Protocol summary
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Study aim
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Determining the effect of endometrial scratching on the expression of angiogenic and anti-angiogenic growth factors
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Design
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A randomized clinical trial with control group, double blind, and two arm parallel group design of 20 patients. Randomization is performed using a computer-generated random assignment schedule for each patient. Sealed and numbered envelopes are used to conceal the treatment allocation until randomization.
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Settings and conduct
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Using a pipelle, endometrial scratching is performed by a gynecologist only in the intervention group in the clinic. In this study, the participating patients (creating the same conditions) and the researcher (through sample coding) will be blinded.
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Participants/Inclusion and exclusion criteria
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Inclusion criteria: Women with Unexplained repeated implantation failure(uRIF), 20 to 40 years, Body max index less (BMI) than 25, good response to previous ovulation stimulation, at least two embryos with good grade in the current cycle, normal uterus. Exclusion criteria: Endometrial thickness is less than 7 mm, congenital anomalies,myoma,endometrioma, adhesions, hydrosalpinx, previous uterine or ovarian surgery, severe male factor infertility, number of embryos less than 2 in the current cycle, diabetes, thyroid disease, any endocrine, genetic, infection or autoimmune disorder
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Intervention groups
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Intervention: In the intervention group, endometrial sampling is obtained twice by Pipelle [one in the follicular phase and the last in the luteal phase of the same cycle preceding the embryo transfer cycle. Control group: In the control group endometrial sampling will be done only in the luteal phase of the cycle preceding the embryo transfer cycle.
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Main outcome variables
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Determination of angiogenic and anti-angiogenic growth factor gene expression in endometrial specimens in the intervention group compared with the control group
General information
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Reason for update
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According to the previous report, the actual recruitment end date of hospitalization is the same as 01/26/1401, and the only date of trial completion date is according to the examination of clinical pregnancy (5 weeks after embryo transfer) and live birth (9 months of pregnancy)in the participant's plan has increased. In addition, according to the evaluation of the secondary variables of implantation rate and clinical pregnancy, the variables related to them that are evaluated are added. A little rewriting has been done in the way the inclusion and exclusion criteria are expressed.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20210316050723N1
Registration date:
2021-07-12, 1400/04/21
Registration timing:
registered_while_recruiting
Last update:
2024-01-27, 1402/11/07
Update count:
4
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Registration date
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2021-07-12, 1400/04/21
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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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2021-06-20, 1400/03/30
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Expected recruitment end date
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2023-06-20, 1402/03/30
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Actual recruitment start date
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2021-06-20, 1400/03/30
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Actual recruitment end date
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2022-04-15, 1401/01/26
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Trial completion date
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2023-01-21, 1401/11/01
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Scientific title
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Evaluation of the effects of endometrial scratching on angiogenic and anti-angiogenic growth factors expression in unexplained repeated implantation failure (uRIF) patients
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Public title
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Evaluation of the effects of endometrial scratching on angiogenic and anti-angiogenic growth factors
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Purpose
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Other
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Inclusion/Exclusion criteria
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Inclusion criteria:
Infertile women with unexplained repeated implantation failure (unknown definite causes of RIF) failed to conceive after three or more embryo transfer cycles using high-quality transferred embryos (at least one blastocyst ET cycle)
Age of 20 to 40 years
Body mass index (BMI) less than 25 kg/m2
Good response to stimulation of previous ovulation
Having at least two embryos with good grade
normal uterus results of hysterosalpingography (HSG) or hysteroscopy
Participant consent was required to join in the study and to complete the consent form
Exclusion criteria:
The thickness of the endometrium on the day of Human chorionic gonadotropin hormone injection is less than 7 mm
Women with congenital anomalies, intramural and subserosal myomas( larger than 5 cm)
Submucosal myoma
Women with endometrioma larger than or equal to 3 cm
With adhesions
With hydrosalpinx
Have previous uterine or ovarian surgery
Severe male factor infertility (sperm extraction from the testis, sperm freezing, sperm DNA fragmentation index equal to or above 16%) Patients with any specific medication
If the number of available embryos is less than 2 in the current cycle
Women with endometrial tuberculosis and those undergoing tuberculosis treatment
Have a history of diabetes, thyroid disease, any endocrine, genetic, infection or autoimmune disorder
Abnormal Pre-implantation Genetic Test (PGT) Results
Any specific medication
Failure to return the patient to prepare an endometrial sample
Women with severe pain during obtaining of tissue samples or the possibility of infection
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Age
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From 20 years old to 40 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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Sample size
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Target sample size:
20
Actual sample size reached:
20
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Consecutive sampling until the required sample size is reached. Women by Balanced Block Randomization method are randomly divided into 2 equal groups of 10 people (intervention group and control group). Block randomization method is designed by epidemiologist using STATA software version 13 and the number of blocks considered is 4. Envelopes are prepared for 20 people and inside each envelope is written the group in which the patient should be placed. The envelopes are prepared in a way that the writing inside is not clear. A nurse before the patient enters the operating room, removes the envelope and sends the patients in one of the two groups.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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In this study, a doctor scratches the endometrium in the intervention group on days 8-11. The biopsy specimen is prepared in the luteal phase of the same cycle during days 19-23 by the same doctor or other. Therefore, in this study, it is not possible to blind the doctor. In order to blind the patients participating in this study, all the conditions will be the same between the two groups, so the patients of the control group also referred to the center on the day of the scratching (8-11) and due to the blinding of the study, all the sampling steps were done except endometrial scratching will be done for the control group as well as the intervention group. Then, biopsy samples are prepared from both groups in the luteal phase on days 19-23. The endometrial biopsy sample of both groups is sent to the laboratory, which does not know whether the tissue sample received is for the intervention group or the control group, and only checks it based on the received code (blinding of the researcher).
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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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2021-06-12, 1400/03/22
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Ethics committee reference number
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IR.IUMS.FMD.REC.1400.147
Health conditions studied
1
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Description of health condition studied
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Unexplained repeated implantation failure (uRIF)
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ICD-10 code
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N97.9
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ICD-10 code description
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Female infertility, unspecified
Primary outcomes
1
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Description
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Evaluation of gene expression
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Timepoint
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In the endometrial sample obtained in the luteal phase during days 19-23
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Method of measurement
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Using PCR Array method and based on the copy number
Secondary outcomes
1
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Description
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Clinical pregnancy
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Timepoint
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5 weeks after embryo transfer
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Method of measurement
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Vaginal ultrasonography (observing the gestational sac and fetal heart rate)
2
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Description
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Implantation
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Timepoint
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5 weeks after embryo transfer
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Method of measurement
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The number of observed sacs divided by the number of transferred embryos
3
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Description
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Total dose of gonadotropin (IU)
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Timepoint
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From ovarian stimulation to human chorionic gonadotropin (hCG) injection
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Method of measurement
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The number of international units (IU) received during the ovarian stimulation cycle
4
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Description
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Duration of ovarian stimulation (day)
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Timepoint
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From the start of gonadotropin administration to human chorionic gonadotropin (hCG) injection
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Method of measurement
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According to the patient's monitoring ultrasound chart (number of days receiving the medicine)
5
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Description
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Number of retrieved oocytes
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Timepoint
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On the day of oocyte pick-up
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Method of measurement
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The number of retrieved oocytes reported in the embryology chart
6
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Description
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Metaphase II oocytes
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Timepoint
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On the day of oocyte pick-up
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Method of measurement
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Based on the presence of the polar body reported by the embryologist
7
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Description
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Number of embryos
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Timepoint
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Three or five days after oocyte pick-up
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Method of measurement
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The number of cleavage embryos reported by the embryologist
8
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Description
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Embryo transfer cancelation
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Timepoint
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Three or five days after oocyte pick-up
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Method of measurement
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Participants with no embryo transfer
9
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Description
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Chemical pregnancy rate/Embryo transfer
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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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Beta human chorionic gonadotropin (beta hCG) titer in blood serum by ELISA method
10
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Description
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Blighted ovum/Embryo transfer
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Timepoint
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5 weeks after embryo transfer
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Method of measurement
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Absence of fetus in gestational sac according to ultrasound report
11
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Description
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Ectopic pregnancy/Embryo transfer
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Timepoint
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5 weeks after embryo transfer
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Method of measurement
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According to the ultrasound report, there is a gestational sac outside the uterus with a positive Beta hCG titer
12
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Description
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Miscarriage rate/Embryo transfer
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Timepoint
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Pregnancy loss before 20 weeks
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Method of measurement
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Excretion of pregnancy remnants with vaginal bleeding (absence of heartbeat according to ultrasound report)
13
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Description
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Multiple Pregnancy (Twin)
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Timepoint
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5 weeks after embryo transfer
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Method of measurement
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Ultrasound report based on the number of gestational sacs with embryo
14
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Description
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Live birth rate/Embryo transfer
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Timepoint
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Time of delivery
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Method of measurement
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Birth of a live baby
15
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Description
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Fertilization rate
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Timepoint
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The day after the sperm injection
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Method of measurement
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number of oocytes with two pronuclei (2PN) divided by the number of injected oocytes
Intervention groups
1
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Description
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Intervention group: In the intervention group, endometrial sampling is obtained twice by Pipelle [one in the follicular phase (during 8-11 days and the last in the luteal phase (during 19-23 days) preceding the embryo transfer cycle. The endometrial scratching is induced with pipelle.
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Category
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Treatment - Other
2
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Description
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Control group: In the control group endometrial sampling will be done only in the luteal phase of the cycle preceding the embryo transfer cycle.
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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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Iran 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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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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Not applicable
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Data Dictionary
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Not applicable
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Title and more details about the data/document
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Clinical study report (published article)
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When the data will become available and for how long
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After the publication of the article
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To whom data/document is available
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Available to the public
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Under which criteria data/document could be used
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Scientific use by citing the source
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From where data/document is obtainable
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Dr. Mehrdad Bakhtiyari
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What processes are involved for a request to access data/document
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Request via e-mail
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Comments
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