or more repeated abortions, probably caused by maternal immunological rejection . Given that maternal immune system encounters semi-allogeneic fetus, pregnancy outcome is associated with the interaction between maternal immune system and immuno-regulatory capability of the fetus. Effectiveness of treatment approaches in RM patients has been controversial and remained to be discovered. Immunomodulatory agents such as corticosteroids and allogeneic lymphocyte immunization showed variable success rates in RM patients. Therapeutic effects of IVIG in unexplained RM is controversial and most positive results were obtained from the trials in RM women with cellular immune abnormalities, such as increased NK cell level and/or cytotoxicity, and T cell abnormalities. 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 at the time of positive pregnancy,400 mg/kg IVIG was administered intravenously. Following the first administration, IVIG well given every 4 weeks through 32 weeks of gestation to suppress the immune system in patients with immunological causes of RPL 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: June 20, 2017
• Est. primary completion date: March 10, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 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:

• Our criteria for exclusion of patients from the study include the following:

• 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

• Abortion, Habitual
• Abortion, Spontaneous
• Fetal Death
• Recurrent Pregnancy Loss

Intervention

Drug:
• IVIg
Patients will take 400mg/kg IVIg at the time of positive pregnancy,Following the first administration, IVIG well given every 4 weeks through 32 weeks of gestation.

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, T reg and Th17 cells frequency.	Flowcytometry	up to 8 month of pregnancy
Primary	Changes in secretion levels of cytokines related to Treg and Th17 cells(IL-17,IL-21)	Elisa	up to 8 month of pregnancy
Primary	Changes in exoression of cytokines gene.	RT pcr	up to 8 month of pregnancy
Secondary	Ongoing pregnancy rate in patients with Recurrent Pregnancy Loss (RPL)	by sonography	up to 8 month of pregnancy
Secondary	Live berth rate in patients with Recurrent Pregnancy Loss (RPL).	Monitoring by gynecologists	up to 1 year