The comparison of intra-uterine injection of autologous lymphocyte and platelet-rich plasma on the pregnancy rate in women with recurrent implantation failure
Providing a new treatment for patients with repeated implantation failure
Design
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 90 patients.
Settings and conduct
This double-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.
Participants/Inclusion and exclusion criteria
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.
Intervention groups
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.
The comparison of intra-uterine injection of autologous lymphocyte and platelet-rich plasma on the pregnancy rate in women with recurrent implantation failure
Public title
The effect of intra-uterine injection of autologous lymphocyte and platelet-rich plasma on the pregnancy rate
Purpose
Treatment
Inclusion/Exclusion criteria
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.
Age
To 40 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Care provider
Data analyser
Sample size
Target sample size:
90
Randomization (investigator's opinion)
Randomized
Randomization description
The way of randomization is that 105 colored cards with white, blue, and red colors - 35 of each - are placed in a box. After accepting each patient and after 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 that 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. While 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.
Blinding (investigator's opinion)
Double blinded
Blinding description
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.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Iranian academic center for education, culture and research
Street address
Secretariat of Ethics in Academic Jihad Research, Research and Technology Vice-Chancellor, No. 1270, In front of the main door of Tehran University, Enghelab st, Tehran
City
Tehran
Province
Tehran
Postal code
1314744513
Approval date
2019-11-17, 1398/08/26
Ethics committee reference number
IR.ACECR.REC.1398.002
Health conditions studied
1
Description of health condition studied
Recurrent implantation failure
ICD-10 code
Z35.0
ICD-10 code description
Supervision of pregnancy with history of infertility
Primary outcomes
1
Description
Biochemical pregnancy: through a quantitative beta-human chorionic gonadotropin pregnancy test assessed 9 days after 3-day embryo transfer and 7 days after blastocyst transfer.
Timepoint
9 days after 3-day embryo transfer and 7 days after blastocyst transfer
Method of measurement
quantitative beta-human chorionic gonadotropin pregnancy test
2
Description
Clinical pregnancy: pregnancy confirmed by high levels of human chorionic gonadotropin-beta and ultrasound confirmation of pregnancy sac or heartbeat.
Timepoint
Four to five weeks after embryo transfer
Method of measurement
Vaginal ultrasound
3
Description
Implantation rate: calculated as the number of gestational sacs/the number of transferred embryos, where gestational sacs is the number of gestational sacs observed at vaginal ultrasound 3–5 weeks after transfer and the number of transferred embryos is the number of transferred embryos.
Timepoint
Four to five weeks after embryo transfer
Method of measurement
calculating the number of gestational sacs/the number of transferred embryos
Secondary outcomes
empty
Intervention groups
1
Description
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.
Category
Treatment - Other
2
Description
Intervention group: 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 20 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. 0.5 ml of the resulting PRP is injected into the uterine cavity with a transfer catheter.
Category
Treatment - Other
3
Description
Intervention group: in this group of patients with recurrent implantation failure, mononuclear cells isolated from peripheral blood (PBMC) are intra-uterine injected two days before embryo transfer. Blood samples are taken from patients on the day of ovulation induction and collected in citrate tubes in a volume of 3 ml for separation with Ficol solution. After centrifugation at 400 g for 30-40 min at 18-20 °C, a distinct layer of PBMC is obtained under the plasma medium. The PBMC layer was transferred to another tube and 3 volumes of phosphate buffer saline (PBS) were added to it, and then centrifuged at 60-100 g for 10 minutes at 18-20°C to obtain a cell pellet. The lymphocyte pellet was washed 2 times with PBS, and then cultured at 37°C. 72 hours after incubation and 2 days before embryo transfer, one million cells in 0.5 ml culture medium are transferred to the endometrial cavity.
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Highly Specialized Infertility Treatment Center of Qom Jihad Daneshgahi
Full name of responsible person
Leila Naserpour
Street address
Highly Specialized Infertility Treatment Center of Qom Jihad Daneshgahi, Shabnam st, Isar Sq, Shahid Karimi Blvd
City
Qom
Province
Ghoum
Postal code
3713189934
Phone
+98 25 3270 0155
Fax
+98 25 3270 0154
Email
leilanasery48@gmail.com
Web page address
https://www.rooyaivf.ir/fa/?page_id=1849
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Leila Naserpour
Street address
Central Building of Jihad Academic Qom Province Branch, Jihad Academic Alley, Safashehr St.
City
Qom
Province
Ghoum
Postal code
3716986466
Phone
+98 25 3285 9856
Email
leilanasery48@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Iranian academic center for education culture and research
Proportion provided by this source
100
Public or private sector
Private
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
Iranian academic center for education culture and research
Full name of responsible person
Leila Naserpour
Position
Instructor
Latest degree
Ph.D.
Other areas of specialty/work
Reproductive Biology
Street address
Central Building of Jihad Academic Qom Province Branch, Jihad Academic Alley, Safashehr St.
City
Qom
Province
Ghoum
Postal code
3716986466
Phone
+98 25 3285 9856
Email
leilanasery48@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Azar Sheikholeslami
Position
Assistant professor
Latest degree
Ph.D.
Other areas of specialty/work
Gynecology and Obstetrics
Street address
Central Building of Jihad Academic Qom Province Branch, Jihad Academic Alley, Safashehr St.
City
Qom
Province
Ghoum
Postal code
3716986466
Phone
+98 25 3285 9856
Email
azareslami10@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Hoda Fazaeli
Position
Instructor
Latest degree
Ph.D.
Other areas of specialty/work
Developmental biology
Street address
Central Building of Jihad Academic Qom Province Branch, Jihad Academic Alley, Safashehr St.
City
Qom
Province
Ghoum
Postal code
3716986466
Phone
+98 25 3285 9856
Email
hodafazaely@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is 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
Yes - There is 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
Title and more details about the data/document
Only part of the data, such as the main outcome information, can be published
When the data will become available and for how long
The access period starts after the publication of the results
To whom data/document is available
It will be available only to researchers working in academic and scientific institutions
Under which criteria data/document could be used
E-mail the project manager and get permission
From where data/document is obtainable
Qom Jihad Daneshgahi
What processes are involved for a request to access data/document