The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure

Repeated Implantation Failure Clinical Trial

Official title:

The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02967419
• Other study ID #: TJ-023
• Status: Not yet recruiting
• Phase: N/A
• First received: November 16, 2016
• Last updated: November 16, 2016
• Start date: January 2017
• Est. completion date: March 2018

Study information

• Verified date: November 2016
• Source: Tongji Hospital
• Contact: Zhang Tao, MD
• Phone: 13349963005
• Email: 584605743[@]qq.com
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: March 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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 Design

Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Repeated Implantation Failure

Intervention

Other:
• No Intervention

Locations

Country	Name	City	State
China	Huazhong University of Science and Technology, Tongji Medicine College, Tongji Hospital, Reproductive Medicine Center	WuHan City

Sponsors (1)

Lead Sponsor	Collaborator
ZhangTao

Country where clinical trial is conducted

China, 

References & Publications (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. — View Citation

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. — View Citation

Brenk M, Scheler M, Koch S, Neumann J, Takikawa O, Häcker 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. — View Citation

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. — View Citation

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. — View Citation

Hill M, Tanguy-Royer S, Royer P, Chauveau C, Asghar K, Tesson L, Lavainne F, Rémy S, Brion R, Hubert FX, Heslan M, Rimbert M, Berthelot L, Moffett JR, Josien R, Grégoire 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. — View Citation

Lédée N, Petitbarat M, Chevrier L, Vitoux D, Vezmar K, Rahmati M, Dubanchet S, Gahéry 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. — View Citation

Lédée 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. Review. — View Citation

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. — View Citation

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. — View Citation

Mas AE, Petitbarat M, Dubanchet S, Fay S, Ledée 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. — View Citation

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. — View Citation

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. — View Citation

Petitbarat M, Rahmati M, Sérazin V, Dubanchet S, Morvan C, Wainer R, de Mazancourt P, Chaouat G, Foidart JM, Munaut C, Lédée 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. — View Citation

Petitbarat M, Serazin V, Dubanchet S, Wayner R, de Mazancourt P, Chaouat G, Lédée 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. — View Citation

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. — View Citation

Yu J, Wang Y, Yan F, Zhang P, Li H, Zhao H, Yan C, Yan F, Ren X. Noncanonical NF-?B 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. — View Citation

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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TWEAK/Fn14, JAK/STAT3 and IDO in Endometrium measured by Western-blot		11/20/2016-12/30/2017	No