Repeated Implantation FailureNCT02967419
The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure
An observational study of Repeated Implantation Failure, run by ZhangTao at 1 site in China.
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). Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Repeated Implantation Failure
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- Jan 2017to Mar 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- antiphospholipid syndrome (APS), endocrine disorder (diabetes, thyroid dysfunction), genetic disorders, uterine malformations, or any current infections
Trial locations and contacts
1 site in 1 country.
China1 site
Huazhong University of Science and Technology, Tongji Medicine College, Tongji Hospital, Reproductive Medicine Center
Wuhan
Zhang Tao, MD, 13349963005, 584605743@qq.com
About this study
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.
Read the 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.
- Conditions
- Repeated Implantation Failure
- Being tested
- No Intervention
- Keywords
- Repeated Implantation Failure; TWEAK;Fn14;JAK/STAT3;Indoleamine 2,3-dioxygenase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No InterventionOther
| Study group | Role | What they receive |
|---|---|---|
| RIF group | People who were diagnosed as repeated implantation failure after IVF-ET Receives: Other: No Intervention | |
| Control group | People who had normal pregnancy Receives: Other: No Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
TWEAK/Fn14, JAK/STAT3 and IDO in Endometrium measured by Western-blot
Measured: 11/20/2016-12/30/2017
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2016 (estimated)
- Study startJan 2017
- Primary completionDec 2017 (estimated)
- Study completionMar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Repeated Implantation FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Cross-sectional
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ZhangTao
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, ZhangTao, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02967419
- Sponsor's protocol ID
- TJ-023
- Status last verified
- Nov 2016
- First submitted
- 16 Nov 2016
- Last updated
- 18 Nov 2016
- Results posted
- No
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.
PubMed 26777262Ashkar 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.
PubMed 12960317Mariee 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.
PubMed 22537815Petitbarat 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.
PubMed 21249128Ledee 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.
PubMed 21334074Lei 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.
PubMed 25421447Mas 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.
PubMed 18336386Petitbarat 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.
PubMed 20004376Chen 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.
PubMed 14676299Hill 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.
PubMed 17948274Brenk 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.
PubMed 19535644Ban 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.
PubMed 23847296Zong 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.
PubMed 26814137Obayashi 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.
PubMed 26511909Orabona 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.
PubMed 15905495
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study of the Relationship Between TWEAK/Fn14, JAK/STAT3 and IDO in the Immune Microenvironment of Endometrium in Repeated Implantation Failure
- ClinicalTrials.gov ID
- NCT02967419
- Acronym / sponsor ID
- TJ-023
- Conditions
- Repeated Implantation Failure
- Keywords
- Repeated Implantation Failure; TWEAK;Fn14;JAK/STAT3;Indoleamine 2,3-dioxygenase
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- ZhangTaoUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 18 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RIF group | – | Other: No InterventionPeople who were diagnosed as repeated implantation failure after IVF-ET |
| Control group | – | Other: No InterventionPeople who had normal pregnancy |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- antiphospholipid syndrome (APS), endocrine disorder (diabetes, thyroid dysfunction), genetic disorders, uterine malformations, or any current infections
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No Intervention | Other | Control group, RIF group |
Primary outcome
TWEAK/Fn14, JAK/STAT3 and IDO in Endometrium measured by Western-blot
Time frame: 11/20/2016-12/30/2017
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2016.
- Background: PubMed 26777262Ledee 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.
- Background: PubMed 12960317Ashkar 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.
- Background: PubMed 22537815Mariee 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.
- Background: PubMed 21249128Petitbarat 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.
- Background: PubMed 21334074Ledee 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.
- Background: PubMed 25421447Lei 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.
- Background: PubMed 18336386Mas 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.
- Background: PubMed 20004376Petitbarat 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.
- Background: PubMed 14676299Chen 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.
- Background: PubMed 17948274Hill 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.
- Background: PubMed 19535644Brenk 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.
- Background: PubMed 23847296Ban 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Repeated Implantation Failure, run by ZhangTao at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zhang Tao, MD (13349963005, 584605743@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TWEAK/Fn14, JAK/STAT3 and IDO in Endometrium measured by Western-blot (time frame: 11/20/2016-12/30/2017). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02967419, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2016.