Protocol summary
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Study aim
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Providing a new treatment for patients with repeated implantation failure
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Design
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A clinical trial with 3 groups including control and platelet-rich plasma and mononuclear cells isolated from peripheral blood intervention groups, double-blind, randomized using a box of colored cards, will be conducted in phase 3 and on 96 patients.
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Settings and conduct
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This Triple-blinded study is conducted on patients with recurrent implantation failure referred to the Qom Jihad daneshgahi Infertility Treatment Center. Two days before embryo transfer, patients receive platelet-rich plasma or mononuclear cells isolated from peripheral blood intervention in order to compare their effect on embryo implantation rate. In this study, patients and doctors are not aware of the type of received intervention.
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Participants/Inclusion and exclusion criteria
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Inclusion criteria: at least 2 implantation failures in IVF/ICSI; primary infertility; endometrial thickness less than 6 mm at the time of ovulation induction; age less than 40 years; regular menstrual cycles; body mass index <30; absence of uterine pathology and infection; unexplained infertility; tubular infertility
Exclusion criteria: polycystic ovary syndrome, uterine pathology, referring due to male infertility, presence of hydrosalpinx, presence of endometriosis.
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Intervention groups
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Patients are divided into 3 groups control, PRP, and mononuclear cells from peripheral blood intervention. The control group receives no treatment before embryo transfer, while 2 days before embryo transfer in the other two groups, PRP and mononuclear cells from peripheral blood will be injected into the uterine cavity by catheter.
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Main outcome variables
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Biochemical pregnancy; clinical pregnancy
General information
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Reason for update
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Corrections
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20221010056132N1
Registration date:
2022-10-31, 1401/08/09
Registration timing:
prospective
Last update:
2024-09-28, 1403/07/07
Update count:
3
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Registration date
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2022-10-31, 1401/08/09
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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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Expected recruitment start date
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2022-11-06, 1401/08/15
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Expected recruitment end date
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2024-01-05, 1402/10/15
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Actual recruitment start date
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2022-11-11, 1401/08/20
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Actual recruitment end date
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2023-12-06, 1402/09/15
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Trial completion date
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2024-03-05, 1402/12/15
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Scientific title
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The comparison of intra-uterine injection of autologous lymphocyte and platelet-rich plasma on the pregnancy rate in women with recurrent implantation failure
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Public title
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The effect of intra-uterine injection of autologous lymphocyte and platelet-rich plasma on the pregnancy rate
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Experience at least 2 implantation failures in IVF/ICSI
Primary infertility
Endometrial thickness less than 6 mm at the time of ovulation induction
Age less than 40 years
Regular menstrual cycles
Body mass index<30
Absence of uterine pathology and infection
unexplained infertility
Infertility with tubal causes
Exclusion criteria:
Polycystic ovary syndrome
Uterine pathology
Referring due to male infertility
Presence of hydrosalpinx
Presence of endometriosis.
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Age
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To 40 years old
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Gender
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Female
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Phase
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3
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Groups that have been masked
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- Participant
- Care provider
- Data analyser
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Sample size
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Target sample size:
96
Actual sample size reached:
96
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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The way of randomization is that 96 colored cards with white, blue, and red colors - 32 of each - are placed in a box. After accepting each patient and obtaining informed consent, the specialist randomly takes one of the colored cards inside the box (without seeing the contents of the box) and in this way, they are classified into different groups. So the white color will represent the control group, the blue color will represent the lymphocyte therapy group, and the red color will represent the PRP therapy group. The control group receives the embryos formed after IVF/ICSI treatment without any other special treatment. The red and blue groups receive PRP and PBMC intervention as an intra-uterine injection 2 days before embryo transfer, respectively, in order to investigate the effect of PRP and PBMC on embryo implantation.
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Blinding (investigator's opinion)
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Triple blinded
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Blinding description
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The method of blinding will be in such a way that the patient is unaware of the type of treatment she will receive and since the doctor who puts the patient in the cycle, the doctor who performs lymphocyte therapy or PRP therapy, and finally, the doctor who carries out the embryo transfer are different people, the embryo transfer is done without knowing about the treatment that the patient has done two days before the transfer so that knowing this issue does not affect the way of their embryo transfer. It should be noted that none of the mentioned doctors will do the statistical analysis of the obtained data and the statistical analysis will be done by another researcher who is unaware of the type of treatment received by the different groups.
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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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2019-11-17, 1398/08/26
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Ethics committee reference number
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IR.ACECR.REC.1398.002
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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Z35.0
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ICD-10 code description
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Supervision of pregnancy with history of infertility
Primary outcomes
1
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Description
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Biochemical pregnancy: through a quantitative beta-human chorionic gonadotropin pregnancy test.
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Timepoint
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2 weeks after embryo transfer
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Method of measurement
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Quantitative beta-human chorionic gonadotropin pregnancy test
2
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Description
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Clinical pregnancy: pregnancy confirmed by high levels of human chorionic gonadotropin-beta and ultrasound confirmation of pregnancy sac or heartbeat.
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Timepoint
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Three to five weeks after embryo transfer
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Method of measurement
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Vaginal ultrasound
Intervention groups
1
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Description
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Control group: transfer of embryos in this group of patients with recurrent implantation failure after being placed in the cycle of ovarian induction, is done without any intervention.
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Category
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Treatment - Other
2
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Description
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Intervention group 1: in this group of patients with recurrent implantation failure, intrauterine platelet-rich plasma PRP is injected two days before embryo transfer. On the day of injection, about 10 ml of peripheral venous blood is drawn into a syringe containing 2.5 ml of citric acid anticoagulant solution and immediately centrifuged for 10-12 minutes at 1700 rpm to separate red blood cells. Then the plasma is centrifuged again at 3800 rpm for 7 minutes to obtain PRP, which contains 4-5 times more platelets than peripheral blood. 1 ml of the resulting PRP is injected into the uterine cavity with a transfer catheter.
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Category
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Treatment - Other
3
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Description
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Intervention group 2: A 3 ml blood sample is collected from RIF patients undergoing ART cycles on the day of ovulation induction and placed in citrated tubes to perform a separation based on the Ficoll solution. A separate layer of PBMC will appear under the median plasma after centrifugation at 18–20°C for 30–40 minutes at 400 g. The PBMC milky layer was transferred to another tube and washed twice with phosphate-buffered saline through centrifugation at 60–100 g for 10 minutes. The pellet was then resuspended in RPMI culture media with 75 IU of human menopausal gonadotropin (hMG) at 37°C. Two days before embryo transfer which coincided with 72 hours of incubation of PBMCs resulted in the development of cell clusters, 1–1.5× 10^6 cells in 0.5 ml medium were transferred into the endometrial cavity.
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Category
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Treatment - Other
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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Iranian academic center for education culture and research
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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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Private
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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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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be 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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Undecided - It is not yet known if there will be 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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Only part of the data, such as the main outcome information, can be published
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When the data will become available and for how long
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The access period starts after the publication of the results
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To whom data/document is available
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It will be available only to researchers working in academic and scientific institutions
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Under which criteria data/document could be used
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The data can only be used to inspire related studies for researchers, and the method of access is to send a request through an email address.
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From where data/document is obtainable
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The responsible person will be the project manager at the email address leilanasery48@gmail.com.
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What processes are involved for a request to access data/document
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3 months
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Comments
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