Protocol summary

Study aim
Determining the effect of probiotics on fertility in women with recurrent implantation failure based on Th1 to Th2 ratio.
Design
Before administering the drug, heparinized blood is taken from the patients, and PBMC are isolated. Then, flow cytometry technique will be used to count the number of Th1 and Th2 cells. In order to investigate the secretion of cytokines, ELISA will be used. QRT-PCR method will be used to measure transcription factors. After performing these steps according to the protocol, the probiotic dose (2 tablets per day) is adjusted based on the ratio of Th1 to Th2. At this stage and after the treatment protocol, all the factors that were measured before prescribing the drug will be measured again to determine the effects of the probiotic drug on the immune system of the patients. Finally, after 9 months, in order to check the number of babies born by people with RIF, we will continuously monitor the people whose β-HCG test was positive after taking the medicine with the help of gynecologists.
Settings and conduct
The study will be conducted in Valiasr International Hospital, Tabriz. Subjects will receive probiotic pills according to the protocol.
Participants/Inclusion and exclusion criteria
Patients will be selected only from Azerbaijan people. Patients who have experienced at least 3 consecutive implantation failures.
Intervention groups
The studied groups are including 3 groups of patients with RIF who receive probiotics, patients who do not receive any type of treatment despite the history of RIF problem as a control group and a group of healthy women with a history of successful pregnancy and delivery are also considered as a control group.
Main outcome variables
The frequency of Th1 and Th2 cells The expression level of cytokines (IL-4, IL-10,IFNγ ,TNFα) and transcription factors (T-bet و GATA3) Secretory levels of cytokines (IL-4, IL-10,IFNγ ,TNFα) Pregnancy rate

General information

Reason for update
Acronym
RIF
IRCT registration information
IRCT registration number: IRCT20160422027520N20
Registration date: 2023-01-23, 1401/11/03
Registration timing: prospective

Last update: 2023-01-23, 1401/11/03
Update count: 0
Registration date
2023-01-23, 1401/11/03
Registrant information
Name
Mehdi Yousefi
Name of organization / entity
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Country
Iran (Islamic Republic of)
Phone
+98 41 3336 4665
Email address
yousefime@tbzmed.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-02-20, 1401/12/01
Expected recruitment end date
2024-08-22, 1403/06/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The effect of probiotics on fertility in women with recurrent implantation failure based on Th1 to Th2 ratio
Public title
The effect of probiotics on fertility
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Patients from East Azerbaijan Having at least three implantation failures Do not have any type of immunotherapy in their medical history. Having regular menstrual cycles
Exclusion criteria:
Patients under 18 years old and over 41 years old Patients with coagulation problems. Patients with intrauterine anomalies. Having chromosomal abnormalities
Age
From 18 years old to 40 years old
Gender
Female
Phase
2
Groups that have been masked
  • Participant
  • Data analyser
Sample size
Target sample size: 50
Randomization (investigator's opinion)
Randomized
Randomization description
At first, the sample size of 50 patients with RIF that met our inclusion criteria was considered as the total sample size. 'Random allocation rule' method was used for randomization, where numbers were randomly assigned to cards on a random order of one to 50. Even numbers were assigned to the treatment group and odd numbers to the control group (who did not receive any treatment). In this method, the balance will be reached at the end of the study in the number of people assigned to each group. Each card was placed in sealed and opaque envelopes to hide the random assignment.
Blinding (investigator's opinion)
Double blinded
Blinding description
The participants and the person who analyzed the results were blinded in this study. Participants were aware of the study before being randomized and informed consent was obtained from them. It should be noted that the person analyzing the results had no other role in this study.
Placebo
Not used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of Tabriz University of Medical Sciences
Street address
Tabriz University of Medical Sciences , Daneshghah st, Tabriz,
City
Tabriz
Province
East Azarbaijan
Postal code
6446-14155
Approval date
2023-01-21, 1401/11/01
Ethics committee reference number
IR.TBZMED.REC.1401.798

Health conditions studied

1

Description of health condition studied
Recurrent implantation failure
ICD-10 code
N98.9
ICD-10 code description
Complication associated with artificial fertilization, unspecified

Primary outcomes

1

Description
The frequency of Th1 and Th2 cells
Timepoint
Before and after interference
Method of measurement
By using flow cytometry

2

Description
Investigating the expression level of transcription factors T-bet and GATA3
Timepoint
Before and after interference
Method of measurement
By using Quantitative Real time PCR

3

Description
Examining the expression level of cytokines IL-4, IL-10, IFNγ, TNFα
Timepoint
Before and after interference
Method of measurement
By using Quantitative Real time PCR

4

Description
Investigating the secretion of cytokines IL-4, IL-10, IFNγ, TNFα
Timepoint
Before and after interference
Method of measurement
using sandwich ELISA method.

Secondary outcomes

1

Description
Pregnancy rate
Timepoint
After positive beta-hCG test, clinical pregnancy was evaluated at 5-6 week
Method of measurement
Examining the formation of gestational sac using Sonography method

Intervention groups

1

Description
Intervention group: probiotic tablets (2 tablets per day) orally
Category
Treatment - Drugs

2

Description
Control group: receive no intervention
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Infertility center at Valiasr Hospital
Full name of responsible person
Dr. Mehdi Yousefi
Street address
Infertility center at Valiasr Hospital, Aflak-nama Sq, Zaferaniyeh Ave, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
6446-14155
Phone
+98 41 3327 3000
Email
mehdi_yusefi@yahoo.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Mehdi Yousefi
Street address
Tabriz University of Medical Sciences
City
Tabriz
Province
East Azarbaijan
Postal code
6446-14155
Phone
+98 41 3334 9525
Email
mehdi_yusefi@yahoo.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tabriz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Mehdi Yousefi
Position
PhD in Medical Immunology, Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Tabriz University of Medical Sciences , Daneshghah st, Tabriz,
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3336 4665
Email
mehdi_yusefi@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Mehdi Yousefi
Position
PhD in Immunology- Associate professor
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 912 670 3953
Email
mehdi_yusefi@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Sanam Dolati
Position
Assistant Professor of Immunology
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 914 402 5684
Email
sanam.dolati@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
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