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

NCT02967419 | Unknown

• 1 other identifier: TJ-023
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Repeated Implantation Failure

Keywords

Repeated Implantation Failure; TWEAK;Fn14;JAK/STAT3;Indoleamine 2,3-dioxygenase

Outcome Measures

Primary Outcomes (1)

• TWEAK/Fn14, JAK/STAT3 and IDO in Endometrium measured by Western-blot

  11/20/2016-12/30/2017

Study Arms (2)

RIF group

People who were diagnosed as repeated implantation failure after IVF-ET

Other: No Intervention

Control group

People who had normal pregnancy

Other: No Intervention

Interventions

No Intervention OTHER

Control group; RIF group

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The population of RIF is determined when transferred embryos fail to implant following in at least three consecutive IVF attempts, in which 1-2 embryos of high grade quality are transferred in each cycle.

You may qualify if:

• \- 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.

You may not qualify if:

• \- antiphospholipid syndrome (APS), endocrine disorder (diabetes, thyroid dysfunction), genetic disorders, uterine malformations, or any current infections

Sponsors & Collaborators

• ZhangTao: lead

Study Sites (1)

Huazhong University of Science and Technology, Tongji Medicine College, Tongji Hospital, Reproductive Medicine Center

Wuhan, China

Location

Related Publications (18)

• 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.

  PMID: 26777262 BACKGROUND

• 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.

  PMID: 12960317 BACKGROUND

• 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.

  PMID: 22537815 BACKGROUND

• 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.

  PMID: 21249128 BACKGROUND

• 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.

  PMID: 21334074 BACKGROUND

• 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.

  PMID: 25421447 BACKGROUND

• 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.

  PMID: 18336386 BACKGROUND

• 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.

  PMID: 20004376 BACKGROUND

• 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.

  PMID: 14676299 BACKGROUND

• 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.

  PMID: 17948274 BACKGROUND

• 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.

  PMID: 19535644 BACKGROUND

• 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.

  PMID: 23847296 BACKGROUND

• 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.

  PMID: 26814137 BACKGROUND

• 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.

  PMID: 26511909 BACKGROUND

• 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.

  PMID: 15905495 BACKGROUND

• 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.

  PMID: 19414739 BACKGROUND

• 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.

  PMID: 25063873 BACKGROUND

• 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.

  PMID: 25955018 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, serum, white cells, urine, endometrium

Central Study Contacts

Zhang Tao, MD

CONTACT

13349963005; 584605743@qq.com

Study Design

• Study Type: observational
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: postgraduate of Tongji Hospital

Study Record Dates

• First Submitted: November 16, 2016
• First Posted: November 18, 2016
• Study Start: January 1, 2017
• Primary Completion: December 1, 2017
• Study Completion: March 1, 2018
• Last Updated: November 18, 2016

Record last verified: 2016-11

Locations

CN (1)