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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment group | Experimental | IVIg group |
|
| control group | No Intervention | Patients who do not receive any treatment despite a history of Recurrent Pregnancy Loss problem as controls |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IVIg | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in NK cells, T reg and Th17 cells frequency. | Flowcytometry | up to 8 month of pregnancy |
| Changes in secretion levels of cytokines related to Treg and Th17 cells(IL-17,IL-21) | Elisa | up to 8 month of pregnancy |
| Changes in exoression of cytokines gene. | RT pcr | up to 8 month of pregnancy |
| Measure | Description | Time Frame |
|---|---|---|
| Ongoing pregnancy rate in patients with Recurrent Pregnancy Loss (RPL) | by sonography | up to 8 month of pregnancy |
| Live berth rate in patients with Recurrent Pregnancy Loss (RPL). | Monitoring by gynecologists |
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Inclusion Criteria:
Exclusion Criteria:
- Our criteria for exclusion of patients from the study include the following:
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| Name | Affiliation | Role |
|---|---|---|
| Mohammad Nouri, Ph.D | Head of SCARM institute | Study Chair |
| Mehdi Yousefi, Immunologist | SCARM institute | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alzahra hospital | Tabriz | Iran |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22889462 | Result | 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. | |
| 19710204 | Result |
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| ID | Term |
|---|---|
| D016756 | Immunoglobulins, Intravenous |
| ID | Term |
|---|---|
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| up to 1 year |
| 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. |
| 19819893 | 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. |
| 24628478 | 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. |
| 12765346 | 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. |
| 17166218 | 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. |
| 21095154 | 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. |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |