Protocol summary
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Study aim
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1.Evaluate the effect of Tacrolimus on gene expression of P53, IL-10, IL-17 and LIF in endometrial sample
2.Evaluate the effect of Tacrolimus on level of secretion of IL-10, IL-17 and LIF in endometrial fluid
3. Evaluate the effect of Tacrolimus on level of secretion of P53 IL-10, IL-17 and LIF in endometrial sample
4.Evaluate the effect of Tacrolimus on level of u-NK-cell in endometrial sample
5.Evaluate the effect of Tacrolimus on chemical pregnancy rate, implantation rate and live birth rate
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Design
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In this research, as a first phase of study, 7 eligible patients referring to Al-Zahra Hospital were chosen purposefully.Implantation factors in endometrial and uterine fluid were assessed before and after treatment and finally pregnancy outcomes will be reviewed.
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Settings and conduct
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Al-Zahra Hospital
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Participants/Inclusion and exclusion criteria
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patients who have at least three-time implantation failure and normal karyotype and have no anatomical problems, autoimmune disease and clotting disorders and have no history of abortion.
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Intervention groups
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1. Endometrial sample and uterine fluid are taken in the first menstrual cycle
2.prescription of Tacrolimus and endometrial sample and uterine fluid are taken in the second menstrual cycle
3.prescription of Tacrolimus and embryo transfer
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Main outcome variables
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1.Gene expression of P-53, IL-10, IL-17 and LIF in endometrial sample
2. Level of secretion of P-53, IL-10, IL-17 and LIF in endometrial sample
3.Level of u-NK-cell in endometrial sample
4. Chemical pregnancy rate, implantation rate and live birth rate
General information
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Reason for update
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20171007036623N1
Registration date:
2017-11-29, 1396/09/08
Registration timing:
prospective
Last update:
2018-01-12, 1396/10/22
Update count:
1
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Registration date
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2017-11-29, 1396/09/08
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Shahid Beheshti University of Medical Science
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Expected recruitment start date
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2017-12-11, 1396/09/20
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Expected recruitment end date
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2018-04-22, 1397/02/02
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Investigation of gene expression and secretion of P53, LIF, IL_10, IL-17 after administration of tacrolimus in endometrial and uterine fluid in patients with repeated implantation failure: Clinical trial
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Public title
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The Effect of Tacrolimus in patients with recurrent implantation failure
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
History of 3 or more failed IVF/ET cycles with morphologically and developmentally average to good-quality embryo( 7 or more blastomeres and less than 10% fragmentation in day 3 ) into an adequately prepared endometrium (endometrial thickness equal or more than 8 mm); Women who had regular menses (25 to 35 days); Women who had normal karyotype;
women who had at least one of these Immunological disorders in their peripheral blood sample between day of 5 to 10 of menstrual cycle: IFN-g/IL-4 equal or more than 10.3 or Nk-cell percentage greater than 12%
Exclusion criteria:
Present of sub mucosal fibroids, endometrial polyps, intrauterine adhesions, congenital anomalies of uterus or hydrosalpinges
History of active autoimmune disease (With assessment of ANA, Anti-TG, Anti-TPO, Anti-dsDNA); Women with acquired or inherited thrombophilia (With assessment of Factor2, Factor5, Factor 8, Fibrinogen, Anti- Cardiolipin, Anti-Phospholipid Antibody, Lupus Anti-Coagulate, s-MTHFR gene)
Pregnant women; History of miscarriage in a former IVF/ET cycle; Women who received vaccine in the last three months; Women who received steroid hormones in the last 2 months; Women receiving immunotherapy; Women with chronic inflammatory diseases
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Age
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From 20 years old to 50 years old
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Gender
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Female
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Phase
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2
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Groups that have been masked
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No information
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Sample size
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Target sample size:
10
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Randomization (investigator's opinion)
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N/A
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Randomization description
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Blinding (investigator's opinion)
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Not blinded
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Blinding description
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2017-02-28, 1395/12/10
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Ethics committee reference number
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IR.SBMU. MSP.REC.1395. 580
Health conditions studied
1
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Description of health condition studied
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Recurrent Implantation Failure
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ICD-10 code
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N-97.2
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ICD-10 code description
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Female infertility of uterin
Primary outcomes
1
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Description
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Expression of P53 gene
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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qRT-PCR
2
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Description
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Expression of LIF gene
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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qRT-PCR
3
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Description
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Expression of IL-10 gene
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Timepoint
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Measure Twice: before and after treatment
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Method of measurement
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qRT-PCR
4
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Description
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Expression of IL-17 gene
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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qRT-PCR
Secondary outcomes
1
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Description
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LIF protein levels in uterine fluid
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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ELISA
2
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Description
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Level Of IL-10 protein in uterine fluid
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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ELISA
3
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Description
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Level Of IL-17 protein in uterine fluid
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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ELISA
4
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Description
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Biochemical Pregnancy Rate
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Timepoint
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Two weeks after embryo transfer
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Method of measurement
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Level of B-HCG in blood
5
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Description
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Live Birth Rate
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Timepoint
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Nine months after embryo transfer
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Method of measurement
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Number of newborns
6
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Description
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Embryo implantation Rate
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Timepoint
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Two weeks after a chemical pregnancy confirmation
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Method of measurement
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Observation of Pregnancy Sac by Ultrasound
7
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Description
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Blood level of Estradiol
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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Measurement in blood
8
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Description
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Blood level of Progestron
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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Measurement in blood
9
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Description
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P53 protein level in endometrium
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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immunohistochemistry
10
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Description
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LIF protein level in endometrium
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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immunohistochemistry
11
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Description
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IL-10 protein level in endometrium
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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immunohistochemistry
12
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Description
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IL-17 protein level in endometrium
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Timepoint
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Measure twice: before and after treatment
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Method of measurement
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immunohistochemistry
Intervention groups
1
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Description
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Prescription of Tacrolimus in the second menstrual cycle for up to 16 days (until 2 days before second biopsy) with 1-3 mg per day upon on IFN-g/IL-4 ratio:
Prescription of 1 mg per day if this ratio is equal or more than10.3 and less than 13
Prescript
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Category
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Treatment - Drugs
2
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Description
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Prescription of Tacrolimus in third cycle of menstruation from 2 days before embryo transfer until 14 days after embryo transfer for overall 16 days with 1-3 mg per day upon on IFN-g/IL-4 ratio.
Prescription of 1 mg per day if this ratio is equal or mo
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Shahid Beheshti University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Yes - There is a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Yes - There is a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available
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Title and more details about the data/document
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Share with other studies and collaborate with other research and clinical centers to increase the effectiveness of the study
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When the data will become available and for how long
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After the study is completed and 6 months after the results are printed
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To whom data/document is available
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Research Centers and Study Groups of Basic Sciences and Clinical Sciences
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Under which criteria data/document could be used
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It is possible to use the analyzed results after receiving written permission from the executor
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From where data/document is obtainable
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Principal Investigator or corresponding author of study
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What processes are involved for a request to access data/document
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After a written request for the use of results in clinical studies
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Comments
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