- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02967419
The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure
The purpose of this study is to find out the possible relationship among TWEAK/Fn14, JAK/STAT3 and IDO as well as their roles in the dysfunction of immune micro-environment of endometrium in people diagnosed as repeated implantation failure after in vitro Fertilization-embryo transfer(IVF-ET).
We will use the technology of Western-blot and Immunohistochemistry to find out the relationship of the expression of TWEAK/Fn14, JAK/STAT3 and IDO in endometrium . Also, we will use technology of Western-blot and Immunohistochemistry to determine whether there are differences of the the expression of TWEAK/Fn14, JAK/STAT3 and IDO in endometrium between RIF group and control group.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The purpose of this study is to find out the possible relationship among TWEAK/Fn14, JAK/STAT3 and IDO as well as their roles in the dysfunction of immune micro-environment of endometrium in people diagnosed as repeated implantation failure after in vitro Fertilization-embryo transfer(IVF-ET).
We will use the technology of Western-blot and Immunohistochemistry to find out the relationship of the expression of TWEAK/Fn14, JAK/STAT3 and IDO in endometrium . Also, we will use technology of Western-blot and Immunohistochemistry to determine whether there are differences of the the expression of TWEAK/Fn14, JAK/STAT3 and IDO in endometrium between RIF group and control group.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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WuHan City, China
- Huazhong University of Science and Technology, Tongji Medicine College, Tongji Hospital, Reproductive Medicine Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Women who had a history of implantation failures in at least three consecutive IVF attempts, in which 1-2 embryos of high grade quality are transferred in each cycle without diagnosis of any specific cause of implantation failure.
Exclusion Criteria:
- antiphospholipid syndrome (APS), endocrine disorder (diabetes, thyroid dysfunction), genetic disorders, uterine malformations, or any current infections
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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RIF group
People who were diagnosed as repeated implantation failure after IVF-ET
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Control group
People who had normal pregnancy
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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TWEAK/Fn14, JAK/STAT3 and IDO in Endometrium measured by Western-blot
Time Frame: 11/20/2016-12/30/2017
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11/20/2016-12/30/2017
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Ledee N, Petitbarat M, Chevrier L, Vitoux D, Vezmar K, Rahmati M, Dubanchet S, Gahery H, Bensussan A, Chaouat G. The Uterine Immune Profile May Help Women With Repeated Unexplained Embryo Implantation Failure After In Vitro Fertilization. Am J Reprod Immunol. 2016 Mar;75(3):388-401. doi: 10.1111/aji.12483. Epub 2016 Jan 18.
- Ashkar AA, Black GP, Wei Q, He H, Liang L, Head JR, Croy BA. Assessment of requirements for IL-15 and IFN regulatory factors in uterine NK cell differentiation and function during pregnancy. J Immunol. 2003 Sep 15;171(6):2937-44. doi: 10.4049/jimmunol.171.6.2937.
- Mariee N, Li TC, Laird SM. Expression of leukaemia inhibitory factor and interleukin 15 in endometrium of women with recurrent implantation failure after IVF; correlation with the number of endometrial natural killer cells. Hum Reprod. 2012 Jul;27(7):1946-54. doi: 10.1093/humrep/des134. Epub 2012 Apr 26.
- Petitbarat M, Rahmati M, Serazin V, Dubanchet S, Morvan C, Wainer R, de Mazancourt P, Chaouat G, Foidart JM, Munaut C, Ledee N. TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. PLoS One. 2011 Jan 7;6(1):e14497. doi: 10.1371/journal.pone.0014497.
- Ledee N, Petitbarat M, Rahmati M, Dubanchet S, Chaouat G, Sandra O, Perrier-d'Hauterive S, Munaut C, Foidart JM. New pre-conception immune biomarkers for clinical practice: interleukin-18, interleukin-15 and TWEAK on the endometrial side, G-CSF on the follicular side. J Reprod Immunol. 2011 Mar;88(2):118-23. doi: 10.1016/j.jri.2011.01.007. Epub 2011 Feb 18.
- Lei M, Qin L, Wang A, Jin Y, Zhao X, Qi X. Fn14 receptor appears as a modulator of ovarian steroid-related regulation of goat endometrial epithelial cell IL-18 expression. Am J Reprod Immunol. 2015 May;73(5):428-36. doi: 10.1111/aji.12343. Epub 2014 Nov 24.
- Mas AE, Petitbarat M, Dubanchet S, Fay S, Ledee N, Chaouat G. Immune regulation at the interface during early steps of murine implantation: involvement of two new cytokines of the IL-12 family (IL-23 and IL-27) and of TWEAK. Am J Reprod Immunol. 2008 Apr;59(4):323-38. doi: 10.1111/j.1600-0897.2007.00567.x.
- Petitbarat M, Serazin V, Dubanchet S, Wayner R, de Mazancourt P, Chaouat G, Ledee N. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible-14 might regulate the effects of interleukin 18 and 15 in the human endometrium. Fertil Steril. 2010 Aug;94(3):1141-3. doi: 10.1016/j.fertnstert.2009.10.049. Epub 2009 Dec 11.
- Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003 Dec 15;198(12):1875-86. doi: 10.1084/jem.20030152.
- Hill M, Tanguy-Royer S, Royer P, Chauveau C, Asghar K, Tesson L, Lavainne F, Remy S, Brion R, Hubert FX, Heslan M, Rimbert M, Berthelot L, Moffett JR, Josien R, Gregoire M, Anegon I. IDO expands human CD4+CD25high regulatory T cells by promoting maturation of LPS-treated dendritic cells. Eur J Immunol. 2007 Nov;37(11):3054-62. doi: 10.1002/eji.200636704.
- Brenk M, Scheler M, Koch S, Neumann J, Takikawa O, Hacker G, Bieber T, von Bubnoff D. Tryptophan deprivation induces inhibitory receptors ILT3 and ILT4 on dendritic cells favoring the induction of human CD4+CD25+ Foxp3+ T regulatory cells. J Immunol. 2009 Jul 1;183(1):145-54. doi: 10.4049/jimmunol.0803277. Epub 2009 Jun 17.
- Ban Y, Chang Y, Dong B, Kong B, Qu X. Indoleamine 2,3-dioxygenase levels at the normal and recurrent spontaneous abortion fetal-maternal interface. J Int Med Res. 2013 Aug;41(4):1135-49. doi: 10.1177/0300060513487642. Epub 2013 Jul 11.
- Zong S, Li C, Luo C, Zhao X, Liu C, Wang K, Jia W, Bai M, Yin M, Bao S, Guo J, Kang J, Duan T, Zhou Q. Dysregulated expression of IDO may cause unexplained recurrent spontaneous abortion through suppression of trophoblast cell proliferation and migration. Sci Rep. 2016 Jan 27;6:19916. doi: 10.1038/srep19916.
- Obayashi Y, Ozaki Y, Goto S, Obayashi S, Suzumori N, Ohyama F, Tone S, Sugiura-Ogasawara M. Role of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase in Patients with Recurrent Miscarriage. Am J Reprod Immunol. 2016 Jan;75(1):69-77. doi: 10.1111/aji.12434. Epub 2015 Oct 29.
- Orabona C, Belladonna ML, Vacca C, Bianchi R, Fallarino F, Volpi C, Gizzi S, Fioretti MC, Grohmann U, Puccetti P. Cutting edge: silencing suppressor of cytokine signaling 3 expression in dendritic cells turns CD28-Ig from immune adjuvant to suppressant. J Immunol. 2005 Jun 1;174(11):6582-6. doi: 10.4049/jimmunol.174.11.6582.
- Sun Y, Chin YE, Weisiger E, Malter C, Tawara I, Toubai T, Gatza E, Mascagni P, Dinarello CA, Reddy P. Cutting edge: Negative regulation of dendritic cells through acetylation of the nonhistone protein STAT-3. J Immunol. 2009 May 15;182(10):5899-903. doi: 10.4049/jimmunol.0804388.
- Yu J, Wang Y, Yan F, Zhang P, Li H, Zhao H, Yan C, Yan F, Ren X. Noncanonical NF-kappaB activation mediates STAT3-stimulated IDO upregulation in myeloid-derived suppressor cells in breast cancer. J Immunol. 2014 Sep 1;193(5):2574-86. doi: 10.4049/jimmunol.1400833. Epub 2014 Jul 25.
- Campia I, Buondonno I, Castella B, Rolando B, Kopecka J, Gazzano E, Ghigo D, Riganti C. An Autocrine Cytokine/JAK/STAT-Signaling Induces Kynurenine Synthesis in Multidrug Resistant Human Cancer Cells. PLoS One. 2015 May 8;10(5):e0126159. doi: 10.1371/journal.pone.0126159. eCollection 2015.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- TJ-023
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